BACKGROUND: LY01005 (Goserelin acetate sustained-release microsphere injection) is a modified gonadotropin-releasing hormone (GnRH) agonist injected monthly. This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer. METHODS: We conducted a randomized controlled, open-label, non-inferiority trial across 49 sites in China. This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections. The primary efficacy endpoints were the percentage of patients with testosterone suppression ≤50 ng/dL at day 29 and the cumulative probability of testosterone ≤50 ng/dL from day 29 to 85. Non-inferiority was prespecified at a margin of -10%. Secondary endpoints included significant castration (≤20 ng/dL), testosterone surge within 72 h following repeated dosing, and changes in luteinizing hormone, follicle-stimulating hormone, and prostate specific antigen levels. RESULTS: On day 29, in the LY01005 and goserelin implant groups, testosterone concentrations fell below medical-castration levels in 99.3% (142/143) and 100% (140/140) of patients, respectively, with a difference of -0.7% (95% confidence interval [CI], -3.9% to 2.0%) between the two groups. The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3% and 97.8%, respectively, with a between-group difference of 1.5% (95% CI, -1.3% to 4.4%). Both results met the criterion for non-inferiority. Secondary endpoints were similar between groups. Both treatments were well-tolerated. LY01005 was associated with fewer injection-site reactions than the goserelin implant (0% vs . 1.4% [2/145]). CONCLUSION: LY01005 is as effective as goserelin implants in reducing testosterone to castration levels, with a similar safety profile. TRIAL REGISTRATION ClinicalTrials.gov, NCT04563936.
Humans ; Male ; Antineoplastic Agents, Hormonal/therapeutic use* ; East Asian People ; Gonadotropin-Releasing Hormone/agonists* ; Goserelin/therapeutic use* ; Prostate-Specific Antigen ; Prostatic Neoplasms/drug therapy* ; Testosterone

Objective: To analyse of risk factors for early complications after pancreaticoduodenectomy. Methods: Retrospective analysis of 280 cases of pancreaticoduodenectomy in the First Affiliated Hospital, Sun Yat-sen University from January 1999 to October 2009, including 175 males and 105 females; the average age was 57 years, the range is 19 to 81 years old. Observe the perioperative condition and postoperative complications of the patient. Logistic regression analysis was used to analyze risk factors associated with early postoperative complications. Results: Among the 280 patients, 81.1% had preoperative jaundice with obstructive jaundice, the median operation time was 5.5 h. the intraoperative blood loss was (558.0±35.0) ml, 16 patients underwent multiple organ resection. The total postoperative complications was 31.1%. Common postoperative complications were abdominal infection/abscess (10.4%), hemorrhage (7.1%), and pancreatic fistula (2.1%). The pancreaticoenterostomy was mainly performed with a nested end-to-end anastomosis (87.1%) and a bundled pancreaticojejunostomy (7.9%). Logistic regression analysis showed that age, comorbidity, jaundice, preoperative yellowing, pancreatic texture, pancreatic duct placement, prophylactic application of somatostatin, combined organ resection and pancreaticojejunostomy were not predictor of major postoperative complications. Conclusions The incidence of early abdominal complication after pancreaticoduodenectomy is high. There is no significant correlation between the common risk factors in perioperative period and the occurrence of serious complications in the early postoperative period.

