Study of Predictors for Successful Pleurodesis in Patients with Malignant Pleural Effusion

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1 Med. J. Cairo Univ., Vol. 85, No. 1, March: 11-20, Study of Predictors for Successful Pleurodesis in Patients with Malignant Pleural Effusion TALAT A. ARAFA, M.D.*; MOHAMMED R. MORSI, M.D.**; SAMEH F. MAKLED, M.D.* and MUSTAFA M. GOMAA, M.Sc.* The Departments of Chest Diseases* and Clinical Pathology**, Faculty of Medicine, Al-Azhar University, Egypt Abstract Background: Most of the Malignant Pleural Effusions (MPEs) are the result of metastasis to the pleura from other sites. The primary tumors were, in the decreasing order of frequency: Lung (37%), breast (17%), unknown site (10%), lymphoma (9%), gastrointestinal (8%), ovary (7%) and mesothelioma (3%).Management of malignant effusions depends on palliation of dyspnea and prevention of the reaccumulation of pleural fluid to provide the highest possible quality of life, regardless of the need for other treatment modalities. Pleurodesis is defined as the symphysis between the visceral and parietal pleural surfaces; its function is to prevent accumulation of either air or fluid into the pleural space. Effusions of malignant origin are the most common indication for pleurodesis. Unfortunately, pleurodesis fails in 10-40% of patients with recurrence of pleural fluid and dyspnea. Because pleurodesis is associated with considerable cost and morbidity, the identification of patients who will experience an unsuccessful pleurodesis would be desirable. Objective: To assess the s of the initial pleural fluid LDH, C Reactive Protein (CRP), cholesterol, Adenosine Deaminase (ADA) and PH characteristics on pleurodesis outcome in patients with Malignant Pleural Effusions (MPEs). Methods: The current study was conducted at the Chest Departments of El-Hussein and Saied Galal University Hospitals in the period between December 2015 and May patients with malignant pleural effusion were included in this study. 15 males and 15 females with age ranging between 38 and 75 years (mean age 58.3 ±9.54) were included. They were diagnosed finally by pleural fluid cytology and/or CT guided biopsy or tissue biopsy (Abrams or thoracoscopic biopsied). Informed consent was obtained from all patients enrolled in the study. 21 patients (70%) showed successful pleurodesis, while the remaining 9 patients (30%) showed failed pleurodesis. Results: Pleural fluid s of proteins and LDH has no significant implication on the results of pleurodesis, while s of pleural fluid glucose, CRP, cholesterol and ADA (adenosine deaminase) significantly affect the results of pleurodesis as patient with high pleural fluid glucose, low Correspondence to: Dr. Talat A. Arafa, The Department of Chest Diseases, Faculty of Medicine, Al-Azhar University, Egypt CRP, high cholesterol and high ADA shows successful pleurodesis. Conclusion: Patients with high PH, high glucose levels, low CRP, high cholesterol and high ADA in pleural fluids are more susceptible to successful pleurodesis than patient with the reverse. Values of pleural fluid proteins and LDH have no effect on pleurodesis results in patients with malignant pleural effusion. Key Words: Malignant pleural effusion Pleurodesis Cholesterol ADA CRP. Introduction MOST of the Malignant Pleural Effusions (MPEs) are the result of metastasis to the pleura from other sites. The primary tumors were, in the decreasing order of frequency: Lung (37%), breast (17%), unknown site (10%), lymphoma (9%), gastrointestinal (8%), ovary (7%) and mesothelioma (3%) [1]. Management of malignant effusions depends on palliation of dyspnea and prevention of the reaccumulation of pleural fluid to provide the highest possible quality of life, regardless of the need for other treatment modalities [2]. Pleurodesis is defined as the symphysis between the visceral and parietal pleural surfaces; its function is to prevent accumulation of either air or fluid into the pleural space. Effusions of malignant origin are the most common indication for pleurodesis [3]. Unfortunately, pleurodesis fails in 10-40% of patients with recurrence of pleural fluid and dyspnea. Because pleurodesis is associated with considerable cost and morbidity, the identification of patients who will experience an unsuccessful pleurodesis would be desirable [4]. The utility of various clinical and biochemical parameters in predicting pleurodesis outcome is 11

