| According to the union for international cancer control (UICC) on TNM staging of lung cancer, malignant pleural effusion (MPE) or pleural malignant tumor nodules are classified as stage Mla, stage IV lung cancer. The main characteristics of the patients is the presence of MPE.Malignant pleural effusion is caused by malignant tumor pleural effusion, which is a common complication of advanced cancer. MPE belongs to theeffusion. It can be caused by a variety of pathological types of lung cancer, the most common in lung adenocarcinoma. The majority of MPS is caused by malignant tumors involving or metastasis to the pleura. This not only reduces the quality of life of patients, but also can cause a decrease in the lifetime of patients. Patients with a large volume of malignant pleural effusion have a poor prognosis. According to the statistical data, the median survival time of patients with malignant pleural effusion caused by pleural metastases was 3-4 months, and mesothelioma patients with MPE is 9-12 months. If a lung cancer patient got MPE, his prognosis will be very poor, because his median survival time is only 2.2-4 months.The main symptom of patients with MPE is a different degree of dyspnea, and this is proportional to the volume of MPE. Some patients was diagnosed with MPE in physical examination but he didn’t have any symptoms. A large volume of MPE can lead to the ipsilateral lung tissue compression and limit its ventilation expansion. Further pulmonary atelectasis and pulmonary infection came. Patients with MPE is often accompanied by irritating cough, chest pain and other symptoms, such as hypoproteinemia, anemia, fatigue, malnutrition, weight loss and so on. More serious is that massive pleural effusion would limit the diaphragmatic movement and push the mediastinum to the contralateral shift.[Objective]To compare the effect of intravenous chemotherapy combined with continuous circulatory intrapleural perfusion hyperthermia (CCIPH) and intravenous chemotherapy alone on life quality and progress free survival of Stage Mia non-small-cell carcinoma, and evaluate the curative effect and safety of CCIPH, to accumulate experience in such conditions.[Subjects and materials]Twenty-one patients with malignant tumor combined with pleural effusion, i.e. Stage M1a patients as classified in the TNM staging system of the Union for International Cancer Control, who visited the Department of thoracic surgery of Nanfang Hospital of Southern Medical University between March 2013 and April 2014, were chosen. All cases showed unilateral pleural effusion, and diagnosed by chest X ray and/or chest ultrasound with medium or massive pleural effusion, with the Karnofsky Performance Status Scale being 40-60 before treatment. Meanwhile, 12 patients with the same conditions who visited Nanfang Hospital for routine intravenous chemotherapy between January 2012 and March 2013 were subject to a retrospective analysis. The BR-TRG-I Hyperthermic Perfusion Intraperitoneal Treatment System manufactured by Guangzhou Bright Medical Technology Co., Ltd was used. Equipment and materials used in the treatment mainly included: supporting equipment and instruments of thoracoscope, sterile water for injection, pethidine hydrochloride injection (dolantin), promethazine hydrochloride injection (phenergan), disposable tubing components, electrocardiogram monitor, oxygen inhalation-related equipment, etc.[Methods and steps]Subjects were divided into Groups A, B and C, samples in Groups A and B were chosen randomly, and those in Group C were patients with the same conditions who visited our hospital before this study started. Group A was treated with circulatory intrapleural hyperthermal perfusion chemotherapy combined with intravenous chemotherapy, Group B treated with circulatory intrapleural hyperthermal perfusion combined with intravenous chemotherapy, and Group C treated with intravenous chemotherapy. No statistic differences existed in sex, age, and pleural effusion volume and nature between the three groups.All cases in Groups A and B received intrapleural hyperthermal perfusion twice, with an interval of at least 24h in between. Four weeks after the hyperthermal perfusion, the intravenous chemotherapy in which 150 mg/m2 paclitaxel and 80 mg/m2 Nedaplatin were used, began and lasted for 4 weeks. Chemotherapy was performed four times, with an interval of 3 weeks. Patients in Group C were subject to the same therapeutic regimen as for those in Groups A and B. A long term follow-up was conducted to assess curative effect and patients’ conditions.(1) Patients subject to intubation via thoracentesis for hyperthermal perfusion under local anesthesia, were treated as follows:1) Selection of point of puncture:In most cases, the 4th intercostal space along the anterior line axilary of the affected side was chosen as the site for intubation, and the corresponding tube was the feeder; no additional intubation was needed for drainage, since the intrathoracic drain placed between the intersection of the 7th intercostal space and the midaxillary line after the VATS procedure was used as the drainage tube.2) Sterization, surgical towel placement and intubation:Sterization, and placement of surgical towel and drain was performed as for routine intubation via thoracentesis.3) Tubing connection:Clipped water inlet and outlet pipes were each connected to a dedicated CCIPH tube, and the dedicated tubes were connected to the BR-TRG-I Hyperthermic Perfusion Intraperitoneal Treatment System, and now a complete circulatory tube system was established.4) Adding perfusate:Sterile water for injection was used for the perfusate. The perfusate totaling 2500 ml was added into the sterile bag in the dedicated component, that of Group A added with 80 mg/m2 Nedaplatin while no chemotherapeutic agent added to that of Group B.5) Setting treatment parameters:Treatment temperature,46 ℃; rates of circulation,100 ml/min at the beginning of feeding and ramped up to 200-300 ml/min within 5min;treatment duration,60min.6) Tranquilizing and pain easing:50 mg of pethidine hydrochloride injection (dolantin) was injected intramuscularly 1h before the perfusion, and 25 mg of promethazine hydrochloride injection (phenergan) was injected intramuscularly half an hour before the perfusion.7) Starting treatment:After preheating, the feeder was open to start perfusion. During treatment, blood pressure, heart rate, electrocardiographic wave, oxygen saturation of blood, respiration, body temperature and other vital signs of the patients were monitored.8) Treatment completion:After the treatment is completed, the feeder and the drainage tube were connected to the closed pleural effusion drainage bottle. Another perfusion was performed after a minimum of 24h, using the same methods as mentioned above.9) Groups A and B were subject to curative effect evaluation and intravenous chemotherapy with the same therapeutic regimen as mentioned above at the 4th week as calculated from the commencement of the last CCIPH. And a long term follow-up was performed.