Efficacy and Safety of Additional S-1 Chemotherapy to S-1 Plus Oxaliplatin Regimen Chemotherapy for Stage III Gastric Carcinoma after Radical Resection.

OBJECTIVE: To investigate the efficacy and safety of additional S-1 chemotherapy to S-1 plus oxaliplatin (SOX) regimen chemotherapy for Stage III gastric carcinoma (GC) after radical resection. PATIENTS AND METHODS: A total of 161 patients who were pathologically diagnosed as Stage III GC after D2 gastrectomy and received SOX regimen adjuvant chemotherapy between January 2012 and April 2016 were included in this retrospective study. SOX regimen postoperative chemotherapy was composed of Oxaliplatin and S-1, administrated every 3 weeks for 8 scheduled courses. After SOX chemotherapy, 76 patients preferred additional chemotherapy with S-1 (the ACT group), while additional S-1 chemotherapy was not given to the other 85 patients (control group). The ACT with S-1 was administrated every 3 weeks for 8 scheduled courses. Treatment was terminated in case of life-threatening adverse events or tumor progression, or patients' demand for termination. Progression-free survival (PFS), overall survival (OS), and adverse events were analyzed. RESULTS: ACT group obtained markedly improved 3-year PFS [p = 0.04; hazard ratio (HR) for disease progression, 0.58; 95% confidence interval (CI), 0.34-0.98] and OS than the control group (p = 0.0469; HR for death, 0.56; 95% CI, 0.32-0.99). No chemotherapy-related mortality occurred. Patients of the ACT group suffered more common and severer hand-foot syndrome (HFS) (p = 0.02). CONCLUSIONS: Additional S-1 chemotherapy may be helpful for improving the disease progression and survival for patients with Stage III GC after radical resection with an acceptable safety profile.

Prolonged Capecitabine Chemotherapy Following Capecitabine and Oxaliplatin (CAPOX) Regimen Chemotherapy Failed to Improve Survival of Stage III Colorectal Cancer After Radical Resection.

BACKGROUND Colorectal cancer (CRC) is considered to be a worldwide health problem because of its increasing incidence and prevalence. Surgery offers an opportunity for cure, but the postoperative recurrence rate is still high despite the advancement of chemotherapy. This study aimed to assess the efficacy and safety of prolonged capecitabine chemotherapy following CAPOX chemotherapy for stage III  CRC after radical surgery. MATERIAL AND METHODS This study included 212 patients with stage III CRC undergoing open radical surgery from July 2010 to June 2015. Among those patients, 104 patients received prolonged capecitabine chemotherapy (prolonged group) following 8 cycles of CAPOX regimen chemotherapy, while the other 108 patients (control group) received no prolonged chemotherapy. The prolonged chemotherapy consisted of capecitabine (1000 mg/m² per day for 2 weeks) and was repeated every 3 weeks for 8 cycles at most. Long-term survival and toxicities were retrospectively compared. RESULTS Patient characteristics did not differ between the 2 groups. For all patients, no significant difference was found in the 3-year disease-free survival (DFS) (P=0.7775) or 3-year overall survival (OS) rates between the 2 groups (P=0.5787). The prolonged group had significantly higher frequency of hand-foot syndrome (P=0.0267) and paresthesia (P=0.0164). In further subgroup analyses, no benefit for 3-year DFS or 3-year OS of prolonged capecitabine chemotherapy was found in colon cancer or rectal cancer. CONCLUSIONS Prolonged capecitabine chemotherapy following CAPOX regimen chemotherapy failed to improve the survival of patients with stage III CRC after radical surgery.

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.

Early Enteral Nutrition Versus Parenteral Nutrition After Resection of Esophageal Cancer: a Retrospective Analysis.

