BRONCHOSCOPY C O U R S E

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1 UNIVERSITY CLINIC OF RESPIRATORY AND ALLERGIC DISEASES GOLNIK BRONCHOSCOPY SCHOOL GOLNIK Golnik, 2011 October BRONCHOSCOPY C O U R S E

2 Publisher UNIVERSITY CLINIC OF RESPIRATORY AND ALLERGIC DISEASES GOLNIK - BRONCHOSCOPY SCHOOL GOLNIK Editors Nadja Triller Aleš Rozman Head of Organizing Committee Nadja Triller Golnik, 2011 October 14 15

3 11 th Golnik Bronchoscopy Course PROGRAM Friday, 14 October Lectures Registration, cofee coffee Opening Nadja Triller, Mitja Košnik How and why did we use bronchoscope 60 th anniversary An overview of training program in ronchoscopy at Nadja Triller Clinic Golnik years of Jacobaeus procedure our story Andrej Debeljak Bronchoscopy what s the next step? Stefano Gasparini COFFEE BREAK Traditional and technology-guided TBNA, pros and cons Is mediastinoscopy an obscure method? (CUS TBNA for complete mediastinal staging) Stefano Gasparini Arthur Szlubowski EBUS mini-probe as a maxi-too Aleš Rozman Precise tissue diagnosis for personalized treatment in Izidor Kern lung cancer Strange bugs in bronchoscopy unit Viktorija Tomič Strange bugs in bronchoscopy unit Case report Aleš Rozman LUNCH Group photo in the park Workshops Room 1. Traditional TBNA Stefano Gasparini, Luka Camlek Room 2. EBUS TBNA Arthur Szlubowski, Mateja Marc Malovrh Room 3. Thoracoscopy Aleš Rozman, Andrej Debeljak COFFEE BREAK Room 4. Different biopsy techniques Katarina Osolnik, Nadja Triller Room 5. Bronchoscopic LVR Ralf Eberhardt GALA DINNER

4 Saturday, 15 October Lectures Coffee Bronchoscopic LVR Ralf Eberhardt Medical thoracoscopy advanced techniques Aleš Rozman Rigid vs. semirigid thoracoscopy Aleš Rozman Case report interactive session (intersticij) Katarina Osolnik Case report interactive session (EBUS) Mateja Marc Case report- interactive session (torakoskopija) Luka Camlek COFFEE BREAK Oral presentations Video presentations Poster discussions Summary and certificates Nadja Triller

5 FACULTY Ralf Eberhardt Germany Arthur Szulbowski - Poland Stefano Gasparini - Italy Nadja Triller - University Clinic of Respiratory and Allergic Diseases Golnik Slovenia Andrej Debeljak - University Clinic of Respiratory and Allergic Diseases Golnik Slovenia Izidor Kern - University Clinic of Respiratory and Allergic Diseases Golnik Slovenia Viktorija Tomič - University Clinic of Respiratory and Allergic Diseases Golnik Slovenia Aleš Rozman - University Clinic of Respiratory and Allergic Diseases Golnik Slovenia Katarina Osolnik - University Clinic of Respiratory and Allergic Diseases Golnik Slovenia Luka Camlek - University Clinic of Respiratory and Allergic Diseases Golnik Slovenia Mateja Marc Malovrh - University Clinic of Respiratory and Allergic Diseases Golnik Slovenia

6 How and why did we use the bronchoscope? Sixty years of bronchoscopy Nadja Triller, Andrej Debeljak, Jurij Šorli University Clinic of Pulmonary Diseases and Allergy, Golnik Bronchoscopy is one of the most commonly performed procedures in pulmonology. Although instruments for inspecting the body cavities (nose, ear, trachea, etc.) had been in use for ages, nobody looked into the trachea until suitable light sources, sufficient anesthesia, and a proper instrument for inspection were developed. The rhinolaryngologist Gustav Killian (Fig. 1) from Freiburg University was the first to use bronchoscopy on tracheotomized patients. He used a modified Rosenheim esophagoscope and introduced it under local cocaine anesthesia into the trachea. He found that the trachea and bronchi were elastic and it was easy to introduce the rigid scope through the trachea to both main bronchi. After his first experiences on tracheotomized patients, he started to practice on cadavers and soon thereafter performed his first bronchoscopy in a volunteer. The first therapeutic bronchoscopy via the translaryngeal route was performed in 1897, when he removed the first foreign body, a pork bone, from the right main bronchi. Killian presented the new method at the meeting of the Society of South German Laryngologists in Heidelberg on 29 May 1898, and that same year his first publication on direct bronchoscopy was published. Killian`s bronchoscope attracted extensive interest. In 1907 Killian was invited to the U.S., where he met Chevalier Jackson. Jackson produced a bronchoscope with a small light bulb at its distal end that incorporated a suction device. However, the main emphasis of the method was on the retrieval of foreign bodies. Figure 1. Gustav Killian performed the first rigid bronchoscopy, and Shigeto Ikeda performed the first flexible bronchoscopy. The image quality was further improved by incorporating a telescopic lens system, which worked on the principle of a series of small lenses installed at various angles. This instrument opened up a new area of examination and expanded the applications

7 beyond foreign-body removal to the localization of hemoptysis and endobronchial diseases, mainly tuberculosis and other infections At the Ninth International Congress of Diseases of the Chest, held in Copenhagen in 1966, Shigeto Ikeda presented his new fiberbronchoscope. With this instrument, the depth of the bronchial tree could be reached to a much greater extent. Figure 2. Stevan Goldman (a) performed the first rigid bronchoscopy (1951) and Jurij Šorli (b) performed the first flexible bronchoscopy in Slovenia (1974). a b Fifty years after the inception of bronchoscopy, the first rigid bronchoscopy in Slovenia was performed at Golnik. The technique was introduced by Ivo Drinković and Stevo Goldman. The first rigid bronchoscope was brought from Paris and for the next few years it was the only such instrument in Slovenia. Bronchoscopic examinations were performed at Golnik and Topolšica, the two main hospitals for pulmonary diseases and tuberculosis at that time. Because of the enthusiastic activities of both pioneers, bronchoscopy became the standard procedure in diagnosing the airways. Drinković and Goldman taught their skills, and in the following years their colleagues started performing diagnostic and therapeutic procedures. Judita Mešič, Leon Fink, Bojan Fortič, Marjan Komar, and Viktor Legiša used a rigid bronchoscope in everyday clinical practice. The pulmonologist Jurij Šorli, trained by Judita Mešič, introduced flexible bronchoscopy in He performed the first bronchoscopic lung biopsy via flexible bronchoscope (Table 1). After Šorli introduced the flexible bronchoscope, he initially used it in combination with a rigid bronchoscope. In an era of expanding interventional procedures, this method of combining both bronchoscopes (flexible and rigid) has attracted new attention today. A new generation of bronchoscopists Andrej Debeljak, Marija Zupančič, Janez Remškar, Marjan Fortuna, Marjeta Terčelj, Matjaž Turel, Nadja Triller, Katarina Osolnik, Damjan Eržen, Peter Kecelj, and others introduced new diagnostic techniques (Table 1) and bronchoscopy became an integral part of respiratory medicine. To date, five heads of the bronchoscopy department have overseen its organization, expanded knowledge, and promoted research (Figure 3). Figure 3. Heads of the Bronchoscopy Department at Golnik Hospital.

8 Judita Mešič Jurij Šorli Andrej Debeljak Nadja Triller Aleš Rozman Currently we are experiencing a new wave of new techniques in diagnostic and therapeutic procedures: endobronchial ultrasound, autofluorescence bronchoscopy, electromagnetic navigation, optical coherence tomography. Recent therapeutic advances include intrabronchial valve placement for nonsurgical treatment of emphysema and thermoplasty for difficult-to-treat asthma. Not all of these new techniques are used at the Chest Clinic at Golnik. Diagnostic indications included tissue diagnosis, detection and staging of lung malignancy, evaluation of diffuse lung diseases such as sarcoidosis and idiopathic interstitial pneumonias, and identification of organisms infecting the respiratory tract. As a therapeutic modality, bronchoscopy has been used to place stents, to remove foreign bodies or masses, and to treat early stage endobronchial malignancy. Today this top-level unit for diagnostics and therapeutic procedures brings together five medical doctors Aleš Rozman (the head of the unit), Mateja Marc Malovrh, Luka Camlek, Katarina Osolnik, and Nadja Triller and five nurse-assistants: Marija Petrinec Primožič (the head of the nursing team), Štefan Duh, Martina Košnik, Slavi Mohorič, and Rudi Sluga (Fig. 4). They perform approximately 2,000 procedures per year. Most of these are bronchoscopies (1,400 to 1,500), but also include needle biopsies of the lung, closed pleural biopsies, and medical thoracoscopies. Their research findings and professional experience have helped prepare the guidelines and theoretical premises for respiratory endoscopy in Slovenia. This well-coordinated team keeps up to date with innovations in the field by regularly visiting and training at top-level European medical centers, especially in similar respiratory endoscopy units, such as Heidelberg, Hemer, and Berlin (Germany), Lille (France), Ancona (Italy), and Amsterdam (the Netherlands).

9 Fig. 4. The bronchoscopy team in The unit is also a teaching center for specialists and their assistants from Slovenia and some other eastern and central European countries. The bronchoscopists research is mainly directed towards early diagnostics of lung cancer with autofluorescence bronchoscopy and endobronchial ultrasound. They have developed an excellent means to prepare patients for bronchoscopy. One of their achievements is an innovative method of reassuring patients during bronchoscopic examinations by playing music. Another major challenge for the staff is working in pure research projects.

