Il trapianto polmonare. Indicazioni, criticità ed esperienza del Centro di Riferimento di Siena Dott.ssa Laura Franceschini Scuola di specializzazione in Allergologia e Immunologia clinica U.O.C Medicina Interna 2, Le Scotte-Siena
TRANSPLANTATION TIMELINE 1963 - Dr. James Hardy single lung tx in male patient, 58 y.o., life sentence in prison, with bronchogenic CA and severe BPCO � immunosuppression: AZA, prednisone, cobalt irradiation � survived 18 days (renal failure; an autopsy showed no evidence of rejection) www.eurotransplant.org early 2000's: double lung transplant more common
… IL POLMONE E’ DIVERSO ! maggiore rischio di danno da riperfusione (ampia area endoteliale) ! contatto con l’ambiente esterno ! ridotti meccanismi di difesa: organo denervato � no riflesso tussigeno http://www.ctstransplant.org
CONTROINDICAZIONI INDICAZIONI
INDICAZIONI a chronic, end-stage lung disease who meet all the following general criteria: 1. High (>50%) risk of death from lung disease within 2 years if lung transplantation is not performed. 2. High (>80%) likelihood of surviving at least 90 days after lung transplantation. 3. High (>80%) likelihood of 5-year post-transplant survival from a general medical perspective provided that there is adequate graft function J Heart Lung Transplant 2015 Jan;34(1):1-15. Epub 2014 Jun 26 . JHJHLT. 2017 Oct; 36(10): 1037-1079
Adult Lung Transplants Major Indications by Year (Number) 2017 JHJHLT. 2017 Oct; 36(10): 1037-1079
Adapted by J Heart Lung Transplant 2015 Jan;34(1):1-15. Epub 2014 Jun 26 .
Adult Lung Transplants Kaplan-Meier Survival by Diagnosis (Transplants: January 1990 – June 2015) 100 A1ATD (N=3,117) CF (N=8,381) COPD (N=17,098) IIP (N=12,710) ILD-not IIP (N=2,730) Retransplant (N=2,226) 75 Median survival (years): A1ATD: 6.7; CF: 9.2; COPD: 5.8; IIP: 4.9; ILD- not IIP: 6.0; Retransplant: 2.9 Survival (%) 50 25 All pair-wise comparisons were significant at p < 0.05 except A1ATD vs. ILD-non IIP and COPD vs. ILD-non IIP 0 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 Years 2017 JHLT. 2017 Oct; 36(10): 1037-1079
CONTROINDICAZIONI ABSOLUTE CONTRAINDICATIONS • malignancy within prior 2 years • another major organ failure (heart, liver, kidney) • chronic infection with highly virulent and/or resistant microbes that are poorly controlled pre-transplant • substance abuse or dependence (alcohol, tobacco, marijuana, ...) • no compliance / psychiatric conditions associated with the inability to cooperate • acute medical instability (acute sepsis, myocardial infarction, liver failure, ...) • uncorrectable bleeding diathesis • BMI ≥ 35 • absence of an adequate social support system
RELATIVE CONTRAINDICATIONS • age >65 years • mechanical support (mechanical ventilation and/or ECLS), but... • chronic colonization or infection with highly resistant or highly virulent bacteria, fungi, and certain strains of mycobacteria � hepatitis B and/or C, HIV+ � Burkholderia cenocepacia, Burkholderia gladioli � multi-drug-resistant Mycobacterium abscessus • other medical conditions with not end-stage organ damage (diabetes mellitus, systemic hypertension, epilepsy, UP, GERD) � should be optimally treated before transplantation • BMI 30-34 or <17 • severe, symptomatic osteoporosis • extensive prior chest surgery with lung resection
CRITICITA’ . THE TRANSPLANT WINDOW . WAITING LIST / REMOVAL FROM WAITING LIST . SPECIAL TRANSPLANT CIRCUMSTANCES . SINGLE or DOUBLE ? . COMPLICATIONS . SUPPLY AND DEMAND
THE TRANSPLANT WINDOW Quezada W, Make B. Chronic Obstr Pulm Dis . 2016; 3(1): 446-453 L. Franceschini
MANAGEMENT OF THE WAITING LIST “…It is imperative that all wait-listed patients be regularly evaluated...ensuring that candidate selection is not simply a one-time static determination but rather a continuous process. “ REMOVAL FROM THE WAITING LIST either temporarily or permanently NEGATIVE DEVELOPMENT Development of any of the above-discussed absolute or relative contraindications: changes in weight or rehabilitation status, renal failure, demonstrable medical non-compliance, or patient ambivalence toward transplantation Patients bridged by mechanical ventilation and/or ECLS, who more frequently develop changes in clinical status that would preclude the likelihood of an acceptable transplant outcome. POSITIVE DEVELOPMENTS Response to medical therapy ( > APH) Improvement in quality of life status that would alter the risk/benefit equation away from transplantation at the current time should prompt a reevaluation of a patient’s transplant candidacy Weill et al, J. Heart Lung Transplant. 2015; 34: 1–15.