2 12 Study of Predictors for Successful Pleurodesis in Patients with MPE still controversial. A better definition of the different characteristics of the patient would help to identify more precisely the population mostly benefiting from pleurodesis. These factors may allow clinicians to make better Introduction 2 treatment decisions in a patient with recurrent malignant pleural effusion [5]. Aim of the work: The aim of this work was to assess the s of the initial pleural fluid LDH, C Reactive Protein (CRP), cholesterol, Adenosine Deaminase (ADA) and ph characteristics on pleurodesis outcome in patients with Malignant Pleural Effusions (MPEs). Patients and Methods The current study is a prospective study conducted at the Chest Departments of El-Hussein and Saied Galal University Hospitals in the period between December 2015 and May patients with malignant pleural effusion were included in this study. They were diagnosed finally by pleural fluid cytology and/or CT guided biopsy or tissue biopsy (Abrams or thoracoscopic biopsy). Informed consent was obtained from all patients enrolled in the study. All the patients underwent the following: 1- Full history taking. 2- Complete clinical examination. 3- Laboratory investigations including CBC, liver and kidney functions. 4- PT, PTT, INR. Serum LDH, CRP and cholesterol. 5- Plain chest X-ray, CT. chest and chest US. 6- Arterial Blood Gases (ABG). 7- Pleural fluid analysis including chemical, physical, cytological and microbiological examination. Inclusion criteria: - Massive or rapidly reaccumulating pleural effusion after drainage, which requires frequent thoracentesis. - Subjective improvement of dyspnea following thoracentesis. - Re-expansion of the lung after drainage. - Life expectancy >6 months, Karnofsky performance score >_60. - Pleural fluid ph >7.2. Exclusion criteria: - Atelectasis due to endobronchial obstruction. - Pleural fluid ph < Prior intrapleural therapy in the previous two weeks. - Significant irradiation to the affected hemithorax. - Patient receiving systemic corticosteroids or nonsteroidal antiinflammatory drugs including pure analgesic medication during the study. Procedures: 1- Tube thoracostomy insertion: Conventional large-bore chest tubes (24-28 French) were inserted in all cases. Patients were premedicated with 0.6ml atropine sulfate given intramuscularly 30min prior to the procedure. Proper position with the patient supine, skin disinfection and anesthesia was infiltrated with 10CC xylocaine 2% followed by aspiration to confirm the presence of the fluid. An incision about 2cm was done in the fifth or sixth intercostals space in the midaxillary line. The incision was made at the upper border of the rib below and parallel to the rib. A large bore chest tube (24-28 French) was used to allow adequate drainage. After appropriate positioning, fixation of the tube was done by the suture. The chest tube was connected to underwater seal to allow slow drainage of the effusion. Amount of drained pleural fluid, drainage time was recorded. When the amount became less than 100ml/24 h and chest X-ray showed complete lung expansion and there was no evidence of bronchopleural fistula, pleurodesis was carried out. 2- Pleurodesis: Premedication with 20cc xylocaine 2% was installed intrapleurally 30min before chemical agent was injected, then 50ml of 10% iodopovidone mixed with 20-30ml of normal saline was injected into the pleural space, clamp chest catheter for 2h, all patients underwent rotational maneuvers during the time that the chest tube was clamped. After 2h, the tube was opened. Amount of pleural fluid drained after pleurodesis was recorded. The chest tube was removed when the drainage fell below 100ml/24h, and a chest X-ray was obtained to confirm complete lung expansion. All complications from the pleurodesis were recorded. Each patient had a pre-drainage baseline

