UNIVERSITY CLINIC OF RESPIRATORY AND ALLERGIC DISEASES GOLNIK BRONCHOSCOPY SCHOOL GOLNIK Golnik, 2011 October 14–15

BRONCHOSCOPY C O U R S E 2 0 1 1

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

11th Golnik Bronchoscopy Course

PROGRAM Friday, 14 October 2011

09.00 - 12. 00 – Lectures

8.30 – 9.00 Registration, cofee coffee 9.00 – 9.10 Opening

Nadja Triller, Mitja Košnik

9.10 – 9.30 How and why did we use bronchoscope – 60th anniversary An overview of training program in ronchoscopy at Clinic Golnik

Nadja Triller

9.30 – 9.50 101 years of Jacobaeus’ procedure – our story Andrej Debeljak 9.50 – 10.10 Bronchoscopy – what’s the next step? Stefano Gasparini

10.10 – 10.30 COFFEE BREAK 10.30 – 10.50 Traditional and technology-guided TBNA, pros and

cons Stefano Gasparini

10.50 – 11.10 Is mediastinoscopy an obscure method? (CUS TBNA for complete mediastinal staging)

Arthur Szlubowski

11.10 – 11.30 EBUS mini-probe as a maxi-too Aleš Rozman 11.30 - 11.50 Precise tissue diagnosis for personalized treatment in

lung cancer

Izidor Kern

11.50 – 12.10 Strange bugs in bronchoscopy unit Viktorija Tomič 12.10 – 12.20 Strange bugs in bronchoscopy unit – Case report Aleš Rozman 12.30 – 13. 30 LUNCH

13.30 Group photo in the park 14.00 - 18.30 - 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

20.00 GALA DINNER

Saturday, 15 October 2011

09.00 - 13.00 – Lectures 8.30 – 9.00 Coffee 9.00 – 9.20 Bronchoscopic LVR Ralf Eberhardt 9.20 – 9.40 Medical thoracoscopy – advanced techniques Aleš Rozman 9.40 – 9.55 Rigid vs. semirigid thoracoscopy Aleš Rozman 9.55 – 10.10 Case report – interactive session (intersticij) Katarina Osolnik

10.10 – 10.25 Case report – interactive session (EBUS) Mateja Marc 10.25 – 10.40 Case report- interactive session (torakoskopija) Luka Camlek 10.40 – 11.00 COFFEE BREAK 11.00 – 13.00 Oral presentations

Video presentations Poster discussions

13.00 – 13.30 Summary and certificates Nadja Triller

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

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

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).

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 1974. 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.

a

b

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).

Judita Mešič

Jurij Šorli

Andrej Debeljak

Nadja Triller

Aleš Rozman

→ 1973 01.09.1973→ 31.12.1981

01.01.1982→ 31.03.1994

01.04.1994→ 31.05.2010

01.06.2010→

Fig. 4. The bronchoscopy team in 2010.

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.

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

lavage 1982 Andrej Debeljak: bronchoalveolar 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 the lung

1968 Leon Fink: catheter biopsy of 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 biopsy

1974 Jurij Šorli: transbronchial lung biopsy

1966 Shigeto Ikeda: first fiberoptic bronchoscope

1974 Jurij Šorli: fiberoptic bronchoscopy

1973 H. Bryan Neel III: endobronchial cryosurgery

2006 Nadja Triller: endobronchial cryosurgery

1974 Georgios Nakratzas: endobronchial electrocautery

1999 Andrej Debeljak, Nadja Triller, Peter Kecelj, & Saša Letonja: endobronchial electrocautery

1978 Lucien Toty: Nd:YAG laser used through a bronchoscope

Never performed at Golnik

1983 Ko Pen Wang: transbronchial needle aspiration through flexible bronchoscope

1992 Andrej Debeljak & Marjeta Tečelj: transbronchial needle aspiration through flexible bronchoscope

1987 Fiberoptic video bronchoscopy 1989 Victor Tsang: airway stenting 2002 Andrej Debeljak: airway stenting 1991 Stephen Lam: autofluorescence

bronchoscopy 2000 Nadja Triller & Andrej Debeljak:

