The role of ultrasound-guided transthoracic Tru-Cut core biopsy in the diagnosis peripheral thorax lesion

The nature of opaque lesions such as effusions, atelectasis, masses, and consolidations can be clarified by sonography. This study investigated the sensitivity and accuracy of ultrasound-guided percutaneous core needle biopsy in different thoracic tumors (lung, pleural, chest wall, and mediastinal). Sixty patients underwent ultrasound-guided percutaneous transthoracic core biopsy of peripheral thoracic masses with a Tru-Cut needle with a big bore. Twenty masses were in the lung, seventeen lesions were in the pleura, ten masses were in the mediastinum, eleven were enlarged palpable lymph nodes, and two masses were in chest wall. The sensitivity, PPV, and accuracy for detection of chest tumors in the chest wall, mediastinum, lung, and pleura were 100% for all, and in LN 88.9, 100, and 90.9%, respectively. The overall diagnostic performance of sonar-guided Tru-Cut needle biopsy in diagnosis was 97.78% sensitivity, 98.18% accuracy, and 100% PPV. Tru-Cut needle percutaneous transthoracic core biopsy is a convenient and sensitive process in obtaining samples under ultrasound guidance for exact histological diagnosis of thoracic tumors. The diagnostic efficiency is high, and the technique can also be used in outpatients, which is relatively simple. NCT, NCT04741958 Registered 5 February 2021, retrospectively registered,


Background
Peripheral intrathoracic shadows are common presentation of different diseases of different origin (chest wall, pleura, pulmonary, and mediastinum); they are increasing in numbers, including peripheral lung cancer, tuberculosis, pneumonia, and atelectasis [1].
Thoracic masses with wall contact represent a frequent pathology that requires complex imaging studies and often interventional procedures, in order to reach the complete diagnosis. In most cases, after a thoracic lesion is found on a thoracic x-ray, the next step is to perform a CT and/or a bronchoscopy exam, but pleural and pulmonary lesions often call for additional investigations.
Therefore, transthoracic ultrasonography (US) permits visualization of these lesions and their structural characterization, while offering suggestive elements for their malignant nature and for the differential diagnosis [2].
Sonography has the ability to clarify the opaque nature of lesions such as effusions, atelectasis, masses, and consolidations [3].
In recent years, the interest of chest physicians in transthoracic ultrasound has risen because it has the advantages of being available at the bedside, not requiring radiation, and allowing for guided aspiration of fluidfilled areas and solid tumors.
In addition, transthoracic US permits percutaneous guided biopsies, with lower risk than radiological guiding methods (fluoroscopy and CT) [2].
Transthoracic US can substitute for other lung imaging methods and guide various processes for diagnosing and managing. In real time, US guidance increases significantly the success rate of transthoracic suction or biopsy (TNB) while the risk of complications is reduced significantly [4].
The goal of this work was just to measure ultrasoundguided percutaneous core needle biopsy sensitivity and accuracy in different thoracic tumors (lung, pleural, chest wall, and mediastinal).

Methods
The current study is a case series study conducted on 60 patients that had radiographic evidence of thoracic mass suspected of malignancy and was selected from Chest Department, Kasr El-Aini Hospital and Beni-Suef University Hospital during the period from September 2020 to December 2020. ClinicalTrials.gov Identifier is NCT04741958 on 5/2/2021 Inclusion criteria 1. Peripheral pulmonary masses that abutted on pleural surface 2. Pleural mass or diffuse pleural thickening 3. Patients with mediastinal tumor anterior, posterior, or at the site that has chest wall touch 4. An acoustic window to penetrate the ultrasound beam This window appears to exist once the lesion is in direct contact with the parietal pleura or when the effusion or collapse takes place between the lesion and the chest wall, so that the ultrasound beam can transmit without being stopped by interposed air through the lesion.
5. Patients who have platelet count more than 100000 and normal prothrombin time Every patient received written informed consent, including the full explanation of the study and the right of the patient to withdraw at any time from the study during his or her participation. The consent also included the acceptance of the patient to use his or her data for publication and presentation after masking his/her name.
