Artur Szlubowski

Endosonography vs Conventional Bronchoscopy for the Diagnosis of Sarcoidosis: The GRANULOMA Randomized Clinical Trial

IMPORTANCE Tissue verification of noncaseating granulomas is recommended for the diagnosis of sarcoidosis. Bronchoscopy with transbronchial lung biopsies, the current diagnostic standard, has moderate sensitivity in assessing granulomas. Endosonography with intrathoracic nodal aspiration appears to be a promising diagnostic technique. OBJECTIVE To evaluate the diagnostic yield of bronchoscopy vs endosonography in the diagnosis of stage I/II sarcoidosis. DESIGN, SETTING, AND PATIENTS Randomized clinical multicenter trial (14 centers in 6 countries) between March 2009 and November 2011 of 304 consecutive patients with suspected pulmonary sarcoidosis (stage I/II) in whom tissue confirmation of noncaseating granulomas was indicated. INTERVENTIONS Either bronchoscopy with transbronchial and endobronchial lung biopsies or endosonography (esophageal or endobronchial ultrasonography) with aspiration of intrathoracic lymph nodes. All patients also underwent bronchoalveolar lavage. MAIN OUTCOMES AND MEASURES The primary outcome was the diagnostic yield for detecting noncaseating granulomas in patients with a final diagnosis of sarcoidosis. The diagnosis was based on final clinical judgment by the treating physician, according to all available information (including findings from initial bronchoscopy or endosonography). Secondary outcomes were the complication rate in both groups and sensitivity and specificity of bronchoalveolar lavage in the diagnosis of sarcoidosis. RESULTS A total of 149 patients were randomized to bronchoscopy and 155 to endosonography. Significantly more granulomas were detected at endosonography vs bronchoscopy (114 vs 72 patients; 74% vs 48%; P < .001). Diagnostic yield to detect granulomas for endosonography was 80% (95% CI, 73%-86%); for bronchoscopy, 53% (95% CI, 45%-61%) (P < .001). Two serious adverse events occurred in the bronchoscopy group and 1 in the endosonography group; all patients recovered completely. Sensitivity of the bronchoalveolar lavage for sarcoidosis based on CD4/CD8 ratio was 54% (95% CI, 46%-62%) for flow cytometry and 24% (95% CI, 16%-34%) for cytospin analysis. CONCLUSION AND RELEVANCE Among patients with suspected stage I/II pulmonary sarcoidosis undergoing tissue confirmation, the use of endosonographic nodal aspiration compared with bronchoscopic biopsy resulted in greater diagnostic yield. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00872612.

Endobronchial ultrasound-guided needle aspiration in the non-small cell lung cancer staging.

OBJECTIVE The aim of the study was to assess the diagnostic yield of the endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-NA) in the mediastinal staging in non-small cell lung cancer (NSCLC) patients. METHODS Consecutive NSCLC patients with enlarged or normal mediastinal nodes on CT scans underwent EBUS-NA. All patients with negative EBUS-NA subsequently underwent the transcervical extended bilateral mediastinal lymphadenectomy (TEMLA) as a confirmatory test. RESULTS Two hundred and twenty-six patients underwent EBUS-NA between 1.02.07 and 30.04.08. There were 320 mediastinal lymph nodes biopsied (stations: 2R - 8, 4R - 83, 2L - 1, 4L - 61, 7 - 167). EBUS-NA revealed metastatic lymph node involvement in 129/226 patients (57.1%) and in 171/320 biopsies (53.4%). In 97 patients with negative EBUS-NA, who underwent subsequent TEMLA, metastatic nodes were diagnosed in 16 patients (7.1%) - in 12 (5.3%) in stations accessible for EBUS-NA (stations: 4R - 3, 4L - 2, 7 - 8) and in 4 (1.8%) in stations not accessible for EBUS-NA (stations: 5 - 4, 6 - 1). All positive N2 nodes diagnosed by the TEMLA contained only small metastatic deposits. A diagnostic sensitivity, specificity, accuracy, PPV and NPV of EBUS-NA were 89.0%, 100%, 92.9%, 100% and 83.5%, respectively. No complications of EBUS-NA were observed. CONCLUSIONS (1) EBUS-NA is an effective and safe technique for mediastinal staging in NSCLC patients. (2) In patients with negative results of EBUS-NA, surgical exploration of the mediastinum should be performed.

