Gastric cancer with peritoneal carcinomatosis is notorious for its dismal prognosis. While the pathophysiology of peritoneal dissemination is still controversial, the rapid downhill course is universal. Patients usual...Gastric cancer with peritoneal carcinomatosis is notorious for its dismal prognosis. While the pathophysiology of peritoneal dissemination is still controversial, the rapid downhill course is universal. Patients usually suffer abdominal distension, intestinal obstruction and various complications before they succumb after a median of 3 - 6 months. Although not adopted in most international treatment guidelines, intraperitoneal chemotherapy has growing evidence compared with conventional systemic chemotherapy for the treatment of peritoneal carcinomatosis. Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy is well-established for clinical benefit but is technically demanding with substantial treatment-related morbidities and mortality. On the other hand, normothermic intraperitoneal chemotherapy in the form of bidirectional neoadjuvant treatment is promising with various newer chemotherapeutic agents. Regardless of the treatment technique applied, the essential element of success is meticulous patient selection and availability of expertise. Future direction is along the line of personalized treatment with the application of translational science.展开更多
The administration of hyperthermic intraperitoneal chemotherapy (HIPEC) is often associated with significant intraoperative electrolyte changes. We retrospectively examined the pre-HIPEC and post-HIPEC intraoperative ...The administration of hyperthermic intraperitoneal chemotherapy (HIPEC) is often associated with significant intraoperative electrolyte changes. We retrospectively examined the pre-HIPEC and post-HIPEC intraoperative basic metabolic panel (BMP) values of the 20 patients who underwent HIPEC at our institution between December 2009 and January 2012. For the five patients who underwent HIPEC with oxaliplatin in 5% dextrose in water (D5W), there were statistically significant changes between the pre- and post-HIPEC values of sodium (135 to 124 mmol/L), chloride (105 to 94 mmol/L), glucose (143 to 388 mg/dl) and sodium corrected for hyperglycemia (135 to 127 mmol/L). For the 14 patients who received HIPEC with mitomycin C in normal saline (NS), there were statistically significant changes in bicarbonate (24 to 21 meQ/L), blood urea nitrogen (BUN) (10 to 9 mg/dl) and glucose (158 to 134 mg/dl). The BMP changes for the one patient who received doxorubicin/cisplatin in peritoneal dialysate are reported separately.展开更多
Objective: To explore the influence of intraperitoneal perfusion chemotherapy combined with deep hyperthermia on the malignant molecule expression in ascites of patients with ovarian cancer complicated by ascites. Met...Objective: To explore the influence of intraperitoneal perfusion chemotherapy combined with deep hyperthermia on the malignant molecule expression in ascites of patients with ovarian cancer complicated by ascites. Methods: A total of 80 patients with ovarian cancer complicated by ascites who were treated in this hospital between March 2015 and January 2017 were retrospectively analyzed and divided into the control group (n=43) and the study group (n=37). Control group received intraperitoneal perfusion chemotherapy and study group underwent intraperitoneal perfusion chemotherapy combined with deep hyperthermia. The differences in the expression of proliferation, invasion, autophagy and other malignant molecules in ascites were compared between the two groups before and after treatment. Results: Before treatment, the differences in the expression of proliferation, invasion, autophagy and other malignant molecules in ascites were not statistically significant between the two groups. After treatment, proliferation gene TCEAL7 mRNA expression in ascites of study group was higher than that of control group whereas Clusterin, HOTAIR, ROCK and TNFAIP8 mRNA expression were lower than those of control group;invasion gene DUSP10 mRNA expression in ascites was higher than that of control group whereas MTA1, Nek2, Stathmin and IFITM1 mRNA expression were lower than those of control group;autophagy genes LC3-Ⅱ, Beclin1 and PTEN mRNA expression in ascites were higher than those of control group. Conclusion:Intraperitoneal perfusion chemotherapy combined with deep hyperthermia can effectively balance the expression of proliferation, invasion and autophagy genes in ascites, and ultimately reduce the malignancy of the tumor in patients with ovarian cancer complicated by ascites.展开更多