Approval of ethical committee was taken. i. Ultrasound was used to detect the lesion, assess a secure route for the needle placement, and therefore select the optimal position of the patient. ii. To recognize surrounding vessels, color-coded Doppler imaging must be required. The entry site is also obtainable; the direction and the depth for the biopsy were achieved by accurate visualization and localization of the lesion with good accessibility using ultrasonography. iii. The patient is then positioned according to the site of lesion to be biopsied-prone or setting for paravertebral lesions and supine for lateral or anterior lesions. iv. There were two or more biopsies carried out at the same place with semi-automatic Tru-Cut needle 16 gauge (Figs. 3 and 4). v. The Tru-Cut biopsy specimen was sent for pathologic examination. A specimen obtained by Tru-Cut biopsy was observed grossly and arbitrarily designated as inadequate if the specimen was smaller than 2 × 4 mm in size. A Tru-Cut biopsy was repeated immediately before the histologic examination was performed. If a lymphoma or Hodgkin's disease was suspected, multiple biopsies were conducted to obtain at least two adequate specimens for both routine histological examination as well as immunohistologic studies to confirm the cell type III. Post-procedural monitoring: 1. The site was reviewed with the US immediately after the procedure. 2. Three hours of surveillance after intervention.  3. All patients were subjected to routine assessment of vital signs as some patients develop vasovagal attacks during the procedure or develop tachypnea during or after the procedure. 4. All patients were observed for occurrence of puncture site hematoma or bleeding which may cause hemodynamic instability [5]. 5. Sonographic inspection of the patient before discharge (pneumothorax? bleeding?) [6].

Statistic methodology
The data collected has been revised, coded, and tabulated using SPSS Inc.  from the equation "Accuracy = (TP + TN)/(TP + TN + FP + FN)" True positive result: the tumor is confirmed by a definite histopathologic diagnosis made by Tru-Cut core biopsy True negative result: case not diagnosed as a tumor by ultrasound Tru-Cut core biopsy and this finding was confirmed by another modality for biopsy False negative results: considered when an ultrasound-guided biopsy had not been diagnosed with the tumor and the tumor was stated with other modalities (CT-guided, thoracoscopic, or surgical biopsy) 4. Chi-square: the comparison test that has been used with qualitative variables. Statistically significant differences have been considered when P values were less than 0.05

Results
This study is conducted on 60 patients that had radiographic evidence of thoracic mass suspected of malignancy and aiming for measuring sensitivity and accuracy of ultrasound-guided percutaneous core needle biopsy in different thoracic tumors (lung, pleural, chest wall, and mediastinal). The patients' ages ranged between 22 years and 85 years with 53.37 years mean age and 14.51 years standard deviations; they included 41 male patients with a percent of 68.33 and 19 female patients with a percent of 31.67. As regards the smoking state, 28 cases (46.67%) were current smokers, 9 cases (15%) were ex-smokers, both with 43.95 mean smoking index and 28.5 standard deviation. Twenty-three cases representing 38.33% were non-smokers. As regards the occupational and residence hazards status, it was found that 10 cases (16.66% of patient's population) were exposed to occupational hazards of malignancies and 5 cases (8.33%) were exposed to residence hazards (Table 1). Chest x-ray, CT chest, and transthoracic ultrasound were performed to all patients. The descriptive data obtained of all patients included in the study from chest x-ray, CT scan, and transthoracic ultrasonography (TUS) are shown in Tables 2, 3, and 4, respectively. In the assessment of pulmonary nodules by US in comparison to CT (Table 5), it was found that they agreed in 3 cases for detection of pulmonary nodules, while CT was able to detect 9 cases and TUS failed to detect these 9 cases. This finding was found to be statistically significant (p value = 0.0246). Transthoracic ultrasound detected central masses in 12 patients only of the studied patients; those central masses were reaching the chest wall or had sonic window through effusion or collapse, and CT chest confirmed this finding and detected additional 21 cases which the ultrasound could not. The difference in this finding between transthoracic ultrasound and CT chest was found to be statistically significant (P value = 0.0001); while US detected 21 cases of parenchymal masses and CT detected 20 cases, this difference was statistically non-significant (P value = 1) ( Table 6). Chest CT and US detected the same cases of unilateral pleural effusion (27 cases), and such results have been found to be statistically insignificant (P value = 1). Also, both modalities detected the same cases of bilateral pleural effusion (4 cases), and this finding was found to be statistically non-significant (P value = 1). US detected 19 cases with pleural thickening while CT detected 16 cases of them, and these results were found to be statistically non-significant (P value = 0.688). US was able to detect 7 cases as pleural nodules while CT detected 5 cases and was unable to detect 2 cases. These results were found to be statistically non-significant (P value = 0.762). Both CT and US had no difference in detection of pleural masses as both modalities detected 3 cases with pleural mass; this result was statistically nonsignificant (P value = 1) ( Table 7). Both US and CT agreed in 6 cases for detection of rib erosion, while US was once capable to detect 2 cases of intercostal muscle  invasion and CT failed to detect these 2 cases; these results were statistically non-significant (P value = 0.777).
