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“Focus on” : Linfedema e Lipedema Full Professor of General Surgery, Director Section & Research Center of Lymphatic Surgery, Lymphology, and Microsurgery. Operative Unit of General Surgery and Lymphatic Surgery. Postgraduate School of Alimentary Tract Surgery (Confederated with Pisa, Florence and Siena) University Polyclinic Hospital San Martino National Institute for Cancer Research, Genoa, Italy [email protected] www.lymphaticsurgery.org Corradino Campisi, MD, PhD, FACS

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“Focus on”: Linfedema e Lipedema

Full Professor of General Surgery, Director Section & Research Center of Lymphatic Surgery, Lymphology, and Microsurgery.

Operative Unit of General Surgery and Lymphatic Surgery.Postgraduate School of Alimentary Tract Surgery

(Confederated with Pisa, Florence and Siena) University Polyclinic Hospital San MartinoNational Institute for Cancer Research,

Genoa, Italy

[email protected] www.lymphaticsurgery.org

Corradino Campisi, MD, PhD, FACS

Lymphedemas

Paris, 1974

President: Prof. Corradino Campisi,MD, PhD. FACS Genoa, Italy

1989 -19901980 - 1981

1965

CHRONIC LIMB LYMPHEDEMATOSATTI’S CLASSIFICATION (1967)

LYM

PHED

EMA

Congenitial with praecox or tardive manifestation

Acquired (there is almost always a congenital manifestation, or else why do they occur?)

Upper Limb (rare: those not secondary to mastectomy)

Lower

Limb

stasis in the interstitialspace and collectors

from gravitationalreflux , from hypoplasia or from dysplasia, from obstruction, from ↑ lymphogenesis

Insufficiency of the collectors (valvular and parietal) and lymph-nodal

Familial praecoxneuro-endocrinal(pubertal, pregnancy, menopausal), postraumaticpostinflammatory(postlymphangitis, postphlebitis, etc.), from radiation, neoplastic(primitive or secondary)

Mixed: associated with phlebopathies, and more rarely with arteriopathies

LYMPHEDEMA CLASSIFICATION(ETIOLOGICAL BASIS)

CONGENITAL OR PRIMARY ACQUIRED OR SECONDARYFROM BIRTH

(CONNATAL)

0-2 Years

PRAECOX < 35 yrs

TARDIVE > 35 yrsSPORADIC

HEREDITARY

(FAMILIAL)

LAAD

LAD I

LAD II

POST-LYMPHANGITIS

POST-SURGICAL

POST-RADIATION

POST-TRAUMATIC

POST-FILARIAL

C.Campisi, 2001

LEGEND:LAD I: LYMPHANGIODYSPLASIALAD II: LYMPHADENODYSPLASIALAAD: LYMPHANGIO-ADENO-DYSPLASIA (C.Papendieck, 2001)

ISL Consensus Document (by C. Campisi, 2009)

STAGING FOR PROGNOSIS OF LYMPHEDEMA

INFLAMMATION!

STAGING FOR PROGNOSIS OF LYMPHEDEMA Lymph Nodal Impairment

I

II

III

Lymph Vessel Impairment Interstitial Matrix

By E. Fulcheri, C. Campisi, F. Boccardo et al.

LymphostasisInflammation & ExcessFibro-Adipose Tissue

Pre-Op and Post-Op EvaluationsClinical ParametersEcho Color Doppler (V/A)

Lymphoscintigraphy (S/P & T. I.)I. G. F. Microlymphography – PDE Test

Derivative Lymphatic Microsurgery

represents, today, the most effective therapeuticprocedure, when performed in the earliest stages of

Peripheral Lymphedema, according to our long clinicalexperience and related long-term clinical outcomes

(>20 yrs)

Single-Site Multiple Lymphatic Venous Anastomoses (MLVA)

Reconstructive Lymphatic-Vein-LymphaticAutologous Interpositioned Graft - Multiple LVLA

An alternative Microsurgical option for casesof Phlebo-Lymphedema with stable and persistent Venous Hypertension (early 1980s)

Single-Site Lymphatic Anastomoses

• MLVA or MLVLA are performed at a single adaptable incision (inguinal-crural region or upper- middle third of the volar surface of the arm ) using both superficial and deep lymphatic vessels, previously stained with blue dye

Campisi CC, Ryan M, Boccardo F, Campisi C. A single-site technique of multiple lymphatic venous anastomoses for the treatment of peripheral lymphedema: Long term clinical outcomes. J. Reconstr Microsurg, 2016 Jan;32(1):42-9.