AIM: To reduce postoperative complications and to make possible an optimal cytoreduction, neoadjuvant chemotherapy(NACT) followed by interval debulking surgery has been applied with encouraging results. METHODS: Betwe...AIM: To reduce postoperative complications and to make possible an optimal cytoreduction, neoadjuvant chemotherapy(NACT) followed by interval debulking surgery has been applied with encouraging results. METHODS: Between December 2009 and February 2012, patients with stage ⅢC-Ⅳ epithelial ovarian cancer(EOC) underwent diagnostic laparoscopy, to assess the feasibility of optimal debulking surgery. The modifi ed Fagotti score was applied to assess the feasibility of resection with zero residual tumor. Patients who were not candidate for upfront debulking surgery were submitted to NACT, then reassessed according to the RECIST 1.1 criteria and submitted to cytoreductive surgery(CRS) and hyperthermic intraperitoneal chemotherapy(HIPEC) if they showed clinical response or stable disease. The remaining cycles of adjuvant systemic chemotherapy(ASCT) were administered postoperatively, to complete 6 cycles of systemic chemotherapy.RESULTS: Nine patients were included. Clinical response to NACT was complete in 3 patients and partial in 5 patients; one patient had stable disease. All patients underwent CRS resulting in CC0 disease prior to HIPEC. Average operative time was 510 min. Average intensive care unit stay was 2 d. Average postoperative hospital stay was 25 d. No postoperative mortality was observed. One patient experienced pelvic abscess. One patient refused ASCT. The remaining 8 patients started ASCT. Average time to chemotherapy was 36 d. All patients are alive, with an average follow up of 11 mo. Eight patients are disease-free at follow up.CONCLUSION: HIPEC after CRS for advanced EOC is feasible with acceptable morbidity and mortality. NACT may increase the chance for achieving complete cytoreduction. Phase 3 studies are needed to determine the effects of HIPEC on survival.展开更多
AIM To investigate the response to hyperthermia and chemotherapy, analyzing apoptosis, cytotoxicity, and cisplatin concentration in different digestive system cancer cells.METHODS AGS(gastric cancer cell line), Caco-2...AIM To investigate the response to hyperthermia and chemotherapy, analyzing apoptosis, cytotoxicity, and cisplatin concentration in different digestive system cancer cells.METHODS AGS(gastric cancer cell line), Caco-2(colon cancer cell line) and T3M4(pancreatic cancer cell line) were treated by cisplatin and different temperature setting(37 ℃ to 45 ℃) either in isolation, or in combination. Treatment lasted for one hour. 48 h after the treatment viability was evaluated by MTT, cell apoptosis by Annexin V-PE and 7 ADD flow cytometry. Intracellular cisplatin concentration was measured immediately after the treatment, using mass spectrometry. Isobologram analysis was performed to evaluate the mathematical combined effect of temperature and cisplatin.RESULTS AGS cells were the most sensitive to isolated application of hyperthermia. Hyperthermia, in addition to cisplatin treatment, did not provoke a synergistic effect at intervals from 37 ℃ to 41 ℃ in neither cancer cell line. However, a temperature of 43 ℃ enhanced cisplatin cytotoxicity for Caco-2 cells. Moreover, isobologram analysis revealed mathematical antagonistic effects of cisplatin and temperature combined treatment in AGS cells; variations between synergistic, additive, and antagonistic effects in Caco-2 cells; and additive and antagonistic effects in T3 M4 cells. Combined treatment enhanced initiation of cell apoptosis in AGS, Caco-2, and T3 M4 cells by 61%, 20%, and 19% respectively. The increase of intracellular cisplatin concentration was observed at 43 ℃ by 30%, 20%, and 18% in AGS, Caco-2, and T3 M4 cells, respectively.CONCLUSION In addition to cisplatin, hyperthermia up to 43 ℃ does not affect the viability of cancer cells in a synergistic manner.展开更多
