For undiagnosed pleural effusion, diagnostic yields and safety were similar between pleuroscopic cryobiopsy and forceps biopsy, but cryobiopsy obtained a larger pleural tissue sample than forceps biopsy.
Pleural effusion is a common problem in medical practice. Undiagnosed pleural effusion is frequently encountered, even after thoracentesis and closed pleural biopsy [
Semirigid pleuroscopy enables the examination of the pleural lesion and guides the biopsy of abnormal pleural lesions. Pleuroscopic biopsy with flexible forceps is limited by the size of the forceps used. Due to inadequate mechanical strength, forceps biopsy is associated with concerns regarding obtaining pleural tissue of adequate size and depth [
The aim of this study was to compare the diagnostic yield, safety, and clinical outcomes between cryobiopsy and forceps biopsy performed under semirigid pleuroscopy.
This study was approved by the Institutional Review Board of Chang Gung Memorial Foundation (IRB No. 201700671B0). This study retrospectively recruited 45 patients from April 2016 to June 2017 from Linkuo Chang Gung Memorial Hospital, Taiwan, a tertiary referral medical center (Figure
Diagnosis of patients who received pleuroscopic cryobiopsy and flexible forceps biopsy.
In all patients, pleuroscopic examination was conducted by an experienced operator and two trained assistants. Additionally, during the procedure, all patients received moderate sedation with fentanyl and midazolam with or without propofol. Before the initiation of the procedure, thoracic ultrasound was performed to determine the optimal entry point. After local administration of 2% lidocaine for anesthesia, a 1.0 cm skin incision was made followed by thoracotomy with an 8 mm flexible trocar (MAJ-1058; Olympus Medical Systems Corp., Japan). A semirigid thoracoscope (LTF-240; Olympus, Tokyo, Japan) was used to drain the effusion initially and explore the pleural cavity. Accessible pleural space would be entirely visualized first, and the next step was to determine the biopsy site. Forceps (FB-15C-1; Olympus) or a cryoprobe was used for biopsy through the working channel of a thoracoscope. A 1.9 mm flexible cryoprobe (Erbokryo CA; Erbe, Germany) was used to perform cryobiopsy with cryogen (carbon dioxide). The cooling time for each cryobiopsy was approximately 3 seconds [
All patients who did not have a specific etiological diagnosis were followed up for a minimum of 6 months. Fibrinous pleuritis was accepted as the final diagnosis in patients with compatible histopathology and no evidence of malignancy or an alternative diagnosis at the end of follow-up [
Student’s
This study included a total of 45 patients admitted to the Linkuo Branch of Chang Gung Memorial Hospital in Taiwan from April 2016 to June 2017. Under semirigid pleuroscopy, 28 patients received cryobiopsy and 17 patients received forceps biopsy. Their demographic data are provided in Table
Baseline characteristics of the study population.
Variables | Total, |
Cryobiopsy, |
Forceps biopsy, |
|
---|---|---|---|---|
Age, median (IQR) | 64.4 (55.4–76.4) | 64.6 (55.3–73.4) | 64.4 (55.4–77.6) | 0.590 |
Male gender | 30 (66.7%) | 21 (75.0%) | 9 (52.9%) | 0.128 |
Smoking status | ||||
Currently smoke | 7 (15.6%) | 3 (10.7%) | 4 (23.5%) | 0.250 |
Had quit smoke | 5 (11.1%) | 5 (17.9%) | 0 (0.0%) | 0.065 |
Never smoke | 32 (71.1%) | 19 (67.9%) | 13 (76.5%) | 0.537 |
Location of pleural effusion | ||||
Right | 20 (40.0%) | 10 (35.7%) | 10 (58.8%) | 0.130 |
Left | 18 (40.0%) | 14 (50.0%) | 4 (23.5%) | 0.079 |
Bilateral | 7 (15.6%) | 4 (14.3%) | 3 (17.6%) | 0.763 |
Pleural effusion LDH (mg/dL), median (IQR) | 394 (187–956) | 635 (275.3–1290.3) | 273 (143–501.5) | 0.030 |
Pleural effusion total protein (mg/dL), median (IQR) | 4.5 (4.0–5.2) | 4.6 (4.0–5.1) | 4.5 (3.9–5.3) | 1.000 |
Serum LDH (mg/dL), median (IQR) | 241.5 (199.8–315.5) | 242 (228.3–307.8) | 215.5 (179.8–321.2) | 0.370 |
Serum total protein (mg/dL), median (IQR) | 6.8 (5.7–7.1) | 6.9 (6.3–7.2) | 6.2 (5.3–6.8) | 0.081 |
Pleural effusion/serum LDH ratio | 2.49 ± 4.38 | 3.16 ± 5.46 | 1.42 ± 1.20 | 0.333 |
Pleural effusion/serum total protein ratio | 0.67 ± 0.13 | 0.66 ± 0.14 | 0.67 ± 0.12 | 0.787 |
Patients were diagnosed with malignancy, tuberculosis pleurisy, Wegener’s granulomatosis, or fibrinous pleuritis. The diagnostic rate was 89.3% and 88.2% in the cryobiopsy and forceps biopsy groups, respectively (Table
Final diagnoses and complications.
