[Advances in endoscopic diagnosis of sarcoidosis]. / Postepy w endoskopowej diagnostyce sarkoidozy.

A diagnosis of pulmonary sarcoidosis is based on the assessment of clinical outcome, radiology findings and detection of noncaseating granulomas in cytology or histology specimens. Cytological material obtained from enlarged lymph nodes and/or histological specimens from bronchial mucosa and lung tissue are examined according to sarcoidosis stage. The most available are standard bronchoscopic methods as conventional transbronchial needle aspiration (cTBNA), endobronchial biopsy (EBB) and transbronchial lung biopsy (TBLB) both performed with use of forceps. The new endoscopic techniques introduced to pulmonary diagnostics are: endobronchial ultrasoundguided transbronchial needle aspiration (EBUS-TBNA) and endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) or if used by the ultrasound bronchoscope (EUS-b-FNA) and transbronchial lung cryobiopsy (TBLC). Considering a dynamic improvement in cytology assessment techniques (processed as cytology smears and cell blocks) the endoscopic methods with use of fine needle aspiration biopsy of enlarged lymph nodes became a method of choice in sarcoidosis with lymphadenopathy, and published data suggest a higher diagnostic yield when performed under endosonographic guidance. The optimal approach (transbronchial or transesophageal) and the selection of mediastinal lymph node stations considered for biopsy still need evaluation. Also TBLC, successfully used in the diagnosis of other diffuse parenchymal lung diseases, requires more experiences and trials to establish its role in diagnosis of pulmonary sarcoidosis.

Cytology smears as diagnostic material for EGFR gene testing in non-small cell lung cancer.

AIMS AND BACKGROUND: Cytology smears can be effectively used for EGFR mutation testing in the qualification of NSCLC patients for EGFR tyrosine kinase inhibitor therapy. However, tissue specimens are preferred for EGFR mutation analysis. The aim of this study was to estimate the effectiveness of the real-time PCR method for EGFR testing in histology and cytology materials obtained simultaneously from NSCLC patients. METHODS: Fourteen adenocarcinoma patients with EGFR-mutation-positive primary tumor tissues were included in the study. Corresponding cytological smears of metastatic lymph nodes obtained by EBUS-TBNA were examined. EGFR Mutation Analysis Kit (EntroGen, USA) and real-time PCR (m2000rt system, Abbott, USA) were used for EGFR mutation analysis in both types of material. RESULTS: In primary tumor tissues, 12 deletions in exon 19 and 2 substitutions in exon 21 (L858R mutation) of the EGFR gene were found. Except for 1 deletion in exon 19, the same EGFR gene mutations were detected in all corresponding cytology samples. The percentage of tumor cells, DNA concentration, percentage of mutated DNA as well as ΔCt values were similar in cytology slides and histology material. In both types of materials, no significant correlations were found between the percentage of tumor cells and the percentage of mutated DNA nor between the DNA concentration and the percentage of mutated DNA. CONCLUSIONS: We demonstrated the high effectiveness of a sensitive real-time PCR method in EGFR gene mutation detection in cytology smears.

Accurate and safe mediastinal restaging by combined endobronchial and endoscopic ultrasound-guided needle aspiration performed by single ultrasound bronchoscope.