As regards vertebral erosion, it was found that CT was able to detect vertebral erosion in 2 cases while US failed to detect them, and this finding was found to be statistically insignificant (P value = 0.496). So, the total chest wall invasion detected by CT was 11 cases while total chest wall invasion detected by ultrasound was 10 cases, and these results was found to be statistically nonsignificant (P value = 1) ( cases with large cell carcinoma, and 10 cases with adenocarcinoma; and just 5 cases (8.33%) had inflammatory lesion of which 3 cases were diagnosed as TB, one case was diagnosed as organizing pneumonia, and one was diagnosed as fibrosis ( Table 9). The total nonmalignant lesions were 10 cases; lesions with size 0.5-3 cm were 4 cases representing 40%, those with size 3-7 cm were 2 cases representing 20%, there was just one lesion with a size of 7-10 cm representing 10%, and there were 3 lesions of size above 10 cm representing 30%. In the same table, the total malignant lesions were 50 cases; 23of them were of size 0.5-3 cm representing 46%, those with size 3-7 cm were 17 cases representing 34%, there was just one lesion with a size of 7-10 cm representing 2%, and there were 9 lesions of size above 10 cm representing 18%, this results was found to be statistically non-significant (P value = 0.426) ( Table 10). All mediastinal and chest wall lesions were successfully diagnosed by histopathologic diagnosis made by Tru-Cut needle core biopsy giving 100% sensitivity, PPV, and accuracy, in 20 patients with lung lesions who had definite histopathologic diagnosis made by Tru-Cut core biopsy, of which19 biopsies showed true positive results for tumor and one represented a true negative, and none showed false positive or false negative. The true negative case was diagnosed as organizing pneumonia, and this diagnosis was confirmed clinically and by a CT-guided biopsy from the lesion. So, the sensitivity, PPV, and the diagnostic accuracy of transthoracic core biopsy in the diagnosis of lung tumor were 100%, 100%, and 100%. All pleural lesions (n = 17) had a definite histologic diagnoses made by Tru-Cut core biopsy, of which 15 biopsies showed true positive results for tumor, two showed true   negative, and none showed false positive or false negative. The true negative cases were diagnosed as pleural TB, and the other case as pleural fibrosis. These true negative results were confirmed by thoracoscopic biopsy. So, the sensitivity, PPV, and the diagnostic accuracy of transthoracic core biopsy in the diagnosis of pleural tumor were 100%, 100%, and 100%. In the same table, in 11 patients with lymph node lesions who had definite histologic diagnosis made by Tru-Cut core biopsy, 8 biopsies showed true positive results for tumor, two showed true negative, one showed false negative, and none showed false positive. One of the true negative cases was diagnosed as TB, and this diagnosis was confirmed by surgical lymph node biopsy, while the other case showing true negative result was diagnosed as TB, and this finding was confirmed by CT-guided biopsy from vertebral lesion. The false negative case was diagnosed as sarcoma by surgical biopsy. So, the sensitivity, PPV, and the diagnostic accuracy of transthoracic core biopsy in the diagnosis of lymph node tumor were 88.9%, 100%, and 90.9%, respectively. The overall diagnostic performance of sonar-guided Tru-Cut needle biopsy in diagnosis was 97.78% sensitivity, 98.18% accuracy, and 100% PPV (Tables 11 and 12). In our study, no complication was reported

Discussion
This study was conducted on 60 patients that had radiographic evidence of thoracic mass suspected of malignancy aiming for measuring sensitivity and accuracy of ultrasound-guided percutaneous core needle biopsy in different thoracic tumors (lung, pleural, chest wall, and mediastinal). In this study, by regarding the overall sensitivity and accuracy of transthoracic US findings in relation to CT chest findings (Tables 3 and 4), it was found that both modalities agreed to each other in detection of pleural effusion, pleural mass, and superior vena cava obstruction. These results agree with the results of [7], Using CT as a gold standard, study compared the diagnostic performance of TUS and bedside CXR for the identification of multiple pathological abnormalities in 200 critically ill patients. He found that the sensitivity,  specificity, and diagnostic accuracy of TUS for pleural effusion were 100%, 100%, and 100%, respectively, and he concluded that TUS may be used as an alternative to thoracic CT for the diagnosis of common pathological disorders such as pleural effusion. In disagreement with our results regarding pleural mass detection, [8] while studying 60 patients with pleural effusion reported that multi-detector computed tomography (100%, n = 12) was superior to US which detected 66.6% (n = 8) pleural masses with statistically significant difference. As shown in Tables 5 and 6), CT chest was superior over TUS in detection of pulmonary nodule, central mass. As regards the assessment of pulmonary nodules by US in comparison to CT (Table 5), it was found