ABSTRACT
Objective To establish a nomogram for overall survival rate after liver resection for primary small hepatocellular carcinoma based on SEER data and external validation of Chinese data. Methods The data of 1809 patients, registered in National Cancer Institute SEER database in 2004-2015, who underwent hepatectomy for primary small hepatocellular carcinoma were extracted as modeling group, and 158 patients with small hepatocellular carcinoma who underwent hepatectomy in Affiliated Hospital of North Sichuan Medical College from 2010 to 2017 were collected as validation group. The univariate Cox risk regression analysis, lasso regression analysis, and multivariate Cox hazard regression analysis were used to investigate the influencing factors for OS after hepatectomy in patients with small hepatocellular carcinoma. A nomogram was established based on the independent influencing factors for OS, and index of concordance (C-index), calibration curves, and receiver operating characteristic (ROC) curve were used to analyze the predictive ability of the nomogram. The Kaplan-Meier survival analysis and the log-rank test were used to investigate the difference in survival between the high- and low-risk groups. Results The multivariate Cox hazard regression analysis showed that sex (hazard ratio [ HR ]=1.22, 95% confidence interval [ CI ]: 1.05-1.41, P =0.010), Seer stage ( HR =1.51, 95% CI : 1.23-1.85, P < 0.001; HR =10.31, 95% CI : 2.53-42.04, P =0.001), tumor diameter ( HR =1.22, 95% CI : 1.06-1.39, P =0.004), vascular invasion or metastasis ( HR =1.43, 95% CI : 1.24-1.65, P < 0.001), and alpha-fetoprotein ( HR =1.33, 95% CI : 1.16-1.54, P < 0.001) were independent risk factors for OS after hepatectomy for small hepatocellular carcinoma. The modeling group had a C-index of 0.621, and its area under the ROC curve at 1, 2, and 3 years was 0.666(95% CI 0.628-0.704), 0.678(95% CI 0.647-0.708), and 0.663(95% CI : 0.635-0.690), respectively; the validation group had a C-index of 0.718, and its area under the ROC curve at 1, 2, and 3 years was 0.695(95% CI : 0.593-0.797), 0.781(95% CI : 0.706-0.856), and 0.759(95% CI 0.669-0.848), respectively. Risk stratification was performed based on the nomogram, and the Kaplan-Meier survival analysis showed that for both the modeling group and the validation group, the low-risk group had a significantly better prognosis than the high-risk group ( P < 0.01). Conclusion The model established for survival rate after liver resection for primary small hepatocellular carcinoma can predict the 1-, 2-, and 3-year OS rates and can thus be used in clinical practice in China.
ABSTRACT
Objective:To explore the effects of Ophiopogon D combined with cyclooxygenase-2 (COX-2) gene silencing on the proliferation, migration and invasion of human pancreatic cancer BxPC-3 cells.Methods:BxPC-3 cells were divided into blank control group, Ophiopogonin D high-dose group (40 μmol/L), medium-dose group (20 μmol/L) and low-dose group (10 μmol/L). The COX-2-slienced cells were divided into control group, COX-2 inhibited group (50 pmol/ml siRNA-COX-2), Ophiopogonin D group (20 μmol/L) and combination treatment group (Ophiopogonin D 20 μmol/L+ 50 pmol/ml siRNA-COX-2). The proliferation activity of BxPC-3 cells was detected by CCK-8, and the migration distance of BxPC-3 cells was detected by scratched assay. The invasion degree of BxPC-3 cells was detected by Transwell, the relative expression level of COX-2 gene in BxPC-3 cells was detected by real-time quantitative PCR (RT-qPCR), and the relative expressions of COX-2, hypoxia inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) proteins in BxPC-3 cells were detected by Western blotting.Results:The cell proliferation rates of blank control group, Ophiopogonin D high-dose, medium-dose and low-dose groups were (100.0±4.9)%, (71.8±5.4)%, (80.5±5.8)% and (89.7±5.7)%, respectively. The migration distances were (279.8±24.0) μm, (141.9±21.2) μm, (168.8±37.1) μm and (224.6±19.9) μm, respectively. The absorbance ( A) values of invasion number were 1.107±0.095, 0.390±0.030, 0.596±0.017 and 0.826±0.034, respectively.There were statistically significant differences ( F=19.770, P<0.001; F=48.270, P<0.001; F=198.400, P<0.001). The above indexes of the Ophiopogonin D high-, medium- and low-dose groups were significantly lower than those in the blank control group (all P<0.05). The relative expression levels of COX-2 gene were 