Single Site:upper-middle third of the volar surface

of the upper arm

Long-Term StableResults

PRE-OP POST-OP

PRE-OP POST-OP

Single Site:inguinal - crural region

Long-TermStableResults

Preop.

Postop.

Preop. Postop.

Preop.

Postop.

The rationale behind the single-site approach is twofold …

Single-Site Lymphatic Anastomoses

Campisi CC, Ryan M, Boccardo F, Campisi C. A single-site technique of multiple lymphatic venous anastomoses for the treatment of peripheral lymphedema: Long term clinical outcomes. J. Reconstr Microsurg. 2016 Jan;32(1):42-9.

Single-Site Lymphatic Anastomoses

1) Lowered Infection Risk:

- A single incision means less surface area exposed to microbes

- The incision is made proximally:

In our experience, infections are more likely to occur distally, starting in the hands and feet. This is most likely due to the poor mobilization of immune cells to lymph nodes due to chronic lymph stasis

Campisi CC, Ryan M, Boccardo F, Campisi C. A single-site technique of multiple lymphatic venous anastomoses for the treatment of peripheral lymphedema: Long term clinical outcomes. J. Reconstr Microsurg. 2016 Jan;32(1):42-9.

Single-Site Lymphatic Anastomoses

2) Increased Vessel Caliber

- Larger Lymphatic vessels are easier to use for anastomoses

Campisi CC, Ryan M, Boccardo F, Campisi C. A single-site technique of multiple lymphatic venous anastomoses for the treatment of peripheral lymphedema: Long term clinical outcomes. J. Reconstr Microsurg. 2016 Jan;32(1):42-9.

2) Increased Vessel Caliber

- Larger Lymphatic vessels allow a greater flow of lymph through each anastomosis

- Multiple LVA are created in close proximity to vein valves; thus the suction induced by these valves is sufficient to overcome the differential pressure

- Lymph is immediately pulled into the vein, preventing thrombosis of the anastomoses

Single-Site Lymphatic Anastomoses

Campisi CC, Ryan M, Boccardo F, Campisi C. A single-site technique of multiple lymphatic venous anastomoses for the treatment of peripheral lymphedema: Long term clinical outcomes. J. Reconstr Microsurg. 2016 Jan;32(1):42-9.

Single Incision

Single Operating Microscope

Multiple Anastomoses(Superficial & Deep)

Multiple Long-Term Effectiveness

Single-Site Multiple LVA

Corradino Campisi & Coll., Genoa, Italy 2017

‘TIMING’: EARLYApplication = LONG-TERM

results!

Genoa Protocol, 2007-2017

CLyFT for LYMPHEDEMAComplete Lymphedema Functional Treatment

Staging - Guided

LM FLLA-LVSP

LYMPHEDEMA STAGING - “SINGLE-SITE” LYMPHATIC MICROSURGERY - PROGNOSIS

1973-2017 4192 Cases Treated by Microsurgery MLVA / MLVLA (FU 5 – more than 20 Years)

Long-Term, Stable Results

0

500

1000

1500

2000

Lower Limb Upper Limb

Primary Lymphedema Secondary Lymphedema

MLVA / MLVLA 1973 - 2017> 80% rate of stable Volume Reduction in the

earliest stages (IB-IIA)

P < 0.01

By C. CampisiLong-Term, Stable Results

LYMPHATIC “SINGLE-SITE” MICROSURGERY GENOA PROTOCOL - 2016

F = Fast (Length of Surgery: 15’-20’ / Anastomosis – 60’-150’ / in total)I = Increasing (both Lymph TransportCapacity & Patient Turnover)E = Effective (Significant Edema Volume Reduction in the Long-Term)R = Recovering (High-Grade Clinical & QoL Restoration)A = Aesthetic (Remarkable & StableCosmetic Results) E = Economic (Low-Cost Surgeryrequiring only 1 OpMi & 2 Surgeons, according to the available budget in everyhospital, in every area of the world!)

MLVA / MLVLA Microsurgery

=F.I.E.R.A.E.Microsurgery

NEW ADVANCES

For Advanced Stages of Lymphedema (IIB-III) LM is able to give onlypartial results.

