il tessuto adiposo come matrice rigenerativa: come… · il tessuto adiposo come matrice...

Bari, 13-15 giugno 2013Bari, 13-15 giugno 2013

NUOVE FRONTIERE IN CHIRURGIA NEOPLASTICA RICOSTRUTTIVANUOVE FRONTIERE IN CHIRURGIA NEOPLASTICA RICOSTRUTTIVA

IL TESSUTO ADIPOSO COME MATRICE IL TESSUTO ADIPOSO COME MATRICE RIGENERATIVA: RIGENERATIVA:

COME, PERCHE’, DOVE, UTILITA’COME, PERCHE’, DOVE, UTILITA’

Dipartimento di Chirurgia Generale Novi L.- TortonaDipartimento di Chirurgia Generale Novi L.- TortonaDirettore: Dr. P. Tava

SOS SenologiaSOS Senologia Responsabile: Dr.ssa M.G. Pacquola

Dr. Pier Carlo RassuDr. Pier Carlo Rassu

20112011


Lipofilling timeline Lipofilling timeline

18931893 - Neuber transferred a small piece of arm fat tissue to correct a scar depression in the

face

18951895 - Czerny first described fat transplantation to the breast using a large lipoma

19111911 - Bruning first described fat transplantation as a injectable procedure using a syringe

1912 - Hollander achieved natural-appearing results for correction of lipoatrophy of the face

1921 - Lexer was the first to propose free fat graft taken from the abdomen or hips for

augmentation mammaplasty

1926 - Miller had applied fat grafting to cicatricial contraction of the face and neck

1975 - Fisher started liposuction and allowed collection of fat that could be applied as graft

1983 - Illouz reported first trial of 3000 fat grafting applied to iatrogenic deformities and facial

lipodystrophies


Lipofilling timeline Lipofilling timeline

19871987 – Bircoll first described the procedure of fat liposuction and transplantation to the breast

by transcutaneous injection

19871987 - American Society of Plastic and Reconstructive Surgeons banned fat gafting because

would compromise breast cancer detection for microcalcifications

19971997 – Coleman described the “lipostructure technique’’ as less traumatic methods of

harvesting, processing, and injecting

20072007 - French Society of Plastic Surgery sent a recommendation to the French plastic

surgeons to postpone the lipofilling in the breast with or without breast cancer history unless it

is carried out under prospective controlled protocol

20092009 - American Society of Plastic Surgeons set up a task force (ASPS Fat Graft Task Force)

to assess the indications, the safety and efficacy of autologous fat grafting


Lipofilling focused on Lipofilling focused on breast reconstructionbreast reconstruction


current recommendation grade for fat grafting is level B

AuthorAuthor YearYear Pubblication typePubblication type N° of pzN° of pz RecurrenceRecurrenceLipofillig from Lipofillig from

surgery surgery (months)(months)

Follow up from Follow up from

oncologic oncologic surgery (months)surgery (months)

ConclusionsConclusions

Petit J.Y.Petit J.Y. 2013 Matched-cohort study 59 (118)Intra epithelial neoplasia: 18%

p = 0.02? > 60> 60

Ki67>14, age < 50, High grade more

studies

Petit J.Y.Petit J.Y. 2012 Retrospective matched-cohort study 321 (642)CIV 8 p = 0.7920.792 HR 1.1HR 1.1

DIN/LIN 3 p < 0.00126 56 Safe, more studies,

attention in DCISattention in DCIS

Claro F.Claro F. 2012 Systematic review (60 articles, 4601 pz) 616 (3 studies) 14 ? 45.2 Safe, more studies

Schultz I.Schultz I. 2012 Retrospective 44 0 ? ? No conclusions

Seth A.K.Seth A.K. 2012 Retrospective 99 (vs 1112) 0 18.3 ? Safe, more studies

Petit J.Y.Petit J.Y. 2011 Multicenter study513 (405 CIV, 108

DCIS) Loco regional event rate 2.4% 39.7 19.219.2more studies (evidence IV)(evidence IV)

Losken A.Losken A. 2011 Retrospective 107 ? ? ? ?

Rietjens M.Rietjens M. 2011 Prospective 155 (158) 1 35 ? (18 months from lipofilling)

Safe,more studies

Rosing J.H.Rosing J.H. 2011 Systematic review (17 articles) 1658 2 (only one article) ? 62 (1-180) More studies

Sarfati I.Sarfati I. 2011 Retrospective 28 0 6 (from RT) 17 No conclusions

Panettiere P.Panettiere P. 2011 Case report 1 0 36 49.5 More studies

Rigotti G.Rigotti G. 2010 Retrospective 137 (911) 5 20 8484 Safe, no local recurrences

Elfadl D.Elfadl D. 2010 Review (12 articles) 433 ? ? ? More studies

Salgarello M.Salgarello M. 2010 Case report 2 0 6 (from RT) ? No conclusions

Illouz Y.G.Illouz Y.G. 2009 Retrospective 381 ? 12 ? No conclusions

Panettiere P.Panettiere P. 2009 Case report 20 ? ? ? No conclusions

Delay E.Delay E. 2009 Retrospective 880 ? ? ? No conslusions

Chan C.W.Chan C.W. 2008 Review (7 articles + 1 Poland) 460 ? ? ? No conslusions

Missana M.C.Missana M.C. 2007 Retrospective 69 (74) ? ? ? No conslusions

Coleman S.R.Coleman S.R. 2007 Retrospective 17 ? ? ? ?

