DOI: https://doi.org/10.21203/rs.3.rs-2099835/v1
For diagnosis of exudative pleural effusion in tuberculous pleurisy, medical thoracoscopic pleural biopsy (MTPB) enables direct vision and is most widely applied, although ultrasound-guided pleural biopsy (USPB) and closed pleural biopsy (CPB) are also viable. This retrospective study compared the diagnostic efficiencies and safety of USPB, CPB, and MTPB.
Patients enrolled from 2014 through 2020 underwent USPB, CPB, or MTPB (n = 69, 69, and 110, respectively). Propensity score matching (PSM) analysis was used to compare the diagnostic sensitivities of CPB, MTPB, and USPB. The secondary outcomes were postoperative complications and hospitalization stay.
PSM analysis resulted in 40 (USPB vs. CPB), 47 (USPB vs. MTPB), and 52 (CPB vs. MTPB) matched pairs. The diagnostic sensitivities of the USPB and CPB groups were 72.5% and 55.0% (P = 0.162); that of USPB and MTPB were 70.2% and 80.9% (P = 0.337); the CPB and MTPB groups were comparable(P = 0.152). The rates of associated pain and subcutaneous emphysema of the MTPB group were higher than that of the USPB or CPB (P = 0.000, both).Hospitalization time of the MTPB group was longest, and significantly longer than that of the USPB (P = 0.029).
While the three techniques were similarly effective in diagnosing tuberculous pleurisy, USPB and CPB showed fewer associated complications and shorter hospital stays compared with MTPB. The image guidance offered by USPB benefited reduction in postoperative complications.
Tuberculosis still accounts for substantial mortality in both developing and developed countries [1–3]. The elimination of tuberculosis as an epidemic and severe public health issue is an aspiration rather than a reality. The World Health Organization (WHO) and the United Nations pledged to provide diagnosis of tuberculosis and treatment for 40 million patients between 2018 and 2022 [4]. Therefore, more effective diagnostic tools are required.
Tuberculous pleurisy is the second most common extrapulmonary manifestation of tuberculosis, and the most frequent cause of lymphocyte-dominant pleural effusion [5, 6]. The gold standard diagnosis is based on detection of Mycobacterium tuberculosis in pleural fluid or pleural biopsy specimens (smear, culture, or histopathology). Yet, the conventional techniques such as acid-fast bacillus smear, tubercle bacillus culture, and molecular test are not sufficiently accurate. The rates of true-positive cultures and molecular tests for mycobacteria in thoracentesis-derived pleural fluid range from 10 to 81% [7].
Pleural biopsy, whether closed, thoracoscopic, or ultrasound-guided (CPB, MTPB, and USPB, respectively) is regarded as a powerful means for diagnosing tuberculous pleurisy. Pleural tissues may be obtained via video-assisted thoracic surgery, open surgery, or medical thoracoscopy [8, 9]. CPB uses Cope or Abrams needles without the assistance of pleural visualization or real-time image guidance. The diagnostic sensitivity of CPB for tuberculous pleurisy varies depending on the operator’s experience, biopsy time, needle type, and pathologist’s expertise [10]. However, given its low cost and accessibility, CPB is relied on in regions with a high pre-test risk of tuberculosis [11].
Over the past decade, image-guided biopsy techniques performed under ultrasound or computed tomography (CT) monitoring have allowed for accurate and secure biopsy of focal pleural thickening or nodules. USPB has practical advantages over CT-guided pleural biopsy, because it eliminates the need for expensive CT facilities, complicated CT positioning, or radiation exposure, and can be performed at the patient's bedside with a shorter wait and procedural time or as an outpatient operation [12]. Furthermore, ultrasound can distinguish the intercostal vessels and their locations within a specific rib space through color Doppler assessment [13, 14], and help the operator choose the most secure location for subsequent pleural intervention while minimizing the risk of vascular injury [15]. USPB has been studied for diagnosing tuberculous pleurisy [16]. Since patients must hold their breath during USPB, its usage may be unsuitable for those with severe respiratory distress caused by significant pleural effusions.
Medical thoracoscopy pleural biopsy (MTPB) is a minimally invasive method that can be utilized to assess and collect pleural tissue under direct visualization, in non-intubated patients receiving local anesthesia [17, 18]. Research has suggested that the MTPB has a sensitivity of 93–100% for detecting tuberculous pleural effusion, with rare complications [19, 20]. However, some patients are too weak to withstand MTPB, and the procedure may fail for those with extensive pleural effusion separation and pleural adhesions.
