¢ËÌ‹ÙÚÈÔ˜ Δ·ÎÔ‡‰·˜ μ·Û›ÏÂÈÔ˜ ¶··ÓÈÎÔÏ¿Ô˘ πˆ¿ÓÓ˘ ºÔ‡˙·˜
£E™™A§ONIKH 2008
ªÂÙ·ÌÔۯ‡ÛÂȘ 2008 ™À°ÃƒON∏ ¶ƒO™∂°°π™∏ ∂π¢π∫ø¡ ¶ƒOB§∏ª∞Δø¡
¢ËÌ‹ÙÚÈÔ˜ Δ·ÎÔ‡‰·˜
μ·Û›ÏÂÈÔ˜ ¶··ÓÈÎÔÏ¿Ô˘
Iˆ¿ÓÓ˘ ºÔ‡˙·˜
ªÂÙ·ÌÔۯ‡ÛÂȘ 2008 ™À°ÃƒON∏ ¶ƒO™∂°°π™∏ ∂π¢π∫ø¡ ¶ƒOμ§∏ª∞Δø¡ ñ ÀÂÚ¢·ÈÛıËÙÔÔÈË̤ÓÔÈ Ï‹Ù˜ ÓÂÊÚÈÎÒÓ ÌÔÛ¯Â˘Ì¿ÙˆÓ ñ OÚÈ·ÎÔ› ‰fiÙ˜ Î·È Ï‹Ù˜ Ë·ÙÈÎÒÓ ÌÔÛ¯Â˘Ì¿ÙˆÓ ñ ∞Ó·ÈÛıËÛ›· Î·È ÂÓÙ·ÙÈ΋ ıÂڷ›· ÛÙË ÌÂÙ·ÌfiÛ¯˘Â˘ÛË ‹·ÙÔ˜
£E™™A§ONIKH 2008
H ÌÂÚÈ΋ ‹ ÔÏÈ΋ ·Ó·Ù‡ˆÛË Â›ÙÂ Ë Î·ı' ÔÈÔÓ‰‹ÔÙ ÙÚfiÔÓ ·Ó··Ú·ÁˆÁ‹ ÙÔ˘ ‚È‚Ï›Ô˘, ηıÒ˜ Î·È Ë ÊˆÙÔÙ‡ËÛË ÙÌ‹Ì·ÙÔ˜ ‹ ÔÏfiÎÏËÚÔ˘ ÙÔ˘ ‚È‚Ï›Ô˘, ¯ˆÚ›˜ ÙËÓ ¤ÁÁÚ·ÊË ¿‰ÂÈ· ÙˆÓ ÂΉÔÙÒÓ, ÙÈ̈ÚÂ›Ù·È ·fi ÙÔ ÓfiÌÔ.
£∂™™∞§O¡π∫∏ 2008
© ¢. Δ∞∫OY¢∞™, μ. ¶∞¶∞¡π∫O§∞OY, π. ºOÀ∑∞™
™ÙÔȯÂÈÔıÂÛ›· – ∂ÎÙ‡ˆÛË:
UNIVERSITY STUDIO PRESS A.E. AÚÌÂÓÔÔ‡ÏÔ˘ 32, 546 35 £∂™™∞§O¡I∫∏ TËÏ. 2310 208731, 2310 209837 Fax 2310-216647 E-mail: info@universitystudiopress.gr HÏÂÎÙÚÔÓÈÎfi ‚È‚ÏÈԈϛÔ: www.universitystudiopress.gr ™TOA TOY BIB§IOY – ¶ÂÛÌ·˙fiÁÏÔ˘ 5, 105 64 A£HNA TËÏ. & Fax 210 3211097
¶EPIEXOMENA
¶PO§O°O™ ...................................................................................................................................................................................................................................................... 7 EK¢OTE™ ........................................................................................................................................................................................................................................................... 9 ™Y°°PAºEI™ ............................................................................................................................................................................................................................................... 11
À¶∂ƒ∂À∞π™£∏ΔO¶Oπ∏ªE¡Oπ §H¶Δ∂™ ¡∂ºƒπ∫ø¡ ªO™Ã∂ÀªAΔø¡ ∞¡O™O§O°π∞ ∞ÓÔÛÔÏÔÁÈÎÔ› ·Ú¿ÁÔÓÙ˜ ÛÙË ÌÂÙ·ÌfiÛ¯Â˘ÛË ÓÂÊÚÔ‡: ∏ ÂÌÂÈÚ›· ÙÔ˘ CTS ª. ¢·ÓÈËÏ›‰Ë˜ °ÂÓˆÌÈ΋ – ¶ÚˆÙˆÌÈ΋ ÛÙË ÌÂÙ·ÌfiÛ¯Â˘ÛË ∞. ªÔ‡ÎÏ·
.......................................................
15
............................................................................................................................................
17
º˘ÛÈ΋ ·ÓÔÛ›· Î·È ÌÂÙ·ÌfiÛ¯Â˘ÛË ....................................................................................................................................................................... 25 ∞. º˘Ï¿ÎÙÔ˘ Dendritic cells (DCs) and regulatory T cells (Tregs) in renal transplantation Daniel V.
........................................................
29
¡∂ºƒO§O°π∞ ∞¢·ÈÛıËÙÔÔ›ËÛË ·ÛıÂÓÒÓ ˘Ô„‹ÊÈˆÓ ÁÈ· ÌÂÙ·ÌfiÛ¯Â˘ÛË ·fi ˙ˆÓÙ·Ófi ‰fiÙË ÓÂÊÚÔ‡ ...................... 31 ¢. ¶··‰ÔÔ‡ÏÔ˘ ∞¢·ÈÛıËÙÔÔ›ËÛË ÓÂÊÚÔ·ıÔ‡˜ Û ηٿÏÔÁÔ ·Ó·ÌÔÓ‹˜ ÁÈ· و̷ÙÈ΋ ÌÂÙ·ÌfiÛ¯Â˘ÛË ∫. ºÔ˘ÚÙÔ‡Ó·˜ O ÚÔ¢·ÈÛıËÙÔÔÈË̤ÓÔ˜ Ï‹Ù˘ ÓÂÊÚÈÎÔ‡ ÌÔۯ‡̷ÙÔ˜ ª. ¢·ÚÂÌ¿, π.¡. ªÔϤÙÙ˘
....................
35
......................................................................................................
43
Kidney Transplantation in Highly sensitized recipients .................................................................................................................. 45 G. Tsoulfas, T. Kawai
Oƒπ∞∫Oπ ¢OΔ∂™ ∫∞π §∏¶Δ∂™ ∏¶∞Δπ∫ø¡ ªO™Ã∂Àª∞Δø¡ ∑ÒÓÙ˜ Û˘ÁÁÂÓ›˜ ‰fiÙ˜ Ë·ÙÈÎÔ‡ ÌÔۯ‡̷ÙÔ˜ ................................................................................................................................... 51 π. ºÔ‡˙·˜, ¢. Δ·ÎÔ‡‰·˜ OÚÈ·ÎÔ› ‰fiÙ˜ ‹·ÙÔ˜ (¢fiÙ˜ Ì ‰È¢ڢṲ̂ӷ ÎÚÈÙ‹ÚÈ· ÂÈÏÔÁ‹˜) ¡. ∞ÓÙˆÓÈ¿‰Ë˜
5
.................................................................................
67
6 ªÂÙ·ÌfiÛ¯Â˘ÛË ·fi ‰fiÙ˜ Ì ÈÛÙÔÚÈÎfi Ë·Ù›Ùȉ·˜ π.°. °Ô˘Ï‹˜
.............................................................................................................................
73
OÚÈ·ÎÔ› Ï‹Ù˜ ......................................................................................................................................................................................................................... 77 ¢.∂. °È·ÎÔ˘ÛÙ›‰Ë˜ ∂Ӊ›ÍÂȘ Î·È ÎÚÈÙ‹ÚÈ· ÌÂÙ·ÌfiÛ¯Â˘Û˘ ‹·ÙÔ˜ ÛÙÔÓ Ë·ÙÔ΢ÙÙ·ÚÈÎfi ηÚΛÓÔ .................................................. 81 ¢. μÚÔ¯›‰Ë˜, ¢. Δ·ÎÔ‡‰·˜ ªÂÙ·ÌfiÛ¯Â˘ÛË ‹·ÙÔ˜ ÁÈ· ÎÈÚÚˆÙÈÎÔ‡˜ ·ÛıÂÓ›˜ Ì ˷ÙÔ΢ÙÙ·ÚÈÎfi ηÚΛÓÔ ÂÎÙfi˜ ÎÚÈÙËÚ›ˆÓ ªÈÏ¿ÓÔ˘ .................................................................................................................................................................................. 91 °.Ã. ™ˆÙËÚfiÔ˘ÏÔ˜
∞¡∞π™£∏™π∞ ∫∞π ∂¡Δ∞Δπ∫∏ £∂ƒ∞¶∂π∞ ™Δ∏ ª∂Δ∞ªO™Ã∂À™∏ ∏¶∞ΔO™ ¢π∞Ã∂πƒπ™∏ ∫ƒπ™πªø¡ ∫∞Δ∞™Δ∞™∂ø¡ ∫∞Δ∞ Δ∏ ¢π∞ƒ∫∂π∞ ª∂Δ∞ªO™Ã∂À™∏™ ∏¶∞ΔO™ ¶Ó¢ÌÔÓÈ΋ ˘¤ÚÙ·ÛË Î·È ÌÂÙ·ÌfiÛ¯Â˘ÛË ‹·ÙÔ˜ ............................................................................................................................... 99 °.π. ªÔ‡ÙÛÈ·ÓÔ˜ ¢ÈÂÁ¯ÂÈÚËÙÈ΋ ÓÂÊÚÈ΋ ‰˘ÛÏÂÈÙÔ˘ÚÁ›· ÛÙË ÌÂÙ·ÌfiÛ¯Â˘ÛË ‹·ÙÔ˜ ................................................................................. 100 ∞. §·Ì·‰·Ú›Ô˘ ∞ÈÌÔÚÚ·Á›· – ∏ ı¤ÛË ÙÔ˘ ÂÓÂÚÁÔÔÈË̤ÓÔ˘ ·Ú¿ÁÔÓÙ· VII ÛÙË ÌÂÙ·ÌfiÛ¯Â˘ÛË ‹·ÙÔ˜ ...................... 106 Ã. ¶··ÁˆÚÁ›Ô˘ ∫ÂÚ·˘ÓÔ‚fiÏÔ˜ Ë·Ù›Ùȉ· ∂. ∫·Ùۛη
...........................................................................................................................................................................................
115
¢π∞Ã∂πƒπ™∏ ∫ƒπ™πªø¡ ∫∞Δ∞™Δ∞™∂ø¡ ™Δ∏¡ ª.∂.£. ª∂Δ∞ Δ∏ ª∂Δ∞ªO™Ã∂À™∏ ∏¶∞ΔO™ ¶ÚÒÈÌË ‰˘ÛÏÂÈÙÔ˘ÚÁ›· ÙÔ˘ Ë·ÙÈÎÔ‡ ÌÔۯ‡̷ÙÔ˜ ÛÙË ªÔÓ¿‰· ∂ÓÙ·ÙÈ΋˜ £Âڷ›·˜ ª.∞. ¶·Û·ÎÈÒÙÔ˘
.......................
119
¢È¿ÁÓˆÛË Î·È ·ÓÙÈÌÂÙÒÈÛË ÛÔ‚·Ú‹˜ Û‹„˘ Î·È ÛËÙÈÎÔ‡ ÛÔÎ ÛÙË ª∂£ Û ·ÛıÂÓ›˜ Ì ÌÂÙ·ÌfiÛ¯Â˘ÛË ‹·ÙÔ˜ ................................................................................................................................................................................ 126 ∂. ªÔ˘ÏÔ‡‰Ë ..........
136
...................................................................
144
¡ÂÊÚÈ΋ ‰˘ÛÏÂÈÙÔ˘ÚÁ›· ÛÙÔ˘˜ ·ÛıÂÓ›˜ Ì ÌÂÙ·ÌfiÛ¯Â˘ÛË ‹·ÙÔ˜. ∞ÓÙÈÌÂÙÒÈÛË ÛÙË ª∂£ Ã. ∫˘‰ÒÓ· ∞›ÙÈ· ¯ÂÈÚÔ˘ÚÁÈ΋˜ ‰ÈÂÚ‡ÓËÛ˘ ÛÙË ÚÒÈÌË ÌÂÙ·ÌÔÛ¯Â˘ÙÈ΋ ÂÚ›Ô‰Ô °. ÿÌ‚ÚÈÔ˜
Infections in liver transplant patients: A short Overview and two case reports F.H. Saner, I. Fouzas, G. Sotiropoulos, A. Radtke, S. Nadalin, A. Paul
..................................................
147
¶PO§O°O™
∂›Ó·È ÌÂÁ¿ÏË Ë ÙÈÌ‹ Ì·˜ Ô˘ Îڷٿ٠ÛÙ· ¯¤ÚÈ· Û·˜ ÙÔ ‚È‚Ï›Ô ·˘Ùfi, ÙÔ ÔÔ›Ô ÂÚÈÏ·Ì‚¿ÓÂÈ Ù· ΛÌÂÓ· ÙˆÓ ÂÈÛËÁ‹ÛÂˆÓ Ô˘ ·Ó·Ù‡¯ıËÎ·Ó ÛÙÔ ™˘ÌfiÛÈÔ ªÂÙ·ÌÔۯ‡ÛÂˆÓ Ô˘ ÁÈ· ÙÚ›ÙË Û˘Ó¯‹ ¯ÚÔÓÈ¿ ‰ÈÔÚÁ·ÓÒÓÂÈ Ë ÃÂÈÚÔ˘ÚÁÈ΋ ∫ÏÈÓÈ΋ ªÂÙ·ÌÔۯ‡ÛÂˆÓ ÙÔ˘ ∞¶£. ™Ù· ı¤Ì·Ù· Ô˘ ÂÈϤ¯ıËÎ·Ó ı· ·Ó·ÁÓˆÚ›ÛÂÙ ÙËÓ ÚÔÛ¿ıÂÈ· ÚÔÛ¤ÁÁÈÛ˘ ÙÚÈÒÓ Â›Î·ÈÚˆÓ ·ÏÏ¿ Î·È ‰‡ÛÎÔÏˆÓ ÚÔ‚ÏËÌ¿ÙˆÓ Ô˘ ··Û¯ÔÏÔ‡Ó ÙËÓ ªÂÙ·ÌÔÛ¯Â˘ÙÈ΋ ∫ÔÈÓfiÙËÙ·. O ˘ÂÚ¢·ÈÛıËÙÔÔÈË̤ÓÔ˜ ·ÛıÂÓ‹˜ Ô˘ ·Ó·Ì¤ÓÂÈ ÓÂÊÚÈÎfi ÌfiÛ¯Â˘Ì·, Ô ÔÚÈ·Îfi˜ ‰fiÙ˘ Î·È Ï‹Ù˘ Ë·ÙÈÎÔ‡ ÌÔۯ‡̷ÙÔ˜ Î·È Ë ·Ó·ÈÛıËÛÈÔÏÔÁ›· Î·È ÂÓÙ·ÙÈ΋ ıÂڷ›· Ù˘ ÌÂÙ·ÌfiÛ¯Â˘Û˘ ‹·ÙÔ˜. ™ÙȘ ÛÂÏ›‰Â˜ ÙÔ˘ ı· ‰È·ÈÛÙÒÛÂÙ ÌÈ· Û ‚¿ıÔ˜ ·Ó·ÛÎfiËÛË Ù˘ ‰ÈÂıÓÔ‡˜ ‚È‚ÏÈÔÁÚ·Ê›·˜ Î·È Ú·ÎÙÈ΋˜ ·ÏÏ¿ Î·È Î·Ù¿ıÂÛË Ù˘ ÁÓÒÛ˘ Î·È Ù˘ ÂÌÂÈÚ›·˜ ÙˆÓ ‰È·ÎÂÎÚÈÌ¤ÓˆÓ ÂÈÛËÁËÙÒÓ, Ô˘ ›¯·Ó ÙËÓ Â˘Î·ÈÚ›· Ó· ÂÎı¤ÛÔ˘Ó ÙȘ ȉ¤Â˜ Î·È Ó· ÌÔÈÚ·ÛıÔ‡Ó ÙÔ˘˜ ÚÔ‚ÏËÌ·ÙÈÛÌÔ‡˜ ÙÔ˘˜ Ì fiÏÔ˘˜ ÙÔ˘˜ Û˘ÌÌÂÙ¤¯ÔÓÙ˜ ÛÙȘ ÂÚÁ·Û›Â˜ Ù˘ ÂÈÛÙËÌÔÓÈ΋˜ ·˘Ù‹˜ Û˘Ó¿ÓÙËÛ˘. ¢ËÌ‹ÙÚÈo˜ Δ·Îo‡‰·˜ ∫·ıËÁËÙ‹˜ ÃÂÈÚÔ˘ÚÁÈ΋˜ ¢È¢ı˘ÓÙ‹˜ ÃÂÈÚÔ˘ÚÁÈ΋˜ ∫ÏÈÓÈ΋˜ ªÂÙ·ÌÔۯ‡ÛÂˆÓ ∞¶£
7
EK¢OTE™
¢ËÌ‹ÙÚÈÔ˜ T·ÎÔ‡‰·˜ ÃÂÈÚÔ˘ÚÁfi˜, ∫·ıËÁËÙ‹˜ ∞¶£, ¢È¢ı˘ÓÙ‹˜ ÃÂÈÚo˘ÚÁÈ΋˜ ∫ÏÈÓÈ΋˜ ªÂÙ·Ìoۯ‡ÛÂˆÓ A¶£ °¡£ «πoÎÚ¿ÙÂÈo»
B·Û›ÏÂÈÔ˜ ¶··ÓÈÎÔÏ¿Ô˘ ÃÂÈÚÔ˘ÚÁfi˜, ∂›ÎÔ˘ÚÔ˜ ∫·ıËÁËÙ‹˜ ∞¶£, ÃÂÈÚo˘ÚÁÈ΋ ∫ÏÈÓÈ΋ ªÂÙ·Ìoۯ‡ÛÂˆÓ A¶£ °¡£ «πoÎÚ¿ÙÂÈo»
πˆ¿ÓÓ˘ ºÔ‡˙·˜ ÃÂÈÚo˘ÚÁfi˜, §¤ÎÙÔÚ·˜ ∞¶£, ÃÂÈÚo˘ÚÁÈ΋ ∫ÏÈÓÈ΋ ªÂÙ·Ìoۯ‡ÛÂˆÓ A¶£ °¡£ «πoÎÚ¿ÙÂÈo»
9
™Y°°PAºEI™ •¤ÓÔÈ ™˘ÁÁÚ·Ê›˜: 1. Daniel Volker MD, Professor, Department of Transplantation Immunology, Institute of Immunology, University of Heidelberg 2. Kawai Tatsuo, Associate Professor of Surgery, Transplant Unit, Massachusetts General Hospital, Harvard Medical School 3. Saner Fuat Hakan, PD Dr. med., Intensive Care Unit, Department of General, Visceral and Transplant Surgery, University Hospital, Essen 4. Sotiropoulos Georgios PD Dr. med., Department of General and Abdominal Surgery, Johannes Gutenberg University Hospital, Mainz, Germany
ŒÏÏËÓ˜ ™˘ÁÁÚ·Ê›˜: 1. ∞ÓÙˆÓÈ¿‰Ë˜ ¡ÈÎfiÏ·Ô˜, ÃÂÈÚÔ˘ÚÁfi˜ §¤ÎÙÔÚ·˜ ∞¶£, ÃÂÈÚÔ˘ÚÁÈ΋ ∫ÏÈÓÈ΋ ªÂÙ·ÌÔۯ‡ÛÂˆÓ ∞¶£, °¡£ πÔÎÚ¿ÙÂÈÔ 2. μÚÔ¯›‰Ë˜ ¢ÈÔÓ‡ÛÈÔ˜, ÃÂÈÚÔ˘ÚÁfi˜, Adj. Professor of Surgery, HepatoPancreatoBiliary and Transplant Department, McGill University, Montreal, ∫·Ó·‰¿˜, ∂ÈÛÙËÌÔÓÈÎfi˜ ™˘ÓÂÚÁ¿Ù˘ ÃÂÈÚÔ˘ÚÁÈ΋˜ ∫ÏÈÓÈ΋˜ ªÂÙ·ÌÔۯ‡ÛÂˆÓ ∞¶£, °¡£ πÔÎÚ¿ÙÂÈÔ 3. °È·ÎÔ˘ÛÙ›‰Ë˜ ¢ËÌ‹ÙÚÈÔ˜, ÃÂÈÚÔ˘ÚÁfi˜ §¤ÎÙÔÚ·˜ ∞¶£, ÃÂÈÚÔ˘ÚÁÈ΋ ∫ÏÈÓÈ΋ ªÂÙ·ÌÔۯ‡ÛÂˆÓ ∞¶£, °¡£ πÔÎÚ¿ÙÂÈÔ 4. °Ô˘Ï‹˜ πˆ¿ÓÓ˘, °·ÛÙÚÂÓÙÂÚÔÏfiÁÔ˜ ∂›ÎÔ˘ÚÔ˜ ∫·ıËÁËÙ‹˜ ∞¶£, ¢’ ¶·ıÔÏÔÁÈ΋ ∫ÏÈÓÈ΋, °¡£ πÔÎÚ¿ÙÂÈÔ 5. ¢·ÓÈËÏ›‰Ë˜ ªÈ¯¿Ï˘, ∫·ıËÁËÙ‹˜ ¶·ıÔÏÔÁ›·˜-∞ÓÔÛÔÏÔÁ›·˜, π·ÙÚÈ΋˜ ™¯ÔÏ‹˜ ∞¶£, ∞’ ¶·ıÔÏÔÁÈ΋ ∫ÏÈÓÈ΋, ¶°¡£ ∞Ã∂¶∞ 6. §·Ì·‰·Ú›Ô˘ ∫·ÙÂÚ›Ó·, ∞Ó·ÈÛıËÛÈÔÏfiÁÔ˜ ∂ÈÌÂÏ‹ÙÚÈ· ∞’, °¡∞ §·˚Îfi 7. ÿÌ‚ÚÈÔ˜ °ÂÒÚÁÈÔ˜, ÃÂÈÚÔ˘ÚÁfi˜ ∞Ó·ÏËÚˆÙ‹˜ ¢È¢ı˘ÓÙ‹˜, ÃÂÈÚÔ˘ÚÁÈ΋ ∫ÏÈÓÈ΋ ªÂÙ·ÌÔۯ‡ÛÂˆÓ ∞¶£, °¡£ πÔÎÚ¿ÙÂÈÔ 8. ∫·Ùۛη ∂ϤÓË, ∞Ó·ÈÛıËÛÈÔÏfiÁÔ˜ ∂ÈÌÂÏ‹ÙÚÈ· ∞’, ∞Ó·ÈÛıËÛÈÔÏÔÁÈÎfi ΔÌ‹Ì·, °¡£ πÔÎÚ¿ÙÂÈÔ 9. ∫˘‰ÒÓ· ÃÚÈÛÙ›Ó·, ¶·ıÔÏfiÁÔ˜-∂ÓÙ·ÙÈÎÔÏfiÁÔ˜, ∂ÈÌÂÏ‹ÙÚÈ· μ’ ª∂£, °¡£ πÔÎÚ¿ÙÂÈÔ 10. ªÔ˘ÏÔ‡‰Ë ∂ϤÓË, ∞Ó·ÈÛıËÛÈÔÏfiÁÔ˜-∂ÓÙ·ÙÈÎÔÏfiÁÔ˜, ∂ÈÌÂÏ‹ÙÚÈ· ∞’, ª∂£, °¡£ πÔÎÚ¿ÙÂÈÔ 11. ªÔ‡ÙÛÈ·ÓÔ˜ °ÂÒÚÁÈÔ˜, ∞Ó·ÈÛıËÛÈÔÏfiÁÔ˜ ∂ÈÌÂÏËÙ‹˜ ∞’, ∞’ ∞Ó·ÈÛıËÛÈÔÏÔÁÈÎfi ΔÌ‹Ì·, °¡£ πÔÎÚ¿ÙÂÈÔ 12. ªÔϤÙ˘ πˆ¿ÓÓ˘, ¡ÂÊÚÔÏfiÁÔ˜ ¢È¢ı˘ÓÙ‹˜ ¡ÂÊÚÔÏÔÁÈ΋˜ ∫ÏÈÓÈ΋˜, °¡∞ §·˚Îfi 13. ªÔ‡ÎÏ· ÕÓÓ·, μÈÔÏfiÁÔ˜, ∂ıÓÈÎfi ¶ÂÚÈÊÂÚÂÈ·Îfi ∫¤ÓÙÚÔ πÛÙÔÛ˘Ì‚·ÙfiÙËÙ·˜-ΔÌ‹Ì· ∞ÓÔÛÔÏÔÁ›·˜, °¡£ πÔÎÚ¿ÙÂÈÔ 14. ¶··ÁˆÚÁ›Ô˘ ÃÚ˘ÛԇϷ, ∞Ó·ÈÛıËÛÈÔÏfiÁÔ˜, ∂ÍÂȉÈ΢fiÌÂÓË ª∂£, °¡£ πÔÎÚ¿ÙÂÈÔ 15. ¶·Û·ÎÈÒÙÔ˘ ª·Ú›ÏË, ÃÂÈÚÔ˘ÚÁfi˜-∂ÓÙ·ÙÈÎÔÏfiÁÔ˜, ∞Ó·ÏËÚÒÙÚÈ· ¢È¢ı‡ÓÙÚÈ· ª∂£, °¡£ πÔÎÚ¿ÙÂÈÔ 16. ¶··‰ÔÔ‡ÏÔ˘ ¢ÒÚ·, ∂ÈÌÂÏ‹ÙÚÈ· ∞’ ¡ÂÊÚÔÏÔÁ›·˜, °¡£ ¶··ÁˆÚÁ›Ô˘ 17. Δ·ÎÔ‡‰·˜ ¢ËÌ‹ÙÚÈÔ˜, ÃÂÈÚÔ˘ÚÁfi˜, ∫·ıËÁËÙ‹˜ ∞¶£, ¢È¢ı˘ÓÙ‹˜ ÃÂÈÚÔ˘ÚÁÈ΋˜ ∫ÏÈÓÈ΋˜ ªÂÙ·ÌÔۯ‡ÛÂˆÓ ∞¶£, °¡£ πÔÎÚ¿ÙÂÈÔ 18. ΔÛÔ˘ÏÊ¿˜ °ÂÒÚÁÈÔ˜, ÃÂÈÚÔ˘ÚÁfi˜, ∂›ÎÔ˘ÚÔ˜ ∫·ıËÁËÙ‹˜ ÃÂÈÚÔ˘ÚÁÈ΋˜ ªÂÙ·ÌÔۯ‡ÛˆÓ, Solid Organ Transplantation, University of Rochester, Medical Center, New York, ∂ÈÛÙËÌÔÓÈÎfi˜ ™˘ÓÂÚÁ¿Ù˘ ÃÂÈÚÔ˘ÚÁÈ΋˜ ∫ÏÈÓÈ΋˜ ªÂÙ·ÌÔۯ‡ÛÂˆÓ ∞¶£, °¡£ πÔÎÚ¿ÙÂÈÔ 19. ºÔ‡˙·˜ πˆ¿ÓÓ˘, ÃÂÈÚÔ˘ÚÁfi˜ §¤ÎÙÔÚ·˜ ∞¶£, ÃÂÈÚÔ˘ÚÁÈ΋ ∫ÏÈÓÈ΋ ªÂÙ·ÌÔۯ‡ÛÂˆÓ ∞¶£, °¡£ πÔÎÚ¿ÙÂÈÔ 20. ºÔ˘ÚÙÔ‡Ó·˜ ∫ˆÓÛÙ·ÓÙ›ÓÔ˜, ∂›ÎÔ˘ÚÔ˜ ∫·ıËÁËÙ‹˜ ¡ÂÊÚÔÏÔÁ›·˜, ¶°¶¡ ¶·ÙÚÒÓ 21. º˘Ï¿ÎÙÔ˘ ∞ÛË̛ӷ, μÈÔ·ıÔÏfiÁÔ˜ ∂ÈÌÂÏ‹ÙÚÈ· ∞’, ∂ıÓÈÎfi ¶ÂÚÈÊÂÚÂÈ·Îfi ∫¤ÓÙÚÔ πÛÙÔÛ˘Ì‚·ÙfiÙËÙ·˜-ΔÌ‹Ì· ∞ÓÔÛÔÏÔÁ›·˜, °¡£ πÔÎÚ¿ÙÂÈÔ
11
Y¶EƒEYAπ™£∏ΔO¶Oπ∏ªE¡Oπ §∏¶ΔE™ ¡Eºƒπ∫ø¡ ªO™ÃEYªAΔø¡
13
AÓÔÛÔÏÔÁÈÎÔ› ·Ú¿ÁÔÓÙ˜ ÛÙË ÌÂÙ·ÌfiÛ¯Â˘ÛË ÓÂÊÚÔ‡: H ÂÌÂÈÚ›· ÙÔ˘ CTS ª. ¢·ÓÈËÏ›‰Ë˜
Ó·È ·ÎfiÌ· ÌÂÁ·Ï‡ÙÂÚÔ˜ fiÙ·Ó Ù· ÚÔÛ¯ËÌ·ÙÈṲ̂ӷ ΢ÙÙ·ÚÔÙÔÍÈο ·ÓÙÈÛÒÌ·Ù· ˘ÂÚ‚·›ÓÔ˘Ó ÙÔ 10%. ™Ù· Ï·›ÛÈ· ÙˆÓ ÂÚ¢ÓÒÓ ÙÔ˘ CTS ·ÔηχÊıËΠ›Û˘ Ô ÌÂȈ̤ÓÔ˜ ÚfiÏÔ˜ Ù˘ ÈÛÙÔÛ˘Ì‚·ÙfiÙËÙ·˜ ÛÙȘ ÓÂÊÚÈΤ˜ ÌÂÙ·ÌÔۯ‡ÛÂȘ Û ·ÛıÂÓ›˜ Ù˘ Ì·‡Ú˘ Ê˘Ï‹˜, Ô ÚfiÏÔ˜ ÙÔ˘ ¯ÚfiÓÔ˘ ·ÈÌÔοı·ÚÛ˘ ÚÈÓ ÙË ÌÂÙ·ÌfiÛ¯Â˘ÛË ÁÈ· ÙËÓ ÂÈ‚›ˆÛË ÙÔ˘ ÓÂÊÚÈÎÔ‡ ÌÔۯ‡̷ÙÔ˜, ο. ™¯ÂÙÈο Ì ÙÔÓ ÚfiÏÔ ÙÔ˘ ÚˆÙÔ·ıÔ‡˜ ÓÔÛ‹Ì·ÙÔ˜, Ì ‚¿ÛË ÌÂϤÙ˜ ÙÔ˘ CTS ‰È·ÈÛÙÒıËΠfiÙÈ ·˘ÍË̤ÓË ÂÈ‚›ˆÛË ÂÌÊ·Ó›˙Ô˘Ó ·ÛıÂÓ›˜ Ì ÓÂÊÚÈ΋ ·Ó¿ÚÎÂÈ· ÔÊÂÈÏfiÌÂÓË Û ·Ó·ÙÔÌÈο ·›ÙÈ· Î·È ‰˘ÛϷۛ˜, ÂÓÒ Û¯ÂÙÈ΋ Ì›ˆÛË ·Ú·ÙËÚÂ›Ù·È Û ·ÛıÂÓ›˜ Ì Û. ‰È·‚‹ÙË, ·ÔÊÚ·ÎÙÈ΋ ÓÂÊÚÔ¿ıÂÈ· Î·È ÓÂÊÚÔÏÈı›·ÛË. ∏ ÌÔÚÊ‹ Ù˘ ÛÂÈÚ·Ì·ÙÔÓÂÊÚ›Ùȉ·˜ ÙÔ˘ Ï‹ÙË Û˘ÁηٷϤÁÂÙ·È Â›Û˘ ÌÂٷ͇ ÙˆÓ ·ÓÔÛÔÏÔÁÈÎÒÓ ·Ú·ÁfiÓÙˆÓ ÔÈ ÔÔ›ÔÈ ÂËÚ¿˙Ô˘Ó ÙËÓ ÂÈ‚›ˆÛË ÙˆÓ Ó. ÌÔÛ¯Â˘Ì¿ÙˆÓ: ηχÙÂÚË ÂÈ‚›ˆÛË ·ÚÔ˘ÛÈ¿˙Ô˘Ó ÔÈ Ï‹Ù˜ Ì ٷ¯¤ˆ˜ ÂÍÂÏÈÛÛfiÌÂÓË Â›Ù ÌÂÛ·ÁÁÂȷ΋ ÛÂÈÚ·Ì·ÙÔÓÂÊÚ›Ùȉ·. ™Â ¿ÏÏË ÌÂϤÙË ÙÔ˘ CTS ·ÔηχÊıËΠfiÙÈ Ë ·˘ÍË̤ÓË ËÏÈΛ· ÙÔ˘ ‰fiÙË, Ë Ê˘Ï‹ ÚÔ¤ÏÂ˘Û‹˜ ÙÔ˘ ηıÒ˜ Î·È Ë Ê˘Ï‹ ÙÔ˘ Ï‹ÙË, ·ÔÙÂÏÔ‡Ó Â›Û˘ ·Ú¿ÁÔÓÙ˜ -ÂӉ¯Ô̤ӈ˜ ·ÓÔÛÔÁÂÓÂÙÈÎÔ‡˜- Ô˘ ÂȉÚÔ‡Ó ÛÙË Ì·ÎÚfi¯ÚÔÓË ÂÈ‚›ˆÛË ÙˆÓ ÌÔÛ¯Â˘Ì¿ÙˆÓ, ÂÓÒ ·Ú¿ÏÏËÏ· Ë ÂÈ‚›ˆÛË ÓÂÊÚÈÎÒÓ ÌÔÛ¯Â˘Ì¿ÙˆÓ Â›Ó·È ÌÂÁ·Ï‡ÙÂÚË fiÙ·Ó Ô ‰fiÙ˘ η٤ÏËÍ ·fi ÙÚ·˘Ì·ÙÈο ·›ÙÈ·, Û˘ÁÎÚÈÙÈο Ì ÌÔۯ‡̷ٷ ÚÔÂÚ¯fiÌÂÓ· ·fi ‰fiÙ˜ Ì ·ÁÁÂÈ·Îfi ÂÁÎÂÊ·ÏÈÎfi ÂÂÈÛfi‰ÈÔ. ∞›ÙÈ· ı·Ó¿ÙÔ˘ ÙÔ˘ ‰fiÙË Ù· ÔÔ›· ¢ÓÔÔ‡Ó ÙË Ì·ÎÚfi¯ÚÔÓË ÂÈ‚›ˆÛË ÙˆÌ·ÙÈÎÒÓ ÌÔÛ¯Â˘Ì¿ÙˆÓ Ê·›ÓÂÙ·È fiÙÈ Â›Ó·È Ë ÌËÓÈÁÁ›Ùȉ·, Ë ‰ËÏËÙËÚ›·ÛË Î·È Ô ÌÔÈÚ·›Ô˜ ÙÚ·˘Ì·ÙÈÛÌfi˜ (ÙÚÔ¯·›· ·Ù˘¯‹Ì·Ù·). OÈ ÌÂϤÙ˜ ÙÔ˘ CTS ¤¯Ô˘Ó ÂÂÎÙ·ı› Î·È ÛÙË ÛËÌ·Û›· ÌË ·ÓÔÛÔÏÔÁÈÎÒÓ ·Ú·Ì¤ÙÚˆÓ, fiˆ˜ ÁÈ· ·Ú¿‰ÂÈÁÌ· Ë ·ÚÙËÚȷ΋ ˘¤ÚÙ·ÛË ‡ÛÙÂÚ· ·fi ÙË ÌÂÙ·ÌfiÛ¯Â˘ÛË.