This study aimed to compare the clinical outcomes and hospitalization cost between early enteral nutrition (EEN) and parenteral nutrition (PN) after resection of esophageal cancer. A total of 79 patients with esophageal cancer who underwent surgical treatment in our hospital from July 2010 to July 2013 were enrolled in this study. They were divided into EEN group (n = 39) and PN group (n = 40) based on the nutrition support modes. The clinical factors such as time to first fecal passage, postoperative albumin infusion, differences of serum albumin value, hospital stay, systematic inflammatory response syndrome (SIRS) duration, complications, initial hospitalization cost, and mortality were retrospectively compared. The EEN group had a significantly shorter hospital stay, lower initial hospitalization cost, earlier first fecal passage, and shorter duration of SIRS than PN group (P < 0.05). The dose of albumin infusion was significantly smaller in EEN group (P < 0.05) and the decreased value of serum albumin (Δalb) was more prominent in PN group compared with EEN group (P < 0.05). The percentage of patients having any postoperative complication was much higher in PN group than EEN group (P < 0.05), but there was no significant difference in in-hospital morbidity between two groups. Pneumonia was found significantly more frequent in PN group compared with EEN group (P < 0.05). Early EN started within 48 h after esophagectomy is safe, economic, and superior for reduction of postoperative complication, for promoting early recovery of intestinal movement, and for early recovery from systemic inflammation.

Chinese herbal medicine, Jianpi Ligan decoction, improves prognosis of unresectable hepatocellular carcinoma after transarterial chemoembolization: a retrospective study.

OBJECTIVE: This study aimed to investigate the efficacy of Jianpi Ligan decoction (JLD) as an adjuvant therapy for patients with unresectable hepatocellular carcinoma (HCC) treated by transarterial chemoembolization (TACE). METHODS: From March 2007 to March 2013, 103 patients with unresectable HCC who underwent TACE in our center were included in this retrospective study. Among the 103 patients, 53 patients accepted JLD along with TACE (JLD group) and 50 patients accepted TACE alone (control group). Indices including complication, toxicity, treatment success rate, and long-term survival were obtained for analysis and comparison. RESULTS: There was no significant difference in patient characteristics between the two groups. No procedure-related deaths or encephalopathy occurred. Fewer patients from the JLD group experienced constipation (7/53 vs 15/50, P=0.0377), abdominal bloating (5/53 vs 12/50, P=0.0466), and lack of appetite (35/53 vs 42/50, P=0.0360). The JLD group had lesser and lighter hepatic toxicity (P=0.0265) and gastrointestinal toxicity (P=0.0445) such as nausea and vomiting. The JLD group had a significantly higher treatment success rate than the control group (51/53 vs 40/50, P=0.0103). Three-year overall survival probability was significantly higher in the JLD group than in the control group (37.74% vs 26.00%; hazard ratio [HR] 0.6171; 95% confidence interval [CI], 0.3832-0.9938; P=0.0365 by log-rank test). No significant difference was found in 3-year overall survival probability (39.22% vs 32.50%; HR, 0.7449; 95% CI, 0.4398-1.2614; P=0.2491 by log-rank test) or 3-year intrahepatic recurrence-free survival probability in patients who achieved treatment success (37.25% vs 30.00%; HR, 0.7280; 95% CI, 0.4332-1.2233; P=0.2087 by log-rank test) between the two groups. CONCLUSION: Application of JLD was effective for reduction of side effects and improvement of long-term survival for patients with unresectable HCC treated by TACE.

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.

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.

Prophylactic hepatic artery infusion chemotherapy improved survival after curative resection in patients with hepatocellular carcinoma.