10 Table 1. Introduction of new bronchoscopy techniques globally and at the Golnik endoscopy unit in the last 60 years. Global Golnik Year Physician and technique Year Physician and technique 1897 Gustav Killian: father of bronchoscopy, first rigid brochoscopy 1951 Ivo Drinković & Stevo Goldman: fathers of bronchoscopy in Slovenia 1947 Ian P. Stevenson: bronchoalveolar 1982 Andrej Debeljak: bronchoalveolar lavage lavage 1955 H. E. Euler: transbronchial needle aspiration of mediastinal mass with rigid bronchoscope 1990 Andrej Debeljak: transbronchial needle aspiration of mediastinal mass with rigid bronchoscope 1956 Antonio O. Perez: catheter biopsy of 1968 Leon Fink: catheter biopsy of the lung the lung 1956 Eitaka Tsuboi: brushing in diagnosis of peripheral lung lesion 1974 Jurij Šorli: brushing in diagnosis of peripheral lung lesion 1964 Eitaka Tsuboi,: transbronchial lung 1974 Jurij Šorli: transbronchial lung biopsy biopsy 1966 Shigeto Ikeda: first fiberoptic 1974 Jurij Šorli: fiberoptic bronchoscopy bronchoscope 1973 H. Bryan Neel III: endobronchial 2006 Nadja Triller: endobronchial cryosurgery cryosurgery 1974 Georgios Nakratzas: endobronchial electrocautery 1999 Andrej Debeljak, Nadja Triller, Peter Kecelj, & Saša Letonja: endobronchial electrocautery Never performed at Golnik 1978 Lucien Toty: Nd:YAG laser used through a bronchoscope 1983 Ko Pen Wang: transbronchial needle 1992 Andrej Debeljak & Marjeta Tečelj: aspiration through flexible transbronchial needle aspiration through bronchoscope flexible bronchoscope 1987 Fiberoptic video bronchoscopy 1989 Victor Tsang: airway stenting 2002 Andrej Debeljak: airway stenting 1991 Stephen Lam: autofluorescence 2000 Nadja Triller & Andrej Debeljak: bronchoscopy autofluorescence bronchoscopy 1999 Heinrich D. Becker: endobronchial 2001 Nadja Triller: endobronchial ultrasound ultrasound 2001 Tudor P. Toma: bronchoscopic lung 2005 Nadja Triller: bronchoscopic lung volume volume reduction for managing reduction for managing emphysema emphysema 2002 Shigeo Tanaka: narrow band imaging 2007 Nadja Triller: narrow band imaging bronchoscopy bronchoscope 2002 James Fujimoto: endoscopic optical Never performed at Golnik coherence tomography 2002 John D. Miller: bronchial thermoplasty Never performed at Golnik 2003 Yehuda Schwarz: electromagnetic Never performed at Golnik navigation

11 Published articles and conference papers Bronchoscopy Department, University Pulmonary Clinic, Golnik Mešič J. The importance of bronchoscopy in the diagnosis of pulmonary diseases. Zdrav Vestn. 1959;28(6 7): [Slovenian] 2.Mešič J. Bronchography in the diagnosis of bronchial carcinoma. Tuberkuloza. 1965;17(1):62 7. [Serbian] 3.Mermolja M. The value of cytodiagnosis in detecting bronchial carcinoma. Zdrav Vestn. 1967;36(11 12): [Slovenian] 4.Mermolja M, Us-Krašovec M, Pavlin A. The importance of atypical bronchial epithelial cells for early cytological diagnosis of lung cancer. Zdrav Vestn. 1974;43(5): [Slovenian] 5.Rott T, Ferluga D, Šorli J, Fink L. Bronchial and transbronchial flexible bronchoscope biopsy in intrathoracic sarcoidosis. 13th international congress of the international academy of pathology, 4th world congress of academic and environmental pathology, Paris 1980, abstract 1980: Zenkovic M, Sorli J. The role of fiberoptic bronchoscopy in differential diagnosis of hemoptysis. Plucne Bolesti Tuberk Jan Mar;33(1): [Croatian] 7.Mermolja M, Sorli J. The importance of cytological examination of the material taken during fiberbronchoscopy in the diagnostics of pulmonary carcinoma. Plucne Bolesti. Tuberk Apr-Sep;33(2 3): [Croatian] 8.Zorman M, Suskovic S, Sorli J. Primary tracheal tumors. Plucne Bolesti Tuberk. 1981;32(4): [Croatian] 9.Meznar B, Sorli J. The application of an ultrasonic nebulizer for local aerosol anesthesia before fiberoptic bronchoscopy. Plucne Bolesti Tuberk. 1981;32(4): [Croatian] 10.Music E, Mermolja M, Debeljak A, Sorli J. Bronchoalveolar lavage in diffuse interstitial lung diseases. Plucne Bolesti. 1984;36(1 2): [Croatian] 11.Debeljak A, Skralovnik-Stern A, Sorli J, Fortuna M, Mermolja M, Rus A. Bronchoalveolar lavage (BAL) in sarcoidosis. Plucne Bolesti. 1985;37(3 4): [Croatian] 12.Fortuna M. Indikacije za bronhoskopiju. Introduction to the fiberbronchoscopy technique, Course packet, 2nd edition, Golnik, 1984; [Slovenian] 13.Remškar J. Mechanical, optical, and technical characteristics of certain fiberbronchoscopies. Introduction to the fiberbronchoscopy technique, Course packet, 2nd edition, Golnik, 1984; [Croatian] 14.Fortuna M. Bronchoalveolar lavage. Introduction to the fiberbronchoscopy technique, Course packet, 2nd edition, Golnik, 1984; [Croatian] 15.Fortuna M. Bronchoscopy in pediatrics. Introduction to the fiberbronchoscopy technique, Course packet, 2nd edition, Golnik, 1984; [Croatian] 16.Fortuna M. The use of fiberbronchoscopy with a critically patient. Introduction to the fiberbronchoscopy technique, Course packet, 2nd edition, Golnik, 1984;92 5. [Croatian] 17.Fortuna M. Bronchography with fiberbronchoscopy. Introduction to the fiberbronchoscopy technique, Course packet, 2nd edition, Golnik, 1984;96 9. [Croatian] 18.Remškar J. Complications of fiberbronchoscopy. Introduction to the fiberbronchoscopy technique, Course packet, 2nd edition, Golnik, 1984; [Croatian] 19.Remškar J. Bronchovideoscopy. Introduction to the fiberbronchoscopy technique, Course packet, 2nd edition, Golnik, 1984; [Croatian] 20.Debeljak A, Skralovnik-Štern A, Šorli J, Fortuna M, Mermolja M, Rus A. Bronchoalveolar lavage (BAL) in sarcoidosis. Plucne Bolesti. 1985;37(3 4): [Croatian] 21.Fortuna M. Aspirin as a bronchodilator. Plucne Bolesti. 1985;37(3 4): [Croatian] 22.Debeljak A, Šorli J, Zupančič M, Remškar J. Bronchoscopic characteristics of sarcoidosis. Plucne Bolesti. 1987; 39(3 4): [Croatian] 23.Debeljak A, Sorli J, Remskar J, Rutar-Zupancic M, Rott T, Mermolja M. Metastasis of extrapulmonary malignancies to the bronchi. Plucne Bolesti Jan Jun;39(1 2):5 10. [Croatian] 24.Sorli J. Guidelines for bronchoscopy with the fiberoptic bronchoscope in adults. Plucne Bolesti Jan Jun; 40(1 2):85 7. [Croatian] 25.Debeljak A, Zupančič M, Remškar J, Šorli J, Zorman M, Rott T, Ferluga D. The role of transbronchial lung biopsy in the diagnosis of diffuse lung disease. Plucne Bolesti. 1988;40(3 4): [Croatian] 26.Remškar Z, Remškar J, Šorli J, Mermolja M, Ferluga D, Rott T. The value of bronchoscopy in the diagnosis of asbestosis. Plucne Bolesti. 1988;40(3 4): [Croatian] 27.Debeljak A, Mermolja M, Šorli J, Zupančič M, Zorman M, Remškar J. Bronchoalveolar lavage in the diagnosis of peripheral primary and secondary malignant lung tumors. Respiration. 1994;61: Debeljak A, Mermolja M, Mušič E, Eržen J, Rott T. Bronchoscopic needle aspiration with flexible and rigid bronchoscope in lung cancer. In: Antypas G, ed. Balkan congress of oncology. Athens. Balkan Union of Oncology, Monduzzi, 1996; Terčelj M, Triller N, Debeljak A, Mermolja M, Kecelj P, Šorli J, Turel M, Zupančič M, Eržen J, Rott T. Bronchoscopic needle aspiration (BNA) improves the sensibility of fexible bronchoscopy (FB) in cancer as well as in benign conditions of mediastinum. In: Antypas G, ed. Balkan congress of oncology; 1996 Jul 3 7; Athens. Bologna: Monduzzi editore, 1996; Triller N, Terčelj M, Debeljak A, Mermolja M, Kecelj P, Šorli J, Turel M, Zupančič M, Eržen J, Rott T. Bronchoscopic needle aspiration in the diagnosis of lung cancer and in benign conditions of mediastinum. Radiol Oncol. 1997;31(4): Tomič V. Transmission of infection at bronchoscopy. Zdravstveno varstvo. [Tiskana izd.], 1997, 36, Šorli J, Eržen D, Triller N, Papler B. Flexible bronchoscopy. Endosk Rev. 1998;3(7): [Slovenian]