Endobronchial ultrasound-guided needle aspiration in non-small-cell lung cancer restaging verified by the transcervical bilateral extended mediastinal lymphadenectomy — a prospective study

OBJECTIVES The aim of the study was to assess the diagnostic yield of the endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) in restaging of the non-small-cell lung cancer (NSCLC) patients after neo-adjuvant therapy. METHODS In a consecutive group of NSCLC patients with pathologically confirmed N2 disease, who underwent neo-adjuvant chemotherapy, EBUS-TBNA was performed. All patients with negative EBUS-TBNA underwent subsequently the transcervical extended bilateral mediastinal lymphadenectomy (TEMLA) as a confirmatory test. RESULTS A total of 61 patients underwent restaging EBUS-TBNA between 1 June 2007 and 31 December 2008. There were 85 mediastinal lymph nodes biopsied (stations: 2R - 2, 4R - 24, 2L - 1, 4L - 18 and 7 - 40). EBUS-TBNA revealed metastatic lymph node involvement in 18 of 61 patients (30%) and in 22 of 85 biopsies (26%). In 43 patients with negative or uncertain EBUS-TBNA, who underwent subsequent TEMLA, metastatic nodes were diagnosed in nine patients (15%) - in seven (12%) in stations accessible for EBUS-TBNA (stations: 2R - 1, 4R - 5, 7 - 4) and in two (3%) in station not accessible for EBUS-TBNA (station: 5 - 2). The false-negative results of biopsies were found only in small nodes (5.8+/-2.8 mm x 7.5+/-2 mm). Moreover, all positive N2 nodes diagnosed by TEMLA contained only small metastatic deposits. There were three of 61 (5%) patients with false-positive results of biopsies in stations: 4R - 1, 4L - 1, and 7 - 2. A diagnostic sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) of the restaging EBUS-TBNA was 67% (95% confidence interval (CI) - 65-90), 86% (95% CI - 82-95), 80%, 91% (95% CI - 80-100) and 78% (95% CI - 73-93), respectively. No complications of EBUS-TBNA were observed. CONCLUSIONS EBUS-TBNA is an effective and safe technique for mediastinal restaging in NSCLC patients, and after the data presented in our study, in patients with negative results of EBUS-TBNA, a surgical restaging of the mediastinum might not be mandatory.

Comparison of Endobronchial Ultrasound and/or Endoesophageal Ultrasound with Transcervical Extended Mediastinal Lymphadenectomy for Staging and Restaging of Non–Small-Cell Lung Cancer

Background: To compare the diagnostic yield of endobronchial ultrasound (EBUS) and/or endoesophageal ultrasound (EUS) with transcervical extended mediastinal lymphadenectomy (TEMLA) for primary staging and repeated staging (restaging) of non–small-cell lung cancer (NSCLC). Methods: In this retrospective study, all consecutive patients undergoing primary staging and restaging after neodjuvant chemo- or chemo-radiotherapy for NSCLC with EBUS, EUS, or EBUS combined with EUS (CUS) with fine needle aspiration biopsy and cytological examination and subsequent TEMLA from January 1, 2007 to December 31 2010, were included. Results: Primary staging was performed in 623 patients: EBUS in 351, EUS in 72, and CUS in 200 patients. TEMLA was performed for primary staging in 276 patients. There was no mortality and morbidity after EBUS or EUS. One patient died after TEMLA and morbidity rate after TEMLA was 7.2%. There was a significant difference between EBUS or EUS and TEMLA for sensitivity (87.8% and 96.2%; p < 0.01) and negative predictive value (82.5% and 99.6%; p < 0.01) in favor of TEMLA. In the restaging group, endoscopic staging was performed in 88 patients and TEMLA in 78 patients. There was a significant difference between EBUS or EUS and TEMLA for sensitivity (64.3% and 100%; p < 0.01) and negative predictive value (82.1% and 100%; p < 0.01) in favor of TEMLA. Conclusions: The results of this largest reported series comparing the endoscopic and surgical primary staging and restaging of NSCLC showed a significantly higher diagnostic yield of TEMLA when compared with that of EBUS or EUS.

Non-small-cell lung cancer restaging with transcervical extended mediastinal lymphadenectomy

