murine-cervical-aortic-transplantation-model-using-modified-non

Murine Cervical Aortic Transplantation Model using a Modified Non-Suture Cuff Technique

With the introduction of powerful immunosuppressive protocols, distinct advances are possible in the prevention and therapy of acute rejection episodes. ...

Ludwig Maximilian University of Munich

Malignant tumors represent a serious problem in transplantation medicine. Tumors passed on by the donor or present in the recipient's history may reappear after transplantation with its need for immunosuppression. On the other hand, in patients with hepatocellular carcinoma (HCC), transplantation is the sole curative therapeutic option. Chronic immunosuppression promotes not only a tendency for the disease to recur, but also the development of various solid and hematological malignancies, and thus makes rigorous prophylactic measures a must. The use of new immunosuppressants (mTOR inhibitors) might, in future, be useful in helping resolve the problem of malignant diseases in organ transplantation.

[Transplantation in cancer disease, and tumors in organ transplantation: current aspects and future prospects].

&#x78F7;&#x9178;&#x9176;&#x6291;&#x5236;&#x5242;&#x7684; (CNI) &#x5E74;&#x521D;&#x8F6C;&#x4E3A;-&#x514D;&#x8D39;&#x7EF4;&#x4FEE;&#x4E0E;&#x897F;&#x7F57;&#x83AB;&#x53F8; (SRL)&#x3001; &#x9709;&#x915A;&#x9178;&#x916F; (MMF) &#x548C;&#x7C7B;&#x56FA;&#x9187;&#x6FC0;&#x7D20;&#x7684;&#x514D;&#x75AB;&#x6291;&#x5236;&#x662F;&#x5173;&#x8054; 1 &#x5E74;&#x4E0E;&#x73AF;&#x5B62;&#x7D20; (CsA) &#x6539;&#x5584;&#x80BE;&#x529F;&#x80FD;-&#x57FA;&#x4E8E;&#x517B;&#x751F; &#xFF08;&#x667A;&#x80FD;&#x6838;&#x5FC3;&#x7814;&#x7A76;&#xFF09;&#x3002;&#x6B64;&#x89C2;&#x6D4B;&#x7684;&#x540E;&#x7EED;&#x884C;&#x52A8;&#x4ECB;&#x7ECD;&#x667A;&#x80FD;&#x7814;&#x7A76;&#x6846;&#x67B6;&#x5185;&#x4E3A; 36 &#x4E2A;&#x6708;&#x8DDF;&#x8FDB;&#x7684; 132 &#x4F8B;&#x3002;&#x5728; 36 &#x4E2A;&#x6708;&#xFF0C;&#x80BE;&#x529F;&#x80FD;&#x7EE7;&#x7EED;&#x4F18;&#x8D8A; SRL &#x6CBB;&#x7597;&#x60A3;&#x8005; [ITT-eGFR(@36m): 60.88 &#x4E0E; 53.72 (CsA) ml/min/1.73 m(2)&#xFF0C;P = 0.031]&#x3002;&#x7136;&#x800C;&#xFF0C;&#x66F4;&#x591A;&#x7684;&#x75C5;&#x4EBA;&#x5927;&#x5927;&#x505C;&#x6B62; SRL &#x7EC4; 59.4 %vs.42.3%(CsA) &#x7684;&#x6CBB;&#x7597;&#x3002;&#x5728; 36 &#x4E2A;&#x6708; [99%(SRL) vs.97%(CsA) &#x548C;&#x79FB;&#x690D; 96%(SRL) vs.94%(CsA)] &#x75C5;&#x4EBA;&#x751F;&#x5B58;&#x662F;&#x6781;&#x597D;&#x7684;&#x8FD9;&#x4E24;&#x79CD;&#x6B66;&#x5668;&#x3002;&#x6CA1;&#x6709;&#x4EFB;&#x4F55;&#x5DEE;&#x522B;&#x5728;&#x665A;&#x62D2;&#x7EDD;&#x5267;&#x96C6;&#x3002;&#x7C7B;&#x4F3C;&#x8FD9;&#x4E24;&#x79CD;&#x6B66;&#x5668;&#x9664;&#x4E86;&#x8F83;&#x9AD8;&#x7684;&#x9AD8;&#x8102;&#x8840;&#x75C7;&#x7684; SRL &#x7387;&#x548C; CsA &#x6CBB;&#x7597;&#x6076;&#x6027;&#x80BF;&#x7624;&#x7684;&#x53D1;&#x751F;&#x7387;&#x8F83;&#x9AD8;&#x7684;&#x540E;&#x671F;&#x611F;&#x67D3;&#x548C;&#x4E0D;&#x826F;&#x4E8B;&#x4EF6;&#x3002;&#x5728;&#x591A;&#x5143;&#x5206;&#x6790;&#x4E2D;&#xFF0C;&#x6350;&#x52A9;&#x8005;&#x5E74;&#x9F84; &gt; 60 &#x5E74;&#x6765;&#xFF0C;&#x5728;&#x8F6C;&#x6362;&#x7684; S &#x808C;&#x9150; &gt; 2 mg/dl&#x3001; &#x5DE8;&#x7EC6;&#x80DE;&#x75C5;&#x6BD2; na&iuml;ve(-) &#x6536;&#x4EF6;&#x4EBA;&#x548C;&#x514D;&#x75AB;&#x6291;&#x5236;&#x4E0E; CsA &#x5728; 36 &#x4E2A;&#x6708;&#x65F6;&#x88AB;&#x9884;&#x6D4B;&#x7684;&#x80BE;&#x529F;&#x80FD;&#x635F;&#x5BB3;&#x3002;&#x65E9;&#x671F;&#x8F6C;&#x6362;&#x4E3A;&#x65E0; CNI &#x7684;&#x57FA;&#x4E8E; SRL &#x7684;&#x514D;&#x75AB;&#x6291;&#x5236;&#x662F;&#x4E0E;&#x80BE;&#x529F;&#x80FD;&#x6301;&#x7EED;&#x6539;&#x8FDB;&#x5173;&#x8054;&#x79FB;&#x690D;&#x672F;&#x540E;&#x7684; 36 &#x4E2A;&#x6708;&#x3002;&#x75C5;&#x4EBA;&#x7684;&#x9009;&#x62E9;&#x5C06;&#x4F1A;&#x5F97;&#x5230;&#x957F;&#x671F;&#x7684;&#x5229;&#x76CA;&#xFF0C;&#x907F;&#x514D;&#x4F7F;&#x7528;&#x8FD9;&#x79CD;&#x57FA;&#x4E8E; mTOR &#x6291;&#x5236;&#x5242;&#x7684;&#x514D;&#x75AB;&#x6291;&#x5236;&#x65B9;&#x6848;&#x6CBB;&#x7597;&#x5931;&#x8D25;&#x7684;&#x5173;&#x952E;&#x3002;