autofluorescence bronchoscopy 1999 Heinrich D. Becker: endobronchial

ultrasound 2001 Nadja Triller: endobronchial ultrasound

2001 Tudor P. Toma: bronchoscopic lung volume reduction for managing emphysema

2005 Nadja Triller: bronchoscopic lung volume reduction for managing emphysema

2002 Shigeo Tanaka: narrow band imaging bronchoscopy

2007 Nadja Triller: narrow band imaging bronchoscope

2002 James Fujimoto: endoscopic optical coherence tomography

Never performed at Golnik

2002 John D. Miller: bronchial thermoplasty Never performed at Golnik 2003 Yehuda Schwarz: electromagnetic

navigation Never performed at Golnik

Published articles and conference papers Bronchoscopy Department, University Pulmonary Clinic, Golnik 1951–2011 1.Mešič J. The importance of bronchoscopy in the diagnosis of pulmonary diseases. Zdrav Vestn. 1959;28(6–

7):174–5. [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):368–

70. [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):247–9. [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 1980:223–33.

6.Zenkovic M, Sorli J. The role of fiberoptic bronchoscopy in differential diagnosis of hemoptysis. Plucne Bolesti Tuberk. 1981 Jan–Mar;33(1):49–54. [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. 1981 Apr-Sep;33(2–3):142–6. [Croatian]

8.Zorman M, Suskovic S, Sorli J. Primary tracheal tumors. Plucne Bolesti Tuberk. 1981;32(4):191–8. [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):216–20. [Croatian] 10.Music E, Mermolja M, Debeljak A, Sorli J. Bronchoalveolar lavage in diffuse interstitial lung diseases. Plucne

Bolesti. 1984;36(1–2):69–72. [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):211–6. [Croatian] 12.Fortuna M. Indikacije za bronhoskopiju. Introduction to the fiberbronchoscopy technique, Course packet, 2nd

edition, Golnik, 1984;20–31. [Slovenian] 13.Remškar J. Mechanical, optical, and technical characteristics of certain fiberbronchoscopies. Introduction to

the fiberbronchoscopy technique, Course packet, 2nd edition, Golnik, 1984;40–47. [Croatian] 14.Fortuna M. Bronchoalveolar lavage. Introduction to the fiberbronchoscopy technique, Course packet, 2nd

edition, Golnik, 1984;78–84. [Croatian] 15.Fortuna M. Bronchoscopy in pediatrics. Introduction to the fiberbronchoscopy technique, Course packet, 2nd

edition, Golnik, 1984; 90–1. [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;110–20. [Croatian] 19.Remškar J. Bronchovideoscopy. Introduction to the fiberbronchoscopy technique, Course packet, 2nd edition,

Golnik, 1984;122–3. [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):211–6. [Croatian] 21.Fortuna M. Aspirin as a bronchodilator. Plucne Bolesti. 1985;37(3–4):221–4. [Croatian] 22.Debeljak A, Šorli J, Zupančič M, Remškar J. Bronchoscopic characteristics of sarcoidosis. Plucne Bolesti.

1987; 39(3–4):175–7. [Croatian] 23.Debeljak A, Sorli J, Remskar J, Rutar-Zupancic M, Rott T, Mermolja M. Metastasis of extrapulmonary

malignancies to the bronchi. Plucne Bolesti. 1987 Jan–Jun;39(1–2):5–10. [Croatian] 24.Sorli J. Guidelines for bronchoscopy with the fiberoptic bronchoscope in adults. Plucne Bolesti. 1988 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):149–52. [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):153–4. [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;61:226–30. 28.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;675–9.

29.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;693–6.

30.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):14.

31.Tomič V. Transmission of infection at bronchoscopy. Zdravstveno varstvo. [Tiskana izd.], 1997, 36, 407-9 32.Šorli J, Eržen D, Triller N, Papler B. Flexible bronchoscopy. Endosk Rev. 1998;3(7):111–3. [Slovenian]

33.Triller N, Terčelj M, Letonja S. Therapeutic bronchoskopy. Endosk Rev. 1998;3(7):173–7. [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;144.

35.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;144.

37.Debeljak A, Šorli J, Mušič E, Kecelj P. Bronchoscopic removal of foreign bodies in adults: experience with 62 patients from 1974–1998. Eur Respir J. 1999;14:792–5.

38.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 2000. Program and abstract book of the 2nd central European oncology congress; 2000 Jun 27–30; Opatija. Zagreb: European society of medical oncology (ESMO), 2000;28–9.

