2 of 51

Athanasios Kleontas

BSc, MD, MSc, BTS, PhD(c)

Thoracic Surgery

THE NETTER COLLECTION OF MEDICAL ILLUSTRATIONS:

RESPIRATORY SYSTEM

Volume 3, Second Edition

Anatomy of pleura

Definitions

Principles

Approval

Indications

Technique

Review

Experience

Bibliography

3 of 51

Athanasios Kleontas

BSc, MD, MSc, BTS, PhD(c)

Thoracic Surgery

THE NETTER COLLECTION OF MEDICAL ILLUSTRATIONS:

RESPIRATORY SYSTEM

Volume 3, Second Edition

Mesothelioma

Definitions

Principles

Approval

Indications

Technique

Review

Experience

Bibliography

4 of 51

Athanasios Kleontas

BSc, MD, MSc, BTS, PhD(c)

Thoracic Surgery

Imaging

Definitions

Principles

Approval

Indications

Technique

Review

Experience

Bibliography

5 of 51

Athanasios Kleontas

BSc, MD, MSc, BTS, PhD(c)

Thoracic Surgery

Extended pleurecomy decortication for malignant mesothelioma in the ederly

The need for an inclusive yet selective approach

A. Sharkey, A. Nakas, S. Tenconi,

Definitions

Principles

Approval

Indications

Technique

Review

Experience

Bibliography

6 of 51

Athanasios Kleontas

BSc, MD, MSc, BTS, PhD(c)

Thoracic Surgery

Asbestos

www.webmd.com/cancer/ss/slideshow-malignant-mesothelioma

Definitions

Principles

Approval

Indications

Technique

Review

Experience

Bibliography

7 of 51

Athanasios Kleontas

BSc, MD, MSc, BTS, PhD(c)

Thoracic Surgery

Mesothelioma Treatment

Surgery

Chemo

Radio

Definitions

Principles

Approval

Indications

Technique

Review

Experience

Bibliography

8 of 51

Athanasios Kleontas

BSc, MD, MSc, BTS, PhD(c)

Thoracic Surgery

www.mesotheliomaguide.com/treatment/surgery

Definitions

Principles

Approval

Indications

Technique

Review

Experience

Bibliography

9 of 51

Athanasios Kleontas

BSc, MD, MSc, BTS, PhD(c)

Thoracic Surgery

www.mesotheliomaguide.com/treatment/surgery

Definitions

Principles

Approval

Indications

Technique

Review

Experience

Bibliography

10 of 51

Athanasios Kleontas

BSc, MD, MSc, BTS, PhD(c)

Thoracic Surgery

Η έκθεση των κυττάρων

σε θερμοκρασία μεγαλύτερη των 40^οC

οδηγεί σε

κυτταρικό θάνατο

ή αναστολή του πολλαπλασιασμού,

φαινόμενα που επιτείνονται

με παράταση του χρόνου έκθεσης

σε δεδομένη θερμοκρασία.

Studies on the quantitative biology of hyperthermic killing of HeLa cells.

Palzer RJ, Heidelberger C.

Cancer Res [Internet]. 1973 Feb [cited 2013 May 18];33(2):415–21.

Available from: http://www.ncbi.nlm.nih.gov/pubmed/4688889

Definitions

Principles

Approval

Indications

Technique

Review

Experience

Bibliography

11 of 51

Athanasios Kleontas

BSc, MD, MSc, BTS, PhD(c)

Thoracic Surgery

Συγκριτικές μελέτες σε καλλιέργειες

ανθρώπινων φυσιολογικών και νεοπλασματικών κυττάρων,

που εκτέθηκαν σε θερμοκρασίες 42.5-43.0^οC για 4-8 ώρες,

ανέδειξαν υψηλότερα ποσοστά θανάτωσης των νεοπλασματικών κυττάρων με στατιστική σημαντικότητα (p<0.01)

Selective lethal effect of supranormal temperatures on human neoplastic cells.

Giovanella BC, Stehlin JS Jr, Morgan AC.