&#x65E9;&#x671F;&#x8F6C;&#x6362;&#x5230;&#x57FA;&#x4E8E;&#x897F;&#x7F57;&#x83AB;&#x53F8;&#x3001; &#x65E0;&#x9499;&#x8C03;&#x795E;&#x7ECF;&#x78F7;&#x9178;&#x7684;&#x6291;&#x5236;&#x5242;&#x514D;&#x75AB;&#x6291;&#x5236;&#x7684;&#x667A;&#x80FD;&#x5BA1;&#x5224;&#xFF1A; &#x5728;&#x79FB;&#x690D;&#x672F;&#x540E;&#x7684; 24 &#x81F3; 36 &#x4E2A;&#x6708;&#x7684;&#x89C2;&#x6D4B;&#x7ED3;&#x679C;&#x3002;

Early conversion to a calcineurin-inhibitor (CNI)-free maintenance immunosuppression with sirolimus (SRL), mycophenolate mofetil (MMF) and steroids was associated with an improved 1-year renal function as compared with a cyclosporine (CsA)-based regimen (SMART core-study). This observational follow-up describes 132 patients followed up within the SMART study framework for 36â€ƒmonths. At 36â€ƒmonths, renal function continued to be superior in SRL-treated patients [ITT-eGFR(@36m) : 60.88 vs. 53.72 (CsA) ml/min/1.73â€ƒm(2) , Pâ€ƒ=â€ƒ0.031]. However, significantly more patients discontinued therapy in the SRL group 59.4% vs.42.3% (CsA). Patient [99% (SRL) vs.97% (CsA) and graft 96% (SRL) vs.94% (CsA)] survival at 36â€ƒmonths was excellent in both arms. There was no difference in late rejection episodes. Late infections and adverse events were similar in both arms except of a higher rate of hyperlipidemia in SRL and a higher incidence of malignancy in CsA-treated patients. In a multivariate analysis, donor age >60â€ƒyears, S-creatinine at conversion >2â€ƒmg/dl, CMV naÃ¯ve(-) recipients and immunosuppression with CsA were predictive of an impaired renal function at 36â€ƒmonths. Early conversion to a CNI-free SRL-based immunosuppression is associated with a sustained improvement of renal function up to 36â€ƒmonths after transplantation. Patient selection will be key to derive long-term benefit and avoid treatment failure using this mTOR-inhibitor-based immunosuppressive regimen.

Early conversion to a sirolimus-based, calcineurin-inhibitor-free immunosuppression in the SMART trial: observational results at 24 and 36â€ƒmonths after transplantation.