That is why we developed a “Lymph Vessel Sparing Procedure (2012)”, with Liposuction-Like technique (i.e. Selective Liposuction) that is called:

FIBRO-LIPO-LYMPH-ASPIRATION (FLLA-LVSP)

The aim of the new FLLA-LVSP procedure is to remove the remaining excess fibro-adipose tissue of the lymphedematous limb

previously treated by MLVA.

FLLAPathophysiological Basis

Aspirated Material from the Liposuction Technique, without any treatment, in a transparent container

Typical Stratification after Formalin Fixation :Supernatant Serum (top), Fat Corpuscles, Blood Serum (bottom)

E. Fulcheri, C. Campisi& Coll. (2012)

Thickened and Fibrous Connective Tissue with small Blood and Lymphatic Vessels E.E. 10 - 20x

CD 31 CD 34

Lymphatic Vessels and Walls with Markedly thickened Peri-Adventitial MatrixThe endothelium of the vessel is clearly positive to immunohistochemical staining with antibodies to CD31. IIC - CD31, 10x and to antibodies

to CD31. IIC - CD34, 10x

E. Fulcheri, C. Campisi& Coll. (2012)

LymphostasisInflammation & ExcessFibro-Adipose Tissue

How Can We Avoid Lymphatic Vessel Injuries during Liposuction?

- Lymphoscintigraphy- Lymphochromic Test by Blue Patent Violet (BPV)

- IndoCyanine Green Fluorescent Microlymphography with PDE Test

- EchoDoppler Mapping of the Principal Superficial Veins in closeproximity to the Lymphatic Network

Progression of Volume Loss with Combined Surgical Treatment

Pre - Surgery Post - MLVA Post - FLLA

MLVA + FLLA

MLVA + FLLA

Surgery Without Age Limits!

70 Yrs

LYMPHEDEMA STAGING - LYMPHATIC MICROSURGERY PROGNOSIS

LYMPHEDEMA

PREVENTION TREATMENT

TO AVOID LYMPHATIC

INJURIES LY.M.P.H.A.* EARLY

STAGELATE

STAGE

MultipleLVA**

MultipleLVLA***

(*) Lymphatic Microsurgical Preventive Healing Approach

(**) Lymphatic Venous Anastomoses (Multiple)(***) Lymphatic Venous Lymphatic Anastomoses(****) Fibro-Lipo-Lymph-Aspiration

by Lymph Vessel Sparing Procedures

1. Multiple LVA **/ LVLA ***

2. FLLA – LVSP ****

EARLY ‘Single-Site’ MLVA Application Avoids LATER Surgery !‘TIMING’!

LIPEDEMALIPEDEMA is a localized swelling of the lower limbs, which is:

• Bilateral• Symmetrical• With a soft consistency• Develops due to the build-up of adipose tissue• “Chaps-style”, starting from the hips and moving down to the ankles

LIPEDEMAPATHOPHYSIOLOGY

Trigger Mechanism: Micro-angiopathy takes place in the adipose tissue leading to higher protein permeability and, at the same time, more fragile capillaries.

As a consequence of higher permeability, high-protein content fluid builds up in the surrounding cell area.

The skin bruises easily due to higher capillary fragility.

Skin resiliency is severely decreased, while skin compliance (skin stiffness, expressed in mmHg, measured with a special device) is increased: The skin loses its helping role as a venous pump in the lower extremities Macrophages, which can scavenge plasma proteins outside lymphatic vessels, are

rarely present in adipose tissues

The lymphatic system eventually becomes overloaded, leading to the onset of lipo-lymphedema in the later stages of disease

LIPEDEMADifferential Diagnosis

LIPEDEMA

TREATMENT

Combined Decongestion Therapy (CDT): • Manual and mechanical lymphatic drainage• Adequate elastic compression and/or proper short stretch bandages,• Therapeutic exercises,• Careful skin hygiene

Adequate BMI Control:• Weight loss program• Diet

Lymphatic Microsurgery:• Single-Site Lymphatic Anastomoses – MLVA• ‘Lymph vessel sparing’ Liposuction of excess adipose tissue – FLLA-LVSP

LIPO-LYMPHEDEMAPreop. Postop.

