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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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Objective To investigate the measurement , feasibility and clinic effect of hyperthermic intraperitoneal chemotherapy (HIPEC) guided by B ultrasound in the treatment of malignant ascites from peritoneal carcinomatosis. Methods From July 2011 to June 2013, B ultrasound-guided approach was used to perform HIPEC on 36 patients affected by malignant ascites secondary to peritoneal carcinomatosis. Every patient underwent HIPEC for three times , by way of continuous circulatory perfusion into peritoneal cavity with saline at 400 ~ 600 mL/min and intraperitoneal perfusion with 5-FU mitomycin-C and cisplatin for 90 minutes with an inflow temperature of (43 ± 0.2)℃. These patients were followed up for a long term. Results Intraoperative course was uneventful in all cases. Complete clinical regression of ascites and related symptoms was achieved in all the 26 patients, partial regression achieved in 8 patients, and no curative effect achieved in 2 cases. The acquired total clinic effectiveness was 94.44%. No postoperative deaths and complication related to the procedure occurred in this study. The KPS grades of patients rose (P < 0.001), the level of tumor markers decreased, including CA199 (P < 0.001), CEA (P < 0.001), CA125 (P = 0.003). Conclusion HIPEC guided by B ultrasound appears to be a safe, feasible and effective procedure for the treatment of debilitating malignant ascites from unresectable peritoneal carcinomatosis , which would have a clinic good perspective in future.
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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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<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 study the construction of training bases for three tumor therapies. Methods Eight training bases in six third-level first-class hospitals with score of technology assessment higher than 90 were investigated. Results There were good hardware in all training bases and qualified teaching staff in six of them. Annual operative quantity of hyperthermia and radioactive particles implantation technology of all training bases were up to the standard , while the coincidence rate of ablation technology was 80%. Besides , quantity of ablation technology and radioactive particles implantation technology trainees participated in during training met the standard, but that of hyperthermia not. There were significant difference in theory and operational test results before and after training (P < 0.01). Conclusions Management system, operative quantity and teaching staff construction need to be improved. Clinical skills training and standardized training assessment should be strengthened in base construction.
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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 Partial hepatectomy, liver transplantation, and radio frequency ablation for hepatocellular carcinoma (HCC) were compared to select the most suitable method for HCC. Methods 1198 patients with HCC in 3 hospitals in Guangzhou were divided into 3 groups: group Ⅰ , small HCC; group Ⅱ > HCC without vascular invasions and group Ⅲ , HCC with vascular invasion. The patients either received partial hepatectomy, transplantation or ablation. The 1-, 2- or 3-year survival rates, the 3-year recurrent rates and Child-Pugh grades in the 3 groups were compared. Results For small HCC, there was a significant increase in the 3-year survival rate (P<0. 05) and a significant decease in the recurrent rate (P<0. 05) in patients who received transplantation, compared with those who received hepatic resection. Patients who received ablation had a higher 3-year survival rate and a lower recurrence (P<0. 05) in comparison with those who received hepatectomy. There was no significant difference(P<0. 05) between transplantation and ablation, but there were more Child A patients who received hepatectomy and ablation, and more Child B and C patients who received transplantation. For advanced HCC, there was no significant different in the 3-year survival rates for the 3 therapies, but the 3-year recurrence was lower (P<0. 05) in the transplantation group. Conclusions For small HCC, superiority of transplantation versus resection was obvious. Ablation (diameter <3 cm) was also superior to resection, whereas ablation was as effective as transplantation. There were more Child B and C patients in the transplantation group than the ablation and resection groups. Therefore, small HCC with hepatic decompensation should receive liver transplantation. Transplantation was advantageous in having less tumor recurrent but there was no difference in the 3 therapies for advanced HCC.
