Peter is fleeing Rome. Outside the city he meets the risen Jesus and asks him:

“Domine, quo vadis?“ “Lord, where are you going?”

Jesus replies: "I am going to Rome to be crucified again".

Domine, quo vadis ? (1602) by Annibale Garracci 1 http://www.sacred-destinations.com/italy/rome-domine-quo-vadis Lymphology Quo Vadis?

Part-1

The fate of lymphology Lymphatic system teaching Lymphatic system history

Borislav Penchev - Unitec NZ Shamim Shaikh - Unitec NZ

2 We asked old school MRTs

 Where is the LS going to?  Is the LS relevant to the Medical Imaging practice?

An NZ MRT role model, researcher and educator stated: “We performed lymphangiograms in the dark ages…alas”

To learn more, we decided to:

3 Content

1) Survey the current LS teaching

2) History of the LS exploration

4 McCracken & Morris, (2001), New Atlas of Human , London, Constable Publishers 1. CURRENT ANATOMY TEACHING OF LS

Survey – conducted between 2012 and 2017

Methods – personal contacts, phone calls and emails – questionnaire completed in class

Participants – students and staff from various tertiary providers, but predominantly from Unitec NZ Student N = 321; staff N = 11

Survey carried out and analysed by the authors

5 Provider LS anatomy teaching time Unitec: MI, Nursing, Osteopathy 10-20 minutes Fiji Med School 20 minutes Auckland Med School 30 minutes New Zealand College of 4 hours Chiropractic Otago Med School 4-5 hours

Disproportionate influx of “soft social” subjects deprived “hard” scientific topics from adequate teaching time. Staff & students from the above institutions

“Curriculum time dedicated to anatomy is decreasing(Patel & Moxham, 2008)

“Anatomy teaching is in the midst of a downward spiral”(Older, 2004) 6 QUESTIONNAIRE

Q1: List four anatomical elements of the LS

Q2: List two principle functions of the LS

Q3: To study, or not to study the LS ?

Q4: If “YES”, how many hours ?

Q5: If “NOT”, why not ?

7 Results

Participants from Unitec Year Numbers Osteopathy students 1, 2 & 3 47 Nursing student 2 & 3 59 321 Med. Imaging students 1, 2 & 3 215

Q1: List four anatomical elements of the LS

59 Nursing students - 4 students listed 3 elements 32% - 15 students listed 4 elements

47 Osteopathy students - 6 students listed 3 elements 12%

215 Med. imaging students - 18 listed 3 elements 12.5% - 9 listed 4 elements 8 Interesting answers Sorry, forgot the LS Have not learned it before Have no idea L. nodes in armpits is all I know Trachea and breasts Pituitary Hypothalamus Q1: List four anatomical Thyroid gland elements of the LS Kidneys Adrenal glands Endocrine glands Liver Pancreas And the winner is: Lymphatic veins Blood “System of nerves, Veins which send signals Arteries from face to other organs” Intercostal spaces

9 Results

Q3: To study, or not to study the LS ?

To study the LS system - 296 students = 92.22%

Not to study the LS - 25 students = 7.78%

10 Results

 Not to study the LS - 25 students = 7.78% Medical Nursing Osteopathy imaging 1=2% 2 =3% 22=10.23% Not to study the LS because: - Not applicable - Too difficult to show on radiographic images - Not required for radiographic interpretation - Does not help us take images - Lymphatics can’t be seen on an X-ray - MRTs don’t need it - Only CT, MRI, sonographers and mammographers need it - Knowledge is not assessed academically - We can’t assess or detect the LS in an image 11 Recently an year-2 MI student shared:

“I don’t see what it has to do with bones and radiography.

I have never seen any knowledge of the LS been used in the clinical practice”

12 Results

TO STUDY the LS system - 296 students = 92.22% These students suggested an average of 3.64 hours

Provider Teaching time Unitec 0 to 15-20 minutes Fiji very similar Auckland Medical School 20-30 minutes NZ College of Chiropractic 4 hours Otago Medical School 4- 5 hours

13 Content D

1) Survey the current LS teaching D

2) History of the LS exploration C B

A

14 McCracken & Morris, (2001), New Atlas of Human Anatomy, London, Constable Publishers 2. History of lymphology - five periods

and molecular imaging of LS 19th AD - Today - “Modern”  Sappey, Poirier, Cuneo - French

 Mascagni (1755-1815), Cruikshank 17th - 18th AD - “Renaissance”  LS in the university curriculum Hunter (1715-1783) and Monroe (1733-1817)