SINGLE or DOUBLE ? BLT SLT en bloc double-lung procedure bilateral sequential single-lung (< incidence of anastomotic complications) Varun Puri, Thorac Surg Clin. 2015; 25(1):47-54
Adult Lung Transplants Indications for Single vs Double Lung Transplants (Transplants: January 1995 – June 2012) SLT BLT *Other includes: *Other includes: Pulmonary Fibrosis, Other: 4.0% Pulmonary Fibrosis, Other: 3.5% Bronchiectasis: 0.4% Bronchiectasis: 4.1% Sarcoidosis: 1.9% Sarcoidosis: 2.9% Connective Tissue Disease: 1.1% Connective Tissue Disease: 1.4% OB (non-ReTx): 0.7% OB (non-ReTx): 1.3% LAM: 1.0% LAM: 1.1% Congenital Heart Disease: 0.4% Congenital Heart Disease: 1.2% 1.1% Miscellaneous: Miscellaneous: 1.8% 2013 JHLT. 2013 Oct; 32(10): 965- 978
SPECIAL TRANSPLANT CIRCUMSTANCES Lung retransplantation • Of the 55.795 reported adult lung transplants that were performed through June 2015: 2.187 (3.9%) had a first retransplantation and 86 (0.2%) had a second retransplantation. • BILATERAL >> SINGLE TX Ipsilateral single-lung retransplantation has been associated with a higher acute risk of death compared with contralateral single-lung retransplantation • patients who are >2 years out from initial transplantation fare better than patients retransplanted earlier. Weill et al, J. Heart Lung Transplant. 2015; 34: 1–15.
Adult Lung Transplants Transplant Type Distribution by Recipient Age Group (Transplants: January 1990 – June 2015) 2016 JHLT. 2016 Oct; 35(10): 1149-1205
Cancer Weill et al, J. Heart Lung Transplant. 2015; 34: 1–15.
COMPLICANZE INFEZIONE RIGETTO batterica iperacuto virale acuto fungina cronico ALTRE: PGD IATROGENE K Versamento pleurico Stenosi bronchiali Ricorrenza malattia primaria Complicanze naturali del polmone
CHEST 2011 139, 402-411 DOI: (10.1378/chest.10-1048)
CHEST 2011 139, 402-411DOI: (10.1378/chest.10-1048)
RIGETTO CRONICO OB: obliterative bronchiolitis BOS/OB: bronchiolitis obliterans syndrome (BOS) dal 2008 RAS: restrictive allograft syndrome CLAD: chronic lung allograft dysfunction ALAD: acute lung allograft dysfunction
INCREMENTO DEL POOL DELLE DONAZIONI 2008: EVLP ex-vivo lung perfusion
… in ITALIA: 12 CENTRI AUTORIZZATI TORINO - OSP. S. GIOV. BATTISTA-MOLINETTE MILANO - PRESIDIO OSP. MAGGIORE POLICLINICO MILANO - OSPEDALE CA' GRANDA MILANO - OSPEDALE NIGUARDA BERGAMO - OSPEDALI RIUNITI PAVIA - OSPEDALE POLICLINICO S. MATTEO UDINE – S. MARIA DELLA MISERICORDIA BOLOGNA - S. ORSOLA-MALPIGHI _________________________________ SIENA - AOU S. MARIA ALLE SCOTTE ROMA - POLICLINICO UMBERTO I ROMA - OSPEDALE PEDIATRICO BAMBINO GESU ’ ________________________________ PALERMO - Is.mE.T
10 12 14 16 0 2 4 6 8 a 2001 a 2002 a 2003 a 2004 a 2005 a 2006 IL TRAPIANTO DI POLMONE A SIENA a 2007 a 2008 a 2009 a 2010 a 2011 a 2012 a 2013 a 2014 a 2015 a 2016 > 140 TX IPF CF COPD OTHER REDO-LTX
IL TRAPIANTO DI POLMONE A SIENA pneumologi Chirurghi toracici immunologi anestesisti team fisioterapisti infettivologi psicologi
KEY POINTS • il trapianto polmonare è diventato un mezzo efficace e affidabile per migliorare la sopravvivenza e la qualità della vita in pazienti accuratamente selezionati con malattia polmonare end-stage • Il successo attuale nel trapianto è attribuito ad un timing corretto di rinvio ed inserimento in lista d’attesa, alla presenza di un team multidisciplinare, al miglioramento della gestione dei donatori e all’attento follow-up dei trapiantati
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