39.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;80.

40.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;75.

41.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;69–70.

42.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;75.

43.Triller N, Debeljak A. Treatment of endobronchial tumours with electrocautery. Lung Cancer. 2001;32(Suppl 1):S49.

44.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):S17. 48.Osolnik K. Comparison of the difficulties of bronchoscopic lung biopsy (BLB) with surgically open lung biopsy

(OLB). Endosk Rev. 2002;7(18):89–90. [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;7:83–4. 51.Debeljak A, Triller N, Kecelj P, Kern I. Autofluorescence bronchoscopy in the diagnosis of pre-neoplastic

changes in bronchial carcinoma. Zdrav Vestn. 2002;71:449–52. [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):256. 56.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):107–8. [Slovenian] 58.Letonja S. Bronchoscopy in the intensive care unit. Endosk Rev. 2002;7(18):22–5. [Slovenian]

59.Debeljak A, Triller N, Kecelj P, Letonja S. Palliative bronchoscopic treatment of tumor-induced narrowing of large airways. Zdrav Vestn. 2003;72:435–8. [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;61–70. [Slovenian]

61.Debevec L, Triller N, Kern I. Tracheobronchopathia osteochondroplastica. Liječ Vjesn, Supl 2003; 125(suppl 2):26.

62.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):14.

63.Triller N. Autofluorescence bronchoscopy and endobronchial ultrasound in the diagnosis and staging of lung cancer. Liječ Vjesn, Supl 2003; 125(Suppl 2):11.

64.Triller N. Endobronchial ultrasound in the diagnosis of tracheobronchial and mediastinal lesions and in peripheral pulmonary tumours. Liječ Vjesn, Supl 2003; 125(suppl 2):12.

65.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):S202.

66.Triller N, Debeljak A, Kecelj P, Eržen D, Kern I, Debevec L. Diagnostic procedures in peripheral pulmonary tumours in 1996 and 2001 - a retrospective comparative study. Lung Cancer 2003; 41(Suppl 2):S196.

67.Debeljak A, Triller N, Kecelj P. Palliative treatment of tumour central airways stenosis. Endoskopska revija 2003; 8(19):74-5.

68.Kern I, Eržen D, Kecelj P, Košnik M, Mermolja M. Cytology of bronchoalveolar lavage in interstitial lung disease. Zdrav Vestn. 2003;72(4):217–21. [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; 57.

70.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;24–31. [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;18–21. [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;56.

75.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;76.

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77.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):95–9.

78.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;70.

79.Debeljak A. Implantation of tracheobronchial stents. In: Triller N, Debeljak A, Rozman A, eds. ERS bronchoscopy course: bronchoscopy school textbook, Bled, October 5–7, 2007. Golnik: University Clinic of Respiratory and Allergic Diseases Golnik; 42–8.

80.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;313–26. [Slovenian]

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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).

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. 26040E 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 2008. In recent years, from 2008

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 1990. 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 CO2 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 26492 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.

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 (1860–1960). Slovenia’s Golnik sanatorium and TB in Central Europe. Peter Lang, Frankfurt am Main, 2011:77–8.

2.Jacobaeus HC. Über die Möglichkeit die Zystoskopie bei Untersuchung seröser Höhlungen anzuwenden. Münchner Medizinishe Wochenschrift 1910;57:2090–2.

3.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;41:83–90.

4.Zupanič Slavec Z. The Golnik surgical experience. In Zupanič Slavec Z. Tuberculosis (1860–1960). Slovenia’s Golnik sanatorium and TB in Central Europe. Peter Lang, Frankfurt am Main, 2011:79–80.

5.Loddenkemper R. Thoracoscopy: state of the art. Eur Respir J 1998;11:213–21. 6.Debeljak A, Kecelj P, Kern I, Vidmar S, Rott T. Medical thoracoscopy: experience with 212 patients. J

BUON 2000;5;169–72. 7.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, 8.–10. 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;11:463–7.

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;127:909–15.

12. Gary Lee YC, Edward Fysh TH. Indwelling pleural catheter. Changing the paradigm of malignant effusion management. Editorial J Thorac Oncol 2011;6:655–7.

Lectures and articles on thoracoscopy at Golnik Hospital 1991–2011

1.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 1991:105.