Cancer Res. 1976 Nov;36(11 Pt 1):3944-50.

Definitions

Principles

Approval

Indications

Technique

Review

Experience

Bibliography

12 of 51

Athanasios Kleontas

BSc, MD, MSc, BTS, PhD(c)

Thoracic Surgery

Στο φυσιολογικό ιστό η αύξηση της θερμοκρασίας οδηγεί σε άμεση αύξηση της αιματικής ροής, γεγονός το οποίο συνοδεύεται

από διαστολή των αγγείων και αύξηση της διαπερατότητας

του τοιχώματος των αγγείων

και μετά από κάποιο χρονικό διάστημα – το οποίο εξαρτάται από το είδος του νεοπλάσματος και το ύψος της θερμοκρασίας ,

σημειώνεται ελάττωση της αιματικής ροής, η οποία οφείλεται σε παχύνσεις του ενδοθηλίου και μικροθρομβώσεις.

Effect of local hyperthermia on blood flow and microenvironment: a review.

Song CW

Cancer Res. 1984 Oct;44(10 Suppl):4721s-4730s.

Definitions

Principles

Approval

Indications

Technique

Review

Experience

Bibliography

13 of 51

Athanasios Kleontas

BSc, MD, MSc, BTS, PhD(c)

Thoracic Surgery

Local tumour hyperthermia as immunotherapy for metastatic cancer

Seiko Toraya-Brown1 & Steven Fiering

Int J Hyperthermia, 2014; 30(8): 531–539

Definitions

Principles

Approval

Indications

Technique

Review

Experience

Bibliography

14 of 51

Athanasios Kleontas

BSc, MD, MSc, BTS, PhD(c)

Thoracic Surgery

Local tumour hyperthermia as immunotherapy for metastatic cancer

Seiko Toraya-Brown1 & Steven Fiering

Int J Hyperthermia, 2014; 30(8): 531–539

Definitions

Principles

Approval

Indications

Technique

Review

Experience

Bibliography

15 of 51

Athanasios Kleontas

BSc, MD, MSc, BTS, PhD(c)

Thoracic Surgery

Local tumour hyperthermia as immunotherapy for metastatic cancer

Seiko Toraya-Brown1 & Steven Fiering

Int J Hyperthermia, 2014; 30(8): 531–539

Definitions

Principles

Approval

Indications

Technique

Review

Experience

Bibliography

16 of 51

Athanasios Kleontas

BSc, MD, MSc, BTS, PhD(c)

Thoracic Surgery

Local tumour hyperthermia as immunotherapy for metastatic cancer

Seiko Toraya-Brown1 & Steven Fiering

Int J Hyperthermia, 2014; 30(8): 531–539

Definitions

Principles

Approval

Indications

Technique

Review

Experience

Bibliography

17 of 51

Athanasios Kleontas

BSc, MD, MSc, BTS, PhD(c)

Thoracic Surgery

Local tumour hyperthermia as immunotherapy for metastatic cancer

Seiko Toraya-Brown1 & Steven Fiering

Int J Hyperthermia, 2014; 30(8): 531–539

Definitions

Principles

Approval

Indications

Technique

Review

Experience

Bibliography

18 of 51

Athanasios Kleontas

BSc, MD, MSc, BTS, PhD(c)

Thoracic Surgery

Best results

Higher

drug concentration

Better

drug penetration

effective time

Reduced

systematic toxicity

Hyperthermia

Regional

Chemotherapy

Hyperthermic

Intra

THOracic

Chemotherapy

Definitions

Principles

Approval

Indications

Technique

Review

Experience

Bibliography

19 of 51

Athanasios Kleontas

BSc, MD, MSc, BTS, PhD(c)

Thoracic Surgery

Pleurectomy

Decortication

Hyperthermic

Intra

THOracic

Chemotherapy

Better

Results

Definitions

Principles

Approval

Indications

Technique

Review

Experience

Bibliography

20 of 51

Athanasios Kleontas

BSc, MD, MSc, BTS, PhD(c)

Thoracic Surgery

https://www.cancer.gov/about-cancer/treatment/types/surgery/hyperthermia-fact-sheet