12 33.Triller N, Terčelj M, Letonja S. Therapeutic bronchoskopy. Endosk Rev. 1998;3(7): [Slovenian] 34.Kecelj P, Šorli J, Debeljak A, Zupančič M, Terčelj M, Triller N, Turel M, Eržen J, Vidmar S, Hrabar B, Sok M, Jerman J. Bronchoscopic local staging of lung cancer in comparison with surgical extent of lung resection. In: Program and abstracts of the jubilee 10th world congress for bronchology and 10th world congress for bronchoesophagology; 1998 Jun 14 17; Budapest. Budapest: World Association for Bronchology, International Broncoesophagological Society, 1998; Šorli J. Basic guidelines for the bronchioscopy technique. In: Učna delavnica o posebni intubaciji; 1998 Nov 6 7. Maribor: Splošna bolnišnica Maribor, 1998;31 2. [Slovenian] 36.Kecelj P, Debeljak A, Šorli J, Zupančič M, Terčelj M, Triller N, Turel M, Kern I, Mermolja M, Ferluga D, Rott T. Comparison of bronchoscopic findings and broncoalveoral lavage in patients with untreated pulmonary sarcoidosis. In: Program and abstracts of the jubilee 10th world congress for bronchology and 10th world congress for bronchoesophagology; 1998 Jun 14 17; Budapest. Budapest: World Association for Bronchology, International Broncoesophagological Society, 1998; Debeljak A, Šorli J, Mušič E, Kecelj P. Bronchoscopic removal of foreign bodies in adults: experience with 62 patients from Eur Respir J. 1999;14: Kecelj P, Debeljak A, Triller N, Kern I, Osolnik K, Šorli J. Bronchoalveolar lavage in patients with lymphangiocarcinimatosis of the lung. In: Šikić BJ, Šamija M, eds. CEOC Program and abstract book of the 2nd central European oncology congress; 2000 Jun 27 30; Opatija. Zagreb: European society of medical oncology (ESMO), 2000; Triller N, Debeljak A, Kecelj P, Eržen D, Osolnik K, Kern I, Žolnir-Dovč M, Šorli J. Diagnosis of sputum negative pulmonary tuberculosis by flexible fibreoptic bronchoscopy. In: Future challenges for chest physicians in Europe. Final program and abstract book of the 1st Congress of the IUATLD, Europe region in association with the 51st congress of the Hungarian respiratory society; 2000 Apr 12 15; Budapest. Budapest: International union against tuberculosis and lung disease, Europe region, 2000; Kecelj P, Debeljak A, Triller N, Kern I, Osolnik K, Žolnir M, Tomič V, Šorli J. Bronchoscopy, bronchoscopic lung biopsy and bronchoalveolar lavage in patients with organ transplantation. In: Košnik M, ed. Zbornik prispevkov 2. slovenski pnevmološki in alergološki kongres z mednarodno udeležbo; 2000 Nov 16 18; Portorož. Portorož: Bolnišnica Golnik, 2000; Triller N, Debeljak A, Kecelj P, Osolnik K, Eržen D, Šorli J. Topical anaesthesia for flexible bronchoscopy comparison of two different methods and premedication with or without atropine. In: Košnik M, ed. Zbornik prispevkov 2. slovenski pnevmološki in alergološki kongres z mednarodno udeležbo; 2000 Nov 16 18; Portorož. Portorož: Bolnišnica Golnik, 2000; Kecelj P, Debeljak A, Triller N, Kern I, Osolnik K, Žolnir M, Tomič V, Šorli J. Bronchoscopy, bronchoscopic lung biopsy and bronchoalveolar lavage in patients with organ transplantation. In: Košnik M, ed. Zbornik prispevkov 2. slovenski pnevmološki in alergološki kongres z mednarodno udeležbo; 2000 Nov 16 18; Portorož. Portorož: Bolnišnica Golnik, 2000; Triller N, Debeljak A. Treatment of endobronchial tumours with electrocautery. Lung Cancer. 2001;32(Suppl 1):S Triller N, Eržen D, Debeljak A, Kecelj P, Osolnik K, Šorli J. Transcricoid versus bronchoscopic administration of lidocaine for topical anaesthesia with or without atropine: a randomised study. Eur Respir J. 2001;18(Suppl 33):60s. 45.Mešič J, Zupanič S, Triller N, Martinjak T, Debeljak A, Šorli J. Fifty years of bronchoscopy at Golnik. Isis. 2002;11(11):64 6. [Slovenian] 46.Šorli J. Bronchoscopy at Golnik past and present. Endosk Rev. 2002;7(18):1 3. [Slovenian] 47.Kecelj P, Debeljak A, Triller N, Osolnik K, Eržen D, Kern I. Transbronchial aspiration of the peripheral lung infiltrate. Lung Cancer. 2002; 37(Suppl 1):S Osolnik K. Comparison of the difficulties of bronchoscopic lung biopsy (BLB) with surgically open lung biopsy (OLB). Endosk Rev. 2002;7(18): [Slovenian] 49.Osolnik K. The role of bronchoalveolar lavage in the diagnosis of interstitial lung disease. Endosk Rev. 2002;7(18):46 9. [Slovenian] 50.Triller N, Kern I, Eržen J, Sok M. Endobronhial ultrasound guided transbronchial needle aspiration in the diagnosis of bronchial and mediastinal lesions. Endosk Rev. 2002;7: Debeljak A, Triller N, Kecelj P, Kern I. Autofluorescence bronchoscopy in the diagnosis of pre-neoplastic changes in bronchial carcinoma. Zdrav Vestn. 2002;71: [Slovenian] 52.Zupanič S, Martinjak T. The history of bronchoscopy at Golniku. Endosk Rev. 2002;7:69. [Slovenian] 53.Šorli J. Bronchoscopy at Golniku past and present. Endosk Rev. 2002;7(18):1 3. [Slovenian] 54.Triller N, Debeljak A, Kecelj P, Žolnir-Dovč M, Tomič V, Kern I, Drinovec I, Trinkaus-Leiler D, Fležar M, Petrinec-Primožič M, Koren I, Terčelj-Zorman M, Eržen J, Šorli J. Guidelines for bronchoscopy with a flexible bronchoscope. Endosk Rev. 2002;7(16 17):3 21. [Slovenian] 55.Triller N. Bronchoscopy in Slovenia. J Bronchol. 2002;9(3): Duh Š, Triller N. Are patients adequately informed prior to endoscopic procedure? Eur Respir J. Suppl 2002;20(Suppl 38):623s. 57.Žolnir-Dovč M, Triller N, Eržen D, Kecelj P. Transfer of tuberculosis bacilli by bronchoscope. Endosk Rev. 2002;7(18): [Slovenian] 58.Letonja S. Bronchoscopy in the intensive care unit. Endosk Rev. 2002;7(18):22 5. [Slovenian]