Une conversion anticip&eacute;e &agrave; un inhibiteur de la calcineurine (CNI) - immunosuppression entretien libre avec le sirolimus (SRL), mycoph&eacute;nolate mof&eacute;til (MMF) et les st&eacute;ro&iuml;des a &eacute;t&eacute; associ&eacute;e avec une fonction r&eacute;nale am&eacute;lior&eacute;e de 1 an contre une ciclosporine (CsA) - selon le sch&eacute;ma posologique (SMART core-&eacute;tude). Ce suivi d&#39;observation d&eacute;crit 132 patients suivis dans le cadre de l&#39;&eacute;tude SMART pendant 36 mois. Au 36 mois, la fonction r&eacute;nale continue d&#39;&ecirc;tre sup&eacute;rieure chez les patients trait&eacute;s SRL [ITT-eGFR(@36m) : 60,88 vs 53 s 72 (CsA) ml/min/1.73 m, P = 0. 031]. Toutefois, significativement plus &eacute;lev&eacute; de patients suspendue th&eacute;rapie dans la SRL groupe 59,4 % vs.42.3% (CsA). Survie du patient [99 % (SRL), vs.97% (CsA) et greffe 96 % (SRL) vs.94% (CsA)] &agrave; 36 mois a &eacute;t&eacute; excellente dans les deux bras. Il n&#39;y n&#39;avait aucune diff&eacute;rence dans les &eacute;pisodes de rejet tardif. Infection tardive et les effets ind&eacute;sirables ont &eacute;t&eacute; similaires dans les deux bras &agrave; l&#39;exception d&#39;un taux plus &eacute;lev&eacute; de l&#39;hyperlipid&eacute;mie dans SRL et une incidence accrue de tumeurs malignes chez les patients trait&eacute;s &agrave; la CsA. Dans une analyse multivari&eacute;e, &acirc;ge des donneurs &gt; 60ans, S-cr&eacute;atinine &agrave; conversion &gt; 2 mg/dl, destinataires na&iuml;ve(-) CMV et l&#39;immunosuppression avec l&#39;ASC &eacute;taient pr&eacute;dictifs d&#39;une insuffisance r&eacute;nale &agrave; 36 mois. Une conversion anticip&eacute;e &agrave; une immunosuppression de SRL-bas&eacute; exempt de CNI est associ&eacute;e &agrave; une am&eacute;lioration soutenue de la fonction r&eacute;nale jusqu&#39;&agrave; 36 mois apr&egrave;s la transplantation. S&eacute;lection des patients seront essentielles pour tirer avantage &agrave; long terme et &eacute;viter l&#39;&eacute;chec du traitement &agrave; l&#39;aide de ce r&eacute;gime immunosuppresseur inhibiteur de mTOR-base.

Une conversion anticip&eacute;e &agrave; une immunosuppression ax&eacute;e sur le sirolimus, exempt d&#39;inhibiteur de la calcineurine dans l&#39;essai SMART : r&eacute;sultats d&#39;observation &agrave; 24 et 36 mois apr&egrave;s la transplantation.

Fr&uuml;he Umstellung auf ein Calcineurin-Inhibitor (CNI) - kostenlose Wartung Immunsuppression mit Sirolimus (SRL), Mycophenolat-Mofetil (MMF) und Steroide war verbunden mit einer verbesserten 1 Jahr Nierenfunktion im Vergleich zu einer Cyclosporin (CsA) - basierte Therapie (intelligente Kern-Studie). Diese Beobachtungen Follow-up beschreibt 132 Patienten folgte im Rahmen der SMART-Studie f&uuml;r 36 Monate. 36 Monate, Nierenfunktion weiterhin in SRL-behandelten Patienten &uuml;berlegen [ITT-eGFR(@36m): 60.88 vs. 53.72 (CsA) ml/min/1.73 m, P = 0.031]. Jedoch eingestellt signifikant mehr Patienten Therapie in der SRL Gruppe 59,4 % vs.42.3% (CsA). &Uuml;berleben der Patienten [99 % (SRL) vs.97% (CsA) und Transplantat 96 % (SRL) vs.94% (CsA)] 36 Monate war ausgezeichnet in beiden Behandlungsarmen. Es gab keinen Unterschied in sp&auml;ten Ablehnung folgen. Sp&auml;te Infektionen und unerw&uuml;nschten Ereignisse waren in beiden Behandlungsarmen au&szlig;er eine h&ouml;here Rate der Hyperlipid&auml;mie in SRL und einer h&ouml;heren Inzidenz von B&ouml;sartigkeit CsA behandelten Patienten. In einer multivariaten Analyse Spender Alter &gt; 60 Jahre, S-Kreatinin bei Conversion &gt; 2 mg/dl, CMV na&iuml;ve(-) Empf&auml;nger und Immunsuppression mit CsA waren der ein eingeschr&auml;nkter Nierenfunktion pr&auml;diktive 36 Monate. Fr&uuml;he Umstellung auf einer CNI-freie SRL-basierte Immunsuppression ist eine nachhaltige Verbesserung der Nierenfunktion zugeordnet bis zu 36 Monaten nach der Transplantation. Patientenauswahl werden Schl&uuml;ssel zum langfristigen Nutzen und Versagen der Therapie mit diesem mTOR-Inhibitor-basierte immunsuppressive Therapie zu vermeiden.

Fr&uuml;he Umstellung auf eine Sirolimus basierende, Calcineurin-Inhibitor-freie Immunsuppression in der SMART-Studie: Beobachtungsstudie Ergebnisse 24 und 36 Monate nach Transplantation.