Definitions

Principles

Approval

Indications

Technique

Review

Experience

Bibliography

21 of 51

Athanasios Kleontas

BSc, MD, MSc, BTS, PhD(c)

Thoracic Surgery

https://vimeo.com/250741423

Definitions

Principles

Approval

Indications

Technique

Review

Experience

Bibliography

22 of 51

Athanasios Kleontas

BSc, MD, MSc, BTS, PhD(c)

Thoracic Surgery

Definitions

Principles

Approval

Indications

Technique

Review

Experience

Bibliography

23 of 51

Athanasios Kleontas

BSc, MD, MSc, BTS, PhD(c)

Thoracic Surgery

Definitions

Principles

Approval

Indications

Technique

Review

Experience

Bibliography

24 of 51

Athanasios Kleontas

BSc, MD, MSc, BTS, PhD(c)

Thoracic Surgery

Definitions

Principles

Approval

Indications

Technique

Review

Experience

Bibliography

Malignant Pleural Effusion

Thymic Carcinoma

Mesothelioma

Athanasios Kleontas

BSc, MD, MSc, BTS, PhD(c)

Thoracic Surgery

Clinical outcomes of cytoreductive surgery combined with intrapleural perfusion

of hyperthermic chemotherapy in advanced lung adenocarcinoma with pleural dissemination.

Eunjue Yi, Daejoong Kim, Sukki Cho, Kwhanmien Kim, Sanghoon Jheon

J Thorac Dis 2016;8(7):1550-1560

Circuit

Definitions

Principles

Approval

Indications

Technique

Review

Experience

Bibliography

33 of 51

Athanasios Kleontas

BSc, MD, MSc, BTS, PhD(c)

Thoracic Surgery

Definitions

Principles

Approval

Indications

Technique

Review

Experience

Bibliography

34 of 51

Athanasios Kleontas

BSc, MD, MSc, BTS, PhD(c)

Thoracic Surgery

Pleurectomy/decortication and hyperthermic intrapleural chemotherapy for malignant pleural mesothelioma: initial experience.

Migliore M, Calvo D, Criscione A, Palmucci S, Fuccio Sanzà G, Caltabiano R, Spatola C, Privitera G, Aiello MM, Parra HS, Ciancio N, Di Maria G.

Future Oncol. 2015;11(24 Suppl):19-22. doi: 10.2217/fon.15.286.

PMID:26638918

Interim results of pleurectomy/decortication and intraoperative intrapleural hyperthermic cisplatin perfusion for patients with malignant pleural mesothelioma intolerable to extrapleural pneumonectomy.

Ishibashi H, Kobayashi M, Takasaki C, Okubo K.

Gen Thorac Cardiovasc Surg. 2015 Jul;63(7):395-400. doi: 10.1007/s11748-015-0535-x. PMID:25750109

Pleurectomy/decortication, hyperthermic pleural lavage with povidone-iodine, prophylactic radiotherapy, and systemic chemotherapy in patients with malignant pleural mesothelioma: a 10-year experience.

Lang-Lazdunski L, Bille A, Papa S, Marshall S, Lal R, Galeone C, Landau D, Steele J, Spicer J.

J Thorac Cardiovasc Surg. 2015 Feb;149(2):558-65; discussion 565-6. doi: 10.1016/j.jtcvs.2014.10.041.PMID:25726878

[Hyperthermic chemoperfusion of the pleural cavity in the combined treatment for malignantpleural mesothelioma].

Levchenko EV, Mamontov OIu, Senchik KIu, Barchuk AS, Gel'fond ML.

Vopr Onkol. 2014;60(4):482-5. Russian.

PMID:25552068

Multimodal management of malignant pleural mesothelioma: where are we today?

Van Schil PE, Opitz I, Weder W, De Laet C, Domen A, Lauwers P, Hendriks JM, Van Meerbeeck JP.

Eur Respir J. 2014 Sep;44(3):754-64. doi: 10.1183/09031936.00207213.