OBJECTIVES: The aim of this prospective trial was to assess the diagnostic utility of combined endobronchial (EBUS) and endoscopic (EUS) ultrasound-guided needle aspiration by use of a single ultrasound bronchoscope (CUSb-NA) in non-small-cell lung cancer (NSCLC) restaging in patients after induction therapy. METHODS: In a consecutive group of NSCLC patients with pathologically confirmed N2 disease (clinical stage IIIa and IIIb) who underwent induction chemotherapy, CUSb-NA was performed. All of the patients with negative or suspected for metastases (uncertain) diagnosed by endoscopy underwent subsequently transcervical extended mediastinal lymphadenectomy (TEMLA) as a confirmatory test. RESULTS: From January 2009 to December 2012, 106 patients met the inclusion criteria and underwent restaging CUSb-NA under mild sedation, in whom 286 (mean 2.7, range 2-5) lymph node stations were biopsied, 127 (mean 1.2, range 1-3) by EBUS-transbronchial needle aspiration (TBNA) and 159 (mean 1.5, range 1-4) by EUS-fine needle aspiration (FNA). The CUSb-NA revealed metastatic lymph node involvement in 37/106 patients (34.9%). In 69 (65.1%) patients with negative and uncertain CUSb-NA in 4 (3.8%) out of them, who underwent subsequent TEMLA metastatic nodes were found in 18 patients (17.0%) and there were single lymph nodes found only in one mediastinal station (minimal N2) in 10 (9.4%) out of them. False-positive results were found in 2 (1.9%) patients. In 9 (8.5%) patients CUSb-NA occurred to be false negative in Stations 2R and 4R (only accessible for EBUS), exclusively in small nodes and in 4 (3.8%) patients in Station 5-not accessible for CUSb-NA. The prevalence of mediastinal lymph node metastases in the present study was 51.9%. Diagnostic sensitivity, specificity, total accuracy, positive predictive value and negative predictive value (NPV) of the restaging CUSb-NA were 67.3% (95% CI [confidence interval]-53-79), 96.0% (95% CI-86-99), 81.0% (95% CI-73-87), 95.0% (95% CI-83-99) and 73.0% (95% CI-61-83), respectively. The sensitivity, accuracy and NPV of CUSb-NA were higher compared with EBUS-TBNA and EUS-FNA alone. No complications of CUSb-NA were observed. CONCLUSIONS: The CUSb-NA is a reasonable and safe technique in mediastinal restaging in NSCLC patients after induction therapy. Following our data, in patients with negative result of CUSb-NA, a surgical restaging of the mediastinum should be considered.

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 neoadjuvant 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.

Fast cytological evaluation of lymphatic nodes obtained during transcervical extended mediastinal lymphadenectomy.

OBJECTIVES: Evaluation of the diagnostic efficiency of the intraoperative cytological examination of lymphatic nodes obtained during transcervical extended mediastinal lymphadenectomy (TEMLA). METHODS: All mediastinal nodes obtained during consecutive TEMLA operations in patients with confirmed lung cancer were examined. Cytological imprints from cross sections of nodes were performed, fixed in 96 proof alcohol and stained with Haematoxylin-Eosin. The cytological slides were evaluated by light microscopy intraoperatively, and a standard paraffin histological examination of the same nodes was done afterwards for confirmation of the final diagnosis. RESULTS: Intraoperative cytological studies were performed in 63 patients (17 women and 46 men; overall in 453 mediastinal nodal stations) from 1 April 2009 to 28 February 2011. The mean number of nodes/procedure was 27.8. The mean time of performance of the examination was 37 min, including 7 min for smears, 13 min for staining and 17 min for microscopic examination (overall 37 min). The cytological study discovered neoplasmatic cells in 12 of 63 patients, nodal stations in 22 of 453 and nodes in 44 of 1724. According to the analysis of the 63 patients, the imprint cytology technique had a sensitivity of 92.3%, specificity of 100%, accuracy of 98.4%, positive predictive value of 100% and negative predictive value of 98.0%, as was confirmed by the final histopathological examination. CONCLUSIONS: (i) Cytological imprints examination was characterized by a very high specificity and sensitivity, is technically simpler and faster and allows for the examination of several dozens of lymphatic nodes during a single TEMLA procedure within an acceptable time, and after the exclusion of N2 nodes enables the simultaneous performance of a radical lung resection. (ii) The presented technique was the alternative for the traditional histopathological examination of the material frozen in cryostat.

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.

[Endoscopic ultrasound-guided needle aspiration in lung cancer]. / Przezprzelykowa biopsja wezlów chlonnych sródpiersia pod kontrola ultrasonografii wewnatrzprzelykowej w czasie rzeczywistym w diagnostyce raka pluca.