Cryobiopsy, |
Forceps biopsy, |
| |
---|---|---|---|
Sample pieces | 7 (3.5–8) | 6 (5–7.5) | 0.686 |
Tissue size | |||
Length (mm) | 9.1 ± 5.7 | 5.3 ± 3.8 | 0.020 |
Area (mm2) | 56.0 ± 61.3 | 10.2 ± 14.3 | 0.001 |
Volume (mm3) | 232.1 ± 411.4 | 13.4 ± 22.6 | 0.009 |
Bleeding | |||
Moderate/severe | 0 | 0 | — |
Mild | 3 | 1 | 0.581 |
No bleeding | 25 | 16 | 0.581 |
Subcutaneous emphysema | 0 | 0 | |
Pneumothorax | 0 | 0 | |
Pneumomediastinum | 0 | 0 | |
Wound infection | 0 | 0 | |
Diagnostic rate | 89.3% (25/28) | 88.2% (15/17) | 0.913 |
Hospital stay after pleuroscopic biopsy (days), median (IQR) | 11 (8–14.5) | 11 (7–18) | 0.916 |
Final diagnosis | |||
Malignancy | 16 (57.1%) | 9 (52.9%) | |
Tuberculosis pleurisy | 4 (14.3%) | 3 (17.6%) | |
Fibrinous pleuritis | 5 (17.9%) | 2 (11.8%) | |
Wegener’s granulomatosis | 0 (0%) | 1 (5.9%) | |
Undiagnosed | 3 (10.7%) | 2 (11.8%) |
Comparison of tissue size between the diagnosed group and the undiagnosed group.
Diagnosed, |
Undiagnosed, |
| |
---|---|---|---|
Tissue size | |||
Length (mm) | 7.5 ± 5.50 | 8.9 ± 4.72 | 0.590 |
Area (mm2) | 38.0 ± 55.7 | 44.4 ± 36.8 | 0.805 |
Volume (mm3) | 153.5 ± 357.9 | 116.5 ± 144.0 | 0.821 |
Neither moderate nor severe bleeding was observed during the procedure or the following clinical course. Three patients in the cryobiopsy group and one patient in the forceps biopsy group developed mild bleeding. There was no subcutaneous emphysema, pneumomediastinum, pneumothorax, or wound infection developed in both groups. Among all patients who received pleuroscopy, no vessels, nerve, muscles, or bones were seen in the histopathological finding of the pleural samples. The median hospital stay after pleuroscopy was similar in the cryobiopsy group (11 days; IQR, 8–14.5) and forceps biopsy group (11 days; IQR, 7–18;
This study demonstrated that pleuroscopic cryobiopsy had a similar diagnostic yield to flexible forceps biopsy. There was no major complication developed in both groups. Larger samples were obtained through cryobiopsy than through forceps biopsy. In patients who failed to reach diagnosis after pleuroscopy, there were no statistical differences in length, area, and volume of tissue samples compared with those with definite diagnosis after pleuroscopy.
In our study, pleuroscopy with either cryobiopsy or forceps biopsy provided diagnostic yields of more than 88% in undiagnosed pleural effusion; the rate is consistent with that reported in previous studies [
Common complications of bronchoscopic cryobiopsy are bleeding, pneumothorax, and pneumomediastinum. In this study, none of the patients developed pneumothorax or pneumomediastinum after procedures were completed. Regarding complications of pleuroscopy-associated bleeding, none of the patients developed moderate or major bleeding. Only 9% of patients experienced mild bleeding in our study group. Therefore, in addition to its remarkable diagnostic yield, pleuroscopic biopsy with cryobiopsy and forceps biopsy is a relatively safe procedure performed by experienced operators.
Semirigid pleuroscopy is a minimally invasive procedure for the examination and biopsy of the pleural space. The procedure is performed by pulmonologists in a spontaneously breathing patient under moderate sedation in a bronchoscopy suite [
First thoracoscopy was performed by Jacobaeus in 1910 [
This study demonstrated that sample size could not explain the failure to reach diagnosis by semirigid pleuroscopic biopsy. These patients were clinical monitored for more than 6 months to exclude malignancy or uncontrolled infection. Although the diagnostic yield of pleuroscopic biopsy may have its own limitation, patients without final diagnosis after pleuroscopy need continuous monitoring [
This study has several limitations: First, its major limitation is its retrospective design, which may have led to bias in patient selection or statistical analysis. Second, the sample size of the study was small; therefore, the results of the study should be interpreted with caution. To further confirm the results of this study, a prospective study with a larger sample size is required to evaluate the utility of semirigid pleuroscopy in patients with undiagnosed pleural effusion.
This study demonstrated that semirigid pleuroscopy is a relatively safe procedure with a low complication rate. Larger pleural tissue specimens were obtained through pleuroscopic cryobiopsy than through forceps biopsy, although both types of biopsies provided similar diagnostic yields regarding undiagnosed pleural effusion.
No data were used to support this study.
This study was approved by the Institutional Review Board of Chang Gung Memorial Foundation (Approval date: April 24, 2017, IRB No. 201700671B0).
The authors declare no conflicts of interest.
CSL, SHL, CHC, FTC, CLC, CWW, and SML conceived the study. SHL and CHC performed data curation and analysis. FTC, CLC, and CWW performed investigation, supervision, and validation. CSL and SML drafted the manuscript. All authors read and approved the final manuscript before submission.
This project was supported by the Ministry of Science and Technology of Taiwan, Republic of China (MOST 105-2314-B-182-043-MY2) and research grants from Chang Gung Memorial Hospital, Taiwan (CMRPG3B1333 to Shu-Min Lin and CMRPG3E1712 to Chung-Shu Lee).