BACKGROUND/AIMS: To explore the effect of prophylactic hepatic artery infusion chemotherapy (HAIC) on survival probability after curative resection in patients with hepatocellular carcinoma (HCC). METHODOLOGY: 85 patients with HCC were randomly assigned to HAIC group (42 cases) and control group (43 patients), all the database of two groups had no significant difference. Patients in HAIC groups underwent hepatic artery infusion chemotherapy (5-FU 1000 mg/m2 on day 1, Oxaliplatin 85 mg/m2 on day 1 and Gemcitabine 1000 mg/m2 on day 1 and 8) starting 3 weeks after operation with intervals of 4 weeks. All patients were followed up for 3 years and intrahepatic recurrence-free survival, disease-free survival rate and overall survival rate were recorded. RESULTS: Intrahepatic recurrence rate of HAIC group and the control group was respectively 19.05% and 39.53%, P < 0.05. Disease-free survival rate was respectively 57.14% and 44.19%, P < 0.05. Overall survival rate was 66.67% and 46.51%, P < 0.05. All patients in HAIC group tolerated the therapy. No adverse effect above grade 3 was reported in HAIC group. CONCLUSION: HAIC effectively and safely prevents intrahepatic recurrence and improves the prognosis of patients with HCC after curative resection.

Hepatic arterial infusion chemotherapy reduced hepatic metastases from pancreatic cancer after pancreatectomy.

BACKGROUND/AIMS: This study aims to investigate the safety and efficacy of hepatic arterial infusion chemotherapy (HAIC) on liver metastases from pancreatic cancer after pancreatectomy. METHODOLOGY: We randomly assigned 106 patients with pancreatic cancer after pancreatectomy between 2005 and 2010 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 5-hour infusion of 5-fluorouracil 1000 mg/m2 on day 1 followed by gemcitabine 800 mg/m2 as an over 30-min infusion on day 1 and day 8. The treatment was started on an average of 21.2 days after surgery and 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 overall survival (Combined Therapy, 23.08 %; Monotherapy, 14.81%; P=0.0473) and liver metastases-free survival (Combined Therapy, 80.77%; Monotherapy, 55.56%; P=0.0014). CONCLUSIONS: HAIC effectively and safely prevents liver metastases and improves the prognosis of patients with pancreatic cancer after pancreatectomy.

Optimal selection of methods for mini-invasive treatment of extrahepatic bile duct stones.

BACKGROUND/AIMS: This study aims to identify the optimal mini-invasive treatment for extrahepatic bile duct stones. METHODOLOGY: One hundred and seventy eight patients with EHBD stones were randomized into 4 groups: laparoscopic cholecystectomy (LC) and laparoscopic common bile duct exploration (LCBDE) plus T-tube drainage (group LT), LC and LCBDE with endonasobiliary drainage (ENBD) tube (group LE), and endoscopic sphincterotomy with ENBD followed by LC (group EE) and T-tube drainage of open CBDE (group OT). Demographic data, perioperative findings, postoperative outcomes, hospital expense, gastrointestinal quality of life index (GIQLI) scores and cost per quality-adjusted life year (QALY) were analyzed. RESULTS: The operating time was longest in group EE. There was less bleeding in group OT and EE. Group LE and EE had shorter hospital stay and recovery time of intestinal motility. The postoperative white blood cell count and serum C-reaction protein level were higher in group LT and OT. Postoperatively, the mean GIQLI scores in group LE and EE were higher. Mean cost were highest in group EE. Patients in group LE had lowest cost per QALY. CONCLUSIONS: The modified laparoscopic procedure, LC combined with LCBDE followed by a primary closure over the ENBD tubes, appears to be the best option for patients with EHBD stones.

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.

Endoscopic Biliary Stenting Versus Percutaneous Transhepatic Biliary Stenting in Advanced Malignant Biliary Obstruction: Cost-effectiveness Analysis.