that they agreed in 3 cases for detection of pulmonary nodules, while CT was able to detect 9 cases and TUS failed to detect these 9 cases. This finding was found to be statistically significant (P value = 0.0246). These agree with [9] who reported that there were 9 patients with pulmonary nodules which were detected by CT and missed by ultrasound, while studying the role of ultrasound in 84 pleural effusion patients in diagnosis and management at Alzahraa University hospital. As shown in Table  6, it was found that transthoracic ultrasound detected central masses in 12 patients only of the studied patients whose central masses were reaching chest wall or had sonic window through effusion or collapse, and CT chest confirmed this finding and detected additional 21 cases which the ultrasound could not detect. The difference in   this finding between transthoracic ultrasound and CT chest was found to be statistically significant (P value = 0.0001). Also, these results agree with [10] who noted that US identified only 4 cases of mediastinal mass and CT identified 15 cases of mediastinal mass while studying the purpose of ultrasound in the diagnosis of chest disease in Kasr El-Aini University Hospital, Cairo, between 31 patients. TUS was superior over CT chest in detection of parenchymal mass, pleural thickening and axillary, SCLN, and lower deep cervical lymph node. This is coinciding with the study done by [11] who stated that ultrasonography could distinguish pleural from parenchymal lesions, interpret ill parenchyma shaded by pleural effusion, and identify pleural septations and other pleural abnormalities. It also diagnoses pulmonary parenchyma conditions such as consolidation, atelectasis and tumor differentially.
According to Table 7, US detected 19 cases with pleural thickening while CT detected 16 cases of them, and these results found to be statistically non-significant (P value = 0.688). These findings of pleural thickening detection agree with [12] who mentioned that as regards pleural thickening recognition, US detected 100% (n = 24) and was significantly more sensitive than CT scan which detected 6.6% (n = 16), while studying the diagnostic role of thoracic ultrasonography in pleural effusion. According to Table 7 in the present study, US was able to detect 7 cases as pleural nodules while CT detected 5 cases and was unable to detect 2 cases. These results were found to be statistically non-significant (P value = 0.762). Furthermore, [12] reported superiority of US (13/32) over CT (5/32) in detection of pleural nodules with statically significant difference.
Regarding chest wall invasion, according to Table 8, total chest wall invasion detected by CT was 11 cases while total chest wall invasion detected by ultrasound was 10 cases, and these results was found to be statistically non-significant (P value = 1). These results agreed with [13] who found that both CT and US agreed in 21 cases for detection of invasion of the lesions to chest wall, and while CT chest failed to detect that in 7 cases, this difference was statistically significant, in comparison of fine aspiration and Tru-Cut needle biopsy-guided ultrasonography in intrathoracic and chest wall lesions among 30 patients with peripheral intrathoracic shadows at Kasr El-Aini Hospital, Cairo University. Also, these results agree with [2] who performed a comparative evaluation of lung tumors in contact with the thoracic wall by transthoracic ultrasonography (US) and computed tomography (CT) among 131 patients with thoracic masses; they found that chest wall invasion detected by CT was greater than those detected by ultrasound, and they stated that the performance of US in diagnosing wall invasion is recognized (89-100%), being at least equal with that of CT (42-68%).
The results of this study showed that the majority of cases had extra-pulmonary tumors, followed by pulmonary tumors and just 8.33% of them had inflammatory lesion (Table 9).
In the current study, Fig. 1 showed that smoking was mainly linked to malignant diseases especially bronchogenic carcinoma. These results agree with [15] while evaluating the clinico-pathological profile of the bronchogenic carcinoma cases in the Chest Department, Cairo University, concluded that smoking still remains the major risk factor in the pathogenesis of bronchogenic carcinoma (Fig. 5).
The current study results showed that occupational and residence hazards are risk factors in the pathogenesis of bronchogenic carcinoma and mesothelioma. These results agree with [16] who mentioned that factories influence a range area of~5-7 km in radius, which clarifies the high rate of malignant pleuralmesothelioma (MPM) in people who live nearby to these factories. Individuals who worked since 1948 in the Egyptian asbestos organization Sigwart factories in greater Cairo (El-Maasara and Shubra El-Kheima) had an expanded hazard for MPM. In Egypt, the ministerial council decided to forbid asbestos imports in 2004 and the Sigwart plants were closed in November 2004. Therefore, along these lines, the anticipated rate of MPM in Egypt will achieve its peak around 2040.
