Expanded Criteria for Liver Transplantation in Patients with Hepatocellular Carcinoma

Liver transplantation (LT) is one of the few effective treatment options for hepatocellular carcinoma (HCC). Our aim in this study was to evaluate the risk factors for HCC recurrence and propose new criteria for LT based on pretransplantation findings. One hundred eighty patients who underwent LT for HCC between 2002 and 2008 were reviewed retrospectively. Outcome measures included maximal tumor size and number of tumors revealed by radiological studies before transplantation, demographics, and tumor recurrence. Maximal tumor size >6 cm, >7 tumors, and alpha-fetoprotein (AFP) levels >1000 ng/mL were identified as independent prognostic factors of HCC recurrence in univariate and multivariate analysis. Disease-free survival rate in patients with a maximal tumor size ≤6 cm, ≤7 tumors, and/or AFP levels ≤1000 ng/mL at 1, 3, and 5 years was 97.9%, 91.5%, and 90.0%, respectively, but the 1-, 3-, and 5-year disease-free survival rate of patients who had a maximal tumor size >6 cm, >7 tumors, and/or AFP levels >1000 ng/mL was 61.9%, 47.6%, and 47.6%, respectively (P < .001). In conclusion, LT can improve the survival of patients with advanced HCC if they have a maximal tumor size ≤6 cm, tumor number ≤7, and/or AFP levels ≤1000 ng/mL.     

Recurrence of hepatitis B is associated with cumulative corticosteroid dose and chemotherapy against hepatocellular carcinoma recurrence after liver transplantation.

The incidence of hepatitis B (HB) recurrence after a liver transplantation has been reduced by prophylaxis with hepatitis B immunoglobulin (HBIG) and lamivudine. However, the long-term incidence of recurrence is <10%, and the factors associated with HB recurrence are unclear. This study analyzed the factors associated with HB recurrence in 203 recipients who underwent liver transplantation for HB in 3 major centers in Korea over 4 years. Eighty-five patients (41.9%) had a hepatocellular carcinoma (HCC). Preoperative active virus replicators with the HBeAg(+) (46.8%) and/or hepatitis B virus DNA(+) (39.4%) were observed in 136 patients (67.0%). The HB prophylaxis consisted of either HBIG monotherapy (n = 95, HBIG group) or combination therapy with lamivudine (n = 108, combination group). HB recurrence was defined as the appearance of the HBsAg. The follow-up period was 28.3 +/- 13.1 months (mean +/- SD). HB recurred in 21 patients (10.3%) after transplantation. The time from transplantation to recurrence was 16.3 +/- 9.4 months. Pre-LT DNA positivity was more prevalent in HBIG group (55.8%) than in the combination group (39.8%) (P = 0.015). However, the incidence of HB recurrence was similar in the HBIG (6.3%) and combination group (13.8%), as well as between the active replicators (12.5%) and nonreplicators (4.1%) (P < 0.05). There was a far higher incidence of HB recurrence in patients receiving corticosteroid pulse therapy (21.0% vs. 7.9%), patients who experienced HCC recurrence (31.3% vs. 8.6%), and patients receiving chemotherapy to prevent HCC recurrence (25.0% vs. 4.4%) (P < 0.05). The cumulative corticosteroid dose was higher in patients who experienced recurrence of HB (P = 0.002). Multivariable analysis confirmed the effect of the cumulative corticosteroid dose and chemotherapy to be risk factors. Liver transplantation for HB is safe, with low recurrence rates if adequate prophylaxis is used. However, the cumulative corticosteroid dose and the chemotherapy used for HCC were risk factors for HB recurrence, so careful monitoring for HB recurrence is needed in these patients.     

Lancemaside A ameliorates colitis by inhibiting NF-κB activation in TNBS-induced colitis mice

Purpose  

In a preliminary study, we found that lancemaside A, which is a main constituent of Codonopsis lanceolata used as an herbal medicine for inflammatory diseases, potently inhibits lipopolysaccharide (LPS)-stimulated, TLR-4-linked NF-κB activation of NF-κB luciferase reporter gene-transfected 293-hTLR4-hemagglutinin (HA) cells. Therefore, we investigated its inhibitory effect in 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis in mice.     

Usefulness of transnasal endoscopy where endoscopic submucosal dissection is difficult

Background  

Early gastric cancer located from the pyloric ring to inside the duodenal bulb (DB) is not easily treated by endoscopic submucosal dissection (ESD). The endoscope needs to be reversed inside the DB to set the resection line at a safe distance from the anal side. Because of the space limitations and limited flexibility of conventional endoscopy (CE), there have been increasing possibilities of complications. Here we report a new ESD technique using a transnasal endoscope (TN-E) that is reversed inside the DB.     

AN ENDOCRINE CELL CARCINOMA WITH GASTRIC‐AND‐INTESTINAL MIXED PHENOTYPE ADENOCARCINOMA COMPONENT IN THE STOMACH

A 77‐year‐old man complained of bodyweight loss, and a Borrmann 3 type lesion was observed endoscopically in the anterior wall of angular region of the stomach. The endocrine cell carcinoma (ECC) having the cytoplasmic staining of chromogranin A (CgA) was detected pathologically in the biopsy samples. The patient underwent distal gastrectomy plus systemic lymph node (LN) dissection (D2 LN dissection), and pathological examination revealed ECC invading the subserosa, and no LN metastasis (pT2N0M0). None of the gastric and intestinal endocrine cell marker expression was apparent in the ECC cells. The lesion also contained a moderately differentiated type tubular adenocarcinoma component, which was judged to be gastric‐and‐intestinal mixed (GI type) phenotype, using gastric and intestinal exocrine cell markers. After the surgery, he left the hospital and started oral doxifluridine (600 mg/day). The patient now (March 2008, about 19 months since the surgery) continues this chemotherapy with no recurrence. In conclusion, we experienced ECC with a GI type adenocarcinoma component. The ECC cases with the GI type adenocarcinoma component may have a relatively good prognosis, being similar to the results of advanced gastric cancers from the viewpoint of gastric and intestinal phenotypic expression.     