BACKGROUND/AIMS: This study aims to compare the clinical outcomes and costs between endoscopic biliary stenting (EBS) and percutaneous transhepatic biliary stenting (PTBS). METHODOLOGY: We randomly assigned 112 patients with unresectable malignant biliary obstruction 2006 and 2011 to receive EBS or PTBS with self-expandable metal stent (SEMS) as palliative treatment. PTBS was successfully performed in 55 patients who formed the PTBS group (failed in 2 patients). EBS was successfully performed in 52 patients who formed the EBS group (failed in 3 patients). The effectiveness of biliary drainage, hospital stay, complications, cost, survival time and mortality were compared. RESULTS: Patients in PTBS group had shorter hospital stay and lower initial and overall expense than the BBS group (P < 0.05). There was no significant difference in effectiveness of biliary drainage (P = 0.9357) or survival time between two groups (P = 0.6733). Early complications occurred in PTBS group was significantly lower than in EBS group (3/55 vs 11/52, P = 0.0343). Late complications in the EBS group did not differ significantly from PTBS group (7/55 vs 9/52, P = 0.6922). The survival curves in the two groups showed no significant difference (P = 0.5294). Conclusions: 3.

Hematological benefits after spleen-preserving distal pancreatectomy: perioperative and long-term outcome analysis.

BACKGROUND/AIMS: Despite the emphasis on its role, the spleen has commonly been removed in distal pancreatectomy. We designed this study to evaluate the efficacy of spleen salvage during distal pancreatectomy for patients with benign and borderline malignant tumors. METHODOLOGY: 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: The demographics and final diagnoses were similar between the two groups. There were no significant differences in estimated blood loss, intraoperative transfusion and operative time between the two groups. More perioperative complications occurred in DPS group than in the SPDP group (p = 0.0344). Consequently, postoperative hospital stay was significantly shorter in SPDP group than in DPS group (p = 0.0273). 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, DPS appeared to result in severer hematological abnormalities. Even an effort to preserve adult spleen in distal pancreatectomy is worthwhile.

Spleen-preserving distal pancreatectomy: perioperative and long-term outcome analysis.

BACKGROUND/AIMS: Despite the emphasis on its role, the spleen has commonly been removed in distal pancreatectomy. We aimed to evaluate the efficacy of spleen salvage during distal pancreatectomy for patients with benign and borderline malignant tumors. METHODOLOGY: 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 two groups. More perioperative complications occurred in DPS group than in the SPDP group (p = 0.0344). Consequently, postoperative hospital stay was significantly shorter in SPDP group than in DPS group (p = 0.0273). On 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 poorer health condition (p = 0.0371). Less newly developed (p = 0.0193) and aggravated diabetes mellitus (p = 0.0361) were also observed in SPDP group. CONCLUSIONS: In addition to frequent higher-grade complications, and prolonged hospital stays, DPS appeared to result in poorer health condition based on follow-up survey. Even an effort to preserve adult spleen in distal pancreatectomy is worthwhile.

Percutaneous transhepatic biliary stenting vs. surgical bypass in advanced malignant biliary obstruction: cost- effectiveness analysis.

BACKGROUND/AIMS: This study aims to compare the clinical outcomes and costs between percutaneous transhepatic biliary stenting (PTBS) and surgical bypass. METHODOLOGY: We randomly assigned 142 patients with unresectable malignant biliary obstruction between 2005 and 2010 to receive PTBS or surgical bypass as palliative treatment. PTBS was successfully performed in 70 patients who formed the PTBS group (failed in 7 patients). Sixty five patients underwent surgical bypass treatment. Additional gastrojejunostomy was performed in five patients. The effectiveness of biliary drainage, hospital stay, complications, cost, survival time and mortality were compared. RESULTS: Patients in PTBS group had shorter hospital stay and lower initial and overall expense than the surgical group (p<0.05). There was no significant difference in effectiveness of biliary drainage (p=0.9307) or survival time between two groups (p=0.4826). Early complications of PTBS group was significantly lower than surgical group (3/75 vs. 11/65, p=0.0342). Late complication in PTBS group did not differ significantly from surgical group (9/70 vs. 6/65, p=0.6823). The survival curves in the two groups showed no significant difference (p=0.1032). CONCLUSIONS: PTBD is a better palliative treatment than surgical bypass for unresectable malignant biliary obstruction for its high effectiveness of biliary drainage and acceptable expense and complication.