3 Talat A. Arafa, et al. 13 Posteroanterior (PA) radiograph. Post-Pleurodesis PA radiographs were obtained at the following time: (1) After removal of the chest tube, (2) 3 days after removal (early response), and (3) 4 weeks (late response) following the procedure [1]. Assessment of the response was based on radiologic appearance: - At the end of the 4 weeks follow-up period, the radiographic response was classified as follows: A) Complete response; no re-accumulation of pleural fluid after postpleurodesis radiography, B) Partial response; re-accumulation above the post-pleurodesis level, but below the pre pleurodesis level, (C) No response; reaccumulation above the pre-pleurodesis level. - Global response refers to the sum of the complete and partial responses. - The patients who died or who were lost to followup within the first month of chest tube removal were excluded from the study [4]. Statistical analysis: Data analysis was performed using Statistical Package for Social Sciences, Version 20.0 (SPSS), p 0.05 was considered statistically significant. Parametric data was expressed as mean ± standard deviation and was compared using paired or independent student t-test. Results Table (3): Histopathological types of malignancy in the studied population. Histopathological types of malignancy N % Pleural mesothelioma Bronchogenic adenocarcinoma 9 30 Infiltrating ductal carcinoma 6 20 Ovarian adenocarcinoma Renal cell carcinoma Gastric adenocarcinoma Total Table (4): Outcome of pleurodesis in the studied population. Total number of patients Successful pleurodesis Failed pleurodesis N % N % N % Table (5): Relation between the age of the patients and pleurodesis outcome. (successful pleurodesis) (Failed pleurodesis) Age 57.57± ±7.42 Table (1): Characteristics of the studied population. Characteristics Patients (N=30) Age (years) (38-75) Gender: Male 15 (50%) Female 15 (50%) Smoking habit: Mean ± S.D (58.3±9.54) Non smoker 20 (66.67%) Smoker 10 (33.33%) Table (2): Side of malignant pleural effusion in the studied population. Side of effusion N % Right sided Left sided Total Table (6): Relation between sex of the patients and pleurodesis outcome. Sex Total Male Female Non-smoker Smoker N % N % N % N % N % N % Total Total Table (7): Relation between smoking habit and pleurodesis outcome. Smoking habits Total

4 14 Study of Predictors for Successful Pleurodesis in Patients with MPE Table (8): Relation between the main complaint of the patients Table (12): Relation between drainage time and pleurodesis outcome. Main complaint Total N % N % N % Drainage time (days) p- Dyspnea Fever Chest pain Cough Total Right Left N 15 6 % N % N % Total Table (9): Relation between the side of effusion and pleurodesis outcome. Side of effusion Total ± ±3.97 Amount of pleural fluid drained before pleurodesis (cc3) Table (13): Relation between amounts of pleural fluid drained before pleurodesis ± ± p- Table (14): Relation between amounts of pleural fluid drained after pleurodesis Amount of pleural fluid drained after pleurodesis (cc3) p- Table (10): Relation between Karnofsky performance score ± ± Karnofsky performance score ± ± Table (15): Relation between the of pleural fluid total proteins Pleural fluid total proteins (gm/dl) p- Table (11): Relation between the histopathological types of malignancy ± ±0.34 Histopathological types of malignancy Pleural mesothelioma Bronchogenic adenocarcinoma Infiltrating ductal carcinoma Ovarian adenocarcinoma Renal cell carcinoma Gastric adenocarcinoma Total N % N % N % Total Table (16): Relation between the of pleural fluid glucose Pleural fluid glucose (mg/dl) ± ±6.42 < This table clarifies that the of pleural fluid glucose in the patients of Group (I) ranged from 91mg/dl to 118mg/dl with mean of mg/dl, while in Group (II) the of pleural fluid glucose in the patients ranged from 43mg/dl to 62mg/dl with mean of 54.9mg/dl. There was highly significant statistical difference between the two groups in relation to the of pleural fluid glucose.