To provide evidence for clinical diagnosis and treatment, we analyzed retrospective data using propensity score matching (PSM) which could eliminate confounding factors between comparisons, to evaluate CPB, USPB, and MTPB in tuberculous pleurisy, in terms of diagnostic accuracy, patient acceptability, contraindication, and adverse events.
This retrospective study of patients with tuberculous pleurisy was conducted at Chongqing University Fuling Hospital, a 1600-bed tertiary hospital. The patients were treated from January 2014 to December 2020, and the records of 425 patients were initially reviewed. For inclusion, the patients conformed to the following criteria (Figure:Flowchart of the patient inclusion and exclusion): older than 18 years; underwent biopsy via USPB, CPB, or MTPB; and received a oral isoniazid, rifampicin, pyrazinamide, ethambutol for 3 monthes and isoniazid, rifampicin for 6 to 9 monthes regimen during the follow-up. Patients with any of the following were excluded: pleural effusion due to heart failure, cirrhosis, hypoproteinemia, pleural tumors, or other causes; experimental anti-tuberculosis treatment; follow-up less than 12 months; lost to follow-up; or lack of laboratory data. Finally, 248 patients were enrolled.
The 248 patients were classified into 3 groups based on the method of biopsy, with 69, 69, and 110 patients given USPB, CPB, and MTPB, respectively.
Figure:Flowchart of the patient inclusion and exclusion
Patients’ demographic and baseline data were retrieved from the Lianzhong electronic medical record database, including: gender; age; body mass index (BMI); tuberculosis history; disease course; hydrothorax adenosine deaminase (ADA); pleural/serum protein ratio; wrap-separated pleural fluid; maximal anteroposterior diameter of the pleural fluid; and comorbidities. The last included: pneumoconiosis; diabetes mellitus; hypertension; coronary heart disease; hepatitis B virus (HBV); tumor; acquired immunodeficiency syndrome (AIDS); and connective tissue disorder.
The primary and secondary outcomes were, respectively, the diagnostic sensitivity of the biopsy methods, and postoperative complications and hospitalization stay.
PSM analysis with a multivariable logistic regression model was performed for matching the following factors: gender, age, BMI, disease course (≥ 21 d), hydrothorax ADA (≥ 40 U/L) [21], pleural/serum protein ratio, wrap-separated pleural fluid, maximum anteroposterior diameter of the pleural effusion, previous pulmonary tuberculosis, diabetes, HBV, pneumoconiosis, coronary heart disease, hypertension, alcoholism, solid tumor, and connective tissue disorder. Matched pairs of patients between the USPB and CPB, USPB and MTPB, and MTPB and CPB groups were derived using a 1:1 greedy nearest neighbor matching within a propensity score of 0.02. There were 40, 47, and 52 matched patient pairs in the USPB and CPB, USPB and MTPB, and MTPB and CPB groups, respectively.
Categorical variables are presented as percentages, and continuous variables as mean ± standard deviation. The distributions of variables were assessed using the Kolmogorov-Smirnov test. Chi-squared or McNemar tests were used to compare categorical variables. Continuous variables were compared by paired Student’s t-test or Mann-Whitney U test. SPSS version 26 for Windows (SPSS, Chicago, IL, USA) was applied for data analyses. P < 0.05 was considered statistically significant.
Patients’ characteristics
USPB vs. CPB before PSM
The demographic characteristics of the patients who received USPB or CPB before PSM are shown in Table 1(Patients’ characteristics between USPB and CPB before and after PSM). Before PSM, the percentage of patients with hydrothorax ADA ≥ 40 was higher in the USPB group compared with the CPB group (P = 0.002), and the percentage of patients in the USPB group with wrap-separated pleural fluid was higher than that of the CPB group (P = 0.041). The maximum anteroposterior diameter of the pleural fluid in the USPB group was less than that of the CPB group (P = 0.047). The remaining variables were not significantly different between the USPB and CPB groups.