Lipofilling focused on breast CANCER reconstructionLipofilling focused on breast CANCER reconstruction


Il tessuto adiposo come matrice rigenerativa: Il tessuto adiposo come matrice rigenerativa: PERCHE’PERCHE’

Resorbable Filler: “AUTOLOGOUS” fat graft

(no histological analysis of complications has been published)

Fat is viewed as the ideal filler: soft, non-allogenic, widely available, easily collected, and transplantation is straight forward with minimal morbidity

Adipose tissue has the highest percentage of adult stem cells of any tissue in the body, with as many as 5000 adipose-derived stem cells per gram5000 adipose-derived stem cells per gram of fat compared with 100 to 1000 stem cells per milliliter of bone marrow

Autologous procedures prevent the risk o f complications associated with the presence of a foreign body as prostheses. Lipomodelling achieves stable long-term improvement and volume can be considered permanent after 6 monthspermanent after 6 months



Histological analysis show that transplanted fat tissue is more compact is more compact than normal onethan normal one and clearly distinguishable for:

- Adipocytes ranging in size from 40 to 80 µm (normal > 100 µm)

- Absence of fibrosis

- Small blood vessels between the fat lobules

Resorbable Filler: “AUTOLOGOUS” fat graft



The rationale for combining whole fat or lipoaspirate is that the organized fat tissueorganized fat tissue may serve as a scaffoldas a scaffold upon which more concentrated stem/progenitor cells can organize and differentiate

An attractive approach for guiding the three-dimensional organization of tissue reconstruction is through the use of scaffolding which may be mineral, synthetic polymers or biological and may incorporate growth factors naturally.


Tolerance to ischemia differs between various cell types and between a differentiated and an undifferentiated state.

Adipocytes tolerate an ischemic period of 4 days4 days maximum after adipose tissue transplantation: in ischaemic conditions, these cells either die, survive or undergo dedifferentiation e dedifferentiated cells can re-accumulate fat and differentiate into adipocytes when an adequate vascular supply is re-established.

Immature preadipocytes have a higher tolerance to ischemia than mature adipocytes


Resorbable Filler: the physiology of fat grafts

Initially, the graft survives via direct diffusion of nutrients from plasma. Thus, smaller grafts, with higher surface area to volume ratios have an advantage over larger grafts, as a greater proportion of the graft is in contact with the graft bed. This facilitates revascularisationrevascularisation, which occurs as early as 48 h post transplantationoccurs as early as 48 h post transplantation. Large grafts exhibit higher rates of liquefaction, necrosis and cyst formation, while too small a graft volume is associated with resorption. To ensure maximal take, many surgeons practice repeated transfers.


Most of the volume loss occurs within the first 4-6 months4-6 months following surgery

Delay’s “twice 30% rule”Delay’s “twice 30% rule”

30%30% of the harvested volume is lost during centrifugation and preparation

30%30% during the first 4 months after surgery due to resorption

15-22% of patients required a repeat procedure because of volume resorption

Resorbable Filler: the physiology of fat grafts



Adipose-derived stem cells are isolated from the vascular stromal componentvascular stromal component of lipoaspirate. A standard lipoaspirate is composed of mature adipocytes, extracellular matrix, adipose stem cells, endothelial cells, mural cells (pericytes and vascular smooth muscle cells)

Il tessuto adiposo come matrice rigenerativa: Il tessuto adiposo come matrice rigenerativa: COMECOME

Subpopulations of Adipose Stem Cells

- Mature endothelial with the endothelial marker CD31- Endothelial stem cell with both CD31+/34+. - Adipose stem cell with CD34+ - Pericyte adjacent to the endothelial cells with CD146+/90+

Recent studies also show that ASCs are able to differentate into tissues of ecto-ecto- and endodermalendodermal lineages such as



Adipose Stem Cells are of mesodermalmesodermal origin, they have the potential to differentiate into multiple lineages of:

adipogenic osteogenic

chondrogenic myogenic

cardiomyogenicangiogenic tenogenic

periodontogenic lineages

neural cellshepatocytes

pancreatic islet cells endothelial cellsepithelial cells

To minimize fat graft loss, studies have shown benefits offered by less traumatic methods of harvesting, processing, and injecting.

