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        Clinical analysis of cavity circulatory hyperthermic perfusion in treatment of malignant effusion

        Date:2014年2月26日 15:46

        Xiufeng Ma,  Jinfang Yi,  Baoli Tang, Lei Wang                                     •Clinical Research•

        Key words   malignant effusion; Circulatory hyperthermic perfusion; hyperthermic perfusion chemotherapy
        [CRC] R 730.53    [Document ID code] A    [Article Number] 1002 - 7386(2012) 16-2484 -02
             Malignant effusion is one of the common complications of advanced malignant tumor. It cause great pain, and reduce survival time obviously. Clinicians always feel lack of good approach for treatment of malignant effusion except common ways such as chemotherapy and pumping. However, these approaches can only make the patients temporary comfort, but the effusion may produce more and faster. At the same time, a lot of protein and other nutrients in the body are lost, resulting progression of disease and systemic failure of patients. In order to solve this problem, cavity circulatory hyperthermic perfusion chemotherapy was used to treat both malignant effusion and metastatic lesions. It can make the patients effectively treated, and can reduce the risk of pain, and prolong the survival time. It reported as following.
        1 Patient and Methods
        1.1 General Information A total of 120 patients with malignant effusion were enrolled between June 2008 and December 2011 in oncology department of our Hospital. All the patients were divided into pleural effusion group and peritoneal effusion group. 1 case of pericardial effusion was excluded. 65 cases were in malignant pleural effusion group, including 21cases received systemic chemotherapy, 48 cases of primary lung cancer (32 males, 16 females, with the mean age of 53 years); 11 cases of pulmonary metastasis lesion (5 males, 6 females, with the mean age of 51 years); 6 cases of pleural endotheliomas (all female, with the mean age of 56);54 cases were in  malignant peritoneal effusion group, including 19 cases received systemic chemotherapy, 15 cases of gastroenteric tumor ( 7 males, 8 females, with the mean age of 54); 24 cases with liver caner(18 cases of primary carcinoma, 6 cases of metastasis tumor, 15 males, 11 females, with the mean age of 53 years); 5 cases of malignant mesothelioma (3 cases complicated with pleural effusion, 2 cases with only peritoneal effusion, 1 male and 4 females, with the mean age of 56 years); 10 cases of ovarian cancer with the mean age of 52 years; and 1 case of pericardial effusion . There were no significantly difference of age, sex, symptoms, treatments between the two groups (P>0.05).
        1.2 Treatment   Cavity Circulatory hyperthermic perfusion was used in both of two groups. The effusion was firstly drained through catheter placed under the guiding of ultrasound. Thick effusion can be replaced by hot saline solution. Encapsulated effusion can first inject with urokinase. The cavity was flooded with 0.9% sodium chloride solution (thoracic cavity 1000~1500ml, abdominal cavity 2500~3000ml). The other catheter for outlet was placed. The two catheters were connected with extracorporeal circulation perfusion machine, and set the input temperature as 43.5~45.5℃, and output temperature as 41~42℃, with the flow rate of 150~200ml/min.  20~30 mg cisplatin was added to the solution. The duration of the treatment was 60~90min. At the end of the treatment, 500ml solution was left, and then 10~20mg cisplatin, 10mg dexamethasone, 20mg furosemide and 0.1g lidocaine was injected in cavity, keeping for 24 hr before drainage. 3 times were considered as one course of treatment. The 1d, 3d and 6d were usually chosen to give the treatment. One catheter was not removed after treatment in order to observe the curative effect.

        1.3 Evaluation of the therapeutic effect and complication Observe cavity effusion through the drainage catheter 1 week after treatment. Effusion disappeared (<300ml) was defined as effective. If the case was defined as effective firstly, it needed to be re-confirmed again 4 weeks after treatment. Effective cases confirmed in the 4 weeks can be considered in further statistical analysis. The lost cases were regarded as invalid.
        1.4 Statistical analysis   SPSS 13.0 was used to statistical analysis. Chi-square test was used. P<0.05 was considered to be significantly different.
        2 Results
        11 cases in pleural effusion group were lost during follow-up. Among 54 of follow-up cases, 48 cases were defined as effective case after 1 course; 43 cases without recurrence after 6 months; the longest one case shown 29 months without recurrence; 3 cases recurred in 3 months and then receiving the second course; and 6 cases recurred in 6 months and then giving up further treatment. 9 cases in peritoneal effusion group were lost. Among 45 of follow-up cases, 24 cases were effective cases after 1 course; 11 cases recurred in 3 months; the longest one without recurrence in 18 months; 33 cases were found subcutaneous effusion with self absorption; 41 patients with the symptoms of mild nausea and vomiting, had been controlled by using 3mg of granisetron hydrochloride. The effective rate in pleural effusion group was 73.8%, and it was 44.4% in peritoneal effusion group. There were significantly difference when compared the effective rate of two groups (p<0.05). Especially in primal liver cancer cases, the effective rate is lower, however, no significantly difference in other groups. Table 1~3.