Single-Site Lymphatic Anastomoses

MLVA + FLLA

LIPO-LYMPHEDEMA

Chylous Disorders

Chylous and Thoracic Duct Disorders

Etiopathogenesis• Chylous dysplasias (45%)

• Thoracic Duct obstructions (15%)• Traumas and iatrogenic damages (15%)• Neoplastic involvement

of abdominal lymph structures• Infections (TBC)• Filariasis

(25%)

Thoracic Duct Dysplasia, Cisterna Chyli, and Chyliferous Vessel Dysplasia, Gravitational Reflux

Syndrome.

Clinical Manifestations

Chylothorax, Chylomediastinum, ChylopericardiumChylous Ascites, Mesenteric Cysts, Malabsorbment SyndromeChyluriaChyledema (lower limbs, external genitalia, other sites)Lymphostatic wartsChylous arthritisChyloceleChylometrorrhea-Chylocolporrhea

Primary (Dysplasia)

- Agenesis, Aplasia, Hypoplasia - Hyperplasia- Atresia- Stenosis- Multiple Fistulas- Cysts- Diffuse Dilatation

Secondary

- Stenosis (neoplastic, filariasis)- Dilatation (adhesions, phlogosis , neoplastic)- Traumatic

1) CHYLOUS DISORDERS NUMBER OF CASES

Chylothorax 49

Chyloperitoneum and AssociatedSyndromes

108

Chyledema 169

Chylous Gravitational Reflux Syndromes and Related Primary / Congenital or Acquired Disorders

Case Series 1973-2017

Diagnostic Protocol for Chylous Gravitational Reflux Syndromes and Related Primary / Congenital or

Acquired Disorders

2) DIAGNOSTIC PROTOCOL

- Blood tests: serum protein, albumin, triglyceride,cholesterol, calcium, and hemoglobin levels

- Thoracocentesis or paracentesis

- Functional Tests – (Fatty meal, a1-antitrypsin clearance, etc.)

- Imaging (US, Eco-Color-Doppler, Lymphoscintigraphy, Lymphochromic Test with Blue Patent Violet (BPV), Photo Dynamic Eye (PDE), Lymphangio-MR, Thoraco-abdominal CT scan, Direct Lymphography – CT)

- Video thoracoscopy or laparoscopy

Angio - CT

MRI

Lymphography

Lymphangio - MR

Treatment Protocol for Chylous Gravitational Reflux Syndromes and Related Primary / Congenital or

Acquired Disorders

3) BASIC MEDICAL TREATMENT PROTOCOL • Nutritional Management

Total Parenteral Nutrition – Hypo-alipid and Hyper-proteic Diet(Medium Chain Triglycerides - MCT) / Chiloil*

• Drug Management

Somatostatin Analogs / Octreotide

Antiobiotics

• Drainage of the Effusion (Thoracocentesis / Paracentesis)

Surgical Treatment Protocol for Chylous Gravitational Reflux Syndromes and Related Primary / Congenital or Acquired Disorders

(Chylothorax, Chyloperitoneum & Related Syndromes)

4) SURGICAL TREATMENT PROTOCOL (AFTER FATTY MEAL)- Drainage of Pleural / Peritoneal Chylous Effusion (Open / VATS / VLS)- Identification of the Site(s) of Chylous Leakage- Ruptured lymphatic vessels can be ligated, oversewn, or clipped- Treatment of the pleural / peritoneal leaking areas ( washing with sclerosing

drugs and Trémollières-like solutions; glues, and other optional haemo-lymphostatic materials ) / Talc Pleurodesis

- Reconstruction of the Thoracic Duct (T.D.-Azygos Vein Anastomosis) when possible (!)

- Thoracic Duct Ligation, if absolutely needed (!)- Removal of lymphocele, chylous cysts, and/or chylomas- Resection of Chylo-lymphangectasic-lymphangiodysplasic tissue (if present)- “Spaced-out” anti-gravitational ligatures of dysplasic and ectasic chylo-

lymphatic collectors- CO₂ LASER complementary welding- Derivative Multiple Lymphatic-Venous Anastomoses (MLVA) or

Reconstructive Multiple Lymphatic-Venous-LymphaticAnastomoses (MLVLA) Microsurgery, when possible and needed (!)

L-V-LShunts

Interposition of autologous vein

shunts

Valvular Continence

MLVA

Multiple LV Anastomoses, with optimal valvular continence of the superimposed vein segment.