Conversione precoce di un inibitore della calcineurina (CNI) - manutenzione gratuita immunosoppressione con sirolimus (SRL), micofenolato mofetile (MMF) e gli steroidi &egrave; stato associato con un 1 anno miglioramento della funzione renale rispetto a ciclosporina (CsA) - base di regime (SMART core-studio). Questo follow-up osservazionale descrive 132 pazienti seguiti nell&#39;ambito di studio intelligente per 36 mesi. A 36 mesi, la funzione renale ha continuato ad essere superiore nei pazienti trattati con SRL [ITT-eGFR(@36m): 60.88 vs 53.72 (CsA) ml/min/1.73 m(2), P = 0.031]. Tuttavia, significativamente pi&ugrave; pazienti interrotto la terapia nella SRL gruppo 59,4% vs.42.3% (CsA). Sopravvivenza del paziente [99% (SRL) vs.97% (CsA) e innesto 96% (SRL) vs.94% (CsA)] a 36 mesi &egrave; stato eccellente in entrambe le braccia. Non non c&#39;era nessuna differenza nel tardo episodi di rigetto. Tarda infezioni e gli eventi avversi erano simili in entrambi i bracci ad eccezione di un pi&ugrave; alto tasso di iperlipidemia in SRL e una maggiore incidenza di neoplasie maligne nei pazienti trattati con CsA. In un&#39;analisi multivariata, et&agrave; donatore &amp;gt; 60 anni, alla conversione di S-creatinina &amp;gt; 2 mg/dl, CMV na&iuml;ve(-) destinatari e immunosoppressione con CsA erano predittivi di un&#39;alterata funzione renale a 36 mesi. Conversione precoce di un&#39;immunosoppressione SRL-Sede CNI-libero &egrave; associata a un miglioramento continuo della funzione renale fino a 36 mesi dopo il trapianto. Selezione dei pazienti sar&agrave; la chiave per trarre beneficio a lungo termine ed evitare il fallimento del trattamento utilizzando questo regime immunosoppressivo basato su inibitore di mTOR.

Precoce conversione di una base di sirolimus, inibitore della calcineurina-senza immunosoppressione nella prova SMART: risultati osservativi a 24 e 36 mesi dopo il trapianto.

&#x30AB;&#x30EB;&#x30B7;&#x30CB;&#x30E5;&#x30FC;&#x30EA;&#x30F3;&#x963B;&#x5BB3;&#x5264; &#xFF08;CNI&#xFF09; &#x3078;&#x306E;&#x65E9;&#x671F;&#x306E;&#x5909;&#x63DB; - &#x30B7;&#x30ED;&#x30EA;&#x30E0;&#x30B9; (SRL)&#x3001;&#x30DF;&#x30B3;&#x30D5;&#x30A7;&#x30CE;&#x30FC;&#x30EB;&#x9178;&#x30E2;&#x30D5;&#x30A7;&#x30C1;&#x30EB; &#xFF08;MMF&#xFF09;&#x3001;&#x30B9;&#x30C6;&#x30ED;&#x30A4;&#x30C9;&#x306E;&#x30E1;&#x30F3;&#x30C6;&#x30CA;&#x30F3;&#x30B9; &#x30D5;&#x30EA;&#x30FC;&#x306E;&#x514D;&#x75AB;&#x6291;&#x5236;&#x3055;&#x308C;&#x305F;&#x6539;&#x826F;&#x3055;&#x308C;&#x305F; 1 &#x5E74;&#x814E;&#x6A5F;&#x80FD;&#x306E;&#x30B7;&#x30AF;&#x30ED;&#x30B9;&#x30DD;&#x30EA;&#x30F3; (CsA) &#x3068;&#x6BD4;&#x8F03;&#x3057;&#x3066;&#x306E;&#x95A2;&#x9023;&#x4ED8;&#x3051; - &#x30EC;&#x30B8;&#x30E1;&#x30F3; &#xFF08;&#x30B9;&#x30DE;&#x30FC;&#x30C8; &#x30B3;&#x30A2;&#x7814;&#x7A76;&#xFF09; &#x306B;&#x57FA;&#x3065;&#x3044;&#x3066;&#x3002;&#x3053;&#x306E;&#x89B3;&#x6E2C;&#x306E;&#x30D5;&#x30A9;&#x30ED;&#x30FC; &#x30A2;&#x30C3;&#x30D7; &#x30B9;&#x30DE;&#x30FC;&#x30C8;&#x7814;&#x7A76;&#x306E;&#x67A0;&#x7D44;&#x307F;&#x306E;&#x4E2D;&#x3067; 