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        Clinical observation of hyperthermia combined with perfusion for malignant pleural effusion

        Date:2014年2月26日 17:08

        doi:10.3969/j.issn.1009-4393.2011.19.074
        Clinical observation of hyperthermia combined with perfusion for malignant pleural effusion Chenyao Zhang,Liru Wang, Wei Sun
        Abstract Objective To investigate the clinical efficacy and adverse reaction of hyperthermia combined with intraperitoneal perfusion chemotherapy for malignant pleural effusion treatment. Method 80 patients with malignant pleural effusion were randomly divided into two groups. 40 cases were in continued circulatory hyperthermic perfusion chemotherapy group, and other 40 cases were in intraperitoneal perfusion chemotherapy group. Treatment was given 1 times per week of a total of 3 times. Then evaluate the efficacy and adverse reaction. Results The effective rate in continued circulatory hyperthermicpeal perfusion chemotherapy group was 85% (34/40), while it was 57.5%(23/40) in intraperitoneal perfusion chemotherapy group. There were significantly difference between two groups, X2=5.52, P=0.019. However, there were no difference of adverse reaction between two groups (P>0.05). Conclusion Hyperthermia combined with intraperitoneal perfusion chemotherapy in the treatment of malignant ascites is efficacy with mild adverse reactions.It is worthy of clinical application.
        Key words: Hyperthermia; intraperitoneal chemotherapy; malignant peritoneal effusion
             Malignant pleural effusion is one of the most common complications in patients with advanced malignant tumor. This kinds of patient always had advanced tumor staging with local and (or) distant recurrence and metastasis. The average way for effusion include diuretics; puncture drainage and local injection of biological agents. Compared with systemic chemotherapy, intraperitoneal injection of biological agents has higher efficiency of 76%~86% with less adverse reaction [1].  Application of hyperthermia combined with chemotherapy has synergistic killing effect on tumor cells.  Continued circulatory hyperthermic perfusion chemotherapy were adopted in this study, it showed satisfactory effect when compared with the traditional treatment of malignant peritoneal effusion. It reported as following.
        1 Clinical data
        1.1patients  
             A total of 80 cases with peritoneal effusion were collected. All the patients had cytological or pathologic results. Peritoneal effusion was confirmed by B ultrasound examination, including 48 males and 32 females.
             The mean age of patients was 56 years (range from 31 to 77).  40 cases were in hyperthermic perfusion group, including 2 cases of lung cancer, 10 cases of primary liver cancer, 15 cases of gastrointestinal tumor, 2 cases of pancreatic carcinoma, 2 cases of bile duct carcinoma, 5 cases of ovarian cancer, 3 cases of breast cancer, 1 cases of lymphoma. 40 cases were in control group, including 3 cases of lung cancer, 11 cases of primary liver cancer, 14 cases of gastrointestinal tumor, 2 cases of pancreatic carcinoma, 2 cases of bile duct carcinoma, 6 cases of ovarian cancer, 2 cases of breast cancer. All the patients enrolled had moderate ascites, with Karnofsky performance score >40, expected survival time>2 months. All the patients did not given any systemic chemotherapy or local therapy for 4 weeks with normal results of liver renal function, routine blood test and electrocardiograph (ECG).

        1.2 Treatment plan
             The high frequency thermotherapy machine HG-2000 produced by Shenzhen Hejia medical equipment limited company were used, with frequency of 13.56MHz, computer-controlled temperature,  800W power, 60min for each heating. The heating temperature depends on patient’s tolerance. The output temperature is 0℃~43.5℃。

