Ying Bao

Combination Therapy of Radiofrequency Ablation and Transarterial Chemoembolization for Unresectable Hepatocellular Carcinoma: A Retrospective Study

Abstract The treatment efficacy of unresectable hepatocellular carcinoma (HCC) is still not promising. This study aimed to compare the efficacy and safety of radiofrequency ablation (RFA) combined with transarterial chemoembolization (TACE) for unresectable HCC with a single treatment. Between June 2009 and June 2012, 132 patients who were diagnosed with unresectable HCC and accepted nonsurgical treatments in our center were enrolled in this retrospective study. On the basis of treatment modality, they were allocated to 3 groups: 49 patients accepted RFA (RFA group); 43 patients accepted TACE (TACE group); and 40 patients accepted RFA following TACE (combination group). Clinical data including complications, treatment success rate, hospitalization costs, intrahepatic recurrence-free survival, overall survival, and factors influencing survival were retrospectively analyzed. Patient characteristics between these groups showed no significant difference. Treatment success was achieved in all patients of 3 groups. The combination group had a significantly higher total hospitalization cost to treatment than the TACE group (63,708.14 ± 9193.81 Chinese yuan vs 37,534.88 ± 6802.84 Chinese yuan; P = 0.0000). All complications were controllable and no permanent adverse sequelae or procedure-related deaths were observed. The 3-year intrahepatic recurrence-free survival probability was significantly better in the combination group than in the TACE group (42.50% vs 20.93%; hazard ratio [HR], 0.5105; 95% confidence interval [CI], 0.3022–0.8625; P = 0.0094) or the RFA group (42.50% vs 22.45%; HR, 0.5233; 95% CI, 0.3149–0.8697; P = 0.0111).The 3-year overall survival probability was significantly better in the combination group than in the TACE group (45.00% vs 26.53%; HR, 0.5069; 95% CI, 0.2936–0.8752; P = 0.0100) or the RFA group (45.00% vs 27.91%; HR, 0.4913; 95% CI, 0.2928–0.8246; P = 0.0054). Main tumor size, number of tumors, and treatment modality were demonstrated to be important factors associated with 3-year intrahepatic recurrence-free survival probability and overall survival probability (P < 0.05) by univariate and multivariate analyses. Combination therapy of RFA and TACE was superior to TACE alone or RFA alone in improving survival for patients with unresectable HCC.

Eukaryotic translation initiation factor 5A2 (eIF5A2) regulates chemoresistance in colorectal cancer through epithelial mesenchymal transition

BackgroundChemoresistance is a major obstacle to successful chemotherapy for colorectal cancer. Eukaryotic translation initiation factor 5A2 (eIF5A2), one of the two isoforms in the eIF5A family, has been reported to be a new oncogene in many types of human cancer. In the present study, we aimed to investigate whether eIF5A2 was involved in the chemoresistance to doxorubicin in colorectal cancer.MethodsCell viability was measured by CCK-8 assay with or without doxorubicin treatment. Protein expression was detected by western blot. Tumor cells were transfected with eIF5A2 siRNA or plasmid encoding eIF5A2 to down- or up regulate the expression of eIF5A2.ResultsWe found that eIF5A2-negtive colon cancer cells (HCT116 and HT29) were more sensitive to doxorubicin compare with the eIF5A2-positive cells (LOVO and SW480). Downregulation of eIF5A2 in LOVO and SW480 cells enhanced the chemosensitivity to doxorubicin. On the contrary, overexpression of eIF5A2 reduced doxorubicin sensitivity in colon cancer cells. In addition, eIF5A2 knockdown increased the protein level of E-cadherin and reduced vimentin expression in LOVO and SW480 cells. Meanwhile, upregulation of eIF5A2 potentiated epithelial mesenchymal transition (EMT) in colon cancer cells. Moreover, blockade of EMT with Twist siRNA abolished eIF5A2-regulated chemoresistance in colon cancer cells.ConclusionOur present study demonstrated that eIF5A2 promoted the chemoresistance to doxorubicin via regulation of EMT in colon cancer cells. Therefore, eIF5A2 inhibition may be a new potential strategy for the reversal of drug resistance in colorectal cancer therapy.