13 59.Debeljak A, Triller N, Kecelj P, Letonja S. Palliative bronchoscopic treatment of tumor-induced narrowing of large airways. Zdrav Vestn. 2003;72: [Slovenian] 60.Kopriva S, Šorli J, Borinc-Beden A. Bronchoscopy in the diagnosis of obstructive lung disease in children. In: Maček V, Kopriva S, eds. Astma pri otroku. Ljubljana: Medicinska fakulteta, Katedra za pediatrijo, 2003; [Slovenian] 61.Debevec L, Triller N, Kern I. Tracheobronchopathia osteochondroplastica. Liječ Vjesn, Supl 2003; 125(suppl 2): Rozman A, Žolnir M, Eržen D, Triller N. The role of flexible fiberoptic bronchoscopy in diagnosing pulmonary tuberculosis. Liječ Vjesn, Supl 2003; 125(suppl 2): Triller N. Autofluorescence bronchoscopy and endobronchial ultrasound in the diagnosis and staging of lung cancer. Liječ Vjesn, Supl 2003; 125(Suppl 2): Triller N. Endobronchial ultrasound in the diagnosis of tracheobronchial and mediastinal lesions and in peripheral pulmonary tumours. Liječ Vjesn, Supl 2003; 125(suppl 2): Triller N, Kecelj P, Kern I. Endobronchial ultrasound guided transbronchial needle aspiration in the diagnosis of tracheobronchial and mediastinal lesions and in peripheral pulmonary tumours. Lung Cancer 2003; 41(Suppl 2):S Triller N, Debeljak A, Kecelj P, Eržen D, Kern I, Debevec L. Diagnostic procedures in peripheral pulmonary tumours in 1996 and a retrospective comparative study. Lung Cancer 2003; 41(Suppl 2):S Debeljak A, Triller N, Kecelj P. Palliative treatment of tumour central airways stenosis. Endoskopska revija 2003; 8(19): Kern I, Eržen D, Kecelj P, Košnik M, Mermolja M. Cytology of bronchoalveolar lavage in interstitial lung disease. Zdrav Vestn. 2003;72(4): [Slovenian] 69.Rozman A, Triller N. Postbronchoscopy fever and potential infection. In: Final program and abstract book of the 13th world congress for bronchology (WCB), World congress for bronchoesophagology (WBCE), 8th international meeting in respiratory endoscopy, 10th National Congress of the Spanish Association for Bronchology, 9th international conference on bronchoalveolar lavage; 2004 Jun 20 23; Barcelona. Barcelona, 2004; Osolnik K, Košnik M. Bronchoscopic lung biopsy (BLB) compared with surgical open lung biopsy (OLB) subjective difficulties in patients. Eur Respir J. Suppl 2004;24(Suppl 48):174s. 71.Debeljak A, Tomič V, Letonja S, Kecelj P. Bacteriological examinations of bronchoscopic samples for pneumonia. In: Rezar L, Poles J, eds. Jesenski sestanek Združenja pnevmologov Slovenije in 85 let Bolnišnice Topolšica; 2004 Dec 10 11; Velenje. Topolšica: Bolnišnica Topolšica, 2004; [Slovenian] 72.Osolnik K. Bronchoscopy and taking cell samples. In: Kern I, ed. Respiratorna citopatologija. Zbornik predavanj 2. tečaj respiratorne citopatologije; 2004 Apr 3; Golnik. Golnik: Klinični oddelek za pljučne bolezni in alergijo, 2004; [Slovenian] 73.Osolnik K, Mušič E. BAL as a diagnostic tool in sarcoidosis and hypersensitivity pneumonitis. Pneumologie. 2004;58(Suppl 1):S2. 74.Osolnik K, Eržen D, Kern I. Comparison of quality and diagnostic accuracy of bronchoscopic lung biopsies made by forceps of two different dimensions in diffuse interstitial lung diseases. In: Zidarn M, Košnik M, Zdolšek S, eds. Book of abstracts of the 3rd Slovenian congress of pneumology and allergology and the 1st Slovenian congress of respiratory nursing; 2004 Oct 20 22; Portorož. Golnik: Bolnišnica KOPA, 2004; Košnik M, Primožič-Petrinec M, Duh S, Triller N. Topical nasal anaesthesia in patients undergoing transnasal bronchoscopy. In: Final program and abstract book of the 13th world congress for bronchology (WCB), World congress for bronchoesophagology (WBCE), 8th international meeting in respiratory endoscopy, 10th national congress of the Spanish association for bronchology, 9th international conference on bronchoalveolar lavage; 2004 Jun 20 23; Barcelona. Barcelona: 2004; Triller N. Bronchoscopic lung volume reduction in patients with severe emphysema. In: Zbornik predavanj 4. golniški simpozij; 2005 okt 10-15; Golnik, Brdo pri Kranju. Golnik: Bolnišnica Golnik, Klinični oddelek za pljučne bolezni in alergijo, 2005; Triller N, Erzen D, Duh S, Petrinec Primozic M, Kosnik M. Music during bronchoscopic examination: the physiological effects. A randomized trial. Respiration. 2006;73(1): Petrinec-Primožič M, Duh S, Pesak S, Hribar I, Triller N. Prebronchoscopic video presentation of the procedure and patients anxiety level. In: Arribalzaga E, ed. Abstracts book of the 14th world congress for bronchology (WCB) and 14th world congress for bronchoesophagology (WCBE); 2006 Jun 25 28; Buenos Aires. Buenos Aires: World Association for Bronchology, 2006; Debeljak A. Implantation of tracheobronchial stents. In: Triller N, Debeljak A, Rozman A, eds. ERS bronchoscopy course: bronchoscopy school textbook, Bled, October 5 7, Golnik: University Clinic of Respiratory and Allergic Diseases Golnik; Debeljak A. Autofluorescence bronchoscopy in diagnosing synchronous bronchial carcinoma. In: Rott T, Luzar B (urednika). Pljučni rak. Ljubljana: Inštitut za patologijo Medicinske fakultete v Univerze v Ljubljani, 2007; [Slovenian] 81.Osolnik K. Bronchoscopy in pulmonary infections. In: Triller N, Debeljak A, Rozman A, eds. Textbook of the bronchoscopy course; 2007 Oct 5 7; Golnik, Bled. Golnik: European respiratory society, 2007; Osolnik K. Bronchoalveolar lavage (BAL). In: Triller N, Debeljak A, Rozman A, eds. Textbook of the bronchoscopy course; 2007 Oct 5 7; Golnik, Bled. Golnik: European respiratory society, 2007; Osolnik K. Tehnična izvedba BAL. In: Kern I, ed. Proceedings of the bronchoalveolar lavage cytology course;

14 2007 Oct 1; Golnik. Golnik: Bolnišnica Golnik, Klinični oddelek za pljučne bolezni in alergijo, 2007;5 7. [Slovenian] 84.Triller N, Debeljak A, Rozman A. Textbook of the bronchoscopy course; 2007 Oct 5 7; Golnik, Bled. Golnik: European respiratory society, 2007; Tomič V. Infection control in the bronchoscopy unit. In: Triller N, Debeljak A, Rozman A, eds. Textbook of the bronchoscopy course; 2007 Oct 5 7; Golnik, Bled. Golnik: European respiratory society, Šorli J. We were part of the revolution, but we did not realize this: A look at a participant s role in the history of bronchology in Slovenia). In: Kadivec S, ed. Golniški simpozij Zbornik predavanj Zdravstvena obravnava bolnika z obstruktivno boleznijo pljuč in alergijo: program za medicinske sestre in zdravstvene tehnike; 2007 Oct 3 4; Golnik, Bled. Golnik: Bolnišnica Golnik, Klinični oddelek za pljučne bolezni in alergijo, 2007; [Slovenian] 87.Triller N. Endobronchial electrocautery and argon plasma coagulation. In: Triller N, Debeljak A, Rozman A, eds. ERS bronchoscopy course: bronchoscopy school textbook, Bled, October 5 7, Golnik: University Clinic of Respiratory and Allergic Diseases Golnik; Triller N, Rozman A, Kern I. Endobronchial ultrasound in the diagnosis of mediastinal and peripheral lung lesions. In: Rott T, Luzar B, eds. Pljučni rak. Ljubljana: Inštitut za patologijo Medicinske fakultete v Univerze v Ljubljani, 2007; [Slovenian] 89.Triller N. Cryotherapy for endobronchial lesions. In: Triller N, Debeljak A, Rozman A, eds. ERS bronchoscopy course: bronchoscopy school textbook, Bled, October 5 7, Golnik: University Clinic of Respiratory and Allergic Diseases Golnik; Rozman A. Anaesthesia in flexible bronchoscopy. In: Triller N, Debeljak A, Rozman A, eds. Textbook of the bronchoscopy course; 2007 Oct 5 7; Golnik, Bled. Golnik: European respiratory society, 2007; Rozman A. Preparation for bronchoscopy. In: Triller N, Debeljak A, Rozman A, eds. Textbook of the bronchoscopy course; 2007 Oct 5 7; Golnik, Bled. Golnik: European respiratory society, 2007; Duh Š, Rozman A. The bronchoscopy equipment. In: Triller N, Debeljak A, Rozman A, eds. Textbook of the bronchoscopy course; 2007 Oct 5 7; Golnik, Bled. Golnik: European respiratory society, 2007; Eržen D. Documentation of bronchoscopic findings. In: Triller N, Debeljak A, Rozman A, eds. Textbook of the bronchoscopy course; 2007 Oct 5 7; Golnik, Bled. Golnik: European respiratory society, 2007; Kern I. Sampling, processing and transportation of bronchoscopic specimens. In: Triller N, Debeljak A, Rozman A, editors. Textbook of the Bronchoscopy course; 2007 Oct 5-7; Golnik, Bled. Golnik: European respiratory society, 2007; Debeljak A. History of interventional bronchology and pneumology at the University Clinic of Respiratory and Allergic Diseases Golnik. In: Rozman A, Triller N, eds. Bronchoscopy course: bronchoscopy school textbook. Golnik: University Clinic of Respiratory and Allergic Diseases Golnik, 2008; Regvat J, Kern I, Triller N, Škrgat-Kristan S, Cesar R, Košnik M. Utility of computed tomography and fiberbronchoscopy in patients with unexplained fixed airway obstruction. In: Kern I, ed. Book of abstracts of the 4th Slovenian pneumology and allergology congress; 2008 Sep 14 16; Portorož. Golnik: University Clinic of Respiratory and Allergic Diseases, 2008; Triller N, Rozman A. Endobronchial ultrasound in the diagnosis of peripheral pulmonary lesions. Endosk Rev. 2008;13(29): Triller N, Debeljak A, Rozman A, Debevec L. Interventional bronchoscopy in patients with central airway obstruction because of unresectable lung cancer. Endosk Rev. 2008;13(29): Kern I. Bronchoalveolar lavage in asbestosis. In: Final program of the 9th WASOG meeting and 11th BAL international conference; 2008 Jun 19-22; Athens. Athens: European respiratory society, 2008; Triller N, Rozman A, Žolnir-Dovč M. Diagnostic yield of bronchoscopy in smear negative pulmonary tuberculosis. In: Bridging east and west: the challenges of respiratory disease in Europe. Final program, abstract book of the 5th congress of the international union against tuberculosis and lung disease; 2009 May 27 30; Dubrovnik. Dubrovnik: International union against tuberculosis and lung disease, 2009; Rozman A, Duh S, Petrinec-Primozic M, Triller N. Flexible bronchoscope damage and repair costs in a bronchoscopy teaching unit. Respiration. 2009;77(3): Rozman A. EBUS in the diagnosing the mediastinum. In: Triller N, ed. Proceedings of the meeting for ultrasound in clinical practice; 2010 May 29; Ljubljana. Ljubljana: Združenje pnevmologov Slovenije, 2010;1 7. [Slovenian] 103.Kern I, Gabrič S, Požek I, Triller N. Telecytology for rapid assessment of cytological specimens. In: Laurinavicius A, editor. From Analogue to Digital - Enabling Precision in Pathology. Program and Abstract Book of the 10th European Congress on Telepathology and 4th International Congress on Virtual Microscopy; 2010 Jul 1'3; Vilnius, Lithuania. Vilnius: Modus agendi, 2010; Rozman A, Marc-Malovrh M, Osolnik K, Camlek L, Triller N. Endobronchial ultrasound in the diagnosis and treatment of mediastinal changes. Zdrav Vestn. 2011; 80(2): [Slovenian] 105.Triller N, Dimitrijevic J, Rozman A. A comparative study on endobronchial ultrasound-guided and fluoroscopic-guided transbronchial lung biopsy of peripheral pulmonary lesions. Respiratory Medicine 2011; 105 S1, S74-S77.

