Observation of the clinical treatment effect of body cavity circulative hyperthermic perfusion chemotherapy to treat malignant pleural effusion

        Date:2014年2月26日 10:43

        Chunmei Zhu, Li Liu. The Second People's Hospital of Tongling City, Tongling city, Anhui province 244000, China

        [Abstract] Objective: To study the clinical treatment effect of body cavity circulative hyperthermic perfusion chemotherapy to treat malignant pleural effusion. Methods: 64 patients were randomly equally divided into treatment group and control group. Treatment group received body cavity circulation hyperthermic perfusion chemotherapy to treat pleural effusion. The chemotherapeutic drugs (cisplatin and dexamethasone) were diluted with 0.9% of physiological saline, and then were poured into the heating system of the body cavity hyperthermic perfusion machine. When the liquid was heated to 42.5℃-43℃, it was infused into the thoracic cavity at a constant temperature and speed. 24 hours later, the liquid was drained out. Control group received simple intrathoracic chemotherapy. Results: In treatment group including 33 cases, CR (complete recovery) was 69.7%, PR (partial recovery) was 15.2%, NC (no change) was 15.2%, and the total effective rate was 84. 8%; in control group including 35 cases, CR was 34. 3%, PR was 25.7%, NC was 40%, and the total effective rate was 60.0%. The total effective rate in treatment group was obviously higher than control group. Conclusion: thoracic cavity circulative hyperthermic perfusion chemotherapy at a constant temperature and speed can significantly increase effective rate of simple thoracic cavity chemotherapy and improve the life quality of a patient with malignant pleural effusion, and has small toxic and side effects and has good safety.
        [Key words] malignant pleural effusion; body cavity hyperthermic perfusion

        Cancerous effusion (also called malignant pleural effusion) is one of common complications of cancer in middle and advanced stage and is also the major clinical manifestation of partial patients. Because of its rapid growth, it can cause respiratory and circulatory disorders to reduce quality of a cancer patient’s life; when it is severe it can be life-threatening [1]. Conventional treatment i.e. drainage of pleural effusion tends to produce it faster and more, and at the same time a lot of protein and other nutrients in the body are lost, resulting in deterioration of a patient’s condition. The effect of simple drug treatment is poor and can cause pleural thickening, and cannot achieve the reabsorption function of the pleura. Body cavity circulative hyperthermic perfusion chemotherapy has significant anti-tumor mechanism and pharmacokinetic advantages. It can effectively kill free intrathoracic tumor cells and inhibit implantation metastasis of tumor cells so that quality of life is improved. It is an effective method with safety, low toxic and side effects, fewer complications and prevention from pleural effusion "resurgence". The heat therapy has achieved relatively good short-term treatment effect because of its safety, effectiveness, low toxic and side effects and certain biological immunomodulatory effect. Our department collected 64 patients with malignant pleural effusion from 2009 to 2012 and randomly divided them into treatment group and control group. Treatment group was treated with body cavity circulative hyperthermic perfusion chemotherapy, and the control group was treated with simple thoracic cavity chemotherapy. Compared with control group, treatment group achieved good treatment effect, now reported as following:  
        Material and Method 
        A. Material
        The diagnoses of 64 patients were confirmed by pathology or cytology, pleural effusion was confirmed by B ultrasound and CT, and cancer cells were discovered by cytology. Inclusion criteria were: Patients needed to be 40 to 75 years old; B ultrasound confirmed that all of patients had more than moderate pleural effusion; no any drug had been injected into thoracic cavity before this treatment; the internal between the end of last treatment in patients treated by systemic chemotherapy and entrance into a group needed to be> 4 weeks; liver, kidney function and routine blood test should be within the normal range; there was expected survival period of > 3 month. Exclusion criteria were: patients had severe cardiac insufficiency, liver cirrhosis decompensation, renal insufficiency etc. Among the patients, 47 suffered from lung cancers (of which 31 belonged to adenocarcinoma, 12 belonged to lung squamous cell carcinoma and 4 belonged to small cell lung cancer), 3 suffered from pleural mesothelioma and 14 suffered from breast cancer; they were randomly divided into treatment group and control group, and treatment group received thoracic cavity heat treatment by body cavity circulative hyperthermic perfusion chemotherapy and control group received simple thoracic cavity chemotherapy.

        B. Method
        After positioning by B ultrasound, first, drainage tube was indwelled to drain, then, the circulation machine pipe was connected. Temperature was set around 45℃, 30% of cisplatin therapeutic dose was infused by one-way. 0.9% sodium chloride 500-2000 ml was added and it was retained for 20 to 30 minutes, then it was drained out. The above operation of 0.9% sodium chloride was repeated 2 to 4 times. In order to make the drug uniformly distribute in the thoracic cavity to facilitate the absorption and to improve treatment effect, drainage would not be performed until a patient changed position with our help after injecting the drug. Attention should be paid to prevent the catheter from falling off and to keep the drainage tube patency. After the last drainage was completed, 70% of cisplatin therapeutic dose and 10 MG dexamethasone were diluted with physiological saline 500ML-750ML and the prepared solution was infused into the thoracic cavity at constant temperature and speed. The drainage tube was occluded, and the patient was instructed to fully change position for facilitating full absorption of the medical liquid. The liquid was retained for 24 hours, and then it was drained out.