Spleen-preserving Distal Pancreatectomy or Distal Pancreatectomy With Splenectomy? Perioperative and Patient-reported Outcome Analysis

Goals: We designed this study to evaluate the efficacy of spleen salvage during distal pancreatectomy for patients with benign and borderline malignant tumors. Background: Despite the emphasis on its role, the spleen has commonly been removed in distal pancreatectomy. Study: From January 2005 to July 2009, 82 patients underwent distal pancreatectomy with splenectomy (DPS) and 78 patients underwent spleen-preserving distal pancreatectomy (SPDP). Medical records were retrospectively reviewed. Results: There were no significant differences in demographics, final diagnoses, estimated blood loss, intraoperative transfusion, and operative time between the 2 groups. More perioperative complications occurred in the DPS group than in the SPDP group (P=0.0344). Consequently, postoperative hospital stay was significantly shorter in the SPDP group than in the DPS group (P=0.0273). In the follow-up survey, episodes of common cold or flu were apparently more frequent in the DPS group (P=0.047). More patients in the DPS group felt fatigue (P=0.0481) and poor health condition (P=0.0371). Less newly developed (P=0.0193) and aggravated diabetes mellitus (P=0.0361) were also observed in the SPDP group. Platelet counts on postoperative day (POD) 5, hemoglobin on POD 3, WBC counts, and CRP level on POD 2 were significantly higher in the DPS group than in the SPDP group and these differences continued to be significant for months after surgery. Conclusions: In addition to frequent higher grade complications, prolonged hospital stays, and severe hematological abnormalities, DPS seemed to result in poor health condition based on the follow-up survey. Even an effort to preserve an adult spleen in distal pancreatectomy is worthwhile.

Endostatin inhibits angiogenesis in hepatocellular carcinoma after transarterial chemoembolization.

BACKGROUND/AIMS This study aims to investigate the influence of endostatin on angiogenesis in hepatocellular carcinoma (HCC) after transarterial chemoembolization (TACE). METHODOLOGY Ninety-five patients with HCC were enrolled. Twenty-six patients received initial liver resection without preoperative TACE (non-TACE), 24 received preoperative TACE without endostatin (TACE), 22 received endostatin (15mg/m2) right after TACE intravenously (TACE-V) and 23 received endostatin (15mg/m2) through the hepatic artery during TACE (TACE-A). TACE was performed using Gemcitabine 1000mg/m2 (emulsified with lipiodol, 10-12mL), cisplatin 40 mg/m2 and 5-fluorouracil 500mg/m2 through the hepatic artery feeding the tumor. Patients received liver resection 4 weeks after second course of TACE. RESULTS The mean microvessel density (MVD) was 32.23±12.71, 57.46±18.38, 44.36±15.13 and 43.48±15.59 in non-TACE, TACE, TACE-V and TACE-A group respectively. The positive rate of vascular endothelial growth factor (VEGF) expression was 46.15%, 91.67%, 77.27% and 73.91% in non-TACE, TACE, TACE-V and TACE-A groups, respectively. Compared to the non-TACE group, MVD and VEGF expression in TACE, TACE-V and TACE-A groups were significantly higher (p<0.05). MVD and VEGF expression in the TACE-V and TACE-A groups were significantly lower than in the TACE group (p<0.05). CONCLUSIONS Endostatin could significantly repress angiogenesis in HCC after TACE by down-regulating expression of VEGF.

Role of glucose metabolism related gene GLUT1 in the occurrence and prognosis of colorectal cancer