∏ ‰ÈÂıÓ‹˜ ÌÂϤÙË CTS (Collaborative Transplant Study) ȉڇıËΠÙÔ 1982 ÛÙË Ã·˚‰ÂÏ‚¤ÚÁË, ·fi ÙÔÓ Î·ıËÁËÙ‹ ∞ÓÔÛÔÏÔÁ›·˜ Gerhard Opelz Ì ¤‰Ú· ÙÔ πÓÛÙÈÙÔ‡ÙÔ ∞ÓÔÛÔÏÔÁ›·˜ ªÂÙ·ÌÔۯ‡ÛÂˆÓ ÙÔ˘ ¶·ÓÂÈÛÙËÌ›Ô˘ ÷˚‰ÂÏ‚¤ÚÁ˘, ÛÙÔ Î·ÈÓÔ‡ÚÁÈÔ ¶·ÓÂÈÛÙ‹ÌÈÔ NeuenHeimerfeld, ÛÂ Û˘ÓÂÚÁ·Û›· ·Ú¯Èο Ì 162 ∫¤ÓÙÚ· ªÂÙ·ÌÔۯ‡ÛÂˆÓ ·fi 28 ¯ÒÚ˜. ™ÎÔfi˜ Ù˘ ¢Ú›·˜ ·˘Ù‹˜ ÂÈÛÙËÌÔÓÈ΋˜ Û˘ÓÂÚÁ·Û›·˜ Â›Ó·È Ë ÌÂϤÙË, ÂÂÍÂÚÁ·Û›· Î·È ‰ËÌÔÛ›Â˘ÛË ·ÓÔÛÔÏÔÁÈÎÒÓ, ·ÓÔÛÔÁÂÓÂÙÈÎÒÓ ·ÏÏ¿ Î·È ¿ÏÏˆÓ ‰Â‰ÔÌ¤ÓˆÓ ·fi ÙÔÓ ¯ÒÚÔ ÙˆÓ ÌÂÙ·ÌÔۯ‡ÛÂˆÓ ÔÚÁ¿ÓˆÓ. ÃÚËÛÈÌÔÔÈÒÓÙ·˜ ‰Â‰Ô̤ӷ ·fi ÂÓÙ˘ˆÛȷο ÌÂÁ¿ÏÔ˘˜ ·ÚÈıÌÔ‡˜ ÓÂÊÚÈÎÒÓ ÌÂÙ·ÌÔۯ‡ÛˆÓ, ÔÈ ÌÂϤÙ˜ ÙÔ˘ CTS ·ÔÙÂÏÔ‡Ó Î·Ù¿ Ù· ÙÂÏÂ˘Ù·›· 24 ¤ÙË ÛÙ·ıÂÚ‹ ËÁ‹ ÏËÚÔÊÔÚÈÒÓ, fi¯È ÌfiÓÔ ÁÈ· ÙÔ˘˜ ‰È¿ÊÔÚÔ˘˜ - ·ÓÔÛÔÏÔÁÈÎÔ‡˜ Î·È ÌË - ·Ú¿ÁÔÓÙ˜ Ô˘ ÂËÚ¿˙Ô˘Ó ÙË Ì·ÎÚfi¯ÚÔÓË ÂÈ‚›ˆÛË ÙˆÓ ÓÂÊÚÈÎÒÓ ÌÔÛ¯Â˘Ì¿ÙˆÓ, ·ÏÏ¿ Î·È ÁÈ· ÙÔÓ ÙÚfiÔ ·ÓÙÈÌÂÙÒÈÛ‹˜ ÙÔ˘˜. Δ· Â˘Ú‹Ì·Ù· ·fi ÙȘ ‰È¿ÊÔÚ˜ ÛÙ·ÙÈÛÙÈΤ˜ ·Ó·Ï‡ÛÂȘ ·ÔÛÙ¤ÏÏÔÓÙ·È ·Ú¯Èο Û ÂÓËÌÂÚˆÙÈο Ê˘ÏÏ¿‰È· Ù·ÎÙÈ΋˜ ·ÏÏËÏÔÁÚ·Ê›·˜ οı 3 Ì‹Ó˜, ÂÓÒ ·fi ÙÔ 1990 ÙÔ ÂÚÈÔ‰ÈÎfi ‰ËÌÔÛ›Â˘Û˘ ÙˆÓ ÌÂÏÂÙÒÓ Â›Ó·È Î·Ù¿ ·ÚÈÔ ÏfiÁÔ ÙÔ “Transplant International”. ∫‡ÚÈ· ·ÓÙÈΛÌÂÓ· ÛÙȘ ÌÂϤÙ˜ ·˘Ù¤˜ ·ÔÙÂÏÔ‡Ó Ô ÚfiÏÔ˜ Ù˘ Û˘Ì‚·ÙfiÙËÙ·˜ ÛÙ· HLA Ù¿Í˘ π Î·È ππ ÁÈ· ÙË Ì·ÎÚÔ¯ÚfiÓÈ· ÂÈ‚›ˆÛË ÙÔ˘ ÓÂÊÚÈÎÔ‡ ÌÔۯ‡̷ÙÔ˜, Ô ÚfiÏÔ˜ Ù˘ ¢·ÈÛıËÙÔÔ›ËÛ˘ ÛÙ· ·ÓıÚÒÈÓ· Ï¢ÎÔ΢ÙÙ·ÚÈο ·ÓÙÈÁfiÓ·, Ô ÚfiÏÔ˜ ÙˆÓ ‰È¿ÊÔÚˆÓ ·Ú·Ì¤ÙÚˆÓ Û˘ÓÙ‹ÚËÛ˘ ÙˆÓ ÌÔÛ¯Â˘Ì¿ÙˆÓ, ·ÏÏ¿ ·ÎfiÌË Î·È ÙÔ˘ ÚˆÙÔ·ıÔ‡˜ ÓÔÛ‹Ì·ÙÔ˜, Ù˘ ËÏÈΛ·˜ Î·È Ù˘ ηÙËÁÔÚ›·˜ ÙÔ˘ ‰fiÙË, η. Ÿˆ˜ ‰È·ÈÛÙÒıËÎÂ, ÛÙÔ˘˜ ·ÛıÂÓ›˜ ˘„ËÏÔ‡ ÎÈÓ‰‡ÓÔ˘ Ú¤ÂÈ Ó· Û˘ÌÂÚÈÏËÊıÔ‡Ó Î·Ù¿ ·ÚÈÔ ÏfiÁÔ ÔÈ ˘Ô„‹ÊÈÔÈ Ì ΢ÙÙ·ÚÔÙÔÍÈο ·ÓÙÈÛÒÌ·Ù· (Panel Reactive Antibodies, PAR) ÂÚÈÛÛfiÙÂÚ· ·fi 50%, ÔÈ ·ÛıÂÓ›˜ Ì ·ӷÌÂÙ·ÌfiÛ¯Â˘ÛË Î·È ÔÈ ·ÛıÂÓ›˜ Ì ‰È·‚‹ÙË. O ÚfiÏÔ˜ Ù˘ Û˘Ì‚·ÙfiÙËÙ·˜ ÛÙ· HLA Ù¿Í˘ ππ Â›Ó·È Ï¤ÔÓ ÁÓˆÛÙfi fiÙÈ Â›-
15
16
ª. ¢∞¡π∏§π¢∏™
∏ ÚÔÛÊÔÚ¿ ÙÔ˘ CTS ‰ÂÓ ÂÚÈÔÚ›ÛÙËΠÛÙËÓ Ú·ÁÌ·ÙÔÔ›ËÛË Î·È ‰ËÌÔÛ›Â˘ÛË Û¯ÂÙÈÎÒÓ ÌÂÏÂÙÒÓ Î·È ÛÙËÓ Ù·ÎÙÈ΋ ·ÏÏËÏÔÁÚ·Ê›· Ì ÙÔ˘˜ Û˘ÌÌÂÙ¤¯ÔÓÙ˜, ·ÏÏ¿ ÚÔ¯ÒÚËÛÂ Î·È ÛÂ Û˘ÓÂÚÁ·Û›· Ì ÙËÓ ·ÔÛÙÔÏ‹ ‰ÂÈÁÌ¿ÙˆÓ ÁÈ· ÚÔÛ‰ÈÔÚÈÛÌfi ÂȉÈÎÒÓ Î˘ÙÙ·ÚÔÙÔÍÈÎÒÓ ·ÓÙÈۈ̿وÓ, ÛÙË ‰È¿ıÂÛË ·ÓÙȉڷÛÙËÚ›ˆÓ ÈÛÙÈ΋˜ Ù˘ÔÔ›ËÛ˘, ÛÙË ÌÂÙÂη›‰Â˘ÛË ÚÔÛˆÈÎÔ‡, Î.¿. ¶Ôχ ·ÍÈfiÏÔÁ˜ ›Û˘ Â›Ó·È Î·È ÔÈ ÏËÚÔÊÔڛ˜ Û¯ÂÙÈο Ì ÙȘ ÌÂÙ·ÌÔۯ‡ÛÂȘ ¿ÏÏˆÓ ÔÚÁ¿ÓˆÓ. ™‹ÌÂÚ·, ÙÔ CTS ÂÚÈÏ·Ì‚¿ÓÂÈ Î·È ÂÂÍÂÚÁ¿˙Â-
Ù·È ‰Â‰Ô̤ӷ ·fi 295.708 ÓÂÊÚÈΤ˜ ÌÂÙ·ÌÔۯ‡ÛÂȘ ÛÂ Û˘ÓÂÚÁ·Û›· Ì 225 ΤÓÙÚ· ªÂÙ·ÌÔۯ‡ÛÂˆÓ ·fi fiϘ ÙȘ Ë›ÚÔ˘˜. ¶·Ú¿ÏÏËÏ·, ¤¯ÂÈ Î·Ù·¯ˆÚ‹ÛÂÈ Î·È ÂÂÍÂÚÁ¿˙ÂÙ·È 51.163 ÌÂÙ·ÌÔۯ‡ÛÂȘ ‹·ÙÔ˜, 32.128 ηډȿ˜, 9.076 Ó¢ÌfiÓˆÓ, 8.444 ·ÁÎÚ¤·ÙÔ˜ Î·È 1.746 ηډȿ˜-Ó¢ÌfiÓˆÓ. ∫·Ù¿ Û˘Ó¤ÂÈ·, Â›Ó·È ‰˘Ó·ÙfiÓ Ó· ˘ÔÛÙËÚȯı› fiÙÈ ¤Ó· ÌÂÁ¿ÏÔ Ì¤ÚÔ˜ Ù˘ Û‡Á¯ÚÔÓ˘ ÁÓÒÛ˘ ÁÈ· ÙÔ˘˜ ·ÓÔÛÔÏÔÁÈÎÔ‡˜ Î·È ÏÔÈÔ‡˜ ·Ú¿ÁÔÓÙ˜ Ô˘ ÂËÚ¿˙Ô˘Ó ÙËÓ ÂÈ‚›ˆÛË ÓÂÊÚÈÎÒÓ ÌÔÛ¯Â˘Ì¿ÙˆÓ Î·È ·ÛıÂÓÒÓ ÔÊ›ÏÂÙ·È ÛÙË ‰ÈÂıÓ‹ ÌÂϤÙË CTS.
°ÂÓˆÌÈ΋ – ¶ÚˆÙˆÌÈ΋ ÛÙË ÌÂÙ·ÌfiÛ¯Â˘ÛË ∞. ªÔ‡ÎÏ·
∂ÈÛ·ÁˆÁ‹
·Ó¿Ï˘Û˘ ÓÔ˘ÎÏÂ˚ÓÈÎÒÓ ÔͤˆÓ, Ì ÛÎÔfi ·ÊÂÓfi˜ ÌÂÓ ÙË ‰È¿ÁÓˆÛË/ÚfiÁÓˆÛË ·ÛıÂÓÂÈÒÓ Î·È ·ÊÂÙ¤ÚÔ˘ ÙËÓ ·Ó›¯Ó¢ÛË ·ıÔÁfiÓˆÓ ÌÈÎÚÔÔÚÁ·ÓÈÛÌÒÓ. To ÎÂÓÙÚÈÎfi ‰fiÁÌ· Ù˘ ‚ÈÔÏÔÁ›·˜ Û˘ÓÔ„›˙ÂÙ·È ÛÙÔ fiÙÈ ÙÔ DNA Έ‰ÈÎÔÔÈ› RNA ÙÔ ÔÔ›Ô ÌÂÙ·ÊÚ¿˙ÂÙ·È Û ڈÙ½Ó˜. ∏ ÚÔËÁÔ‡ÌÂÓË ‰ÂηÂÙ›· Ì ÙËÓ Â›Ù¢ÍË Ù˘ ÔÏÔÎÏ‹ÚˆÛ˘ Ù˘ ·Ó¿ÁÓˆÛ˘ ÙÔ˘ ·ÓıÚÒÈÓÔ˘ ÁÔÓȉÈÒÌ·ÙÔ˜ (genomics) ¯·Ú·ÎÙËÚ›ÛÙËÎÂ Û·Ó ‰ÂηÂÙ›· ÙˆÓ –omics. OÈ ÂÈÛÙ‹ÌÔÓ˜ ÛÙfi¯Â˘·Ó ΢ڛˆ˜ ÛÙËÓ ·Ó¿Ù˘ÍË Ù¯ÓÔÏÔÁ›·˜ ÁÈ· ÙËÓ ÌÂϤÙË ÙˆÓ transcriptonics (mRNA transcripts – ·ÓÙ›ÁÚ·Ê·), proteomics (ÚˆÙ½Ó˜), metabolonics (ÚÔ˚fiÓÙ· ÌÂÙ·‚ÔÏÈÛÌÔ‡), glycomics (ÌÂÙ·‚ÔϤ˜ ˘‰ÚÔÁÔÓ·ÓıÚ¿ÎˆÓ Û ۯ¤ÛË Ì ڈÙ½Ó˜), phenomics (·ÏÏ·Á‹ Ê·ÈÓfiÙ˘Ô˘ Û·Ó ·ÔÙ¤ÏÂÛÌ· ÙÔ˘ ÁÂÓfiÙ˘Ô˘), Î.Ô.Î. ΔÂÏÈÎfi˜ ÛÙfi¯Ô˜ ÙˆÓ –omics ‹Ù·Ó ΢ڛˆ˜ Ë ÌÂϤÙË ÌÂÙ·-ÌÂÙ·ÊÚ·ÛÙÈÎÒÓ ÙÚÔÔÔÈ‹ÛÂˆÓ ÌÈ·˜ ÚˆÙ½Ó˘ fiˆ˜ Ë ÊˆÛÊÔÚ˘Ï›ˆÛË ‹ Ë ÚÔÛı‹ÎË ÔÏÈÁÔ۷ί·ÚÈÙÒÓ, ÔÈ Ù˘¯fiÓ ÌÂÙ·ÙÔ›ÛÂȘ Ù˘ ̤۷ ÛÙÔ Î‡ÙÙ·ÚÔ, .¯. ·fi ÙÔ Î˘Ù·ÚfiÏ·ÛÌ· ÛÙÔÓ ˘Ú‹Ó·, Î·È Ù¤ÏÔ˜ Ô ÌÂÙ·‚ÔÏÈÛÌfi˜ Ù˘. ŸÏ˜ ÔÈ ·Ú·¿Óˆ ÌÂÙ·ÙÚÔ¤˜ ·ÔÙÂÏÔ‡Ó ‚ÈÔÏÔÁÈο ÌÔÓÔ¿ÙÈ· ÙˆÓ ÔÔ›ˆÓ Ë ÔÚ›· ÈÛÔÚÚÔ› ·Ó¿ÌÂÛ· ÛÙȘ ¤ÓÓÔȘ ˘Á›·-·Ûı¤ÓÂÈ·.