BACKGROUND To analyse a diagnostic yield of the transcervical extended mediastinal lymphadenectomy (TEMLA) in restaging of the mediastinal nodes after neoadjuvant chemo- or chemo-radiotherapy for non-small-cell lung cancer (NSCLC). METHODS From 1 January 2004 to 30 April 2009, 63 patients who underwent induction chemotherapy or chemo-radiotherapy for N2 and N2/3 metastatic nodes discovered preoperatively were restaged. There were 12 women and 51 men in the age group of 43-71 (mean 57.8) years. There were 45 squamous cell carcinomas, 13 adenocarcinomas, one pleomorphic carcinoma and four NSCLCs. A total of 54 patients underwent neoadjuvant chemotherapy and nine chemo-radiotherapy. Seven patients had mediastinoscopy before neoadjuvant therapy. As many as 34 patients underwent endobronchial ultrasound (EBUS), one patient underwent endo-oesophageal ultrasound (EUS) and 10 patients underwent combined EBUS/EUS. The diagnostic results of TEMLA were compared with the results of the largest published series of restaging patients. The results of subsequent thoracotomies after negative TEMLA were presented. RESULTS There were no serious complications or mortality after TEMLA. Metastatic nodes were discovered in 22 patients including three patients with N3 nodes and 19 patients with N2 nodes. Stations 7, 4R, 2R and 4L were the most prevalent. Of the 63 patients, 42 underwent subsequently thoracotomy. Resectability for negative TEMLA was 92.7%. There were 37 R0 resections and four R1 resections. There was no postoperative mortality, two bronchial fistulas were developed (after inferior bilobectomy and right pneumonectomy; the second one healed spontaneously) and there were no other serious complications. During thoracotomy with completion lymphadenectomy one false-negative result was found (single node in station 8). Sensitivity of TEMLA in the discovery of N2/3 nodes during restaging was 95.5%, specificity 100%, accuracy 98.3%, negative predictive value (NPV) 97.4% and positive predictive value (PPV) 100%. TEMLA was found to have significantly better sensitivity and NPV (p<0.05) than other series of restaging. During follow-up a local recurrence was noted in six of 37 (15.7%) patients after pulmonary resection. CONCLUSIONS (1) The results of TEMLA in restaging of NSCLC (N2/3) patients after induction chemotherapy or chemo-radiotherapy were significantly better than those achieved with remediastinoscopy, EBUS and positron emission tomography/computed tomography (PET/CT). (2) The results of future studies will show if TEMLA should be considered the gold standard of mediastinal nodal restaging after neoadjuvant therapy in patients with NSCLC.

Staging algorithm for diffuse malignant pleural mesothelioma

An algorithm of preoperative mediastinal nodal staging with endobronchial/endoesophageal ultrasonography (EBUS/EUS) and transcervical extended mediastinal lymphadenectomy (TEMLA) combined with laparoscopy/peritoneal lavage and cytology was analyzed to establish the realistic criteria for radical multimodality treatment of malignant pleural mesothelioma (MPM). The algorithm included computed tomography (CT), thoracoscopy with multiple pleural biopsies and talc pleurodesis, EBUS/EUS and one-stage TEMLA and laparoscopy/peritoneal lavage and cytology of the fluid. Forty-two patients were diagnosed from 1 January 2004 to 31 December 2008. There were 16 women and 26 men in ages ranging from 43 to 77 years (mean 57.8); 31 epithelioid, 2 sarcomatoid and 9 biphasic type MPM. 21/42 patients were considered possible candidates for multimodality treatment. Three patients who received neoadjuvant chemotherapy were excluded from this study. EBUS/EUS was performed to stage the mediastinal nodes. In 3/18 patients metastatic nodes were discovered. In the rest of the 15 patients simultaneous TEMLA and laparoscopy/peritoneal lavage and cytology of the fluid were performed. In three patients TEMLA was positive, in six patients laparoscopy was positive and in two patients both TEMLA and laparoscopy were positive. Finally, 4/42 (9.5%) patients underwent thoracotomy with one exploration (chest wall infiltration) and three pleuropneumonectomies with the subsequent chemo- and radiotherapy. The proposed algorithm of preoperative staging spared the majority of MPM patients from futile surgery.

Resection of thymomas with use of the new minimally-invasive technique of extended thymectomy performed through the subxiphoid-right video-thoracoscopic approach with double elevation of the sternum

OBJECTIVES To present the new technique of minimally invasive extended thymectomy performed through the subxiphoid-right video-thoracoscopic (VATS) approach with double elevation of the sternum and the early results of resection of thymomas with the use of this technique. METHODS OPERATIVE TECHNIQUE whole dissection was performed through a 4- to 7-cm transverse subxiphoid incision, and a single 5-mm port was inserted into the right chest cavity for the video thoracoscope and subsequently for the chest tube. The sternum was elevated with two hooks connected to the sternal frame (Rochard bar, Aesculap-Chifa, Nowy Tomysl, Poland). The lower hook was inserted through the subxiphoid incision, and the superior hook was inserted percutaneously after the mediastinal tissue including the major mediastinal vessels was dissected from the inner surface of the sternum. The fatty tissue of the anterior mediastinum and the aorta-pulmonary window was completely removed. RESULTS There were 24 patients operated on for the Masaoka Stage I-III thymoma in the period from 1 January 2009 to 30 March 2012. There was no mortality and complications occurred in 1 patient necessitating revision for bleeding (morbidity rate 4.2%). The median operative time was 105.0 (range 70-195) min. In 2 patients it was possible to completely resect Masaoka Stage III tumour infiltrating the right lung, which was resected with the use of an endostapler. The dimensions of the thymomas ranged from 1.8 × 1.5 × 1.5 to 12 × 9 × 5 cm. CONCLUSIONS In our opinion, the presented technique is probably the least invasive and the most complete technique of VATS thymectomy with excellent cosmetic results and is a valid alternative to sternotomy approach for the Masaoka Stage I-III thymomas.

