Juliusz Pankowski

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.

Constitutional CHEK2 mutations are associated with a decreased risk of lung and laryngeal cancers

Mutations in the CHEK2 gene have been associated with increased risks of breast, prostate and colon cancer. In contrast, a previous report suggests that individuals with the I157T missense variant of the CHEK2 gene might be at decreased risk of lung cancer and upper aero-digestive cancers. To confirm this hypothesis, we genotyped 895 cases of lung cancer, 430 cases of laryngeal cancer and 6391 controls from Poland for four founder alleles in the CHEK2 gene, each of which has been associated with an increased risk of cancer at several sites. The presence of a CHEK2 mutation was protective against both lung cancer [odds ratio (OR) = 0.3; 95% confidence interval (CI) 0.2-0.5; P = 3 x 10(-8)] and laryngeal cancer (OR = 0.6; 95% CI 0.3-0.99; P = 0.05). The basis of the protective effect is unknown, but may relate to the reduced viability of lung cancer cells with a CHEK2 mutation. Lung cancers frequently possess other defects in genes in the DNA damage response pathway (e.g. p53 mutations) and have a high level of genotoxic DNA damage induced by tobacco smoke. We speculate that lung cancer cells with impaired CHEK2 function undergo increased rates of cell death.

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.

Ectopic thymic tissue in the mediastinum: limitations for the operative treatment of myasthenia gravis

OBJECTIVES The aim of the study was to investigate the distribution of ectopic thymic tissue in the mediastinum and to evaluate the possible relevance of this distribution to the therapeutic yield of thymectomies in patients with myasthenia gravis. METHODS In this prospective autopsy study, mediastinal dissections were performed on 50 cadavers without any previously known intrathoracic pathology. The initial dissection was performed in the same way as during the maximal thymectomy. The second stage consisted of dissecting areas of fatty tissue located out of reach of the standard maximal thymectomy, such as the perithyroid, periaortic, peritracheal and retrotracheal areas, as well as the areas adjacent to the right and left phrenic and recurrent laryngeal nerves. Each specimen was independently examined by two pathologists for ectopic thymic tissue. RESULTS There were 41 (82%) male and 9 (18%) female cadavers, with a mean age of 44.3 years (range: 15-75). Ectopic thymic tissue was detected in 32 out of 50 cadavers (64%). In 10 (20%) cadavers thymic foci were found in locations accessible to the standard surgical intervention and in 22 (44%)-in inaccessible locations. Thymic tissue incidence in individual locations was as follows: retrothyroid, 3 (6%); peritracheal, 5 (10%); retrotracheal, 1 (2%); right phrenic nerve, 2 (4%); left phrenic nerve, 14 (28%); right recurrent laryngeal nerve, 2 (4%); left recurrent laryngeal nerve, 2 (4%) and periaortic, 0. CONCLUSIONS The incidence of ectopic thymic tissue in the mediastinum is common. Although some improvements in the results of thymectomies may be expected with more extensive dissection, the frequent presence of thymic foci in anatomical locations hardly accessible to surgical intervention may be the true limitation for surgical treatment of myasthenia.

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.

Initial Polish experience of Flexible 19 gauge Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration

INTRODUCTION EBUS is a well established minimally invasive diagnostic tool for mediastinal and hilar lymphadenopathy. The novel ViziShot Flex 19G needle (Olympus Respiratory America, Redmond, WA, USA) was introduced in 2015 in order to improve loaded scope flexion and to obtain larger tissue samples for analysis. The aims of this study were to assess diagnostic yield of Flex 19G needles and to present endoscopists feedback about the endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA). MATERIAL AND METHODS The Flex 19G needles were used in patients with hilar and/or mediastinal adenopathy in two Polish pulmonology centers. Cytology smears and cell blocks (CB) were prepared. The prospective analysis was performed due to collected data. RESULTS Twenty two selected patients with confirmed adenopathy on chest-CT (mean age 58 ± 12) underwent EBUS-TBNA with use of Flex 19G needles. All procedures occurred to be diagnostic for smears (yield 100%). The malignancy was found in 15 cases (68.2%), and benign adenopathy in 7 (31.8%). In 12 of 14 cases of lung cancer (yield 85.7%) CB were diagnostic for immunohistochemical and molecular staining. After puncturing nodes, especially in hilar position not extensive bleeding was observed. Comparing to standard 21/22G EBUS-TBNA endoscopists underlined better flexion of loaded scope and sample adequacy and found non-significant differences in another biopsy details. CONCLUSIONS The first Polish experience with use of Flex 19G EBUS-TBNA needle occurs to be similar in performance with standard technique with use of 22/21G needles and presents high diagnostic yield for lung cancer diagnostics, especially when preparing CB. A safety profile of the biopsy is acceptable.