PURPOSE: Various inflammation-based prognostic biomarkers such as the platelet to lymphocyte ratio and neutrophil to lymphocyte ratio, are related to poor survival in patients with intrahepatic cholangiocarcinoma (ICC). This study aims to investigate the prognostic value of the aspartate aminotransferase to neutrophil ratio index (ANRI) in ICC after hepatic resection. MATERIALS AND METHODS: Data of 184 patients with ICC after hepatectomy were retrospectively reviewed. The cut-off value of ANRI was determined by a receiver operating characteristic curve. Preoperative ANRI and clinicopathological variables were analyzed. The predictive value of preoperative ANRI for prognosis of ICC was identified by univariate and multivariate analyses. RESULTS: The optimal cut-off value of ANRI was 6.7. ANRI was associated with tumor size, tumor recurrence, white blood cell, neutrophil count, aspartate aminotransferase, and alanine transaminase. Univariate analysis showed that ANRI, sex, tumor number, tumor size, tumor differentiation, lymph node metastasis, resection margin, clinical TNM stage, neutrophil count, and carcinoembryonic antigen were markedly correlated with overall survival (OS) and disease-free survival (DFS) in patients with ICC. Multivariable analyses revealed that ANRI, a tumor size > 6 cm, poor tumor differentiation, and an R1 resection margin were independent prognostic factors for both OS and DFS. Additionally, preoperative ANRI also had a significant value to predict prognosis in various subgroups of ICC, including serum hepatitis B surface antigen‒negative and preoperative elevated carbohydrate antigen 19-9 patients. CONCLUSION: Preoperative declined ANRI is a noninvasive, simple, and effective predictor of poor prognosis in patients with ICC after hepatectomy.
Alanine Transaminase ; Aspartate Aminotransferases* ; Aspartic Acid* ; Biomarkers ; Blood Platelets ; Carcinoembryonic Antigen ; Cholangiocarcinoma* ; Disease-Free Survival ; Hepatectomy* ; Hepatitis B ; Humans ; Leukocytes ; Lymph Nodes ; Lymphocytes ; Multivariate Analysis ; Neoplasm Metastasis ; Neutrophils* ; Prognosis* ; Recurrence ; Retrospective Studies ; ROC Curve

Objective To compare the prognosis prediction value of the 8th edition with the 7th edition of the American Joint Committee on Cancer Staging System in patients with resectable hepatocellular carcinoma (HCC).Methods A total of 311 HCC patients after hepatectomy were retrospectively analysed.Patients were staged according to both the 7th edition (TNM-7) and 8th edition (TNM-8) AJCC TNM staging criteria.The survival rates were estimated using Kaplan-Meier methods.Multivariate analysis was assessed by Cox proportional hazards regression analysis.The predictive ability of staging systems was evaluated by receiver operating characteristic curve (ROC) and area under curve (AUC).Results When stratified according to the TNM-7 system,the overall survival(OS) of stage T1 was higher than that of stage T2,stage T2 higher than stage T3a,however,the 5-year OS rates of stage T4 (16.7％) was higher than those of stage T3a (14.3％) and T3b(10.9％).The difference in survival was significant between stages T1 and stage T3a,T3b,T4 (all P ＜0.05),and that between stages T2 and stage T3b,T4 (all P ＜0.05).When stratified according to the TNM-8 system,the survival rates decreased as the T stage going high.OS rates vary significantly between stagesT1a and stageT3,T4 (P =0.004,0.001),between stage T1b and stage T3,T4 (both P ＜ 0.001),and between stage T2 and stage T4 (P =0.009).The difference in disease free survival (DFS) rates was significant between stages T1a,T1b,T2 and stage T3,T4 (all P ＜0.01).Finally,the area under ROC of TNM-8 is bigger than that of TNM-7.Conclusions Compared with TNM-7 staging,new TNM-8 staging can predict more accurately the prognosis of patients with resectable hepatocellular carcinoma.

[ ABSTRACT] AIM:To investigate the effects of microRNA145 ( miRNA145 ) on the viability, apoptosis, inva-sion and metastasis of hepatoma HepG2 cells.METHODS: HepG2 cells were randomly allocated into 3 groups: blank control group, empty mimic transfected group and miRNA145 mimic transfected group.Under the induction of Lipofectami-neTM 2000, the recombinant was transfected into HepG2 cells.After transfection, the expression level of miRNA145 was detected by real-time PCR.The protein level of N-cadherin and the mRNA expression levels of miRNA145 and N-cadherin were detected by Western blot and real-time PCR.The cell viability was detected by MTS assay.The cell cycle and apopto-sis were analyzed by flow cytometry.Invasion and metastasis were detected by Transwell assay.RESULTS:Compared with negative control, miRNA145 expression was up-regulated significantly, while the expression of N-cadherin was down-regu-lated significantly.Meanwhile, the cell viability, cell cycle, apoptosis, invasion and metastasis of hepatoma HepG2 cells were all significantly inhibited (P<0.05).CONCLUSION:miRNA145 dramatically inhibits viability, apoptosis, inva-sion and metastasis of hepatoma cells.