A B

C D

A – drainage of chylous ascitesB - exeresis of lymphangestasic-lymphangiodysplastic tissuesC - chylous-venous shuntD – several liters of chyle removed during surgical treatment

Clinical Case49yr old woman with congenital thoracic ductdysplasia. The spontaneous rupture caused bilateralchylothorax, treated with thoracentesis and pleurodesis. Post-operatively, the patient developed a voluminous left cystic neoformation, laterocervicaland supraclavicular.

Some more of our clinical casuistry…

•Surgical excision of the elephantasictissue with assiociated derivative/ reconstructive lymphatic-venousmicrosurgery of the left thigh, and CO2

LASER Treatment of the lymphostaticpapillomatosis

•Congenital Chyledema with gravitationalreflux due to chylo-lymphangio-adeno-dysplasia of the left leg.•Saccular deformation of the medial surface of the left thigh with lymphostaticverrucae papillomatosis

After

Before

Before After

Spontaneous, recurrent, Chyloperitoneum related to Chylous-Lymphangio-Dysplasia.Reactive Chylous Peritonitis, Acute Appedicitis, and right Hydrocele

- Resection of chylous-lymphangio--dysplastic omentum. - Closure of multiple chylous-peritoneal fistulas with anti-gravitational ligatures-Appendectomy, cholecystectomy-Eversion/resection of tunica vaginalisof right testis

TAKE HOME MESSAGELymphatic Disorders Surgical Management

The Best Practice: State of the Art

Corradino Campisi & Coll., Genoa, Italy 2017

Modern Surgical Treatment of Lymphatic DisordersEBM Latest Main References 2000-2017

1. Dellachà A, Boccardo F, Zilli A, Napoli F, Fulcheri E, Campisi C. Unexpected Histopathological Findings in Peripheral Lymphedema. Lymphology 2000;33(Suppl):62-64.

2. Campisi C, Boccardo F. Vein graft interposition in treating peripheral lymphoedemas. Handchir Mikrochir Plast Chir. 2003 Jul;35(4):221-4.

3. Campisi C, Boccardo F. Microsurgical techniques for lymphedema treatment: derivative lymphatic-venous microsurgery. World J Surg. 2004 Jun;28(6):609-13.

4. Campisi C, Bellini C,Eretta C, Zilli A, Da Rin E, Davini, Bonioli E, Boccardo F. Diagnosis and management of primary chylous ascites. J VascSurg. 2006 Jun;43(6):1244-8.

5. Campisi C, Eretta C, Pertile D, Da Rin E, Campisi C, Macciò A, Campisi M, Accogli S, Bellini C, Bonioli E, Boccardo F. Microsurgery for treatment of peripheral lymphedema: long-term outcome and future perspectives. Microsurgery 2007;27(4):333-8;

6. Boccardo F, Bellini C, Eretta C, Pertile D, Da Rin E, Benatti E, Campisi M, Talamo G, Macciò A, Campisi C, Bonioli E, Campisi C. The lymphatics in the pathophysiology of thoracic and abdominal surgical pathology: immunological consequences and the unexpected role of microsurgery. Microsurgery 2007;27(4):339-45.

7. Pardini M, Bonzano L, Roccatagliata L, Boccardo F, Mancardi G, Campisi C. Functional magnetic resonance evidence of cortical alterations in a case of reversible congenital lymphedema of the lower limb: a pilot study. Lymphology 2007 Mar;40(1):19-25.

8. Bellini C, Boccardo F, Campisi C, Villa G, Taddei G, Traggiai C, Bonioli E. Lymphatic dysplasias in newborns and children: the role of lymphoscintigraphy. J Pediatr. 2008 Apr;152(4):587-9.

9. Campisi C, Da Rin E, Bellini C, Bonioli E, Boccardo F. Pediatric lymphedema and correlated syndromes: role of microsurgery. Microsurgery 2008;28(2):138-42.

10. Gloviczki P. Handbook of Venous Disorders. Third Edition. Guidelines of the American Venous Forum. Edward Arnold Publ. 2009;658-672.

11. Boccardo F, Casabona F, De Cian F, Friedman D, Villa G, Bogliolo S, Ferrero S, Murelli F, Campisi C. Lymphedema microsurgical preventive healing approach: a new technique for primary prevention of arm lymphedema after mastectomy. Ann Surg Oncol 2009: 16(3):703-8

12. Campisi C, Boccardo F. Sistema Linfatico. In: R. Bellantone, G. De Toma, M. Montorsi (eds.). Chirurgia Generale (Metodologia, Patologia, Clinica Chirurgica). Torino: Edizioni Minerva Medica; 2009:54.