2.Debeljak A, Remškar Z, Ferluga D, Rott T, Mermolja M. Difuzni maligni plevralni mezoteliom. Diagnostični problemi. Zdrav Vestn 1993;62:195–8.

3.Debeljak A, Drinovec I, Eržen J, Rott T, Mermolja M. Diagnostična torakoskopija. Zdrav Vestn 1996;65, Suppl 2:9–12.

4.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 1997:183–5.

5.Debeljak A, Kecelj P, Kern I, Eržen J, Rott T. Diagnostična torakoskopija pri 201 bolniku od 1985 do 1997. Endosk Rev 1998;3:135–9.

6.Turel M, Debeljak A, Kecelj P. Torakoskopska plevrodeza s smukcem pri malignem plevralnem izlivu. Endosk Rev 1998;3:189–95.

7.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–159.

8.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.

11.Debevec M, Kovač V, Debeljak A, Eržen J, Kern I. Malignant pleural mesothelioma (MPM). Analysis of patients in Slovenia 1980-1997. 2nd Slovenian Slovenian Congress of Pneumology and Allergology. Klinika za pljučne bolezni in alergijo Golnik, Združenje pnevmologov Slovenije, Alergološko imunološka sekcija SZD, Portorož 2000:80.

12.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 2000:79.

13.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 2000:79.

14.Debeljak A, Kecelj P, Kern I, Vidmar S, Rott T. Medical thoracoscopy: experience with 212 patients. J BUON 2000;5:167–72.

15.Debevec M, Kovač V, Debeljak A, Eržen J, Remškar Z, Kern I. Maligni plevralni mezoteliom. Zdrav Vestn 2000;69:599–606.

16.Debeljak A, Kecelj P, Kern I. Naše izkušnje z internistično videotorakoskopijo. Endoscopic Rev 2001;6(14):93.

17.Debeljak A, Kecelj P, Kern I. Medical thoracoscopy in diffuse malignant pleural mesothelioma. Lung Cancer 2001:32, Suppl 1:S40.

18.Kovač V, Debevec M, Plaper-Vernik M, Debeljak A, Eržen J, Remškar Z, Kern I. Malignant pleural mesothelioma (MPM) in Slovenia 1980–1997. Lung Cancer 2001;32, Suppl 1:S57.

19.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 2002:61–62.

20.Debeljak A. Diagnostična torakoskopija. Endoscopic Rev, 2002;7:54–7. 21.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

2000-2003. Simpozij Bolezni plevre Združenje pnevmologov Slovenije, Zbornik predavanj, Nova Gorica 2. in 3. aprila 2004:27–34.

23.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;P094:89.

24.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 2004:15.

26.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 2004:43–8.

27.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 2004:57–66.

28.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, 10.-11. december, Zbornik predavanj. Velenje 2004:86–91.

29.Debeljak A, Kecelj P, Kern I, Sok M. Pet let videotorakoskopije na Golniku. Izvlečki 8. kongresa endoskopske kirurgije Slovenije, Portorož, 8.-10. maja 2005, Endoscopic Rev 2005;10:25.

30.Debeljak A. Mezoteliom in azbestna bolezen. Diagnostika. Histološka preiskava je imperativ. Skrb zase. Priloga Vive, revije za zdravo življenje. Ljubljana 2006:4–5.

31.Debeljak A, Letonja S, Triller N,Kecelj P. Talc pleurodesis. Lung cancer 2006;52, Suppl 2:O.6, S20. 32.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;11:463–7.

33.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;P046:34.

35.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.

EBUS mini probe- a maxi tool

Aleš Rozman

11th Bronchoscopy School Golnik

14 – 15 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.

US-probe Catheter

A miniature ultrasound probe (20 MHz, mechanical-radial

Type UM S20-20R (Olympus Optical; Tokyo, Japan)

Endoscopic US system

Olympus EU-M30

Equipment for EBUS miniprobe guided TBB

PPL – diagnostic methods:

1. Bronchoscopic sampling

• no guidance (sens. < 20%)

• fluoroscopic guidance (sens. 20-84% mlg. / 35-56% ben.)

• CT guidance + virtual bronchoscopy (65,4%)

• EM – guidance (sens. 59%)

• EM + EBUS guidance (sens. 88%)

• EBUS guidance (sens. 49-88% mlg. / 73% overall sens.)

