Control study of body cavity constant temperature circulative hyperthermic perfusion chemotherapy to treat malignant pleural effusion

        Date:2014年2月26日 10:40

        Liufei Wang, Wei Li.
        Author’s unit: 529600 Department of Oncology, The People’s Hospital of YangChun City, Guangdong Province, P. R. China

        [ Abstract ] Objective: To investigate the treatment effect of thoracic cavity constant temperature (42-43℃) circulative hot perfusion chemotherapy to treat malignant pleural effusion. Methods: 50 patients with malignant pleural effusion from January to December, 2008 were randomly divided into two groups. Observation group including 25 patients received treatment of conventional puncture needle to build circulative dual channels, and first the patients’ thoracic cavities were rinsed and pleural effusion was replaced by thoracic cavity infusion liquid. 3-5 minutes after the beginning of thoracic cavity constant temperature(45℃-45.5℃)circulation, DDP60mg was added into the tube and constant temperature circulation hot chemotherapy lasted for 60 minutes. After the end of the therapy, the therapeutic liquid was drained out and the remaining liquid was less than 500ml. In control group including 25 cases, the drainage tube was indwelled in the thoracic cavity, and first, pleural effusion was drained out from the thoracic cavity and then 100ml solution containing chemotherapeutic DDP 60mg was infused. Result: The total effective rate in observation group was 86.3% and was significantly higher than control group (P<0.05). Conclusion: Compared with conventional indwelling tube drainage perfusion chemotherapy, thoracic cavity continuing constant temperature circulation hot chemotherapy significantly improves effective rate of treating malignant pleural effusion, and at the same time the talent of controlling resurgence of malignant effusion has been significantly improved, so that the life quality of a patient in late stage of cancer has been improved. The method is convenient for mastering and the cost is cheap, so that it is suitable for popularization in grass-root hospitals.
        [Key words] malignant pleural effusion, continuing constant temperature circulative hot perfusion, chemotherapy
        Malignant thoracic effusion is the main clinical symptom and sign of most of patients in moderate and late stage of tumor. Its production and development directly affect a patient’s life quality and survival period and when it is severe it can be life-threatening, therefore, the treatment of malignant pleural effusion is very important in the whole tumor comprehensive treatment. At present, there are many methods to treat malignant pleural effusion, but the common main method is simple local drainage plus single drug chemotherapy of which efficacy is limited and pleural effusion is easy to recur. Despite limited survival period of a patient in late stage of tumor, successful palliative treatment can reduce the production of pleural effusion, relieve suffering from chest pain and short breath, and exert active effect on the life quality and prognosis of a patient. In our hospital, continuing constant temperature hot perfusion circulative chemotherapy was used to treat 25 patients with cancerous pleural effusion and had achieved good effect. Now the comparative analysis results are reported as following.

        1 Material and method
        1.1 General material: 50 patients in our department were selected and were randomly divided into continuing constant temperature circulative chemotherapy group (observation group) including 25 cases and simple drainage chemotherapy (control group) including 25 cases. Inclusion criteria were: patients were needed to be 38-70 years old; physical assessment criteria (ECOG) NCI should be 0-3; B ultrasound had confirmed that all patients had more than moderate pleural effusion; no drug had been injected into the thoracic cavity before this treatment; the interval between the end of the last treatment of a patient treated by systemic chemotherapy and entrance into a group needed to be >4 weeks; hepatic, renal function and routine blood test needed to be within the normal range; there was expected survival period of >3 months. Exclusion criteria were: a patient had severe cardiac dysfunction, hepatocirrhosis decompensation, renal dysfunction etc. In observation group including 25 patients aged 39-65 years old, 18 patients suffered from lung cancer, 5 suffered from pleural mesothelioma, 2 suffered from breast cancer, and 15 patients were males and 10 were females. In control group including 25 patients aged 38-68 years old, 16 patients suffered from lung cancer, 6 suffered from pleural mesothelioma, 3 suffered from breast cancer, and 16 patients were males and 9 were females. All patients were examined by chest CT and chest B ultrasound, and their diagnoses were confirmed by cytology or histopathology. The two groups were comparable in age, disease kinds etc.
        1.2 Treatment method  Observation group was: after positioning by B ultrasound, a puncture needle or an indwelling tube was used to build passage, the puncture needle was confirmed to be in the cavity, pleural effusion 500-1000ml was drained out, the circulation machine tube was connected, temperature was set at 45℃-45.5℃, and hot saline 500-1000ml was infused by one-way till the patient felt mild chest tightness; the patient was punctured again and the output end of the needle was connected to the circulation machine tube, and hot circulative treatment began; during circulation, temperature of liquid just into the body was set at 43.5℃-44.5℃, temperature of liquid just outside the body was 41℃-42℃, flow speed was 150-220ml/minute, continuing constant temperature circulation lasted for 50-60minutes, the temperature of perfusion liquid in the body was kept at 42℃-43℃, at last, partial liquid was drained out and the remaining liquid was less than 500ml. Chemotherapeutic drug cisplatin 60mg (it was dividedly administered during or after circulation) was infused. Dexamethasone 10mg and furosemide 20mg were routinely infused once every 3 days for 3 continuous times. In order to avoid brain impairment by ≥39℃ temperature, cool towel was routinely dressed on the head. Any patient in control group was routinely punctured into the thoracic cavity, a single-cavity deep venous catheter was indwelled in the thoracic cavity and continuous drainage was performed. After the pleural effusion was drained 500-1000ml, chemotherapeutic drug cisplatin 60mg was infused once every 3 days for continuous 3 times. During therapeutic period, systemic chemotherapy and interferon, interleukin-2 and other immunotherapies were not used in the patients of the two groups.
        1.3 Judging the effect of treating pleural effusion  The amount of pleural effusion before and after treatment was measured by B ultrasound, and Kamofsky score was observed. The treatment effect was judged according to WHO criteria. The criteria of complete relief (CR) were: pleural effusion was completely absorbed and the state lasted for more than 1 month; the criteria of partial relief (PR) were: the pleural effusion reduced by ≥50% and the state lasted for more than 1 month; the criteria of no change(NC) were: the pleural effusion reduced by ≤50% and the state lasted for more than 1 month; the criteria of progressive disease(PD) were: the amount of pleural effusion increased or did not change. Safety evaluation was judged according to anticancer drug toxic reaction criteria.
        1.4 Statistical treatment  χ2 was used to compare the rates between the two groups, based on SPSS11.0 statistical software.