36 &#x30F6;&#x6708;&#x9593;&#x7D9A;&#x304F;&#x60A3;&#x8005; 132 &#x540D;&#x306B;&#x3064;&#x3044;&#x3066;&#x8AAC;&#x660E;&#x3057;&#x307E;&#x3059;&#x3002;36 &#x30F6;&#x6708;&#x3067;&#x814E;&#x6A5F;&#x80FD;&#x7D9A;&#x3051;&#x305F; SRL &#x306E;&#x6CBB;&#x7642;&#x3092;&#x53D7;&#x3051;&#x305F;&#x60A3;&#x8005;&#x3067;&#x512A;&#x308C;&#x3066;&#x3044;&#x308B;&#x3053;&#x3068; [ITT-eGFR(@36m): 60.88 53.72 &#xFF08;CsA&#xFF09; ml/min/1.73 m(2)&#x3001;P &#x5BFE; 0.031 &#x73FE;&#x5728; =]&#x3002;&#x305F;&#x3060;&#x3057;&#x3001;&#x5927;&#x5E45;&#x306B;&#x3088;&#x308A;&#x591A;&#x304F;&#x306E;&#x60A3;&#x8005;&#x6CBB;&#x7642;&#x3067; SRL &#x30B0;&#x30EB;&#x30FC;&#x30D7; 59.4 %vs.42.3% (CsA) &#x306F;&#x4E2D;&#x6B62;&#x3002;[99% (SRL) vs.97% (CsA) &#x3068;&#x30B0;&#x30E9;&#x30D5;&#x30C8; 96% (SRL) vs.94% (CsA)] &#x60A3;&#x8005;&#x751F;&#x5B58; 36 &#x30F6;&#x6708;&#x3067;&#x306F;&#x3001;&#x4E21;&#x65B9;&#x306E;&#x8155;&#x306E;&#x4E2D;&#x3067;&#x512A;&#x79C0;&#x3060;&#x3063;&#x305F;&#x3002;&#x5F8C;&#x534A;&#x306E;&#x62D2;&#x7D76;&#x3067;&#x5DEE;&#x306F;&#x306A;&#x304B;&#x3063;&#x305F;&#x3002;&#x5F8C;&#x534A;&#x306E;&#x611F;&#x67D3;&#x75C7;&#x3068;&#x6709;&#x5BB3;&#x4E8B;&#x8C61;&#x4E21;&#x8155;&#x3092;&#x9664;&#x3044;&#x3066; SRL &#x306E;&#x9AD8;&#x8102;&#x8840;&#x75C7;&#x306E;&#x7387;&#x304C;&#x9AD8;&#x3044;&#x3068; CsA &#x6295;&#x4E0E;&#x60A3;&#x8005;&#x306B;&#x60AA;&#x6027;&#x816B;&#x760D;&#x306E;&#x767A;&#x751F;&#x7387;&#x304C;&#x9AD8;&#x3044;&#x306B;&#x985E;&#x4F3C;&#x3057;&#x3066;&#x3044;&#x305F;&#x3002;&#x591A;&#x5909;&#x91CF;&#x89E3;&#x6790;&#x3067;&#x30C9;&#x30CA;&#x30FC;&#x5E74;&#x9F62;&#x76EE; S-&#x30AF;&#x30EC;&#x30A2;&#x30C1;&#x30CB;&#x30F3;&#x63DB;&#x7B97;&#x3067; 60 &#x5E74;&#x76EE; 2 &#x30DF;&#x30EA;&#x30B0;&#x30E9;&#x30E0;/dl&#x3001;CMV na&iuml;ve(-) &#x53D7;&#x4FE1;&#x8005;&#x304A;&#x3088;&#x3073; CsA &#x306E;&#x514D;&#x75AB;&#x6291;&#x5236; 36 &#x30F6;&#x6708;&#x3067;&#x3001;&#x814E;&#x6A5F;&#x80FD;&#x969C;&#x5BB3;&#x306E;&#x4E88;&#x6E2C;&#x3055;&#x308C;&#x307E;&#x3057;&#x305F;&#x3002;&#x814E;&#x6A5F;&#x80FD;&#x306E;&#x6301;&#x7D9A;&#x7684;&#x306A;&#x6539;&#x5584;&#x306B;&#x95A2;&#x9023;&#x4ED8;&#x3051;&#x3089;&#x308C;&#x3066;&#x3044;&#x308B;&#x521D;&#x671F;&#x5909;&#x63DB;&#x7121;&#x6599;&#x306E; CNI SRL &#x30D9;&#x30FC;&#x30B9;&#x514D;&#x75AB;&#x306B;&#x79FB;&#x690D;&#x5F8C; 36 &#x30F6;&#x6708;&#x307E;&#x3067;&#x3002;&#x60A3;&#x8005;&#x306E;&#x9078;&#x629E;&#x306F;&#x3001;&#x9577;&#x671F;&#x7684;&#x306A;&#x5229;&#x76CA;&#x3092;&#x5F97;&#x308B;&#x3053;&#x306E; mTOR &#x963B;&#x5BB3;&#x5264;&#x30D9;&#x30FC;&#x30B9;&#x306E;&#x514D;&#x75AB;&#x6291;&#x5236;&#x7642;&#x6CD5;&#x3092;&#x4F7F;&#x7528;&#x3057;&#x3066;&#x6CBB;&#x7642;&#x306E;&#x969C;&#x5BB3;&#x3092;&#x56DE;&#x907F;&#x3059;&#x308B;&#x9375;&#x3068;&#x306A;&#x308A;&#x307E;&#x3059;&#x3002;