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Hepatocellular carcinoma(HCC) is one of the most common malignant tumors with the highest cause of death and increasing incidence worldwide, and the annual incidence rate is rising. The early diagnosis of HCC is very essential to its prognosis. At present, AFP has been widely used in the survey of HCC diagnosis, therapeutic effect and predict recurrence. However, the sensitivity and specificity of AFP is not satisfactory. In recent years a variety of new serum tumor markers have emerged one after another. A new serum marker-Golgi glycoprotein-73(GP-73) in early diagnosis of HCC is expected to become the new target maker,its sensitivity and specificity are better than AFP.
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Objective To investigate the effective regimen to treat the hepatitis C virus (HCV) recurrence after orthotopic liver transplantation (OLT). Methods The clinical data of 4 cases of HCV recurrence after OLT were retrospectively analyzed. Of the 4 cases, there were 3 cases of HCV related liver cirrhosis and 1 case of HCV related liver cirrhosis in combination with hepatocellular carcinoma. The immunosuppression regimen as FK506, MMF and corticosteroids was used after OLT. As soon as HCV recurrence was confirmed by liver biopsy during 8 to 12 weeks after OLT, pegylated interferonα-2a (PEG-IFNα-2a) and ribavirin (RIB) were used for 48 weeks. PEG-IFNα-2a was started at a dose of 180 μg per week subcutaneously and RIB at a dose of 1000 mg per day orally, respective-ly. Blood routine, liver and kidney function test, HCV-RNA and transplanted liver biopsy were per-formed when necessary and biochemical response, sustained virologic response and histological re-sponse were tested in due time. Remits All of the 4 cases except for 1 achieved sustained virologic re-sponse and the liver function was as normal as before. The histological activity index was improved significantly for both inflammatory activity and fibrosis according to liver biopsy in 0, 48, 72 week srespectively. Case 4 was given corticosteroids for consecutively 3 days when acute rejection was veri-fied by liver biopsy and the condition improved. None of them stopped treatment or withdrew from them directly. Conclusion The combination of PEG-IFNα-2a and RIB was an effective regimen to treat the HCV recurrence after OLT and the side effects could be overcame easily.
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Objective To investigate the clinical efficacy and safety of hyperthermic intraperitoneal perfusion chemotherapy (HIPC) in treatment of advanced colorectal cancer.Methods The Meta-analysis was applied to analyze 8 randomized controlled quantitative studies published at domestic and abroad.These patients treated by HIPC after radical operation with colorectal cancer were included for the treatment group,and those treated only by radical operation with colorectal cancer for the control group.Relative risk (RR) of outcome variable of 3-year and 5-year survival rate and safety between the two groups were compared.Results There were 8 selected literatures,including 1 501 cases,in which 765 cases for treatment group,and 736 cases for control group.RR of 5-year survival rate of the total patients was 2.39 (95% CI:1.66-3.45).RR of 3-year survival rate of the total patients was 2.13 (95% CI:1.45-3.13).The results demonstrated that HIPC could improve 5-year and 3-year survival rate,and sensitivity analysis confirmed the conclusions more reliable.The security was described in 5 literatures,the available information showed smaller potential security issue.Conclusions HIPC after radical operation of advanced colorectal cancer can increase 5-year and 3-year survival rate of patients,improve the prognosis of patients.Whether patients with increased incidence of postoperative complications related to the HIPC is no clear-cut conclusions for lack of related research.
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Objective To investigate the effect of radiofrequency ablation(RFA) in the treatment of small liver cancer.Methods In recent 6 years,130 patients with primary or secondary liver cancer(≤5cm in diameter)were treated by RFA,among which 86 cases were primary,and 44 cases were secondary liver cancer.Among the 130 cases,18 received RFA plus TAEC,and 20 had RFA combined with PEI.Results Overall 1-and 3-year survival rate was 91.3% and 77.7% respectively.Complications occurred in 7 cases,including biliary fistula,intestinal fistula,and slight burn of skin.There was no death in this series.Conclusions RFA is an effective and safe therapeutic approach for small liver cancer ≤5cm in diameter.Its effect may be similar to that of surgical resection.