2. Percutaneous image – guided aspiration / biopsy

• CT – guidance (sens. 90%)

Sensitivity of EBUS guided TBBSteinfort DP, et al. Eur Respir J 2011

Steinfort DP, et al. Eur Respir J 2011

Sensitivity of EBUS guided TBB

Chest 2009;136:229-36.

Sensitivity of EBUS guided TBB

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)

Position of the probe and sensitivity

Within the lesion

(sens. = 83%)

Adjacent to the lesion

(sens. = 61%)

Outside the lesion

(sens. = 4%)

Yamada N et al. CHEST 2007; 132:603–608

Chao et al. Chest 2006;130:1191-1197

• 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

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;122:1887-1894

Benign vs. malignant lesion

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

EBUS guided transbronchial lung biopsy

in peripheral pulmonary lesions

Analysis 2011

Golnik University ClinicGolnik University Clinic

Peripheral pulmonary lesions

• 579 patients / 136 pt’s with periph. lesion (23,5%)

• Mean (±SD) diameter 42 ± 21 mm (range 8-120mm)

Malignant lesions Lesions

Diagnostic method

EBUS TBB Fluroscopy

TBB

CT guided

TTNA

Metastasis

NA

Adenocarcinoma 60 48 2 6 4

Squamous cell ca 30 26 3 1

Large cell ca 5 3 1 1

Small cell ca 6 6

Non small cell ca 1 1

Lymphoma 2 2

Carcinoid 1 1

Metastatic lung tu 7 5 2

Other 3 0 1 2

ΣΣΣΣ 115 92 (80%) 3 (2,6%) 13 (11,3%) 7 (6,1%)

Benign lesions

Lesions

Diagnosis method

EBUS

TBB

CT

guided

TTNA

Surgery Other

Orgnizing

pneumonia

7 6 1

Tuberculosis 5 3 2 - cultures

Abscess 4 3 1 – clin. response

Fibrosis 3 1 1 1 – follow up

Hamartoma 3 0 1 2

Sarcoidosis 3 2 1

Pneumonia 2 2

Other* 5 2 1 1 1 - undiagnosed

ΣΣΣΣ 32 19 (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

Diagnostic yield of EBUS guided

TBB by location of the lesion

RS1-64%

RS2-72%

RS3-81%

RS4-67%

RS5-50%

RS6-90%

RS7-0

RS8-50%

RS9-67%

RS10-56%

LS1,2-89%

LS3 - 67%

LS4-100%

LS5-50%

LS6-86%

LS8-100%

LS9-100%

LS10-89%

48/35

13/8

31/21

24/20

7/5

24/22

Diagnostic yield and the lesion size : ≤≤ 3 cm: > 3 cm3 cm: > 3 cm→→60%:86%60%:86%

Position of the probe and diagnostic yield

Within the lesion

(DG yield = 92,2%)

Adjacent to the

lesion

(DB yield= 77,8%)

Outside the lesion

(fluoroscopic

guidance)

(DG yield = 43,2%)

Within the lesion,

not at the end of

the bronchus

(DG yield =

80,0%)

Overall DG yield = 75,5%

Steinfort DP, et al. Eur Respir J 2011

Sensitivity of EBUS guided TBB

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

Thank you.University Clinic Golnik,

Slovenia

Rigid versus semiflexible thoracoscopyin diagnosing pleural diseases.

Aleš Rozman

11th Bronchoscopy School Golnik14 – 15 October 2011

Rozman A

Marc – Malovrh M

Camlek L

Triller N

Kern I

University Clinic Golnik,

Slovenia

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.

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 2010.

Rigid versus semiflexible thoracoscopy in diagnosing pleural diseases.

M e t h o d s :

1. rigid thoracoscope Olympus A5252A vs. semiflexible Olympus LTF-160

2. 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 = 84

2. 60 (71,4%) male / 24 (28,6%) female

3. average age 63,5y (SD 10,1) from 41 to 78y

4. 29 (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 - 4

3. amount of artefacts

no artefacts - 0

small amounts - 1

large amounts - 2

Rigid versus semiflexible thoracoscopy in diagnosing pleural diseases.