Table 1 Patients’ characteristics between USPB and CPB before and after PSM
Variables |
Before PSM |
|
|
After PSM |
|
|
USPB (n=69) |
CPB (n=69) |
P-value |
USPB (n=40) |
CPB (n=40) |
P-value |
|
Gender (male%) |
45 (65.2) |
45 (65.2) |
1.000 |
28 (70.0) |
27(67.5) |
1.000 |
Age (y, Mean ± SD) |
44.86±1 9.34 |
44.28±1 9.80 |
0.862 |
42.40±1 8.67 |
42.20±19.26 |
0.962 |
BMI (kg/m2) |
22.05±3. 19 |
21.82±3. 66 |
0.693 |
22.01±2.89 |
21.42±3.94 |
0.472 |
History of tuberculosis (%) |
2(2.9) |
3(4.3) |
1.000 |
2(5.0) |
2(5.0) |
1.000 |
Course of disease (days, n,%) |
|
|
|
|
|
|
≥21 |
18(26.1) |
21(30.4) |
0.706 |
10(25.0) |
10(25.0) |
1.000 |
<21 |
51(73.9) |
48(69.6) |
|
30(75.0) |
30(75.0) |
|
Hydrothorax ADA (U/L) |
|
|
|
|
|
|
≥40 |
51(73.9) |
32(46.4) |
0.002 |
26(65.0) |
28(70.0) |
0.500 |
<40 |
18(26.1) |
37(53.6) |
|
14(35.0) |
12(30.0) |
|
Pleural/serum protein ratio(%) |
76.01±7.49 |
76.92±7.06 |
0.464 |
76.73±7.53 |
74.87±7.77 |
0.246 |
Wrap-separated pleural fluid (%) |
40(58.0) |
27(39.1) |
0.041 |
23(57.5) |
19(47.5) |
0.424 |
Maximum anteroposterior
Diameter of pleural fluid(cm) |
5.35±2.23 |
6.13±2.33 |
0.047 |
5.62±2.17 |
5.63±2.33 |
0.980 |
Comorbidities (%) |
|
|
|
|
|
|
Pneumoconiosis |
3(4.3) |
3(4.3) |
1.000 |
2(5.0) |
2(5.0) |
1.000 |
Diabetes mellitus |
6 (8.7) |
3 (4.3) |
0.493 |
1(2.5) |
2(5.0) |
1.000 |
Hypertension |
7(10.1) |
2 (2.9) |
0.165 |
1(2.5) |
1(2.5) |
1.000 |
Coronary heart disease |
3(4.3) |
3(4.3) |
1.000 |
1(2.5) |
2(5.0) |
1.000 |
HBV |
22(31.9) |
16(23.2) |
0.341 |
11(27.5) |
10(25.0) |
1.000 |
Tumor |
1(1.4) |
0(0) |
1.000 |
0(0) |
0(0) |
|
AIDS |
0(0) |
1(1.4) |
1.000 |
0(0) |
0(0) |
|
CTD |
0(0) |
1(0.9) |
1 |
0(0) |
0(0) |
|
Alcoholism |
0(0) |
2(2.9) |
0.496 |
0(0) |
0(0) |
|
MTPB :Medicine thoracoscopic pleural biopsy
USPB :Ultrasound-guided pleural biopsy
CPB :Closed pleural biopsy
PSM: Propensity score matching
ADA:Aadenosine Deaminase
HBV:hepatitis B virus
AIDS:Acquired immunodeficiency syndrome
CTD:Connective tissue disorder
BMI: Body Mass Index
SD: standard deviation
USPB vs. MTPB before PSM
Table 2 (Patients’ characteristics between USPB and MTPB before and after PSM) displays the demographic characteristics of the USPB and MTPB groups before PSM. Before PSM, compared with the MTPB group, patients in the USPB group were older (0.406); the maximum anteroposterior diameter of pleural fluid was less (P = 0.000); and both the percentages with hydrothorax ADA ≥40 or HBV were less (P = 0.026, 0.043, respectively).
The percentage of those with wrap-separated pleural fluid was higher (P = 0.002). The remaining variables under study were not significantly different between these two groups.