&#x514D;&#x75AB;&#x6291;&#x5236;&#x7642;&#x6CD5;&#x30B7;&#x30ED;&#x30EA;&#x30E0;&#x30B9; &#x30D9;&#x30FC;&#x30B9;&#x3001;&#x30AB;&#x30EB;&#x30B7;&#x30CB;&#x30E5;&#x30FC;&#x30EA;&#x30F3;&#x963B;&#x5BB3;&#x5264;&#x30D5;&#x30EA;&#x30FC;&#x306E;&#x30B9;&#x30DE;&#x30FC;&#x30C8;&#x306E;&#x88C1;&#x5224;&#x3067;&#x3078;&#x306E;&#x65E9;&#x671F;&#x306E;&#x5909;&#x63DB;: &#x79FB;&#x690D;&#x5F8C; 24 &#x3068; 36 &#x30F6;&#x6708;&#x3067;&#x306E;&#x89B3;&#x6E2C;&#x7D50;&#x679C;&#x3002;

Calcineurin &#xC5B5;&#xC81C;&#xC81C; (CNI) &#xCD08;&#xAE30; &#xBCC0;&#xD658;-&#xBB34;&#xB8CC; &#xC720;&#xC9C0; &#xBCF4;&#xC218; &#xBA74;&#xC5ED; &#xC5B5;&#xC81C; sirolimus (SRL), mycophenolate mofetil (MMF), &#xC2A4;&#xD14C;&#xB85C;&#xC774;&#xB4DC;&#xC640; cyclosporine (CsA)&#xC5D0; &#xBE44;&#xD574; &#xD5A5;&#xC0C1; &#xB41C; 1 &#xB144; &#xC2E0;&#xC7A5; &#xAE30;&#xB2A5;&#xACFC; &#xAD00;&#xB828; &#xB41C;&#xB294;-&#xAE30;&#xBC18; &#xCC98;&#xBC29; (&#xC2A4;&#xB9C8;&#xD2B8; &#xD575;&#xC2EC; &#xC5F0;&#xAD6C;). &#xC774; &#xAD00;&#xCE21; &#xD6C4;&#xC18D; 132 &#xD658;&#xC790;&#xB97C; 36 &#xAC1C;&#xC6D4; &#xC2A4;&#xB9C8;&#xD2B8; &#xC5F0;&#xAD6C; &#xD504;&#xB808;&#xC784; &#xC6CC;&#xD06C; &#xB0B4;&#xC5D0;&#xC11C; &#xB2E4;&#xC74C;&#xC5D0; &#xB300;&#xD574; &#xC124;&#xBA85; &#xD569;&#xB2C8;&#xB2E4;. 36 &#xAC1C;&#xC6D4;&#xC5D0;&#xC11C; &#xC2E0;&#xC7A5; &#xAE30;&#xB2A5; SRL &#xCE58;&#xB8CC; &#xD658;&#xC790;&#xC5D0;&#xC11C; &#xC6B0;&#xC218;&#xD55C; &#xACC4;&#xC18D; [ITT-eGFR(@36m): 60.88 &#xB300; 53.72 (CsA) ml/min/1.73 m(2), P = 0.031]. &#xADF8;&#xB7EC;&#xB098;, &#xC0C1;&#xB2F9;&#xD788; &#xB354; &#xB9CE;&#xC740; &#xD658;&#xC790; &#xCE58;&#xB8CC; SRL &#xADF8;&#xB8F9; 59.4 %vs.42.3% (CsA)&#xC5D0; &#xB2E8;&#xC885;. 36 &#xAC1C;&#xC6D4;&#xC5D0;&#xC11C; &#xC0DD;&#xC874; &#xD658;&#xC790; [99% (SRL) vs.97% (&#xCCB4;&#xCF54;)&#xC640; &#xC774;&#xC2DD; 96% (SRL) vs.94% (CsA)] &#xB450; &#xD314;&#xC5D0;&#xC11C; &#xC6B0;&#xC218; &#xD588;&#xB2E4;. &#xB2A6;&#xC740; &#xAC70;&#xBD80; &#xC5D0;&#xD53C;&#xC18C;&#xB4DC;&#xC5D0; &#xCC28;&#xC774;&#xAC00; &#xC788;&#xC5C8;&#xB2E4;. &#xB2A6;&#xC740; &#xAC10;&#xC5FC;&#xACFC; &#xBD80;&#xC791;&#xC6A9; SRL&#xC5D0;&#xC11C; &#xD608;&#xC758; &#xB192;&#xC740; &#xC18D;&#xB3C4;&#xC640; &#xCCB4;&#xCF54; &#xCE58;&#xB8CC; &#xD658;&#xC790;&#xC5D0;&#xC11C; &#xC545;&#xC131; &#xC885;&#xC591;&#xC758; &#xB192;&#xC740; &#xBC1C;&#xBCD1; &#xB960;&#xC744; &#xC81C;&#xC678; &#xD558; &#xACE0; &#xB450; &#xD314;&#xC5D0;&#xC11C; &#xC720;&#xC0AC; &#xD588;&#xB2E4;. &#xBCF5;&#xC218; &#xBCC0;&#xC218; &#xBD84;&#xC11D;&#xC5D0; &#xAE30;&#xC99D;&#xC790; &#xB098;&#xC774; &amp;gt; 60 &#xB144;, &#xBCC0;&#xD658;&#xC5D0;&#xC11C; S-creatinine &amp;gt; 2 mg/dl, CMV na&iuml;ve(-) &#xBC1B;&#xB294; &#xC0AC;&#xB78C; &#xBC0F; Csa&#xC640; &#xBA74;&#xC5ED; &#xC5B5;&#xC81C; &#xC7A5;&#xC560; &#xC2E0;&#xC7A5; &#xAE30;&#xB2A5; &#xC608;&#xCE21; 36 &#xAC1C;&#xC6D4; &#xD588;&#xB2E4;. &#xCD08;&#xAE30; &#xBCC0;&#xD658; &#xBA74;&#xC5ED;&#xB294; CNI &#xBB34;&#xB8CC; SRL &#xAE30;&#xBC18; &#xC5B5;&#xC81C; &#xD558;&#xB294; &#xC5F0;&#xAD00; &#xB41C; &#xC2E0;&#xC7A5; &#xAE30;&#xB2A5;&#xC758; &#xC9C0;&#xC18D;&#xC801;&#xC778;&#xB41C; &#xD5A5;&#xC0C1;&#xC744; &#xC774;&#xC2DD; &#xD6C4; &#xCD5C;&#xB300; 36 &#xAC1C;&#xC6D4;&#xAE4C;&#xC9C0;. &#xD658;&#xC790; &#xC120;&#xD0DD; &#xC7A5;&#xAE30;&#xC801;&#xC778; &#xC774;&#xC775;&#xC744; &#xD30C;&#xC0DD;&#xC774; mTOR &#xC5B5;&#xC81C;&#xC81C; &#xAE30;&#xBC18; &#xBA74;&#xC5ED; &#xCC98;&#xBC29;&#xC744; &#xC0AC;&#xC6A9; &#xD558; &#xC5EC; &#xCC98;&#xB9AC; &#xC624;&#xB958;&#xB97C; &#xBC29;&#xC9C0; &#xD558;&#xB294; &#xD0A4; &#xAC83;&#xC785;&#xB2C8;&#xB2E4;.