Objective To investigate the application value of precise hepatectomy in huge hepatocellular carcinoma (HCC). Methods The objects of this prospective study were 110 patients with huge HCC undergoing precise hepatectomy in the First Afifliated Hospital of Sun Yat-sen University from May 2009 to May 2013. There were 92 males and 18 females with the age ranging from 26 to 75 years old and a median age of 48 years old. The range of tumor diameter was 10-21 cm. The informed consents of all patients were obtained and local ethical committee approval had been received. All patients underwent thin-slice computer tomography (CT) scan. The livers, tumors and vessels were three-dimensionally reconstructed using Myrian XP Liver surgery simulation software with the original data of thin-slice CT scan. The standard remnant liver volume (SRLV) was calculated, and the simulated operation was performed. Hepatectomy after conventional dissecting of the liver or hepatectomy with presetting hanging band in front of inferior vena cava through anterior approach were performed. The accordance rate of preoperative simulated operation plan and the actual performed intraoperative operation plan was observed. The difference between the predicted SRLV before operation and the actual measured SRLV was compared. The operative time, intraoperative blood loss, blood transfusion, length of hospital stay and complications were observed. The comparison of predicted SRLV and the actual measured SRLV was conducted using t test. Results The accordance rate of preoperative simulated operation plan and the actual intraoperative operation plan was 92.7%(102/110). The predicted SRLV before operation was (392±96) ml/m2, and the intraoperative actual measured SRLV was (406±71) ml/m2, where no significant difference was observed (t=-1.230, P>0.05). The median of operative time was 200 (150-375) min. The intraoperative blood loss was 500 (150-2 000) ml. The intraoperative blood transfusion was 300 (0-1 500) ml. The length of postoperative hospital stay was 11 (8-67) d. No perioperative death was observed. The incidence of postoperative complications was 20.0%(22/110). Eighteen cases suffered hepatic dysfunction and were cured by symptomatic treatments such as liver protection. Three cases suffered biliary leakage and were relieved by persistent catheter drainage. One case suffered abdominal bleeding and underwent the second surgery to stop bleeding. Conclusions Precise hepatectomy can help to better resect huge HCC, retain more residual liver volume, and reduce the incidence of postoperative hepatic dysfunction. It is an effective and safe method of treating huge HCC.

ObjectiveTo investigate the predictive value of preoperative indocyanine green retention rate at 15 min (ICGR15) combined with standard remnant liver volume (SRLV) to postoperative liver dysfunction after precise hepatectomy for huge hepatocellular carcinoma (HCC).MethodsA total of 110 patients with huge HCC undergoing precise hepatectomy at the First Afifliated Hospital of Sun Yat-sen University between May 2009 and May 2013 were enrolled in this prospective study. The informed consents of all patients were obtained and the local ethical committee approval had been received. Among the 110 patients, 92 were males and 18 were females with the age ranging from 26 to 75 years old and the median of 48 years old. The tumor size was from 10.1 to 20.5 cm. ICGR15 of all patients were detected and all underwent thin-slice computer tomography (CT) scan before hepatectomy. The livers, tumors and blood vessels of patients were three-dimensionally reconstructed by using the data of CT scan. The surgery was simulated and SRLV was calculated. All patients underwent precise hepatectomy. According to whether postoperative hepatic dysfunction developed, the patients were divided into two groups, the liver dysfunction group (n=18) and non-liver dysfunction group (n=92). The risk factors of postoperative liver dysfunction were analyzed by univariate analysis. The screened factors ICGR15 combined with SRLV were taken as diagnostic indicators for diagnostic tests to explore the best combination of sensitivity and specificity and regression equation for predicting postoperative liver dysfunction was calculated by logistic regression analysis.ResultsThe incidence of liver dysfunction for patients with HCC after precise hepatectomy was 16.4% (18/110). The occurrence of liver dysfunction was associated with the preoperative ICGR15 and SRLV (Z=2.805,t=4.365;P<0.05). When the preoperative ICGRl5 and SRLV taken as diagnostic indicators, the sensitivity was 0.78 and the speciifcity was 0.89. Its logistic linear regression equation was SRLV (ml/m2) = 1 104 × ICGR15 + 298.6. The regression equation may directly relfect the relationship between ICGR15 and SRLV and the regression line chart may better predict the occurrence of liver dysfunction after precise hepatectomy.Conclusion Preoperative ICGR15 combined with SRLV may efficiently predict the occurrence of postoperative liver dysfunction after precise hepatectomy for huge HCC.