5 Talat A. Arafa, et al. 15 Table (17): Relation between the of pleural fluid LDH Pleural fluid LDH (IU/L) p ± ± This table clarifies that the of pleural fluid ADA in the patients of Group (I) ranged from 21IU/L to 44IU/L with mean of 33.33IU/L, while in Group (II) the of pleural fluid ADA in the patients ranged from 6IU/L to 15IU/L with mean of 12.33IU/L. There was highly significant statistical difference between the two groups as regard the of pleural fluid ADA. Table (18): Relation between the of pleural fluid CRP Table (21): Relation between the of pleural fluid ph Pleural fluid CRP (mg/l) Pleural fluid ph p ± ±0.56 < ± ±0.023 < This table clarifies that the of pleural fluid CRP in the patients of Group (I) ranged from 2.1mg/L to 3.1mg/L with mean of 2.64mg/L, while in Group (II) the of pleural fluid CRP in the patients ranged from 3.6mg/L to 5.1 mg/l with mean of 4.53mg/L. There was highly significant statistical difference between the two groups in relation to the of pleural fluid CRP. Table (19): Relation between the of pleural fluid cholesterol Pleural fluid cholesterol (mg/dl) ± ±9.28 < This table clarifies that the of pleural fluid cholesterol in the patients of Group (I) ranged from 65mg/dl to 160mg/dl with mean of mg/dl, while in Group (II) the of pleural fluid cholesterol in the patients ranged from 63mg/dl to 85mg/dl with mean of 75.44mg/dl. There was highly significant statistical difference between the two groups in relation to the of pleural fluid cholesterol. Table (20): Relation between the of pleural fluid ADA Pleural fluid ADA (IU/L) ± ±3.28 < This table clarifies that the of pleural fluid ph in the patients of Group (I) ranged from 7.33 to 7.45 with mean of 7.38, while in Group (II) the of pleural fluid ph in the patients ranged from 7.22 to 7.29 with mean of There was highly significant statistical difference between the two groups in relation to the of pleural fluid ph. Discussion In this study, 22 patients (73.33%) had right side pleural effusion while, 8 patients (26.67%) had left side pleural effusion. This correlates with the study of Kabil et al., [6]. They reported that right side pleural effusion was more common than left side. In their study, 56.67% of the patients had right side pleural effusion and 43.33% of patients had left side pleural effusion. The study by Alwakil et al., [7] also reported that right side pleural effusion was more common than left side. In their study, 53.3% of the patients had right side pleural effusion and 46.7% of patients had left side pleural effusion. In this study, 12 patients (40%) had pleural mesothelioma, 9 patients (30%) had bronchogenic adenocarcinoma, 6 patients (20%) had infiltrating ductal carcinoma, 1 patient (3.33%) had ovarian adenocarcinoma, 1 patient (3.33%) had renal cell carcinoma and 1 patient (3.33%) had Gastric adenocarcinoma. This correlates with the study of Hasanen et al., [8]. They reported that pleural mesothelioma was the most common malignancy producing MPE. In their study, 66% of the patients had pleural mesothelioma, 14% of patients had breast cancer and 6% of patients had lung cancer. The study by Yildirim et al., [5] also reported that pleural mesothelioma was more common than lung

6 16 Study of Predictors for Successful Pleurodesis in Patients with MPE cancer. In their study, 53.2% of the patients had pleural mesothelioma and 27.3% of patients had lung cancer. Lung cancer is the most common malignancy producing MPE, followed by breast cancer and lymphoma. However, malignant mesothelioma was the most common primary malignancy observed in this series. The high incidence of malignant mesothelioma in the present study can be attributed to the fact that environmental asbestos exposure due to the use of asbestos-contaminated white-soil is very widespread in our rural region [5]. This deviation may be due to the large number of patients in the current study inhabiting Shobra El-Kheima, where malignant mesothelioma is not a rare tumor due to previous heavy asbestos exposure [8]. In this study, after 4 weeks follow-up, pleurodesis was found to be successful in 21 patients (representing 70% of the studied population), while it failed in the remaining 9 patients. The current study results on iodopovidine pleurodesis agreed with a study done by Hasanen et al., [8] who treated 25 malignant pleural effusion patients with iodopovidine pleurodesis. A successful pleurodesis was accomplished in 18 (72%). We had two groups: Group (I), 21 patients of successful pleurodesis. Group (II), 9 patients of failed pleurodesis. The age of patients in Group (I) ranged from 38 years to 75 years with a mean age of years and standard deviation of In Group (II) patients, the age of patients ranged from 50 years to 72 years with a mean age of 60 years and standard deviation of There was no statistical difference between the two groups as regard age of patients in each group. As regard sex of patients in the studied groups, 9 patients (42.9%) were males and 12 patients (57.1%) were females in Group (I) patients while, 3 patients (33%) were males and 6 patients (67%) were females in Group (II) patients. However there