 Integrating system of the body - Rudbeck (Forrester, 1996)

 Cysterna chyli - Percquet (1622-1674), Bartholini (1616-1680), Rudbeck (1630-1702) Thoracic duct - Eustachius (1500-1574) The Golden Age  Watery channels - Glisson (1597-1677) (Forrester, 1996)

 Milky veins - Aselli (1581-1626) (Choi, 2012)  Lympha - “Clear spring water” (Latin) http://www.gettyimages.co.nz/event/years-since- http://evolution.berkeley.edu/ the-birth-of-andreas-vesalius-510580389 evolibrary/article/history_02 16th - 17th AD - “Awakening” Vesalius (1514-1564) - founder of modern anatomy “De humani corporis fabrica ” - 1543 - Padua

1st BC - 16th AD – 1700 “Fruitless” years partially due to Galen’s doctrine

th st  Chyle - “juice”, “Peri Adenon” - Hippocrates (Grotte, 5 - 1 BC - “Fruitful” 1979)  “white veins” - Herophilus & Erasistratus (Lord, th 1968) 15 To 5 BC - “Prehistoric”  “... liquid “other than blood” (Chilky, 1997) The 16th - 17th “Golden age” Gaspar Aselli (1581-1626) - Italian

In 1622, while performing a vivisection on a well fed dog, Aselli rediscovered the lacteal vessels.

These remained unnoticed for:

- 18 centuries since described by Herophilus and Erasistratus

- 14 centuries since last reported by Galen Aselli published “De lactibus sive https://en.wikipedia.org/wiki/Gaspare_Aselli#/media/File:Aseli_Bassano.jpg Lacteis venis…” in 1627 16 17 http://www.vivo.colostate.edu/hbooks/pathphys/digestion/smallgut/absorb_lipids.html Aselli’s publication may well be the first to use coloured illustrations for better scientific clarity.

18 https://www.sophiararebooks.com/pages/books/3940/gaspare-aselli/de-lactibus-sive-lacteis- venis-quarto-vasorum-mesaraicorum-genere-novo-invento-dissertatio/?soldItem=true During Aselli’s time - early 17th century digestion was seen as:

Aselli thought, that the “milky veins” empty into the liver.

http://www.desicomments.com/de si/cartoons/fred-flintstone/page/5/

19 http://www.nature.com/ajg/journal/v103/n1s/full/ajg2008669a.html Francis Glisson (1597-1677) - English Published “De Rachitide” in1650 & “Anatomy of the liver” in 1665, And described the “Watery channels and hepatic lymphatics”

20 http://fn.bmj.com/content/78/2/F154 http://exhibits.hsl.virginia.edu/treasures/francis-glisson-1597-1677/ Jean Percquet (1622-1674) - French

In 1651, he published the discovery of:

http://www.sciencedirect.com/scienc e/article/pii/S0039606000022546

Chyli receptaculum = cisterna chyli = cisterna of Percquet

Thoracic duct, which drains into the venous system at the jugular- subclavian union

https://blog.lib.uiowa.edu/hardin/2014/08/07/notes-from-the-john-martin-rare-book-room-jean-pecquet/ https://en.wikipedia.org/wiki/Jean_Pecquet 21 Thomas Bartholin (1616-1680)-Dutch

https://www.generalanaesthesia.com/people/thomasbartholin.html

In 1952, he described cisterna chyli & thoracic duct in his book “Circulation via the lymphatic vessels” . 22 https://babel.hathitrust.org/cgi/pt?id=ucm.5327360967;view=1up;seq=7 http://cheap-auto-insurance-in-florida.com/learn-more-about-humanatlas23 - anatomy/human-atlas-anatomy-wink-books-the-best-there-isofanatomical- https://hagstromerlibrary.ki.se/uploads/images/1225/slideshow.jpg https://babel.hathitrust.org/cgi/pt?id=ucm.5327360967;view=1up;seq=7 by-frank-thoracic-duct-celiac-nodes-subclavian-trunk-lymphatic/ Olaus (Olof) Rudbeck (1630-1702) - Swedish Drew the entire LS

https://en.wikipedia.org/wiki/Olaus_Rudbeck

Diagram by Rudbeck - 1656

https://hagstromerlibrary.ki.se/books/16113

24 https://hagstromerlibrary.ki.se/books/16113 Rudbeck suggested, that similarly to the nervous and the endocrine systems, the LS is an integrating system of the entire body. (Forester, 1996)

25 By 1650 it was known that:

Cisterna chyli is located: - at level T12 - L2 - between aorta and IVC The cisterna receives - two lumbar trunks - intestinal trunks - descending thoracic and hepatic trunks C - renal & suprarenal trunks B Thoracic duct: - length - 38 to 45 cm, diameter - 3-5 mm A - through aortic hiatus ascends in the posterior mediastinum between aorta and azygos vein - from T5 gradually inclines to the left - runs posterior to the left subclavian artery - joins the left subclavian / jugular vein with a valve 2

McCracken & Morris, (2001),6 New Atlas of Hu Anatomy, London, Constable Publishers https://www.pulsus.com/scholarly-articles/azygos-ladder-and-looped-thoracic-duct--a-case-report.html 27 What was not clear yet was the LS of

McCracken & Morris, (2001), New Atlas of Human 28 Anatomy, London, Constable Publishers Niels Steensen (1638-1686) - Danish

Right Founder of lymphatic modern geology duct

A bishop

Why not an anatomists too?

https://en.wikipedia.org/wiki/Nicolas_Steno

https://www.ncbi.nlm.nih.gov/pubmed/20559086

McCracken & Morris, (2001), New Atlas of Huma Anatomy, London, Constable Publishers 29 CSF

https://plasticsurgerykey.com/lymphedema/ SVC 30 History of lymphology

19th AD - Today “Modern”

 Injecting of mercury into lymphatics P. Mascagni (1755 - 1815), Cruikshank 17th-18th AD-“Renaissance”  LS in the university curriculum W. Hunter (1715-1783) and A. Monroe (1733-1817)

16th - 17th AD - “Awakening”

1st BC - 15th AD – 1500 “Fruitless” years

5th - 1st BC - “Fruitful”

To 5th BC - “Prehistoric” 31 The LS gained popularity, when two famous 18th century anatomists included the LS in the curriculum of the universities they worked for.

English - William Hunter (1715-1783) Scotish - Alexander Monro Jr. (1733 1817)

The Hunter-Monro controversy

http://neurology.mhmedical.com/data/ https://pbs.twimg.com/medi https://en.wikipedia.org/wiki/William_Hunter_(anat https://en.wikipedia.org/wiki/Alexander_Monro_(secun books/1477/rop_ch29_f001.png a/CaEyzQLUsAEqGFQ.jpg omist)#/media/File:William_Hunter_(anatomist).jpg dus)#/media/File:Alexander_Munro_secundus.jpg

John Hunter 32 https://en.wikipedia.org/wiki/John_Hunter_(surgeon https://en.wikipedia.org/wiki/William_Hunter_(a )#/media/File:John_Hunter_by_John_Jackson.jpg natomist)#/media/File:Hunterw_table_12.jpg Paolo Mascagni - (1755 - 1815) - Italian

In 1771, Mascagni introduced the dyeing of lymphatics with mercury

This technique enabled him to determine, that: http://library.uthscsa.edu/2014/03/a-landmark-in-anatomical- illustration-paolo-mascagni-and-the-lymphatic-system/ - lymphatics are related to absorption

- lymphatics originate from interstitial space & serous cavities

Mascagni mapped, named and described ALL principal lymphatic vessels and nodes

33 Published by Pazzini Carli, Siena, 1787 https://en.wikipedia.org/wiki/Paolo_Mascagni Published in 1787

.

34 https://nz.pinterest.com/pin/409053578625829100/ https://pictures.abebooks.com/MILESTONEBOOKS/18765559530_5.jpg In the same 1787 year Cruikshank located the breast - axilla l. pathway using mercury.

But, once again, the LS was forgotten for almost a century until

1874, when M. Ph. C. Sappey (1810-1896) published the mercury based superficial lymphatic drainage of the torso.

35 https://en.wikipedia.org/wiki/Marie_Philibert_Constant_Sappey Cutaneous lymphatics by Sappey Surgical cutaneous incisions to be parallel to the lymphatic vessels

Watershed L2

https://www.researchgate.net/publication/304358392_Lymphosome_conce pt_Anatomical_study_of_the_lymphatic_system_Lymphosome_Concept https://clinicalgate.com/diseases-of-the-lymphatic-circulation/ 36  19th AD - Today - “Modern” Immunology & molecular imaging  Sappey, Poirier, Cuneo – all French

Poirier & Cuneo

A 1903 diagram of the breast lymphatics by Poirer & Cuneo as seen in the Gray’s Anatomy.