∏ Û‡Á¯ÚÔÓË ¤Ú¢ӷ Û ı¤Ì·Ù· ÌÂÙ·ÌfiÛ¯Â˘Û˘, ÂÈÎÂÓÙÚÒÓÂÙ·È Ù· ÙÂÏÂ˘Ù·›· ¯ÚfiÓÈ·, ΢ڛˆ˜ ÛÙË ÌÂϤÙË ıÂÌÂÏȈ‰ÒÓ Ì˯·ÓÈÛÌÒÓ Ô˘ Û¯ÂÙ›˙ÔÓÙ·È Ì ÙËÓ ·fiÚÚÈ„Ë ÌÔÛ¯Â˘Ì¿ÙˆÓ Î·È ·Ó·Ï‡ÂÈ in vitro Î·È in vivo ÙË Ê˘ÛÈÎÔ¯ËÌÈ΋ ‰ÔÌ‹ Ì·ÎÚÔÌÔÚ›ˆÓ Î·È ÙÔÓ ÏÂÈÙÔ˘ÚÁÈÎfi ÚfiÏÔ Û˘ÁÎÂÎÚÈÌ¤ÓˆÓ ÁÔÓȉ›ˆÓ ÛÙËÓ ·ÓÔÛȷ΋ ·fiÎÚÈÛË. ∏ ηٷÓfiËÛË Ù˘ ÌÔÚȷ΋˜ ‚¿Û˘ ‚ÈÔÏÔÁÈÎÒÓ Ê·ÈÓÔ̤ӈÓ, Ô˘ Û¯ÂÙ›˙ÔÓÙ·È Ì ÙËÓ ‚Ï¿‚Ë Î·È ÙËÓ ·ÔηٿÛÙ·ÛË ÈÛÙÒÓ Î·È ÙˆÓ ·ÓÔÛÈ·ÎÒÓ Ì˯·ÓÈÛÌÒÓ Ô˘ ÂÌϤÎÔÓÙ·È ÛÙȘ ·Ú·¿Óˆ ‰È·ÊÔÚÔÔÈ‹ÛÂȘ, ·ÔÙÂÏ› ÙÔ Û‡ÓıÂÙÔ ÂÚ¢ÓËÙÈÎfi Úfi‚ÏËÌ· Ù˘ ÌÔÚȷ΋˜ ‚ÈÔÏÔÁ›·˜ ÛÙÔÓ ÙÔ̤· ÙˆÓ ÌÂÙ·ÌÔۯ‡ÛˆÓ. OÈ ·Ú·Î¿Ùˆ ̤ıÔ‰ÔÈ Ù˘ ÌÔÚȷ΋˜ ‚ÈÔÏÔÁ›·˜ ÛÂ Û˘Ó‰˘·ÛÌfi Ì ÙËÓ ‰˘Ó·ÌÈ΋ ·Ó¿Ù˘ÍË Ù˘ ‚ÈÔÏËÚÔÊÔÚÈ΋˜ ˘fiÛ¯ÔÓÙ·È ÚfiÔ‰Ô ÛÙË ‰È·Ï‡ηÓÛË Ù˘ ‚ÈÔÏÔÁ›·˜ ΢ÙÙ¿ÚÔ˘, Ô˘ Ô‰ËÁ› Û ÂÈ‚›ˆÛË ÙÔ˘ ÌÔۯ‡̷ÙÔ˜: ➤ ➤ ➤ ➤ ➤ ➤ ➤ ➤ ➤ ➤ ➤ ➤
ÀÂÚÊ˘ÁÔΤÓÙÚËÛË ∏ÏÂÎÙÚÔÊfiÚËÛË À‚ÚȉÈÛÌfi˜ ÓÔ˘ÎÏÂ˚ÓÈÎÒÓ ÔͤˆÓ DNA sequencing ªÂÙ·ÌfiÚʈÛË Â˘Î·Ú˘ˆÙÈÎÒÓ Î˘ÙÙ¿ÚˆÓ Δ¯ÓÈΤ˜ ÎψÓÔÔ›ËÛ˘ °ÂÓÂÙÈ΋ ÌÂÙ·ÌfiÚʈÛË ˙ÒˆÓ ªÔÓÔÎψÓÈο ·ÓÙÈÛÒÌ·Ù· ÷ÚÙÔÁÚ¿ÊËÛË mRNA ÛÙÔ DNA DNA arrays ∞Ó·Û˘Ó‰˘·Ṳ̂ÓÔ DNA ¢ËÌÈÔ˘ÚÁ›· ÁÂӈ̷ÙÈÎÒÓ Î·È cDNA ‚È‚ÏÈÔıËÎÒÓ ➤ Δ¯ÓÈΤ˜ ·Ó¿Ï˘Û˘ ÔÏ˘ÌÔÚÊÈÛÌÔ‡ ÌÔÓfiÎψÓ˘ ·Ï˘Û›‰·˜ ➤ ª¤ıÔ‰ÔÈ ÔÏ˘ÌÔÚÊÈÛÌÔ‡ ÌÂÁ¤ıÔ˘˜ ÂÚÈÔÚÈÛÙÈÎÒÓ ÙÌËÌ¿ÙˆÓ
ªÂϤÙ˜ ÌÔÚȷ΋˜ ‚ÈÔÏÔÁ›·˜ Î·È DNA arrays ÛÙË ÌÂÙ·ÌfiÛ¯Â˘ÛË ™ÎÔfi˜ Ù˘ ÁÂÓˆÌÈ΋˜ (genomics) ‰ÂÓ Â›Ó·È ·Ï¿ Ó· ‰ÒÛÂÈ ¤Ó· ηٿÏÔÁÔ Ì fiÏ· Ù· ÁÔÓ›‰È· Ô˘ ·ÔÙÂÏÔ‡Ó ÙÔ ·ÓıÚÒÈÓÔ ÁÔÓȉ›ˆÌ· Î·È ÏËÚÔÊÔڛ˜ ÁÈ· ÙË ÏÂÈÙÔ˘ÚÁ›· ÙÔ˘˜, ·ÏÏ¿ ΢ڛˆ˜ Ó· Á›ÓÔ˘Ó Î·Ù·ÓÔËÙÔ› ÔÈ ÂÈ̤ÚÔ˘˜ Ì˯·ÓÈÛÌÔ› ̤ۈ ÙˆÓ ÔÔ›ˆÓ ·ÏÏËÏÂȉڿ ÙÔ ÁÔÓȉ›ˆÌ· Ì ÙÔÓ Â·˘Ùfi ÙÔ˘ ·ÏÏ¿ Î·È Ì ÙÔ ÂÚÈ‚¿ÏÏÔÓ. O ·ÚÈÔ˜ ÙÂÏÈÎfi˜ ÛÙfi¯Ô˜ Â›Ó·È Ë ·Ó·ÁÓÒÚÈÛË ‚ÈÔÏÔÁÈÎÒÓ ÌÔÚ›ˆÓ-‰ÂÈÎÙÒÓ, ··Ú·›ÙËÙˆÓ ÁÈ· ÙË ‰È¿ÁÓˆÛË ·ÛıÂÓÂÈÒÓ Ù· ÔÔ›· fï˜ ı· Ô‰ËÁ‹ÛÔ˘Ó Î·È ÛÙË ıÂڷ›·. OÈ ÚÒÙ˜ ÂÊ·ÚÌÔÁ¤˜ Ù˘ ÁÂÓˆÌÈ΋˜ ÛÂ Â›Â‰Ô ‰È¿ÁÓˆÛ˘/ÚfiÁÓˆÛ˘ ¤ÁÈÓ·Ó ÛÙËÓ ¤-
¶·Ú¿ÏÏËÏ·, ·Ó·Ù‡ÛÛÂÙ·È Ô ÎÏ¿‰Ô˜ Ù˘ ÌÔÚȷ΋˜ ‰È·ÁÓˆÛÙÈ΋˜, Ë ÔÔ›· ·ÍÈÔÔÈ› Ù¯ÓÈΤ˜
17
18
∞. ª¶√À∫§∞
Ú¢ӷ ÙÔ˘ ηÚΛÓÔ˘, Ù˘ ·ÓÔÛ›·˜ Î·È ÙˆÓ Î·Ú‰È·ÁÁÂÈ·ÎÒÓ ÓÔÛËÌ¿ÙˆÓ. ¶ÚfiÛÊ·Ù· Ë ¤Ú¢ӷ ·˘Ù‹ ¤¯ÂÈ ÂÂÎÙ·ı› Î·È ÂÊ·ÚÌfi˙ÂÙ·È ÛÙË ‚ÈÔÏÔÁ›· Ù˘ ÌÂÙ·ÌfiÛ¯Â˘Û˘. ΔÔ ÂӉȷʤÚÔÓ ÂÓÙÔ›˙ÂÙ·È ÛÙËÓ Ù·˘ÙÔÔ›ËÛË ÙˆÓ ÌÔÚÈ·ÎÒÓ Ì˯·ÓÈÛÌÒÓ Û ÔÍ›· Î·È ¯ÚfiÓÈ· ·fiÚÚÈ„Ë ÌÔۯ‡̷ÙÔ˜, ηıÒ˜ Î·È ÛÙÔÓ ÂÓÙÔÈÛÌfi ‚ÈÔÏÔÁÈÎÒÓ ‰ÂÈÎÙÒÓ, Ô˘ Û¯ÂÙ›˙ÔÓÙ·È Ì ÙË Ú‡ıÌÈÛË Ù˘ ·ÓÔÛÔηٷÛÙÔÏ‹˜ Ì ÛÙfi¯Ô ÙËÓ ÂÈ‚›ˆÛË ÙÔ˘ ÌÔۯ‡̷ÙÔ˜. °È· ÙË Ú‡ıÌÈÛË Ù˘ ·ÓÔÛÔηٷÛÙÔÏ‹˜ ¤¯Ô˘Ó ‹‰Ë ·Ó·Ù˘¯ı› ÌÔÓ٤Ϸ Û ÂÈÚ·Ì·Ùfi˙ˆ· Î·È Î˘ÙÙ·ÚÔηÏÏȤÚÁÂȘ. ™ÙȘ ÚÒÙ˜ ‚ÈÔÏÔÁÈΤ˜ ÌÂϤÙ˜ Ô˘ ‰ڷÈÒÓÔ˘Ó ÙËÓ ·Ú·ÎÔÏÔ‡ıËÛË Ù˘ ·fiÚÚȄ˘ ÌÔۯ‡̷ÙÔ˜ ¯ÚËÛÈÌÔÔÈÒÓÙ·˜ ÔÛÔÙÈ΋ ¤ÎÊÚ·ÛË ÁÔÓȉ›ˆÓ Ì ˘ÏÈÎfi ·fi ‚ÈÔ„›Â˜ ÂÌϤÎÔÓÙ·È Î˘Ú›ˆ˜: ΢ÙÔΛÓ˜ .¯. TNF-a (tumor necrosis factor alpha), PDGF (platelet-derived growth factor) , bFGF (basic fibroblast growth factor) Û ηډȷο ÌÔۯ‡̷ٷ 1 , IFN-Á (interferon-gamma), ICAM-1 (intercellular adhesion molecule) Û ÌÔۯ‡̷ٷ Ó¢ÌfiÓˆÓ2, Î·È Ù¤ÏÔ˜ cytotoxic T-cell ÌfiÚÈ·, .¯. granzyme A Î·È B, ÚˆÙÂ˚Ó¿Û˜ ÛÂÚ›Ó˘, Î·È Ê˘ÛÈο ΢ÙÙ·ÚÔÎÙfiÓ· Û ÓÂÊÚÈο ÌÔۯ‡̷ٷ3. ∂›Û˘ Ë ÈÓÙÂÚÏ¢ΛÓË-10, Î·È -2 Û¯ÂÙ›˙ÔÓÙ·È Ì ÔÍ›· ·fiÚÚÈ„Ë ÓÂÊÚÈÎÔ‡ ÌÔۯ‡̷ÙÔ˜4 ÂÓÒ Ë ÚˆÙ½ÓË TGF‚-1 (transforming growth factor) Ì ¯ÚfiÓÈ· ÓÂÊÚÔ¿ıÂÈ· ÌÔۯ‡̷ÙÔ˜. ™˘ÌÂÚ·›ÓÔ˘Ì ‰ËÏ·‰‹ ‰È·ÊÔÚÂÙÈ΋ ÁÔÓȉȷ΋ ¤ÎÊÚ·ÛË Û ‰È·ÊÔÚÂÙÈÎÔ‡˜ Ù‡Ô˘˜ ·fiÚÚȄ˘. ÃÚËÛÈÌÔÔÈÒÓÙ·˜ real time PCR ‰È·ÈÛÙÒıËΠ›Û˘ (¢·ÈÛıËÛ›· 100% ,ÂȉÈÎfiÙËÙ· 100%), ·˘ÍË̤ÓË ‰Ú·ÛÙÈÎfiÙËÙ· ÙˆÓ ÚˆÙÂ˚ÓÒÓ perforin, granzyme B, Î·È fas ligant Û ÔÍ›˜ ÓÂÊÚÈΤ˜ ·ÔÚÚ›„ÂȘ4. ¶ÏËıÒÚ· ÂÚÁ·ÛÈÒÓ Ì ELIS∞ Î·È ELISPOT Û ÏÂÌÊÔ·ÙÙ·Ú· ÂÚÈÊÂÚÈÎÔ‡ ·›Ì·ÙÔ˜ (ƒμL) ‰Â›¯ÓÔ˘Ó ÙË Û˘Û¯¤ÙÈÛË ‰Ú·ÛÙÈÎfiÙËÙ·˜ IFN-Á, Î·È ÙˆÓ ÈÓÙÂÚÏ¢ÎÈÓÒÓ-5,-7,-10,-15,-4, -6 Ì ÙÔÓ ·˘ÍË̤ÓÔ Î›Ó‰˘ÓÔ ÔÍ›·˜ ·fiÚÚȄ˘ ·ÏÏÔÌÔۯ‡̷ÙÔ˜5. ∏ ÌÂϤÙË Ù˘ ÁÔÓȉȷ΋˜ ¤ÎÊÚ·Û˘ Û ۯ¤ÛË Ì ÙËÓ ÎÏÈÓÈ΋ ÂÈÎfiÓ· ·ÛıÂÓÒÓ ÌÂÙ¿ ÙË ÌÂÙ·ÌfiÛ¯Â˘ÛË, ¤¯ÂÈ ÂÈÎÂÓÙÚˆı› ΢ڛˆ˜ ÛÙȘ ÚˆÙ½Ó˜ perforin, granzyne Î·È granulysin6,7,8 Î·È ¯ÚËÛÈÌÔÔÈ› ‰Â›ÁÌ·Ù· Ô‡ÚˆÓ. Δ· ÙÂÏÂ˘Ù·›· ¯ÚfiÓÈ· ·Ó·Ù‡¯ıËΠӤ· ÁÂÓÈ¿ Ù¯ÓÔÏÔÁÈÒÓ ÁÈ· ÙÔÓ Ù·˘Ùfi¯ÚÔÓÔ ÚÔÛ‰ÈÔÚÈÛÌfi Î·È ÙËÓ ÔÛÔÙÈ΋ ̤ÙÚËÛË ‰Âο‰ˆÓ ΢ÙÔÎÈÓÒÓ Û ÔÚfi, Ï¿ÛÌ·, Ô‡Ú·, ÈÛÙÔ‡˜ Î·È ÂÓÂÚÁÔÔÈË̤ӷ ·ÙÙ·Ú· fiˆ˜ Ë Ù¯ÓÔÏÔÁ›· Lunimex (beads). ¶·Ú¿ÏÏËÏ· ·Ó·Ù‡¯ıËÎ·Ó ÚÔ-
ÌÔÙÈΤ˜ ̤ıÔ‰ÔÈ PCR ÈηӤ˜ Ó· ·Ó·Ï‡ÛÔ˘Ó ÂηÙÔÓÙ¿‰Â˜ ÁÔÓȉȷΤ˜ ı¤ÛÂȘ. °È· Ù· DNA micro-arrays Ô˘ ¯ÚËÛÈÌÔÔÈ‹ıËÎ·Ó ·Ú¯Èο ÛÙË ÌÂϤÙË ÙˆÓ ÌÂÙ·ÌÔۯ‡ÛÂˆÓ ·Ó·Ù‡¯ıËÎ·Ó ‰‡Ô ÂȉÒÓ Ù¯ÓÔÏÔÁ›Â˜: Ù· Affymetrix GeneChips (Affymetrix inc, Santa Clara California) Ô˘ ·ÔÙÂÏÔ‡ÓÙ·È ·fi arrays ÌÈÎÚÒÓ ÔÏÈÁÔÓÔ˘ÎÏÂÔÙȉ›ˆÓ (25 mers) Î·È arrays ·fi ÚÔ˚fiÓÙ· PCR Ô˘ ÚÔ¤Ú¯ÔÓÙ·Ó ·fi cDNA ‚È‚ÏÈÔı‹Î˜ ÁÂÓÂÙÈÎÔ‡ ˘ÏÈÎÔ‡ (200-1000 base pairs). ¶ÚfiÛÊ·Ù· ·Ó·Ù‡¯ıËÎ·Ó ÂÓ·ÏÏ·ÎÙÈο spotted arrays ÔÏÈÁÔÓÔ˘ÎÏÂÔÙȉ›ˆÓ (30-70 bases). ∞Ó·Ù‡¯ıËÎ·Ó Â›Û˘ Ù· 60-mer arrays Ì Ù¯ÓÔÏÔÁ›· inkjet print ·fi ÙËÓ Agilent, ÂÓÒ Ë General Electric Healthcare Ì Ù¯ÓÔÏÔÁ›· covalent linking Û 3D gel matrix, ·Ó¤Ù˘Í 30 mer arrays. ™Ùfi¯Ô˜ fiÏˆÓ ÙˆÓ ÂÈÛÙËÌfiÓˆÓ ‹Ù·Ó Ë Ù·˘ÙÔÔ›ËÛË ‚ÈÔÌÔÚ›ˆÓ Ù· ÔÔ›· ·ÚÔ˘ÛÈ¿˙Ô˘Ó ·˘ÍË̤ÓË ¤ÎÊÚ·ÛË ·ÚÎÂÙfi ¯ÚfiÓÔ ÚÈÓ ÙËÓ ÂӉ¯fiÌÂÓË ·fiÚÚÈ„Ë ÙÔ˘ ÌÔۯ‡̷ÙÔ˜ Î·È Ù· ÔÔ›· ı· ¯ÚËÛÈÌÔÔÈËıÔ‡Ó Ì ÛÎÔfi ·ÊÂÓfi˜ ÌÂÓ ÙËÓ Úfi‚ÏÂ„Ë Ù˘ ÔÚ›·˜ ÙÔ˘ ÌÔۯ‡̷ÙÔ˜ Î·È ·ÊÂÙ¤ÚÔ˘ ÙË ıÂڷ›·. ÃÚËÛÈÌÔÔÈÒÓÙ·˜ ÙȘ ·Ú·¿Óˆ Ù¯ÓÔÏÔÁ›Â˜ ÙˆÓ DNA arrays, ÔÌ¿‰Â˜ ÂÚ¢ÓËÙÒÓ ·Ó¤Ù˘Í·Ó Ï‹ıÔ˜ ·fi ÂÚ¢ÓËÙÈο ÚˆÙfiÎÔÏÏ· ÌÂϤÙ˘ ÁÔÓȉȷ΋˜ ¤ÎÊÚ·Û˘ Û ۯ¤ÛË Ì ÙËÓ ÔÚ›· ÌÂÙ·ÌÔÛ¯Â˘Ì¤ÓˆÓ ·ÛıÂÓÒÓ. ™Â Ì›· ·fi ÙȘ ÚÒÙ˜ ÚÔÛ¿ıÂȘ fiÔ˘ ‹Ú·Ó ̤ÚÔ˜ 7 ·ÛıÂÓ›˜ Ì ÌÂÙ·ÌfiÛ¯Â˘ÛË ÓÂÊÚÔ‡ Î·È ÔÍ›· ·fiÚÚÈ„Ë, Ô˘ ·Ô‰ÂÈÎÓ‡ÔÓÙ·Ó Ì ‚ÈÔ„›·, Î·È 3 ÌÂÙ·ÌÔÛ¯Â˘Ì¤ÓÔÈ ·ÛıÂÓ›˜ ¯ˆÚ›˜ ·fiÚÚÈ„Ë, ¯ÚËÛÈÌÔÔÈ‹ıËÎ·Ó Affymetix Gene Chips FL6800 Ù· ÔÔ›· ÂÚÈ›¯·Ó 6,800 probe sets ÁÈ· ·ÓıÚÒÈÓ· ÁÔÓ›‰È·9. ¢È·ÈÛÙÒıËΠfiÙÈ 4 ·ÓÙ›ÁÚ·Ê· ÁÔÓȉ›ˆÓ (human monokine induced by interferon-Á, T cell receptor active ‚ chain protein, interleukin – 2 stimulated phosphoprotein Î·È transporter associated with antigen presentation TADI) ›¯·Ó ·˘ÍË̤ÓË Ú‡ıÌÈÛË Î·È ÛÙ· 7 ·Ú·¿Óˆ ‰Â›ÁÌ·Ù· Û ۯ¤ÛË Ì ٷ ‰‡Ô ·fi Ù· ÙÚ›· Ê˘ÛÈÔÏÔÁÈο ‰Â›ÁÌ·Ù·. μÚ¤ıËΠ›Û˘ fiÙÈ ¤ÍÈ ¿ÏÏ· ÁÔÓ›‰È· (interferon-stimulated growth factor 3, complement factor 3, nicotinamide N-methyltranferase, macrophage inflammatory protein 3‚,myeloid differatiation protein Î·È CD18) ÂÎÊÚ¿ÛÙËÎ·Ó ·Ú·¿Óˆ Û ¤ÍÈ ·fi Ù· ÂÙ¿ ‰Â›ÁÌ·Ù· ·ÛıÂÓÒÓ Ì ÔÍ›· ·fiÚÚÈ„Ë. ∞ÓÙ›ıÂÙ·, ‰ÂÓ ·Ú·ÙËÚ‹ıËΠ·˘ÍË̤ÓË ‰Ú·ÛÙÈÎfiÙËÙ· Û ÌfiÚÈ· cytoxine T-cell effectror fiˆ˜ Ë perforin Î·È ÙÔ
METAMO™XEY™Eπ™ 2008
granzyme Ù· ÔÔ›· ›¯·Ó ÚÔÛ‰ÈÔÚÈÛÙ› Û ÔÛÔÙÈ΋ PCR ÚÔËÁÔ‡ÌÂÓ˘ ÌÂϤÙ˘ Î·È Â›¯·Ó ·Ó·ÁÓˆÚÈÛı› Û·Ó ‰Â›ÎÙ˜ ÔÍ›·˜ ·fiÚÚȄ˘ ÓÂÊÚÔ‡. ™Â ¿ÏÏË ÌÂϤÙË Ì ÂfiÌÂÓ˘ ÁÂÓÈ¿˜ Affymetrix Gene Chips (Hu95Av2) Î·È Ì ·ÚÈıÌfi ÁÔÓȉ›ˆÓ 12,625, ‰ËÌÈÔ˘ÚÁ‹ıËÎ·Ó ÚˆÙfiÎÔÏÏ· Ì ‰Â›ÁÌ·Ù· ·fi ‚ÈÔ„›Â˜ ·ÛıÂÓÒÓ Ô˘ ›¯·Ó ˘ÔÛÙ› ÌÂÙ·ÌfiÛ¯Â˘ÛË ÓÂÊÚÔ‡ ÚÈÓ ·fi 6 Ì‹Ó˜ Î·È ‹Ù·Ó ˘ÁÈ›˜10. ™Â ÌÂÚÈÎÔ‡˜ ·fi ·˘ÙÔ‡˜ ÙÔ˘˜ ·ÛıÂÓ›˜ ·Ú·ÙËÚ‹ıËΠ·fiÚÚÈ„Ë ÌÔۯ‡̷ÙÔ˜ ÌÂÙ¿ ·fi 12 Ì‹Ó˜. ¢ËÌÈÔ˘ÚÁ‹ıËÎ·Ó ‰ËÏ·‰‹ ‰‡Ô ÔÌ¿‰Â˜ ·ÛıÂÓÒÓ, ·˘ÙÔ› Ô˘ ÌÂÙ¿ ·fi 12 Ì‹Ó˜ ·Ú¤ÌÂÈÓ·Ó ˘ÁÈ›˜ Î·È ·˘ÙÔ› Ô˘ ·¤ÚÚÈ„·Ó. ¶ÚÔÛ‰ÈÔÚ›ÛÙËÎ·Ó 10 ÁÔÓ›‰È· Ô˘ ›¯·Ó ¿ÓÈÛË ¤ÎÊÚ·ÛË ÛÙÔ˘˜ ·ÛıÂÓ›˜ Ì ¯ÚfiÓÈ· ·fiÚÚÈ„Ë ÌÔۯ‡̷ÙÔ˜ Û ۯ¤ÛË Ì ÙÔ˘˜ ·ÛıÂÓ›˜ ÌÂ Ê˘ÛÈÔÏÔÁÈ΋ ÏÂÈÙÔ˘ÚÁ›· ÓÂÊÚÈÎÔ‡ ÌÔۯ‡̷ÙÔ˜ ÌÂÙ¿ ·fi 12 Ì‹Ó˜. ∞˘Ù‹ Ë ÔÌ¿‰· ÙˆÓ ÁÔÓȉ›ˆÓ ‹Ù·Ó ·ÚÎÂÙ‹ ÁÈ· Ó· ÂÈÙÚ¤„ÂÈ ÙË ÛˆÛÙ‹ Úfi‚ÏÂ„Ë ÁÈ· ·Ó¿Ù˘ÍË ¯ÚfiÓÈ·˜ ÓÂÊÚÔ¿ıÂÈ·˜ Û 15 ·fi 17 ·ÛıÂÓ›˜ (88%). ΔÔ ÌÂÈÔÓ¤ÎÙËÌ· Ù˘ ÌÂϤÙ˘ ‹Ù·Ó Ë ¤ÏÏÂÈ„Ë ‚ÈÔ„›·˜ Û 12 ÌËÓÒÓ follow-up ÁÈ· ÙËÓ ÎÏÈÓÈ΋ ÂȂ‚·›ˆÛË Ù˘ ¯ÚfiÓÈ·˜ ÓÂÊÚÔ¿ıÂÈ·˜ ·ÏÏÔÌÔۯ‡̷ÙÔ˜. O Stegall Î·È ÔÈ Û˘ÓÂÚÁ¿Ù˜ ÙÔ˘11 ¯ÚËÛÈÌÔÔ›ËÛ·Ó ÂÈÚ·Ì·Ùfi˙ˆ· ,ÔÓÙ›ÎÈ·, ÁÈ· Ó· ÌÂÏÂÙ‹ÛÔ˘Ó ÙȘ ÚˆÙ½Ó˜ Ô˘ Û¯ÂÙ›˙ÔÓÙ·È Ì ÔÍ›· ·fiÚÚÈ„Ë ÌÔÛ¯Â˘Ì¿ÙˆÓ Î·Ú‰È¿˜. ∞ÔÌfiÓˆÛ·Ó RNA ·fi ÈÛÙfi ηډȿ˜ 3, 5, Î·È 7 Ë̤Ú˜ ÌÂÙ¿ ÙË ÌÂÙ·ÌfiÛ¯Â˘ÛË Î·È Ù· ‰Â›ÁÌ·Ù· ˘¤ÛÙËÛ·Ó ˘‚ÚȉÈÛÌfi Û Affymetrix U34A rat micro arrays Ô˘ ·ÔÙÂÏÔ‡ÓÙ·Ó ·fi probe sets ÁÈ· 8,800 ÁÔÓ›‰È·. ™Ù·ÙÈÛÙÈ΋ ·Ó¿Ï˘ÛË ·¤‰ÂÈÍ fiÙÈ 2,864 ÁÔÓ›‰È· ›¯·Ó ·˘ÍË̤ÓË ‰Ú·ÛÙÈÎfiÙËÙ· ÙËÓ 3Ë Ë̤ڷ, 1,418 ÁÔÓ›‰È· ÙËÓ 5Ë Ë̤ڷ Î·È 2,745 ÁÔÓ›‰È· ÙËÓ 7Ë Ë̤ڷ. Δ· ·ÔÙÂϤÛÌ·Ù· ÙˆÓ micro arrays ÂȂ‚·ÈÒıËÎ·Ó ÁÈ· 13 ÛËÌ·ÓÙÈο ·ÓÙ›ÁÚ·Ê· Î·È Ì real timePCR. ∞fi ÙËÓ ÌÂϤÙË ·˘Ù‹ ‚Ú¤ıËΠfiÙÈ ÂÎÙfi˜ ·fi Ù· ÁÓˆÛÙ¿ ÌfiÚÈ· Ô˘ ·›˙Ô˘Ó ÚfiÏÔ ÛÙËÓ ÔÍ›· ·fiÚÚÈ„Ë, Û˘ÌÌÂÙ¤¯Ô˘Ó Î·È ÂÈϤÔÓ ÌfiÚÈ· fiˆ˜ ÁÈ· ·Ú¿‰ÂÈÁÌ· Ô ÌÂÙ·ÁÚ·ÊÈÎfi˜ ·Ú¿ÁÔÓÙ·˜ 19 Î·È Ë ÚˆÙ½ÓË decotin (ÚˆÙÂÔÁÏ˘Î¿ÓË Ô˘ ‰Ú· Ì ÙÔÓ ÂȉÂÚÌÈÎfi ·Ú¿ÁÔÓÙ· ·Ó¿Ù˘Í˘ ÁÈ· ÙÔÓ ¤ÏÂÁ¯Ô ÙÔ˘ ΢ÙÙ·ÚÈÎÔ‡ ·ÎÏÔ˘). ª›· ·ÍÈfiÏÔÁË ÌÂϤÙË ¤ÁÈÓ Ì Lymphochip (Stanford University, National Cancer Institute), ¤Ó· spotted cDNA array ·ÔÙÂÏÔ‡ÌÂÓÔ ·fi 12,440 ÂÈÏÂÁ̤ӷ ÁÔÓ›‰È· ·fi ÙËÓ ÔÌ¿‰· ÙÔ˘ Stanford12. ΔÔ ÂÈÚ·Ì·ÙÈÎfi ˘ÏÈÎfi Ô˘ ¯ÚËÛÈÌÔÔÈ‹ıËΠ‹Ù·Ó 67 ÓÂÊÚÈΤ˜ ‚ÈÔ„›Â˜ ·fi ·È‰È·ÙÚÈο ÂÚÈÛÙ·ÙÈ-
19
