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Objective@#To investigate the value of texture analysis based on diffusion-weighted magnetic resonance imaging (DWI) in the differential diagnosis of atypically enhanced small hepatocellular carcinoma (sHCC) and dysplastic nodules (DNs) in liver cirrhosis.@*Methods@#Data of 59 cases with atypical enhancement and solitary cirrhotic nodule (≤2 cm) confirmed by dynamic contrast enhanced MRI and surgical pathology specimen were analyzed retrospectively. Among them, 37 cases were of atypically enhanced sHCC and 22 cases of DNS. The DWI signal characteristics of the lesions were analyzed to measure the average apparent diffusion coefficient (ADC) value of the lesions, and the ADC ratio of the lesion to the liver parenchyma. MaZda software was used to manually draw the region of interest to extract the texture parameters of DWI lesions. The three sets (combination of Fisher coefficient, classification of error probability combined with average correlation coefficient and interactive information) were used to select the thirty optimal texture parameters. Raw data analysis (RDA), principal component analysis (PCA), linear discriminant analysis (LDA) and non-linear discriminant analysis (NDA) were performed for texture classification. The difference of ADC value and ADC ratio between sHCC and DNS group was compared by independent sample t-test, and χ2 test was used to compare the count data (or rate). ROC curve analysis was used to evaluate the diagnostic efficiency.@*Results@#The sensitivity, specificity and accuracy of DWI high-signal in the identification of atypically enhanced sHCC and DNs were 94.6% (35/37), 68.2% (15/22), and 84.7% (50/59), respectively. The ADC ratio of atypically enhanced sHCC was significantly lower than DNs, and the difference was statistically significant (t = 2.99, P = 0.002). The sensitivity, specificity, and accuracy for the diagnosis of atypically enhanced sHCC were 73.0% (27/37), 72.7% (16/22) and 72.9% (43/59), respectively. The sensitivity, specificity and accuracy of DWI texture analysis in diagnosing atypically enhanced sHCC were 94.6% (35/37), 95.5% (21/22) and 94.9% (56/59).The diagnostic efficiency of DWI texture analysis (AUC = 0.94) was significantly higher than DWI high-signal (AUC = 0.81) and ADC ratio (AUC = 0.72).@*Conclusion@#The texture analysis based on DWI can identify atypically enhanced sHCC and dysplastic nodules under the background of cirrhosis, and its efficacy is better than qualitative and quantitative DWI.
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Hyperthermic intraperitoneal chemotherapy (HIPEC) has a unique effect on the prevention and treatment of peritoneal metastasis from malignancies. Recently, the first prospective, multicenter, randomized controlled clinical trial of HIPEC to prevent the development of peritoneal metastasis after curative surgery for patients with locally advanced colon cancer was published in the "Lancet Gastroenterol Hepatol" (COLOPEC). Regrettably, no significant difference was observed in 18-month peritoneal metastasis-free survival between postoperative adjuvant HIPEC and standard systemic chemotherapy for patients with T4 stage or perforated colon cancer. However, we wonder whether we might achieve better outcomes by further optimizing the following issues: (1) We propose that the inclusion criteria for that trial may not be entirely reasonable, which included pT4N0-2M0 and perforation. Additionally, we found that 91% of patients underwent HIPEC 5-8 weeks after primary tumor resection. (2) The imbalance in starting time of postoperative systemic chemotherapy between the two groups may have a negative impact.(3) Nine patients with peritoneal metastasis preceding HIPEC might weaken the potential efficacy of HIPEC. (4) We wonder whether HIPEC using high-dese oxaliplatin (460 mg/m2) perfusing 30 minutes for one cycle is the optimal regimen. Therefore, we are planning to conduct a randomized controlled trial (HIPEC-06) in accordcance with the characteristics of Chinese patients, to explore the clinical efficacy of curative surgery combined with HIPEC in the treatment of cT4 colorectal cancer.