1.007±0.178, 0.387±0.169, 0.567±0.142 and 0.740±0.030, respectively, and the relative protein expression levels were 1.000±0.033, 0.654±0.085, 0.762±0.110 and 0.881±0.049, respectively, with statistically significant differences ( F=10.280, P=0.004; F=11.780, P=0.003). The above indexes of the Ophiopogonin D high- and medium-dose groups were significantly lower than those in the blank control group (all P<0.05), and there was no statistically significant difference between the Ophiopogonin D low-dose group and blank control group (both P>0.05). The medium-dose of Ophiopogonin D (20 μmol/L) was selected as the subsequent concentration.After COX-2 silencing, the proliferation rates of the control group, COX-2 inhibited group, Ophiopogonin D group and combination treatment group were (100.0±2.8)%, (68.4±6.7)%, (67.7±5.9)% and (57.0±8.5)%, respectively, the migration distances were (274.4±23.8) μm, (217.0±18.8) μm, (186.2±18.6) μm and (115.7±15.8) μm, respectively, and the A values of invasion number were 1.143±0.092, 0.791±0.058, 0.715±0.026 and 0.424±0.058, respectively, with statistically significant differences ( F=34.430, P<0.001; F=103.400, P<0.001; F=131.100, P<0.001). The proliferation rates, migration distances and invasion numbers in each treatment group were significantly lower than those in the control group (all P<0.001). Compared with the COX-2 inhibited group and Ophiopogonin D group, the cell proliferation, migration and invasion were significantly inhibited in the combination treatment group (all P<0.05). Compared with the Ophiopogonin D group, only the migration distance of the COX-2 inhibited group was significantly different ( P<0.05). The relative expression levels of COX-2 protein in the above groups were 0.995±0.037, 0.779±0.060, 0.806±0.076 and 0.645±0.079, respectively, the relative expression levels of HIF-1α were 1.083±0.104, 0.749±0.070, 0.736±0.070 and 0.394±0.016, respectively, and the relative expression levels of VEGF protein were 1.016±0.103, 0.757±0.090, 0.745±0.021 and 0.603±0.023, respectively, with statistically significant differences ( F=14.650, P=0.001; F=45.220, P<0.001; F=18.180, P<0.001). The expression levels of the three proteins in each treatment group were significantly lower than those in the control group (all P<0.05). Compared with the COX-2 inhibited group and Ophiopogonin D group, the relative protein expression levels of COX-2, HIF-1α and VEGF in the combination treatment group were significantly decreased (all P<0.05). Compared with the Ophiopogonin D group, there were no significant differences in the expression of the three proteins in the COX-2 inhibited group (all P>0.05). Conclusion:Ophiopogon D combined with COX-2 gene silencing can inhibit the proliferation, migration and invasion of pancreatic cancer cells, and the mechanism may be related to the inhibition of COX-2 pathway and the decrease of HIF-1α and VEGF protein expression levels.
ABSTRACT
Objective To establish an Early Warning System for Recurrence Scoring after Radical Resection of BCLC stage 0/A Primary Liver Cancer (PLC-EWSPRS), and to investigate its predictive value. Methods A retrospective analysis was performed for the clinical data of 232 patients with BCLC stage 0/A liver cancer who underwent radical resection in Affiliated Hospital of Chuanbei Medical College from January 2009 to January 2015, and according to the presence or absence of recurrence within 5 years after surgery based on telephone or outpatient follow-up data, the patients were divided into recurrence group with 103 patients and non-recurrence group with 129 patients. The t -test was used for comparison of normally distributed continuous data between groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups; the chi-square test or Fisher's exact test was used for comparison of categorical data between groups. The indices with statistical significance were included in the binary logistic regression analysis to investigate the risk factors for recurrence of BCLC stage 0/A liver cancer after surgery. Two points were assigned for independent risk factors and one point was assigned for risk factors to establish the PLC-EWSPRS system. The receiver operating characteristic (ROC) curve and the area under the ROC curve (AUC) were used to evaluate the diagnostic efficiency of this system. Results Compared with the non-recurrence group, the recurrence group had significantly higher levels of aspartate aminotransferase and alanine aminotransferase (ALT) and a significantly lower level of albumin (Alb) before surgery ( Z =3.864 and 4.587, t =-5.628, all P < 0.001), as well as a significantly higher proportion of patients with positive HBsAg, capsular invasion, microvascular invasion (MVI), tumor diameter ≥5 cm, liver cirrhosis (moderate-to-severe), non-R0 resection, or death within 5 years ( χ 2 =35.539, 22.325, 13.398, 7.130, 4.312, 4.034, and 18.527, all P < 0.05). The regression analysis showed that preoperative Alb < 40 g/L (odds ratio [ OR ]=5.796, P < 0.001), preoperative ALT ≥40 U/L ( OR =3.029, P =0.002), MVI ( OR =3.981, P =0.003), positive HBsAg ( OR =7.829, P < 0.001), capsular invasion ( OR =5.357, P < 0.001), and non-R0 resection ( OR =3.048, P =0.018) were independent risk factors for recurrence of BCLC stage 0/A liver cancer within 5 years after surgery. According to the assignment criteria of the PLC-EWSPRS system, the recurrence group had the lowest score of 2 points and the highest score of 14 points, while the non-recurrence had the lowest score of 0 point and the highest score of 11 points, and the recurrence group had a significantly higher score than the non-recurrence group ( P < 0.05). The ROC curve analysis showed that the PLC-EWSPRS system had an AUC of 0.918 (95% confidence interval [ CI ]: 0.883-0.953, P < 0.001) in predicting recurrence within 5 years after surgery in patients with BCLC stage 0/A liver cancer undergoing radical resection, and subgroup analysis showed that the system had an AUC of 0.796 (95% CI : 0.695-0.896, P =0.002), 0.859 (95% CI : 0.791-0.927, P < 0.001), and 0.944 (95% CI : 0.839-1.000, P =0.044), respectively, in predicting recurrence within 5 years after surgery in patients with a low score of 0-5 points, a moderate score of 6-10 points, and a high score of 11-14 points. Conclusion The PLC-EWSPRS system has a good value in predicting the recurrence of BCLC stage 0/A liver cancer within 5 years after surgery and thus has important guiding significance for postoperative reexamination and treatment strategy for patients with BCLC stage 0/A liver cancer undergoing radical resection.
ABSTRACT
Objective To explore the risk factors for upper gastrointestinal haemorrhage (UGH) in hepatocellular carcinoma (HCC) with portal hypertension (PH). Methods We retrospectively reviewed the medical records of 231 patients with HCC-PH treated in our Department from 1st January 2005 to 1st August 2009. The clinicopathologic factors were evaluated for their possible association with UGH in univariate analysis followed by multivariate analysis using Logistic regression model. The overall survival (OS) was calculated by the Kaplan-Meier method. Receiver operating characteristics (ROC) analysis with calculation of the area under the curve (AUC), sensitivity, and specificity were carried out to assess the predictive ability of the independent risk factors. Results Among 247 patients diagnosed with HCC-PH, 231 patients met the inclusion criteria and were entered into this study. UGH occurred in 28 patients (12.12 %, 28/231). Patients suffering from UGH had a higher 30-and 60-d mortality when compared with the non UGH group (53.57% vs. 4.43%, 96.43%vs. 10.34%, P＜0. 001, 0. 001). The 1-,2-and 3-year overall survival (OS) rates in the non-UGH and the UGH groups were 3. 57% (1/28), 0% (0/28), 0% (0/28) and 21.18% (43/203), 14.29% (29/203), 4.43% (9/203), respectively. There was a trend towards a non-significantly statistical difference in long-term (≥3 yr) survival (P=0. 605). UGH had a dismal prognosis with a median OS of 0. 8 months (0. 10-2. 40 months). Multivariate analysis of the risk factors showed elevated alpha-fetoprotein (AFP) (P = 0. 026) and aspartate aminotransferase (AST) more than twice normal (2N)(P=0. 004) were predictive factors, in particular, AST≥2N. A cutoff value (PI≥7. 242) predicted UGH with an AUC of 0.828 (95%CI, 0.698-0.957), sensitivity of 81.0% and a specificity of 81.0%, as calculated from the ROC. Risk score stratification predicted UGH to show a statistically significant difference (P＜0. 001). Conclusions UGH, as one of the end-stage incidents of HCC-PH,had a dismal prognosis. Patients with elevated AFP levels and AST levels above 2N were associated with high risks for UGH and should be monitored carefully or offered prophylactic treatments. Risk score stratification was useful for prediction of UGH.