ObjectiveTo investigate the value of preoperative prognostic nutritional index (PNI) in postoperative survival prognosis of hepatocellular carcinoma (HCC) patients.Methods Clinical data of 322 HCC patients undergoing radical resection in the First Affiliated Hospital of Sun Yat-sen University between January 2006 and December 2009 were retrospectively studied. Among the 322 patients, 286 were males and 36 were females with the age ranging from 21 to 79 years old and the median age of 51 years old. The informed consents of all patients were obtained and the local ethical committee approval had been received. PNI value was calculated according to the examination results 1 week before surgery, then the patients were divided into the high PNI group (n=253) and low PNI group (n=69). The relationship between PNI and postoperative survival time was observed, and the value of preoperative PNI in postoperative survival prognosis was analyzed. The survival analysis was conducted using Kaplan-Meier method and Log-rank test, and the multivariate analysis was conducted using Cox proportional hazards model.ResultsThe 1-, 3-, 5-year disease free survival rate was respectively 48.0%, 34.9% and 31.3% in high PNI group, and 33.3%, 15.8% and 11.7% in low PNI group. The disease free survival in high PNI group was significantly better than that in low PNI group (χ2=9.990,P<0.05). The 1-, 3-, 5-year overall survival rate was respectively 72.3%, 49.0% and 42.6% in high PNI group, and 65.2%, 36.2% and 25.9% in low PNI group. The overall survival in high PNI group was significantly better than that in low PNI group (χ2=8.172,P<0.05). The results of the multivariate analysis showed that AFP, tumor number, tumor diameter, portal vein tumor thrombus (PVTT) and PNI were the independent risk factors for disease free survival rate (HR=1.355, 0.783, 2.295, 1.920, 0.710;P<0.05), and tumor number, tumor diameter, PVTT and PNI were the independent risk factors for overall survival rate (HR=0.780, 2.340, 2.013, 0.653;P<0.05).ConclusionsPreoperative PNI is the independent risk factor for postoperative survival prognosis of HCC patients and can be used as the common index for predicting postoperative survival of HCC patients.

OBJECTIVETo study the concentrations and pharmacokinetics of 6 different kinds of antibiotics in rabbit bile, and evaluate their microbicidal potential.

METHODSThirty-six health rabbits were randomly divided into 6 groups, and each group was 6 rabbits. After anaesthesia, the common bile duct of rabbit was isolated and cumulated with a silicone tube. The rabbits were administered intravenously with the equal-effect dose of antibiotics. Bile (1.5 ml) was collected at different time points after administration, and the concentration of antibiotics of bile was assayed by high performance liquid chromatography. The bile drug concentration-time data were processed by software to figure out the pharmacokinetic parameters such as maximum concentration (C(max)), peak time (T(max)), half-life time (T(1/2)), clearance (CL) and apparent volume of distribution (VD). The bile antibiotics concentration contrasted to the minimum inhibitory concentration (MIC), and attained the bactericidal index (C(max)/MIC) and the time when the drug concentration exceeded the MIC (T(>MIC)).