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.

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.

Delayed administration of D-Ala2-D-Leu5-enkephalin, a delta-opioid receptor agonist, improves survival in a rat model of sepsis.

Sepsis is the major cause of death in intensive care units, despite enormous efforts in the development of antimicrobial therapies. Sepsis is mediated by early [e.g., tumor necrosis factor (TNF)-α and interleukin (IL)-1ß] and late [e.g., high-mobility group box 1 protein (HMGB1)] proinflammatory cytokines. HMGB1, which is secreted into extracellular milieu by activated macrophages or passively released by destroyed macrophages, stimulates intensive inflammatory responses. D-Ala2-D-Leu5-enkephalin (DADLE), a synthetic δ-opioid receptor agonist, has been shown to protect rats from sepsis. Here we elucidated the mechanism for protective effect of DADLE against sepsis. Sepsis was established in Sprague-Dawley rats by means of cecal ligation and puncture (CLP). In this model, the serum levels of TNF-α and IL-1ß were increased after 2-3 h, while those of HMGB1 were increased after 18 h. Administration of DADLE (5 mg/kg) concurrently with CLP improved survival, which was associated with the decreases in the serum levels of TNF-α, IL-1ß and HMGB1. Importantly, DADLE administrated 4 h after CLP showed comparable protective effect as the concurrent administration, with decreased serum HMGB1 levels. Moreover, peritoneal macrophages isolated from rats were challenged with lipopolysaccharide (LPS). Concurrent or delayed DADLE administration at 10(-6) M suppressed the LPS-induced cell death. DADLE also suppressed the release of HMGB1 from macrophages that was induced by LPS, TNF-α or interferon-γ. In conclusion, DADLE protects rats from sepsis probably by decreasing the serum level of HMGB1. We propose DADLE as a candidate for septic shock therapy, even if it is administered after the onset of sepsis.

[Dual regulation effect of somatostatin on immunity in patients with severe sepsis caused by abdominal diseases].

OBJECTIVE: to investigate the effect of somatostatin on inflammatory immune disorders and prognosis in patients with severe sepsis caused by abdominal diseases. METHODS: fifty-three patients with severe abdominal sepsis (age > 18 years, APACHE-II score > 15) from June 2005 to June 2009 were randomly divided into Somatostatin group (n = 23) and SSC Group (n = 30). Fifteen healthy volunteers of the same age range were chosen as Control group. The SSC group was treated with classical SSC therapy, and the Somatostatin Group was treated with the same regime plus 14-peptide somatostatin continuous infusion at the dose of 6 mg/24 h for 7 days. The serum levels of interleukin-10 (IL-10), tumor necrosis factor-α (TNF-α) were determined by using ELISA. CD(4)(+), CD(8)(+) T cell subsets were determined by fluorescence activated cell sorter(FACS) and CD(4)(+)/CD(8)(+) was calculated. APACHE-II score was observed on admission (d1) and day 3, 7 and 14 after treatment. Morality rates in 28 days in two groups were recorded. RESULTS: compared with Control group, IL-10 and TNF-α levels were significantly elevated in patients with severe abdominal sepsis (P < 0.05), while CD(4)(+), CD(8)(+) T cell and CD(4)(+)/CD(8)(+) decreased significantly (P < 0.05). Compared with the Somatostatin group CD(4)(+), CD(8)(+) T cell and CD(4)(+)/CD(8)(+) on d7 and d14 in SSC Group were significantly increased (P < 0.05), while IL-10 and TNF-α decreased significantly(P < 0.05). APACHE-II scores on d3, d7, d14 of Somatostatin group were significantly lower than those of SSC group, and 28 d mortality rate also declined. CONCLUSIONS: in patients with severe abdominal sepsis, systemic inflammatory response and immune suppression exist simultaneously. Somatostatin has a dual immunomodulatory activity in these patients.