Table 2 Patients’ characteristics between USPB and MTPB before and after PSM
Variables |
Before PSM |
|
|
After PSM |
|
|
USPB (n=69) |
MTPB (n=110) |
P-value |
USPB (n=47) |
MTPB (n=47) |
P-value |
|
Gender (male%) |
45 (65.2) |
79(71.8) |
0.406 |
30 (63.8) |
31(66.0) |
1.000 |
Age (y, Mean ± SD) |
44.86±1 9.34 |
55.14±1 5.34 |
0.000 |
49.94±1 9.07 |
49.53±14.79 |
0.903 |
BMI (kg/m2) |
22.05±3. 19 |
21.91±3.0 5 |
0.764 |
22.20±3. 44 |
22.14±2.92 |
0.934 |
History of tuberculosis (%) |
2(2.9) |
10(9.1) |
0.133 |
2(4.3) |
1(2.1) |
1.000 |
Course of disease (days, n,%) |
|
|
|
|
|
|
≥21 |
18(26.1) |
42(38.2) |
0.106 |
13(27.7) |
13(27.7) |
1.000 |
<21 |
51(73.9) |
68(61.8) |
|
34(72.3) |
34(72.3) |
|
Hydrothorax ADA (U/L) |
|
|
|
|
|
|
≥40 |
51(73.9) |
63(57.3) |
0.026 |
32(68.1) |
25(53.2) |
0.167 |
<40 |
18(26.1) |
47(42.7) |
|
15(31.9) |
22(46.8) |
|
Pleural/serum protein ratio(%) |
76.01±7.49 |
76.60±8.13 |
0.621 |
77.93±7.08 |
76.79±6.36 |
0.426 |
Wrap-separated pleural fluid (%) |
40(58.0) |
37(33.6) |
0.002 |
23(48.9) |
21(44.7) |
0.824 |
Maximum anteroposterior
Diameter of pleural fluid(cm) |
5.35±2.23 |
6.92±2.41 |
0.000 |
6.04±2.11 |
5.55±1.97 |
0.201 |
Comorbidities (%) |
|
|
|
|
|
|
Pneumoconiosis |
3(4.3) |
9(8.2) |
0.375 |
3(6.4) |
2(4.3) |
1.000 |
Diabetes mellitus |
6 (8.7) |
8 (7.3) |
0.779 |
5(10.6) |
5(10.6) |
1.000 |
Hypertension |
7(10.1) |
12 (10.9) |
1.000 |
7(14.9) |
3(6.4) |
0.344 |
Coronary heart disease |
3(4.3) |
10(9.1) |
0.375 |
3(6.4) |
2(4.3) |
1.000 |
HBV |
22(31.9) |
53(48.2) |
0.043 |
22(46.8) |
21(44.7) |
1.000 |
Tumor |
1(1.4) |
0(0) |
0.385 |
0(0) |
0(0) |
|
AIDS |
0(0) |
0(0) |
|
0(0) |
0(0) |
|
CTD |
0(0) |
1(0.9) |
1 |
0(0) |
0(0) |
|
Alcoholism |
0(0) |
0(0) |
|
0(0) |
0(0) |
|
MTPB:Medicine thoracoscopic pleural biopsy
USPB:Ultrasound-guided pleural biopsy
CPB:Closed pleural biopsy
AIDS:Acquired immunodeficiency syndrome
CTD:Connective tissue disorder
BMI: Body Mass Index
ADA:Aadenosine Deaminase
HBV:hepatitis B virus
PSM: Propensity score matching
SD: standard deviation
CPB vs. MTPB before PSM
Table 3 (Patients’ characteristics between CPB and MTPB before and after PSM) shows the demographic characteristics of the CPB and MTPB groups before PSM. Compared with the MTPB group, patients in the CPB group were significantly younger (P = 0.000), the maximum anteroposterior diameter of the pleural fluid was less (P = 0.031), and the percentage with HBV was lower (P = 0.001). However, the ADA and wrap-separated pleural fluid of the two groups were comparable.
After PSM, there were 40, 47, and 52 matched pairs from, respectively, the USPB and CPB, USPB and MTPB, and CPB and MTPB groups. The baseline characteristics were balanced well among the three groups.