        Table1 Compared of effective rate in two groups

        Groups

        Follow-up (n)

        Effective (n)

        Effective rate (%)

        pleural effusion group (n=65)

        54

        48

            73.8

        peritoneal effusion  group (n=54)

        45

        24

        44.4*

         

        * compared with pleural effusion group, p<0.05


        Table2 Effective rate according to different causes in pleural effusion group

        Causes

        Follow-up

        Effective

        Effective rate(%)

        Primary lung cancer (n=48)

        42

        39

        81.3

        Pleural endotheliomas (n=6)

        4

        3

        50.0

        Metastatic carcinoma (n=11)

        8

        6

        54.5

         

         

         

         

         

        Table3 Effective rate according to different causes in peritoneal effusion group

        Causes

        Follow-up

        Effective

        Effective rate (%)

        Primary liver cancer (n=18)

        15

        3

        16.7

         liver metastasis (n=6)

        5

        2

        33.3

        Mesothelioma (n=5)

        4

        3

        60.0

        Ovarian cancer (n=10)

        8

        6

        60.0

        Gastrointestinal tumor (n=15)

        13

        10

        66.7

         

        3 Discussion
            Constant temperature circulating perfusion chemotherapy in treatment of malignant effusion clinical effect is remarkable, especially for primary pleural effusion caused by lung cancer, its principle is based on the following: (1) tumor tissue had different tolerance to heat compared with normal tissue, and heat have the synergistic effect on tumor killing. Tumor cells have relative weak ability of high temperature resistance, and tumor cells begin to apoptosis and degeneration at 42℃. While none injured effect was found in normal tissue at the temperature at 45~47℃ [1]. (2) Constant temperature circulating perfusion chemotherapy can make the drug diffuse evenly with less die cavity residue. (3) Thermal cycling perfusion can flush out free cancer cells and necrosis cells. (4) Chemotherapy sensitizing effect [2]: Heat can sensitize many drugs, such as cisplatin [3, 4]. .Cisplatin under high temperature can penetrate tumor tissue of 5mm. So it had good effect on free cancer cells and small lesions.
              The effect of hyperthermic perfusion on liver cancer is poor, the following reasons were suggested: (1) Liver cancer often be complicated by liver cirrhosis, portal venous obstruction, portal vein pressure increased, as well as vein tumor thrombus [5]. The high pressure of portal venous and portal vein is an important cause of ascites of liver cancer, then tissue fluid backflow obstruction and leakage into the abdominal cavity. (2) Cancer embolus blockage or tumor compression can block blood circulation of portal vein or hepatic vein. If the blood pressure is too high, it will lead to vascular congestion, increase pressure of hydrostatic, and result imbalance and extravascular fluid exchange. With tissue fluid backflow obstruction, and leakage into the intraperitoneal, ascites formation was found. (3) Hypoproteinemia: Primary liver cancer often occurs in chronic hepatitis, and cirrhosis. Patients often with symptoms of anorexia, nausea, vomiting and so on, and can be associated with different levels of malnutrition and liver function damage. Then hypoproteinemia happened. When plasma protein is low to 25 ~ 30 g /L, decreased plasma colloid osmotic pressure in plasma extravasation make ascites formation.

             In summary, the therapeutic effect of hyperthermic perfusion for malignant effusion not caused by liver cancer was remarkable with high safety. But for those malignant effusion caused by hepatocellular carcinoma or associated with impaired liver, the effect were unfavorable.

        References 
        [1]Yanguang Zhu, Wenchao Liu, et al. The progress of continued hyperthermia perfusion cycle to prevent and cure metastasis cancer in cavity. Journal of modern oncology, 2009, 17: 1165 -1167.
        [2]Duhu Liu, Wenchao Liu, Zhaocai Yu, et al. Clinical effect of coelom hyperthermia perfusion extracorporeal circulatory system in combination with cisplatin in treatment of malignant effusions. Chinese journal of cancer prevention and treatment, 2009, 16: 381-383.
        [3]Xuehui Fang, Qian Wu, Xuemei Han, et al. Hyperthermic Chemoperfusion in the Treatment for 34 Cases with Malignant Ascites. Journal of modern oncology, 2011, 17: 479 -480.
        [4] Jinrong Qiu, Kaihua Lu, Lianke Liu, et al. Clinical observation on high dose cisplatin combining with hyperthermia perfusion chemotherapy on the treatment of malignant ascites. Journal of clinical and experimental medicine, 2006, 5: 1964 -1965.
        [5]Changjiang Li, Jinhua Huang. The present status of treatment in primary hepatic cancer complicated with portal venous tumor. Journal of interventional radiology. 2006, 15: 763.

        TypeInfo: academic articles

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