Colorectal cancer (CRC) ranks the third most commonly diagnosed cancer in males and the second in females worldwide. However, the functional and causal SNPs for CRC remain to be mined. Glucose transporter 1 (GLUT1), a pivotal rate-limiting element in the transport of glucose in malignancy cells, has been identified to be associated with many cancers. Here, we aim to explore the role of GLUT1 in the occurrence and prognosis of colorectal cancer in a Chinese population. We found that GLUT1 expression levels in CRC tumor tissues were significantly higher than those in the corresponding adjacent normal tissues, and Cox multivariate analysis demonstrated that the GLUT1 expression was an independent prognostic factor for CRC (HR = 2.11, 95% CI = 1.33-3.34, P=0.001). For a functional polymorphism of GLUT1 (rs710218), we found that individuals with TT genotype (OR = 1.68, 95% CI = 1.02-2.75, P = 0.041) or AT genotype (OR = 1.47, 95% CI = 1.09-1.99, P = 0.012) of rs710218 had a significantly increased risk of CRC compared to those with AA homozygote. These findings strongly suggest that glucose metabolism related gene GLUT1, and its functional SNP, rs710218 might contribute to CRC susceptibility and prognosis, and the exact biological mechanism awaits further research.Colorectal cancer (CRC) ranks the third most commonly diagnosed cancer in males and the second in females worldwide. However, the functional and causal SNPs for CRC remain to be mined. Glucose transporter 1 (GLUT1), a pivotal rate-limiting element in the transport of glucose in malignancy cells, has been identified to be associated with many cancers. Here, we aim to explore the role of GLUT1 in the occurrence and prognosis of colorectal cancer in a Chinese population. We found that GLUT1 expression levels in CRC tumor tissues were significantly higher than those in the corresponding adjacent normal tissues, and Cox multivariate analysis demonstrated that the GLUT1 expression was an independent prognostic factor for CRC (HR = 2.11, 95% CI = 1.33–3.34, P=0.001). For a functional polymorphism of GLUT1 (rs710218), we found that individuals with TT genotype (OR = 1.68, 95% CI = 1.02-2.75, P = 0.041) or AT genotype (OR = 1.47, 95% CI = 1.09-1.99, P = 0.012) of rs710218 had a significantly increased risk of CRC compared to those with AA homozygote. These findings strongly suggest that glucose metabolism related gene GLUT1, and its functional SNP, rs710218 might contribute to CRC susceptibility and prognosis, and the exact biological mechanism awaits further research.

A Chinese Herbal Decoction, Huoxue Qingyi Decoction, Promotes Rehabilitation of Patients with Severe Acute Pancreatitis: A Retrospective Study

Severe acute pancreatitis (SAP) still remains an important surgical problem with high morbidity and mortality. The utilization of Traditional Chinese Medicine shows good prospects in therapy of SAP since it has advantages of more extensive pharmacological effects and fewer adverse effects. In this retrospective study, 38 patients received standardized treatment (control group) and 37 patients received Chinese herbal decoction, Huoxue Qingyi Decoction (HQD group), in addition to standard treatment for SAP. We found that the HQD group had a shorter hospital stay and lower initial expense than the control group (P < 0.05). The duration of hyperamylasemia and systemic inflammatory response syndrome (SIRS) were significantly shorter in HQD group (P < 0.05). The percentage of patients having any complication was much lower in HQD group than control group (27/38 versus 17/37, P < 0.05), especially pancreatic pseudocyst (10/38 versus 2/37, P < 0.05). No adverse effect induced by HQD was found. We concluded that the HQD was effective, safe, and economic for reduction of complication, for early recovery from systemic inflammation, and for promoting earlier rehabilitation from SAP.

Prognostic value of serum cholinesterase activities in sepsis patients.

BACKGROUND/AIMS This study aims to explore the prognostic value of Serum cholinesterase (SchE) activity in patients with sepsis. METHODOLOGY The evaluation variable of APACHE II score was assessed and the SchE concentrations were determined in 359 patients immediately upon admission and 24 hours after admission. All patients were divided into two groups based on their prognosis. The relationships of SchE concentration and APACHE II score with prognosis were analyzed. RESULTS The SchE activity was significantly higher (p <0.01) and the APACHE II score was significantly lower (p <0.01) in survivors than in non-survivors. The areas under the receiver operating characteristic curve (AUC) were more than 0.9 for both the loss of SchE activity (delta SchE) and the loss of APACHE II score (delta APACHE II) during 24 h in patients admitted 24 h after onset (D1). The AUC for SchE activity and APACHE II were similar in most groups except hepatobiliary infection group. CONCLUSIONS The SchE activity and APACHE II score were useful for prognosis of septic patients. Although SchE activity was not as powerful as APACHE II in the prognosis of sepsis, dynamic monitoring of SchE and APACHE II had similar value in outcome prediction.

Prophylactic adjuvant hepatic arterial infusion chemotherapy reduced hepatic metastases from Stage III colorectal cancer after curative resection.