13. Boccardo F, Bellini C, Girino M, Campisi C, Vidali F, Corazza GR, Campisi C. Diagnostic assessment and therapeutic approach for immunodeficiency due to chylous dysplasia: a case report. Microsurgery 2010 Jul;30(5):401-4.

14. Boccardo F, Campisi C, Murdaca G, Benatti E, Boccardo C, Puppo F, Campisi C. Prevention of lymphatic injuries in surgery.Microsurgery 2010 May;30(4):261-5.

15. Campisi C, Bellini C, Campisi C, Accogli S, Bonioli E, Boccardo F. Microsurgery for lymphedema: clinical research and long-term results. Microsurgery 2010 May;30(4):256-60.

16. Suami H, Chang DW. Overview of surgical treatments for breast cancer-related lymphedema. Plastic and Reconstructive Surgery Journal 2010 Dec;126(6):1853-63.

17. Lee B, Andrade M, Bergan J, et al. Diagnosis and treatment of primary lymphedema. Consensus document of the International Union of Phlebology (IUP)-2009. Int. Angiol 2010;29(5):454-70.

18. Boccardo F, Casabona F, Friedman D, Puglisi M, De Cian F, Ansaldi F, Campisi C. Surgical prevention of arm lymphedema after breast cancer treatment. Ann Surg Oncol 2011: 18(9):2500-5.

19. Witte MH, Dellinger MT, McDonald DM, Nathanson SD, Boccardo FM, Campisi CC, Sleeman JP, Gershenwald JE. Lymphangiogenesisand hemangiogenesis: potential targets for therapy. J Surg Oncol. 2011 May;103(6):489-500.

20. Campisi C, Boccardo F, Witte M, Bernas M. Lymphatic Surgery and Surgery of Lymphatic Disorders. In: Dieter R, Dieter Jr. RA, Dieter IIIRA (eds.). Venous and Lymphatic Diseases. New York, USA: Eds. The Mc Graw Hill Companies, Inc.; 2011 Chapter 42.

21. Campisi C, Campisi C, Boccardo F. Topics in cancer survivorship. Chapter 4 (pp. 43-52), Surgical prevention of arm lymphedema inbreast cancer treatment. InTech Publisher, January 2012.

Modern Surgical Treatment of Lymphatic DisordersEBM Latest Main References 2000-2017

22. Campisi CC, Spinaci S, Lavagno R, Larcher L, Boccardo F, Santi PL, Campisi C. Immunodeficiency due to chylous dysplasia: diagnostic andtherapeutic considerations. Lymphology 2012 Jun; 45(2):58-62.

23. Boccardo F, Campisi CC, Molinari L, Dessalvi S, Santi PL, Campisi C. Lymphatic complications in surgery: possibility of prevention andtherapeutic options. Updates Surg. 2012 Sep.;64(3):211-6. Epub 2012 Jul. 21.

24. Campisi CC, Larcher L, Lavagno R, Spinaci S, Adami M, Boccardo F, Santi PL, Campisi C. Microsurgical primary prevention of lymphaticinjuries following breast cancer treatment. Plast Reconstr Surg 2012 Nov;130(5):749-750.

25. Boccardo F, Fulcheri E, Villa G, Molinari L, Campisi C, Dessalvi S, Murdaca G, Campisi C, Santi PL, Parodi A, Puppo F, Campisi C.Lymphatic microsurgery to treat lymphedema: techniques and indications for better results. Ann Plast Surg 2012; 71:191-195

26. Campisi C, Boccardo F, Campisi C.C. Patologia dei Linfatici. In: Carlo Setacci (ed.). Chirurgia Vascolare. Turin:Italy. Edizione MinervaMedica;2012:Chapter18.