15 101 years of the Jacobaeus procedure: Our story Andrej Debeljak University Clinic of Pulmonary Diseases and Allergy, Golnik Abstract This article presents historical information about diagnostic thoracoscopy at Golnik Hospital. The following were determined: when the procedure was introduced into the diagnostic armamentarium, the medical staff that carried out the examinations, indications and contraindications for the procedure, the instruments that were used, the anesthesia methods, insufflation of pneumothorax, the introduction of the instrument, and biopsies. The results of thoracoscopy and the role of the therapeutic procedure (pleurodesis) are also shown. The titles of published lectures and articles on thoracoscopy in the last 20 years have been appended. Introduction In 1882 the Italian physician Carlo Forlanini introduced artificial pneumothorax, which became the most frequently applied method among the collapse therapies for pulmonary tuberculosis (1). The application of pneumothorax also enabled thoracoscopic endoscopy. Insufflation of air into the pleural cavity made its exploration possible, making the virtual cavity real. The Swedish internist Hans Christian Jacobaeus is credited as the first to perform an endoscopic exploration of the thorax. In 1910 he described endoscopic exploration of the pleural cavity with a cystoscope, which he referred to as thoracoscopy, in two patients with tuberculous pleurisy (2). However, even before him in 1866 Samuel Gordon published a report on a thoracoscopy performed by Francis Richard Cruse from Ireland with a binocular endoscope in an 11-year-old girl with left-sided pleural empyema and thoracostoma (3). Initially pneumothorax as a collapse therapy method was used to treat tuberculous caverns of the lungs. In patients with extensive pleural adhesions, the lungs could not be collapsed by pneumothorax. Thoracocautery (also known as Jacobaeus operation ) was performed in these patients, and electrocautery was applied to the pleural adhesions through the thoracoscope to enable the lung to collapse. The Golnik story Thoracocautery was performed at Golnik for the first time in 1931 by Robert Neubauer. Through the thoracoscope, electrocautery was used to burn the pleural adhesions caused by tuberculosis (4). Diagnostic thoracoscopy (i.e., endoscopic exploration of the pleural cavity with a thoracoscope to diagnose pleural disease) was the first invasive endoscopic examination used at Golnik Hospital. This procedure was developed because a thoracoscope had been used in previous years at Golnik Hospital to perform collapse therapy in patients with lung tuberculosis and pleural adhesions. After that time, antituberculosis drugs made collapse therapy unnecessary. The number of consumptive patients declined. Golnik Hospital gradually became a hospital for nonspecific respiratory diseases. In many centers in the world, thoracoscopy became a forgotten art. During that time, thoracic surgeons began to use the thoracoscope with increasing frequency for video-assisted thoracic surgery (VATS). They used general anesthesia and usually three ports: one for a video camera and two for operating instruments designed especially for thoracoscopic operations (5).

16 At Golnik, diagnostic thoracoscopy remained in the diagnostic armamentarium through the 1950s, 1960s, and 1970s. It was used in patients in whom malignant infiltration of the pleura was suspected. Our predecessors at Golnik, Leon Fink and Judita Mešič, performed diagnostic thoracoscopy. In 1985, Andrej Debeljak learned the procedure from his teacher Leon Fink. The instrument was a rigid Storz thoracoscope with Hopkins optics. The procedure was carried out under general anesthesia in an operating room. The day before the thoracoscopy, pneumothorax was insufflated with an Erka pneumothorax apparatus and confirmed with a chest X-ray. Before the introduction of the thoracoscope, the depth of pneumothorax was controlled by needle aspiration. The procedure was performed in the operating theatre. A specially designed operating table that could rotate the patient was used. A forceps biopsy with monopolar electrocautery was possible. The procedures were rarely performed, only three to five time a year. The most frequent diagnosis was mesothelioma or secondary malignant infiltration of the pleura. In 1993, Andrej Debeljak visited the Clinic for Respiratory Diseases Hecheshorn in Berlin, where Hand-Jürgen Brandt and later Robert Loddenkemper were using thoracoscopy in the diagnostic workup of patients with pleural diseases. He wanted to assess the possibilities and usefulness of diagnostic thoracoscopy and its place in managing lung diseases, especially in relation to surgical thoracoscopy. Debeljak taught younger doctors how to perform thoracoscopy: Peter Kecelj, Matjaž Turel, Aleš Rozman, and Nadja Triller. Saša Letonja also carried out examinations. The number of thoracoscopies rose to 30 per year. In recent years Aleš Rozman has taught Mateja Marc and Luka Camlek how to perform thoracoscopies. The medical technicians that assisted in the procedures were the same as those that assisted in other endoscopic procedures: Marija Petrinec Primožič, Štefan Duh, Martina Košnik, Slavica Mohorič, Katica Zlatar, and Breda Papler. Thoracoscopies were performed on the operating table in the Endoscopy Department in the bronchoscopy room. Generally, in addition to the operating physician, there was also an assistant physician. The indication for thoracoscopy was pleural exudate, suspicious malignant infiltration of the pleura, and previous failure of non-invasive diagnostic methods. An important indication was pleural exudate in patients with non small-cell lung cancer that were considered otherwise resectable. An absolute contraindication was obliteration of the pleural space, and relative contraindications were bleeding disorders, hypoxemia, unstable cardiovascular status, and persistent uncontrollable cough. Prior to thoracoscopy, systemic diseases, accompanied by pleural effusion, were excluded. Biochemical, bacteriological, and cytological examinations of the pleural effusion were carried out. If tuberculosis had been suspected, blind-needle biopsy of the pleura was performed. Today blind-needle biopsy of the parietal pleura is less important because of the lower incidence of consumptive patients in Slovenia (10/100,00). In the first 5 years, general anesthesia was used. Marija Wolf from the Kranj maternity hospital administered the anesthesia. From 1990 onwards, we applied local anesthesia. We used local anesthesia with 30 ml of 1% lidocaine and analgesia with fentanyl 0.1 mg iv. As a premedication, 1 mg of atropine sulphas sc. was used E and 26172EB Storz rigid thoracoscopes (Tuttlingen, Germany) were used, followed by an Olympus A5252A videothoracoscope after 1999 and an Olympus videothoracoscope visera (Tokyo, Japan) after In recent years, from 2008

17 onwards, Aleš Rozman studied the usefulness of the semiflexible LFT 160 Olympus thoracoscope and carried out the majority of examinations using this instrument. The day before thoracoscopy, we insufflated 1,200 ml (0 2,400 ml) of air using an Erka pneumothorax apparatus. Pneumothorax was confirmed by chest X-ray and before introducing thoracoscope by needle aspiration until We used Veress needles. Later, pneumothorax was insufflated on the operating table using an Erka pneumothorax apparatus immediately before thoracoscopy and confirmed with a chest X-ray, and from 1996 onwards by fluoroscopy with a Phillips BV 29 with a C arm. After 2008, pneumothorax was introduced by a B7050 CO 2 insufflator and 120 mm Surgineedle. The typical point of entry was the sixth intercostal space in the mid-axillary line. If the disease was in the apical regions of the lung or pleura, the upper intercostal spaces were selected. We predominantly used the trocar technique to introduce the thoracoscope. When the pneumothorax was small, we used a blunt preparation to the pleura and entered the pleural cavity with the finger first. After aspiration of ca. 1,350 ml pleural effusion (range 0 5,000 ml), forceps biopsies of pleural and lung tissue were performed (11.5 samples on average, range 2 5), in addition to electrocautery, lysis of fibrinous adhesions, and talc insufflation for pleurodesis. In patients with large, usually malignant pleural effusions, or rarely recurrent pneumothorax and small emphysematous blebs, 3 to 5 g of talc were insufflated into the pleural cavity under direct optical control with a TH Storz insufflator. Samples of pleura and pleural exudates were examined cytologically and histologically in the Pathology Department (Izidor Kern) and bacteriologically in the Bacteriology Department (Viktorija Tomič) and Mycobacteriology Department (Manca Žolnir Dovč). A chi-square test was used to compare the sensitivity of thoracoscopy, needle pleural biopsy, and cytological examination in patients with malignant infiltration of the pleura. In the group of patients with malignant diseases, we determined accuracy, sensitivity, and positive and negative predictive value. Sensitivity was 94%. The procedure was most useful for diagnosing mesothelioma, secondary malignant infiltration of the pleura, pleural asbestosis and lymphoma, localized pleural tumors, and rarely peripheral lung tumors (6, 7, 8). In patients with non small-cell lung cancer and pleural effusion, medical thoracoscopy can exclude pleural carcinosis but it cannot be used for confirmation of tumor infiltration or sampling the mediastinal lymph nodes. Among 30 patients with non small-cell bronchial carcinoma with pleural effusion without malignant cells, thoracoscopy confirmed malignant infiltration in 10 patients (33%). Talc pleurodesis was performed in two of them. In 20 patients (67%), non-specific inflammation was found. Four were not surgically treated because of local progression of the tumor or cardiorespiratory dysfunction. Successful resection was performed in 11 patients (37%). In two patients the N2 stage was found, and in two patients the T3 stage was found (9). Pleurodesis with talc insufflation (3 to 5 grams of Luzenac talc) under visual control was equally successful as talc slurry instillation in 71 patients with malignant pleural effusion, success rate 81% and 93% (10). It was considered a success if pleural effusion did not reaccumulate in the first month after pleurodesis and the patient was not dyspneic. The most frequent complications were subcutaneous emphysema and pain after talc insufflation, and the most serious complications were bronchopleural fistula and trapped lung. We did not observe other serious systemic complications or mortality.