Technique of the transcervical-subxiphoid-videothoracoscopic maximal thymectomy

Background: The aim of this study is to present the new technique of transcervical-subxiphoid-videothoracoscopic “maximal”thymectomy introduced by the authors of this study for myasthenia gravis. Materials and Methods: Two hundred and sixteen patients with Osserman scores ranging from I–III were operated on from 1/9/2000 to 31/12/2006 for this study. The operation was performed through four incisions: a transverse 5–8 cm incision in the neck, a 4–6 cm subxiphoid incision and two 1 cm incisions for videothoracoscopic (VTS) ports. The cervical part of the procedure was performed with an open technique while the intrathoracic part was performed using a video assisted thoracoscopic surgical (VATS) technique. The whole thymus with the surrounding fatty tissue containing possible ectopic foci of the thymic tissue was removed. Such an operation can be performed by one surgical team (the one team approach) or by two teams working simultaneously (two team approach). The early and late results as well as the incidence and localization of ectopic thymic foci have been presented in this report. Results: There were 216 patients in this study of which 178 were women and 38 were men. The ages of the patients ranged from 11 to 69 years (mean 29.7 years). The duration of myasthenia was 2–180 months (mean 28.3 months). Osserman scores were in the range of I–III. Almost 27% of the patients were taking steroids or immunosuppressive drugs preoperatively. The mean operative time was 201.5 min (120–330 min) for a one-team approach and it was 146 (95–210 min) for a two-team approach (P < 0.05). While there was no postoperative mortality, the postoperative morbidity was 12%. The incidence of ectopic thymic foci was 68.4%. The rates of complete remission after one, two, three, four and five years of follow-up were 26.3, 36.5, 42.9, 46.8 and 50.2%, respectively. Conclusion: Transcervical-subxiphoid-VTS maximal thymectomy is a complete and highly effective treatment modality for myasthenia gravis. The need for sternotomy is avoided while the completeness of the operation is retained.

EUS-B-FNA vs conventional EUS-FNA for left adrenal gland analysis in lung cancer patients

INTRODUCTION In patients with lung cancer, left adrenal glands (LAG) suspected for distant metastases (M1b) based on imaging require further evaluation for a definitive diagnosis. Tissue acquisition is regularly performed using conventional EUS-FNA. The aim of this study was to investigate the success rate of endoscopic ultrasound guided fine-needle aspiration using the EBUS scope (EUS-B-FNA) for LAG analysis. METHODS This is a prospective multicenter study in consecutive patients with (suspected) lung cancer and suspected mediastinal and LAG metastases. Following complete mediastinal staging using the EBUS scope (EBUS+EUS-B), the LAG was evaluated and sampled by both EUS-B (experimental procedure) and conventional EUS (current standard of care). RESULTS The success rate for LAG analysis (visualized, sampled and adequate tissue obtained) was 89% (39/44; 95% CI 76-95%) for EUS-B-FNA, and 93% (41/44; 95%CI 82-98%) for EUS-FNA. In the absence of metastases at EUS-B and/or EUS, surgical verification of the LAG or 6 months clinical and radiological follow-up was obtained, but missing for 5 patients. The prevalence of LAG metastases was 54% (21/39). In patients in whom LAG was seen and sampled, sensitivity for LAG metastases was at least 87% (95%CI 65-97%) for EUS-B, and at least 83% (95%CI 62-95%) for conventional EUS. CONCLUSION LAG analysis by EUS-B shows a similar high success rate in comparison to conventional EUS. IMPLICATION Both a mediastinal nodal and LAG evaluation can be adequately performed with just an EBUS scope and single endoscopist. This staging strategy is likely to reduce patient-burden and costs.

Ultrasound-Guided Transbronchial and Transesophageal Needle Biopsy in the Mediastinal Staging of Lung Cancer

This review presents the current state of two endosonographic techniques, endobronchial ultrasonography (EBUS) and endoscopic ultrasonography (EUS), and their application in the mediastinal staging of patients with lung cancer. The technique for these procedures is presented and their diagnostic yield is discussed, based on the published evidence. EBUS and EUS, especially in combination with needle aspiration biopsy, emerge as the primary modalities for mediastinal staging because of their high diagnostic yield, minimal invasiveness, low cost, and avoidance of disruption of mediastinal lymphatic pathways before the final treatment.