        C.  Judging the treatment effect 
        CR(complete recovery): Symptoms had disappeared, complete absorption of pleural effusion was confirmed by X-ray and B ultrasound, pleural thickening area was less than half of the original pleural effusion area for more than 1 month, and drainage of pleural effusion was not needed again; PR(partial recovery): Symptoms had improved, X-ray and B ultrasound had confirmed that pleural effusion reduced by more than 1/2, or pleural thickening was significant for more than 1 month and no drainage of pleural effusion was needed; NC(no change): Pleural effusion persisted or continued to be rapidly generated, or pleural effusion reduced by less than half of the original amount and within 1 month after treatment the pleural effusion was needed to be drained again [2]. 
        D.  The statistical methods
        SPSS 10.0 software was used to count effective rates and toxic and side reaction rates. χ2 test was used to compare them . P <0.05 was considered to be statistically significant.

        a. Treatment effect and follow-up for at least one month for two groups (see Table 1)
        b. Adverse reactions 
        3 cases in control group had mild chest pain; 2 cases in treatment group had mild chest pain and 1 had low fever. There was no significant difference between the two groups. Because the amount of cisplatin was not large and it was locally administered, the patients in the two groups had no significant renal function impairment; further, compared with simple cisplatin retaining group, patients in body cavity circulative hyperthermic perfusion chemotherapy group had no increased toxic and side reactions and tolerated the therapy well.

        Table 1 Clinical treatment effect of the two groups



        (case number)

        CR   PR

        Effective rate (%)






        23    5
        12    9







        Hyperthermic Perfusion chemotherapy is a new therapy combining chemotherapy with heat treatment to treat tumor. According to clinical reports [3], hyperthermic perfusion combined with intracavitary chemotherapy to treat malignant pleural effusion and ascites has affirmative treatment effect and small side effects, so it is worth clinical application. The principle is: chemotherapeutic drugs with good physical energy heating effect are infused into the tumor site to heat tumor tissue to effective treatment temperature and to maintain at the temperature for a certain time; the heat at the temperature can kill metastatic tumor cells which were widely planted on the serosa, resulting in degeneration and apoptosis of the tumor cells on the involving serosa and in the pleural effusion, and then these tumor cells are eliminated from the body and are drained out. Therefore, the cause of malignant effusion is eliminated and the goal that the apoptosis of tumor cells emerges and normal tissue is not harmed is achieved by making use of the difference between normal tissue and tumor cell tolerance to temperature. The scheme is intrathoracic chemotherapy once a week and generally lasts three to four weeks. The advantages of the therapeutic technology are: large volume of the high concentration chemotherapy liquid is locally offered, contact with the lesion is kept for a long time, and at the same time metastatic tumor cells in the thoracic cavity are attacked by high concentration anti-tumor drugs; only a very small amount of the drug goes into the systemic circulation, so systemic toxic and side effects are small. Direct killing effect of heat treatment to tumor is: it makes tumor cells maintain in malnourished state with hypoxia, low glucose and low PH value, while tumor angiogenesis is suppressed, therefore, tumor cells are damaged; heat effect makes the protein on the membrane of cancer cells degenerate, resulting in embolism of tiny blood vessels within tumor, hypoxia of cancer cells, acidosis or nutrient intake disorders, ultimately leading to necrosis of tumor cells. In addition, due to the presence of thoracic cavity-blood barrier, the drug concentration with the direct administration of intrathoracic chemotherapy may be several times higher than the intravenous administration route. Cisplatin is clinically commonly used cell cycle non-specific broad-spectrum anticancer drugs. By local administration, drug concentration is high and clearance rate is low, so that effective concentration for directly killing cancer cells is provided [4]. Heat effect can increase sensitivity of tumor cells to certain chemotherapeutic drugs, resulting in not simple additive effect, but doubled enhancement. Hyperthermic perfusion chemotherapy makes heat treatment and chemotherapy perfusion drugs produce organic complementary effect to increase sensitivity of a patient to chemotherapy. So, cancer cells can be more effectively killed to improve the patient's quality of life and to prolong the patient's life; at the same time hyperthermic perfusion chemotherapy reduces poisonous and side effects caused by radiotherapy and chemotherapy, and fully exerts its anti- tumor effect.

        [1] Chi Yumin, Sun Baohua, Lv Jing. Treatment effect observation of indwelling the central venous catheter in the thoracic cavity and injecting elemene and cisplatin to treat malignant pleural effusion[J]. Journal of Clinical Pulmonary Medicine, 2012,17 (8): 1529.
        [2] Han Junqing, Liu Qi. Clinical oncology manual[M]. 1st edition. Shandong Science and Technology Press, 2008: 326 - 327.
        [3] Zhang Chunzhen. Treatment effect observation of hot perfusion combined intracavitary chemotherapy to treat malignant pleural effusion and ascites [J]. Clinical Medicine of China, 2010, (7): 721 - 722.
        [4] Xin Qinghong, Li Jicheng, Chen Hangwei. Comparative observation of the treatment effects of intrathoracic injection of different drugs to treat lung cancer pleural effusion [J]. Journal of Clinical Pulmonary Medicine, 2012, 17 (8): 1424.
        [Receiving Date: November 9, 2012]

        doi: 10.3969/j.issn.1009-6663.2013.02.015l

        TypeInfo: academic articles

        Keywords for the information: