Rigid Medical Minithoracoscopy Versus the Rigid Standard Medical Thoracoscopy in Patients with Loculated Pleural Effusion

Background: Surgical intervention is the preferred modality for management of loculated pleural effusions in many studies. The role of the medical thoracoscopy including the standard or the minithoracoscopy for diagnosis of loculated pleural effusions is still not clearly established.

Methods: A prospective interventional randomized study that included 60 patients with undiagnosed loculated pleural effusions admitted to the Chest medicine department, Mansoura university hospitals, Mansoura, Egypt. Patients were divided randomly into two groups. group-1 of 30 patients, they underwent rigid standard medical thoracoscopy and group-2 of 30 patients and they underwent rigid medical minithoracoscopy.

Results: Most patients were males, comprising 73.3% of patients in group-1 and 86.7% of patients in group-2. The mean time of the procedure was shorter in group-1 compared to group-2 with no significant difference. The biopsy sizes were significantly larger in group-1 compared to group-2. Post-procedure pain was significantly less severe in group-2 compared to the group-1 and no mortality reported in both groups. The diagnostic yield was 80% in group-1 and 66.7% in group-2 with no statistically significant difference between the two groups. Thoracoscopic biopsies revealed tuberculosis in 36.67%, malignancy in 36.67% and nonspecific pleurisy in 26.67% of patients. Hospital stay was significantly shorter in group-2 compared to group-1 patients.

Conclusion: Minithoracoscopy is recommended to be used as an alternative procedure to the standard medical thoracoscopy before considering surgical intervention for undiagnosed loculated pleural effusions. Minithoracoscopy is well tolerated with less severe post-procedure pain, comparable diagnostic yield and shorter hospital stay compared to the standard thoracoscopy.

Pleural effusion is an excessive accumulation of fluid in the pleural space due to imbalance between pleural fluid formation and removal. Pleural effusions accompany a wide variety of disorders of the lung, pleura and systemic disorders. The pleural fluid may become encapsulated by adhesions anywhere between the parietal and the visceral pleura or in the interlobar fissures. Encapsulation occurs most frequently in association with conditions that cause intense pleural inflammation, such as empyema, hemothorax, tuberculosis, malignancy, collagen vascular diseases and other inflammatory states [1,2].  Thoracoscopy is a procedure that allows examination of the pleural space and intrathoracic structures, aids in obtaining tissue and performing interventions under direct visual guidance. Minithoracoscopy is defined as an endoscopy with instruments of a diameter between 2 and 5 mm to distinguish it from micro-/needle endoscopy [3]. 

Aim of the Study

This study was planned to assess the efficacy and safety of minithoracoscopy in patients with undiagnosed loculated pleural effusions in comparison with the standard medical thoracoscopy.

A prospective interventional randomized study that included 60 patients with undiagnosed loculated pleural effusions admitted to the Chest medicine department, Mansoura university hospitals, Mansoura, Egypt. It is conducted in the period from October 2017 to October 2019. Patients older than 18 years with loculated pleural effusion were included in the study. Exclusion criteria were patients who refused the procedure and presence of contraindications for performing medical thoracoscopy as the lack of pleural space due to advanced empyema, previous pleurodesis, uncontrolled bleeding diathesis, intractable arrhythmias and uncorrectable hypoxemia despite oxygen therapy [4].

Study Design

The patients were divided randomly into two groups. Group-1 included 30 patients, they underwent rigid standard medical thoracoscopy (Karl Storz Company, Germany) according to the protocol of Astoul and Breen [5]. Group-2 included 30 patients and they underwent rigid medical minithoracoscopy (Richard Wolf company, Germany) according to the protocol of Tassi and Marchetti [6]. All patients were subjected to complete history taking, clinical examination, routine laboratory investigations and radiological studies including plain chest x-ray, computed tomography and chest ultrasonography.

The Procedure

Thoracoscopy was performed in a clean, draped endoscopy room. The patient was placed in the lateral decubitus position and accurate identification of the level of incision was identified based on chest ultrasound. Sedation was induced using a bolus of propofol (30-50 mg) and lidocaine 2% was used as a local anesthesia for infiltration of the subcutaneous tissue and periosteum of ribs above and below the site of incision. After complete visualization of the pleural cavity and surfaces, thoracoscopic findings were documented and multiple forceps biopsies were taken from suspicious areas of the pleura and adhesions. Biopsy sizes and the time of the procedure were recorded for all patients. Continuous monitoring was done for ECG and O2 saturation throughout the procedure for tachycardia [7] and hypoxemia [8]. Follow up chest X-ray was done after thoracoscopy to evaluate lung expansion and the presence of surgical emphysema. In addition, post-procedure pain was evaluated up to 3 hours after termination of the procedure via a numerical rating scale [9] and the duration of hospitalization was recorded for both groups. The histopathological diagnosis and the duration of hospitalization were recorded for both groups. 

Statistical Analysis

Statistical analysis of the collected data was performed using IBM SPSS statistics (Statistical Package for the Social Sciences) for windows (version 25, 2017), whereas charts were created using SPSS chart builder and Microsoft Excel for Windows 2019. The normality of data was assessed via the Shapiro-Wilk test. All tests were conducted with 95% confidence interval. P (probability) value.

Ethics

The experimental protocol was approved by the institutional research board of the faculty of medicine at Mansoura university on 20/8/2017 (Code Number: MS/17.07.86).

Table 1: Demographic characters of both groups.

RSMT: Rigid Standard Medical Thoracoscopy. RMMT: Rigid Medical Minithoracoscopy

P-value >0.05= Nonsignificant; P-value lessthan 0.05= Significant; P-value lessthan 0.01= highly significant. Chi-square test; Student t-test (t). Group-1 included 22 males (73.3%) and 8 females (26.7). Group-2 included 26 males (86.7%) and 4 females (13.3%). The mean ages of patients in groups-1 and group-2 were 44.87 years and 44.53 years, respectively. * Current & ex-smokers included 66.7% in group-1 and 33.3% in group-2. The percentages of non-smokers, smokers and ex-smokers in group-1 were 33.3%, 60%, 6.7% respectively and in group-2 were 66.7%, 33.3% and 0% respectively.

Table 2: Time of procedure, thoracoscopic findings and the sizes of biopsy samples in both groups.

RSMT: Rigid Standard Medical Thoracoscopy. RMMT: Rigid Medical Minithoracoscopy.

The mean time of the procedure was 20.07 minutes for group-1 and 25.53 minutes for group-2, with no significant difference (P=0.713). Thoracoscopic findings were nodules, adhesions, plaques and anthracotic patches with percentages of 80%, 66.7%, 0%, 6.7% respectively in group-1 and 53.3%, 53.3%, 13.3%, and 0% respectively in group-2, with no statistically significant differences between the two groups. The biopsy sizes were significantly larger in group-1 (64 mm2 in group-1 versus 54.7 mm2 in group-2, P=0.045*).

Table 3: Complications of thoracoscopy in both groups.

RSMT: Rigid Standard Medical Thoracoscopy. RMMT: Rigid Medical Minithoracoscopy.

Hypoxemia and arrhythmia during thoracoscopy were reported in 46.7% and 40% respectively in group-1 and in 20% and 13.3% respectively in group-2 with no statistically significant differences between the two groups. According to the numerical rating scale, the degrees of pain, three hours after the procedure were mild, moderate and severe in 56.7%, 33.3%, and 10% respectively in group-1 and were 93.3%, 6.7%, and 0.0% respectively in group-2. Pain was significantly less severe in group-2 compared to the group-1 patients (P=0.004*). There were no significant differences between two groups concerning development of surgical emphysema (P=0.553). No significant bleeding was recorded during or after the procedures and no mortality was reported in both groups.

Table 4: Histopathological studies, diagnostic yield and the hospital stays in both groups.

RSMT: Rigid Standard Medical Thoracoscopy. RMMT: Rigid Medical Minithoracoscopy.

Thoracoscopic biopsies revealed tuberculosis in 22 patients (36.67%), malignancy in 22 patients (36.67%) and nonspecific pleurisy in 16 patients (26.67%). There were no significant statistical differences between both groups (P>0.05). The diagnostic yield was 80% in group-1 and 66.7% in group-2 with no statistically significant difference between the two groups (P =0.409). Hospital stay was significantly shorter in group-2 compared to group-1 (6.4 days versus 9.53 days, P=0.004*).

The rigid Standard medical thoracoscopy (RSMT) is a minimally invasive procedure that allows direct visualization of the pleural space and intrathoracic structures as well as simultaneous therapeutic interventions. Its excellent yield and favorable safety profile have led to it replacing the closed pleural biopsy and surgical approaches for the diagnosis and treatment of many thoracic diseases10. The rigid medical mini-thoracoscopy (RMMT) with smaller caliber is used for small pleural effusions, effusions in patients with narrow intercostal spaces and suspected tuberculous pleurisy in areas of low incidence of tuberculosis [11]. Pleural loculations are usually associated with the presence of fibrotic scar tissues that create pockets and prevent the pleural fluid from moving freely. A loculated pleural effusion needs early diagnosis and treatment as it prevents effective drainage of the pleural fluid and may result in nonexpendable lungs [12]. The aim of the current prospective study was to compare the efficacy and safety of the RMMT with the RSMT in patients with loculated pleural effusions. Sixty patients with undiagnosed loculated pleural effusion were included in the study and divided randomly into two groups: group-1 (RSMT group) and group-2 (RMMT group) with thirty patients in each group. Male gender is considered a risk factor of loculated effusions, as most cases were males representing 73.3% of group-1 patients and 86.7% of group-2 patients (Table 1). Gender difference has been widely evaluated in previous studies. With the exception of malignant effusions and effusions due to systemic lupus erythematosus, pleural effusions were more common in males than in females including parapneumonic effusions [13,14], tuberculous effusions [15], effusions due to decompensated heart failure [16] and rheumatoid effusions [17].

Both current and ex-smokers represent 66.7% of group-1 and 33.3% of group-2 (Table 1). A strong association exists between smoking and both the tuberculous [18,19] and malignant effusions [20]. Increased risk of tuberculosis in smokers may be related to reduction in the natural killer cytotoxic activity, suppression of T cell function, impairment of mucociliary clearance and increase in the number of alveolar macrophages in the lower respiratory tract [21,22]. Smoking fuels the mutagenesis, initiation and progression of lung cancer. Nicotine favors the proliferation and survival of lung cancer and malignant mesothelioma cells [23]. The procedure time was longer in group-2 compared to group-1 (23.53 versus 20.07 minutes, Table-2) with no significant difference (P=0.713), because a relatively longer time was needed for the RMMT to cut adhesions of loculated effusions and fulfill the procedure. A procedure time of 27.5 minutes was reported for the RMMT procedure in the study of Padmindra et al [24] who studied 44 patients with undiagnosed and malignant pleural effusions, comparing the duration of the RMMT and semirigid thoracoscopy procedures. Although they reported a longer procedure time with the RMMT compared to the current study, they concluded that the rigid-minithoracoscopy had a lower procedure time compared to the semirigid thoracoscopy and it had got larger sample sizes and operator satisfaction without any difference in dose of analgesia, sedation, patient’s pain score and diagnostic yield. The recorded time for the RSMT in cases of pleural effusion is about 45 minutes [25], such a time is needed for full examination of the pleural space and performing the interventional procedures. Shorter procedure times were reported in the present study (Table-2) because the pleural space was limited in loculated effusions concerning the area of thoracoscopic examination compared to that of non-loculated effusions.

Nodules were the most common thoracoscopic findings (80% in group-1 & 53.3% in group-2, Table 2). Similar findings were reported in the studies of Yousef et al [26], Prabhu & Narasimhan [27] and Mohamed et al [28]. The biopsy sizes were significantly larger with the RSMT compared to the RMMT group (P=0.045, Table 2), such difference in biopsy sizes is related to the difference in the size of the thoracoscope and its accessories. However, smaller biopsy size does not affect the diagnostic yield, as there were no statistically significant differences between the two groups in the diagnostic yields (Table 4). The average size of biopsies was 54.7 mm with the RMMT in the current study and comparable results were attained in the study of Padmindra et al [24] who reported biopsy size of 50.5 mm with the RMMT group. The present study displayed no significant difference between the RSMT and the RMMT groups as regard hypoxemia and tachycardia during the procedure (Table 3). Mild and moderate chest pain were reported after thoracoscopy in 56.7 % and 33.3% respectively with the RSMT compared to 93.3% and 6.7% respectively with the RMMT. Severe postprocedural chest pain was experienced in only 2 patients (10%) with the RSMT but not with the RMMT patients. Surgical emphysema developed in 20 patients (66.7%) with the RSMT and in 14 patients (46.7%) with the RMMT, with no significant statistical difference between the two groups (P=0.553, Table 3). No major complications or mortality were reported after thoracoscopy in the current study and also in the studies of Patil et al [29], Prabhu & Narasimhan [27] and Yousef et al [26], however, other studies [30-34] reported major complications including re-expansion pulmonary edema, severe sepsis, severe hemorrhage, shock, pulmonary embolism, hypercapnic coma and rarely death.