RESULTSThe C(max) and T1/2 of each antibiotic were as the followings: piperacillin (7 950 ± 3 023) mg/L and (1.97 ± 1.23) h, ceftriaxone (1 104 ± 248) mg/L and (3.14 ± 0.57) h, cefoperazone (5 215 ± 2 225) mg/L and (0.89 ± 0.13) h, meropenem (31.97 ± 12.44) mg/L and (0.36 ± 0.11) h, levofloxacin (66.3 ± 36.9) mg/L and (3.32 ± 2.57) h, metronidazole (28.2 ± 10.2) mg/L and (0.81 ± 0.33) h, respectively. Piperacillin/tazobactam and cefoperazone/sulbactam had the largest bactericidal index and the longest T(>MIC), and their bactericidal indexes were (62.1 ± 23.6) - (993.8 ± 377.9) and (164.8 ± 69.0) - (659.3 ± 275.9), their T(>MIC) were (6.00 ± 2.53) - (8.00 ± 0.00) h and (6.33 ± 1.97) - (8.00 ± 0.00) h. The bactericidal index and T(>MIC) of levofloxacin were the smallest, which were (2.1 ± 1.2) - (8.3 ± 4.6) and (0.54 ± 0.25) - (2.67 ± 1.03) h . Ceftriaxone and meropenem were as the medium, and their bactericidal indexes and T(>MIC) were (4.3 ± 1.0) - (69.2 ± 15.5) , (1.42 ± 0.65) - (8.00 ± 0.00) h and (2.0 ± 0.8) - (1 031.3 ± 401.4) , (0.29 ± 0.10) - (1.83 ± 0.26) h. The bactericidal index of metronidazole to anaerobic ranged from 7.4 to 294.9, and the T(>MIC) ranged from 1.88 to 5.00 h.

CONCLUSIONSThe bile concentrations of six antibiotics all exceed their effective bactericidal concentrations. The concentration-time curves of piperacillin, cefoperazone, meropenem and metronidazole conformed to one-compartment model, and ceftriaxone and levofloxacin are conformed to two-compartment model. Piperacillin/tazobactam and cefoperazone/sulbactam have the largest bactericidal index and the longest T(>MIC), so they can be chosen as the first choice for the therapy of hepatobiliary infection.For the anaerobic, the microbicidal potential of metronidazole is high.

Animals ; Anti-Bacterial Agents ; analysis ; pharmacokinetics ; Bile ; chemistry ; drug effects ; Cefoperazone ; analysis ; pharmacokinetics ; Drug Combinations ; Metronidazole ; analysis ; pharmacokinetics ; Microbial Sensitivity Tests ; Penicillanic Acid ; analogs & derivatives ; analysis ; pharmacokinetics ; Piperacillin ; analysis ; pharmacokinetics ; Rabbits ; Random Allocation ; Sulbactam ; analysis ; pharmacokinetics ; Thienamycins ; analysis ; pharmacokinetics

Objective To investigate the risk factors for reoperation after pancreaticoduodenectomy (Whipple). Methods Clinical data of 339 patients who underwent Whipple in the First Afifliated Hospital of Sun Yat-sen University from January 2000 to December 2009 were analyzed retrospectively. The informed consents of all patients or relatives were obtained and the ethical committee approval was received. There were 206 males and 133 females with age ranging from 1 to 86 years old and the median age of 55 years old. According to whether the patients received reoperation after operation, they were divided into reoperation group (n=24) and non-reoperation group (n=315). The reoperation of patients and its risk factors were analyzed. The relations between reoperation and clinical parameters were analyzed using Chi-square test and the risk factors for reoperation were analyzed using Logistic regression analysis. Results The reoperation rate of patients was 7.1%(24/339). The main causes of reoperation included abdominal bleeding (n=8, 5 cases were complicated with pancreatic fistula), upper gastrointestinal bleeding (n=7, 2 cases were complicated with pancreatic ifstula), pancreatic ifstula complicated with abdominal infection (n=2), biliary leakage (n=1) and wound rupture (n=6). In 24 patients receiving reoperation, 9 cases were related with pancreatic ifstula. Four out of 5 death cases were with pancreatic ifstula. The reoperation was related to preoperative diabetes, intraoperative blood loss (χ2=5.588, 4.565;P<0.05). Preoperative diabetes, intraoperative blood loss>400 ml were independent risk factors for reoperation after Whipple (OR=5.80, 2.74; P<0.05). Conclusions The main causes of reoperation after Whipple are pancreatic ifstula and wound rupture. Preoperative diabetes, intraoperative blood loss>400 ml are independent risk factors for reoperation after Whipple.