ο. ∞ÔÌÔÓÒıËΠRNA ·fi 18 ‚ÈÔ„›Â˜ ÓÂÊÚÔ‡ ÁÈ· οı ÌÂϤÙË, Ô˘ ÂÓÈÛ¯‡ıËΠ̠1 ‹ 2 ·ÎÏÔ˘˜ ·fi in vitro ·ÓÙÈÁÚ·Ê‹ ÚÈÓ ˘ÔÛÙ› ˘‚ÚȉÈÛÌfi ÛÙ· chips: ∏ ·ÍÈÔÏfiÁËÛË Ù˘ ¤ÎÊÚ·Û˘ ÙˆÓ ÔÌ¿‰ˆÓ ÁÔÓȉ›ˆÓ Ô˘ ÂÓÙÔ›ÛıËηÓ, ·Ô‰Â›ÎӢ ÙÚ›· ›‰Ë ÔÍ›·˜ ·fiÚÚȄ˘ Ô˘ Û¯ÂÙ›˙ÔÓÙ·Ó Ì ‰‡Ô ¯ÚfiÓÈ· ÂÈ‚›ˆÛ˘ ÌÔۯ‡̷ÙÔ˜. ∏ ·˘ÍË̤ÓË ¤ÎÊÚ·ÛË ÁÔÓȉ›ˆÓ ÂÚÈÏ¿Ì‚·Ó ÂÎÙfi˜ ·fi Ù· ÁÔÓ›‰È· Ô˘ Έ‰ÈÎÔÔÈÔ‡Ó ÙȘ ÚˆÙ½Ó˜ granzyme Î·È PRF Î·È ¿ÏÏ· ¿ÁÓˆÛÙ· ̤¯ÚÈ ÙfiÙ ÁÔÓ›‰È· Ù· ÔÔ›· Û¯ÂÙ›˙ÔÓÙ·Ó Ì ÙËÓ ¤Î‚·ÛË ÂÈ‚›ˆÛ˘ ÌÔۯ‡̷ÙÔ˜ Î·È ÙËÓ Èı·ÓfiÙËÙ· ÔÍ›·˜ ·fiÚÚȄ˘. Δ· ›‰È· ·ÔÙÂϤÛÌ·Ù· ÂȂ‚·ÈÒıËÎ·Ó Ì ÔÛÔÙÈ΋ ÌÂϤÙË PCR. ∞Ô‰ÂÈÎÓ‡ÔÓÙ·È ‰ËÏ·‰‹ Ó¤ÔÈ Ì˯·ÓÈÛÌÔ› Î·È ÌÔÓÔ¿ÙÈ· Û ۯ¤ÛË Ì ÙËÓ ¤Î‚·ÛË Ù˘ ÌÂÙ·ÌfiÛ¯Â˘Û˘. ∂›Û˘ ·Ô‰ÂÈÎÓ‡ÂÙ·È fiÙÈ ¤Ó· ηÏÔۯ‰ȷṲ̂ÓÔ array ·ÔÙÂÏ› ‰˘Ó·Ùfi ÂÈÛÙËÌÔÓÈÎfi ÂÚÁ·ÏÂ›Ô ÁÈ· ÙËÓ ·Ó›¯Ó¢ÛË ‚ÈÔÏÔÁÈÎÒÓ Ì˯·ÓÈÛÌÒÓ. ¶ÚfiÛÊ·Ù·, Ú·ÁÌ·ÙÔÔÈ‹ıËÎ·Ó ‰‡Ô ÌÂϤÙ˜, Û ̛· ÚÔÛ¿ıÂÈ· Ó· ‚ÚÂıÔ‡Ó ÎÔÈÓÔ› ÌÔÚÈ·ÎÔ› ‰Â›ÎÙ˜ ÁÈ· ÙËÓ ÔÍ›· Î·È ÙË ¯ÚfiÓÈ· ÓÂÊÚÔ¿ıÂÈ· ÌÔۯ‡̷ÙÔ˜, ÙfiÛÔ Û ‚ÈÔ„›Â˜ ÓÂÊÚÔ‡ fiÛÔ Î·È Û ‰Â›ÁÌ·Ù· ·fi ÏÂÌÊÔ·ÙÙ·Ú· ÂÚÈÊÂÚÈÎÔ‡ ·›Ì·ÙÔ˜ (PBL). ™ÙȘ ÌÂϤÙ˜ ·˘Ù¤˜ ¯ÚËÛÈÌÔÔÈ‹ıËÎ·Ó arrays Ì ˘„ËÏ‹ Û˘ÁΤÓÙÚˆÛË ÔÏÈÁÔÓÔ˘ÎÏÂÔÙȉ›ˆÓ. ™ÙËÓ ÚÒÙË13 ¯ÚËÛÈÌÔÔÈ‹ıËÎ·Ó Affymetrix HG-U95Av2 Genes Chips ÚÔÎÂÈ̤ÓÔ˘ Ó· ÚÔÛ‰ÈÔÚÈÛÙ› Ë ÁÔÓȉȷ΋ ¤ÎÊÚ·ÛË Û ٤ÛÛÂÚÂȘ ÔÌ¿‰Â˜ ÌÂÙ·ÌÔÛ¯Â˘Ì¤ÓˆÓ ·ÛıÂÓÒÓ: Ê˘ÛÈÔÏÔÁÈÎÔ› ‰fiÙ˜, ÌÂÙ·ÌÔÛ¯Â˘Ì¤ÓÔÈ ·ÛıÂÓ›˜ Ì ηϿ ÏÂÈÙÔ˘ÚÁÈÎÔ‡˜ ÓÂÊÚÔ‡˜, ·ÛıÂÓ›˜ Ì ÔÍ›· ‰˘ÛÏÂÈÙÔ˘ÚÁ›· ÓÂÊÚÔ‡ ÛÙÔ˘˜ ÔÔ›Ô˘˜ ‰Â ‰È·ÁÓÒÛÙËΠÔÍ›· ·fiÚÚÈ„Ë Û ÈÛÙÔÏÔÁÈο ·Ú·Û΢¿ÛÌ·Ù· Î·È Ù¤ÏÔ˜ ·ÛıÂÓ›˜ Ô˘ ·ÚÔ˘Û›·Û·Ó ÔÍ›· ·fiÚÚÈ„Ë. ΔÔ Û˘Ì¤Ú·ÛÌ· ÛÙÔ ÔÔ›Ô Î·Ù¤ÏËÍ·Ó ÔÈ ÂÈÛÙ‹ÌÔÓ˜ ‹Ù·Ó fiÙÈ ÙfiÛÔ Ù· ‰Â›ÁÌ·Ù· ·fi ‚ÈÔ„›Â˜, fiÛÔ Î·È Ù· ‰Â›ÁÌ·Ù· PBLs Î·È ÛÙȘ Ù¤ÛÛÂÚÂȘ ÔÌ¿‰Â˜ ·ÛıÂÓÒÓ ·ÚÔ˘Û›·˙·Ó ‰È·ÊÔÚÂÙÈ΋ ÁÔÓȉȷ΋ ¤ÎÊÚ·ÛË. °È· ÙÔÓ ¤ÏÂÁ¯Ô ·ÍÈÔÈÛÙ›·˜ Ù˘ ÌÂıfi‰Ô˘ ¤ÁÈÓ ÂȂ‚·›ˆÛË ÙˆÓ ·ÔÙÂÏÂÛÌ¿ÙˆÓ Û real time PCR ÁÈ· 15 ÁÔÓ›‰È·. ŒÙÛÈ ÁÈ· ÚÒÙË ÊÔÚ¿ ·Ô‰ÂÈÎÓ‡ÂÙ·È fiÙÈ ÔÈ ·ÓÔÛÔÏÔÁÈÎÔ› Ì˯·ÓÈÛÌÔ› Ô˘ ÂÌϤÎÔÓÙ·È ÛÙËÓ ÔÍ›· ·fiÚÚÈ„Ë Â›Ó·È ‰È·ÊÔÚÂÙÈÎÔ› ÛÙ· PBL Î·È ÛÙÔ ÌÂÙ·ÌÔÛ¯Â˘Ì¤ÓÔ ÓÂÊÚfi. ∂ÚÌËÓ‡ÔÓÙ·È Â›Û˘ Î·È ÔÈ ÚÔËÁÔ‡ÌÂÓ˜ ÂÚ¢ÓËÙÈΤ˜ ·ÔÙ˘¯›Â˜ Ó· Û˘Û¯ÂÙÈÛıÔ‡Ó ÁÔÓ›‰È· ÛÙ· PBLs Ì ÁÔÓ›‰È· Ô˘ Û¯ÂÙ›˙ÔÓÙ·È Ì ·fiÚÚÈ„Ë ÌÔۯ‡̷ÙÔ˜ Û ‚ÈÔ„›Â˜ ÓÂÊÚÔ‡. £· Ú¤ÂÈ Â›Û˘
20
∞. ª¶√À∫§∞
Ó· ÙÔÓÈÛı› fiÙÈ ÁÈ· ÚÒÙË ÊÔÚ¿ ÂÊ·ÚÌfiÛıËÎ·Ó ÂÈÙ˘¯Ò˜ Ù· DNA microarrays Û PBLs Û·Ó ¤Ó· ‰È·ÁÓˆÛÙÈÎfi ÂÚÁ·ÏÂ›Ô ÛÙȘ ÌÂÙ·ÌÔۯ‡ÛÂȘ. ™ÙË ‰Â‡ÙÂÚË ÌÂϤÙË14 ‰ËÌÔÛȇÙËÎ·Ó ·ÔÙÂϤÛÌ·Ù· ·ÛıÂÓÒÓ Ì ÌÂÙ·ÌfiÛ¯Â˘ÛË Î·Ú‰È¿˜. ¢Â›ÁÌ·Ù· PBL ·ÔÌÔÓÒıËÎ·Ó Ù·˘Ùfi¯ÚÔÓ· Ì ‰Â›ÁÌ·Ù· ‚ÈÔ„›·˜ Ì˘Ôηډ›Ô˘ Î·È ·Ó·Ï‡ıËÎ·Ó Û Affymetrix HU1331A microarrays ·ÔÙÂÏÔ‡ÌÂÓ· ·fi probe sets ÁÈ· 22,283 ÁÔÓ›‰È·. ¢È·ÈÛÙÒıËΠfiÙÈ 91 ·ÓÙ›ÁÚ·Ê· ›¯·Ó ¿ÓÈÛË ¤ÎÊÚ·ÛË Û ·ÛıÂÓ›˜ Ì ·fiÚÚÈ„Ë Û ۯ¤ÛË ÌÂ Ê˘ÛÈÔÏÔÁÈο ‰Â›ÁÌ·Ù·. μÚ¤ıËΠ›Û˘ fiÙÈ ÙÔ 98% ÙˆÓ ·ÓÙÈÁÚ¿ÊˆÓ Ì ÙËÓ ¿ÓÈÛË ¤ÎÊÚ·ÛË Â·ÓÂÚ¯fiÙ·Ó ÛÙ· Ê˘ÛÈÔÏÔÁÈο ›‰· ÌÂÙ¿ ÙËÓ ·fiÚÚÈ„Ë. ¶ÔÛÔÙÈ΋ PCR Ô˘ Û˘ÌÏ‹ÚˆÛ ÙËÓ ·Ú·¿Óˆ ÌÂϤÙË ¤‰ÂÈÍ ÛËÌ·ÓÙÈ΋ ·‡ÍËÛË ¤ÎÊÚ·Û˘ ÁÈ· ÙÔ˘˜ ‰Â›ÎÙ˜ caspase 8, Fadd-like apoptosis regulator, Î·È superoxide dismutase 2. Δ· ·Ú·¿Óˆ ·ÔÙÂϤÛÌ·Ù· ˘ÔÛÙËÚ›˙Ô˘Ó ÙËÓ ¿Ô„Ë fiÙÈ Ë ÁÔÓȉȷ΋ ¤ÎÊÚ·ÛË Û PBL Û¯ÂÙ›˙ÂÙ·È Ì ÙËÓ ·fiÚÚÈ„Ë ÌÔۯ‡̷ÙÔ˜ Ô˘ ·Ô‰ÂÈÎÓ‡ÂÙ·È Ì ‚ÈÔ„›·. O Flechner Î·È ÔÈ Û˘ÓÂÚÁ¿Ù˜ ÙÔ˘15 ÌÂϤÙËÛ·Ó ÙËÓ ÁÔÓȉȷ΋ ¤ÎÊÚ·ÛË Û ڈÙfiÎÔÏÏÔ ·fi ‚ÈÔ„›Â˜ ÌÂÙ·ÌÔÛ¯Â˘Ì¤ÓˆÓ ÓÂÊÚÒÓ (‰‡Ô ¯ÚfiÓÈ· ÌÂÙ¿ ÙËÓ ÌÂÙ·ÌfiÛ¯Â˘ÛË) Û˘ÁÎÚ›ÓÔÓÙ·˜ Ì›· calcineurin inhibitor-free ·ÓÔÛÔηٷÛÙÔÏ‹ ‚·ÛÈṲ̂ÓË Û sirolimus (Rapamycin, Wyeth, Collegeville, Pennsylvania) Î·È mycophenolate mofetil (CellCept, Roche, Nutley, New Jersey) Û ۯ¤ÛË Ì ıÂڷ›· calcineurin inhibitor ‚·ÛÈṲ̂ÓË Û ΢ÎÏÔÛÔÚ›ÓË (Neoral, Novartis, East Hanover, New Jersey). OÈ ·ÛıÂÓ›˜ Ù˘ ÚÒÙ˘ ÔÌ¿‰·˜ ›¯·Ó ηχÙÂÚË ÓÂÊÚÈ΋ ÏÂÈÙÔ˘ÚÁ›· Î·È Ù·˘Ùfi¯ÚÔÓ· ·ÚÔ˘Û›·˙·Ó ÛËÌ·ÓÙÈ΋ Ì›ˆÛË Ù˘ ¯ÚfiÓÈ·˜ ÓÂÊÚÔ¿ıÂÈ·˜ ÌÔۯ‡̷ÙÔ˜. ΔÔ ÚÔÊ›Ï Ù˘ ÁÔÓȉȷ΋˜ ¤ÎÊÚ·Û˘ Û ‰Â›ÁÌ·Ù· ·ÛıÂÓÒÓ Ì ¯ÚfiÓÈ· ÓÂÊÚÔ¿ıÂÈ· ÌÔۯ‡̷ÙÔ˜ ÂÚÈÏ¿Ì‚·Ó ̛· ·ÍÈÔÛËÌ›ˆÙË ·‡ÍËÛË Ú‡ıÌÈÛ˘ ÁÔÓȉ›ˆÓ Ô˘ Û¯ÂÙ›˙ÂÙ·È Ì ·ÓÔÛ›·/ÊÏÂÁÌÔÓ‹ Î·È ÈÛÙÈÎfi ÙÚ·˘Ì·ÙÈÛÌfi / ·Ó·‰fiÌËÛË Î·ıÒ˜ ›Û˘ Ì ›ÓˆÛË ÙÔ˘ ÈÛÙÔ‡. OÈ ÂÈÛÙ‹ÌÔÓ˜ ÈÛÙÂ‡Ô˘Ó fiÙÈ Ë ÈÛÔÚÚÔ›·, Ú‡ıÌÈÛË, ‰‡Ô Ì˯·ÓÈÛÌÒÓ ·ÓÔÛ›· / ÊÏÂÁÌÔÓ‹ Î·È ÙÚ·˘Ì·ÙÈÛÌÔ‡ Û ۯ¤ÛË Ì ÙÔ Ì˯·ÓÈÛÌfi ·Ó·‰fiÌËÛ˘ ηıÔÚ›˙ÂÈ ÙËÓ ÚÔԉ¢ÙÈ΋ ÔÚ›· ÌÂÙ¿ ·fi Ì›· ÌÂÙ·ÌfiÛ¯Â˘ÛË. Δ· cDNA microarrays ¯ÚËÛÈÌÔÔÈ‹ıËÎ·Ó Â›Û˘ ÚÔÎÂÈ̤ÓÔ˘ Ó· ÌÂÏÂÙËı› Ë ÁÔÓȉȷ΋ ¤ÎÊÚ·ÛË Û Ì˯·ÓÈÛÌÔ‡˜ Ô˘ Û¯ÂÙ›˙ÔÓÙ·È Ì ÙËÓ Ê˘ÛÈÔÏÔÁ›· Ù˘ ÓÂÊÚÈ΋˜ ÌÂÙ·ÌfiÛ¯Â˘Û˘. ™Â Ì›· ÌÂϤ-
ÙË16 ¯ÚËÛÈÌÔÔÈ‹ıËÎ·Ó ‰‡Ô ÔÌ¿‰Â˜ ‰ÂÈÁÌ¿ÙˆÓ ·fi ‚ÈÔ„›Â˜ Ô˘ ÚÔÂÚ¯fiÙ·Ó ÙfiÛÔ ·fi Ù· ÛˆÏËÓ¿ÚÈ· fiÛÔ Î·È ·fi ÙÔ Û›ڷ̷ ÓÂÊÚÒÓ. OÈ ÌÂÙ·ÌÔÛ¯Â˘Ì¤ÓÔÈ ÓÂÊÚÔ› ·Ó‹Î·Ó Û و̷ÙÈÎÔ‡˜ Î·È ˙ÒÓÙ˜ ‰fiÙ˜. Œ¯ÂÈ ·Ô‰Âȯı› fiÙÈ Ù· ÌÔۯ‡̷ٷ Ô˘ ÚÔ¤Ú¯ÔÓÙ·È ·fi ˙ÒÓÙ˜ ‰fiÙ˜ ¤¯Ô˘Ó ÌÂÁ·Ï‡ÙÂÚË ‚ȈÛÈÌfiÙËÙ· Û ۯ¤ÛË Ì ·˘Ù¿ ·fi و̷ÙÈÎÔ‡˜, ·ÚfiÏÔ Ô˘ ‰ÂÓ Â›Ó·È Ï‹Úˆ˜ ηٷÓÔËÙfi˜ Ô Ì˯·ÓÈÛÌfi˜ ·˘Ù‹˜ Ù˘ ‰È·ÊÔÚ¿˜. ™ÙË ÌÂϤÙË ·˘Ù‹ ·ÔÌÔÓÒıËÎ·Ó 113 ÁÔÓ›‰È·, ÂÎ ÙˆÓ ÔÔ›ˆÓ Ù· 62 ‹Ù·Ó ÌÔÓ·‰Èο ÛÙÔ Û›ڷ̷ Û ۯ¤ÛË Ì ٷ ÛˆÏËÓ¿ÚÈ· ÙÔ˘ ÓÂÊÚÔ‡. ¢ÂÓ ‰È·ÈÛÙÒıËΠη̛· ‰È·ÊÔÚ¿ ÛÙËÓ ÁÔÓȉȷ΋ ¤ÎÊÚ·ÛË ·Ó¿ÌÂÛ· ÛÙȘ ÚˆÙ½Ó˜ ÙÔ˘ ÛÂÈÚ¿Ì·ÙÔ˜ ÓÂÊÚÒÓ ·fi ÙÔ˘˜ و̷ÙÈÎÔ‡˜ Î·È ˙ÒÓÙ˜ ‰fiÙ˜. ∞ÓÙ›ıÂÙ·, 9 ÁÔÓ›‰È· ÂÎÊÚ¿˙ÔÓÙ·Ó Û ·ÊıÔÓ›· ÛÙ· ÛˆÏËÓ¿ÚÈ· ÓÂÊÚÒÓ ·fi و̷ÙÈÎÔ‡˜ ‰fiÙ˜ Û ۯ¤ÛË Ì ˙ÒÓÙ˜. ∏ ÌÂϤÙË ·˘Ù‹ ·Ô‰ÂÈÎÓ‡ÂÈ ‰È·ÊÔÚ¤˜ ÛÙËÓ ÁÔÓȉȷ΋ ¤ÎÊÚ·ÛË ·ÎfiÌË Î·È Û ‰È·ÊÔÚÂÙÈο ÙÌ‹Ì·Ù· ÙÔ˘ ȉ›Ô˘ ÔÚÁ¿ÓÔ˘ Î·È ÂȂ‚·ÈÒÓÂÈ ÙËÓ ÌÂÁ¿ÏË Â˘·ÈÛıËÛ›· ÙˆÓ DNA microarrays Û·Ó ‰È·ÁÓˆÛÙÈÎfi ̤ÛÔ.
Proteomics O ÙÔ̤·˜ Ù˘ ÚˆÙˆÌÈ΋˜ Â›Ó·È ¤Ó·˜ ·fi ÙÔ˘˜ Ù·¯‡ÙÂÚ· ·Ó·Ù˘ÛÛfiÌÂÓÔ˘˜ ÎÏ¿‰Ô˘˜ ÛÙË Û‡Á¯ÚÔÓË μÈÔÏÔÁ›· Î·È Û˘Ì‚¿ÏÏÂÈ ·ÔÊ·ÛÈÛÙÈο ÙfiÛÔ ÛÙËÓ Î·Ù·ÓfiËÛË ‚·ÛÈÎÒÓ ‚ÈÔÏÔÁÈÎÒÓ Ì˯·ÓÈÛÌÒÓ fiÛÔ Î·È ÛÙËÓ ·Ó¿Ù˘ÍË Ó¤ˆÓ ‰È·ÁÓˆÛÙÈÎÒÓ Î·È ÚÔÁÓˆÛÙÈÎÒÓ ÌÂıfi‰ˆÓ ÛÙËÓ ÎÏÈÓÈ΋ Ú·ÎÙÈ΋. ∏ ÚˆÙˆÌÈ΋ ÏÂÈÙÔ˘ÚÁ› Û˘ÌÏËڈ̷ÙÈο Ì ¿ÏϘ ·Ó·Ù˘ÛÛfiÌÂÓ˜ Ù¯ÓÔÏÔÁ›Â˜ Ù˘ ÏÂÈÙÔ˘ÚÁÈ΋˜ ÁÔÓȉȈ̷ÙÈ΋˜, fiˆ˜ ÔÈ Û˘ÛÙÔȯ›Â˜ ÁÔÓȉ›ˆÓ (chips, arrays) Î·È ·Ô‚ϤÂÈ ÛÙËÓ ·Ó¿Ï˘ÛË Î·È ¯·Ú·ÎÙËÚÈÛÌfi ÙÔ˘ Û˘ÓfiÏÔ˘ ÙˆÓ ÂÎÊÚ·˙fiÌÂÓˆÓ ÚˆÙÂ˚ÓÒÓ ÂÓfi˜ ÁÔÓȉÈÒÌ·ÙÔ˜. ¶ÚfiÛÊ·Ù˜ ‚ÂÏÙÈÒÛÂȘ Û ·Ó·Ï˘ÙÈΤ˜ Ù¯ÓÔÏÔÁ›Â˜, ¤¯Ô˘Ó ‚ÔËı‹ÛÂÈ ÒÛÙ ӷ Â›Ó·È ‰˘Ó·Ù‹ Ë ÌÂϤÙË Ù˘ ‰È·ÊÔÚÈ΋˜ ¤ÎÊÚ·Û˘ ÚˆÙÂ˚ÓÒÓ Û ̛· Û˘ÁÎÂÎÚÈ̤ÓË Ê˘ÛÈÔÏÔÁÈ΋ ‹ ·ıÔÁfiÓÔ ·fiÎÚÈÛË ·ÏÏ¿ Î·È ÙˆÓ ÌÂÙ·-ÌÂÙ·ÊÚ·ÛÙÈÎÒÓ ÙÚÔÔÔÈ‹ÛÂˆÓ Ì ÙȘ Ôԛ˜ Ú˘ıÌ›˙ÂÙ·È Î·È ÂÍÂȉÈ·ÂÙ·È Ë ÏÂÈÙÔ˘ÚÁ›· ÂÓ˙‡ÌˆÓ Î·È ¿ÏÏˆÓ ÚˆÙÂ˚ÓÒÓ. ø˜ ÚˆÙˆÌÈ΋ ıˆÚÂ›Ù·È Ë ÌÂϤÙË ÙˆÓ ÚˆÙÂ˚ÓÒÓ ÛÂ Â›Â‰Ô Î˘ÙÙ¿ÚÔ˘, ÈÛÙÔ‡ ‹ ÔÚÁ¿ÓÔ˘. ∫·Ù·Ú¯‹Ó οı ·ÙÙ·ÚÔ ÛÙÔÓ ›‰ÈÔ ÈÛÙfi ÌÔÚ› Ó· ·ÚÔ˘ÛÈ¿˙ÂÈ ‰È·ÊÔÚÂÙÈΤ˜ ÚˆÙ½Ó˜ Ô˘ ÂÍ·ÚÙÒÓÙ·È ·fi ÙËÓ ÏÂÈÙÔ˘ÚÁÈ΋ ηٿÛÙ·ÛË ÙÔ˘ ΢ÙÙ¿ÚÔ˘. ™Â Â›Â‰Ô ÔÏfiÎÏËÚÔ˘ ÈÛÙÔ‡ ·˘Ùfi Ô˘ ¤¯ÂÈ ÛËÌ·Û›· Â›Ó·È Ë Î·Ù¿ÛÙ·ÛË ÙˆÓ ÂÚÈÛÛÔÙ¤ÚˆÓ
METAMO™XEY™Eπ™ 2008
΢ÙÙ¿ÚˆÓ Ô˘ ··ÚÙ›˙Ô˘Ó ÔÏfiÎÏËÚÔ ÙÔ Û‡ÛÙËÌ· ‹ ÙÔÓ ÈÛÙfi (.¯. ÔÍ›· ÈÛ¯·ÈÌ›· ‹ Ê˘ÛÈÔÏÔÁÈ΋ ÏÂÈÙÔ˘ÚÁ›·). ªÂ Û‡Á¯ÚÔÓ˜ Ù¯ÓÈΤ˜ ÌÔÚԇ̠ӷ ‰ËÌÈÔ˘ÚÁ‹ÛÔ˘Ì ÙÔ ÚÔÊ›Ï ÈÛÙÒÓ ¤¯ÔÓÙ·˜ Û·Ó ÛÙfi¯Ô ·ÊÂÓfi˜ ÌÂÓ ÙËÓ ÂÊ·ÚÌÔÁ‹ ‰È·ÁÓˆÛÙÈÎÒÓ ÌÂıfi‰ˆÓ Î·È ·ÊÂÙ¤ÚÔ˘ ÙË ‰˘Ó·ÙfiÙËÙ· ÌÂϤÙ˘ ηÈÓÔ‡ÚÁÈˆÓ ÁÔÓȉ›ˆÓ Î·È Ì˯·ÓÈÛÌÒÓ Ô˘ Û¯ÂÙ›˙ÔÓÙ·È ÌÂ Û˘ÁÎÂÎÚÈ̤Ó˜ ÎÏÈÓÈΤ˜ ηٷÛÙ¿ÛÂȘ. ∏ ÚfiÎÏËÛË ÛÙË ÌÂϤÙË ÙˆÓ proteomics Â›Ó·È Ô ÌÂÁ¿ÏÔ˜ ·ÚÈıÌfi˜ ÙˆÓ ÚˆÙÂ˚ÓÒÓ, ÂÚÈÛÛfiÙÂÚ˜ ·fi 100,000 ÚˆÙ½Ó˜, Û ۯ¤ÛË Ì ÙÔ transcriptome Ô˘ ÂÚÈÏ·Ì‚¿ÓÂÈ mRNA ÚÔ˚fiÓÙ· Ô˘ ÚÔ¤Ú¯ÔÓÙ·È ·fi 30,000 ÁÔÓ›‰È·. ∏ ÏÂÈÙÔ˘ÚÁ›· Î·È Ë ‰Ú·ÛÙÈÎfiÙËÙ· ÙˆÓ ÚˆÙÂ˚ÓÒÓ Ú˘ıÌ›˙ÂÙ·È ‹ ÂÚÈÔÚ›˙ÂÙ·È ·fi ÔÌÔÈÔÔÏÈΤ˜ ‰È·ÊÔÚÔÔÈ‹ÛÂȘ ÛÙË ‰ÔÌ‹ ÌÈ·˜ ÚˆÙ½Ó˘ (.¯. ʈÛÊÔÚ˘Ï›ˆÛË), ÂÓ·ÏÏ·ÎÙÈÎfi splicing, ·ÔÌfiÓˆÛË ‹ ÂÓÙfiÈÛË ÚˆÙÂ˚ÓÒÓ Û ˘Ô΢ÙÙ·ÚÈο ÙÌ‹Ì·Ù· ̤ۈ ·ÏÏËÏ›‰Ú·Û˘ ÚˆÙ½Ó˘ – ÚˆÙ½Ó˘, ‹ ÚˆÙ½Ó˘ – ÌÈÎÚÔÌÔÚ›Ô˘. ŒÙÛÈ, ÁÈ· Ó· Á›ÓÂÈ Î·Ù·ÓÔËÙ‹ Ë ÏÂÈÙÔ˘ÚÁ›· ÙˆÓ ÚˆÙÂ˚ÓÒÓ Û ‚ÈÔÏÔÁÈο Û˘ÛÙ‹Ì·Ù·, ··ÈÙÂ›Ù·È Ë ÂÊ·ÚÌÔÁ‹ ·ÁÎÔÛÌ›ˆÓ ÌÂıfi‰ˆÓ ÈηÓÒÓ Ó· ‰ÒÛÔ˘Ó ·ÔÙÂϤÛÌ·Ù·, Û¯ÂÙÈο Ì ÙÔÓ ÂÓÙÔÈÛÌfi ÚˆÙÂ˚ÓÒÓ, ÙȘ ÌÂÙ·ÙÚÔ¤˜- ÙÚÔÔÔÈ‹ÛÂȘ Ô˘ ˘Ê›ÛÙ·ÓÙ·È ·˘Ù¤˜, ÙËÓ Ì¤ÙÚËÛË ·ÏÏ·ÁÒÓ ÛÙËÓ ÔÛfiÙËÙ· ÙÔ˘˜, ÙȘ ·ÏÏËÏÂȉڿÛÂȘ ÙÔ˘˜ Î·È Ù¤ÏÔ˜ ÙËÓ Ï‹ÚË Î·Ù·ÓfiËÛË Ù˘ ‰Ú·ÛÙÈÎfiÙËÙ¿˜ ÙÔ˘˜. ™ÙȘ ÚÒÙ˜ ÌÂϤÙ˜ ÙÔ˘ Û˘ÓfiÏÔ˘ ÙˆÓ ÚˆÙÂ˚ÓÒÓ Û ÓÂÊÚÈο ·ÙÙ·Ú· ÙfiÛÔ ÛÂ Ê˘ÛÈÔÏÔÁÈÎÔ‡˜˘ÁÈ›˜, fiÛÔ Î·È Û ·ıÔÏÔÁÈÎÔ‡˜ ÓÂÊÚÔ‡˜ ÂÊ·ÚÌfiÛÙËÎ·Ó Ù¯ÓÈΤ˜ fiˆ˜ Ë ·Ó¿Ï˘ÛË ·ÌÈÓÔͤˆÓ, Ë N-terminal ‹ C-terminal sequencing Î·È Ë ·ÓÔÛÔ·Ó›¯Ó¢ÛË/·Ó¿Ï˘ÛË ‚·ÛÈṲ̂ÓË Û ·ÓÙÈÛÒÌ·Ù·. ŸÏ˜ ·˘Ù¤˜ ÔÈ ÚÔÛÂÁÁ›ÛÂȘ ›¯·Ó Ù¯ÓÈΤ˜ ‰˘ÛÎÔϛ˜, Û¯ÂÙÈο ¯·ÌËÏ‹ ¢·ÈÛıËÛ›· Î·È ‹Ù·Ó Ôχ ¯ÚÔÓÔ‚fiÚ˜. ™Â ÈÔ ÚfiÛÊ·Ù˜ ÌÂϤÙ˜ ¯ÚËÛÈÌÔÔÈ‹ıËÎÂ Ë ËÏÂÎÙÚÔÊfiÚËÛË ÔÏ˘·ÎÚ˘Ï·Ìȉ›Ô˘ ‰‡Ô ‰È·ÛÙ¿ÛÂˆÓ (2D PAGE), Ù· ·ÔÙÂϤÛÌ·Ù· Ù˘ ÔÔ›·˜, Ù· ÙÂÏÂ˘Ù·›· ¯ÚfiÓÈ·, Û˘Ó‰˘¿˙ÔÓÙ·È Ì ٷ ·ÔÙÂϤÛÌ·Ù· Ù˘ Ê·ÛÌ·ÙÔÛÎÔ›·˜ Ì¿˙·˜ (Mass Spectrometry MS), ¶›Ó.1. ∏ Ê·ÛÌ·ÙÔÛÎÔ›· Ì¿˙·˜ ‚·Û›˙ÂÙ·È ÛÙÔ fiÙÈ ÈfiÓÙ· ‰È·ÊÔÚÂÙÈ΋˜ Ì¿˙·˜ Î·È ÊÔÚÙ›Ô˘ ÌÂٷʤÚÔÓÙ·È Ì ‰È·ÊÔÚÂÙÈ΋ Ù·¯‡ÙËÙ· Î·È ÙÚԯȿ Û ¤Ó· ËÏÂÎÙÚÔÌ·ÁÓËÙÈÎfi ‰›Ô. ŒÙÛÈ, ·Ó·Ï‡ÔÓÙ·È ÚˆÙ½Ó˜ Î·È ÚÔÛ‰ÈÔÚ›˙ÂÙ·È Ë ¯ËÌÈ΋ Û‡ÓıÂÛË ÂÓfi˜ ¿ÁÓˆÛÙÔ˘ ‰Â›ÁÌ·ÙÔ˜. °È· ÙË Ì›ˆÛË Ù˘ ÔÏ˘ÏÔÎfiÙËÙ·˜ ÙÔ˘ Ì›ÁÌ·ÙÔ˜, ÚÔËÁÂ›Ù·È Ù˘ ªS Ë ÙÚȯÔÂȉÈ΋ ËÏÂÎÙÚÔÊfiÚËÛË ‹ ˘ÁÚ‹ ¯ÚˆÌ·ÙÔÁÚ·Ê›· ˘„ËÏ‹˜ ›ÂÛ˘.