27. Campisi CC, Larcher L, Lavagno R, Spinaci S, Adami M, Boccardo F, Santi P, Campisi C. Microsurgical primary prevention of lymphaticinjuries following breast cancer treatment. Plast Reconstr Surg. 2012 ;130:749-750

28. Campisi CC, Boccardo F, Piazza C, Campisi C. Evolution of chylous fistula management after neck dissection. Curr Opin OtolaryngolHead Neck Surg. 2013 ;21: 150-156

29. Campisi C, Boccardo F, Campisi CC, Ryan M. Reconstructive microsurgery for lymphedema: while the early bird catches the worm, thelate riser still benefits. J Am Coll Surg. 2013;216:506-7

30. Ryan M, Campisi CC, Boccardo F, Campisi C. Surgical treatment for lymphedema: optimal timing and optimal techniques. J Am CollSurg. 2013;216:1221-3.

31. Morotti M, Menada MV, Boccardo F, Ferrero S, Casabona F, Villa G, Campisi C, Papadia A. Lymphedema microsurgical preventivehealing approach for primary prevention of lower limb lymphedema after inguinofemoral lymphadenectomy for vulvar cancer. Int JGynecol Cancer. 2013 May;23(4):769-74.

Modern Surgical Treatment of Lymphatic DisordersEBM Latest Main References 2000-2017

32. Boccardo F, De Cian F, Campisi CC, Molinari L, Spinaci S, Dessalvi S, Talamo G, Campisi CS, Villa G, Bellini C, Parodi A, Santi PL, Campisi C.Surgical prevention and treatment of lymphedema after lymph node dissection in patients with cutaneous melanoma. Lymphology. 2013Mar;46(1):20-6.

33. Bellini C, Ergaz Z, Boccardo F, Bellini T, Campisi CC, Bonioli E, Ramenghi LA. Dynamics of pleural fluid effusion and chylothorax in the fetusand newborn: Role of the Lymphatic System. Lymphology. 2013;46:75-84.

34. Campisi CC, Ryan M, Boccardo F, Campisi C. Ly.M.P.H.A. and the prevention of lymphatic injuries: A rationale for early microsurgicalintervention. J Reconstr Microsurg. 2014 Jan;30(1):71-2.

35. Boccardo F, Dessalvi S, Campisi CC, Molinari L, Spinaci S, Talamo G, Campisi C. Microsurgery for groin lymphocele and lymphedema afteroncologic surgery. Microsurgery. 2014 Jan;34(1):10-3.

36. Campisi C, Ryan M, Campisi CS, Boccardo F, Campisi CC. (2015). Lymphatic Truncular Malformations of the Limbs: Surgical Treatment. In:R. Mattassi et al. (eds.). Hemangiomas and Vascular Malformations: An Atlas of Diagnosis and Treatment (pp. 451-461). Springer –VerlagItalia 2009, 2015

37. Campisi C, Ryan M, Campisi CS, Boccardo F, Campisi CC. (2015). Thoracic Duct Dysplasias and Chylous Reflux. In: R. Mattassi et al. (eds.).Hemangiomas and Vascular Malformations: An Atlas of Diagnosis and Treatment (pp. 463-473). Springer-Verlag Italia 2009, 2015

38. C.C. Campisi, M. Ryan, C.S. Campisi, P. Di Summa, F. Boccardo, C. Campisi. Intermittent negative pressure therapy in the combined treatment of peripheral lymphedema. Lymphology 2015; 48:197-204

39. Campisi CC, Ryan M, Campisi C. (2015-2016). Multiple Lymphaticovenous Anastomoses and Multiple Lymphatic-Venous-Lymphatic Anastomose / Fibro-Lipo-Lympho-Aspiration with the Lymph Vessel-Sparing Procedure. In: PC Neligan, J Masia, NB Piller (eds.). Lymphedema: Complete Medical and Surgical Management (Chapter 33 pp. 447-462). CRC Press Taylor & Francis Group, Boca Raton, FL, USA

40. Campisi CC, Ryan M, Boccardo F, Campisi C. A single-site technique of multiple lymphatic venous anastomoses for the treatment of peripheral lymphedema: Long term clinical outcomes. J. Reconstr Microsurg. 2016 Jan;32(1):42-9.

41. Campisi CC, Ryan M, Boccardo F, Campisi C Fibro-Lipo-Lymph-Aspiration with a Lymph Vessel Sparing Procedure (FLLA-LVSP) to Treat Advanced Lymphedema after Multiple Lymphatic-Venous Anastomoses (MLVA): the Complete Treatment Protocol. Annals of Plastic Surgery. 2017 Feb;78(2):184-190

Modern Surgical Treatment of Lymphatic DisordersEBM Latest Main References 2000-2017