PMID:24525443

Intraoperative hyperthermic chemotherapy perfusion for malignant pleural mesothelioma: an in vitro evaluation.

Cameron RB, Hou D.

J Thorac Cardiovasc Surg. 2013 Feb;145(2):496-504. doi: 10.1016/j.jtcvs.2012.10.042.

PMID:23174177

https://www.ncbi.nlm.nih.gov/pubmed

Definitions

Principles

Approval

Indications

Technique

Review

Experience

Bibliography

35 of 51

Athanasios Kleontas

BSc, MD, MSc, BTS, PhD(c)

Thoracic Surgery

https://www.ncbi.nlm.nih.gov/pubmed

Hyperthermic intraoperative pleural cisplatin chemotherapy extends interval to recurrence and survival among low-risk patients with malignant pleural mesothelioma undergoing surgical macroscopic complete resection.

Sugarbaker DJ, Gill RR, Yeap BY, Wolf AS, DaSilva MC, Baldini EH, Bueno R, Richards WG.

J Thorac Cardiovasc Surg. 2013 Apr;145(4):955-63. doi: 10.1016/j.jtcvs.2012.12.037. PMID:23434448

Local and systemic exposure of cisplatin during hyperthermic intrathoracic chemotherapy perfusion after pleurectomy and decortication for treatment of pleural malignancies.

Ried M, Potzger T, Braune N, Diez C, Neu R, Sziklavari Z, Schalke B, Hofmann HS.

J Surg Oncol. 2013 Jun;107(7):735-40. doi: 10.1002/jso.23321.

PMID:23386426

Intraoperative hyperthermic chemotherapy perfusion for malignant pleural mesothelioma: an in vitro evaluation.

Cameron RB, Hou D.

J Thorac Cardiovasc Surg. 2013 Feb;145(2):496-504. doi: 10.1016/j.jtcvs.2012.10.042. PMID:23174177

Cytoreductive surgery and hyperthermic intrathoracic chemotherapy perfusion for malignant pleural tumours: perioperative management and clinical experience.

Ried M, Potzger T, Braune N, Neu R, Zausig Y, Schalke B, Diez C, Hofmann HS.

Eur J Cardiothorac Surg. 2013 Apr;43(4):801-7. doi: 10.1093/ejcts/ezs418.

PMID:22885228

Pharmacokinetics of Hyperthermic Intrathoracic Chemotherapy following Pleurectomy and Decortication.

Sugarbaker PH, Stuart OA, Eger C.

Gastroenterol Res Pract. 2012;2012:471205. doi: 10.1155/2012/471205.

PMID:22548052

Extrapleural pneumonectomy followed by intracavitary intraoperative hyperthermic cisplatin with pharmacologic cytoprotection for treatment of malignant pleural mesothelioma: a phase II prospective study.

Tilleman TR, Richards WG, Zellos L, Johnson BE, Jaklitsch MT, Mueller J, Yeap BY, Mujoomdar AA, Ducko CT, Bueno R, Sugarbaker DJ.

J Thorac Cardiovasc Surg. 2009 Aug;138(2):405-11. doi: 10.1016/j.jtcvs.2009.02.046.

PMID:19619785

Definitions

Principles

Approval

Indications

Technique

Review

Experience

Bibliography

36 of 51

Athanasios Kleontas

BSc, MD, MSc, BTS, PhD(c)

Thoracic Surgery

https://www.ncbi.nlm.nih.gov/pubmed

A phase I study of extrapleural pneumonectomy and intracavitary intraoperative hyperthermic cisplatin with amifostine cytoprotection for malignant pleural mesothelioma.

Zellos L, Richards WG, Capalbo L, Jaklitsch MT, Chirieac LR, Johnson BE, Bueno R, Sugarbaker DJ.

J Thorac Cardiovasc Surg. 2009 Feb;137(2):453-8. doi: 10.1016/j.jtcvs.2008.07.055.

PMID:19185169

Hyperthermic chemoperfusion for the treatment of malignant pleural mesothelioma.

Mujoomdar AA, Sugarbaker DJ.