The total non-malignant lesions were 10 cases; lesions with size 0.5-3 cm were 4 cases representing 40%, those with size 3-7 cm were 2 cases representing 20%, there was just one lesion with a size 7-10 cm representing 10%, and there were 3 lesions of size above 10 cm representing 30%. The total malignant lesions were 50 cases; 23 of them were of size 0.5-3cm representing 46%, those with size 3-7 cm were 17 cases representing 34%, there was just one lesion with size 7-10 cm representing 2%, and there were 9 lesions of size above 10 cm representing 18%. This result was found to be statistically nonsignificant (P value = 0.426). In both malignant and nonmalignant lesions, the most abundant lesion size was 0.5-3 cm (Table 10). These results disagree with [2] who performed a comparative evaluation of lung lesions in contact with the thoracic wall by transthoracic ultrasonography (US) and computed tomography (CT); they stated that between the patients with benign lesions and those with malignant lesions there are differences regarding the size of the masses, malignant lesions being significantly larger in size (p < 0.001).
In this study (Tables 11 and 12), all mediastinal and chest wall lesions were successfully diagnosed by histopathologic diagnosis made by Tru-Cut needle core biopsy giving 100% sensitivity, PPV, and accuracy, In 20 patients with lung lesions, there were 19 true positive tumor biopsies, one true negative biopsies, and no false positive or false negative biopsies among those who had a definite histopathologic diagnosis made by Tru-Cut core biopsy. The true negative case was diagnosed as organizing pneumonia, and this diagnosis was confirmed clinically and by CT-guided biopsy from the lesion. So, the sensitivity, PPV, and the diagnostic accuracy of transthoracic core biopsy in the diagnosis of lung tumor were 100%, 100%, and 100%. In the same context, in all pleural lesions (n = 17) having been definitely diagnosed histologically by Tru-Cut core biopsy, 15 biopsies have shown true tumor positive results, two have shown true negative results, and none have shown false positive or false negative results. True negative cases have been diagnosed as pleural TB, and the other as pleural fibrosis. Thoracoscopic biopsy confirmed the true negative results. Therefore, in the diagnosis of pleural tumors, the sensitivity, PPV, and the diagnostic accuracy of core transthoracic biopsy were 100%, 100%, and 100%. In 11 patients with lymph node lesions who had definite histologic diagnosis made by Tru-Cut core biopsy, 8 biopsies showed true positive results for tumor, two showed true negative, one showed false negative, and none showed false positive. One of the true negative cases was diagnosed as TB and this diagnosis was confirmed by surgical lymph node biopsy, while the other case showing true negative result was diagnosed as TB, and this finding was confirmed by CT-guided biopsy from vertebral lesion. The false negative case was diagnosed as sarcoma by surgical biopsy. So, the sensitivity, PPV, and the diagnostic accuracy of transthoracic core biopsy in the diagnosis of lymph node tumor were 88.9%, 100%, and 90.9%, respectively.
The overall diagnostic performance of sonar-guided Tru-Cut needle biopsy in diagnosis was 97.78% sensitivity, 98.18% accuracy, and 100% PPV. These results agree with [17] who stated that transthoracic US-guided lung biopsy had a specificity and sensitivity of 91.52%, while being a safe method, with a low complication rate of 8.47%, in a study of 89 patients with peripheral lung tumors, hospitalized at the Municipal Clinical Hospital Oradea. Also, these results agree with [18] who reported that the yield and safety of sonar-guided transthoracic cutting-needle biopsies of thoracic lesions were very good with an overall diagnostic accuracy rate of 84% and a sensitivity of 85.5% for malignant lesions. Also, these results agree with [19] who mentioned that ultrasound can be helpful in guiding a percutaneous transthoracic core biopsy with a sizeable bore Tru-Cut needle. The diagnostic sensitivity in malignant thoracic tumors was up to 96% and accuracy was 97%. Our study has several limitations. First, the number of the patients was small despite the observable variations regarding diagnosis, lesion size, and location. Second, there was a selection bias because only lesions that were in contact with pleural tissue were selected for biopsy. Further future study can be done on a large number of patients with peripheral lung lesions comparing the Tru-Cut needle with other types of needles.

Conclusion
Percutaneous transthoracic core biopsy with a Tru-Cut needle under ultrasound guidance is a secure and sensitive way of obtaining specimens for accurate histological diagnosis of thoracic tumors. The diagnostic yield is significant, and the approach is simple enough to be used as an outpatient procedure. The limitations of this study include the following: