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Clinical observation on cycle thermo chemotherapy of intraperitoneal perfusion for malignant peritoneal effusion

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Modern Oncology 2009,17(11):21 85-2 187
Clinical observation on cycle thermo chemotherapy of intraperitoneal perfusion for malignant peritoneal effusion
Jihua Yang , Jie Min , Weimin Li , Hong Wang , Rui Liu , Ningqiang Ma , Helong Zhang
Department of Oncology , Tang du Hospital,Fourth Military Medical University,Xi’an 710 038,China .
[Abstract] Objective : To evaluate the efficacy of cycle thermochemotherapy of intraperitoneal perfusion for malignant peritoneal effusion . Methods : Fifty six cases with malignant peritoneal effusion were randomly divided into two groups . After abdominal paracentesis and lavation , 29 cases were treated with cycle thermochemotherapy of intraperitoneal perfusion and 27 cases were treated with thermochemotherapy of intraperitoneal perfusion as control.Then the treatment effect and toxicities were assessed . Results : The response rate was 93.1%in treated group and 6 6.7%in the control group(P<0.025) . The hyperhidrosis is more frequently happened in therapy group(89.7%)than in control group(29.6%)(P<0.05) Conclusion : Cycle thermochemotherapy of intraperitoneal perfusion for malignant peritoneal effusion is an effective and well tolerated method for the malignant peritoneal effusion with slight side effect .
[Key words] Malignant pleural effusion ; thermotherapy ; perfusion ; cisplatine
Modern Oncology 2009,17(11):2185-2187
[CLC]R 730.53[Document ID code]A
[Article number]1672-4992-(2009)11-2185-03
  The application of thermo chemotherapy of intraperitoneal perfusion for malignant peritoneal effusion with pharmacokinetic advantages and warm effect[1]had been wildly reported recently[2-4] . The traditional treatments of thermo chemotherapy using pre-warmed solution for perfusion and then heat the abdomen with microwave or radio frequency . However the constant hyperthermia temperature is hardly to reach , so the effect is hardly to be improved.The advent of cavity extracorporeal circulation perfusion machine may solve these problems , while the application of circulating perfusion thermochemotherapy in treatment of malignant peritoneal effusion had been rarely reported . Malignant ascites patients treated with circulating perfusion thermochemotherapy and simple hyperthermic perfusion chemotherapy were reviewed in this study to evaluate the therapeutic effect of circulating perfusion thermochemotherapy .
1Patients and Methods
  56 patients diagnosed as malignant peritoneal effusion by pathology in our treatment center were collected from January 2007 , including 33 males,23 females,the median age of 55 years(54±16),the expected survival>3months.Encapsulated effusion were not formed,Including 17 cases of gastric carcinoma , 12 cases of liver cancer,colorectal cancer in 15 cases,12 cases of ovarian cancer . All the cases had B ultrasound examination results,by which ascites were classified :16 cases of grade I,21 cases of grade II and 19 cases of grade III . (Patients were in supine position when underwent B ultrasound examination,grade I : effusion exist between intestinal ; grade II : effusion exist between liver and kidney and paracolic sulci ; grade III : effusion exist before liver)
  All of the cases met the inclusion criteria . And stratified randomization method was used . Firstly disease and ascites grade were stratified . Then simple randomized method was used in each layer to further divide the patients into treated group and control group . No heterogeneity of basic information was found between two groups(disease P>0.5;ascites P>0.75),Table1.
1.2.1Treatment plan All patients underwent bilateral abdominal paracentesis and lavage:abdominal paracentesis was performed in the left and right lower abdomen puncture point under the guided of B ultrasound . After that two needles were left and fixed , and connected with the disposable extracorporeal circulation catheter(one as input way and the other as output way)started the perfusion machine , and flooded abdominal cavity with preheating physiology saline at the temperature of 37~38℃。And the same time,output catheter was opened , and drained ascites and perfusion solution until the solution with lighter color of near to colorless . After drainage of fluid , further treatment was given according to treatment plan of each group .
  Treated group①the centrifugal pump infusion hole of extracorporeal circulation perfusion machine(Harbin aerospace Technical Developing Company)was connected with inlet catheter , and centrifugal pump liquid hole is connected with the outlet catheter . So a closed loop of “ inlet catheter-Abdominal cavity.-outlet catheter-perfusion machine-inlet catheter ” was formed . The perfusion fluid(1500~3000ml saline+cisplatin 40~80mg , with concentration of 26.7%)was heated to 44.0~47.0℃before intraperitoneal injecting to the closed system .②Regulation of the perfusion machine to make the perfusion fluid circulating in the abdnominal cavity,and keep a constant temperature by real-time temperature measuring and heating when needed.The perfusion time was 60min.③Released amount of liquid after perfusion,then intraperitoneal injected of interleukin-II 3000000 u , 10mg dexamethasone , 200000U gentamicin.Pull out the puncture needles after routine disinfection.Pressure dressed the puncture point,ask patient to change position every fifteen minutes.Patients were in Observation wards until 30min after the treatment . ④The treatment was repeated every 3 days.4 times were considered to be 1 course of treatment .
  Control group had the same treatment plan except perfusion fluid circulating.