目的:评估腹腔热灌注化疗(hyperthermic intraperitoneal chemotherapy,HIPEC)对腹腔游离癌细胞的杀灭作用,探索腹膜癌细胞学根治的可行性。方法:收集45例腹膜转移癌患者HIPEC前、后的腹腔灌洗液(或腹水)样本,分别行腹腔灌洗液细胞学(pe...目的:评估腹腔热灌注化疗(hyperthermic intraperitoneal chemotherapy,HIPEC)对腹腔游离癌细胞的杀灭作用,探索腹膜癌细胞学根治的可行性。方法:收集45例腹膜转移癌患者HIPEC前、后的腹腔灌洗液(或腹水)样本,分别行腹腔灌洗液细胞学(peritoneal lavage cytology,PLC)检查;普通RT-PCR及实时定量RT-PCR检测CEA m RNA、CK20 m RNA;化学发光法检测HIPEC前、后患者血清肿瘤标志物CEA、CA125、CA19-9;分析各项指标HIPEC前、后的变化特点。结果:HIPEC前、后PLC检查阳性率分别为93.3%vs.24.4%(P<0.001);CEA m RNA阳性率分别为97.8%vs.84.4%(P=0.058);CK20 m RNA阳性率HIPEC前、后均为95.6%(P=1.000)。分别有32.5%和30.0%的患者HIPEC后CEA m RNA表达量、CK20 m RNA表达量较HIPEC前显著下降(均P<0.001)。HIPEC前、后CEA、CA125、CA19-9阳性率分别为50.0%vs.23.6%(P=0.016)、52.6%vs.47.4%(P=0.409)、36.8%vs.26.3%(P=0.121)。结论:HIPEC可有效杀灭腹腔游离癌细胞,为实现腹膜癌的细胞学根治提供了一个可行的方法。展开更多
文摘Gastric cancer with peritoneal carcinomatosis is notorious for its dismal prognosis. While the pathophysiology of peritoneal dissemination is still controversial, the rapid downhill course is universal. Patients usually suffer abdominal distension, intestinal obstruction and various complications before they succumb after a median of 3 - 6 months. Although not adopted in most international treatment guidelines, intraperitoneal chemotherapy has growing evidence compared with conventional systemic chemotherapy for the treatment of peritoneal carcinomatosis. Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy is well-established for clinical benefit but is technically demanding with substantial treatment-related morbidities and mortality. On the other hand, normothermic intraperitoneal chemotherapy in the form of bidirectional neoadjuvant treatment is promising with various newer chemotherapeutic agents. Regardless of the treatment technique applied, the essential element of success is meticulous patient selection and availability of expertise. Future direction is along the line of personalized treatment with the application of translational science.
文摘The administration of hyperthermic intraperitoneal chemotherapy (HIPEC) is often associated with significant intraoperative electrolyte changes. We retrospectively examined the pre-HIPEC and post-HIPEC intraoperative basic metabolic panel (BMP) values of the 20 patients who underwent HIPEC at our institution between December 2009 and January 2012. For the five patients who underwent HIPEC with oxaliplatin in 5% dextrose in water (D5W), there were statistically significant changes between the pre- and post-HIPEC values of sodium (135 to 124 mmol/L), chloride (105 to 94 mmol/L), glucose (143 to 388 mg/dl) and sodium corrected for hyperglycemia (135 to 127 mmol/L). For the 14 patients who received HIPEC with mitomycin C in normal saline (NS), there were statistically significant changes in bicarbonate (24 to 21 meQ/L), blood urea nitrogen (BUN) (10 to 9 mg/dl) and glucose (158 to 134 mg/dl). The BMP changes for the one patient who received doxorubicin/cisplatin in peritoneal dialysate are reported separately.
文摘Objective: To explore the influence of intraperitoneal perfusion chemotherapy combined with deep hyperthermia on the malignant molecule expression in ascites of patients with ovarian cancer complicated by ascites. Methods: A total of 80 patients with ovarian cancer complicated by ascites who were treated in this hospital between March 2015 and January 2017 were retrospectively analyzed and divided into the control group (n=43) and the study group (n=37). Control group received intraperitoneal perfusion chemotherapy and study group underwent intraperitoneal perfusion chemotherapy combined with deep hyperthermia. The differences in the expression of proliferation, invasion, autophagy and other malignant molecules in ascites were compared between the two groups before and after treatment. Results: Before treatment, the differences in the expression of proliferation, invasion, autophagy and other malignant molecules in ascites were not statistically significant between the two groups. After treatment, proliferation gene TCEAL7 mRNA expression in ascites of study group was higher than that of control group whereas Clusterin, HOTAIR, ROCK and TNFAIP8 mRNA expression were lower than those of control group;invasion gene DUSP10 mRNA expression in ascites was higher than that of control group whereas MTA1, Nek2, Stathmin and IFITM1 mRNA expression were lower than those of control group;autophagy genes LC3-Ⅱ, Beclin1 and PTEN mRNA expression in ascites were higher than those of control group. Conclusion:Intraperitoneal perfusion chemotherapy combined with deep hyperthermia can effectively balance the expression of proliferation, invasion and autophagy genes in ascites, and ultimately reduce the malignancy of the tumor in patients with ovarian cancer complicated by ascites.