             Patients were randomly divided into 2 groups, 40 cases of patients treated with intraperitoneal hyperthermic perfusion chemotherapy. Firstly, effusion was drained after abdominal paracentesis (no more than 2000ml for the first time). Secondly, the abdomen was flooded with 1500ml ~ 2000ml saline containing 80mg~100mg cisplatin at 48℃. Then, heated the abdominal cavity with thermotherapy machine for 120min, keeping the temperature for 41~43℃. Temperature control was performed through rectum by thermometer (rectal temperature is close to abdominal cavity temperature). Treatment was given once a week, and evaluated the treatment effect after 3 times. The other 40 cases in control group were given intraperitoneal injection of cisplatin at equivalent dose once a week the efficacy was evaluated after 3 times.
        1.3 Curative effect criterion
             Patients were underwent B ultrasound ever week during the treatment period, the change of ascites, liver and renal function, routine blood test were also observed. 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; Stable disease (SD), the change of ascites with less than 50% decreased or no more than 25% increased; Progressive disease (PD), ascites increased or advanced [2].. Adverse reaction was classified as level 0-Ⅳ according to the WHO anticancer drug toxicity evaluation criterion [2].
        2    Results
        2.1 short-term effects
             Compare the short-term effects of the two groups, after 3 courses of treatment, the effective rate of hyperthermic perfusion chemotherapy was 85% (34/40), which was significantly higher than that in control group ,showing as 57.5% (23/40), X²=5.52, P=0.019.
        2.2 Adverse reaction
             The main adverse reactions were digestive system reactions, mainly classified as grade 0-Ⅱ. No grade of Ⅲ-Ⅳ happened. No significantly difference of adverse reactions were found in two groups (x²=1.20, P=0.27). Bone marrow depression were defined as grade 0-Ⅱ, and no significantly difference of adverse reactions were found in two groups (x2=0.004, P=0.95). No obvious injured of liver and kidney was found. All the patients showed good tolerance.
        3   Discussion
             The prognosis of patients with malignant pleural effusion is poor, with 1 year survival less than 10% [3]. Malignant ascites caused by peritoneal metastasis of tumor cells is generated due to hypoproteinemia and obstruction of lymph circulation. These patients were often in advanced stage with poor fitness and tolerance to therapy. The treatments of malignant pleural effusion include systemic chemotherapy and local treatment. Due to the low concentration of intraperitoneal drug, systemic chemotherapy had poor therapeutic effect. However, local treatment had better effect by increasing the concentration of intraperitoneal drug and prolonging the contact time of drug to tumor cells. Hyperthermia combined with intraperitoneal perfusion chemotherapy based on the mechanism of both hyperthermia effect and thermochemotherapy can increase permeability and toxicity of chemotherapy drugs of tumor, improve the local concentration of chemotherapeutic drugs, and reduce or reverse the multidrug resistance of chemotherapeutic agents. It can also produce heat shock protein (HSP), induce specific immunity, enhance the effect of IL and TNF, inhibit the effect of VEGF (vascular endothelial growth factor), and finally inhibit tumor angiogenesis [4].. Compare the short-term effects of the two groups, after 3 courses of treatment; the effective rate of hyperthermic perfusion chemotherapy was higher than the control group (85% versus 57.5%). The main adverse reactions were digestive system reactions, mainly classified as grade 0-Ⅱ.No grade Ⅲ-Ⅳ happened. No significantly difference of adverse reactions was found in two groups. Bone marrow depression was classified to grade 0-Ⅱ, and no significantly difference of adverse reactions was found in two groups. All the adverse reaction disappeared. In conclusion, hyperthermia combined with intraperitoneal perfusion chemotherapy for malignant pleural effusion treatment had remarkable effect with mild adverse reaction. Especially for advanced stage disease, it is good choice for clinical application.

        References 
        [1] Guangwei Xu.  Clinical Oncology [M], Shenyang: Liaoning Education Press, 1999
        686-687.
        [2] Yan Suu, Jichang Zhou. Handbook if Oncology [M] Beijing: people's medical publishing house, 2003: 102-104.
        [3]Hui Yan, Yueshan Zhang, Chao Qi, et al. Intraperitoneal thermal-chemotherapy infusion combined with external hyperthermia for intraperitoneal metastasis cancer[J]. Chinese Journal of physical therapy. 2000, 23(5):273-275.
        [4]Shirong Li, Zhihong Xue, Xiaomei Zheng. Clinical observation of therapeutic effect and nursing of intraperitoneal chemotherapy combined with abdominal thermotherapy in the treatment of malignant ascites[J]. Contemporary Medicine, 2009, 15(25):10-11.

        TypeInfo: academic articles

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