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Objective To investigate the effect of hyperthermic intraperitoneal perfusion and cisplatinon apoptosis in human ovarian cancer cells.Methods Two human ovarian cancer cells (OVCAR-3,A2780) were divided into control group,cisplatin group,hyperthermia group and thermo-chemotherapy group;microscopy was used to observe the morphological changes of the four groups;AO/GV stain and flow cytometry(FCM) was used to analyze cell apoptosis;Apoptosis related genes caspase7,caspase8 and Bax in ovarian cancer cells were detected by fluorescence quantitative PCR.Results Inverted microscopy observeed that the ovarian cancer cells retracted and suspended partially in the cisplatin group and hyperthermia group,especially in the thermo-chemotherapy group.After AO/GV staining,the apoptotic cells were increased in the cisplatin group and hyperthermia group compared with the control group,and the thermo-chemotherapy group was more than cisplatin group and hyperthermia group.FCM results indicated that the proportion of cells apoptosis were higher in the cisplatin group and hyperthermiagroup,the thermo-chemotherapy group is the higher than the all other groups(P＜0.05).q-PCR results showed that in the thermo-treatment group the expression of pro-apoptotic genes,including caspase3,caspase6,caspase7,caspase8,caspase9,Bax,Bak and Bid,was significantly higher than other groups,apoptosis inhibitory gennes,such as Bcl-2,Bcl-xL,Mcl-1,c-FLIP,was significantly decreased than the others.Conclusions Cisplatin plus hyperthermia can promote the apoptosis in ovarian cancer cells.
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<p><b></b>To study the role and molecular mechanism of epigallocatechin gallate (EGCG) in reversing drug-resistance to 5-fluorouracil (5-FU) in gastric cancer drug-resistant cell line SGC-7901/5-FU.</p><p><b>METHODS</b>Drug-resistance gastric cancer cell line (SGC-7901/5-FU) was established by high doses of repeated impact joint drug concentration increment methods. The cell viability of the parent cell line and the drug-resistance cell line were determined by standard MTT assay. Cell survival rate of drug-resistance was calculated by the formula [(Aof the treatment group / Aof the control group) × 100%]. Cell half inhibitory concentration (IC) and resistance index (RI) were calculated by the Graphpad prime 6.0 software(RI=ICvalue of drug-resistance cells / ICvalue of parent cells). The apoptosis rate of SGC-7901/5-FU cells was quantified by flow cytometry after staining with annexin-V and PI. Western blot was used to detect the protein expression of drug-resistance-related proteins (ABCG2, P-gp, MDR-1 and GST-π) and apoptosis-related proteins (PARP, Survivin, Bax and bcl-2).</p><p><b>RESULTS</b>ICvalue was significantly increased in drug-resistant cells compared with parental cells [(64.7±3.9) mg/L and (4.1±0.3) mg/L, respectively, t=26.46, P=0.000], and the RI was 15.6. Proliferation activity in the drug-resistant cells was higher than that in parental cells at different 5-FU concentrations (all P<0.05). In drug-resistant cells, the ICvalue of 5-FU combined with EGCG group obviously decreased compared with 5-FU group [(7.3±0.1) mg/L and (63.1±1.4) mg/L respectively, t=40.84, P=0.000], and the RI was 0.12. Proliferation activity in drug-resistant cells was significantly decreased after EGCG treatment at different 5-FU concentrations (all P<0.05). Cell apoptosis rates in control group, 5-FU group, EGCG group and 5-FU combined with EGCG group were (3.0±1.0)%, (7.0±1.3)%, (6.0±1.2)% and (18.0±1.4)%, while apoptosis rate in 5-FU combined with EGCG group was significantly higher than those of other 3 groups(F=129.5, P=0.000). Western blot revealed that after EGCG treatment, the expression levels of drug-resistance-related proteins (ABCG2, P-gp, MDR-1 and GST-π) in the drug-resistant cell line SGC-7901/5-FU decreased significantly; the expression levels of apoptosis marker protein PARP and pro-apoptotic protein Bax increased significantly; and the expression levels of anti-apoptotic protein Survivin and Bcl-2 decreased significantly (all P<0.05).</p><p><b>CONCLUSION</b>EGCG can reduce the resistance of gastric cancer resistant cell line SGC-7901/5-FU, whose role may be via the inhibition of the expression of drug-resistance-related proteins, and the elevation of the protein expression ratio of PARP/Survivin and Bax/Bcl-2.</p>
Subject(s)
Humans , Anticarcinogenic Agents , Pharmacology , Apoptosis , Apoptosis Regulatory Proteins , Catechin , Pharmacology , Cell Line, Tumor , Cell Proliferation , Cell Survival , Drug Resistance, Neoplasm , Fluorouracil , Pharmacology , Stomach Neoplasms , Drug Therapy , Pathology , bcl-2-Associated X ProteinABSTRACT
Objective To investigate the factors affecting the survival and prognosis of patients with stage Ⅲ～ Ⅳgastric cancers.Methods A total of 156 cases of Ⅲ ～ Ⅳ gastric cancer was studied retrospectively from September 1,2006 to December 31,2012.Kaplan-Meier analysis,Log-rank univariate analysis,Cox proportional hazards model analysis were used to analyze survival and prognostic factors.Results Twelve cases were lost,to the end of the follow-up,22 cases were alive.The median survival time was 29.3 months.1-year,3-year,and 5-year overall survival rates were 83.3％,37.8％,and 21.2％,respectively.Univariate analysis showed that tumor size,tumor node metastasis (TNM) staging,curative resection,hyperthermic intraperitoneal perfusion chemotherapy (HIPEC),and postoperative chemotherapy were correlated with prognosis (P ＜0.05 for all).Multivariate analysis showed that TNM staging,curative resection,HIPEC,and postoperative chemotherapy were independent prognostic factors (P ＜ 0.01 for all).Conclusions TNM staging,curative resection,hyperthermic intraperitoneal perfusion chemotherapy and postoperative chemotherapy are the independent factors affecting the prognosis of stage Ⅲ～ Ⅳ gastric cancer after resection.Hyperthermic intraperitoneal perfusion chemotherapy and postoperative chemotherapy can improve their survival.
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Objective To investigate the efficacy of precise hyperthermic intraperitoneal perfusion chemotherapy (HIPEC) in the treatment of advanced pancreatic cancer.Methods Thirty-six patients with advanced pancreatic cancer were analyzed retrospectively.Eighteen patients who received HIPEC combined with radiotherapy and chemotherapy were assigned as the treatment group and the other 18 patients who received chemotherapy and radiotherapy were assigned as the control group.Recent curative efficacy,Karnofsky Performance Status (KPS) score,postoperative complications and survivals between the two groups were analyzed,respectively.Results Significant differences were found between two groups in total short-term effective rate (P ＜ 0.05).The total short-term effective rate of treatment group and control group were 66.67％ (12/18) and 27.78％ (5/18),respectively.The increment of KPS score of treatment group was significantly higher than that of control group (P ＜ 0.05).There was no significant difference between two groups in postoperative complications (P ＞ 0.05).The median overall survival time (OS) of treatment group was 11 months (7 ～ 31 months),and the median OS of control group was 7 months (4 ～ 18 months).The survival of the treatment group was longer than the control group (P ＜ 0.05).Conclusions HIPEC treatment improved significantly the survival and life quality of advanced pancreatic cancer patients.With acceptable morbidity and mortality rates,HIPEC regime was an effective treatment modality for patients with advanced pancreatic cancer.
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Objective To evaluate laparoscopic continuous circulatory hyperthermic intraperitoneal chemotherapy (CHIPC) in the treatment of malignant ascites from peritoneal carcinomatosis.Methods From March 2006 to March 2008, 21 patients of malignant ascites secondary to peritoneal carcinomatosis received CHIPC with three courses of treatment for each patient. The first course was performed in operation room under general anesthesia, the second and third were performed in patients ward or intensive care unit (ICU), NS solution of mitomycin-C and cisplatin was delivered by continuous circulatary perfusion into peritoneal cavity at a rate of 500 ml/min for 90 min with an inflow temperature of 43 degrees C. Results Intraoperative course was uneventful in all cases, and mean operative time was (80 ± 18) min. There was no postoperative deaths and severe complications. After treatment patients KPS KPS (Karnofsky,KPS)grades rose from 10-40, with an average rise of (22.2 ± 2.4) (P ＜ 0.01). After laparoscopic CHIPC, clinical complete regression of ascites and related symptoms was achieved in 19 patients, and partial remission achieved in 2 patients. Follow-up was made to all patients until the death which occurred at post laparoscope-assisted CHIPC 1 - 9 months, with a median survival time of 6 months.Two patients who underwent partial remission suffered from port site seeding and tumor metastasis leading to death after treatment at 1 and 2 months respectively. Conclusions Laparoscopy-assisted CHIPC is effective for the treatment of malignant ascites from inoperable peritoneal carcinomatosis and improves the quality of life of these patients.