Efficacy of the No. 10 lymphadenectomy with spleen preservation on patients with gastric cancer and/or esophagogastric junction adenocarcinoma who underwent total gastrectomy: a systematic review and meta-analysis.

Background: Surgery with total gastrectomy and D2 lymph node dissection (LND) has been recommended as the standard treatment for patients with advanced upper and middle gastric carcinoma and/or Siewert type II/III adenocarcinoma of the esophagogastric junction (AEG). However, whether the No. 10 lymph node (No. 10 LN, also known as splenic hilar LN) should be dissected in total gastrectomy remains controversial. We aimed to evaluate whether the No. 10 LND with spleen preservation has survival benefit for patients with gastric cancer and/or AEG who underwent the total gastrectomy. Methods: The PubMed, Embase, the Cochrane Library, ClinicalTrials.gov and American Society of Clinical Oncology.org (ASCO.org) were electronically searched to identify eligible studies. The primary outcome was the survival rate, and secondary outcomes included the disease-free survival (DFS) rate and side effects. The Review Manager 5.3.5 software was used for the meta-analysis. The odds ratio (OR) and mean difference with 95% confidence interval (CI) were calculated. The statistical heterogeneity was assessed using chi-square (χ2) and I2 tests. Results: Eight studies enrolling a total of 4,131 patients were eligible for our review. The meta-analysis results demonstrated that the No. 10 LND group was significantly better than the non-No. 10 LND group in terms of the 3- (OR =0.71, 95% CI: 0.62-0.81, P<0.00001) and the 5-year (OR =0.66, 95% CI: 0.58-0.75, P<0.00001) survival rates but not in the 1-year survival rate (OR =0.91, 95% CI: 0.75-1.11, P=0.36). The DFS rates in the No. 10 LND group were significantly increased after 1 (OR =0.76, 95% CI: 0.61-0.93, P=0.008), 3 (OR =0.69, 95% CI: 0.60-0.81, P<0.00001), and 5 (OR =0.66, 95% CI: 0.56-0.76, P<0.00001) years compared with those in the non-No. 10 LND group. Discussion: Evidence shows that the No. 10 LND with spleen preservation can improve the survival and the DFS rates for patients with gastric cancer and/or Siewert type II/III AEG who underwent the total gastrectomy. High-quality prospective trials are expected.

Expression heterogeneity research of ITGB3 and BCL-2 in lung adenocarcinoma tissue and adenocarcinoma cell line.

OBJECTIVE: To analyze expression heterogeneity of Integrin beta 3 (ITGB3) and B-cell lymphoma 2 (BCL-2) in lung adenocarcinoma tissue and adenocarcinoma cell line and further provide theoretical direction for molecular biological research of lung adenocarcinoma. METHODS: Tissue microarray was used to observe relation among expression, heterogeneitpy and clinical characteristics of ITGB3 and BCL-2 in lung cancer. RESULTS: ITGB3 and BCL-2 increased significantly in A549 cells in CAFs group withß-actin as control; the expression level of BCL-2 also increased in ITGB3 transfected cells with GFP plasmid transfected A549 cells as control; immunohistochemistry staining showed that positive rates of ITGB3, ITGB1 and BCL-2 in normal lung tissues were 0, the positive rates in lung adenocarcinoma were 7.04%, 84.51% and 4.23%, respectively; in the results of immunohistochemistry staining, the expression of Girdin protein in lung adenocarcinoma was homogeneous, however protein expression of ITGB3, ITGB1 and BCL-2 showed different patterns in the same location with significant heterogeneity; majority of ITGB3, ITGB1 or BCL-2 positive tissue showed heterogeneity that expression in trailing edge was higher than that of trailing edge in lung adenocarcinoma tissue, the patients with BCL-2 heterogeneity showed higher lymph node metastasis ratio and lower clinical stage (P<0.05); and the expression of ITGB3 and the clinical characteristics of patients were not significant related (P>0.05). CONCLUSIONS: Expression of ITGB3 and BCL-2 in lung adenocarcinoma and adenocarcinoma cell line showed heterogeneity that expression in trailing edge was higher than that of trailing edge, which may play an important role in promoting tumor lymph node metastasis and vascular invasion, and provides a new research direction for exploration of lung adenocarcinoma metastasis mechanism.

Construction of a plasmid vector for liver-specific inhibition of hepatocyte nuclear factor 4 alpha expression.

