Preliminary study on proteomics of gastric carcinoma and its clinical significance

AIM： To explore the preliminary identification of serum protein pattern models that may be novel potential biomarkers in the detection of gastric cancer. METHODS： A total of 130 serum samples, including 70 from patients with gastric cancer and 60 from healthy adults, were detected by surface-enhanced laser desorption and ionization time-of-flight mass spectrometry （SELDI-TOF-MS）. The data of spectra were analyzed by Biomarker Patterns Software （BPS）. Thirty serum samples of gastric cancer patients and 30 serum samples of healthy adults were grouped into the training group to build models, and the other 70 samples were used to test and evaluate the models. The samples of the test group were judged only with their peaks＇ height and were separated into cancer group or healthy control group by BPS automatically and the judgments were checked with the histopathologic diagnosis of the samples. RESULTS： Sixteen mass peaks were found to be potential biomarkers with a significant level of P〈0.01. Among them, nine mass peaks showed increased expression in patients with gastric cancer. Analyzed by BPS, two peaks were chosen to build the model for gastric cancer detection. The sensitivity, specificity, and accuracy of the model were 90%, 36/40, 86.7%, 26/30, and 88.6%, 62/70, respectively, which were greatly higher than those of clinically used serum biomarkers CEA （carcinoembryonic antigen）, CAlg-g and CA72-4. Stage Ⅰ/Ⅱ gastric cancer samples of the test group were all judged correctly.CONCLUSION： The novel biomarkers in serum and the established model could be potentially used in the detection of gastric cancer. However, large-scale studies should be carried on to further explore the clinical impact on the model.

Radiofrequency Ablation for Postoperative Recurrences of Intrahepatic Cholangiocarcinoma

Objective: Most recurrent intrahepatic cholangiocarcinoma (RICC) lost the opportunity of radical resection while most nonsurgical management failed to prolong patients’ survival. The efficacy and safety of radiofrequency ablation (RFA) as a local treatment for recurrent hepatocellular carcinoma have been confirmed by many clinical studies. The purpose of this study was to evaluate the efficacy, long-term survival and complications of RFA for RICC. Methods: A total of 12 patients with 19 RICCs after radical resection were included in this study. The tumors were 1.9–6.8 cm at the maximum diameter (median, 3.2±1.6 cm). All patients were treated with ultrasound guided RFA. There were two RFA approaches including percutaneous and open. Results: A total of 18 RFA treatment sessions were performed. Ablation was successful (evaluated by 1-month CT after the initial RFA procedure) in 18 (94.7%) of 19 tumors. By a median follow-up period of 29.9 months after RFA, 5 patients received repeated RFA because of intrahepatic lesion recurrence. The median local recurrence-free survival period and median event-free survival period after RFA were 21.0 months and 13.0 months, respectively. The median overall survival was 30 months, and the 1- and 3-year survival rates were 87.5% and 37.5%, respectively. The complication rate was 5.6% (1/18 sessions). The only one major complication was pleural effusion requiring thoracentesis. Conclusion: This study showed RFA may effectively and safely manage RICC with 3-year survival of 37.5%. It provides a treatment option for these RICC patients who lost chance for surgery.

Role of a liver-first approach for synchronous colorectalliver metastases

AIM: To evaluate the feasibility and survival outcomes of a liver-first approach.METHODS: Between January 2009 and April 2013, 18 synchronous colorectal liver metastases(s CRLMs) patients with a planned liver-first approach in the Hepatopancreatobiliary Surgery Department Ⅰ of the Beijing Cancer Hospital were enrolled in this study. Clinical data, surgical outcomes, morbidity and mortality rates were collected. The feasibility and long-term outcomes of the approach were retrospectively analyzed.RESULTS: Sixteen patients(88.9%) completed the treatment protocol for primary and liver tumors. The main reason for treatment failure was liver disease recurrence. The 1 and 3 year overall survival rates were 94.4% and 44.8%, respectively. The median survival time was 30 mo. The postoperative morbidity and mortality were 22.2% and 0%, respectively, following a hepatic resection, and were 18.8% and 0%, respectively, after a colorectal surgery.CONCLUSION: The liver-first approach appeared to be feasible and safe. It can be performed with a comparable mortality and morbidity to the traditional treatment paradigm. This approach might offer a curative opportunity for s CRLM patients with a high liver disease burden.