18 Acute respiratory distress syndrome after talc pleurodesis killed 2.3% of patients in a cancer and leukemia group B study (11). This acute lung injury can be avoided by using large talc particle preparations (such as Lusenac talc). Such products are not readily available in many countries, including the United States. Instead of talc pleurodesis, a small indwelling tunneled pleural catheter that improves dyspnea and quality of life, with minimal intervention, minimal, hospitalization and minimal complications, is gaining increasing popularity (12). In recent years at Golnik a small indwelling catheter has also been used for symptomatic therapy of malignant pleural effusions. References: 1.Zupanič Slavec Z. Arteficial pneumothorax. In Zupanič Slavec Z. Tuberculosis ( ). Slovenia s Golnik sanatorium and TB in Central Europe. Peter Lang, Frankfurt am Main, 2011: Jacobaeus HC. Über die Möglichkeit die Zystoskopie bei Untersuchung seröser Höhlungen anzuwenden. Münchner Medizinishe Wochenschrift 1910;57: Gordon S. Clinical reports of rare cases occurring in the Whitworth and Hardwicke Hospitals: most extensive pleuritic effusion rapidly becoming purulent, paracentesis, introduction of a drainage tube, recovery, examination of interior of pleura by endoscope. Dublin Quarterly Journal of Medical Science 1866;41: Zupanič Slavec Z. The Golnik surgical experience. In Zupanič Slavec Z. Tuberculosis ( ). Slovenia s Golnik sanatorium and TB in Central Europe. Peter Lang, Frankfurt am Main, 2011: Loddenkemper R. Thoracoscopy: state of the art. Eur Respir J 1998;11: Debeljak A, Kecelj P, Kern I, Vidmar S, Rott T. Medical thoracoscopy: experience with 212 patients. J BUON 2000;5; Rozman A, Debeljak A, Kern I. Thoracoscopy, study of 129 procedures. Abstract book, 4th Congress of the Macedonian Respiratory Society with international participation, Ohrid September 27 30,2008;P046:34. 8.Debeljak A, Kecelj P, Kern I, Sok M. Pet let videotorakoskopije na Golniku. Izvlečki 8. kongresa endoskopske kirurgije Slovenije, Portorož, maja 2005, Endoscopic Rev 2005;10:25. 9.Debeljak A, Kecelj P, Eržen J, Kern I. The role of diagnostic thoracoscopy in patients with lung cancer and pleural effusion. Eur Resp J 2003;22, Suppl. 45:542S. 10. Debeljak A, Kecelj P, Triller N, Letonja S, Kern I, Debevec L, Rozman A. Talc pleurodesis: comparison of talc slurry instillation with thoracoscopic talc insufflation for malignant pleural effusions. J BUON 2006;11: Dresler CM, Olak J, Herndon JE 2nd, et al. Phase III intergroup study of talc poudrage vs. talc slurry sclerosis for malignant pleural effusion. Chest 2005;127: Gary Lee YC, Edward Fysh TH. Indwelling pleural catheter. Changing the paradigm of malignant effusion management. Editorial J Thorac Oncol 2011;6: Lectures and articles on thoracoscopy at Golnik Hospital Debeljak A, Remškar Z, Ferluga D, Rott T, Mermolja M. Diffuse malignant pleural mesothelioma. Diagnostic problems. 8th Congress of pneumology Alpe-Adria-Pannonia. Lung and Environment. Trieste 1991: Debeljak A, Remškar Z, Ferluga D, Rott T, Mermolja M. Difuzni maligni plevralni mezoteliom. Diagnostični problemi. Zdrav Vestn 1993;62: Debeljak A, Drinovec I, Eržen J, Rott T, Mermolja M. Diagnostična torakoskopija. Zdrav Vestn 1996;65, Suppl 2: Debeljak A, Turel M, Drinovec I, Eržen J, Rott T, Kern I. Diagnostic thoracoscopy, experience with 165 patients. 2nd Congress of the Macedonian respiratory society. Macedonian respiratory society, Ohrid 1997: Debeljak A, Kecelj P, Kern I, Eržen J, Rott T. Diagnostična torakoskopija pri 201 bolniku od 1985 do Endosk Rev 1998;3: Turel M, Debeljak A, Kecelj P. Torakoskopska plevrodeza s smukcem pri malignem plevralnem izlivu. Endosk Rev 1998;3: Debeljak A, Turel M, Eržen J, Kecelj P, Rott T, Kern I. Medical thoracoscopy, experience with 189 patients. 10th World Congress for Bronchology and Bronchooesophagology, Budapest 1998:O Debeljak A, Kecelj P, Eržen J, Rott T, Kern I. Internistična torakoskopija. In Poles J ed. Sodobna diagnostika in zdravljenje bolezni organov prsnega koša. Bolnišnica Topolšica, Topolšica 1999:14. 9.Debeljak A, Kecelj P, Eržen J, Rott T, Kern I. Medical thoracoscopy, experience with 212 patients. ERS annual congress Madrid. Eur Respir J 1999;14, Suppl 14:154S 10.Turel M, Debeljak A, Kecelj P. Thoracoscopic pleurodesis for malignant pleural effusion. ERS annual congress Madrid. Eur Respir J 1999;14, Suppl 30:303S.