Hepatocyte nuclear factor-4alpha (HNF-4a) is an important transcription factor in the liver, and regulates a large number of genes involved in many aspects of hepatocyte functions. In this study, a liver-specific transcriptional regulatory element comprised of albumin promoter (ALBp) and alpha-fetoprotein enhancer (AFPe) was obtained and cloned into the plasmid pHNF4sh-CMV(short hairpin RNA targeting HNF4α) with original CMV promoter removed, resulting to pHNF4sh-EP for liver-specific knockdown of HNF4α expression. In an attempt to verify its characteristics, pHNF4sh-EP was transfected to L02, HepG2, and COS1 cell lines in vitro and delivered into mice in vivo. pHNF4sh-CMV and pNCsh-EP were used as controls. For in vitro, the level of HNF4α mRNA and protein was decreased in all cell lines transfected with pHNF4sh-CMV whereas HNF4α mRNA and protein decreasing was only observed in L02 and HepG2 cell lines upon transfection with pHNF4sh-EP, and this decreasing was more significant as compared with pHNF4sh-CMV transfected cells. For in vivo, the decreasing of HNF4α mRNA and protein was observed in both liver and kidney tissues upon transfection with pHNF4sh-CMV. After transfection with pHNF4sh-EP, decreasing of HNF4α mRNA and protein was only found in liver tissue and this decreasing was more significant. No obvious HNF4α mRNA and protein decreasing was detected either in vitro or in vivo after transfected with pNCsh-EP. In conclusion, pHNF4sh-EP could highly-active and liver-specific knockdown of HNF4α expression liver and it will be useful for further study of the funcitions of HNF4α in liver.

[KRAS and epidermal growth factor receptor gene mutation in non-small cell lung cancer].

OBJECTIVE: To study KRAS and epidermal growth factor receptor (EGFR) mutations in primary non-small cell lung cancer (NSCLC) and their association with the effects of targeted therapy. METHODS: Gene mutations of KRAS and EGFR in both primary tumors and local lymph node metastases from 150 patients with NSCLC were analyzed by direct sequencing. Twelve of the patients were given gefitinib as neoadjuvant therapy after EGFR-TKI sensitive mutations had been detected in biopsies of mediastinal lymph node metastases. RESULTS: Two primary tumors and 10 metastases were identified to have KRAS mutations, while 35 primary tumors and 44 metastases were found to have EGFR mutations. KRAS and EGFR mutation status was different between primary tumors and corresponding metastases in 6.7% (10/150) and 8.67% (13/150) patients, respectively. One patient with no TKI sensitive mutations in the primary tumor showed disease progression with gefitinib therapy. CONCLUSIONS: Our results suggest that a considerable proportion of NSCLC in Chinese patients showed discrepancy in KRAS and EGFR mutation status between primary tumors and corresponding metastases. This observation may have important implications for the use of targeted TKI therapy in the treatment of NSCLC patients.

Nucleoside analogue can improve the long-term prognosis of patients with hepatitis B virus infection-associated acute on chronic liver failure.

BACKGROUND: The prognosis of patients with hepatitis B virus (HBV)-associated acute on chronic liver failure (ACLF) is extremely poor. AIM: This study was designed to evaluate the efficacy and safety of nucleoside analogue treatment of patients with HBV-associated ACLF. METHODS: We used a retrospective review of eligible patients from April 2006 to December 2008. Eligible subjects received 0.5 mg entecavir daily until October 2009 (group A), 100 mg lamivudine daily until October 2009 (group B), or no nucleoside analogue (group C). The primary endpoints were three-month survival and the rate of recurrence of HBV-associated ACLF. The secondary endpoints were HBV DNA levels, liver function, the model of end-stage liver disease (MELD) score, and adverse events. RESULTS: A total of 104 consecutive patients were recruited, and 33, 34, and 37 patients were randomly allocated to groups A, B, and C, respectively. Although no significant difference in three-month survival was observed, levels of HBV DNA and rates of recurrence of HBV-associated ACLF were lower. Liver function and MELD score were not significantly improved despite significantly reduced HBV DNA levels. CONCLUSIONS: These data indicated that nucleoside analogue treatment did not improve the short-term prognosis of patients with HBV-associated ACLF although it was efficacious and safe in the management of HBV DNA levels. Intriguingly and importantly, continuous nucleoside analogue treatment can significantly reduce the rate of recurrence, which might be indicative of the further benefit of long-term survival.

Recombinant human hepatocyte growth factor for liver failure.

The purpose of this paper is to evaluate the efficacy and safety of recombinant human hepatocyte growth factor (rh-HGF) for liver failure (LF) using meta-analysis of data from the literature involving available randomized controlled trials of rh-HGF plus comprehensive therapy (CT) compared with that of CT alone (Therapy I versus II) in treating LF. We searched the Cochrane Library, MEDLINE, EMBASE, CBMdisc, and CNKI as well as employing manual searches. Based on our search criteria, we found 21 trials, involving 5902 patients. Our results showed that Therapy I, compared with therapy II, significantly reduced the overall mortality (RR=0.62; 95% CI, 0.59-0.66; p=0.0001). Compared to two clinical types of LF (acute and acute-on-chronic), therapy I perhaps had significant effect on mortality due to sub-acute LF, RR and 95% CI were 0.76 [0.65, 0.89], 0.66 [0.60, 0.74], and 0.58 [0.53, 0.64], respectively. Additionally, there was a reduction in mortality of patients that had evidence for an early stage of LF compared to the two other clinical stages of LF (Middle and Advanced); RR and 95% CI were 0.34 [0.24, 0.49], 0.49 [0.44, 0.55], and 0.87 [0.82, 0.93], respectively. No serious adverse events were reported. We conclude that Therapy I may reduce mortality in LF, especially in sub-acute LF and the early stage of LF. However, considering the strength of the evidence, additional randomized controlled trials are needed before Therapy I can be recommended routinely.