https://www.researchgate.net/figure/5803842_fig8_FIG-8-Poirier-and- Cuneo-O-s-summary-diagram-of-the-breast-lymph-drainage-26-This By the end of the 19th - beginning of 20th century the LS mapping was completed on a macroscopic level. 37 EMBRYOLOGICAL DEVELOPMENT Starts at 5th week (Heart beats at 3rd week)

 Jugular lymphatic sacs  Cisterna chyli  Mesenteric lymphatic sac

https://healtheappointments.com/chapter-2-abdomen-essays/13/

 Iliac lymphatic sacs http://www.neonatology.org/classics/hess1922/hess.3.html38 This theoretical basis is used for injection of dye and/or isotope for sentinel node mapping and biopsy.

https://www.researchgate.net/publication/236277213_Map ping_Superficial_Lymphatic_Territories_in_the_Rabbit

UPPER LATERAL

39 https://www.researchgate.net/publication/5803842 The Lymphatic Anatomy of the https://www.researchgate.net/figure/236277213_fig4_Figure-5-The- Breast and its Implications for Sentinel Lymph Node Biopsy A Human Cadaver Study lymphatic-vessels-white-arrow-ran-along-the-thoracodorsal-vein-black Lymphology Quo Vadis?

Your current. teaching needs updating

40 REFERENCES:

Chilky, A., (1997). Who Discovered the Lymphatic System? Lymphology, 30: p. 186-193. Lord, R.S., (1968). The White Veins: Conceptual Difficulties in the History of the Lymphatics Medical History, Cambridge Journals Medical History12(2): p. 174-184. Grotte, G., (1979). The Discovery of the Lymphatic Circulation. Acta Physiologica Scandinavica. Supplementum,. 463: p. 9-10. Choi, I., Lee, S., Hong, Y.K., (2012). The New Era of the Lymphatic System: No Longer Secondary to the Blood Vascular System. Cold Spring Harbor Perspectives in ,. 2(4): p. 1-23. Forrester, J.M., (1996). English manuscripts of Francis Glisson: from Anatomia hepatis 1654. Medical History, 40(1): p. 121. Miller, J.F., (2002). The Discovery of Thymus Function and of Thymus-derived Lymphocytes. Immunological reviews, 185: p. 7-14. Witte, M.H., Witte, C. L., (1995). Epilogue: beyond the sphere of knowledge in lymphology. Clinics in , 13(5): p. 511-514. Pal, I., Ramsay, J. D., (2011) The Role of the Lymphatic System in Vaccine Trafficking and Immune Response. Advanced Drug Delivery Reviews,. 10(63): p. 909-922. Patel, K.M., Moxham, B.J., The relationships between learning outcomes and methods of teaching anatomy as perceived by professional anatomists. Clin Anat. 2008 Mar;21(2):182-9. doi: 10.1002/ca.20584. Dillaman, R.M., Roer, R. D., Gay, D. M., (1991). Fluid movement in bone: theoretical and empirical. Journal of Biomechanics, 24: p. 163-177. Weller, R.O., Galea, I., Carare, R. O., Minagar, A., (2010). Pathophysiology of the lymphatic drainage of the central nervous system: Implications for pathogenesis and of multiple sclerosis. Pathophysiology, 17(4): p. 295-306. IIiff, J., Wag, M., Liao, Y., Plogg, B.A., Peng, W., Gundersen, G. A., Benveniste, H., Vates, G. E., Deane, R., Goldman, R., Nagelhus, E. A., Nedergaard, M., (2012) A paravascular pathway facilitates CSF flow through the brain parenchyma and the clearance of interstitial solutes, including amyloid β. Science Translational Medicine. 15(4): p. 147ra111. The Lymphatic Anatomy of the Breast and its Implications for Sentinel Lymph Node Biopsy: A Human Cadaver Study . Retrieved from: https://www.researchgate.net/publication/5803842 The Lymphatic Anatomy of the Breast and its Implications for Sentinel Lymph Node Biopsy A Human Cadaver Study Netter, F., (2006) Atlas of Human Anatomy, 4th edition Older, J., Anatomy: a must for teaching the next generation. Surgeon. 2004 Apr;2(2):79-90. Natale, G., Bocci, G., Ribatti, D., (2017) Scholars and scientists in the history of the lymphatic system. Journal of Anatomy. DOI: 10.1111/joa.12644. Web link http://onlinelibrary.wiley.com/doi/10.1111/joa.12644/full

41