was no significant statistical difference between the studied groups as regard sex of patients. These results were in accordance with the results obtained in the study performed by Shehata et al., [9] who found no correlation between the sex of patients and the success or failure of pleurodesis. The study by Yildirim et al., [5] reported that the overall success rate of pleurodesis was significantly higher in females than in males. One possible explanation for the differences in the results as a function of gender may be that chemotherapysensitive tumors, such as breast cancer, are more common in females. The patients received systemic chemotherapy for underlying malignancies after pleurodesis. In this study, there were 15 patients (71.43%) non-smoker and 6 patients (28.57%) were smoker in Group (I). In Group (II) 5 patients (55.56%) were non-smoker and 4 patients (44.44%) were smoker with no significant statistical difference between the studied groups as regard smoking habits. Dyspnea was the main complaint in 13 patients (61.9%) in Group (I) and 5 patients (55.56%) in Group (II). Fever was the main complaint in 3 patients (14.29%) in Group (I) and 1 patient (11.11%) in Group (II). Chest pain was the main complaint in 3 patients (14.29%) in Group (I) and 2 patients (22.22%) in Group (II). Cough was the main complaint in 2 patients (9.52%) in Group (I) and 1 patient (11.11%) in Group (II). There was no statistical difference between the two groups as regard main complaint of patients. This correlates with the study of Kabil et al., [6]. They reported that the commonest complaint was dyspnea in 60% of patients, while chest pain was the main complaint in 16.67% of patients, fever was the main complaint of 11.67% of patients and cough was the main complaint of 11.67% of patients. Elbalsha et al., [10] reported that the commonest complaint was dyspnea in 76.67% of patients, while chest pain was the main complaint of 16.67% of patients and fever was the main complaint of 6.67% of patients. Baess et al., [11] reported that dyspnea was the most common presenting complaint in their study. Symptoms encountered were dyspnea in 98.3% patients, cough in 28.3% of patients, chest pain in 40% of patients, wheezes in 13.3% of patients, fever in 5% of patients and loss of weight in 46.7% of patients which correlates with this study. In this study, in Group (I) 15 patients (71.43%) had right sided pleural effusion and 6 patients (28.57%) had left sided pleural effusion, in Group (II) 7 patients (77.78%) had right sided pleural effusion and 2 patients (22.22%) had left sided pleural effusion. There was no significant statistical difference between the two groups in relation to the diseased side. This correlates with the study of Rafei et al., [12]. They reported that no significant

7 Talat A. Arafa, et al. 17 differences were found among the outcome of pleurodesis and the side of effusion. Their study was conducted upon 44 patients. Pleurodesis succeed in 19 patients and failed in the remaining 25 patients. In group of successful pleurodesis, 10 patients (52.63%) had right sided pleural effusion, 7 patients (36.84%) had left sided pleural effusion and 2 patients (10.53%) had bilateral pleural effusion, while in group of failed pleurodesis, 13 patients (52%) had right sided pleural effusion, 9 patients (36%) had left sided pleural effusion and 3 patients (12%) had bilateral pleural effusion. In this study, Karnofsky performance score in Group (I) ranged from 60 to 100 with mean of and standard of deviation of 15.6, while in Group (II) Karnofsky performance score ranged from 60 to 90 with mean of and standard of deviation of There was no significant statistical difference between the two groups in relation to Karnofsky performance score. These results were in accordance with the results obtained in the study performed by Shehata et al., [9] who found no correlation between Karnofsky performance score and the success or failure of pleurodesis. The KPS score index allows patients to be classified according to their functional impairment. A higher score means the patient is better able to carry out daily activities [5]. The study by Yildirim et al., [5] reported that the KPS score was significantly higher in successful patients as compared with the unsuccessful group. As regard the histopathological types of malignancy, in Group (I) 9 patients (42.86%) had pleural mesothelioma, 6 patients (28.57%) had bronchogenic adenocarcinoma, 4 patients (19.05%) had infiltrating ductal carcinoma, 1 patients (4.76%) had ovarian adenocarcinoma and 1 patients (4.76%) had Gastric adenocarcinoma, in Group (II) 3 patients (33.33%) had pleural mesothelioma, 3 patients (33.33%) had bronchogenic adenocarcinoma, 2 patients (22.22%) had infiltrating ductal carcinoma and 1 patients (11.11%) had renal cell carcinoma. There was no significant statistical difference between the two groups in relation to the histopathological types of malignancy. These results were in accordance with the results obtained in the study performed by Shehata et al., [9] who found no correlation between the pathological etiology of malignant pleural