21
¶›Ó. 1. μ·ÛÈΤ˜ Ù¯ÓÈΤ˜ ÚˆÙˆÌÈ΋˜. ¢Â›ÁÌ· (.¯. ΢ÙÙ·ÚÈÎfi Âί‡ÏÈÛÌ·, ‚ÈÔÏÔÁÈÎfi ˘ÁÚfi) 2D PAGE
Ãڈ̷ÙÔÁÚ·Ê›· ÔÏÏ·ÏÒÓ ‰È·ÛÙ¿ÛˆÓ
∞Ó›¯Ó¢ÛË ÚˆÙÂ˚ÓÒÓ (.¯. Ì AgNO3) ¶¤„Ë (ıÚ˘„›ÓË) ¢È·¯ˆÚÈÛÌfi˜ ÂÙȉ›ˆÓ Ì HPLC ‹ capillary ËÏÂÎÙÚÔÊfiÚËÛË πÔÓÈÛÌfi˜ Nanospray LC-MS (ÚÔÛ‰ÈÔÚÈÛÌfi˜ ªμ Ì ʷÛÌ·ÙÔÛÎÔ›· Ì¿˙·˜) ¢È¿Û·ÛË ÚˆÙÂ˚ÓÒÓ Ì MS/MS (m/q) ™‡ÁÎÚÈÛË ·ÔÙÂÏÂÛÌ¿ÙˆÓ Ì ‚¿ÛË ‰Â‰ÔÌ¤ÓˆÓ Δ·˘ÙÔÔ›ËÛË ÚˆÙÂ˚ÓÒÓ (·ÏÏËÏÔ˘¯›· ·ÌÈÓÔͤˆÓ)
™Ùfi¯Ô˜ Ù˘ ¤Ú¢ӷ˜ Ù˘ ÚˆÙˆÌÈ΋˜ ÛÙË ÌÂÙ·ÌfiÛ¯Â˘ÛË Â›Ó·È Ó· ‚ÚÂıÔ‡Ó ÚˆÙ½Ó˜-‰Â›ÎÙ˜ Ù˘ ÔÍ›·˜ ·fiÚÚȄ˘ Û ÔÚfi ‹ Ô‡Ú·, ÔÈ Ôԛ˜ ı· ·ÓȯÓ‡ÔÓÙ·È ÚÈÓ ÙËÓ ÂÌÊ¿ÓÈÛË ÙˆÓ ÎÏÈÓÈÎÒÓ Û˘Ìو̿وÓ. OÈ ‚ÈÔ„›Â˜ Û·Ó ÂÈÚ·Ì·ÙÈÎfi ˘ÏÈÎfi ·ÏÏ¿ Î·È Û·Ó Ì¤ÛÔ ‰È¿ÁÓˆÛ˘ ÌÂÈÔÓÂÎÙÔ‡Ó ÏfiÁˆ ‰˘ÛÎÔÏ›·˜ ·Ú·Ï·‚‹˜ ÙÔ˘ ˘ÏÈÎÔ‡ Î·È ÙÔ˘ ÎfiÛÙÔ˘˜. H ËÏÂÎÙÚÔÊfiÚËÛË ÔÏ˘·ÎÚ˘Ï·Ìȉ›Ô˘ ‰‡Ô ‰È·ÛÙ¿ÛÂˆÓ ¯ÚËÛÈÌÔÔÈ‹ıËΠ·fi ÙÔÓ Yamani Î·È ÙÔ˘˜ Û˘ÓÂÚÁ¿Ù˜ ÙÔ˘17 Û ‚ÈÔ„›Â˜ ÂÓ‰ÔÌ˘Ôηډ›Ô˘ ·ÛıÂÓÒÓ Ô˘ ›¯·Ó ˘ÔÛÙ› ÌÂÙ·ÌfiÛ¯Â˘ÛË Î·Ú‰È¿˜. OÈ ÂÚ¢ÓËÙ¤˜ ÂÓÙfiÈÛ·Ó ÙËÓ ·˘ÍË̤ÓË ¤ÎÊÚ·ÛË ‰‡Ô ÚˆÙÂ˚ÓÒÓ (‰‡Ô ÎËÏ›‰Â˜) ÌÔÚÈ·ÎÔ‡ ‚¿ÚÔ˘˜ ÂÚ›Ô˘ 12 kDa ÛÙ· ‰Â›ÁÌ·Ù· ÙˆÓ ·ÛıÂÓÒÓ Ô˘ ›¯·Ó ˘ÔÛÙ› ÔÍ›· ·fiÚÚÈ„Ë, Û ۯ¤ÛË Ì ٷ ‰Â›ÁÌ·Ù· ·fi ‚ÈÔ„›Â˜ ÌÂÙ·ÌÔÛ¯Â˘Ì¤ÓˆÓ ·ÛıÂÓÒÓ Ô˘ ‰ÂÓ ·ÚÔ˘Û›·˙·Ó Úfi‚ÏËÌ· ÛÙËÓ Î·Ú‰È·Î‹ ÏÂÈÙÔ˘ÚÁ›·. °È· ÙÔÓ ÚÔÛ‰ÈÔÚÈÛÌfi ÙˆÓ ÚˆÙÂ˚ÓÒÓ, ÔÈ ÎËÏ›‰Â˜ ·ÔÌÔÓÒıËÎ·Ó ·fi ÙËÓ ËÎÙ‹ ÔÏ˘·ÎÚ˘Ï·Ìȉ›Ô˘, ÔÈ ÚˆÙ½Ó˜ ˘¤ÛÙËÛ·Ó Î·ÙÂÚÁ·Û›· Ì ÙÚ˘„›ÓË, ηı·Ú›ÛıËÎ·Ó Ì ÛًϘ ˘ÁÚ‹˜ ¯ÚˆÌ·ÙÔÁÚ·Ê›·˜ Î·È Ù¤ÏÔ˜ ·Ó·Ï‡ıËÎ·Ó Û ªS, fiˆ˜ ÂÚÈÁÚ¿ÊÂÙ·È Î·È ÛÙÔÓ ¶›Ó. 1. ∏ Û‡ÁÎÚÈÛË ÙˆÓ ·ÔÙÂÏÂÛÌ¿ÙˆÓ Û ÁÓˆÛÙ‹ ‚¿ÛË ‰Â‰ÔÌ¤ÓˆÓ ·¤‰ÂÈÍ fiÙÈ Ë Ì›· ÚˆÙ½ÓË ‹Ù·Ó Ë ‚·ÚÈ¿ ·Ï˘Û›‰· Ù˘ ‚-Ì˘ÔÛ›Ó˘, ÂÓÒ Ë ‰Â‡ÙÂÚË ‰ÂÓ ‹Ù·Ó ÁÓˆÛÙ‹. OÈ ‚¿ÛÂȘ ‰Â‰ÔÌ¤ÓˆÓ Ô˘ ¯ÚËÛÈÌÔ-
22
∞. ª¶√À∫§∞
ÔÈ‹ıËÎ·Ó ‹Ù·Ó Ë ∏eart Science Center-2-Dimensional Polyacrylamide Gel Electrophoresis (HSC2DPAGE), Ë HEART-2PAGE, Î·È Ë High Heart Performance 2D PAGE (HP-2DPAGE). ™Â ÌÈ· ·fi ÙȘ ÚÒÙ˜ ÌÂϤÙ˜ ÚˆÙˆÌÈ΋˜18 Û˘ÁÎÚ›ıËÎ·Ó ÔÈ ÚˆÙ½Ó˜ Ê˘ÛÈÔÏÔÁÈÎÒÓ ÓÂÊÚÒÓ Û ۯ¤ÛË Ì ڈÙ½Ó˜ ÓÂÊÚÒÓ Ì ΢ÙÙ·ÚÈÎfi ηÚΛӈ̷. OÈ ÂÚ¢ÓËÙ¤˜, ¯ÚËÛÈÌÔÔÈÒÓÙ·˜ 2D PAGE, ÚÔÛ‰ÈfiÚÈÛ·Ó Ù¤ÛÛÂÚÂȘ ÚˆÙ½Ó˜ ÔÈ Ôԛ˜ ÂÎÊÚ¿˙ÔÓÙ·Ó ÌfiÓÔ ÛÂ Ê˘ÛÈÔÏÔÁÈÎÔ‡˜ ÓÂÊÚÔ‡˜. ∏ ·ÒÏÂÈ· ÙˆÓ ‰‡Ô, ·fi ÙȘ Ù¤ÛÛÂÚÂȘ ÚˆÙ½Ó˜, ÔÈ Ôԛ˜ Â›Ó·È ÌÈÙÔ¯ÔÓ‰ÚÈο ¤Ó˙˘Ì· (ubiquijnol cytochrome c reductase Î·È ÌÈÙÔ¯ÔÓ‰ÚÈ·Îfi NADH ubiquinone oxido-reductase complex I), Ô‰ËÁ› ÛÙÔ Û˘Ì¤Ú·ÛÌ· fiÙÈ ÌÔÚ› Ó· ˘¿Ú¯Ô˘Ó ·ÏÏ·Á¤˜ ÛÙË ÌÈÙÔ¯ÔÓ‰Úȷ΋ ÏÂÈÙÔ˘ÚÁ›· Ô˘ Ì οÔÈÔ ÙÚfiÔ ·˘Í¿ÓÔ˘Ó ÙÔÓ Î›Ó‰˘ÓÔ ÓÂÊÚÈÎÔ‡ ΢ÙÙ·ÚÈÎÔ‡ ηÚÎÈÓÒÌ·ÙÔ˜. ™Â ÌÂϤÙ˜ ÌÂÙ·ÌfiÛ¯Â˘Û˘ ÓÂÊÚÔ‡19, Ë ÂÍÂÏÈÁ̤ÓË Ù¯ÓÈ΋ Ù˘ Ê·ÛÌ·ÙÔÛÎÔ›·˜ Ì¿˙·˜ ¯ÚËÛÈÌÔÔÈ‹ıËΠÁÈ· ÙÔ ÚÔÊ›Ï Ê¿ÛÌ·ÙÔ˜ ÚˆÙÂ˚ÓÒÓ ·fi Ô‡Ú· ·ÛıÂÓÒÓ ÔÈ ÔÔ›ÔÈ ¯ˆÚ›ÛıËÎ·Ó Û ٤ÛÛÂÚÂȘ ηÙËÁÔڛ˜: (1) ·ÛıÂÓ›˜ Ì ÔÍ›· ·fiÚÚÈ„Ë, (2) ·ÛıÂÓ›˜ Ì ÔÍ›· ÛˆÏËÓ·Úȷ΋ Ó¤ÎÚˆÛË, (3) ·ÛıÂÓ›˜ Ì ·ӷϷ̂·ÓfiÌÂÓË ‹ de-novo ÛÂÈÚ·Ì·ÙÔ¿ıÂÈ· Î·È (4) control ·ÛıÂÓÒÓ Ì ÌÔۯ‡̷ٷ Ô˘ ·ÚÔ˘ÛÈ¿˙Ô˘Ó Ê˘ÛÈÔÏÔÁÈ΋ ÏÂÈÙÔ˘ÚÁ›· [34]. ∫·Ù¿ ÙË Û‡ÁÎÚÈÛË ‰ÂÈÁÌ¿ÙˆÓ control (4) Ì ‰Â›ÁÌ·Ù· ·ÛıÂÓÒÓ Ì ÔÍ›· ·fiÚÚÈ„Ë (1) ·Ú·ÙËÚ‹ıËÎ·Ó ‰‡Ô ‰È·ÊÔÚÂÙÈο ÚÔÊ›Ï ÚˆÙÂ˚ÓÒÓ Ô‡ÚˆÓ. ™Ù· ‰Â›ÁÌ·Ù· ÙˆÓ ·ÛıÂÓÒÓ Ì ÔÍ›· ·fiÚÚÈ„Ë ˘‹Ú¯·Ó 3 ÛÙ·ıÂÚ¤˜ ÂÚÈÔ¯¤˜ Ì¿˙·˜/ÊÔÚÙ›Ô˘: ∏ ÂÚÈÔ¯‹ π 5270-5550 (5 ÎÔÚ˘Ê¤˜), Ë ÂÚÈÔ¯‹ ππ 70507360 (3 ÎÔÚ˘Ê¤˜) Î·È Ë ÂÚÈÔ¯‹ πππ 10530-11100 (5 ÎÔÚ˘Ê¤˜). OÈ ÎÔÚ˘Ê¤˜ ·˘Ù¤˜ ˘‹Ú¯·Ó ¿ÓÙ· Ì·˙› Û fiÏ· Ù· ‰Â›ÁÌ·Ù·, ÂÓÒ ·Ô˘Û›·˙·Ó ÂÓÙÂÏÒ˜ ·fi Ù· ÚÔÊ›Ï ÚˆÙÂ˚ÓÒÓ ÙˆÓ Ê˘ÛÈÔÏÔÁÈÎÒÓ ‰ÂÈÁÌ¿ÙˆÓ. ™‡Ìʈӷ Ì ÙÔ˘˜ ÂÚ¢ÓËÙ¤˜, ÙÔ Û˘ÁÎÂÎÚÈ̤ÓÔ ·˘Ùfi ÚÔÊ›Ï ÚˆÙÂ˚ÓÒÓ, Ô˘ Û¯ÂÙ›˙ÂÙ·È Ì ÙËÓ ÔÍ›· ·fiÚÚÈ„Ë, ‰›ÓÂÈ ÙË ‰˘Ó·ÙfiÙËÙ· Û ¤Ó· ÎÏÈÓÈÎfi test Ó· ÂϤÁ¯ÂÈ ·Ó·›Ì·ÎÙ· Ù· ÓÂÊÚÈο ÌÔۯ‡̷ٷ ÌÂÙ¿ ÙË ÌÂÙ·ÌfiÛ¯Â˘ÛË. ™Â ¿ÏÏË ÎÏÈÓÈ΋ ÌÂϤÙË20 ·Ó·Ï‡ıËÎ·Ó Ì ʷÛÌ·ÙÔÛÎÔ›· Ì¿˙˘ ‰Â›ÁÌ·Ù· Ô‡ÚˆÓ ·fi 17 ÌÂÙ·ÌÔÛ¯Â˘Ì¤ÓÔ˘˜ ·ÛıÂÓ›˜ Ì ÔÍ›· ·fiÚÚÈ„Ë Î·È ‰Â›ÁÌ·Ù· ·fi 15 ÌÂÙ·ÌÔÛ¯Â˘Ì¤ÓÔ˘˜ ·ÛıÂÓ›˜ Û ÛÙ·ıÂÚ‹ ηٿÛÙ·ÛË (controls). ΔÔ Ê¿ÛÌ· ÂÍÂÙ¿ÛıËÎÂ Î·È ˘Ô‚Ï‹ıËΠ۠‚ÈÔÏËÚÔÊÔÚÈ΋ ·Ó¿Ï˘ÛË ÒÛÙ ӷ ÚÔÛ‰ÈÔÚÈÛÙ› Ë Ù·˘ÙfiÙËÙ· ˘Ô„Ë-
Ê›ˆÓ ‚ÈÔÏÔÁÈÎÒÓ Ì·ÚÙ‡ÚˆÓ ÁÈ· ·fiÚÚÈ„Ë. OÈ ˘Ô„‹ÊȘ ÚˆÙ½Ó˜ ·Ó·Ï‡ıËÎ·Ó Û ۯ¤ÛË Ì ÙÔ ÌÔÚÈ·Îfi ‚¿ÚÔ˜ Î·È Î·Ù·Ù¿¯ıËÎ·Ó Û ‰‡Ô ηÙËÁÔڛ˜: ÚˆÙ½Ó˜ ·fiÚÚȄ˘ Î·È ÚˆÙ½Ó˜ fi¯È ·fiÚÚȄ˘. OÈ ÚˆÙ½Ó˜ ·˘Ù¤˜ ¤‰ˆÛ·Ó ÙË ‰˘Ó·ÙfiÙËÙ· Ó· ηٷٷ¯ı› ÛˆÛÙ¿ ÔÛÔÛÙfi 91% ·fi 34 ‰Â›ÁÌ·Ù· Ô‡ÚˆÓ (¢·ÈÛıËÛ›· 83% Î·È ÂȉÈÎfiÙËÙ· 100%). O Û˘Ó‰˘·ÛÌfi˜ ÙˆÓ ·ÔÙÂÏÂÛÌ¿ÙˆÓ ÙˆÓ ‰‡Ô ·Ú·¿Óˆ ÌÂÏÂÙÒÓ ‰›ÓÂÈ ÙË ‰˘Ó·ÙfiÙËÙ· ÚÔÛ‰ÈÔÚÈÛÌÔ‡ ˘Ô„ËÊ›ˆÓ ‚ÈÔÏÔÁÈÎÒÓ ‰ÂÈÎÙÒÓ ÛÙ· Ô‡Ú· ·ÛıÂÓÒÓ Ì ÌÂÙ·ÌfiÛ¯Â˘ÛË ÓÂÊÚÔ‡, ÔÈ ÔÔ›ÔÈ ı· ÌÔÚÔ‡Ó Ó· Ù·˘Ù›˙ÔÓÙ·È Ì ÔÍ›· ·fiÚÚÈ„Ë ÙÔ˘ ÌÔۯ‡̷ÙÔ˜. £· Ú¤ÂÈ ÂÔ̤ӈ˜ Ó· ·Ó·Ù˘¯ıÔ‡Ó Î·È Î·ÈÓÔ‡ÚÁÈ· ÚˆÙfiÎÔÏÏ· ‰È¿ÁÓˆÛ˘ – ıÂڷ›·˜ Ì ‚¿ÛË ÙËÓ ÚfiÁÓˆÛË Ù˘ ÔÚ›·˜ Ù˘ ÌÂÙ·ÌfiÛ¯Â˘Û˘ Û ۯ¤ÛË Ì ÙËÓ ‡·ÚÍË ÙˆÓ ‚ÈÔÏÔÁÈÎÒÓ ‰ÂÈÎÙÒÓ ÛÙ· Ô‡Ú·. À¿Ú¯Ô˘Ó ·Ó·ÊÔÚ¤˜ ÁÈ· ÙËÓ Â¤ÎÙ·ÛË Ù˘ ÂÊ·ÚÌÔÁ‹˜ Ù˘ ·Ú·¿Óˆ ÌÂıfi‰Ô˘ Û ·ÛıÂÓ›˜ Ì ÌÂÙ·ÌÔۯ‡ÛÂȘ ‹·ÙÔ˜, ηډȿ˜ Ó‡ÌÔÓ· Î·È ·ÁÎÚ¤·ÙÔ˜21. ΔÔ ÌÂÈÔÓ¤ÎÙËÌ· ÛÙȘ ÌÂϤÙ˜ ·˘Ù¤˜ Â›Ó·È fiÙÈ Ù· ·ÔÙÂϤÛÌ·Ù· ‰›ÓÔÓÙ·È Û ÌÂÙÚ‹ÛÂȘ Ê¿ÛÌ·ÙÔ˜ Î·È fi¯È Û ٷ˘ÙÔÔ›ËÛË ÚˆÙÂ˚ÓÒÓ ‹ ÛÙËÓ ·Ó·ÁÓÒÚÈÛË ÙÔ˘ ‚ÈÔÏÔÁÈÎÔ‡ Ì˯·ÓÈÛÌÔ‡ ÛÙÔÓ ÔÔ›Ô ÂÌϤÎÔÓÙ·È ÔÈ Û˘ÁÎÂÎÚÈ̤Ó˜ ÚˆÙ½Ó˜. ∏ ¯Ú‹ÛË Ù˘ 2D PAGE ÌÔÚ› Ó· ‰ÒÛÂÈ ÙË ‰˘Ó·ÙfiÙËÙ· ÚÔÛ‰ÈÔÚÈÛÌÔ‡ ÌÂÚÈÎÒÓ ÂȉÈÎÒÓ ÚˆÙÂ˚ÓÒÓ. ƒÔÌÔÙÈο Û˘ÛÙ‹Ì·Ù· ÌÂÙ·ÙÚ¤Ô˘Ó Ù· spots Ù˘ Á¤Ï˘ Ù˘ ËÏÂÎÙÚÔÊfiÚËÛ˘ Û ÎÔÚ˘Ê¤˜ ÔÈ Ôԛ˜ Û˘Ó‰˘¿˙ÔÓÙ·È Ì ÙÔ ·ÔÙ¤ÏÂÛÌ· Ù˘ Ê·ÛÌ·ÙÔÌÂÙÚ›·˜ Ì¿˙·˜. Δ· ·ÔÙÂϤÛÌ·Ù· ·˘Ù¿ ÌÔÚÔ‡Ó Ó· Û˘ÁÎÚÈıÔ‡Ó Û ‚¿ÛË ‰Â‰ÔÌ¤ÓˆÓ 2D PAGE ÁÈ· ÙËÓ ·Ó·ÁÓÒÚÈÛË ÂȉÈÎÒÓ ÚˆÙÂ˚ÓÒÓ. ¢˘ÛÙ˘¯Ò˜ Ë ‚¿ÛË ‰Â‰ÔÌ¤ÓˆÓ 2D PAGE ÂÚÈÔÚ›˙ÂÙ·È Û ÌÂÚÈΤ˜ ÂηÙÔÓÙ¿‰Â˜ ÚˆÙÂ˚Ó˜ Ì ·ÔÙ¤ÏÂÛÌ· Ó· ÌËÓ ˘¿Ú¯ÂÈ Ï‹Ú˘ ÁÓÒÛË ÙÔ˘ ÚˆÙÂ˚ÓÈÎÔ‡ ÚÔÊ›Ï Û ˘ÁÚ¿, ·ÙÙ·Ú· ‹ ÈÛÙÔ‡˜. ¶Ôχ ÚfiÛÊ·Ù˜ ¤Ú¢Ó˜ ÙˆÓ ÔÌ¿‰ˆÓ Kurian, Yates Î·È Û˘ÓÂÚÁ·ÙÒÓ ÙÔ˘˜22 ¯ÚËÛÈÌÔÔ›ËÛ·Ó Ì›· ·Ó¿Ï˘ÛË Ë ÔÔ›· ÂÚÈÏ·Ì‚¿ÓÂÈ Ù· ·ÔÙÂϤÛÌ·Ù· ·fi ‚ÈÔ„›Â˜ ÓÂÊÚÔ‡ ÌÂÙ¿ ·fi ÌÂÙ·ÌfiÛ¯Â˘ÛË Î·È ·Ó¿Ï˘ÛË ÚˆÙÂ˚ÓÒÓ ÂÚÈÊÂÚÈÎÔ‡ ·›Ì·ÙÔ˜ ‚·ÛÈṲ̂ÓË Û ۇÛÙËÌ· ·Ó¿Ï˘Û˘ tandem Ô˘ ÂÚÈÏ·Ì‚¿ÓÂÈ Û ÛÂÈÚ¿ ˘ÁÚ‹ ¯ÚˆÌ·ÙÔÁÚ·Ê›· Î·È Ê·ÛÌ·ÙÔÁÚ·Ê›· Ì¿˙·˜. ΔÔ Û‡ÛÙËÌ· ·˘Ùfi ·Ó¿Ï˘Û˘ ÔÓÔÌ¿ÛÙËΠMuDPIT (multi dimensional protein identification tool). Δ· ‰Â›ÁÌ·Ù· ÂÚÈÂÏ¿Ì‚·Ó·Ó Ì›ÁÌ· ÚˆÙÂ˚ÓÒÓ Ô˘ ÚÔÂÚ¯fiÙ·Ó Â›Ù ·fi ÔÏfiÎÏËÚÔ ÈÛÙfi ‹ ·ÙÙ·Ú· ›Ù ·fi ˘ÔÛ‡ÓÔÏÔ ÚˆÙÂ˚-
METAMO™XEY™Eπ™ 2008
ÓÒÓ Ô˘ ÚÔÂÚ¯fiÙ·Ó ÌÂÙ¿ ·fi ηÙÂÚÁ·Û›· Ì ڈÙ¿Û˜. °È· ÙÔ ‰È·¯ˆÚÈÛÌfi ÙÔ˘ Ì›ÁÌ·ÙÔ˜ ÙˆÓ ÚˆÙÂ˚ÓÒÓ Ô˘ ÚԤ΢„ ¯ÚËÛÈÌÔÔÈ‹ıËΠ̛· ÛÂÈÚ¿ ·fi ÛًϘ ˘ÁÚ‹˜ ¯ÚˆÌ·ÙÔÁÚ·Ê›·˜ (˘‰ÚfiÊԂ˜ Î·È ·ÓÙ·ÏÏ·Á‹˜ ÈfiÓÙˆÓ ion exchange). Δ· ÎÏ¿ÛÌ·Ù· ·˘Ù¿ ÙˆÓ ÚˆÙÂ˚ÓÒÓ ·Ó·Ï‡ıËÎ·Ó Û ʷÛÌ·ÙÔÌÂÙÚ›· Ì¿˙·˜ Î·È ‰È·¯ˆÚ›ÛÙËÎ·Ó Û‡Ìʈӷ Ì ̿˙·/ÊÔÚÙ›Ô. Δ· ·ÔÙÂϤÛÌ·Ù· Ù˘ ·Ó¿Ï˘Û˘ ‰fiıËÎ·Ó Û ‚¿ÛË ‰Â‰ÔÌ¤ÓˆÓ ÁÓˆÛÙÒÓ ÚˆÙÂ˚ÓÒÓ fiˆ˜ ÙÔ Swiss-Prot Î·È Ù· “translations” ÂÚÁ·ÛÙ‹ÚÈ· Ù˘ ∂˘Úˆ·˚΋˜ ªÔÚȷ΋˜ μÈÔÏÔÁ›·˜, ÒÛÙ ӷ Ù·˘ÙÔÔÈËıÔ‡Ó ÔÈ ˘fi ÌÂϤÙË ÚˆÙ½Ó˜. ∏ ·Ú·¿Óˆ Ù¯ÓÔÏÔÁ›· (MuDPIT) ¤¯ÂÈ ÙË ‰˘Ó·ÙfiÙËÙ· Ó· Ù·˘ÙÔÔÈ‹ÛÂÈ Ù·˘Ùfi¯ÚÔÓ· ¿Óˆ ·fi 10,000 ‰È·ÊÔÚÂÙÈΤ˜ ÚˆÙ½Ó˜ Û ¤Ó· Û˘ÁÎÂÎÚÈ̤ÓÔ ‰Â›ÁÌ·. OÈ ·Ú¯ÈΤ˜ ÌÂϤÙ˜ ÙˆÓ ÂÚ¢ÓËÙÈÎÒÓ ·˘ÙÒÓ ÔÌ¿‰ˆÓ Û ‰Â›ÁÌ·Ù·, ÙfiÛÔ ·fi ‚ÈÔ„›Â˜ ÓÂÊÚÔ‡ ÌÂÙ¿ ·fi ÌÂÙ·ÌfiÛ¯Â˘ÛË, fiÛÔ Î·È Û ‚ÈÔ„›Â˜ ÓÂÊÚÔ‡ Ì ¯ÚfiÓÈ· ÓÂÊÚÔ¿ıÂÈ· ·ÏÏÔÌÔۯ‡̷ÙÔ˜ ·ÔÎ¿Ï˘„·Ó ·ÚÎÂÙ¤˜ ¯ÈÏÈ¿‰Â˜ ÚˆÙ½Ó˜ ˘„ËÏ‹˜ ·Ó¿Ï˘Û˘, ÔÈ Ôԛ˜ ÂÎÊÚ¿˙ÔÓÙ·È ‰È·ÊÔÚÂÙÈο, Û ·Ó¿Ï˘ÛË Ê¿ÛÌ·ÙÔ˜. O Û˘Ó‰˘·ÛÌfi˜ ÙˆÓ ·ÔÙÂÏÂÛÌ¿ÙˆÓ, ÙÔ˘ ÚˆÙÂ˚ÓÈÎÔ‡ ÚÔÊ›Ï Ô˘ ·Ó·ÁÓˆÚ›˙ÂÙ·È Ì ÌÂıfi‰Ô˘˜ ÚˆÙˆÌÈ΋˜ Û ۯ¤ÛË Ì ٷ ‰Â‰Ô̤ӷ, ·fi ·Ú¿ÏÏËϘ ¤Ú¢Ó˜, ÁÔÓȉȷ΋˜ ¤ÎÊÚ·Û˘ ‰›ÓÂÈ ÙË ‰˘Ó·ÙfiÙËÙ· Ù˘ ÌÂϤÙ˘ ·ÏÏËÏÔ›‰Ú·Û˘ ÁÔÓȉ›Ô˘ – ÚˆÙ½Ó˘ Î·È Ù˘ ·Ó¿Ù˘Í˘ ÂÓfi˜ Ó¤Ô˘ ÂÚ¢ÓËÙÈÎÔ‡ ÎÏ¿‰Ô˘ ÙˆÓ “proteogenomics”. OÈ ›‰ÈÔÈ ÂÚ¢ÓËÙ¤˜ ·Ó·Ù‡ÛÛÔ˘Ó ÂÚ¢ÓËÙÈΤ˜ ÌÂϤÙ˜ ÁÈ· ÙËÓ ÊˆÛÊÔÚ˘Ï›ˆÛË ÂȉÈÎÒÓ ÚˆÙÂ˚ÓÒÓ Ô˘ Û˘ÌÌÂÙ¤¯Ô˘Ó Û·Ó Û‹Ì·Ù· ÁÈ· ÂȉÈο ‚ÈÔÏÔÁÈο ÌÔÓÔ¿ÙÈ·. OÈ ÚˆÙ½Ó˜ ·˘Ù¤˜ ı· ÌÔÚÔ‡Û·Ó Ó· ıˆÚËıÔ‡Ó Û·Ó ÂȉÈÎÔ› ‰Â›ÎÙ˜ ÁÈ· ÙËÓ ÂÓÂÚÁÔÔ›ËÛË Î˘ÙÙ¿ÚˆÓ Î·È ÈÛÙÒÓ. ΔÔ ÌÂÈÔÓ¤ÎÙËÌ· Ù˘ ·Ú·¿Óˆ ÂÚ¢ÓËÙÈ΋˜ ÚÔÛ¿ıÂÈ·˜ Â›Ó·È fiÙÈ ‰ÂÓ Â›Ó·È ‰˘Ó·ÙfiÓ Ó· ÚÔÛ‰ÈÔÚÈÛÙÔ‡Ó ÔÛÔÙÈο ÔÈ ÚˆÙ½Ó˜ Ô˘ ·ÓȯÓ‡ÔÓÙ·È. °È· ÙË ÌÂϤÙË ·˘Ù‹ Â›Ó·È ··Ú·›ÙËÙË Ë ·Ú·ÁˆÁ‹ Û˘ÓıÂÙÈÎÒÓ ÂÙȉ›ˆÓ ÂÈÛËÌ·ÛÌ¤ÓˆÓ Ì ÈÛfiÙÔ·, ÒÛÙ ӷ ‰ËÌÈÔ˘ÚÁËıÔ‡Ó Î·Ì‡Ï˜ ·Ó·ÊÔÚ¿˜. ŒÙÛÈ, Ù· ÂÚÁ·ÛÙ‹ÚÈ· ·˘Ù¿ ÂÈÚ·Ì·Ù›˙ÔÓÙ·È ·Ú¿ÏÏËÏ· Û ÌÂıfi‰Ô˘˜ ÁÈ· ÙË ‰˘Ó·ÙfiÙËÙ· ÔÛÔÙÈÎÒÓ ÌÂÙÚ‹ÛˆÓ23. ¶Ú¤ÂÈ Ó· ÂÈÛËÌ·Óı› fiÙÈ ÙÔ Ï‹ıÔ˜ ÙˆÓ 10,000 ÚˆÙÂ˚ÓÒÓ, Ô˘ Â›Ó·È ‰˘Ó·ÙfiÓ Ó· ÌÂÏÂÙËıÔ‡Ó Ì ÙÔ Û˘Ó‰˘·ÛÌfi ÙˆÓ ·Ú·¿Óˆ ÌÂıfi‰ˆÓ, Â›Ó·È Û¯ÂÙÈο ÌÈÎÚfi Û ۯ¤ÛË Ì ÙÔÓ Û˘ÓÔÏÈÎfi ·ÚÈıÌfi ÙˆÓ 100,000 ÚˆÙÂ˚ÓÒÓ. °È· ÙÔ ÏfiÁÔ ·˘Ùfi ·Ó·Ù‡ÛÛÂÙ·È ÌÈ· ÂfiÌÂÓË ÁÂÓÈ¿ Ù¯ÓÔÏÔÁ›·˜ Ë ÔÔ›· ÂÚÈÏ·Ì‚¿ÓÂÈ
23
Fourier-transformed tandem Ê·ÛÌÔʈÙfiÌÂÙÚ· Ì¿˙·˜ Ù· ÔÔ›· ı· Û˘Ó‰˘·ÛÙÔ‡Ó ÌÂ Û˘ÛÙ‹Ì·Ù· fiˆ˜ ÙÔ ªuDPIT ÛÙÔ ÔÔ›Ô ·Ó·ÊÂÚı‹Î·Ì ÈÔ ¿Óˆ. ¶ÈÛÙ‡ÂÙ·È fiÙÈ Û‡ÓÙÔÌ· ı· Â›Ó·È ‰˘Ó·Ù‹ Ë ·Ó¿Ï˘ÛË Ì¤¯ÚÈ 50,000 ÚˆÙÂ˚ÓÒÓ.