Semin Thorac Cardiovasc Surg. 2008 Winter;20(4):298-304. doi: 10.1053/j.semtcvs.2008.11.002. Review.

PMID:19251168

Induction of apoptosis by intrapleural perfusion hyperthermo-chemotherapy for malignant pleuralmesothelioma.

Matsuzaki Y1, Tomita M, Shimizu T, Hara M, Ayabe T, Onitsuka T.

Ann Thorac Cardiovasc Surg. 2008 Jun;14(3):161-5.

Intrapleural hyperthermic perfusion with chemotherapy increases apoptosis in malignant pleuritis.

Matsuzaki Y1, Edagawa M, Shimizu T, Hara M, Tomita M, Ayabe T, Onitsuka T.

Ann Thorac Surg. 2004 Nov;78(5):1769-72.

Definitions

Principles

Approval

Indications

Technique

Review

Experience

Bibliography

37 of 51

Athanasios Kleontas

BSc, MD, MSc, BTS, PhD(c)

Thoracic Surgery

Effect of hyperthermic intrathoracic chemotherapy (HITHOC) on the malignant pleural effusion

A systematic review and meta-analysis

Hua Zhou, Wei Wu, Xiaoping Tang, Jianying Zhou, Yihong Shen

Medicine (Baltimore). 2017 Jan;96(1):e5532.

Definitions

Principles

Approval

Indications

Technique

Review

Experience

Bibliography

38 of 51

Athanasios Kleontas

BSc, MD, MSc, BTS, PhD(c)

Thoracic Surgery

Effect of hyperthermic intrathoracic chemotherapy (HITHOC) on the malignant pleural effusion

A systematic review and meta-analysis

Hua Zhou, Wei Wu, Xiaoping Tang, Jianying Zhou, Yihong Shen

Medicine (Baltimore). 2017 Jan;96(1):e5532.

Definitions

Principles

Approval

Indications

Technique

Review

Experience

Bibliography

39 of 51

Athanasios Kleontas

BSc, MD, MSc, BTS, PhD(c)

Thoracic Surgery

Definitions

Principles

Approval

Indications

Technique

Review

Experience

Bibliography

40 of 51

Athanasios Kleontas

BSc, MD, MSc, BTS, PhD(c)

Thoracic Surgery

http://www.athenscrossroad.com/programme/

Our Experience

Definitions

Principles

Approval

Indications

Technique

Review

Experience

Bibliography

41 of 51

Athanasios Kleontas

BSc, MD, MSc, BTS, PhD(c)

Thoracic Surgery

A.Kleontas, C.Emmanouilidis, S.Baka, H. Titopoulos,

D.Oikonimou, E.Konstantinou, D.Filippou

Our Experience

14 late years retrospective analysis,

26 patients with malignant pleural mesothelioma

in European Interbalkan Medical Center

Median age: 64±8 years - (16M-10F)

Histologic type

Epithelioid	Mixed	Sarcomatoid
18	7	1

Definitions

Principles

Approval

Indications

Technique

Review

Experience

Bibliography

42 of 51

Athanasios Kleontas

BSc, MD, MSc, BTS, PhD(c)

Thoracic Surgery

Our Experience

Posterolateral

Thoracotomy

Pleurectomy

Decortication

A.Kleontas, C.Emmanouilidis, S.Baka, H. Titopoulos,

D.Oikonimou, E.Konstantinou, D.Filippou

Definitions

Principles

Approval

Indications

Technique

Review

Experience

Bibliography

43 of 51

Athanasios Kleontas

BSc, MD, MSc, BTS, PhD(c)

Thoracic Surgery

Our Experience

Complete Mediastinal

Lymph nodes dissection

HITHOC

A.Kleontas, C.Emmanouilidis, S.Baka, H. Titopoulos,

D.Oikonimou, E.Konstantinou, D.Filippou

Definitions

Principles

Approval

Indications

Technique

Review

Experience

Bibliography

44 of 51

Athanasios Kleontas

BSc, MD, MSc, BTS, PhD(c)