&#xC2A4;&#xB9C8;&#xD2B8; &#xC7AC;&#xD310;&#xC5D0;&#xC11C; sirolimus &#xAE30;&#xBC18;, calcineurin &#xC5B5;&#xC81C;&#xC81C; &#xC5C6;&#xB294; &#xBA74;&#xC5ED; &#xC5B5;&#xC81C;&#xB97C; &#xCD08;&#xAE30; &#xBCC0;&#xD658;: &#xC774;&#xC2DD; &#xD6C4; 24 &#xBC0F; 36 &#xAC1C;&#xC6D4;&#xC5D0;&#xC11C; &#xAD00;&#xCE21; &#xACB0;&#xACFC;.

Conversi&oacute;n temprana a un inhibidor de la calcineurina (CNI) - inmunosupresi&oacute;n de mantenimiento libre con sirolimus (SRL), micofenolato mofetil (MMF) y los esteroides se asoci&oacute; con una funci&oacute;n renal mejorada de 1 a&ntilde;o en comparaci&oacute;n con un ciclosporina (CsA) - basado en el r&eacute;gimen (SMART core-estudio). Este seguimiento observacional describe 132 pacientes seguidos en el marco del estudio inteligente para 36 meses. A los 36 meses, la funci&oacute;n renal sigue siendo superior en los pacientes tratados con SRL [ITT-eGFR(@36m): 60,88 vs 53,72 (CsA) ml/min/1.73 m(2), P = 0.031]. Sin embargo, significativamente m&aacute;s pacientes suspender terapia en la SRL Grupo 59,4% vs.42.3% (CsA). La supervivencia del paciente [99% (SRL) vs.97% (CsA) e injerto 96% (SRL) vs.94% (CsA)] en 36 meses fue excelente en ambos brazos. No hubo diferencias en los &uacute;ltimos episodios de rechazo. Infecciones finales y los eventos adversos fueron similares en ambos brazos excepto de una tasa m&aacute;s alta de la hiperlipidemia en SRL y una mayor incidencia de malignidad en pacientes tratados con CsA. En un an&aacute;lisis multivariante, edad del donante &gt; a&ntilde;os 60, S-creatinina en conversi&oacute;n &gt; 2 mg/dl, CMV na&iuml;ve(-) beneficiarios e inmunosupresi&oacute;n con CsA eran prof&eacute;ticos de un deterioro de la funci&oacute;n renal a los 36 meses. Conversi&oacute;n temprana una inmunosupresi&oacute;n SRL-basado de CNI-libre se asoci&oacute; con una mejor&iacute;a sostenida de la funci&oacute;n renal hasta 36 meses despu&eacute;s del trasplante. Selecci&oacute;n de los pacientes ser&aacute; clave para obtener beneficios a largo plazo y evitar el fracaso del tratamiento con este r&eacute;gimen inmunosupresor basado en el inhibidor de mTOR.

Conversi&oacute;n temprana una inmunosupresi&oacute;n basadas en sirolimus, libre de inhibidor de la calcineurina en el juicio inteligente: resultados observacionales en 24 y 36 meses despu&eacute;s del trasplante.

Surgical problems during organ procurement may propagate complications in the transplant recipient. Ultimately, these problems may result in the complete loss of already scarce donor organs.Donor reports (Eurotransplant donor report) of 1,492 donor organs from January 2010 to August 2012 in the German Foundation of Organ Transplantation (DSO) region of Bavaria and corresponding organ quality forms were analyzed. Surgical problems were classified into 3 categories: (I) surgical problems recognized and reported by the donor surgeon, (II) surgical problems observed by the recipient surgeon but not reported by the donor surgeon and (III) surgical problems leading to organ loss. Surgical problems during this 20-month time period were reported for 17.6  % of organs; category I in 5.5  %, category II in 11.1  % and category III in 1  %. Damage of graft vasculature in 9.1  % was the most frequently reported problem. The mean error index for individual surgeons was 16  % and one out of the five Bavarian organ procurement centers had significantly more problems in all categories (30  %). Interestingly, surgeons who performed rapid retrieval procedures had more problems with quality than surgeons who took more time. Organ retrieval is prone to surgical problems. Especially in a system of organ transport, consistent reporting of surgical problems and quality assurance is needed to maintain and to improve surgical quality.

[Surgical quality of organ retrieval in Bavaria].

Liver transplantation is the optimal therapy for patients with non-resectable early stage hepatocellular carcinoma (HCC) which is limited to the liver. During the sometimes long waiting period patients usually receive neoadjuvant bridging therapy to avoid tumor progression. The armamentarium of bridging therapies includes local ablative and systemic therapies as well as liver resection. The oncological benefit of neoadjuvant therapy for patients who receive a liver transplantation is unclear; however, bridging therapy keeps patients eligible for transplantation in the formal framework of current allocation rules. Moreover, response to therapy may serve as a surrogate marker for favorable tumor biology and may therefore help to guide the selection process for patients undergoing liver transplantation for HCC.