™˘ÌÂÚ¿ÛÌ·Ù· ∞Ó·Ù‡ÛÛÔÓÙ·È Î·ÈÓÔ‡ÚÁȘ Ù¯ÓÔÏÔÁ›Â˜ Ì ÛÎÔfi ÙË Û˘ÓÔÏÈ΋ Î·È ÁÚ‹ÁÔÚË ÌÂϤÙË ÙˆÓ ÌÂÙ·‚ÔÏÒÓ ÛÙËÓ ¤ÎÊÚ·ÛË ÁÔÓȉ›ˆÓ Î·È ÚˆÙÂ˚ÓÒÓ Î·È ÙËÓ ÂÚÌËÓ›· ÌÂÙ·‚ÔÏÈÎÒÓ ÌÔÓÔ·ÙÈÒÓ Ô˘ Û˘Ó‰¤ÔÓÙ·È Ì ÙËÓ ÎÏÈÓÈ΋ ÂÈÎfiÓ· Ù˘ ÌÂÙ·ÌfiÛ¯Â˘Û˘. OÈ ·ÏÏËÏÂȉڿÛÂȘ ¤ÎÊÚ·Û˘ ÁÔÓȉ›ˆÓ – ÚˆÙÂ˚ÓÒÓ Î·È ÔÈ ÏÂÈÙÔ˘ÚÁÈΤ˜ Û¯¤ÛÂȘ ÙˆÓ ‚ÈÔÏÔÁÈÎÒÓ ÌÔÚ›ˆÓ ‰Â›¯ÓÔ˘Ó ÙË ÏÂÙ‹ ÈÛÔÚÚÔ›· ÛÙÔ˘˜ Ì˯·ÓÈÛÌÔ‡˜ ·˘ÙÔ‡ Ô˘ ÔÚ›˙ÂÙ·È ˘Á›· – ·Ûı¤ÓÂÈ·. ŒÓ·˜ ·fi ÙÔ˘˜ ÚÔÛ¯›˜ ÂÚ¢ÓËÙÈÎÔ‡˜ ÛÙfi¯Ô˘˜ Â›Ó·È Ë ‚ÂÏÙ›ˆÛË ÌÂıfi‰ˆÓ Ô˘ ı· ηٷϋÁÂÈ Û ̷ıËÌ·ÙÈο ÌÔÓ٤Ϸ-·ÏÁÔÚ›ıÌÔ˘˜ ۯ‰ȷṲ̂ӷ Ó· ÂÎÊÚ¿˙Ô˘Ó ‰˘ÓËÙÈο ÌÂÙ·‚ÔÏÈο ‚ÈÔÏÔÁÈο ÌÔÓÔ¿ÙÈ· Û ۯ¤ÛË Ì ÙË ÁÔÓȉȷ΋ ÏÂÈÙÔ˘ÚÁ›·. ¢ËÌÈÔ˘ÚÁÔ‡ÓÙ·È Â›Û˘ ‚È‚ÏÈÔı‹Î˜ ·fi ÌÈÎÚ¿ ÎÔÌÌ¿ÙÈ· RNA (siRNA small interferma) Ì ÛÎÔfi Ó· ·ÚÂÌ‚·›ÓÔ˘Ó ÛÙËÓ ÌÂÙ·ÁÚ·Ê‹ ÂȉÈÎÒÓ ÁÔÓȉ›ˆÓ. Δ· siRNA ı· ÌÔÚÔ‡Ó Ó· ÂȂ‚·ÈÒÓÔ˘Ó ÙËÓ ÔÚ›· ‚ÈÔÏÔÁÈÎÒÓ ÌÔÓÔ·ÙÈÒÓ ‹ Ó· ¯ÚËÛÈÌÔÔÈÔ‡ÓÙ·È Û·Ó Ì›· ‰˘Ó·ÌÈ΋ Û˘Ó‰˘·ÛÙÈ΋ Ô˘ ‚ÔËı¿ ÛÙËÓ ‰È¢ÎÚ›ÓÈÛË ÙˆÓ Û‡ÓıÂÙˆÓ ·ÓÔÛÔÏÔÁÈÎÒÓ Ì˯·ÓÈÛÌÒÓ Ô˘ Û¯ÂÙ›˙ÔÓÙ·È Ì ÙËÓ ·Ô‰Ô¯‹ ‹ ·fiÚÚÈ„Ë ÌÔۯ‡̷ÙÔ˜. ∏ Û˘ÏÏÔÁÈ΋ ÚÔÛ¿ıÂÈ· ÔÏÏÒÓ ÔÌ¿‰ˆÓ ÂÚ¢ÓËÙÒÓ Ì ‰È·ÊÔÚÂÙÈΤ˜ ÂȉÈÎfiÙËÙ˜ Î·È ÎÏÈÓÈÎÒÓ È·ÙÚÒÓ Ô˘ ÂÈϤÁÔ˘Ó Û˘ÁÎÂÎÚÈ̤ӷ ‰Â›ÁÌ·Ù· ·ÛıÂÓÒÓ ÚÔ˜ ·Ó¿Ï˘ÛË ı· ‰È¢ÎÔχÓÂÈ ÙËÓ ÂÚÌËÓ›· ÙˆÓ ·ÔÙÂÏÂÛÌ¿ÙˆÓ Ù˘ ÂÚ¢ÓËÙÈ΋˜ ·Ó¿Ï˘Û˘ Û ۯ¤ÛË Ì ÙËÓ ÎÏÈÓÈ΋ ÂÈÎfiÓ· ÙˆÓ ·ÛıÂÓÒÓ. ΔÂÏÈÎfi˜ ÛÙfi¯Ô˜ fiÏˆÓ ÙˆÓ ÂÚ¢ÓËÙÒÓ Â›Ó·È Ë Úfi‚ÏÂ„Ë ÙˆÓ ÎÈÓ‰‡ÓˆÓ, Ë Î·Ï‡ÙÂÚË ıÂڷ›· Î·È Ê˘ÛÈο Ë Î·Ï‡ÙÂÚË ÔÈfiÙËÙ· ˙ˆ‹˜ fiÏˆÓ ÙˆÓ ·ÛıÂÓÒÓ Ô˘ ¤¯Ô˘Ó ˘ÔÛÙ› ÌÂÙ·ÌfiÛ¯Â˘ÛË.
μÈ‚ÏÈÔÁÚ·Ê›· 1. De Groot-Kruseman HA, Mol WM, Niesters HG, et al. Differential intragraft cytocine messenger RNA profiles during rejection and repair of clinical heart transplants: a longitudinal study. Transpl Int 2003; 16:9-14. 2. Moudgil A, Bagga A, Toyoda M, et al. Expression of gamma-IFN mRNA in bronchoalveolar lavage fluid correlates with early acute allograft rejection in lung transplant recipients. Clin Transplant 1999; 13:20-207.
24
∞. ª¶√À∫§∞
3. Sabek O, Dorak MT, Kotb M, et al. Quantitative detection of T-cell activation markers by real-time PCR in renal transplant rejection and correlation with histopathologic evaluation. Transplantation 2002; 74:701-707. 4. Strehlau J, Pavlakis M, Lipman M, et al. Quantitative detection of immune activation transcripts as a diagnostic tool in kidney transplantation. Proc Natl Acad Sci U S A 1997; 94:695-700. 5. Nickel P, Presber F, Bold G, et al. Enzyme-linked immunosorbent spot assay for donor-reactive interferon-gamma-producing cells identifies T-cell presensitization and correlates with graft function at 6 and 12 months in renal-transplant recipients. Transplantation 2004; 78:1640-1646. 6. Li B, Hartono C, Ding R, et al. Noninvasive diagnosis of renal-allograft rejection by measurement of messenger RNA for perforin and granzyme B in urine. N Engl J Med 2001; 344:947-954. 7. Dadhania D, Muthukumar T, Ding R, et al. Molecular signatures of urinary cells distinguish acute rejection of renal allografts from urinary tract infection. Transplantation 2003; 75:1752-1754. 8. Kotsch K, Mashreghi MF, Bold G, et al. Enhanced granulysin mRNA expression in urinary sediment in early and delayed acute renal allograft rejection. Transplantation 2004; 77:1866-1875. 9. Akalin E, Hendrix RC, Polavarapu RG, et al. Gene expression analysis in human renal allograft biopsy samples using high-density oligoarray technology. Transplantation 2001; 72:948-953. 10 Scherer A, Krause A, Walker JR, et al. Early prognosis of the development of renal chronic allograft rejection by gene expression profiling of human protocol biopsies. Transplantation 2003; 75:1323-1330.
lymphocytes. Cold Spring Harb Symp Quant Biol 1999; 64:71-78. 13. Flechner SM,Kurian SM, Head SR, et al. Kidney transplant rejection and tissue injury by gene profiling of biopsies and peripheral blood lymphocytes. Am J Transplant 2004; 4:1475-1489. 14. Horwitz PA, Tsai EJ, Putt ME, et al. Detection of cardiac allograft rejection and response to immunosuppressive therapy with peripheral blood gene expression. Circulaton 2004; 110:3815-3821. 15. Flechner SM, Kurian SM, Solez K, et al. De novo kidney transplantation without use of calcineurin inhibitors preserves renal structure and function at two years. Am J Transplant 2004; 4:1776-1785. 16. Kainz A, Mitter Bauer C, Hauser P, et al. Alterations in gene expression in cadaveric vs. live donor kidneys suggest impaired tubular counter balance of oxidative stress at implantation. Am J Transplant 2004; 10:1595-1604. 17. Yamani MH, Kinter MT, Starling RC, et al. Increased beta-myosin heavy chain in acute cellular rejection following human heart transplantation. Am J Transplant 2002; 2:386-388. 18. Sarto C, Marocchi A, Sanchez JC, et al. Renal cell carcinoma and normal kidney protein expression. Electrophoresis 1997; 18:599-604. 19. Schaub S, Rush D, Wilkins J, et al. Proteomic-based detection of urine proteins associated with acute renal allograft rejection. J Am Soc Nephrol 2004; 15:219-227. 20. Clarke W, Silverman BC, Zhang Z, et al. Characterization of renal allograft rejection by urinary proteomic analysis. Ann Surg 2004; 237:660-665. 21. Traun AZ, Schachter AD. Transplantation proteomics. Pediatr Transplantation 2005; 9:700-711.
11. Stegall M, Park W, Kim D, Kremers W. Gene expression during acute allograft rejection: novel statistical analysis of microarray data. Am J Transplant 2002; 2:913-925.
22. Figeys D. Functional proteomics: mapping proteinprotein interactions and pathways. Curr Opin Mol Ther 2002; 4:210-215.
12. Alizadeh A, Eisen M, Davis RE, et al. The lymphochip : a specialized cDNA microarray for the genomic-scale analysis of gene expression in normal and malignant
23. Liu H, Sadygov RG, Yates JR 3rd. Amodel for random sampling and estimation of relative protein abundance in shotgun proteomics. Anal Chem 2004; 76:4193-4201.
º˘ÛÈ΋ ·ÓÔÛ›· Î·È ÌÂÙ·ÌfiÛ¯Â˘ÛË ∞. º˘Ï¿ÎÙÔ˘
ÛÙË Ú‡ıÌÈÛË Ù˘ ÂȉÈ΋˜ ·ÓÔÛ›·˜ ¤¯ÂÈ ·ÔÙÂϤÛÂÈ Â‰›Ô ÌÂÁ¿ÏÔ˘ ÂÚ¢ÓËÙÈÎÔ‡ ÂӉȷʤÚÔÓÙÔ˜4. ™Ù· ıËÏ·ÛÙÈο, ÔÈ Toll-like receptors (TLRs) ÂÎÊÚ¿˙ÔÓÙ·È Û ‰È·ÊÔÚÂÙÈÎÔ‡˜ Ù‡Ô˘˜ ΢ÙÙ¿ÚˆÓ, ΢ڛˆ˜ ÛÙ· ·ÓÙÈÁÔÓÔ·ÚÔ˘ÛÈ·ÛÙÈο ·ÙÙ·Ú· (APC) Û˘ÌÂÚÈÏ·Ì‚·ÓÔÌ¤ÓˆÓ ÙˆÓ ‰ÂÓ‰ÚÈÙÈÎÒÓ Î˘ÙÙ¿ÚˆÓ [DCs], Ì·ÎÚÔÊ¿ÁˆÓ, ÏÂÌÊÔ΢ÙÙ¿ÚˆÓ, ÂÈıËÏÈ·ÎÒÓ Î·È ÂÓ‰ÔıËÏÈ·ÎÒÓ Î˘ÙÙ¿ÚˆÓ). ∞˘ÙÔ› ÔÈ ˘Ô‰Ô¯Â›˜ ·Ó·ÁÓˆÚ›˙Ô˘Ó Û˘ÁÎÂÎÚÈ̤Ó˜ ‰Ô̤˜ ÙˆÓ ÌÈÎÚÔÔÚÁ·ÓÈÛÌÒÓ, (pathogen-associated molecular patterns-PAMPs) Û·Ó Â͈ÁÂÓ›˜ Û˘Ó‰¤Ù˜, ηıÒ˜ ›Û˘ Î·È ÚÔηÏÔ‡ÌÂÓ˜ ·fi ÙÚ·‡Ì·-‚Ï¿‚Ë Î·Ù¿ ÙËÓ IRI ‰È·ÊÔÚÔÔÈË̤Ó˜ ‰Ô̤˜ ÙÔ˘ ÍÂÓÈÛÙ‹ (damage associated molecular patterns-DAMPs) Û·Ó ÂÓ‰ÔÁÂÓ›˜ Û˘Ó‰¤Ù˜4. ªÂÙ¿ ÙËÓ ·Ó·ÁÓÒÚÈÛË, ÔÈ TLRs ‰›ÓÔ˘Ó ¤Ó·˘ÛÌ· Û ÌÔÓÔ¿ÙÈ· ÂÓ‰Ô΢ÙÙ¿ÚÈ·˜ ÌÂÙ·‚›‚·Û˘ ÌËÓ˘Ì¿ÙˆÓ Ô˘ ηٷϋÁÔ˘Ó, ‰È·Ì¤ÛÔ˘ Ù˘ ÂÓÂÚÁÔÔ›ËÛ˘ ÌÂÙ·ÁÚ·ÊÈÎÒÓ ·Ú·ÁfiÓÙˆÓ fiˆ˜ ÔÈ NFÎB, AP-1, Î·È IRF3, ÛÙËÓ ¤ÎÊÚ·ÛË ÁÔÓȉ›ˆÓ Ô˘ ÂÌϤÎÔÓÙ·È ÛÙË ÊÏÂÁÌÔÓ‹, ÛÙȘ ·ÓÙȉڿÛÂȘ ¤Ó·ÓÙÈ ÙˆÓ ÈÒÓ, Î·È ÛÙËÓ ˆÚ›Ì·ÓÛË ÙˆÓ ¿ˆÚˆÓ ‰ÂÓ‰ÚÈÙÈÎÒÓ Î˘ÙÙ¿ÚˆÓ (iDCs)5. Δ· ÒÚÈÌ· DCs ·ÏÏËÏÂȉÚÔ‡Ó Ì ٷ ·Úı¤Ó· Δ ÏÂÌÊÔ·ÙÙ·Ú·, ¿ÁÔÓÙ·˜ ÙËÓ ·¿ÓÙËÛË ÙˆÓ ÂȉÈÎÒÓ Δ-΢ÙÙ¿ÚˆÓ, ·ÔÙÂÏÒÓÙ·˜ ¤ÙÛÈ ÙÔÓ Û˘Ó‰¤ÙË Ì ÙËÓ ÂȉÈ΋ ·ÓÔÛ›·. Ÿˆ˜ ·ÚÔ˘ÛÈ¿˙ÂÙ·È ÛÙÔ Û¯‹Ì· 1, ·Ú¯Èο Ë ·ÓÔÛȷ΋ ·¿ÓÙËÛË ÂÌÊ·Ó›˙ÂÙ·È Ó· ¤¯ÂÈ ÌÔÚÊ‹ «ÎÏ„‡‰Ú·˜». ∂ÓÙÔ‡ÙÔȘ, fiˆ˜ ÚÔÙ¿ıËΠÙÔ 2002, Î·È ÂȂ‚·ÈÒıËΠÚÔÛÊ¿Ùˆ˜6, Ë «ÎÏ„‡‰Ú·» Èı·Ó¿ Ó· ÌËÓ Â›Ó·È ÙfiÛÔ ÛÙÂÓ‹ ÛÙÔ Î¤ÓÙÚÔ Ù˘ ηıÒ˜ ÔÏϤ˜ ·fi ÙȘ ÂÓÂÚÁ¤˜ ÎÈÓ¿Û˜ Î·È ÌÂÙ·ÁÚ·ÊÈÎÔ‡˜ ·Ú¿ÁÔÓÙ˜ ÌÔÚ› Ó· ηıÔÚ›˙ÔÓÙ·È Ì¤Ûˆ ÂÍ·ÚÙˆÌ¤ÓˆÓ ·fi ÙÔ ÔÍÂȉˆÙÈÎfi stress ÌÂÙ¿-ÌÂÙ·ÁÚ·ÊÈÎÒÓ ÙÚÔÔÔÈ‹ÛˆÓ, Ô˘ ηٷϋÁÔ˘Ó Û ¤Ó· ÂÈÚfiÛıÂÙÔ (˘„ËÏfiÙÂÚÔ) Â›Â‰Ô TLR ÌËӇ̷ÙÔ˜. ∂›Ó·È ÛËÌ·ÓÙÈÎfi ›Û˘, fiÙÈ Ë ‰È·Ì¤ÛÔ˘ ÙˆÓ ΔLR ˆÚ›Ì·ÓÛË ÙˆÓ ‰ÂÓ‰ÚÈÙÈÎÒÓ Î˘ÙÙ¿ÚˆÓ, ˆ˜ ÚÔ¸fiıÂÛË ÁÈ· ÙËÓ ¤Ó·ÚÍË Ù˘ ·-
¶·Ú·‰ÔÛȷο ÙfiÛÔ Ë ·Ó·ÁÓÒÚÈÛË, fiÛÔ Î·È Ë ·ÓÔ¯‹ ÛÙÔ ·ÏÏÔÌfiÛ¯Â˘Ì· ηٿ ÙË ÌÂÙ·ÌfiÛ¯Â˘ÛË ÂÛÙÈ¿˙ÔÓÙ·È ÛÙÔ˘˜ Ì˯·ÓÈÛÌÔ‡˜ Ù˘ ÂȉÈ΋˜ ·ÓÔÛ›·˜. ΔÔ Û‡ÛÙËÌ· Ù˘ ÂȉÈ΋˜ ·ÓÔÛ›·˜ Â›Ó·È ¤Ó· ÂÍ·ÈÚÂÙÈο ÔχÏÔÎÔ Û‡ÛÙËÌ· ÙÔ ÔÔ›Ô ‰È·ÌÂÛÔÏ·‚Â›Ù·È ·fi Ù· ÂȉÈο ÛÙÔ ·ÓÙÈÁfiÓÔ Δ Î·È μ ÏÂÌÊÔ·ÙÙ·Ú·. O ÚfiÏÔ˜ ÙÔ˘ ÛÙË ÌÂÙ·ÌfiÛ¯Â˘ÛË ÔÚÁ¿ÓˆÓ ¤¯ÂÈ ·ÔÙÂϤÛÂÈ ÙÔ Î¤ÓÙÚÔ Ù˘ ¤Ú¢ӷ˜ ÁÈ· ‰ÂηÂٛ˜. ∞fi ÙËÓ ¿ÏÏË ÏÂ˘Ú¿ ÙÔ Û‡ÛÙËÌ· Ù˘ Ê˘ÛÈ΋˜ ·ÓÔÛ›·˜ Â›Ó·È ·ÚfiÓ Û fiÏÔ˘˜ ÙÔ˘˜ ÔÏ˘Î‡ÙÙ·ÚÔ˘˜ ÔÚÁ·ÓÈÛÌÔ‡˜ ˆ˜ ÚÒÙË ÁÚ·ÌÌ‹ ¿Ì˘Ó·˜ ÙÔ˘ ÍÂÓÈÛÙ‹ ¤Ó·ÓÙÈ ÙˆÓ ·ıÔÁfiÓˆÓ ÌÈÎÚÔÔÚÁ·ÓÈÛÌÒÓ. øÛÙfiÛÔ, ÓÂfiÙÂÚ· ‰Â‰Ô̤ӷ ‰Â›¯ÓÔ˘Ó fiÙÈ ÙÔ Û‡ÛÙËÌ· Ù˘ Ê˘ÛÈ΋˜ ·ÓÔÛ›·˜ ·ÓÙȉڿ Û οı ηٿÛÙ·ÛË ÂÈΛӉ˘Ó˘ ‚Ï¿‚˘-ÙÚ·˘Ì·ÙÈÛÌÔ‡ ÙˆÓ ÈÛÙÒÓ Î·È Â¿ÁÂÙ·È fi¯È ÌfiÓÔ ·fi Ù· ·ıÔÁfiÓ· ·ÏÏ¿ Î·È ·fi οı ‚Ï·ÙÈÎfi ÁÂÁÔÓfi˜, fiˆ˜ ·Ú¿‰ÂÈÁÌ· ·˘Ùfi Ô˘ Û˘Ì‚·›ÓÂÈ Î·Ù¿ ÙË ‰È¿ÚÎÂÈ· Ù˘ ·ӷÈÌ¿ÙˆÛ˘ ÙÔ˘ ·ÏÏÔÌÔۯ‡̷ÙÔ˜1,2. ™‡Ìʈӷ Ì ÙË ıˆڛ· ÙÔ˘ ÎÈÓ‰‡ÓÔ˘ Ù˘ Matzinger ÙÔ ·ÓÔÛÈ·Îfi Û‡ÛÙËÌ·, ·Ó·ÁÓˆÚ›˙ÂÈ Î·È ·ÓÙȉڿ ÛÙ· Û‹Ì·Ù· ÎÈÓ‰‡ÓÔ˘ ·ÓÂÍ¿ÚÙËÙ· ·fi ÙËÓ ÚÔ¤ÏÂ˘Û‹ ÙÔ˘˜3. ∏ ‚Ï¿‚Ë ·fi ÙËÓ ÈÛ¯·ÈÌ›· / ·ӷÈÌ¿ÙˆÛË (ischemia/reperfusion injury-IRI) Â›Ó·È ÌÈ· ÔÏ˘·Ú·ÁÔÓÙÈ΋ ÊÏÂÁÌÔÓ҉˘ ·ÓÙ›‰Ú·ÛË, ·ÓÂÍ¿ÚÙËÙË ·fi ÙËÓ ·ÚÔ˘Û›· ÙÔ˘ ·ÏÏÔ·ÓÙÈÁfiÓÔ˘ ÙÔ˘ ÌÔۯ‡̷ÙÔ˜, Ë ÔÔ›· Âȉڿ ÛËÌ·ÓÙÈο ÛÙËÓ ¿ÌÂÛË Î·È ·ÒÙÂÚË ÂÈ‚›ˆÛË ÙˆÓ ÌÔÛ¯Â˘Ì¿ÙˆÓ, fiˆ˜ ¤¯ÂÈ ·Ô‰Âȯı› ·fi ÎÏÈÓÈο Î·È ÂÈÚ·Ì·ÙÈο ‰Â‰Ô̤ӷ [4]. ¶ÚfiÛÊ·Ù·, Ë ÔÍ›· Ê¿ÛË Ù˘ IRI ıˆÚÂ›Ù·È ÙÌ‹Ì· Ù˘ Ê˘ÛÈ΋˜ ·ÓÔÛÔ·¿ÓÙËÛ˘, ˆ˜ ÙÔ ÌË ÂȉÈÎfi ·ÔÙ¤ÏÂÛÌ· Ù˘ ‚Ï¿‚˘ Ô˘ ÔÊ›ÏÂÙ·È ÛÙÔÓ ÙÚfiÔ Û˘ÓÙ‹ÚËÛ˘ ÙˆÓ ÌÔÛ¯Â˘Ì¿ÙˆÓ Î·È ÛÙËÓ ¯ÂÈÚÔ˘ÚÁÈ΋ ¤̂·ÛË Ù˘ ÌÂÙ·ÌfiÛ¯Â˘Û˘ Ô˘ Ô‰ËÁÔ‡Ó Û ¤ÏÏÂÈ„Ë ·ÁÁÂȷ΋˜ ·ÈÌ¿ÙˆÛ˘ Î·È Î·Ù¿ Û˘Ó¤ÂÈ· Ô͢ÁfiÓÔ˘ [4]. ªÂ ÙËÓ ·Ó·Î¿Ï˘„Ë ÙˆÓ toll-like receptors (TLRs) Î·È ÙˆÓ ÂÓ‰ÔÁÂÓÒÓ Û˘Ó‰ÂÙÒÓ ÙÔ˘˜ Ô ÚfiÏÔ˜ Ù˘ Ê˘ÛÈ΋˜ ·ÓÔÛ›·˜ ηٿ ÙËÓ IRI fiÛÔ Î·È
25
∞. ºÀ§∞∫Δ√À
26
PAMP’s e.g. LPS
DAMP’s e.g. HSPs, HMGB-1
TLR 4
TL
TL
R
7
TLR 5
TLR
Allograft repesfusion injury
ROS
TIRAP
TRAM
MyD88
TRIF
R
1
TLR
2
3
Gram-negative bacterial infection:
IRAK
TRAF6
R TL
R TL
9
R TL
TBK1
IKKs-Complex
8
10
IKKs
NF-kB rejection, inflammation, ???? defense
IRF-3
AP-1 MAPks NF-kB
AP-1 >500
cytokines, chemikines, type I-interferons adhesive and costimulatory molecules
IRF-3 genes
transcroptional gene activation
e.g. innate dendritic cell
™¯‹Ì· 1. ∂Ó‰Ô΢ÙÙ¿ÚÈ· ÌÔÓÔ¿ÙÈ· ÌÂÙ·‚›‚·Û˘ ÌËÓ˘Ì¿ÙˆÓ ÙˆÓ TLR (Land WG. Innate immunity-mediated allograft rejection and strategies to prevent it. Transplant Proc. 2007 Apr; 39(3):667-72).