1.2.2 Observation index①the change of perfusion fluid:the input volume , output volume and temperature ; ②Volume of ascites : abdominal ultrasound were performed before and 4 weeks after the fourth courses of treatment . ③Laboratory examination : routine blood test and serum alanine aminotransferase were tested at the the ninth day and 4 weeks after the first course of treatment . ④adverse reactions:record all kinds of adverse reactions during and after treatment .
1.2.3 Criterion of therapeutic evaluation
  Therapeutic evaluation was classified according to WHO criteria : Complete remission(CR) , ascites disappeared completely , lasting more than 4 weeks ; Partial remission(PR) , ascites reduced at least 50% , and remission of symptoms continued for more than 4 weeks;No response(NR) , the change of ascites with less than 50%decreased or no more than 25%increased;Progressive disease(PD) , ascites increased or advanced . Complete remission and partial remission were defined as effective results.Adverse reactions were also concerned . It was classified according to the criteria of WHO.
1.3 Statistical analysis
Chi-square test and Fisher exact probability test were used.
2.1The change of perfusion fluid:the input volume,output volume and temperature
  Treated group:The total volume was 1500ml~3000ml(mean of 2750ml)with the temperature of 46℃~47℃(mean of 46.5℃).The output volume was 1000ml~3000ml(mean of 2000ml)with the temperature of 39.4℃~43.4℃(mean of 41.4℃).Perfusion time was 60min.
  Control group:The total volume was 1500ml~3000ml(mean of 2750ml)with the temperature of 46℃~47℃(mean of 46.5℃) . The output volume was 1000ml~3000ml(mean of 2000ml)with the temperature of 37.4~39.4℃(mean of 38.4℃).Perfusion time was 60min .
2.2 Effect of treatment
  The Effective rate of treatment in the treated group was CR 13.8%cases(4/29),PR 79.3%(23/29) , NR 6.9%(2/29) , with effective rate of 93.1%.In control group , the therapeutic effect was CR 3.7%(1/27),PR 63%(17/27) , NR 25.9%(7/27) , PD 7.4%(2/27)with the effective rate of the 66.7% . The effective rate of the treatment group was significantly higher than that in control group(X2=6.191,P<0.025) .Table2
  2.3 adverse reactions
  There were no significantly difference of adverse reactions between two groups except sweating(p<0.05) . The incidence rate of bone marrow suppression , gastrointestinal reaction , abdominal pain , abnormal liver function etc . And adverse reactions have no significantly difference . See table 3
3 Discussions
  Malignant ascites had high incidence in patients with malignant tumor . It affect the quality of life seriously . We applied cyclic heat perfusion chemotherapy for malignant peritoneal effusion , and achieved good effect . Circulation heat perfusion chemotherapy in tumor treatment has the following characteristics[5-6] . ①High temperature can kill the tumor cells directly.Malignant cells are 2 times more sensitive to high temperature than the normal cells[7] . The ability of heat to killing tumor cells will increase 2 times with 1℃increased when the temperature is more than 42℃ . Or if prolong the time ,the ability still enhanced . Besides that , heat can accelerate the apoptosis of tumor cells,and activate the immune response . ②Synergistic effect of hyperthermia and chemotherapy . Heat has the effect of dilating of blood vessels and lymphatic vessels,increasing the cancer cell membrane fluidity,thus increase the concentration of chemotherapeutic agents in cancer cells . Heat can catalyze the reaction between drugs and tumor cells,and enhances the sensitivity of chemotherapy drugs,such as cisplatin . ③Intraperitoneal hyperthermic perfusion can wash away a number of cancer cells,and reduce tumor burden . Perfusion chemotherapy in abdominal cavity prolong the contact time of drug to tumor cells,so as to enhance the local concentration 10 times than the plasma concentration . From the above we know that,keeping the constant temperature of perfusion solution , complete contact of perfusion solution to organs and tissues were the key point to the ensure the effect of perfusion thermotherapy . So we let the perfusion solution circulating , and monitor the temperature in real-time mode in order to keep a constant temperature . Flow and heat carrier characteristics of water were also utilized to make the drug contact with organs completely . In this way , tumor cells can be killed effectively[8] . That is to say ,“ circulating and temperature control ” were the key point .
  According to the Y Ellin[9]study , abdominal perfusion , temperature was equally to the average temperature of the inflow and outflow of perfusion . The proposed temperature in abdominal cavity was 43.9℃in this study , which ensure the safety and effective of the treatment . This is probably the most important reason for the test group has a good curative effect . While in the control group , traditional method without continued heating cannot make sure a constant temperature of 43℃in 1h . The traditional method without circulation of perfusion cannot wash away the tumor cells.So there was only 66.7%efficiency .
  The experimental group used the method of cycle perfusion fluid , overcome the defects,to ensure the effective treatment temperature of thermo chemotherapy . The effective rate was 93.1%.Most of the patients in the treated group had the symptom of sweating in the circulation process ; it may be due high temperature induced by intraperitoneal perfusion therapy . For those patients , fluid infusion was given during treatment , and sweating symptoms disappear after the end of treatment . In the treatment process,the vital signs of the patients remain stable , no patients who could not tolerate the perfusion.Except for sweating,no grade III/IV hematologic adverse reactions were found[10] . This study suggests that the circulating perfusion chemotherapy in treatment of malignant peritoneal effusion have the advantages of easy to operation,safety,good curative effect,fewer side effects .
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