Table 3 Patients’ characteristics between CPB and MTPB before and after PSM
Variables |
Before PSM |
|
|
After PSM |
|
|
CPB
(n=69) |
MTPB
(n=110) |
P-value |
CPB
(n=52) |
MTPB
group (n=52) |
P-value |
|
Gender (male%) |
45 (65.2) |
79(71.8) |
0.406 |
36 (69.2) |
34(65.4) |
0.845 |
Age (y, Mean ± SD) |
44.28±1 9.80 |
55.14±1 5.34 |
0.000 |
48.88±1 9.80 |
51.77±15.89 |
0.341 |
BMI (kg/m2) |
21.82±3. 66 |
21.91±3.0 5 |
0.871 |
21.93±3. 77 |
22.05±3.41 |
0.860 |
History of tuberculosis (%) |
3(4.3) |
10(9.1) |
0.375 |
2(3.8) |
1(1.9) |
1.000 |
Course of disease (days, n,%) |
|
|
|
|
|
|
≥21 |
21(30.4) |
42(38.2) |
0.336 |
15(28.8) |
23(44.2) |
0.115 |
<21 |
48(69.6) |
68(61.8) |
|
37(71.2) |
29(55.8) |
|
Hydrothorax ADA (U/L) |
|
|
|
|
|
|
≥40 |
32(46.4) |
63(57.3) |
0.169 |
26(50.0) |
20(38.5) |
0.327 |
<40 |
37(53.6) |
47(42.7) |
|
26(50.0) |
32(61.5) |
|
Pleural/serum protein ratio(%) |
76.92±7.06 |
76.60±8.13 |
0.781 |
76.08±7.61 |
76.33±7.12 |
0.874 |
Wrap-separated pleural fluid (%) |
27(39.1) |
37(33.6) |
0.522 |
23(44.2) |
17(32.7) |
0.362 |
Maximum anteroposterior Diameter of pleural fluid(cm) |
6.13±2.33 |
6.92±2.41 |
0.031 |
6.04±2.38 |
6.25±2.38 |
0.603 |
Comorbidities (%) |
|
|
|
|
|
|
Pneumoconiosis |
3(4.3) |
9(8.2) |
0.375 |
3(5.8) |
1(1.9) |
0.625 |
Diabetes mellitus |
3 (4.3) |
8 (7.3) |
0.534 |
3(5.8) |
7(13.5) |
0.344 |
Hypertension |
2 (2.9) |
12 (10.9) |
0.083 |
2(3.8) |
1(1.9) |
1.000 |
Coronary heart disease |
3(4.3) |
10(9.1) |
0.375 |
3(5.8) |
5(9.6) |
0.687 |
HBV |
16(23.2) |
53(48.2) |
0.001 |
13(25.0) |
19(36.5) |
0.286 |
Tumor |
0(0) |
0(0) |
|
0(0) |
0(0) |
|
AIDS |
1(1.4) |
0(0) |
0.385 |
0(0) |
0(0) |
|
CTD |
1(0.9) |
1(0.9) |
1 |
0(0) |
0(0) |
|
Alcoholism |
2(2.9) |
0(0) |
0.147 |
0(0) |
0(0) |
|
MTPB :Medicine thoracoscopic pleural biopsy
CPB :Closed pleural biopsy
AIDS:Acquired immunodeficiency syndrome
CTD:Connective tissue disorder
BMI: Body Mass Index
ADA:Aadenosine Deaminase
HBV:hepatitis B virus
PSM: Propensity score matching
SD: standard deviation
Diagnostic sensitivities
Diagnostic sensitivity is measured according to the percentage of patients within a particular population given a definitively positive diagnosis [22]. The pathological diagnoses of the three groups are displayed in Table 4(The analysis of diagnostic sensitivity, complications and hospital stay for the three pairs after PSM). After PSM, no significant differences in diagnostic sensitivities were found between the USPB and CPB (72.5 vs. 55.0%; P = 0.162), USPB and MTPB (70.2 vs. 80.9%; P = 0.337), or CPB and MTPB (61.5 vs. 76.9%; P = 0.152) groups.
Safety findings
The post-procedural complications were inspected, including pleural response, pain, subcutaneous emphysema, subcutaneous hematoma, hemothorax, and iatrogenic pneumothorax (Table 4). The rates for pain and subcutaneous emphysema were higher in the MTPB group than in the USPB or CPB groups (all, P = 0.000). There were nine (19.1%) and two (4.3%) cases of iatrogenic pneumothorax in the MTPB and USPB groups, which was statistically similar. These complications either resolved on their own or treated symptomatically. All these patients underwent closed thoracic drainage and recovered within 3 to 5 days.
Hospitalization
Hospitalization was longer in the MTPB group compared with the other two groups (Table 4). Specifically, the hospitalization of patients given MTPB was significantly longer than that of the USPB group (P = 0.029). While the hospitalization of the MTPB group was longer than that of the CPB group, the difference was not significant (P = 0.313). The hospitalizations of the USPB and CPB groups were similar (P = 0.543).