¿ÓÙËÛ˘ Ù˘ ÂȉÈ΋˜ ·ÓÔÛ›·˜, ‰ÂÓ Â›Ó·È Ô ÌfiÓÔ˜ Ì˯·ÓÈÛÌfi˜ ˆÚ›Ì·ÓÛ˘ ÙˆÓ Î˘ÙÙ¿ÚˆÓ. ¶ÚfiÛÊ·Ù˜ ÌÂϤÙ˜ ¤¯Ô˘Ó ‰Â›ÍÂÈ fiÙÈ Ù· NK-, NKT-, Î·È Ù· Á‰ T ·ÙÙ·Ú·, ˘ÚÔ‰ÔÙÔ‡Ó ÙËÓ ˆÚ›Ì·ÓÛË ÙˆÓ ‰ÂÓ‰ÚÈÙÈÎÒÓ Î˘ÙÙ¿ÚˆÓ Î·Ù¿ ÙËÓ ·Ó·ÁÓÒÚÈÛË ÙˆÓ PAMPs Î·È DAMPs)7. ¶ÔÏϷϤ˜ ÌÂϤÙ˜ ·Ô‰ÂÈÎÓ‡Ô˘Ó fiÙÈ ‰Ú·ÛÙÈÎÔ› ÌÂÙ·‚Ôϛ٘ ÙÔ˘ Ô͢ÁfiÓÔ˘ (reactive oxygen species-ROS), ÚÔηÏÔ‡Ó ‚Ï¿‚Ë ÙÔ˘ ·ÏÏÔÌÔۯ‡̷ÙÔ˜ Ô˘ Ï·Ì‚¿ÓÂÈ ¯ÒÚ· ÛÙÔ ‰fiÙË Î·Ù¿ ÙË ‰È¿ÚÎÂÈ· ÙÔ˘ ÂÁÎÂÊ·ÏÈÎÔ‡ ı·Ó¿ÙÔ˘, Î·È ÛÙÔ Ï‹ÙË Î·Ù¿ ÙËÓ Â·Ó·ÈÌ¿ÙˆÛË ÙÔ˘ ÌÔۯ‡̷ÙÔ˜ Î·È Ô‰ËÁÔ‡Ó ÛÙË ‰È·Ì¤ÛÔ˘ ÙˆÓ TLR ˆÚ›Ì·ÓÛË ÙˆÓ DCs ÙÔ˘ ‰fiÙË Î·È ÙÔ˘ Ï‹ÙË. ∏ ÚfiÛÏË„Ë Î·È Ë Â·ÎfiÏÔ˘ıË ·ÚÔ˘Û›·ÛË ÙˆÓ ·ÏÏÔ·ÓÙÈÁfiÓˆÓ ÛÙÔ Ì›˙ˆÓ Û‡ÌÏÂÁÌ· ÈÛÙÔÛ˘Ì·‚ÙfiÙËÙ·˜ (MHC) ·fi Ù· DCs fiˆ˜ Î·È Ë ·‡ÍËÛË Ù˘ ¤ÎÊÚ·Û˘ ÙˆÓ Û˘Ó‰ÈÂÁÂÚÙÈÎÒÓ ÌÔÚ›ˆÓ ÛÙ· ÒÚÈÌ· DCs, ‰È·Ì¤ÛÔ˘ ÙˆÓ TLRs, ÂÓÔÚ¯ËÛÙÚÒÓÔ˘Ó ÙËÓ ·Ó¿Ù˘ÍË Ù˘ ÂȉÈ΋˜ ÛÙÔ ·ÓÙÈÁfiÓÔ Â›ÎÙËÙ˘ ·ÓÔÛ›·˜. ¶ÂÈÚ·Ì·ÙÈΤ˜ ÌÂϤÙ˜ ‰Â›¯ÓÔ˘Ó fiÙÈ Î·Ù¿ ÙË ‚Ï¿‚Ë ·fi ÙËÓ Â·Ó·ÈÌ¿ÙˆÛË ÔÈ TLRs, Î·È ÂȉÈÎfiÙÂÚ· ÔÈ TLR4
Î·È TLR2 ·ÏÏËÏÂȉÚÒÓÙ·˜ Ì ٷ DAMPs fiˆ˜ HSP70 Î·È (high mobility group box 1) HMGB-1, Ê·›ÓÂÙ·È Ó· ÍÂÎÈÓÔ‡Ó ÂÓ‰Ô΢ÙÙ¿ÚÈ· ÌÔÓÔ¿ÙÈ· ÌÂÙ·‚›‚·Û˘ ÌËÓ˘Ì¿ÙˆÓ fiˆ˜ ·˘Ù¿ ηٿ ÙËÓ ·Ó·ÁÓÒÚÈÛË ÙˆÓ PAMPs ·fi ÙÔ˘˜ TLRs. ∂›Û˘, ÔÈ ·˘ÍË̤Ó˜ Û˘ÁÎÂÓÙÚÒÛÂȘ ÙˆÓ ROS, ÏÂÈÙÔ˘ÚÁÔ‡Ó Û·Ó ÂÈÚfiÛıÂÙ· ÌfiÚÈ· ‰È·‚›‚·Û˘ ÌËÓ˘Ì¿ÙˆÓ ·˘Í¿ÓÔÓÙ·˜ ÙËÓ ¤ÎÊÚ·ÛË ÌÂÙ·ÁÚ·ÊÈÎÒÓ ÁÔÓȉ›ˆÓ. ΔÔ ·ÔÙ¤ÏÂÛÌ· Â›Ó·È ÌÈ· ‰Ú·Ì·ÙÈο ·˘ÍË̤ÓË ·¿ÓÙËÛË ·fi ÙË Ê˘ÛÈ΋ ·ÓÔÛ›· (Û¯‹Ì· 1)4. OÌÔ›ˆ˜ , Ë ‰È·Û‡Ó‰ÂÛË ÙˆÓ DAMPs Ì ÙÔ˘˜ TLRs ÙˆÓ ÂÓ‰ÔıËÏÈ·ÎÒÓ Î·È Ï›ˆÓ Ì˘˚ÎÒÓ Î˘ÙÙ¿ÚˆÓ ÙˆÓ ·ÁÁ›ˆÓ ÙÔ˘ ÌÔۯ‡̷ÙÔ˜, Ô‰ËÁ› Û ÂÓÂÚÁÔÔ›ËÛ‹ ÙÔ˘˜ Î·È ¯ÚfiÓÈ· ·fiÚÚÈ„Ë, ÏfiÁˆ ·ıËÚÔÛÎÏ‹ÚˆÛ˘ ÙÔ˘ ÌÔۯ‡̷ÙÔ˜1,8-11. ∂ÎÙfi˜ ·fi Ù· ·ÙÙ·Ú·, ¯˘ÌÈÎÔ› ·Ú¿ÁÔÓÙ˜ fiˆ˜ ÙÔ Û˘Ìϋڈ̷ Î·È Ê˘ÛÈο ÌÔÓÔÎψÓÈο IgM ·ÓÙÈÛÒÌ·Ù· ·ÔÙÂÏÔ‡Ó ÎÏ·ÛÛÈο ÂÚÁ·Ï›· ÙÔ˘ Û˘ÛÙ‹Ì·ÙÔ˜ Ê˘ÛÈ΋˜ ·ÓÔÛ›·˜. ¡¤· ‰Â‰Ô̤ӷ ‰Â›¯ÓÔ˘Ó fiÙÈ «Ê˘ÛÈο» IgM ·ÓÙÈÛÒÌ·Ù· ·Ú¯Èο Û˘Ó‰¤ÔÓÙ·È Û Ӥ· ·ÓÙÈÁfiÓ· ÙÔ˘ Ï‹ÙË Ô˘ ‰ËÌÈÔ˘ÚÁÔ‡ÓÙ·È ·fi ÙËÓ ‚Ï¿‚Ë Â·Ó·ÈÌ¿ÙˆÛ˘ ÚÔ-
METAMO™XEY™Eπ™ 2008
ÛʤÚÔÓÙ·˜ ÌÈ· ı¤ÛË Û‡Ó‰ÂÛ˘ ÁÈ· ÙËÓ mannan binding lectin (MBL). ∏ Û˘Ó‰Â‰Â̤ÓË ªBL, fiÙ·Ó ÂÌϷΛ Û ·˘Ù‹Ó ÙËÓ «Ê˘ÛÈ΋˜ ·ÓÔÛ›·˜» ·ÓÙ›‰Ú·ÛË «·ÓÙÈÁfiÓÔ˘-·ÓÙÈÛÒÌ·ÙÔ˜», ÂÓÂÚÁÔÔÈ› ÙÔÓ Î·Ù·ÚÚ¿ÎÙË ÙÔ˘ Û˘ÌÏËÚÒÌ·ÙÔ˜ ̤ۈ Ù˘ Ô‰Ô‡ Ù˘ ÏÂÎÙ›Ó˘. Δ· ÁÂÁÔÓfiÙ· ·˘Ù¿ Èı·Ó¿ Û˘Ì‚¿ÏÔ˘Ó Û ÂÈÚfiÛıÂÙË ÈÛÙÈ΋ ‚Ï¿‚Ë ÙÔ˘ ÌÔۯ‡̷ÙÔ˜12,13. O ÚfiÏÔ˜ ÙÔ˘ Û˘ÛÙ‹Ì·ÙÔ˜ ÙÔ˘ Û˘ÌÏËÚÒÌ·ÙÔ˜ ÛÙËÓ IRI Â›Ó·È ·fi ηÈÚfi ·Ô‰Â‰ÂÈÁ̤ÓÔ˜. ∏ ·‡ÍËÛË Ù˘ ·Ú·ÁˆÁ‹˜ ÙˆÓ ÌÔÚ›ˆÓ ÙÔ˘ Û˘ÌÏËÚÒÌ·ÙÔ˜ Ú˘ıÌ›˙ÂÙ·È ·fi ÚÔÊÏÂÁÌÔÓÒ‰ÂȘ ΢ÙÔΛÓ˜, ΢ڛˆ˜ IL-6, TNF-· Î·È IFN-Á. ∂ÓÒ Ë ÛËÌ·Û›· Ù˘ ÂÓ·ÏÏ·ÎÙÈ΋˜ Ô‰Ô‡ ÂÓÂÚÁÔÔ›ËÛ˘ ¤¯ÂÈ Î·Ù·‰Âȯı›, ÚfiÛÊ·Ù· ‰Â‰Ô̤ӷ ·fi ÔÓÙ›ÎÈ· ÚÔÙ›ÓÔ˘Ó ¤Ó· ÂÈÚfiÛıÂÙÔ ÚfiÏÔ ÁÈ· ÙËÓ Ô‰fi Û‡Ó‰ÂÛ˘ Ì ÏÂÎÙ›ÓË. ∏ ÈÛ¯·ÈÌ›· Î·È Ë Û˘Ó·ÎfiÏÔ˘ıË Â·Ó·ÈÌ¿ÙˆÛË Ô‰ËÁ› Û ÂÓ·fiıÂÛË Ù˘ mannose-binding lectin (MBL) ÛÙÔ ÓÂÊÚfi, ÛÙËÓ ÚÒÈÌË Ê¿ÛË Â·Ó·ÈÌ¿ÙˆÛ˘, Ô˘ ·ÎÔÏÔ˘ıÂ›Ù·È ·fi ÂÓ·fiıÂÛË C3, C6 Î·È C9 ÛÙËÓ fi„ÈÌË Ê¿ÛË Â·Ó·ÈÌ¿ÙˆÛ˘. ™ÙÔ ÓÂÊÚfi, Ë ÂÓ·fiıÂÛË ÙÔ˘ MBL-A Î·È -C Û˘Á¯ÚfiÓˆ˜ Î·È Ì·˙› Ì C6, ‰Â›¯ÓÂÈ fiÙÈ Ë MBL ÂÌϤÎÂÙ·È ÛÙËÓ ÂÓÂÚÁÔÔ›ËÛË ÙÔ˘ Û˘ÌÏËÚÒÌ·ÙÔ˜. ∏ ÂÓ·fiıÂÛË MBL ÛÙ· ÂÚÈÛˆÏËÓ·Úȷο ÙÚȯÔÂȉ‹ Î·È ÛÙ· ÂÈıËÏȷο ·ÙÙ·Ú· ÙˆÓ ÛˆÏËÓ·Ú›ˆÓ ÌÔÚ› ›Û˘ Ó· ·Ú·ÙËÚËı› ÚÒÈÌ· ÌÂÙ¿ ·fi ÙËÓ ÌÂÙ·ÌfiÛ¯Â˘ÛË ÓÂÊÚÒÓ Ì ‚Ï¿‚Ë ·fi ÈÛ¯·ÈÌ›·14,15. ™ÙÔ ÓÂÊÚfi, Ù· ÂÓ‰ÔıËÏȷο ·ÙÙ·Ú· Î·È Ù· Ï›· Ì˘˚ο ·ÙÙ·Ú· ÂÎÊÚ¿˙Ô˘Ó C3. ∂ÈÚÔÛı¤Ùˆ˜, ÚˆÙ½Ó˜ Ú˘ıÌÈÛÙÈΤ˜ ÙÔ˘ Û˘ÌÏËÚÒÌ·ÙÔ˜ (΢ڛˆ˜ ·Ó·ÛÙ·ÏÙÈΤ˜) fiˆ˜ Ë CD55 ÂÎÊÚ¿˙ÔÓÙ·È ÂÏ¿¯ÈÛÙ¿ Û ·˘Ù¿ Ù· ·ÙÙ·Ú·. ∏ ÛËÌ·Û›· Ù˘ ÙÔÈ΋˜ ·Ú·ÁˆÁ‹˜ ÙÔ˘ Û˘ÌÏËÚÒÌ·ÙÔ˜ ÛÙÔ ÓÂÊÚfi ·Ô‰ÂÈÎÓ‡ÂÙ·È ·fi knockout ÌÂϤÙ˜ ηٿ ÙȘ Ôԛ˜ ÓÂÊÚÈο ·ÏÏÔÌÔۯ‡̷ٷ Ô˘ ÛÙÂÚÔ‡ÓÙ·Ó C3 ›¯·Ó Ôχ ηχÙÂÚË ÂÈ‚›ˆÛË Û ıÂÙÈÎÔ‡˜ Û C3 Ï‹Ù˜ ·fi fiÙÈ Ù· ıÂÙÈο Û C3 ÌÔۯ‡̷ٷ. Δ· ·ÏÏÔÌÔۯ‡̷ٷ ›Û˘ ·fi ÓˆÚ›˜ ·ÚÔ˘ÛÈ¿˙Ô˘Ó ·‡ÍËÛË Ù˘ ÙÔÈ΋˜ ·Ú·ÁˆÁ‹˜ Û˘ÌÏËÚÒÌ·ÙÔ˜ Ì ÌÈ· ÂÈÚfiÛıÂÙË ‰Â‡ÙÂÚË Ê¿ÛË Á‡Úˆ ÛÙËÓ Ù¤Ù·ÚÙË Ë̤ڷ. ¶·Ú·ÙËÚÂ›Ù·È ·fiÙÔÌË ·‡ÍËÛË ÙˆÓ ÂȤ‰ˆÓ ηٿ ÙËÓ ·fiÚÚÈ„Ë Î·È ¿Óˆ ·fi ÙÔ 10% ÙÔ˘ ÔÏÈÎÔ‡ ΢ÎÏÔÊÔÚÔ‡ÓÙÔ˜ C ÌÔÚ› Ó· ÂÎÎÚÈı› ·fi ÙÔ ÌfiÛ¯Â˘Ì·16. ™ÙÔ ÛËÌÂ›Ô ·˘Ùfi ı· Ú¤ÂÈ Ó· ÙÔÓÈÛÙ› fiÙÈ ÙÔ Û‡ÛÙËÌ· ÙÔ˘ Û˘ÌÏËÚÒÌ·ÙÔ˜ ‰Â Û¯ÂÙ›˙ÂÙ·È ÌfiÓÔ Ì ÙËÓ IRI ·ÏÏ¿ ·ÔÙÂÏ› ›Û˘ Á¤Ê˘Ú· (fiˆ˜ Î·È ÔÈ TLRs) ÌÂٷ͇ Ê˘ÛÈ΋˜ Î·È Â›ÎÙËÙ˘ ·ÓÔÛÔ·¿ÓÙËÛ˘17.
27
ΔÔ Û‡ÛÙËÌ· Ù˘ ‹Í˘ ÙÔ ÔÔ›Ô ¤¯ÂÈ ÂÍÂÏȯı› ·Ú¿ÏÏËÏ· Ì ÙË Ê˘ÛÈ΋ ·ÓÔÛ›· ÛÙÔ˘˜ ¢ηÚȈÙÈÎÔ‡˜ ÔÚÁ·ÓÈÛÌÔ‡˜, Û˘Ì‚¿ÏÂÈ ÛÙËÓ ¿Ì˘Ó· ÙÔ˘ ÍÂÓÈÛÙ‹ ¤Ó·ÓÙÈ ÙË ÈÛÙÈ΋˜ ‚Ï¿‚˘ ηÈ/‹ Ù˘ ÂÈÛ‚ÔÏ‹˜ ÙˆÓ ·ıÔÁfiÓˆÓ. ∏ ÂÓÂÚÁÔÔ›ËÛË ÙÔ˘ ηٷÚÚ¿ÎÙË Ù˘ ‹Í˘ ¤¯ÂÈ ÛËÌ·ÓÙÈ΋ ÂÌÏÔ΋ ÛÙËÓ IRI, fiˆ˜ ¤¯ÂÈ ·Ô‰Âȯı› Û ÌÂÙ·ÌÔۯ‡ÛÂȘ ‹·ÙÔ˜, ÓÂÊÚÔ‡, ·ÁÎÚ¤·ÙÔ˜ Î·È Î·Ú‰È¿˜. ∏ ¿ÌÂÛË Ì¤Ûˆ ÙÔ˘ ·›Ì·ÙÔ˜ ÊÏÂÁÌÔÓ҉˘ ·ÓÙ›‰Ú·ÛË (instant blood-mediated inflammatory reactionIBMIR) Ô˘ ·Ú·ÙËÚÂ›Ù·È Û ÌÂÙ·ÌfiÛ¯Â˘ÛË ÓËÛȉ›ˆÓ ÙÔ˘ ·ÁÎÚ¤·ÙÔ˜ ıˆÚÂ›Ù·È ÌÈ· ÌÔÚÊ‹ Ê˘ÛÈ΋˜ ·ÓÔÛ›·˜ Ô˘ ÔÊ›ÏÂÙ·È ÙfiÛÔ Û ·Ú¿ÁÔÓÙ˜ Ù˘ ‹Í˘ (ıÚÔÌ‚›ÓË) fiÛÔ Î·È ÛÂ Û˘ÛÙ·ÙÈο Ô˘ ·ÂÏ¢ıÂÚÒÓÔÓÙ·È ·fi Ù· ÓËÛ›‰È· ˆ˜ Û˘Ó¤ÂÈ· Ù˘ ÈÛÙÈ΋˜ ‚Ï¿‚˘. ¶ÚfiÛÊ·Ù·, ¤¯Ô˘Ó ÂÈÛ·¯ı› Ӥ˜ ÛÙÚ·ÙËÁÈΤ˜ ÚÔ˜ ‚ÂÏÙ›ˆÛË ÙÔ˘ ·ÔÙÂϤÛÌ·ÙÔ˜ Ù˘ ÌÂÙ·ÌfiÛ¯Â˘Û˘ ÓËÛȉ›ˆÓ, Ô˘ ÂÚÈÏ·Ì‚¿ÓÔ˘Ó ·Ó·ÛÙÔÏ›˜ Ù˘ ıÚÔÌ‚›Ó˘, ¯ÔÚ‹ÁËÛË ·fi ÚÈÓ ÓÈÎÔÙÈÓ·Ì›‰Ë˜ ÁÈ· Ó· ÌÂȈı› ‹ ¤ÎÎÚÈÛË ÈÛÙÈÎÒÓ ·Ú·ÁfiÓÙˆÓ ·fi Ù· ÓËÛ›‰È·18,19. ∂ÈϤÔÓ ÙÔ Û‡ÛÙËÌ· ÙˆÓ ¯ËÌÂÈÔÎÈÓÒÓ (˘Ô‰Ô¯Â›˜ Î·È Û˘Ó‰¤Ù˜ ÙÔ˘˜) ÂÌϤÎÔÓÙ·È ÛÙË ÌÂÙ·ÌfiÛ¯Â˘ÛË ‰È·Ì¤ÛÔ˘ Ù˘ Ú‡ıÌÈÛ˘ Ù˘ ÌÂÙ·Ó¿ÛÙ¢Û˘ ÙˆÓ Ï¢ÎÔ΢ÙÙ¿ÚˆÓ ·fi ÙËÓ Î˘ÎÏÔÊÔÚ›· ÂÓÙfi˜ ÙÔ˘ ÌÔۯ‡̷ÙÔ˜. ™ËÌ·ÓÙÈÎfi˜ ›Û˘ Â›Ó·È Ô ÚfiÏÔ˜ ÙÔ˘˜ ÛÙË ‰È¢ÎfiÏ˘ÓÛË Ù˘ ΢ÎÏÔÊÔÚ›·˜ DCs Î·È ÙˆÓ Δ Î˘ÙÙ¿ÚˆÓ ÌÂٷ͇ ÙˆÓ ÏÂÌÊ·‰¤ÓˆÓ Î·È ÙÔ˘ ÌÔۯ‡̷ÙÔ˜ ÛÙ· ÚÒÈÌ· Î·È ÛÙ· fi„ÈÌ· ÛÙ¿‰È· Ù˘ ·ÏÏÔÁÂÓÔ‡˜ ·¿ÓÙËÛ˘. ™Ù· ÌÂÙ·ÌÔÛ¯Â˘Ì¤Ó· fiÚÁ·Ó· Ë ÈÛ¯·ÈÌ›·/·ӷÈÌ¿ÙˆÛË, Ë ÂÓÂÚÁÔÔ›ËÛË ÙˆÓ TLR, ÙˆÓ Î˘ÙÙ·ÚÔÎÈÓÒÓ Î·È ÙÔ˘ Û˘ÌÏËÚÒÌ·ÙÔ˜ ¿ÁÔ˘Ó ÙËÓ ¤ÎÊÚ·ÛË ÔÏÏ·ÏÒÓ ÚÔÊÏÂÁÌÔÓˆ‰ÒÓ ¯ËÌÂÈÔÎÈÓÒÓ ÛÙÔ ÌfiÛ¯Â˘Ì·. ∞˘Ù¤˜ ÔÈ ·ÏÏ·Á¤˜ ·˘Í¿ÓÔ˘Ó ÙËÓ IRI Î·È ÔÏÏ·Ï·ÛÈ¿˙Ô˘Ó ÙËÓ Èı·ÓfiÙËÙ· ·fiÚÚȄ˘ ÙÔ˘ ÌÔۯ‡̷ÙÔ˜. ™ÙȘ ¯ËÌÂÈÔΛÓ˜ Ô˘ ¿ÁÔÓÙ·È Û˘ÌÂÚÈÏ·Ì‚¿ÓÔÓÙ·È Ë ÈÓÙÂÚÏ¢ΛÓË 8 (IL-8/CXCL8), growth-related oncogene (GRO/CXCL1), monocyte chemoattractant protein 1 (MCP-1/CCL2), MCP- 2 (CCL8), MCP-3 (CCL7), MCP-4 (CCL13), macrophage inflammatory protein, (MIP-1/CCL3-), CCL4- Î·È RANTES (CCL5)20,21. ∏ ÁÓÒÛË fiÏˆÓ ÙˆÓ ·ÓˆÙ¤ÚˆÓ Ì˯·ÓÈÛÌÒÓ Ô‰ËÁ› ÛÙÔ Û˘Ì¤Ú·ÛÌ· fiÙÈ Â›Ó·È ··Ú·›ÙËÙË Ë ·Ó¿Ù˘ÍË ıÂڷ¢ÙÈÎÒÓ ÛÙÚ·ÙËÁÈÎÒÓ Ô˘ ·ÔÛÎÔÔ‡Ó ÛÙËÓ Î·Ù·ÛÙÔÏ‹ ÙˆÓ Ì˯·ÓÈÛÌÒÓ Ù˘ Ê˘ÛÈ΋˜ ·ÓÔÛ›·˜, Î·È ı· ·ÊÔÚÔ‡Ó ÙfiÛÔ ÙÔ ‰fiÙË Î·Ù¿ ÙË ‰È¿ÚÎÂÈ· Ù˘ Ï‹„˘ ÙÔ˘ ÌÔۯ‡̷ÙÔ˜, fiÛÔ Î·È
28
∞. ºÀ§∞∫Δ√À
ÙÔ Ï‹ÙË Î·Ù¿ ÙË ‰È¿ÚÎÂÈ· Î·È ·Ì¤Ûˆ˜ ÌÂÙ¿ ÙËÓ Â·Ó·ÈÌ¿ÙˆÛË ÙÔ˘ ÌÔۯ‡̷ÙÔ˜. ∫·Ù¿ ·˘ÙfiÓ ÙÔÓ ÙÚfiÔ ÔÈ ÛÙÚ·ÙËÁÈΤ˜ ·˘Ù¤˜ ı· Ú¤ÂÈ Ó· ·ÓÙ·Ó·ÎÏÔ‡Ó ¤Ó· a priori «ıÂڷ¢ÙÈÎfi ·Ú¿ı˘ÚÔ ÂÚÈÔÚÈṲ̂ÓÔ˘ ¯ÚfiÓÔ˘» (time restricted therapeutic window). OÈ ÛÙfi¯ÔÈ ·˘ÙÒÓ ÙˆÓ ·ÚÂÌ‚¿ÛÂˆÓ ı· Ú¤ÂÈ Ó· ›ӷÈ: (1) Ë ÂÏ·¯ÈÛÙÔÔ›ËÛË Ù˘ ‚Ï¿‚˘ ·fi ÙÔ ÔÍÂȉˆÙÈÎfi stress, (2) Ë ·Ó·ÛÙÔÏ‹ Ù˘ ÂÓÂÚÁÔÔ›ËÛ˘ ÙÔ˘ Û˘ÌÏËÚÒÌ·ÙÔ˜ ΢ڛˆ˜ ̤ۈ Ù˘ Ô‰Ô‡ Ù˘ MBL, (3) Ë ·Ó·ÛÙÔÏ‹ Ù˘ ˆÚ›Ì·ÓÛ˘ ÙˆÓ ‰ÂÓ‰ÚÈÙÈÎÒÓ Î˘ÙÙ¿ÚˆÓ ÌÏÔοÚÔÓÙ·˜ ÙËÓ ¤ÎÊÚ·ÛË ÙÔ˘ TLR4 ‹ ÙÔ˘ NFÎμ-gene Î·È (4) Ô ·ÔÎÏÂÈÛÌfi˜ ÙˆÓ ‰Ú·ÛÙÈÎÒÓ ÏÂÈÙÔ˘ÚÁÈÒÓ Ù˘ Ê˘ÛÈ΋˜ ·ÓÔÛ›·˜ fiˆ˜ Â›Ó·È Ë ¤ÎÎÚÈÛË ¯ËÌÂÈÔÎÈÓÒÓ, ΢ÙÙ·ÚÔÎÈÓÒÓ Î·È ÌÔÚ›ˆÓ ÚÔÛÎfiÏÏËÛ˘22-25.