Thoracoscopic biopsies of the studied 60 patients revealed malignancy in 22 patients (36.67%) and tuberculosis in 22 patients (36.67%) with no significant statistical differences between both groups (P>0.05, Table 4). Variable results of thoracoscopic biopsies were reported in other studies including the diagnosis of malignancy in 33.35 up to 69.4& and tuberculosis in 5.6& up to 91.4% [35]. Out of all 22 patients with malignant loculated pleural effusions (Table 4), 6 patients had mesothelioma (10%), one patient had non-Hodgkin’s lymphoma (1.67%) and 15 patients had metastatic adenocarcinoma (25%) with the primary from the lungs, breast, liver and kidneys. Comparable results were reported in the study of Yousef et al [26] with mesothelioma in 16.7%, metastatic adenocarcinoma in 25% and non-Hodgkin lymphoma in 5.6%. Malignancy was the commonest cause of pleural effusions in most of the thoracoscopic studies compared to tuberculosis including 66.4% versus 28.2% with Patil et al [29], 94.8% versus 9.9% with Goh et al [30], 48.6% versus 22.8% with Mootha et al [32], 75% versus 17% with Kumar et [36], 70% versus 22.5% with Helala et al [37], and 63% versus 6% with Valsecchi et al [38]. No tuberculosis was reported in the studies of Kendall et al [39] and Hucker et al [40]. This gross difference in diagnosis of tuberculosis may be related to the low prevalence of tuberculosis in the Western countries. The yield of thoracoscopic biopsies reported higher frequency of tuberculosis compared to malignancy including 91.4%, 5.2% respectively in the study of Thomas et al [35] and 66.7%, 33.3% respectively in the study of Kim et al [41], both studies were done in Asian countries with higher prevalence of tuberculosis. The current study revealed equal frequencies of both malignancy and tuberculosis (36.67% of each, Table 4), such different results compared to other studies may be related to the nature of the cases studied being of loculated effusions and the local prevalence of tuberculosis and malignancy in the studied community.

Nonspecific pleurisy was reported in 6.3% of cases with Kumar et al36, 10% with Elshabrawy and Elhawary [42], 19.4% with Yousef et al [26], 21.4% with Mohamed et al28, 25% with Mootha et al [32] and in 26.67% in the current study (Table 4). Nonspecific pleurisy was considered a false negative result or an underlying benign condition such as parapneumonic effusion or viral pleuritis by Valsecchi et al38 in their large cohort study including 2752 patients admitted over 30 years. In such study, the frequency of nonspecific pleurisy decreased progressively from about 43% to 21%. This reduction was attributed to more technical skills acquired by the thoracoscopy team in patient selection, the implementation with chest ultrasonography in patients’ selection and during preoperatory evaluation, more effective specimen collection and the anatomopathological examination improvements. The diagnostic yield of the rigid thoracoscopy was 66.7% with the RMMT and 80% with the RSMT group with no statistical differences between the two groups (P =0.409, Table 4). A relatively similar diagnostic yield of 69.4% was reported with the RMMT by Bansal et al [43] in their study including 36 patients with undiagnosed exudative pleural effusions and a higher diagnostic yield of 86.6% was reported with the RMMT in the study of Padmindra et al24 for undiagnosed pleural effusions. Although effusions in the current study were all loculated, relatively similar diagnostic yields were reported with the use of the RSMT for undiagnosed exudative pleural effusions in the studies of Yousef et al [26] and Patil et al [29] (80.6% and 85.3% respectively versus 80% in the current study). 

Some studies [44,45] do not consider the medical thoracoscopy as an alternative to surgical intervention in loculated parapneumonic effusions and empyema. However successful management of loculated effusions in the current study and multiloculated empyema in the studies of Ravaglia et al [46] and Brutsche et al [47] with the medical thoracoscopy was reported obviating the need for surgical intervention in such cases. Also, with the advantages of medical thoracoscopy being much less invasive procedure than video assisted thoracic surgery, being done in the endoscopy suite via a single port of entry, requires no intubation or general anesthesia with lower cost and better tolerance by frail patients.

Thoracoscopy is a valuable tool for the diagnosis of loculated pleural effusions and its diagnostic yield can be improved by practice and accurate selection of patients. The RMMT provided comparable diagnostic yield as the RSMT with no significant statistical difference, despite smaller biopsy sizes, similar procedure time, significantly less severe post-procedure pain and significantly shorter hospital stay. The results of the present study suggest that the rigid medical minithoracoscopy can successfully replace the rigid standard medical thoracoscopy for diagnosis of patients with loculated pleural effusions, particularly when the initial pleural fluid analysis and closed pleural biopsies are inconclusive. The main limitation of the study was the relatively small sample size and further study is recommended on larger sample size.

Acknowledgements

Nil.

Conflicts of Interest

None declared.