Table 4 The analysis of diagnostic sensitivity, complications and hospital stay for the three pairs after PSM
USPB vs. CPB after PSM |
|
USPB vs. MTPB after PSM |
|
CPB vs. MTPB after PSM |
|
||||||
Variables |
USPB(n=40) |
CPB(n=40) |
P value |
|
USPB(n=47) |
MTPB(n=47) |
P value |
|
CPB(n=52) |
MTPB(n=52) |
P value |
Serum albumin (g/L) |
33.88±4.49 |
34.85±4. 75 |
0.202 |
|
33.88±4.49 |
34.85±4. 75 |
0.349 |
|
33.85±3.69 |
35.44±4. 35 |
0.062 |
ESR(mm/h) |
47.94±21.02 |
47.72±22.08 |
0.839 |
|
47.94±21.02 |
47.72±22.08 |
0.964 |
|
41.23±20.92 |
48.46±23.30 |
0.101 |
TB-Ab(+) |
1(2.1) |
3(6.4) |
0.103 |
|
1(2.1) |
3(6.4) |
0.625 |
|
6 (11.5) |
3 (5.8) |
0.508 |
Hydrothorax/Serum
CEA(%) |
75.47±26.16 |
74.30±30.03 |
0.185 |
|
78.01±24.85 |
77.61±22.98 |
0.934 |
|
76.01±27.48 |
80.40±33.18 |
0.463 |
Hydrothorax WBC
(×10 6/L) |
2397±2214 |
2669±1936 |
0.820 |
|
2397±2214 |
2669±1936 |
0.514 |
|
2206±1590 |
2370±1882 |
0.598 |
Hydrothorax L% (%) |
84.22±9.71 |
83.87±9.34 |
0.549 |
|
84.22±9.71 |
83.87±9.34 |
0.860 |
|
84.98±10.95 |
82.15±12.82 |
0.252 |
Hydrothorax albumin (g/L) |
29.82±4. 48 |
29.39±4.16 |
0.005 |
|
29.82±4. 48 |
29.39±4.16 |
0.651 |
|
27.80±4. 15 |
29.22±4.05 |
0.079 |
Hydrothorax ADA (U/L) |
50.03±20.02 |
44.20±16.00 |
0.311 |
|
50.03±20.02 |
44.20±16.00 |
0.136 |
|
40.55±13.97 |
40.35±16.46 |
0.949 |
Hydrothorax LDH (U/L) |
552.85±533.56 |
490.95±227.51 |
0.468 |
|
593.89±535.82 |
482.57±268.29 |
0.234 |
|
443.69±214.62 |
407.08±201.68 |
0.371 |
Parietal pleura thickness
(mm) |
3.46±1.72 |
4.33±1.90 |
0.057 |
|
3.26±1.76 |
3.64±2.27 |
0.315 |
|
4.00±1.78 |
3.52±2.15 |
0.220 |
Pathological results |
|
|
0.264 |
|
|
|
0.169 |
|
|
|
0.065 |
Tuberculosis |
29(72.5) |
22(55.0) |
|
|
33(70.2) |
38(80.9) |
|
|
32(61.5) |
40(76.9) |
|
Chronic inflammation |
9 (22.5) |
15 (37.5) |
|
|
11 (23.4) |
9(19.1) |
|
|
16(30.8) |
12(23.1) |
|
Skeletal muscle |
2 (5.0) |
3 (7.5) |
|
|
3 (6.4) |
0(0) |
|
|
4(7.7) |
0(0) |
|
Diagnostic sensitivity (n%) |
29(72.5) |
22(55.0) |
0.162 |
|
33(70.2) |
38(80.9) |
0.337 |
|
32(61.5) |
40(76.9) |
0.152 |
Complication |
|
|
|
|
|
|
|
|
|
|
|
Pleural response |
2(5.0) |
2(5.0) |
0.494 |
|
0 (0) |
1(2.1) |
1.000 |
|
2(3.8) |
0(0) |
0.495 |
Pain |
2(5.0) |
7(17.5) |
0.154 |
|
3 (6.4) |
27(57.4) |
0.000 |
|
7(13.5) |
26(50.0) |
0.000 |
Subcutaneous emphysema |
1(2.5) |
1(2.5) |
1 |
|
2 (4.3) |
18(38.3) |
0.000 |
|
1(1.9) |
16(30.8) |
0.000 |
Subcutaneous hematoma |
1(2.5) |
1(2.5) |
1 |
|
3 (6.4) |
1(2.1) |
0.617 |
|
1(1.9) |
0(0) |
1 |
Hemothorax |
0(0) |
0(0) |
|
|
0 (0) |
0(0) |
|
|
2(3.8) |
0(0) |
0.495 |
Air embolism |
0(0) |
0(0) |
|
|
0 (0) |
0(0) |
|
|
0(0) |
0(0) |
|
Iatrogenic pneumothorax |
1(2.5) |
2(5.0) |
1 |
|
2 (4.3) |
9(19.1) |
0.050 |
|
2(3.8) |
6 (11.5) |
0.269 |
Hospital stay(d) |
9.03±3.64 |
9.60±4. 71 |
0.543 |
|
8.74±3.19 |
10.30±3. 59 |
0.029 |
|
9.60±4.46 |
10.46±3. 56 |
0.313 |
USPB :Ultrasound-guided pleural biopsy
CPB :Closed pleural biopsy
MTPB :Medicine thoracoscopic pleural biopsy
PSM: Propensity score matching
WBC: white blood cell
ADA: Aadenosine Deaminase
LDH: lactate dehydrogenase
ESR: erythrocyte sedimentation rate
TB-Ab: tuberculosis antibodies