GASTRIC SCHWANNOMA WITH ADJACENT EXTERNAL PROGRESSION HARBORED ABERRANT NF2 GENE

Gastric schwannomas are rare benign mesenchymal tumors. We describe a schwannoma of gastric origin with adjacent external progression. Sections showed a spindle cell tumor arranged in interlaced bundles and fascicles that was S‐100 and CD34 positive but c‐KIT protein negative. Histology and immunohistochemistry revealed the typical appearance of a gastric schwannoma. Genetic evaluation revealed that the tumor harbored a point mutation in exon 6 of the tumor suppressor neurofibromatosis 2 (NF2) gene, which resulted in an amino acid substitution of NF2 protein, and no mutation in exon 4b of the NF1 gene. In conclusion, we identified a rare mutation of the NF2 gene in gastric schwannoma. A diagnosis can only be definitive when based on histological and immunohistochemical findings. Digestive tract schwannomas are rare mesenchymal tumors that are differentiated from gastrointestinal stromal tumors by the absence of KIT protein. Follow up suggested that complete resection is an effective long‐term treatment strategy.     

CpG island hypermethylation of SOCS-1 gene is inversely associated with HBV infection in hepatocellular carcinoma

The CpG island hypermethylation of the suppressor of cytokine signaling-1 (SOCS-1) gene is frequently methylated in hepatocellular carcinoma (HCC), but its clinicopathological significance and the potential risk factors for the epigenetic change in HCC remain poorly understood. The methylation status of SOCS-1 CpG island was evaluated in fresh-frozen tissues from 284 HCC patients using the methylation-specific polymerase chain reaction. The expression of SOCS-1 protein was analyzed by immunohistochemical staining. SOCS-1 methylation was found in 163 (57%) of 284 HCCs. SOCS-1 methylation was positively associated with patient age (P = 0.002) and HCV infection status (P = 0.004), and was inversely associated with HBV infection (P = 0.0002). In the multivariate logistic regression analysis, the HB_sAg-negative HCCs showed a 2.78 (95% CI = 1.31–5.89, P = 0.007) times greater risk of SOCS-1 methylation than the HB_sAg-positive HCCs. SOCS-1 methylation also occurred at a 4.34 times (95% CI = 1.24–14.25, P = 0.02) higher prevalence in antiHCV-positive cases than in antiHCV-negative cases. No prognostic effect of SOCS-1 methylation was observed in the HCCs. In conclusion, the present study suggests that SOCS-1 methylation in HCC may be negatively associated with HB_sAg status.     

Effects of red ginseng upon postoperative immunity and survival in patients with stage III gastric cancer

In this paper, we present evidence that the red ginseng powder from Panax ginseng C.A. Meyer inhibits the recurrence of AJCC stage III gastric cancer and shows immunomodulatory activities during postoperative chemotherapy, after a curative resection with D2 lymph node dissection. Flow cytometric analyses for peripheral T-lymphocyte subsets showed that the red ginseng powder restored CD4 levels to the initial preoperative values during postoperative chemotherapy. Depression of CD3 during postoperative chemotherapy was also inhibited by the red ginseng powder ingestion. This study demonstrated a five-year disease free survival and overall survival rate that was significantly higher in patients taking the red ginseng powder during postoperative chemotherapy versus control (68.2% versus 33.3%, 76.4% versus 38.5%, respectively, p < 0.05). In spite of the limitation of a small number of patients (n = 42), these findings suggest that red ginseng powder may help to improve postoperative survival in these patients. Additionally, red ginseng powder may have some immunomodulatory properties associated with CD3 and CD4 activity in patients with advanced gastric cancer during postoperative chemotherapy.     

APP knockout attenuates microglial activation and enhances neuron survival in substantia nigra compacta after axotomy

Focal microglial activation and progressive dopaminergic neurodegeneration in substantia nigra compacta (SNc) have characterized Parkinson's disease (PD). We have hypothesized that the microglial response may be provoked by molecular signals from chronically stressed SNc neurons. To test whether amyloid precursor protein (APP) could serve as such a signal, we evaluated microglial activation in SN after unilateral transection of the medial forebrain bundle (MFB) in mice either wild-type (WT) or null (KO) for APP. WT and KO mice displayed comparable microglial response at the MFB transection site. In WT mice microglial activation was first apparent in the ipsilateral SN at 3 days postlesion (dpl), marked by morphological change and increased isolectin immunoreactivity. The microglial response intensified at 7 dpl and persisted in the medial nigra through 14 dpl. In contrast, in KO mice activated microglia appeared predominantly at 7 dpl, with little activation at 3 dpl and none at 14 dpl. Neuron number in affected WT SNc at 14 dpl was significantly reduced compared with loss in affected KO SNc. The delayed and limited local microglial activation and increased neuron survival in response to distal axotomy of SNc neurons in APP KO mice are consistent with the important role APP in neuronal stress responses in vivo.