effusion and the success or failure of pleurodesis. The study by Yildirim et al., 2008 [5] also reported that no significant differences were found among the outcome of pleurodesis and histopathologic types of malignant disease. In this study, the drainage time of the patients in Group (I) ranged from 1 day to 22 days with mean drainage time of 6.9 days and standard of deviation of 4.45 days, while in Group (II) the drainage time of the patients ranged from 1 day to 12 days with mean drainage time of 5.44 days and standard of deviation of 3.97 days. There was no significant statistical difference between the two groups in relation to drainage time. These results were in accordance with the results obtained in the study performed by Shehata et al., [9] and Yildirim et al., [5] who found no correlation between drainage time and the success or failure of pleurodesis. In this study, the amount of pleural fluid drained before pleurodesis in Group (I) ranged from 1850 cc3 to 3250 cc3 with mean amount of cc3 and standard of deviation of cc3, while in Group (II) the amount of pleural fluid drained before pleurodesis ranged from 1700 cc3 to 3100 cc3 with mean amount of cc3 and standard of deviation of cc3. There was no significant statistical difference between the two groups in relation to amount of pleural fluid drained before pleurodesis. These results were in accordance with the results obtained in the study performed by Yildirim et al., [5] who found no correlation between the amount of pleural fluid drained before pleurodesis and the success or failure of pleurodesis. In this study, the amount of pleural fluid drained after pleurodesis in Group (I) ranged from 750 cc3 to 1350 cc3 with mean amount of cc3 and standard of deviation of cc3, while in Group (II) the amount of pleural fluid drained after pleurodesis ranged from 600 cc3 to 1400 cc3 with mean amount of cc3 and standard of deviation of cc3. There was no significant statistical difference between the two groups in relation to amount of pleural fluid drained after pleurodesis. These results were in accordance with the results obtained in the study performed by Yildirim et al., [5] who found no correlation between the amount of pleural fluid drained after pleurodesis and the success or failure of pleurodesis. In this study, the of pleural fluid total proteins in the patients of Group (I) ranged from 4.4gm/dl to 5.4gm/dl with mean of 4.96gm/dl and standard of deviation of 0.33gm/dl, while in Group (II) the of pleural fluid total proteins in the patients ranged from 4.3gm/dl to 5.3gm/dl with mean of 4.81 gm/dl and standard of deviation of 0.34gm/dl. There was no significant statistical difference between the two groups in relation to the of pleural fluid total proteins. These results were in accordance with the results

8 18 Study of Predictors for Successful Pleurodesis in Patients with MPE obtained in the study performed by Yildirim et al., [5] who found no correlation between the of pleural fluid total proteins and the success or failure of pleurodesis. In this study, the of pleural fluid glucose in the patients of Group (I) ranged from 91mg/dl to 118mg/dl with mean of mg/dl and standard of deviation of 7.59mg/dl, while in Group (II) the of pleural fluid glucose in the patients ranged from 43mg/dl to 62mg/dl with mean of 54.9mg/dl and standard of deviation of 6.42 mg/dl. There was highly significant statistical difference between the two groups in relation to the of pleural fluid glucose. These results were in accordance with the results obtained in the study performed by Shehata et al., [9] who found highly significant correlation between the of pleural fluid glucose and the success or failure of pleurodesis. Heffner et al., [4] reported that pleural fluid levels of glucose carried significant statistical difference between the two groups of patients with cut-off points that discriminated failure from success 72mg/dl. In this study, the of pleural fluid LDH in the patients of Group (I) ranged from 410IU/L to 1100IU/L with mean of IU/L and standard of deviation of IU/L, while in Group (II) the of pleural fluid LDH in the patients ranged from 570IU/L to 1120IU/L with mean of IU/L and standard of deviation of IU/L. There was no significant statistical difference between the two groups in relation to the of pleural fluid LDH, these results were in accordance with the results obtained in the study performed by Yildirim et al., [5] and Rafei et al., [12] who found no correlation between the of pleural fluid LDH and the success or failure of pleurodesis. In this study, the of pleural fluid CRP in the patients of Group (I) ranged from 2.1mg/L to 3.1mg/L with mean of 2.64mg/L and standard of deviation of 0.35mg/L, while in Group (II) the of pleural fluid CRP in the patients ranged from 3.6mg/L to 5.1mg/L with mean of 4.53 mg/l and standard of deviation of 0.56mg/L. There was highly significant statistical difference between the two groups in relation to the of pleural fluid CRP. These results were in accordance with the results obtained in the study performed by Shehata et al., [9] who found highly significant correlation between