[Therapy of hepatocellular carcinoma before liver transplantation].

Tumor treatment and transplantation-associated with unavoidable mandatory immunosuppression-appear to be unreconcilable opposites. The clinical reality shows, however, that transplantation in many early stage primary tumors is the most effective treatment. The essential immunosuppression after transplantation can however promote tumor recurrence. Immunosuppression also leads to a significant increased rate of de novo tumors-in all organ transplant recipients. However, not all immunosuppressant drugs have the same effect on tumors. In experimental and clinical settings, the class of mTOR inhibitors has a clear antitumoral effect and is recommended as the immunosuppression treatment of choice in patients with increased tumor risk. The purpose of this review is to provide the reader with the scientific background regarding the clinical problem of tumors and transplantation. 

[Tumor and transplantation].

Center volume, competition, and outcome in German liver transplant centers.

Post-hepatectomy liver failure (PHLF) is the major cause of death following liver resection. The aim of this study was to evaluate the feasibility of an intraoperative simulation of post-resection liver function.

Intraoperative simulation of remnant liver function during anatomic liver resection with indocyanine green clearance (LiMON) measurements.

Retroperitoneal lipomas are an extremely rare condition with only 17 cases described in the literature since 1980. They can reach enormous size and cause significant abdominal symptoms. The most important differential diagnosis is the well-differentiated liposarcoma, which preoperatively often may not definitely be ruled out.

En-bloc resection of a giant retroperitoneal lipoma: a case report and review of the literature.

[Safety of brain dead organ donors].

The allocation of any scarce health care resource, especially a lifesaving resource, can create profound ethical and legal challenges. Liver transplant allocation currently is based upon urgency, a sickest-first approach, and does not utilize capacity to benefit. While urgency can be described reasonably well with the MELD system, benefit encompasses multiple dimensions of patients' well-being. Currently, the balance between both principles is ill-defined.

Benefit in liver transplantation: a survey among medical staff, patients, medical students and non-medical university staff and students.

Liver resection is a curative treatment for hepatocellular carcinoma (HCC). Tumor-infiltrating leukocytes (TILs) are important players in predicting HCC recurrence. However, the invasive margin could not be confirmed as relevant for HCC. The migration of immune cells into HCC may originate from intratumoral vessels. No previous study has examined perivascular (PV) infiltration. Tumors from 60 patients were examined. Immunohistochemistry was performed against CD3, CD8, CD20, and CD66b. TILs were counted in the PV regions using an algorithm for quantification of the tumor immune stroma (QTiS). The results were correlated with overall (OS) and disease-free survival (DFS), clinical parameters, and laboratory values. PV infiltration of TILs was predominant in resected HCC. Higher PV infiltration of CD3⁺ ( = 0.016) and CD8⁺ ( = 0.028) independently predicted better OS and DFS, respectively. CD20⁺ showed a trend towards better DFS ( = 0.076). Scoring of CD3⁺, CD8⁺, and CD20⁺ independently predicted OS and DFS ( < 0.01). The amount of perivascular-infiltrating CD3⁺ cells is an independent predictor of better OS, and CD8⁺ cells independently predict prolonged DFS. Our novel perivascular infiltration scoring (PVIS) can independently predict both DFS and OS in resected HCC patients.

Article	Year
[Transplantation in cancer disease, and tumors in organ transplantation: current aspects and future prospects]. MMW Fortschritte der Medizin\| PubMed ID: 15366488	2004
Early conversion to a sirolimus-based, calcineurin-inhibitor-free immunosuppression in the SMART trial: observational results at 24 and 36â€ƒmonths after transplantation. Transplant international : official journal of the European Society for Organ Transplantation\| PubMed ID: 22320241	2012
[Surgical quality of organ retrieval in Bavaria]. Der Chirurg; Zeitschrift fur alle Gebiete der operativen Medizen\| PubMed ID: 23479276	2013
[Therapy of hepatocellular carcinoma before liver transplantation]. Der Chirurg; Zeitschrift fur alle Gebiete der operativen Medizen\| PubMed ID: 23519379	2013
[Tumor and transplantation]. Der Chirurg; Zeitschrift fur alle Gebiete der operativen Medizen\| PubMed ID: 23831889	2013
Center volume, competition, and outcome in German liver transplant centers. Transplantation research\| PubMed ID: 24513092	2014
Intraoperative simulation of remnant liver function during anatomic liver resection with indocyanine green clearance (LiMON) measurements. HPB : the official journal of the International Hepato Pancreato Biliary Association\| PubMed ID: 25581073	2015
En-bloc resection of a giant retroperitoneal lipoma: a case report and review of the literature. BMC research notes\| PubMed ID: 25890295	2015
[Safety of brain dead organ donors]. MMW Fortschritte der Medizin\| PubMed ID: 26019096	2015
Benefit in liver transplantation: a survey among medical staff, patients, medical students and non-medical university staff and students. BMC medical ethics\| PubMed ID: 29433496	2018
Perivascular Tumor-Infiltrating Leukocyte Scoring for Prognosis of Resected Hepatocellular Carcinoma Patients. Cancers\| PubMed ID: 30340430	2018

Markus Guba

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