(2) Patients diagnosed with malignancy combined with malignant pleural effusion (MPE) during VATS procedure were subject to the first CCIPH after the procedure. The remaining steps were the same as of CCIPH under local anesthesia.(3) Evaluation system:The safety and pleural effusion control effect of hyperthermal perfusion were evaluated in terms of heart rate, blood pressure, body temperature and oxygen saturation of blood obtained during the treatment and based on the malignant pleural effusion evaluation standard proposed by the Union for International Cancer Control. The effectiveness of the three therapies was evaluated by means of Karnofsky Performance Status Scale and progression free survival.(4) Statistical analyses:Categorical data were analyzed with X2 test, progression free survival analyzed with K-M method, statistical significance was defined as p< 0.05.[Results]All patients in Groups A and B completed hyperthermal perfusion successfully, no failure or interruption of treatment. The equipment and instruments functioned properly without accidents. Main adverse reactions in all patients of Groups A and B during hyperthermal perfusion were slight pain, increased heart rate and elevated body temperature, to all of which no special treatment was given and which were well tolerated by all patients. Adverse reactions in all patients of Groups A, B and C after intravenous chemotherapy were common side effects seen after intravenous chemotherapy, such as myelosuppression, gastrointestinal reaction, and so on.(1) Adverse reactions1) Increased heart rate:Heart rate increased to different degrees in all patients of Groups A and B during the first hyperthermal perfusion, the increment being 0-31 beats/min and only two cases beyond the normal value (60-100 beats/min). Heart rate also increased to different degrees but exceeded the normal value during the second hyperthermal perfusion, with an increment of 18-33 beats/min; moderate tachycardia (116-130 beats/min) occurred in 9 cases, no severe tachycardia; for all patients, the electrocardiographic wave indicated nodal tachycardia, no proiosystole and change in the ST segment, and no special treatment needed. After the treatment, the situation was restored to the baseline level within 1h after patients rested without movement. Moderate tachycardia occurred in 33.3%(3/9) and 50%(6/12) of cases in Groups A and B respectively, no statistical differences between these two groups (P=0.660).2) Elevated body temperature:During hyperthermal perfusion, patients sweated profusely, their body temperature increased to varied degrees, and their axillary temperature increased by 0.2-1.6℃, no severe temperature elevation and no special treatment given; temperature of all patients returned automatically to the baseline level within 1h after the treatment. Mild to moderate elevation of body temperature occurred in 55.6%(5/9) and 66.7%(8/12) of patients of Groups A and B, respectively. No statistical differences existed between the two groups (P=0.673).3) During the treatment, patients complained of varied degrees of choking sensation and constriction in the chest, which became tolerated after appropriate adjustment of perfusion rate and volume was made. All patients had stable oxygen saturation of blood, and showed no nausea, vomiting, electrolyte imbalance and hepatic and renal functional impairment after the treatment; no observable side effect occurred in Group A after the chemotherapy.(2) Curative effect1) Pleural effusion control:Total pleural effusion remission rates (CR+PR) were 100% for both Groups A and B; Group A had a CR of 88.9%, a PR of 11.1%, and Group B had a CR of 75.0% and a PR of 25.0%. No statistical differences existed between the two groups (P= 0.603).2) Life quality improvement:After the treatment, the Karnofsky Performance Status Scale increased for both Groups A and B; 5 (55.6%,5/9) cases in Group A improved significantly, and 5 (41.7%,5/12) cases in Group B improved significantly, no statistical differences existing between the two groups (P=0.670). After the treatment, some patients of Group C had an unchanged or decreased Karnofsky Performance Status Scale, the significant improvement rate and the improvement rate for Group C were 0 and 58.3%(7/12) respectively. Groups B and C were statistically different (P=0.007).3) Progress free survival:The mean progression free survival (months) for Groups A, B and C were 12.511 (95% confidence intervals (95% CI),11-14),12.224 (95% CI,10-14) and 8.183 (95% CI,8-9) respectively, and the median progression free survival (months) for Groups A, B and C were 11.9 (95% CI,10-14),11.6 (95% CI,10-13) and 7.9 (95% CI,7-8) respectively. Inter-group comparison between Groups A, B and C:No differences existed in the effect of therapy on progression free survival between Groups A and B (P=0.818), whereas there were significant differences in the effect of therapy on progression free survival between Groups A and C (P=0.001) and between Groups B and C (P=0.009).[Conclusion](1) Topical therapy with continuous circulatory intrapleural perfusion hyperthermia is safe, simple, well-tolerated, with a good short-term curative effect and a bright prospect with respect to application; it is worth promotion.(2) Continuous circulatory intrapleural perfusion hyperthermia, alone or combined with a chemotherapeutic agent, is better than intravenous chemotherapy alone in terms of curative effect, life quality improvement and progress free survival, can be used as the routine topical therapy for Stage Mla lung cancer; it has the positive effect of prolonging patients’survival in conjunction with systemic therapy. |
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