INTRODUCTION: The aim of the study was to assess the diagnostic yield of transoesophageal endoscopic ultrasound-guided needle aspiration (EUS-NA) in lung cancer (LC). MATERIAL AND METHODS: Real time EUS-NA was performed under local anaesthesia and sedation in consecutive LC patients. All negative EUS-NA results in NSCLC patients were verified by transcervical extended bilateral mediastinal lymphadenectomy (TEMLA). RESULTS: In 146 patients there were 206 biopsies performed in lymph node stations: subcarinal (7):124, left lower paratracheal (4L):70, paraoesophageal (8):9 and pulmonary ligament (9):3. A mean short axis of punctured node was 10+/-6.3 (95% CI) mm. Lymph node biopsy was technically successful in 95.6% and was diagnostic in 40.1% of LC patients. In NSCLC staging, the sensitivity of EUS-NA calculated on the per-patient basis was 85.5%, specificity 100%, accuracy 93.6% and negative predictive value (NPV) 89.7% in stations accessible for EUS-NA, but in all mediastinal stations it was 70.7%, 100%, 84.3% and 74.7, respectively (p=0.009). The sensitivity of EUS-NA in NSCLC staging patients, calculated on the per-biopsy basis was 88.6%, specificity 100%, accuracy 95.4% and NPV 91.4%. A diagnostic yield of EUS-NA on the per-biopsy basis was higher for station 4L than 7, but the difference was not significant (chi2 p=0.4). CONCLUSIONS: The diagnostic value of EUS-NA in LC is high. In NSCLC staging EUS-NA is insufficient and should be complemented by other invasive techniques, especially those that give access to the right paratracheal region.

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.

[Ultrasound guided transbronchial needle aspiration as a diagnostic tool for lung cancer and sarcoidosis]. / Przezoskrzelowa biopsja wezlów chlonnych sródpiersia i wnek pluca pod kontrola ultrasonografii wewnatrzoskrzelowej w czasie rzeczywistym w diagnostyce raka pluca i sarkoidozy.

INTRODUCTION: The aim of the study was to assess the diagnostic yield of ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) in mediastinal or hilar adenopathy in: 1) staging of non-small cell lung cancer (NSCLC) (97); 2) other malignant neoplasms including: small cell lung cancer (SCLC), metastatic neoplasms and Hodgkin's disease (16); 3) NSCLC recurrence (7); 4) sarcoidosis and other non-malignant diseases (29). MATERIAL AND METHODS: Real time EBUS-TBNA was performed under local anaesthesia and sedation in 149 consecutive patients - 237 biopsies in groups of lymph nodes: subcarinal (7) - 107, all paratracheal (2R, 2L, 4R, 4L) - 86, hilar (10R, 10L) - 41 and interlobar (11R, 11L) - 3. A mean axis of punctured node was 15 mm (range: 7-42 mm). All negative results were verified by transcervical extended bilateral mediastinal lymphadenectomy (TEMLA), mediastinoscopy or thoracotomy. RESULTS: Lymph node biopsy was technically successful in 92% and was diagnostic in 55% of lung cancer patients and in 85.7% of sarcoidosis patients. In NSCLC staging sensitivity of EBUS-TBNA was 88.7%, specificity 100%, accuracy 92.8% and NPV 83.3% (89.7%, 100%, 94.9% and 90.9% per biopsy), and in the whole group it was 91.5%, 98.7%, 94.6% and 87.3% respectively. In 7.2% of NSCLC staging patients with false negative results of EBUS-TBNA (mainly subcarinal) there was observed partial involvement of metastatic lymph nodes, mean 34.3% (range 10-50%), confirmed by TEMLA. CONCLUSION: The diagnostic value of EBUS-TBNA is very high in lung cancer, NSCLC staging and sarcoidosis.