BACKGROUND/AIMS This study aims to investigate the safety and efficacy of hepatic arterial infusion chemotherapy (HAIC) on liver metastases of Stage III colorectal cancer patients after curative resection. METHODOLOGY We randomly assigned 287 Stage III colorectal cancer patients after curative resection between 2002 and 2008 to receive 2 cycles of HAIC plus 4 cycles of systemic chemotherapy (combined therapy) or 6 cycles of systemic chemotherapy alone (monotherapy). Both the HAIC and systemic chemotherapy regimen consisted of a 2-hour infusion of Oxaliplatin (85mg/m2) on day 1 followed by folinic acid 200mg/m2 as a 2-hour infusion on days 2 and 3 and by 5-fluorouracil 2400mg/m2 as a 48-hour infusion on days 2 and 3. The treatment repeated every 4 weeks. The disease-free survival, overall survival and liver metastases-free survival were compared. RESULTS There was no significant difference in adverse effects between two groups. Significant differences were found in 3-year disease-free survival (Combined therapy, 75.00%; Monotherapy, 63.27%; p=0.0035), overall survival (Combined therapy, 84.29%; Monotherapy, 65.31%; p=0.0006) and liver metastases-free survival (Combined therapy, 80.00%; Monotherapy, 69.39%; p=0.0451). CONCLUSIONS HAIC effectively and safely prevents metachronous liver metastases and improves the prognosis of patients with Stage III colorectal cancer after curative resection.

WP1130 attenuates cisplatin resistance by decreasing P53 expression in non–small cell lung carcinomas

Cisplatin-based combination chemotherapy significantly improves the survival outcomes in non–small cell lung carcinomas (NSCLCs), but drug resistance commonly contributes to disease progression and relapse. Recently, accumulating evidence has indicated that deubiquitinases (DUBs) are involved in regulating tumor cell proliferation, apoptosis, and chemoresistance. We designed this study to investigate the role of WP1130, a DUB inhibitor, in regulating cisplatin cytotoxicity in NSCLCs. After being combined with WP1130, cisplatin sensitivity was significantly increased in A549 and HCC827 cells with decreased p53 expression, inhibiting their proliferation, but not in p53-deficient NCI-H1299 cells. The synergistic cytotoxicity of the cisplatin and WP1130 co-treatment was abolished in p53-knockdown cells. Western blotting verified the decreased p53 expression in A549 and HCC827 cells treated with cisplatin and WP1130. The administration of MG132, a proteasome inhibitor, or knockdown of ubiquitin-specific peptidase 9, X-linked (USP9X) both eliminated the effect of WP1130 in decreasing p53 expression. Taken together, our findings confirm that the inclusion of WP1130 is potentially contributes to better therapeutic effects of cisplatin-based chemotherapy of NSCLCs in a manner dependent on the USP9X–p53 ubiquitination–mediated degradation pathway.

Prolonged adjuvant capecitabine chemotherapy improved survival of stage IIIA gastric cancer after D2 gastrectomy

GOALS This study aims to investigate the safety and efficacy of prolonged adjuvant capecitabine chemotherapy on survival of gastric cancer after D2 gastrectomy. BACKGROUND Inadequate evidence is available on optimal duration of chemotherapy and the number of administered cycles is generally based on patient responsiveness and individual tolerability as well as physician preferences. STUDY We randomly assigned 307 gastric cancer patients after D2 gastrectomy between January 2006 and December 2010 to XELOX group and Prolonged group. XELOX consisted of a 2-h intravenous infusion of oxaliplatin 130mg/mg on day 1 and oral capecitabine 1000mg/m(2) twice daily on days 1-14 of a 3-week cycle for eight cycles in half a year. In Prolonged group, patients underwent extra oral capecitabine 1000mg/m(2) twice daily on days 1-14 of a 3-week cycle for eight cycles after eight cycles of XELOX. The disease-free survival and overall survival were compared. RESULTS Significant differences were found in 3-year disease-free survival (Prolonged group 56.6%, XELOX group 48.4%, P=0.0357). Subgroup analysis by TNM staging showed that patients with stage IIIA gastric cancer in the Prolonged group had significantly higher DFS (50.00% vs 40.96, P=0.0178) and OS (71.95% vs 57.83, P=0.0230) than that of patients in the XELOX group. No grade 4 adverse effects or treatment-related deaths were reported. More patients in the Prolonged group experienced hand-foot syndrome than in the XELOX group. CONCLUSIONS Prolonged capecitabine chemotherapy prevents improves the prognosis of patients with stage IIIA gastric cancer after D2 gastrectomy.