19 11.Debevec M, Kovač V, Debeljak A, Eržen J, Kern I. Malignant pleural mesothelioma (MPM). Analysis of patients in Slovenia nd Slovenian Slovenian Congress of Pneumology and Allergology. Klinika za pljučne bolezni in alergijo Golnik, Združenje pnevmologov Slovenije, Alergološko imunološka sekcija SZD, Portorož 2000: Debeljak A, Kecelj P, Eržen J, Kern I. Medical thoracoscopy in the assessment of operability of the lung cancer accompanied by pleural effusion. 2nd Slovenian Congress of Pneumology and Allergology. Klinika za pljučne bolezni in alergijo Golnik, Združenje pnevmologov Slovenije, Alergološko imunološka sekcija SZD, Portorož 2000: Kecelj P, Debeljak A, Triller N, Kern I, Vidmar S, Šorli J. Benign solitary tumours of the pleura. 2nd Slovenian Congress of Pneumology and Allergology. Klinika za pljučne bolezni in alergijo Golnik, Združenje pnevmologov Slovenije, Alergološko imunološka sekcija SZD, Portorož 2000: Debeljak A, Kecelj P, Kern I, Vidmar S, Rott T. Medical thoracoscopy: experience with 212 patients. J BUON 2000;5: Debevec M, Kovač V, Debeljak A, Eržen J, Remškar Z, Kern I. Maligni plevralni mezoteliom. Zdrav Vestn 2000;69: Debeljak A, Kecelj P, Kern I. Naše izkušnje z internistično videotorakoskopijo. Endoscopic Rev 2001;6(14): Debeljak A, Kecelj P, Kern I. Medical thoracoscopy in diffuse malignant pleural mesothelioma. Lung Cancer 2001:32, Suppl 1:S Kovač V, Debevec M, Plaper-Vernik M, Debeljak A, Eržen J, Remškar Z, Kern I. Malignant pleural mesothelioma (MPM) in Slovenia Lung Cancer 2001;32, Suppl 1:S Debeljak A, Kecelj P, Kern I, Eržen J. Pomen diagnostične torakoskopije za predoperativno oceno plevralnega izliva pri bolniku s pljučnim rakom. III. kongres Združenja kirurgov Slovenije in Strokovni seminar Sekcije operacijskih medicinskih sester Slovenije. Portorož, 22. do 25. maj 2002, Zbornik predavanj, Portorož 2002: Debeljak A. Diagnostična torakoskopija. Endoscopic Rev, 2002;7: Debeljak A, Kecelj P,Eržen J,Kern I. The role of diagnostic thoracoscopy in patients with lung cancer and pleural effusion. Eur Resp J 2003; 22, Suppl 45:542S. 22.Debeljak A, Kecelj P, Kern I et al. Diagnoza malignega plevralnega mezotelioma. Analiza 70 bolnikov od Simpozij Bolezni plevre Združenje pnevmologov Slovenije, Zbornik predavanj, Nova Gorica 2. in 3. aprila 2004: Kecelj P, Debeljak A, Triller N, Kern I, Vidmar S, Šorli J. Benign solitary pleural lesions diagnosed by medical thoracoscopy. 13 World Congress for Bronchology (WCB), Final programme & abstract book, Barcelona, Spain June 20 23, 2004;P094: Debeljak A, Kecelj P, Kern I, Vidmar S, Kovač V. Diagnosis of pleural mesothelioma. Eur Resp J 2004; 24, Suppl 48:527 ff. 25.Debeljak A, Kecelj P, Kern I, Vidmar S, Kovač V. Diagnosis of malignant pleural mesothelioma. 3rd Slovenian Congress of Pneumology and Allergology, Portorož, October 20th 22nd 2004, Zbornik predavanj, Portorož 2004: Kecelj P, Debeljak A, Kern I, Vidmar S. Benigne solitarne spremembe na plevri opredeljene s torakoskopijo. Splošna bolnišnica Maribor in Medicinska fakulteta Univerze v Mariboru. Strokovni simpozij z mednarodno udeležbo ob 50-letnici oddelka za torakalno kirurgijo. Zbornik predavanj. Maribor 2004: Debeljak A, Kecelj P, Kern I, Eržen J, Kovač V, Debevec L. Diagnostična torakoskopija pri malignem plevralnem mezoteliomu. Splošna bolnišnica Maribor in Medicinska fakulteta Univerze v Mariboru. Strokovni simpozij z mednarodno udeležbo ob 50-letnici oddelka za torakalno kirurgijo. Zbornik predavanj. Maribor 2004: Kovač V, Zwitter M, Smrdel U, Debeljak A, Cesar R, Debevec L, Kern I. Izkušnje sodobnega zdravljenja malignih plevralnih mezoteliomov v Sloveniji. Jesenski sestanek Združenja pnevmologov Slovenije in 85 let bolnišnice Topolšica. Bolnišnica Topolšica. Velenje, december, Zbornik predavanj. Velenje 2004: Debeljak A, Kecelj P, Kern I, Sok M. Pet let videotorakoskopije na Golniku. Izvlečki 8. kongresa endoskopske kirurgije Slovenije, Portorož, maja 2005, Endoscopic Rev 2005;10: Debeljak A. Mezoteliom in azbestna bolezen. Diagnostika. Histološka preiskava je imperativ. Skrb zase. Priloga Vive, revije za zdravo življenje. Ljubljana 2006: Debeljak A, Letonja S, Triller N,Kecelj P. Talc pleurodesis. Lung cancer 2006;52, Suppl 2:O.6, S Debeljak A, Kecelj P, Triller N, Letonja S, Kern I, Debevec L, Rozman A. Talc pleurodesis: comparison of talc slurry instillation with thoracoscopic talc insufflation for malignant pleural effusions. J BUON 2006;11: Debeljak A, Kecelj P, Sok M, Kern I. Diagnostic thoracoscopy in patients with lung cancer and pleural effusion Eur Resp J 2007;30, Suppl 51:102S. 34.Rozman A, Debeljak A, Kern I. Thoracoscopy, study of 129 procedures. Abstract book, 4th Congress of Macedonian Respiratory Society with international participation, Ohrid September 27 30, 2008;P046: Rozman A, Debeljak A, Triller N, Kern I. Evaluation of rigid thoracoscopy in the diagnosis of suspected pleural tumours: accuracy, safety and outcome. Endoscopic Rev 2008;29:63.

20 EBUS mini probe - a maxi tool Aleš Rozman 11 th Bronchoscopy School Golnik October 2011 Peripheral pulmonary lesion (PPL) focal radiographic opacity, that may be characterised as nodule (<= 3cm) or mass (> 3cm) not visible by bronchoscopy (no findings of endobronchial lesion / extrinsic compression / submucosal infiltration / orifice narrowing) PPL prevalence of malignancy: 0,8 2 cm: 18% / > 2cm: 50% (Leef JL - Radiol Clin North Am 2002, Midthun DE Lung Cancer 2003) 18 34% of lobectomies (without previous histological confirmation) in patients with benign lesions (Wilson DO Am J Respir Crit Care Med 2008, Swensen SJ Radiology 2005, Pastorino U Lancet 2003) Accurate tissue diagnosis of PPL is strongly favoured before surgery.

21 Equipment for EBUS miniprobe guided TBB A miniature ultrasound probe (20 MHz, mechanical-radial Type UM S20-20R (Olympus Optical; Tokyo, Japan) Endoscopic US system Olympus EU-M30 US-probe Catheter PPL diagnostic methods: 1. Bronchoscopic sampling no guidance (sens. < 20%) fluoroscopic guidance (sens % mlg. / 35-56% ben.) CT guidance + virtual bronchoscopy (65,4%) EM guidance (sens. 59%) EM + EBUS guidance (sens. 88%) EBUS guidance (sens % mlg. / 73% overall sens.) 2. Percutaneous image guided aspiration / biopsy CT guidance (sens. 90%) Sensitivity of EBUS guided TBB Steinfort DP, et al. Eur Respir J 2011

22 Steinfort DP, et al. Eur Respir J 2011 Sensitivity of EBUS guided TBB Sensitivity of EBUS guided TBB Chest 2009;136: Sensitivity of EBUS guided TBB Factors affecting the diagnostic yield: size of the lesion position of the mini-probe in relation to the lesion malignant / benign lesion bronchus sign operator additional guiding (fluoroscopy, EMN, guiding sheath) biopsy method (forceps, TBNA, brush, catheter aspirate, washing,...) number of biopsy samples (at least 5)

23 Position of the probe and sensitivity Outside the lesion (sens. = 4%) Adjacent to the lesion (sens. = 61%) Within the lesion (sens. = 83%) Yamada N et al. CHEST 2007; 132: Benign vs. malignant lesion Continuous hyperechoic margin: malignant disease Internal echoes: homogeneous internal echo: benign lesions (rarely adenocarcinoma) heterogeneous internal echo: malignant lesions Hyperechoic dots: benign or malignant lesions Concentric circles: benign lesions Chao et al. Chest 2006;130:

24 Benign vs. malignant lesion Type I:Homogeneous Pattern Type Ia: with patent vesels and patent bronchioles pneumonia Type Ib: without vesels and bronchioles: organising pneumonia, tuberculoma Type II: Hyperechoic dots and linear arcs pattern Type IIa: without vesels: well differentiated adenocarcinoma Type IIb_ with patent vesels: well differentiated adenocarcinoma, lymphoma Type III: Heterogeneous pattern IIIa:with hyperechoic dots and short lines : moderately differentiated adenocarcinoma, or squamous cell carcinoma (multiple cysts!) IIIb: without hyperechoic dots and short lines:poorly differentiated adenocarcinoma Kurimoto et al. Chest 2002;122: EBUS guided transbronchial lung biopsy in peripheral pulmonary lesions Analysis 2011 Golnik University Clinic Characteristics of the patients Female/Male 43/93 Age, yrs Median 67 (17-88) No. of peripheral lesions 147 Peripheral lesions 3 cm 60 Peripheral lesions >3 cm 87 Peripheral pulmonary lesions 579 patients / 136 pt s with periph. lesion (23,5%) Mean (±SD) diameter 42 ± 21 mm (range 8-120mm)

25 Malignant lesions Lesions Diagnostic method EBUS TBB Fluroscopy TBB CT guided TTNA Adenocarcinoma Squamous cell ca Large cell ca Small cell ca 6 6 Non small cell ca 1 1 Lymphoma 2 2 Carcinoid 1 1 Metastatic lung tu Other Metastasis NA Σ (80%) 3 (2,6%) 13 (11,3%) 7 (6,1%) Benign lesions Orgnizing pneumonia Lesions Diagnosis method EBUS TBB CT guided TTNA Surgery Other Tuberculosis cultures Abscess clin. response Fibrosis follow up Hamartoma Sarcoidosis Pneumonia 2 2 Other* undiagnosed Σ (59,4%) 2 (6,3%) 6 (18,8%) 5 (15,6%) *actinomicosis, aspegillosis, lung infarction, RA, undiagnosed False negative (24,5%) diagnostic procedures CT guided TTNA 15 Metastasis NA 7 Surgery 6 Fluoroscopy TBLB 3 Other 5 Complications: 5 moderate bleedings after TBLB 1 PTHX

26 Diagnostic yield of EBUS guided TBB by location of the lesion 48/35 RS1-64% RS2-72% LS1,2-89% LS3-67% 24/20 13/8 RS3-81% RS4-67% RS5-50% LS4-100% LS5-50% 7/5 31/21 RS6-90% RS7-0 RS8-50% RS9-67% RS10-56% LS6-86% LS8-100% LS9-100% LS10-89% 24/22 Diagnostic yield and the lesion size : 3 cm: > 3 cm 60%:86% Position of the probe and diagnostic yield Outside the lesion (fluoroscopic guidance) (DG yield = 43,2%) Adjacent to the lesion (DB yield= 77,8%) Within the lesion, not at the end of the bronchus (DG yield = 80,0%) Within the lesion (DG yield = 92,2%) Overall DG yield = 75,5% Sensitivity of EBUS guided TBB Steinfort DP, et al. Eur Respir J 2011

27 Conclusions EBUS is well tolerated and safe procedure diagnostic yield is high combination of guidance techniques improves DG yield take cytology specimen too radiation exposure for patients and medical personel is reduced University Clinic Golnik, Slovenia Thank you.