ABSTRACT
Objective To explore the main causes for death due to severe acute pancreatitis (SAP) to improve the level of diagnosis and treatment. Methods The clinical data of 1162 SAP cases treated in our hospital from June 1997 to May 2005 were retrospectively analyzed. Among which, 144patients (12. 39%) died, 82(7.06%)abandoned treatment and 936(80.55%)were cured. Results the APACHE Ⅱ scores and pancreas Balthazar CT scores of the death group were higher than that of the survival group. The percentage of single one organ dysfunction and multiple organ dysfunction syndrome (MODS) was significantly higher in the death group than in the survival group. The mortality rate of SAP without obvious inducing factors was significantly higher than that of SAP with inducing factors. Conclusion Integrated traditional and western non-surgical treatment is effective for SAP.The treatment for SAP without obvious inducing factors is a challenge. The mortality rate of SAP is primarily related to the pathological changes of pancreas and the patient's general condition. Early diagnosis and treatment is important to decrease mortality rate and maintaining the function of important organs is basic to ensure curative effect.
ABSTRACT
Objective To evaluate factors affecting early recurrence and overall survival after curative hepatectomy for hepatocellular carcinoma (HCC) in cirrhotic patients. Methods Sixty two HCC cases with concomitant liver cirrhosis were retrospectively reviewed after curative hepatectomy in our department during the period between Jan. 2002 and Jan. 2009. Clinicopathologic data were evaluated for their possible association with postoperative early recurrence (ER) and overall survival (OS) in univariate analysis followed by multivariate analysis using COX proportional hazard model. Receiver operating characteristics (ROC) analysis with calculation of the area under the curve (AUC), sensitivity, and specificity was applied to assess predictive ability of independent risk factors. Results During follow-up period, 47 patients developed postoperative ER. The 1-, 2-, 3-and 5-year cumulative recurrence rate was 62.9% (39/62) ,75.8% (47/62), 80.7% (50/62), 83.9% (53/62) ,respectively. The 1-, 3- and 5-year OS rates were 59. 7% (37/62), 21.0% (13/62) and 1.6% (1/62), respectively. Multivariate analysis revealed that increased BCLC staging, severity of liver cirrhosis and tumoral residue resectional edge as independent risk factors influencing ER. Cutoff point value ( PI ≥2.171 ) predicted ER with AUC of 0.874(95%CI, 0.757～0.990), sensitivity was 85. 1% and specificity was 77. 8% calculated from ROC.Difference of median recurrence time according to risk stratification reached statistical significance ( 18.7mons, 7.7 mons vs. 2.9 mons, Log-rank test,λ2 =25. 288, P =0.000. While ER, post-recurrence treatment and severity of liver cirrhosis affected OS, cutoff point value ( PI ≥ 2. 893 ) predicted OS with sensitivity 86. 8%, and specificity 88.9%, with AUC 0.894(95% CI,0.798 ～ 0.990). Median OS time according to risk stratification demonstrated significant difference (27.8 mons, 21.5 mons vs. 8.5 mons,Log-rank test, λ2 = 30. 869, P = 0. 000). Conclusion Severity of liver cirrhosis and surgical tumor margin determines postoperative ER and OS for HCC after curative hepatectomy. Effective management of ER also contributes to good prognosis. Risk stratification can be used for evaluation of ER and OS of HCC.
ABSTRACT
Objective To explore the feasibility and validity of laparoscopic choledochotomy and choledochoscopy for treament of patients with acute pancreatitis accompanying commom bile duct stones. Methods A total of 102 patients acute pancreatitis accompanying common bile duct gall stones were treated in our institution between January 2007 and November 2009. Among them, 43 patients underwent laparoscopic choledochotomy and choledochoscopy within 72h after admission entered our study group. They all had a laparscopic cholecystectomy and choleldochotomy and choledochoscopy to retrieve common bile duct stones. Of these, 13 patients undergoing pancreatic capsule incision and peritoneal lavage. Fifty-nine patients undergoing traditional conservative treatment firstly were used as a control group. Of these, 46 were performed laparscopic surgery and choledochotomy after smoothly recovery from pancreatitis. 13 underwent emergency open operation due to complications of pancreatitis. Results In the gastrointestinal function recovery time, amylase recovery time, length of stay and hospitalization cost, there was a significant difference between study group and the control group (P<0.05). Conclusions Our study provides evidence for the good clinical efficacy of early implementation of laparoscopic choledochotomy and choledochoscope for treatment of choledocholithiasis and acute pancreatitis.