CEA: carcinoembryonic antigen
The WHO estimated 10.4 million new tuberculosis infections and 1.7 million tuberculosis-related deaths in 2016 worldwide. Enhancing tuberculosis diagnosis and treatment remained a critical global health issue [23]. Tuberculous pleurisy was a common extrapulmonary manifestation of tuberculosis. It was closely related to pleural fibrosis, calcification, and residual thickening, which could severely impair ventilation [24, 25]. Along with etiological and molecular biological tests, histopathological examination was considered the most crucial tool for identifying tuberculous pleurisy because conventional diagnostic techniques had extremely low detection sensitivity [7].
MTPB and USPB could carry out multi-point sampling under the guidance of a direct endoscope or ultrasound image. Their theoretically higher diagnostic sensitivity than CPB was supported by several investigations [26, 27]. However, there were different voices around the world. Some believed that tuberculosis played a crucial role in diagnosing tuberculous pleurisy even though CPB, a traditional approach for identifying pleural malignancies, was less effective than USPB and MTPB because it affected the pleura diffusely [28]. Wei Y et al. [29] proposed that CPB was comparable to MTPB in the diagnostic sensitivity of tuberculous pleurisy (69% vs. 68%). In line with the above research, the sensitivity of CPB and MTPB in our investigation was 61.5% and 76.9%, respectively, and the difference was not statistically significant. The CPB sensitivity was 55% compared to USPB's 72.5%, but the difference showed similar insignificance. Although the CPB sensitivity in this study for the diagnosis of tuberculous pleurisy was lower than previously reported at 62%-80% [30, 31], it was necessary to consider that PSM was performed on the baseline characteristics of our subjects, which eliminated confounding variables and reduced the sample size. Sperandeo M et al. [10] stated that the operator’s experience, the number of biopsies, the biopsy needle, and the pathologist's expertise might significantly impact the diagnostic sensitivity of the procedure, which perhaps made our conclusions more credible. Zhang Y et al. [32] believed that the thickness of the parietal pleura would affect the diagnostic sensitivity of USPB. The diagnostic sensitivity of USPB was higher when the pleural thickness reached 3 mm or more. However, USPB and MTPB showed similar efficacy in identifying tuberculous pleurisy in a prospective, randomized, controlled trial by Yuxin Z et al. [16] (82% vs. 90%). In addition, the sensitivity of the two modalities to the extent of pleural thickening was not substantially different. There was no significant difference in the thickness of the parietal pleura between the groups in our study. The diagnostic sensitivity of USPB and MTPB was 70.2% and 80.9%, respectively. The difference was not statistically significant, reaffirming that USPB and CPB were equally sensitive to the diagnosis of tuberculous pleurisy as MTPB. A multi-center large-sample study can be conducted to verify the effect of various pleural thicknesses on diagnostic sensitivity in the future.
Most comparative studies have shown that subcutaneous emphysema, hemorrhage, iatrogenic pneumothorax, and respiratory failure were the primary complications of MTPB [26, 33–35]. There was no hemothorax or respiratory failure in this study. However, the proportions of pain and subcutaneous emphysema following MTPB were significantly higher than those following USPB and CPB. There was no statistically significant difference in the proportion of iatrogenic pneumothorax between the USPB and CPB groups. However, the proportion of iatrogenic pneumothorax was the second most common complication in the MTPB group. The slight differences between our study and the above studies were probably caused by the sample size, general conditions of the included subjects, various disease conditions, and pain tolerance degree. Previous research has identified pneumothorax and hemothorax as the most frequent side effects of CPB [36]. However, the CPB group had a higher incidence of pneumothorax and pain than the USPB group, even though the difference was not statistically significant. Therefore, we believed that USPB and CPB were safer than MTPB for identifying tuberculous pleurisy. The advantage of image guidance allowed USPB to further lower the incidence of postoperative complications.
Relevant studies have shown that the hospital stay of MTPB was longer than that of CPB and USPB. They hypothesized that the result was related to increased postoperative complications and the requirement for indwelling chest drainage tubes due to iatrogenic pneumothorax [16, 29]. The present study revealed that patients had a more extended hospital stay in the MTPB group than in the USPB group (10.30 ± 3.59 vs. 8.74 ± 3.19, P < 0.05). The hospital stays for the CPB and USPB groups were comparable (9.03 ± 3.64 vs. 10.46 ± 3.56, P = 0.543). In contrast, the MTPB group had a slightly longer hospital stay than the CPB group (10.46 ± 3.56 vs. 9.60 ± 4.46, P = 0.313). The outcome differed from the above studies, and the following factors should be considered. First, the hospital stay in our study was counted from the day of admission to the day of discharge rather than from the day of surgery to the day of discharge. Variables like thorough preoperative preparation and the time for family members to sign the informed consent might affect the length of hospital stay during the preoperative period. Second, the sample size of this study was relatively small, which could contribute to selection bias.
Thoracoscopy was the gold standard for diagnosing unexplained exudative pleural effusion. However, if the symptoms were typical of tuberculosis, and biochemical analyses showed that tuberculous pleurisy was an exudative pleural effusion with a high ADA concentration, we believed that the diagnostic effectiveness of USPB and CPB were comparable to that of MTPB, with fewer complications, shorter hospital stay, and better health and economic value.We suggest that the USPB efficacy might be preferred over MTPB for diffuse pleural disease pathological sampling in units with ultrasound image guidance. Nevertheless, the validity of the conclusion needs to be verified by multi-center and large-sample studies due to the single-center and limited sample size in this study design.
MTPB:Medicine thoracoscopic pleural biopsy
USPB :Ultrasound-guided pleural biopsy
CPB:Closed pleural biopsy
PSM:Propensity score matching
ADA:Aadenosine Deaminase
HBV:Hepatitis B virus
AIDS:Acquired immunodeficiency syndrome
CTD:Connective tissue disorder
BMI: Body Mass Index
SD: Standard deviatio
WBC: White blood cell
LDH: Lactate dehydrogenase
ESR: Erythrocyte sedimentation rate
TB-Ab: Tuberculosis antibodies
CEA: Carcinoembryonic antigen
WHO:World Health Organization
CT:Computed tomography
Acknowledgement:We thank Medjaden Inc. for scientific editing of this manuscript.
Ethics approval and consent to participate:The study was approved by the ethics committee of Chongqing University Fuling Hospital (No. 2022CQSFLZXYYEC-009). All methods were conducted in accordance with the relevant guidelines and regulations. Because this study was a retrospective study,which is a analysis of clinical data with no relevant to human biological ethic problems, the informed consent of the participants was waived by the ethics committee of Chongqing University Fuling Hospital.
Consent for publication:Not applicable.
Availability of data and materials:The datasets used and/or analysed during the current study available from the corresponding author on reasonable request.
Competing interests:The authors declared no conflict of interest.
Funding:This research was funded by the Chongqing Regional Key Discipline Construction Project (Grant No. zdxk201702).
Authors' contributions: Conceptualization: Nan Tang, Yangzhong Wang, Tao Tao, and Xiaoli Bao. Data curation: Tao Tao, Xiaoli Bao, and Nan Tang. Formal analysis: Nan Tang. Methodology: Tao Tao and Nan Tang. Project administration: Nan Tang, Xiaoli Bao, and Tao Tao. Validation: Nan Tang, Xiaoli Bao, and Tao Tao. Original draft: Tao Tao, Nan Tang, and Xiaoli Bao. Review and editing: Tao Tao, Xiaoli Bao, Yangzhong Wang, and Nan Tang. All authors have read and agreed to the published version of the manuscript.