28 Rigid versus semiflexible thoracoscopy in diagnosing pleural diseases. Aleš Rozman 11 th Bronchoscopy School Golnik October 2011 University Clinic Golnik, Slovenia Rozman A Marc Malovrh M Camlek L Triller N Kern I Rigid versus semiflexible thoracoscopy in diagnosing pleural diseases. Thoracoscopy with semirigid instrument recent, successfully employed technique in DG of pleural diseases concerns about diagnostic adequacy of biopsy specimens obtained inferiority to rigid bronchoscopy? Rigid versus semiflexible thoracoscopy in diagnosing pleural diseases.

29 Rigid versus semiflexible thoracoscopy in diagnosing pleural diseases. The purpose of the study... was to compare rigid and semiflexible instrument prospectively in randomized fashion to determine: 1. size of the samples 2. quality of the samples 3. diagnostic adequacy 4. complications / safety in patients, who underwent thoracoscopy between 2008 and Rigid versus semiflexible thoracoscopy in diagnosing pleural diseases. M e t h o d s : 1. rigid thoracoscope Olympus A5252A vs. semiflexible Olympus LTF rigid 5mm forceps vs. flexible FB-55CD-1 Olympus forceps 3. local anaesthesia (lidocain) + i.v. Fentanyl analgesia / sedation 4. single point of entry P a t i e n t s : 1. n = (71,4%) male / 24 (28,6%) female 3. average age 63,5y (SD 10,1) from 41 to 78y (34,5%) patients had history of asbestous exposure Rigid versus semiflexible thoracoscopy in diagnosing pleural diseases. B i o p s y s a m p l e q u a l i t y : 1. area: program ImageJ 1.43u 2. sample quality: easily interpretable - 1 interpretable with some difficulty -2 interpretable with great difficulty - 3 non interpretable amount of artefacts no artefacts - 0 small amounts - 1 large amounts - 2

30 Rigid versus semiflexible thoracoscopy in diagnosing pleural diseases. R e s u l t s : Rigid th. Semiflexible th. Total No. of patients male female age 63,3y (SD 11,6y) 63,7y (SD 8,7y) 63,5y (SD 10,1y) number of biopsies 11.4 (SD 3,6) 10,8 (SD 2,3) 11,1 (SD 3,0) Malignant disease 19 (50,0%) 28 (69,3%) 47 (59,5) mesothelioma secondary carcinoma lymphoma Benign disease 19 (50,0%) 13 (30,7%) 32 (40,5%) Asbestous pleuritis Non specific pleuritis TBC pleuritis lipoma Rigid versus semiflexible thoracoscopy in diagnosing pleural diseases. R e s u l t s : Rigid th. Semiflexible th. Total Talc pleurodesis Chest tube (days) 2,45 (SD 1,81) 3,47 (SD 2,84) 2,99 (SD 2,44) Complications 1 (2,6%) 1 (2,4%) 2 (2,5) severe bleeding after biopsy empyema Rigid versus semiflexible thoracoscopy in diagnosing pleural diseases. R e s u l t s s a mp l e s i z e : Semiflexible Rigid t-test Area (mm2) 11,7 (SD 7,6) 24,7 (SD 12,9) 5,5 (p < 0,001) Semiflexible Rigid

31 Rigid versus semiflexible thoracoscopy in diagnosing pleural diseases. Results sample quality: Quality Semiflexible Rigid Total 1 easily interp. 30 (73,2%) 30 (78,9%) 60 (75,9%) 2 interp. with some diff 10 (24,4%) 8 (21,1%) 18 (22,8%) 3 interp. with great diff. 1 (2,4%) 0 1 (1,3%) 4 - noninterpretable Chi-square =1,110, sp=2 p=0,574 Semiflexible Rigid Rigid versus semiflexible thoracoscopy in diagnosing pleural diseases. Results sample quality: Artefacts Semiflexible Rigid Total 1 no artefacts 16 (39,0%) 18 (47,4%) 34 (43,0%) 2 small amounts 23 (56,1%) 18 (47,4%) 41 (51,9%) 3 large amounts 2 (4,9%) 2 (5,3%) 4 (5,1%) Chi-square =0,614, sp=2 p=0,736 Semiflexible Rigid Rigid versus semiflexible thoracoscopy in diagnosing pleural diseases. C o n c l u s i o n s : 1. Biopsy samples are smaller with semiflexible instrument. 2. Adequate biopsies and pleurodesis can be performed with semiflexible instrument. 3. The quality of samples according to diagnostic addequacy and artefacts doesn t differ significantly. 4. Both procedures are safe.

32 Rigid versus semiflexible thoracoscopy in diagnosing pleural diseases. University Clinic Golnik, Slovenia Thank you.

33 Precise tissue diagnosis for personalized treatment in lung cancer Izidor Kern University Clinic Golnik historical perspective 1. to look 2. to sample 3. to treat 4. to diagnose on one cell experience excellence technology quality & quantity matter new step, switch in mentality sampling BRONCHOSCOPY Benefits & limitations request specimen transport processing LABORATORY Optimal specimen handling is essential for the accurate interpretation 1

34 bronchoscopic specimens guided BRONCHIAL central, visible - aspirates - lavates - brushings - bronchial biopsies - imprints of biopsies -transbronchial needle aspirations - transbronchial needle biopsies PERIHILAR mediastinal, peribronchial - transbronchial needle aspirations - transbronchial needle aspirations PARENCHYMAL peripheral, nonvisible - transbronchial biopsies - imprints of biopsies - brushing - bronchoalveolar lavage - transbronchial needle aspirations - transbronchial needle biopsies BIOPSY - tissue sampling What to expect? pretest probability do we need tissue diagnosis Where to sample? How much? size & number of biopsies molecular biology microbiological studies research biopsy bronchial high diagnostic yield (~100% - >4 to 5 samples) transbronchial histopathological detection of changes in lung parenchyma adjacent to bronchi (mlg, infection, sarcoidosis) Value of negative results / nonspecific changes to narrow differential diagnosis Diagnostic yield of TBB? 30% 60% 2

35 TRANSBRONCHIAL BIOPSY TBB sufficent fragmented lung parenchymal tissue for the pathologist to reconstruct distribution and reaction pattern but with careful clinical and radiological correlation! No inflammation, no fibrosis ILD not excluded Interstitial inflammation and fibrosis nonspecific change - not necessarily ILD. TBB is not helpful in making the diagnosis of UIP. One of major diagnostic criteria of IPF is TBB showing no features to support an alternative diagnosis. variety of cell specimens cell sampling Classical exfoliative & FNAB cytopathology lab processing depends on type of specimen and clinical information BRONCHOALVEOLAR LAVAGE insight in great volume of lung parenchyma - alveoli Parameters of good quality / specimen adequacy: 1. V recovered / V instilled > 30% 2. < 40 red blood cells / 40x objective 3. > 10% of epithelial cell (contamination) 4. Cell viability > 60-70% 5. TCC > 2x10 6 clinical information influence lab procedure (filtration!) infection alveolar lipoproteinosis 3

36 TRANSBRONCHIAL NEEDLE BIOPSY & ASPIRATION guided sampling of lung masses (central or peripheral) and mediastinal lymph nodes (lung cancer staging) or tumours diagnostic yield up to 90%, also for benign lesions representativity of lymph node TBNA: presence of lymphocytes ± malignant cells sample processing TISSUE cold ischemia Time of fixation = time of sampling Drying artifacts (prolonged exposure to air) Formalin fixation - 4% NBF = 10% formalin, volume ratio 10:1 - Formalin safety (special nonaldehyde fixatives) sterile transport medium for direct immunofluorescence (vasculitis, CTD) fresh (snap frozen) EM special fixative CELL Do smears if possible air dried spray or ethanol fixed Rinse the needles Fluid samples BAL / sterile saline ethanol fixative transport immediate fresh tissue specimen BAL, non-fixed fluid cell specimens delayed request!!! safety boxes, closed vials,... 4

37 ROSE = to improve the yield of TBNA, immediate evaluation of specimen adequacy on-site presence of cytopathologist telepathology system 1. representative (sufficent material, provisional dg) positive neoplastic cells negative lymphoid but no tumor cells 2. non representative no lymphoid cells, necrosis, acellular specimen ROSE rapid technique toluidine blue Diff Quick rapid HE, Papanicolaou quick answer (< 5 min) criteria of specimen representativity enough, well preserved cells diagnostic cells presence of lymphatic cells (lymph nodes) lung cancer major indication for bronchoscopy key advances in the terapeutic management substantial changes in the diagnostic pathway, including bronchoscopic techniques improved acquisition of tumor tissue accurate histological typing tumor genotype & phenotype information EGFR mutation testing EGFR amplification? EML4-ALK testing ERCC1 IHK? pemetrexed for nonscc gemcitabine for SCC EGFR TKI for A, mu+ bevacizumab for nonscc crizotinib for A, ALK+ nonplatinum for ERCC

38 IASLC/ATS/ERS proposed new classification of lung cancers for small biopsies and cytological specimens A vs SCC p63 TTF1 CK7 CK5/6 A A: SPA+, napsin+, CK20- SCC: 34betaE12+ - SCC TTF1 NSCLC NOS < 10% CK7 tumor genotype & phenotype information molecular markers diagnostic prognostic predicitve 6

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