Microinjection of fat via the ‘‘lipostructure technique’’ or the “Coleman’s technique” distributes fat grafts in small aliquots by injection through multiple tunnels



The concept of structural fat graftingstructural fat grafting is that the fat must be inserted in small amounts using multiple tunnels, in many layers and directions, so that the largest possible number of adipocytes are in contact with host tissue and thus receive adequate nutrition for their survival


Coleman’s technique:Coleman’s technique: fat harvestingfat harvesting


Blunt liposuction cannula of Ø 3 mm, connected to a 10 ml syringe with low pressure vacuum created by withdrawing the plunger 2-3 cc

Klein solution: Ringer’s lactate 1000 ml, Lidocaine 25 ml, Adrenaline 1 ml, Sodium bic. 8,4% 12,5ml

The cannula is passed rapidly to and from within the subcutaneous tissue with minimal trauma to neurovascular bundles, dermis and fibrous septa

Low vs high pressure method with liposuction detected a significant difference (p < 0.05) in levels of apoptotic enzymatic activity and cell viability in favour of Coleman’s method


Coleman’s technique: Coleman’s technique: fat processing / preparationfat processing / preparation


Centrifugation


fat preparationfat preparation


“No touch technique”: fat is harvested and immediately injected into the recipient site without any processing. In this way, no blood or tumescent solution is aspirated, allowing the collection of pure fat

Sedimentation

Washing with 5% glucose solution, 0.9% normal saline or sterile water before centrifugation

Filtration: fat is placed on sterile gauze over a sterile cup, the fat is carefully washed with Ringer’s lactate and dried before loading into syringes

Towel-processed: fat aspirates are placed on to sterile cotton towels, which absorb blood, oil and fluids, before loading into syringes.


Coleman’s technique: Coleman’s technique: fat preparationfat preparation


Centrifugation Centrifugation

separates fat from substances that increase degradation: blood proteases, lipases

concentrates adipocytes resulting in an increased number of adipocytes per millilitre of fat transplanted

concentrate the adipose stem cell fraction

Centrifugation is commonly performed at 3000 rpm for 3 min



Coleman’s technique:Coleman’s technique: fat injectionfat injection

Fat is injected in small parcels and thin strips, at different levels in the subcutis. The volume of fat injected varies between practitioners from 0.2 ml per pass, to 2-3 ml fat per tunnel

5 principles of lipofiling5 principles of lipofiling

1) the ideal plane for breast autologous fat injection is the subcutaneous tissuesubcutaneous tissue, which is rich in adipose tissue and subsequently has a rich blood supply.

2) Injection method has to be in a radial retrograde fashionradial retrograde fashion, using the ‘‘drop-to-drop’’ technique‘‘drop-to-drop’’ technique and injecting in different planesdifferent planes.

3) the final expected result of breast fat grafting should not be the aim of a single procedure but rather that of a multisession proceduremultisession procedure in order to prevent major complications

4) the division of the breast into four cosmetic units and systematic lipofilling of those cosmetic unitssystematic lipofilling of those cosmetic units in each treatment session

5) 3-month interval3-month interval between treatment sessions is needed in order to perform successful fat grafting in the breast.



Il tessuto adiposo come matrice rigenerativa: Il tessuto adiposo come matrice rigenerativa: DOVEDOVE

- Filler for defects following breast-conserving surgery- In implant reconstructions to improve implant coverage and mask implant rippling- Correction of contour deformities after flap reconstruction (TRAM/LD, etc.)- In small breasts, it may be one option for reconstruction following breast-conserving surgery- To improve skin quality/soft tissue cover after mastectomy and radiotherapy- As a total breast reconstruction - Treatment of postmastectomy pain syndrome

Autologous fat transfer is widely used in plastic surgery for both reconstructive and aesthetic purposes

breast surgerybreast surgery


current recommendation grade is level D

Il tessuto adiposo come matrice rigenerativa: Il tessuto adiposo come matrice rigenerativa: UTILITA’UTILITA’

Monocentric studyMonocentric studyIST - S.Martino Hospital - University of GenoaIST - S.Martino Hospital - University of Genoa

Dati cortesemente forniti dalla Cattedra di Chirurgia Plastica e Ricostruttiva, Università degli Studi di Genova Dati cortesemente forniti dalla Cattedra di Chirurgia Plastica e Ricostruttiva, Università degli Studi di Genova

Direttore: Prof. PL SantiDirettore: Prof. PL Santi

Dati cortesemente forniti dalla Cattedra di Chirurgia Plastica e Ricostruttiva, Università degli Studi di Genova Dati cortesemente forniti dalla Cattedra di Chirurgia Plastica e Ricostruttiva, Università degli Studi di Genova

Direttore: Prof. PL SantiDirettore: Prof. PL Santi

Monocentric studyMonocentric studyIST - S.Martino Hospital - University of GenoaIST - S.Martino Hospital - University of Genoa

Bari, 13-15 giugno 2013Bari, 13-15 giugno 2013

NUOVE FRONTIERE IN CHIRURGIA NUOVE FRONTIERE IN CHIRURGIA NEOPLASTICA RICOSTRUTTIVANEOPLASTICA RICOSTRUTTIVA

Gustave Courbet, Gustave Courbet, The woman in the waves, The woman in the waves, 18681868

il tessuto adiposo come matrice rigenerativa: come… · il tessuto adiposo come matrice...

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