Diagnosis and Treatment of Cholangiocarcinoma: A Consensus from Surgical Specialists of China

Cholangiocarcinoma refers to malignant tumors that develop in epithelial lining of biliary system, and it is divided into two categories according to tumor location, intrahepatic cholangiocarcinoma （ICC） and extrahepatic cholangiocarcinoma （ECC）. ICC occurs from the epithelial cells of the intrahepatic bile duct, its branches and interlobular biliary tree; and ECC is divided into hilar cholangiocarcinoma and distal cholangiocarcinoma by the circumscription at the confluence of cystic duct and the common hepatic duct.

Cortactin Overexpression Correlates with Poor Prognosis in Hepatocellular Carcinoma

Objective： To investigate cortactin expression in hepatocellular carcinoma （HCC） and explore its significance in the prognosis of HCC patients. Methods： Immunohistochemistry was performed for paraffin samples of 119 pairs of HCC tissues （HCCs） and paratumorous liver tissues （PTLTs） to evaluate cortactin expression. The cortactin expression difference in HCCs and PTLTs were analyzed by the McNemar＇s test. The relationship of cortactin expressions in HCCs and clinicopathologic factors was analyzed with Mann-Whitney U test. The Kaplan-Meier method and log-rank test were employed to compare the overall survival between Cortactin negative expression group, weak expression group and strong expression group. Expression of cortactin was further determined in 19 pairs of fresh HCCs and PTLTs specimens with Western blotting. Results： Cortactin expression rate was significantly higher in HCCs （53/119, 44.5%） than that in PTLTs （2/119, 1.7%） （P〈0.001）. The upregulated cortactin expression in HCCs was significantly correlated to absence of capsule formation （P=0.012）, vascular invasion （P=0.037） and high Edmondson-Steiner grade （P=0.020）, and predicted shorter overall survival. Western blotting demonstrated that cortactin expression was upregulated in 9 out of 19 HCCs （47.4%） compared to corresponding PTLTs. Conclusion： Cortactin expression is upregulated in HCC and is related to shorter overall survival of patients, suggesting that cortactin might play roles in the metastasis of HCC and predict a poor prognosis of HCC patients.

Expression of Plasminogen Activator Inhibitor-2 is Negatively Associated with Invasive Potential in Hepatocellular Carcinoma Cells

Objective To investigate the association between plasminogen activator inhibitor(PAI)-2 expression and invasive potential in hepatocellular carcinoma(HCC) cells.Methods The HCC cell lines with high,low,and non-metastatic potentials,namely MHCC97-H,MHCC97-L,and SMMC-7721 respectively,were cultured in vitro.Matrigel invasion assay and Western blot of PAI-2 protein expression were conducted.Results The number of invaded cells in MHCC97-L was significantly higher than that in SMMC-7721(P=0.005),whereas that in MHCC97-H was higher than in MHCC97-L(P=0.017) and SMMC-7721(P=0.001).Contrarily,PAI-2 protein expression was gradually reducing from SMMC-7721,MHCC97-L,to MHCC97-H(MHCC97-H vs.MHCC97-L,P<0.001;MHCC97-H vs.SMMC-7721,P=0.001;MHCC97-L vs.SMMC-7721,P=0.001).The Pearson's correlation analysis revealed a significant negative association between invaded cell number and PAI-2 expression(r= 0.892,P=0.001).Conclusion PAI-2 expression may be negatively associated with the invasive potential of HCC.

Irinotecan-vs oxaliplatin-based regimens for neoadjuvant chemotherapy in colorectal liver metastasis patients:A retrospective study

BACKGROUND Neoadjuvant chemotherapy(NC)improves the survival outcomes of selected patients with colorectal liver metastasis(CRLM).The benefits of irinotecan-based regimens in these patients are still under debate.AIM To compare the benefits of irinotecan-and oxaliplatin-based regimens in patients with resectable CRLM.METHODS From September 2003 to August 2020,554 patients received NC and underwent hepatectomy for CRLM.Based on a 1:1 propensity score matching(PSM)model,175 patients who received irinotecan were matched to 175 patients who received oxaliplatin to obtain two balanced groups regarding demographic,therapeutic,and prognostic characteristics.RESULTS Chemotherapy was based on oxaliplatin in 353(63.7%)patients and irinotecan in 201(36.3%).After PSM,the 5-year progression-free survival(PFS)and overall survival(OS)rates with irinotecan were 18.0%and 49.7%,respectively,while the 5-year PFS and OS rates with oxaliplatin were 26.0%and 46.8%,respectively.Intraoperative blood loss,operating time,and postoperative complications differed significantly between the two groups.In the multivariable analysis,carbohydrate antigen 19-9,RAS mutation,response to NC,tumor size>5 cm,and tumor number>1 were inde-pendently associated with PFS.CONCLUSION In NC in patients with CRLM,irinotecan is similar to oxaliplatin in survival outcomes,but irinotecan is superior regarding operating time,intraoperative blood loss,and postoperative complications.

Human U Three Protein 14a Expression is Increased in Hepatocellular Carcinoma and Associated with Poor Prognosis

Background： Human U three protein 14a （hUTP 14a） promotes p53 degradation. Moreover, hUTP 14a expression is upregulated in several types of tumors. However, the expression pattern of hUTP 14a in hepatocellular carcinoma （HCC） remains unknown. The aim of this study was to investigate hUTP 14a expression and its prognostic value in HCC. Methods： The hUTP 14a expression was evaluated using immunohistochemistry （IHC） in HCC tissue specimens. The correlations between hUTP 14a expression and clinicopathological variables were analyzed. The Kaplan-Meier method was used to analyze the association between hUTP14a expression and survival. Independent prognostic factors associated with overall survival （OS） and disease-free survival （DFS） were analyzed using the Cox proportional-hazards regression model. Results： The IHC data revealed that the hUTP 14a positivity rate in HCC tissue specimens was significantly higher than that in nontumorous tissue specimens （89.9% vs. 72.7%, P 〈 0,05）. The hUTP14a expression was detected in both the nucleolus and the cytoplasm. The positivity rate of nucleolar hUTP14a expression in HCC tissue specimens was higher than that in the nontumorous tissue specimens （29.3% vs. 10.1%, P 〈 0.05）. No significant difference was found between HCC and nontumorous tissue specimens of cytoplasmic hUTP 14a expression （60.6% vs. 62.6%, P 〉 0.05）. In addition, no significant correlation was found between nucleolar hUTP 14a expression and other clinicopathological variables. The 5-year OS and DFS rates in patients with positive nucleolar hUTP14a expression were significantly lower than those in patients with negative hUTP 14a expression （P = 0.004 for OS, P = 0.003 for DFS）. Multivariate analysis showed that nucleolar hUTP 14a expression was an independent prognostic factor for OS （P = 0.004） and DFS （P 〈 0.001 ）. Conclusions： The positivity rate of hUTP 14a expression was significantly higher in HCC specimens. Positive expression of nucleolar hUTP 14a might act as a novel prognostic predictor for patients with HCC.

Quality over quantity:a necessary path for clinical research transformation in China

Since the Chinese economic reform in 1978,its medical field has made remarkable progress in the past 40 years.In most medical fields,China’s diagnosis and treatment methods are comparable to the international high standards.In recent years,with the continuous expansion of the medical research team and the improvement of laboratory research equipment and methods,China has achieved some influential and internationally recognized research outcomes.However,overall,China still lags behind developed countries in terms of high-level original medical research,especially in high evidence-based medical research(1).