Feasibility and safety of sorafenib treatment in hepatocellular carcinoma patients with spontaneous rupture.

AIM: To report the outcome of patients with ruptured hepatocellular carcinoma (HCC) treated at a single center during a 5-year period. METHODS: We retrospectively analyzed 32 patients who presented with ruptured HCC at Shandong Provincial Hospital Affiliated to Shandong University between 2008 and 2013. RESULTS: The mean age of the patients was 53 years (range 39-71 years). Of these patients, 22 received surgical management, 10 underwent transarterial embolization (TAE) or transarterial chemoembolization (TACE), and 12 received sorafenib after surgery, TAE or TACE. Cumulative survival rates at 4, 8 and 12 mo were 72.9%, 50.0% and 33.3%, respectively, in the surgery only group and were 90.0%, 80.6% and 64.1%, respectively, in the surgery plus sorafenib group. Cumulative survival rates at 4, 8 and 12 mo were 68.4%, 43.6% and 19.4%, respectively, in the surgery only or TAE/TACE only groups, and were 91.7%, 75.0% and 60.2%, respectively, in the sorafenib combination groups (P = 0.04). No unexpected side effects due to sorafenib were observed. The most common side effect was hand-foot skin reaction. To date, 5 patients have died. Median follow-up from the start of sorafenib therapy for the remaining 7 patients is 12.7 mo (range 5.8-32.2 mo). CONCLUSION: Sorafenib can be used in patients with ruptured HCC as it has interesting activity and is well tolerated; dose adjustment is generally not required. However, a larger prospective study is necessary to determine the efficacy of sorafenib in this group of patients.

Possible benefit of splenectomy in liver transplantation for autoimmune hepatitis.

Liver transplantation for autoimmune hepatitis (AIH) is usually successful with excellent long-term outcomes, but primary disease may recur. The recurrence of AIH is a significant cause of graft loss. This study was to analyze the effect of splenectomy in preventing AIH relapse. The clinical courses of 12 patients who had transplantation for AIH were analyzed retrospectively. All patients were subjected to transplantation for end-stage liver disease caused by chronic AIH. Based on the duration of immunosuppressive treatment before liver transplantation, simultaneous splenectomy was performed in ten patients. Two patients underwent liver transplantation without splenectomy, one of them developed recurrent AIH and died from graft failure caused by AIH relapse. However, no episode of AIH recurrence was observed in patients who had undergone simultaneous splenectomy. Splenectomy might be an option to prevent AIH relapse in some patients with high risk factors.

Protein phosphatase magnesium-dependent 1δ (PPM1D) mRNA expression is a prognosis marker for hepatocellular carcinoma.

BACKGROUND: Protein phosphatase magnesium-dependent 1δ (PPM1D) is an oncogene, overexpressed in many solid tumors, including ovarian cancer and breast cancer. The current study examined the expression and the prognostic value of PPM1D mRNA in human hepatocellular carcinoma (HCC). METHODS: Total RNA was extracted from 86 HCC and paired non-cancerous liver tissues. PPM1D mRNA expression was determined by real-time quantitative reverse transcriptase-polymerase chain reaction (qPCR). Immunohistochemistry assay was used to verify the expression of ppm1d protein in the HCC and non-cancerous liver tissues. HCC patients were grouped according to PPM1D mRNA expression with the average PPM1D mRNA level in non-cancerous liver tissue samples as the cut-off. Correlations between clinicopathologic variables, overall survival and PPM1D mRNA expression were analyzed. FINDINGS: PPM1D mRNA was significantly higher in HCC than in the paired non-cancerous tissue (p<0.01). This was confirmed by ppm1d staining. 56 patients were classified as high expression group and the other 30 patients were categorized as low expression group. There were significant differences between the two groups in term of alpha-fetoprotein (α-FP) level (p<0.01), tumor size (p<0.01), TNM stage (p<0.01), recurrence incidence (p<0.01) and family history of liver cancer (p<0.01). The current study failed to find significant differences between the two groups in the following clinical characteristics: age, gender, portal vein invasion, lymphnode metastasis, hepatitis B virus (HBV) infection and alcohol intake. Survival time of high expression group was significantly shorter than that of low expression group (median survival, 13 months and 32 months, respectively, p<0.01). CONCLUSION: Up-regulation of PPM1D mRNA was associated with progressive pathological feature and poor prognosis in HCC patients. PPM1D mRNA may serve as a prognostic marker in HCC.

[The structure and viability analysis of corneal epithelial flap in the rabbit cornea after Epi-LASIK].

OBJECTIVE: To evaluate the changes of ultrastructure and viability in the rabbit corneal epithelial flap after Epi-LASIK (epiploic laser in-situ keratomileusis) surgery and its effect on keratocyte apoptosis and proliferation of peripheral corneal epithelium (out of corneal epithelial flap). METHODS: Fifty-eighty eyes of 29 New Zealand rabbits were used, Epi-LASIK was performed in 28 eyes and Photorefractive keratectomy (PRK) was carried out in 24 eyes. treated-eyes were randomly divided into four groups and were sacrificed at 1, 3, 5, 7 days after surgery, six eyes without treatment were served as blank controls. Histological structure from The specimens of Epi-LASIK and controls eyes were assessed by light, transmission electron microscopy; epithelial cells viability were assessed by enzyme-histochemistry and Immunohistochemistry staining (proliferating cell nuclear antigen, PCNA) were performed to detect proliferation of peripheral corneal epithelial cells. Apoptotic cells were detected by TUNEL assay (TdT-mediated dUTP nick-end labeling) from the specimens of Epi-LASIK and PRK. RESULTS: The study from Transmission electron microscopy demonstrated that epithelial flap separated by KM5000D type epikeratome retained its typical stratification and integrity and the basement membrane including lamina densa and lamina lucida were compaginated with stroma. The expression of ATP enzyme, G-6-P enzyme from epithelial flap to peripheral epithelium of Epi-LASIK-treated eyes were (79%, 58%, 69%, 86%), (79%, 63%, 77%, 97%) at 1, 3, 5, 7 days after surgery respectively. There was no statistically significant difference in the cell Viability and the number of PCNA in peripheral epithelial cells among four Epi-LASIK groups and control group. At 1 day after surgery, no difference in TUNEL positive cells were seen between specimens of Epi-LASIK (3.429 +/- 1.693) and PRK (3.796 +/- 1.998); At 3, 5, 7 days, there was a significant difference in the number of keratocyte apoptosis in PRK compared to Epi-LASIK specimens. CONCLUSIONS: Epithelial flap separated by KM5000D type epikeratome retained its typical stratification and integrity. The flap keeps high viability and no peripheral epithelial cell proliferation and therefore it may play a role in the inhibition of keratocyte apoptosis.