the of pleural fluid CRP and the success or failure of pleurodesis. Lapidot et al., [13] stated that pleural fluid CRP levels may reliably predict pleurodesis success and symptomatic failure among malignant pleural effusion patients. The high level of CRP is an indication of the inflammatory response within the pleural cavity induced by neoplastic progression [14]. In this study, the of pleural fluid cholesterol in the patients of Group (I) ranged from 65mg/dl to 160mg/dl with mean of mg/dl and standard of deviation of 19.34mg/dl, while in Group (II) the of pleural fluid cholesterol in the patients ranged from 63mg/dl to 85mg/dl with mean of 75.44mg/dl and standard of deviation of 9.28mg/dl. There was highly significant statistical difference between the two groups in relation to the of pleural fluid cholesterol. These results were in accordance with the results obtained in the study performed by Yildirim et al., 2008 [5] who found highly significant correlation between the of pleural fluid cholesterol and the success or failure of pleurodesis with cut-off point 82mg/dl. In this study, the of pleural fluid ADA in the patients of Group (I) ranged from 21IU/L to 44IU/L with mean of 33.33IU/L and standard of deviation of 6.61IU/L, while in Group (II) the of pleural fluid ADA in the patients ranged from 6IU/L to 15IU/L with mean of IU/L and standard of deviation of 3.28IU/L. There was highly significant statistical difference between the two groups in relation to the of pleural fluid ADA. These results were in accordance with the results obtained in the study performed by Yildirim et al., [5] who found highly significant correlation between the of pleural fluid ADA and the success or failure of pleurodesis with cutoff point 18IU/L. In this study, the of pleural fluid ph in the patients of Group (I) ranged from 7.33 to 7.45 with mean of 7.38 and standard of deviation of 0.034, while in Group (II) the of pleural fluid ph in the patients ranged from 7.22 to 7.29 with mean of 7.25 and standard of deviation of There was highly significant statistical difference between the two groups in relation to the of pleural fluid ph. These results were in accordance with the results obtained in the study performed by Yildirim et al., 2008 [5] who found highly significant correlation between the of pleural fluid ph and the success or failure of pleurodesis with cut-off point 7.34 The study by Shoukry et al., [15] showed that there was highly significant statistical difference between the two groups of patients as regards:

9 Talat A. Arafa, et al. 19 Pleural fluid ph, glucose and LDH levels, while there was no significant statistical difference between the two groups of patients as regards: Pleural fluid level of total proteins and serum level of LDH. It was found that the most sensitive markers that discriminated those with failed pleurodesis from those with successful pleurodesis were pleural fluid levels of ph and LDH where the cut-off points that discriminated success from failure were: ph <7.33 and LDH >1023IU/L (with decreasing ph <7.33 and increasing LDH >1023IU/L, there was increased probabilities of pleurodesis failure). Heffner et al., [4] reported that pleural fluid levels of ph carried significant statistical difference between the two groups of patients with cut-off points that discriminated failure from success <_7.28. Furthermore, they found that at very low ph s (<7.15), the specificity and negative predictive s of ph for predicting symptomatic pleurodesis failure exceeded 90% and 80% respectively with positive predictive of 45.7%. The American Thoracic Society and European Respiratory Society guideline for the management of MPE recommends that pleurodesis should be limited to patients with pleural fluid ph s >7.30 because of the direct correlation between low ph and poor short term survival [12]. Alsayed et al., [16] reported that there is relationship between glucose and ph levels in pleural fluid and their effect on pleurodesis success. The mechanisms that cause pleural fluid glucose and PH to drop are intimately related since glucose metabolism brings about intrapleural H+ ion generation and the cells in the pleural fluid as well as those in the lining play an active role in this metabolic process. The abnormal pleural membrane, a result of tumor infiltration and fibrosis appears primarily responsible for low ph and glucose. There is impaired glucose transfer from blood to pleural fluid and vice versa in patients with low ph. Glucose in pleural fluid is metabolized into the end products CO 2 and Lactic acid. Due to abnormal pleura in patients with low ph effusions, the rate of transport of CO 2 and lactic acid out of pleural space is slowed and accumulation occurs resulting in decreased pleural fluid ph. The results showed that there was highly significant statistical difference between the two groups of patients as regards pleural fluid glucose, CRP, cholesterol, ADA and ph levels, while there is no significant statistical difference between the two groups of patients as regards pleural fluid level of total proteins and LDH. 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