        2 Result
        2.1 Clinical treatment effect  The treatment was completed more than 3 times in all patients. In observation group, the effective rate was 84% (21/25) and the complete relief rate was 32% (8/25); in control group, the effective rate was 52% (12/25) and the complete relief rate was 16% (4/25). There was statistical difference between the two groups(P<0.05). The tumor maker reduced significantly.
        2.2 Poisonous and side reactions  The patients in the two groups all had nausea, vomiting, leukopenia, chest pain and other mild side reactions, and the patients quickly returned to normal state by symptomatic treatment. Particular attention should be paid to the fact that compared with the patients in control group the appetite and mental condition of the patients in observation group did not weaken but strengthen. None of the patient had pneumothorax and pleural infection. All patients had no hepatic and renal function impairment.
        3 Discussion
        Most of malignant pleural effusions are bloody, mainly because cancer cells invade pleura and are planted into thoracic cavity. Malignant pleural effusion is the common complication in late stage of tumor, especially is the commonest in NSCLC (non-small-cell lung cancer), and severely impacts the life quality of a patient. This kind of patients is not suitable for operative treatment and radiotherapy. Due to the barrier effect of pleura, systemic chemotherapy exerts no good effect on controlling pleural effusion. At present, it is the opinion that first intracavitary constant temperature circulative hot perfusion chemotherapy is performed and after controlling pleural effusion the systemic chemotherapy was performed so that expected effect can be achieved. The effective rate in observation group is high and reasons can be analyzed as following: (1) Hot chemotherapy exerts killing effect: hot chemotherapy kills tumor by different tolerance of tumor tissue cells and normal tissue cells to temperature and by synergistic effect [1]. Tumor cell tolerance to heat is low, therefore, prolonging heating time can increase the impairment of cancerous cells and suppress their reproduction. Heat treatment at 40℃ for 50-60minutes can increase adverse reactions of cells to a drug by 20%. At 42℃ cancer cells begin to degenerate and their apoptosis appears. At 43℃ coagulation and necrosis emerge. However, normal tissue cells can tolerate 45℃-47℃ and cannot be harmed[2]. (2) Cisplatin exerts direct killing effect. Cisplatin is the metal complex and is a cell cycle non-specific drug. Its mechanism of action is to combine DNA, damage DNA function and suppress mitosis of cells. It is the broad-spectrum antitumor drug. When it is infused into the thoracic cavity it directly exerts effect on cancer cells on the pleura and in the pleural effusion, and can be absorbed into blood to suppress the original focus and the metastatic foci [3]. (3) Physical clearance exists: the circulative perfusion therapy can change effusion from “dead water” to “active water” along with circulation, make fibrin and necrosis tissue and other tangible materials depositing on intestinal loops, between organs and on the surface of cells fall off and swim along with mechanical circulation. Therefore, after treatment once or twice, relatively much fibrin, necrosis tissue and even wrapped cyst membrane can be seen to be drained out with drainage fluid. Circulative hot perfusion exerts rinsing effect [4]. (4) Biological repair exists: circulative perfusion of hot saline better cleans the pleura and clears fibrin and necrosis tissue, facilitates the infiltration of drugs; wet heat also facilitates the repair of pleura to reduce exudation and to change the conventional therapeutic opinion that drugs are used to stimulate adhesions to reduce pleural effusion. After the treatment, many patients not only effectively control malignant effusion, but also complications are significantly reduced.
        In summary, if thoracic cavity continuing constant temperature circulative hot perfusion chemotherapy is used to treat malignant pleural effusion, patient compliance is good and the treatment has safety and high effect.

        [1] Spratt JS,Adcoek RA,Muxeovin M,et al. Clinical defiverysystem for intraperitoneal hypeahermie chemotherapy [J].Cancer Res,1980,40(2):256-260.
        [2] Fujimoto S,Takahashi M,Mutou T,et al. Improved mortality rate of gastric carcinoma patients with peritoneal earcinomatosis treated with intraperitonealhyperthermie chemoperfusion combined with surgery[J]. Cancer, 1997,79(5):884-891.
        [3] Luo Ciwen, Li Changsheng, Hu Hao. Diagnostics and therapeutics of pleural effusion [M]. Beijing: Science Press, 2001: 145.
        [4] Gilly FN,Beaujard A,Glehen 0,et al. Peritonectomy combined with intraperitioneal chemohyperthennia in abdominal cancer with peritoneal carcinomatosis: phase I-II stud [J]. Anticancer, 1999,19(3B):2317-2321.

        TypeInfo: academic articles

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