文摘AIM: To reduce postoperative complications and to make possible an optimal cytoreduction, neoadjuvant chemotherapy(NACT) followed by interval debulking surgery has been applied with encouraging results. METHODS: Between December 2009 and February 2012, patients with stage ⅢC-Ⅳ epithelial ovarian cancer(EOC) underwent diagnostic laparoscopy, to assess the feasibility of optimal debulking surgery. The modifi ed Fagotti score was applied to assess the feasibility of resection with zero residual tumor. Patients who were not candidate for upfront debulking surgery were submitted to NACT, then reassessed according to the RECIST 1.1 criteria and submitted to cytoreductive surgery(CRS) and hyperthermic intraperitoneal chemotherapy(HIPEC) if they showed clinical response or stable disease. The remaining cycles of adjuvant systemic chemotherapy(ASCT) were administered postoperatively, to complete 6 cycles of systemic chemotherapy.RESULTS: Nine patients were included. Clinical response to NACT was complete in 3 patients and partial in 5 patients; one patient had stable disease. All patients underwent CRS resulting in CC0 disease prior to HIPEC. Average operative time was 510 min. Average intensive care unit stay was 2 d. Average postoperative hospital stay was 25 d. No postoperative mortality was observed. One patient experienced pelvic abscess. One patient refused ASCT. The remaining 8 patients started ASCT. Average time to chemotherapy was 36 d. All patients are alive, with an average follow up of 11 mo. Eight patients are disease-free at follow up.CONCLUSION: HIPEC after CRS for advanced EOC is feasible with acceptable morbidity and mortality. NACT may increase the chance for achieving complete cytoreduction. Phase 3 studies are needed to determine the effects of HIPEC on survival.
基金Supported by the Research Council of Lithuania,No.SEN-01/2015
文摘AIM To investigate the response to hyperthermia and chemotherapy, analyzing apoptosis, cytotoxicity, and cisplatin concentration in different digestive system cancer cells.METHODS AGS(gastric cancer cell line), Caco-2(colon cancer cell line) and T3M4(pancreatic cancer cell line) were treated by cisplatin and different temperature setting(37 ℃ to 45 ℃) either in isolation, or in combination. Treatment lasted for one hour. 48 h after the treatment viability was evaluated by MTT, cell apoptosis by Annexin V-PE and 7 ADD flow cytometry. Intracellular cisplatin concentration was measured immediately after the treatment, using mass spectrometry. Isobologram analysis was performed to evaluate the mathematical combined effect of temperature and cisplatin.RESULTS AGS cells were the most sensitive to isolated application of hyperthermia. Hyperthermia, in addition to cisplatin treatment, did not provoke a synergistic effect at intervals from 37 ℃ to 41 ℃ in neither cancer cell line. However, a temperature of 43 ℃ enhanced cisplatin cytotoxicity for Caco-2 cells. Moreover, isobologram analysis revealed mathematical antagonistic effects of cisplatin and temperature combined treatment in AGS cells; variations between synergistic, additive, and antagonistic effects in Caco-2 cells; and additive and antagonistic effects in T3 M4 cells. Combined treatment enhanced initiation of cell apoptosis in AGS, Caco-2, and T3 M4 cells by 61%, 20%, and 19% respectively. The increase of intracellular cisplatin concentration was observed at 43 ℃ by 30%, 20%, and 18% in AGS, Caco-2, and T3 M4 cells, respectively.CONCLUSION In addition to cisplatin, hyperthermia up to 43 ℃ does not affect the viability of cancer cells in a synergistic manner.
文摘目的:评估腹腔热灌注化疗(hyperthermic intraperitoneal chemotherapy,HIPEC)对腹腔游离癌细胞的杀灭作用,探索腹膜癌细胞学根治的可行性。方法:收集45例腹膜转移癌患者HIPEC前、后的腹腔灌洗液(或腹水)样本,分别行腹腔灌洗液细胞学(peritoneal lavage cytology,PLC)检查;普通RT-PCR及实时定量RT-PCR检测CEA m RNA、CK20 m RNA;化学发光法检测HIPEC前、后患者血清肿瘤标志物CEA、CA125、CA19-9;分析各项指标HIPEC前、后的变化特点。结果:HIPEC前、后PLC检查阳性率分别为93.3%vs.24.4%(P<0.001);CEA m RNA阳性率分别为97.8%vs.84.4%(P=0.058);CK20 m RNA阳性率HIPEC前、后均为95.6%(P=1.000)。分别有32.5%和30.0%的患者HIPEC后CEA m RNA表达量、CK20 m RNA表达量较HIPEC前显著下降(均P<0.001)。HIPEC前、后CEA、CA125、CA19-9阳性率分别为50.0%vs.23.6%(P=0.016)、52.6%vs.47.4%(P=0.409)、36.8%vs.26.3%(P=0.121)。结论:HIPEC可有效杀灭腹腔游离癌细胞,为实现腹膜癌的细胞学根治提供了一个可行的方法。