Thoracic Surgery

Our Experience

A.Kleontas, C.Emmanouilidis, S.Baka, H. Titopoulos,

D.Oikonimou, E.Konstantinou, D.Filippou

3 cases 🡪laparoscopy

5 cases 🡪partial hemidiaphram resection & reconstruction

6 cases 🡪partial pericardiectomy

4 cases 🡪lung resection

(1 lobectomy)

(3 wedge resection)

Definitions

Principles

Approval

Indications

Technique

Review

Experience

Bibliography

45 of 51

Athanasios Kleontas

BSc, MD, MSc, BTS, PhD(c)

Thoracic Surgery

Gender	Age	Hemithorax	Histology	Lymph Node Invasion	Pleurectomy	Decortication	Hemidiaphram Resection	Pericardial Resection	Lung Resection	HITHOC	Adjuvant
M	65	L	Epithelioid	0	(+)	(+)	(+)	(-)	(-)	(+)	Carboplatin�Pemetrexed
M	65	R	Mixed	0	(+)	(+)	(-)	(+)	Multiple wedge	(+)	(-)
M	68	L	Epithelioid	0	(+)	(+)	(+)	(+)	LLL lobectomy	(+)	(-)
M	88	R	Epithelioid	0	(+)	(+)	(-)	(-)	Multiple wedge	(+)	(-)

A.Kleontas, C.Emmanouilidis, S.Baka, H. Titopoulos,

D.Oikonimou, E.Konstantinou, D.Filippou

Definitions

Principles

Approval

Indications

Technique

Review

Experience

Bibliography

46 of 51

Athanasios Kleontas

BSc, MD, MSc, BTS, PhD(c)

Thoracic Surgery

Our Experience

A.Kleontas, C.Emmanouilidis, S.Baka, H. Titopoulos,

D.Oikonimou, E.Konstantinou, D.Filippou

R1 resection

(R1:16 > R2:10)

Staging

45% (12/26) IIIa

55% (14/26) IIIb

Zero

Perioperative mortality

Morbidity

Prolonged air leak (3/26),

Lung infection (2/26),

Pulmonary embolism (1/26)

Definitions

Principles

Approval

Indications

Technique

Review

Experience

Bibliography

47 of 51

Athanasios Kleontas

BSc, MD, MSc, BTS, PhD(c)

Thoracic Surgery

Our Experience

A.Kleontas, C.Emmanouilidis, S.Baka, H. Titopoulos,

D.Oikonimou, E.Konstantinou, D.Filippou

Median overall survival

14.3 μήνες

(1-140)

Better outcome

R1 resection

HITHOC

Definitions

Principles

Approval

Indications

Technique

Review

Experience

Bibliography

48 of 51

Athanasios Kleontas

BSc, MD, MSc, BTS, PhD(c)

Thoracic Surgery

Our Experience

A.Kleontas, C.Emmanouilidis, S.Baka, H. Titopoulos,

D.Oikonimou, E.Konstantinou, D.Filippou

No case with extra pleural pneumonectomy

Resections

Radical 🡪 cytoreductive

Zero perioperative mortality

HITHOC

Staging or restriction

of residual disease

Definitions

Principles

Approval

Indications

Technique

Review

Experience

Bibliography

49 of 51

Athanasios Kleontas

BSc, MD, MSc, BTS, PhD(c)

Thoracic Surgery

Bibliography

Survival by Histologic Subtype of Malignant Pleural Mesothelioma

and the Impact of Surgical Resection on Overall Survival

Vivek Verma et al, 8/2018, Clinical Lung Cancer

Definitions

Principles

Approval

Indications

Technique

Review

Experience

Bibliography

50 of 51

Athanasios Kleontas

BSc, MD, MSc, BTS, PhD(c)

Thoracic Surgery

Bibliography

Survival by Histologic Subtype of Malignant Pleural Mesothelioma

and the Impact of Surgical Resection on Overall Survival

Vivek Verma et al, 8/2018, Clinical Lung Cancer

Definitions

Principles

Approval

Indications

Technique

Review

Experience

Bibliography

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