R e s u l t s :Rigid th. Semiflexible th. Total

No. of patients 38 41 79

male 23 35 58

female 15 6 21

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 12 20 32

secondary carcinoma 6 8 14

lymphoma 1 0 1

Benign disease 19 (50,0%) 13 (30,7%) 32 (40,5%)

Asbestous pleuritis 3 4 7

Non – specific pleuritis 13 9 22

TBC pleuritis 2 0 2

lipoma 1 0 1

Rigid versus semiflexible thoracoscopy in diagnosing pleural diseases.

R e s u l t s :

Rigid th. Semiflexible th. Total

Talc pleurodesis 8 8 16

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

Rigid versus semiflexible thoracoscopy in diagnosing pleural diseases.

Results – sample quality:

Semiflexible

Rigid

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 0 0 0

Chi-square =1,110, sp=2

p=0,574

Rigid versus semiflexible thoracoscopy in diagnosing pleural diseases.

Results – sample quality:

Semiflexible

Rigid

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

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.

Rigid versus semiflexible thoracoscopy in diagnosing pleural diseases.

Thank you.University Clinic Golnik,

Slovenia

Rigid versus semiflexible thoracoscopy in diagnosing pleural diseases.

1

Precise tissue diagnosisfor 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

excellencetechnology

quality & quantity matter

new step, switch in mentality

sampling

processing

transp

ort

BRONCHOSCOPY

LABORATORY

request

specimen

Optimal specimen handling is essential for

the accurate interpretation

Benefits&

limitations

2

bronchoscopic specimens

- transbronchial needle

aspirations

- transbronchial needle aspirations

PERIHILARmediastinal, peribronchial

- transbronchial biopsies

- imprints of biopsies

- brushing

- bronchoalveolar lavage

- transbronchial needle

aspirations

- transbronchial needle

biopsies

- aspirates

- lavates

- brushings

- bronchial biopsies

- imprints of biopsies

-transbronchial needle aspirations

- transbronchial needle

biopsies

PARENCHYMALperipheral, nonvisible

BRONCHIALcentral, visible

guided

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%

3

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 specimenscell 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. Vrecovered / Vinstilled > 30%

2. < 40 red blood cells / 40x objective

3. > 10% of epithelial cell (contamination)

4. Cell viability > 60-70%

5. TCC > 2x106

• clinical information influence lab procedure (filtration!)

– infection

– alveolar lipoproteinosis

4

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 processingTISSUE

• cold ischemiaTime of fixation = time of sampling

Drying artifacts (prolonged exposure to air)

• Formalin fixation - 4% NBF = “10%” formalin,

volume ratio 10:1

- Formalin safety (special non-aldehyde 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,...

5

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 typingtumor genotype & phenotype information

•EGFR mutation testing•EGFR amplification?

•EML4-ALK testing

•ERCC1 IHK?

pemetrexed for nonSCCgemcitabine for SCCEGFR TKI for A, mu+

bevacizumab for nonSCCcrizotinib for A, ALK+nonplatinum for ERCC1+

.

.

.

6

IASLC/ATS/ERS

proposed new classification

of lung cancers for

small biopsiesand

cytological specimens

A vs SCC

+-CK5/6

-+CK7

-+TTF1

+-p63

SCCA

A: SPA+, napsin+, CK20-SCC: 34betaE12+

TTF1

CK7NSCLC NOS < 10%

tumor genotype & phenotype information

• molecular markers

– diagnostic

– prognostic

– predicitve

7

EGFR testing requirements

1. quality of specimen, choose the best one• high % of tumour (>25 or 50%)

• > 200-400 cells

• does the tumour specimen represents the patient’s tumour

• tissue > cell

2. specimen– BB (2-3)

– TBB (4-5)

– needle biopsies (>2)

– cytological (TBNA, brushing, lavates,...)

quantity is essential

fate of one biopsy1. H&E 5x

2. AB (mucin staining) 1x

3. IHC 5x (histo typing)

4. H&E first control

5. DNA extraction min 3x10µm (EGFR testing)

6. IHC (additional) 2x

7. ISH & IHC 2x (ALK testing)

8. H&E last control

What does influence the pathology result?

• sampling: “Was the lesion targeted?”• Specimen quality: necrosis• Experience of bronchoscopy team• Processing & transport• Acquisition of sample in lab, request

• Lab technique

• Pathology examination

• Clinical & radiologic information

• Limitations of pathology

Even a nonspecific dg is important in patient management.

8

precise tissue diagnosis for all

our team goal