μÈ‚ÏÈÔÁÚ·Ê›· 1. Land, W.G. The role of postischemic reperfusion injury and other nonantigen-dependent inflammatory pathways in transplantation. Transplantation, 2005. 79(5): p. 505-14. 2. Land, W.G. Injury to allografts: innate immune pathways to acute and chronic rejection. Saudi J Kidney Dis Transpl, 2005. 16(4): p. 520-39. 3. Matzinger, P. The danger model: a renewed sense of self. Science, 2002. 296(5566): p. 301-5. 4. Land, W.G. Innate immunity-mediated allograft rejection and strategies to prevent it. Transplant Proc, 2007. 39(3): p. 667-72. 5. Takeda, K. and S. Akira. Toll-like receptors in innate immunity. Int Immunol, 2005. 17(1): p. 1-14. 6. Thimmulappa, R.K., et al. Nrf2 is a critical regulator of the innate immune response and survival during experimental sepsis. J Clin Invest, 2006. 116(4): p. 984-95. 7. Munz, C., R.M. Steinman, and S. Fujii. Dendritic cell maturation by innate lymphocytes: coordinated stimulation of innate and adaptive immunity. J Exp Med, 2005. 202(2): p. 203-7. 8. Andrade, C.F., et al. Innate immunity and organ transplantation: the potential role of toll-like receptors. Am J Transplant, 2005. 5(5): p. 969-75. 9. Boros, P. and J.S. Bromberg. New cellular and molecular immune pathways in ischemia/reperfusion injury. Am J Transplant, 2006. 6(4): p. 652-8. 10. Goldstein, D.R. Toll like receptors and acute allograft rejection. Transpl Immunol, 2006. 17(1): p. 11-5.
11. Obhrai, J. and D.R. Goldstein. The role of toll-like receptors in solid organ transplantation. Transplantation, 2006. 81(4): p. 497-502. 12. Walsh, M.C., et al. Mannose-binding lectin is a regulator of inflammation that accompanies myocardial ischemia and reperfusion injury. J Immunol, 2005. 175(1): p. 541-6. 13. Zhang, M., et al. Identification of a specific self-reactive IgM antibody that initiates intestinal ischemia/reperfusion injury. Proc Natl Acad Sci U S A, 2004. 101(11): p. 3886-91. 14. Collard, C.D., et al. Complement activation after oxidative stress: role of the lectin complement pathway. Am J Pathol, 2000. 156(5): p. 1549-56. 15. de Vries, B., et al. The mannose-binding lectin-pathway is involved in complement activation in the course of renal ischemia-reperfusion injury. Am J Pathol, 2004. 165(5): p. 1677-88. 16. Pratt, J.R., S.A. Basheer, and S.H. Sacks. Local synthesis of complement component C3 regulates acute renal transplant rejection. Nat Med, 2002. 8(6): p. 582-7. 17. Lin, T., W. Zhou, and S.H. Sacks. The role of complement and Toll-like receptors in organ transplantation. Transpl Int, 2007. 20(6): p. 481-9. 18. Johansson, U., et al. Composite islet-endothelial cell grafts: a novel approach to counteract innate immunity in islet transplantation. Am J Transplant, 2005. 5(11): p. 2632-9. 19. Moberg, L. The role of the innate immunity in islet transplantation. Ups J Med Sci, 2005. 110(1): p. 17-55. 20. Chen, D., et al. Viral IL-10 gene transfer inhibits the expression of multiple chemokine and chemokine receptor genes induced by inflammatory or adaptive immune stimuli. Am J Transplant, 2003. 3(12): p. 1538-49. 21. Moser, B., et al. Chemokines: multiple levels of leukocyte migration control. Trends Immunol, 2004. 25(2): p. 75-84. 22. Mahaffey, K.W., et al. Effect of pexelizumab on mortality in patients with acute myocardial infarction or undergoing coronary artery bypass surgery: a systematic overview. Am Heart J, 2006. 152(2): p. 291-6. 23. Masini, E., et al. Protective effects of M40403, a selective superoxide dismutase mimetic, in myocardial ischaemia and reperfusion injury in vivo. Br J Pharmacol, 2002. 136(6): p. 905-17. 24. Saemann, M.D., et al. Hyporesponsiveness in alloreactive T-cells by NF-kappaB inhibitor-treated dendritic cells: resistance to calcineurin inhibition. Am J Transplant, 2004. 4(9): p. 1448-58. 25. Tahara, M., et al. A radical scavenger, edaravone, protects canine kidneys from ischemia-reperfusion injury after 72 hours of cold preservation and autotransplantation. Transplantation, 2005. 80(2): p. 213-21.
Dendritic cells (DCs) and regulatory T cells (Tregs) in renal transplantation V. Daniel
maintenance of graft acceptance and transplant tolerance. Treg and Ts were shown to produce IL-10 but not IFN-Á and it was suggested that IL-10 might in part account for the immunosuppressive effect of Treg and Ts. Recently, we described in long-term stable kidney transplant recipients a domination of myeloid IL-10-producing DC 1. In contrast to our expectation, the patients showed abnormally high IFN-Á and IL-2, and low IL-10 plasma levels. More than 10 years posttransplant, some patients showed IFN-Á plasma levels three-times higher than healthy controls. We confirmed these data in another study and speculated that the abnormally increased IFN-Á plasma levels might be associated with IFN-Áproducing Treg and might contribute to graft acceptance2. In a further study we showed that renal transplant recipients with good long-term graft function had more often detectable CD3+CD4+ CD25 + Foxp3 + IFN-Á + peripheral blood lymphocytes (PBL) late posttransplant than patients with impaired graft function3. Apparently, CD3+CD4+ CD25+Foxp3+IFN-Á+ PBL may contribute to the maintenance of immunological quiescence and absence of CD3+CD4+CD25+Foxp3+IFN-Á+ PBL promotes chronic graft dysfunction. In a current study we show that high IFN-Á plasma levels are associated with low numbers of B lymphocytes and activated CD8 + T lymphocytes in the blood of patients with good long-term graft function. These low B and T cell counts might be involved in preventing the development of an immunological alloresponse against the graft and support the maintenance of graft acceptance. An immunosuppressive capacity of CD3 + CD4+CD25+IFN-Á+ Treg in mice was described by Sawitzki et al. and Wood et al.4,5. As proposed by Wood et al., IFN-Á might indirectly prevent further T-cell activation by creating a microenvi-
Dendritic cells (DCs) and regulatory T cells (Tregs) are supposed to contribute to the induction and maintenance of graft acceptance and transplant tolerance. Transplant recipients with functioning grafts were shown to possess increased circulating lineage - HLA-DR + CD11c - CD123 + plasmacytoid dendritic cells type 2 (DC2) precursors, forkehead/winged helix transcription factor (Foxp3)-expressing CD3 + CD4 + CD25 + regulatory T cells (Treg), CD3 +CD8 +CD28 - T suppressor lymphocytes (Ts), TGF-ß2-producing T helper lymphocytes type 3 (Th3), TCR+CD4-CD8T, and NK Treg cells. However, the contribution of these cell subsets to the establishment and maintenance of graft acceptance is unclear. DCs start out on every immune reaction. They can initiate or suppress an immune response against antigen. Their diagnostic and therapeutic utilization are major research topics in transplantation medicine. One goal of studies in transplantation-immunology is the identification of transplanted patients, whose immunosuppressive treatment can be reduced or potentially discontinued without a subsequent impairment of graft function. The induction of tolerogenic DCs and their immunological monitoring in the patient blood would be an option for the realization of this goal. In experiments with cell cultures and animals, DCs were identified as target cells of immunosuppressive drugs. Clinical studies with transplant recipients showed alterations of DC subpopulations in the patient blood depending on the immunosuppressive drugs and their dosage. Up to now, no DC subpopulation could be identified in the blood of transplant recipients that would allow prospectively a discontinuation of the immunosuppressive protocol. Further studies in vitro and in vivo are necessary to define the DC subsets that are relevant for the induction and
29
30
V. DANIEL
ronment that influences the function of antigenpresenting cells as a result of IFN-Á-induced nitric oxide synthase, indoleamine-2,3-dioxygenase and heme oxygenase-1 expression5. Obviously, IFN-Á mediated immune mechanisms orchestrate interactions of DCs, Tregs, IFN-Á producing Tregs, IFN-Á plasma levels, B cells and cytotoxic T lymphocytes late posttransplant that might contribute to the establishment and maintenance of graft acceptance.
References: 1. Daniel V, Naujokat C, Sadeghi M, Wiesel M, Hergesell O, Opelz G. Association of circulating IL-12- and IL-10producing dendritic cells with time posttransplant, dose of immunosuppression, and plasma cytokines in renal transplant recipients. Transplantation 2005; 79: 1498.
2. Sadeghi M, Daniel V, Naujokat C, Schmidt J, Mehrabi A, Zeier M, Opelz G. Evidence for IFN-g Up- and IL-4 Down-Regulation Late Posttransplant in Patients With Good Kidney Graft Outcome. Clin Transplant. 2007; 21: 449. 3. Daniel V, Naujokat C, Sadeghi M, Weimer R, Renner F, Yildiz S, Opelz G. Observational support for an immunoregulatory role of CD3(+)CD4(+)CD25(+)IFNgamma(+) blood lymphocytes in kidney transplant recipients with good long-term graft outcome. Transpl Int. 2008 (in press). 4. Sawitzki B, Kingsley CI, Oliveira V, Karim M, Herber M, Wood KJ. IFN-gamma production by alloantigen-reactive regulatory T cells is important for their regulatory function in vivo. J Exp Med 2005; 201: 1925. 5. Wood KJ, Sawitzki B. Interferon gamma: a crucial role in the function of induced regulatory T cells in vivo. Trends Immunol 2006; 27: 183.
A¢·ÈÛıËÙÔÔ›ËÛË ·ÛıÂÓÒÓ ˘Ô„‹ÊÈˆÓ ÁÈ· ÌÂÙ·ÌfiÛ¯Â˘ÛË ·fi ˙ˆÓÙ·Ófi ‰fiÙË ÓÂÊÚÔ‡ ¢. ¶··‰ÔÔ‡ÏÔ˘
ø˜ ıÂڷ›· ·ÁˆÁ‹˜ ¯ÚËÛÈÌÔÔÈ‹ıËÎÂ Ë ÔÏ˘ÎψÓÈ΋ ·ÓÙÈı˘ÌÔ΢ÙÙ·ÚÈ΋ ÛÊ·ÈÚ›ÓË (thymoglobulin), Û ‰fiÛË 1mg/Kg μ™ ËÌÂÚËÛ›ˆ˜, ÁÈ· ¯ÚÔÓÈÎfi ‰È¿ÛÙËÌ· 10 ËÌÂÚÒÓ, ÂÓÒ Ë ıÂڷ›· Û˘ÓÙ‹ÚËÛ˘ ÂÚÈÂÏ¿Ì‚·Ó MMF, ÎÔÚÙÈÎÔÛÙÂÚÔÂȉ‹ Î·È tacrolimus. ŒÓ· ÌfiÛ¯Â˘Ì· ¯¿ıËΠÂÍ·ÈÙ›·˜ ıÚfiÌ‚ˆÛ˘ Î·È ¤Ó· ‰Â‡ÙÂÚÔ ÂÍ·ÈÙ›·˜ ·fiÚÚȄ˘. ™Ù· ˘fiÏÔÈ· ÌÔۯ‡̷ٷ, ‰ÂÓ ˘‹ÚÍ·Ó ¿ÏÏ· ÂÂÈÛfi‰È· ·fiÚÚȄ˘, ÁÈ· ¯ÚÔÓÈÎfi ‰È¿ÛÙËÌ· Ô˘ ÍÂÂÚÓÔ‡Û ÙÔ 1 ¤ÙÔ˜. ™ÙË ‰Â‡ÙÂÚË ÌÂϤÙË4, 45 ˘ÂÚ¢·ÈÛıËÙÔÔÈË̤ÓÔÈ ·ÛıÂÓ›˜ (15 ˘Ô„‹ÊÈÔÈ ÁÈ· ÌÂÙ·ÌfiÛ¯Â˘ÛË ÓÂÊÚÔ‡ ·fi و̷ÙÈÎfi Î·È 28 ·fi ˙ˆÓÙ·Ófi ‰fiÙË Î·È 2 ˘Ô„‹ÊÈÔÈ ÁÈ· ÌÂÙ·ÌfiÛ¯Â˘ÛË Î·Ú‰È¿˜) ˘Ô‚Ï‹ıËÎ·Ó Û ·Â˘·ÈÛıËÙÔÔ›ËÛË Ì ·ÚfiÌÔÈÔ Û¯‹Ì·. ŸÏÔÈ ÔÈ ˘Ô„‹ÊÈÔÈ ÁÈ· ÌÂÙ·ÌfiÛ¯Â˘ÛË ÓÂÊÚÔ‡ ·fi ˙ˆÓÙ·Ófi ‰fiÙË Â›¯·Ó ıÂÙÈÎfi crossmatch Ì ÙÔ˘˜ ‰fiÙ˜ ÙÔ˘˜. ΔÔ ıÂڷ¢ÙÈÎfi ÚˆÙfiÎÔÏÏÔ ÂÚÈÂÏ¿Ì‚·Ó ÙËÓ ÂÓ‰ÔÊϤ‚È· ¯ÔÚ‹ÁËÛË ·ÓÔÛÔÛÊ·ÈÚ›Ó˘ Û ‰fiÛË 2g/ Kg μ™ (̤ÁÈÛÙË ‰fiÛË 140 g). ™ÙË Û˘Ó¤¯ÂÈ·, Â¿Ó Î¿ÔÈÔ ·fi Ù· ·ÓÂÈÏËÌ̤ӷ crossmatch ·¤‚·ÈÓ ·ÚÓËÙÈÎfi, Ô ·ÛıÂÓ‹˜ ˘Ô‚·ÏÏfiÙ·Ó Û ÌÂÙ·ÌfiÛ¯Â˘ÛË ÓÂÊÚÔ‡ Û ¯ÚÔÓÈÎfi ‰È¿ÛÙËÌ· 24 ¤ˆ˜ 72 ˆÚÒÓ. ∏ ›‰È· ‰fiÛË IVIg ·ӷϷ̂·ÓfiÙ·Ó Û 1 Ì‹Ó· ÌÂÙ¿ ÙË ÌÂÙ·ÌfiÛ¯Â˘ÛË. ™Â 26 ·fi ÙÔ˘˜ 28 ˘Ô„ËÊ›Ô˘˜ ÁÈ· ÌÂÙ·ÌfiÛ¯Â˘ÛË ÓÂÊÚÔ‡ ·fi ˙ˆÓÙ·Ófi ‰fiÙË, ÙÔ crossmatch ·ÚÓËÙÈÎÔÔÈ‹ıËΠ̛̠· Î·È ÌfiÓÔ ‰fiÛË ·ÓÔÛÔÛÊ·ÈÚ›Ó˘, ÂÓÒ ÛÙÔ˘˜ ˘fiÏÔÈÔ˘˜ 2 ·ÛıÂÓ›˜, ··ÈÙ‹ıËÎÂ Ë ÌËÓÈ·›· ¯ÔÚ‹ÁËÛË ÂÈϤÔÓ ‰fiÛÂˆÓ ÙÔ˘ Ê·ÚÌ¿ÎÔ˘ ÚÈÓ Ô‰ËÁËıÔ‡Ó ÛÙÔ ÂÈı˘ÌËÙfi ·ÔÙ¤ÏÂÛÌ·. ŸÏÔÈ ÔÈ ·ÛıÂÓ›˜ ¤Ï·‚·Ó ıÂڷ›· ·ÁˆÁ‹˜ Ì daclizumab, ÂÓÒ Ë ·ÓÔÛÔηٷÛÙ·ÏÙÈ΋ ·ÁˆÁ‹ Û˘ÓÙ‹ÚËÛ˘ ÂÚÈÂÏ¿Ì‚·Ó MMF, ÎÔÚÙÈÎÔÛÙÂÚÔÂȉ‹ Î·È tacrolimus. ™‡Ìʈӷ Ì ٷ ·ÔÙÂϤÛÌ·Ù· Ù˘ ÌÂϤÙ˘, 13 ·fi ÙÔ˘˜ 42 ·ÛıÂÓ›˜ (31%) ·ÚÔ˘Û›·Û·Ó ·fi ¤Ó· ÂÂÈÛfi‰ÈÔ ÔÍ›·˜ ·fiÚÚȄ˘ ( fiÏÔÈ ÛÙÔ˘˜ 2 ÚÒÙÔ˘˜ Ì‹Ó˜ ÌÂÙ¿ ÙË ÌÂÙ·ÌfiÛ¯Â˘ÛË) Î·È 3 ÌÔۯ‡̷ٷ ¯¿ıËÎ·Ó ÂÍ·È-
Δ· ΢ÚÈfiÙÂÚ· ÚˆÙfiÎÔÏÏ· Ô˘ ÂÊ·ÚÌfi˙ÔÓÙ·È ÁÈ· ÙËÓ ·Â˘·ÈÛıËÙÔÔ›ËÛË ·ÛıÂÓÒÓ ˘Ô„‹ÊÈˆÓ ÁÈ· ÌÂÙ·ÌfiÛ¯Â˘ÛË ÓÂÊÚÔ‡ ·fi ˙ˆÓÙ·Ófi ‰fiÙË Â›Ó·È: ·) Ë ÂÓ‰ÔÊϤ‚È· ¯ÔÚ‹ÁËÛË ÌÂÁ¿ÏˆÓ ‰fiÛÂˆÓ ·ÓÔÛÔÛÊ·ÈÚ›Ó˘ (intravenous immunoglobulin, IVIg) Î·È ‚) Ë ÂÓ‰ÔÊϤ‚È· ¯ÔÚ‹ÁËÛË ÌÈÎÚÒÓ ‰fiÛÂˆÓ ·ÓÔÛÔÛÊ·ÈÚ›Ó˘ ÛÂ Û˘Ó‰˘·ÛÌfi Ì ÙË ‰ÈÂÓ¤ÚÁÂÈ· Û˘Ó‰ÚÈÒÓ Ï·ÛÌ·Ê·›ÚÂÛ˘ (plasmapheresis, PP). ™Â οÔÈ· ÌÂÙ·ÌÔÛ¯Â˘ÙÈο ΤÓÙÚ·, Û˘ÌÂÚÈÏ·Ì‚¿ÓÂÙ·È ÛÙ· ıÂڷ¢ÙÈο Û¯‹Ì·Ù· ·Â˘·ÈÛıËÙÔÔ›ËÛ˘ Î·È Ë ¯ÔÚ‹ÁËÛË ÙÔ˘ ÌÔÓÔÎψÓÈÎÔ‡ ·ÓÙÈ-CD20 ·ÓÙÈÛÒÌ·ÙÔ˜ rituximab, Ì ÛÎÔfi ÙËÓ ·ÔÊ˘Á‹ ·ӷ‰ËÌÈÔ˘ÚÁ›·˜ ÙˆÓ HLA·ÓÙÈÛˆÌ¿ÙˆÓ ÌÂÙ¿ ÙË ÌÂÙ·ÌfiÛ¯Â˘ÛË.
¶ÚˆÙfiÎÔÏÏ· ÂÓ‰ÔÊϤ‚È·˜ ¯ÔÚ‹ÁËÛ˘ ÌÂÁ¿ÏˆÓ ‰fiÛÂˆÓ ·ÓÔÛÔÛÊ·ÈÚ›Ó˘ (IVIg) OÈ ÚÒÙ˜ ·Ó·ÊÔÚ¤˜ Û¯ÂÙÈο Ì ÙË ¯Ú‹ÛË ÌÂÁ¿ÏˆÓ ‰fiÛÂˆÓ ·ÓÔÛÔÛÊ·ÈÚ›Ó˘ ÁÈ· ÙËÓ ·Â˘·ÈÛıËÙÔÔ›ËÛË ·ÛıÂÓÒÓ ˘Ô„‹ÊÈˆÓ ÁÈ· ÌÂÙ·ÌfiÛ¯Â˘ÛË ÓÂÊÚÔ‡ ¤ÁÈÓ·Ó ÛÙȘ ·Ú¯¤˜ Ù˘ ‰ÂηÂÙ›·˜ ÙÔ˘ ’901,2. ™ÙË Û˘Ó¤¯ÂÈ·, ÙÔ ·Ú·¿Óˆ ÚˆÙfiÎÔÏÏÔ ¤ÁÈÓ ·Ô‰ÂÎÙfi Î·È Â‰Ú·ÈÒıËÎÂ, Ì ‚¿ÛË Ù· ÂÓı·ÚÚ˘ÓÙÈο ·ÔÙÂϤÛÌ·Ù· ·fi ÙȘ ÌÂϤÙ˜ ÙˆÓ Glotz Î·È Û˘Ó.3 Î·È Jordan Î·È Û˘Ó.4. ™ÙËÓ ÚÒÙË ÌÂϤÙË3, Û 15 ·ÛıÂÓ›˜ Ì ٛÙÏÔ ·ÓÙÈ-HLA ·ÓÙÈÛˆÌ¿ÙˆÓ >50% ‹ Ì ıÂÙÈÎfi crossmatch Ì ÙÔ˘˜ ˘Ô„‹ÊÈÔ˘˜ ˙ˆÓÙ·ÓÔ‡˜ ‰fiÙ˜ ÙÔ˘˜, ¯ÔÚËÁ‹ıËΠIVIg, Û ‰fiÛË 2g/ Kg μ™ ·Ó¿ Ì‹Ó·, ÁÈ· ¯ÚÔÓÈÎfi ‰È¿ÛÙËÌ· 3 ÌËÓÒÓ. ¢ÂηÙÚ›˜ ·fi ÙÔ˘˜ ·Ú·¿Óˆ ·ÛıÂÓ›˜ ÂÌÊ¿ÓÈÛ·Ó ÂӉ›ÍÂȘ ·Â˘·ÈÛıËÙÔÔ›ËÛ˘ (ÂÏ¿ÙÙˆÛË ÙÔ˘ Ù›ÙÏÔ˘ ÙˆÓ ·ÓÙÈ-HLA ·ÓÙÈÛˆÌ¿ÙˆÓ ÙÔ˘Ï¿¯ÈÛÙÔÓ Î·Ù¿ 50% ‹ ·ÓÂÈÏËÌ̤ӷ ·ÚÓËÙÈÎfi crossmatch Ì ÙÔ˘˜ ˙ˆÓÙ·ÓÔ‡˜ ‰fiÙ˜ ÙÔ˘˜) Î·È ˘Ô‚Ï‹ıËÎ·Ó Û ÌÂÙ·ÌfiÛ¯Â˘ÛË ÓÂÊÚÔ‡ (11 ·fi و̷ÙÈÎfi Î·È 2 ·fi ˙ˆÓÙ·Ófi ‰fiÙË). ∏ IVIg ·ӷ¯ÔÚËÁ‹ıËΠÛÙËÓ ›‰È· ‰fiÛË ÙȘ Ë̤Ú˜ 0 Î·È 1 ÌÂÙ¿ ÙË ÌÂÙ·ÌfiÛ¯Â˘ÛË Î·È, ¿ÏÈ, ÙȘ Ë̤Ú˜ 20 ‹ 21 Î·È 40 ‹ 41.
31
32
¢. ¶∞¶∞¢O¶OÀ§OÀ
Ù›·˜ ·fiÚÚȄ˘. ™Ù· 2 ¤ÙË, Ë Ì¤ÛË ÙÈÌ‹ Ù˘ ÎÚ·ÙÈÓ›Ó˘ ÔÚÔ‡ ‹Ù·Ó 1,4mg/dl Î·È Ë ÂÈ‚›ˆÛË ÙˆÓ ·ÛıÂÓÒÓ ¤Êı·Ó ÙÔ 98%. ∏ ÂÈ‚›ˆÛË, ÂÍ¿ÏÏÔ˘, ÙˆÓ ÌÔÛ¯Â˘Ì¿ÙˆÓ ·ÓÂÚ¯fiÙ·Ó ÛÙÔ 89% Î·È ‹Ù·Ó Û˘ÁÎÚ›ÛÈÌË Ì ÙËÓ ·ÓÙ›ÛÙÔÈ¯Ë ÙˆÓ ÌË ˘ÂÚ¢ÛıËÙÔÔÈËÌ¤ÓˆÓ ÏËÙÒÓ. OÈ ·ÓÂÈı‡ÌËÙ˜ ÂÓ¤ÚÁÂȘ ·fi ÙË ¯ÔÚ‹ÁËÛË ÌÂÁ¿ÏˆÓ ‰fiÛÂˆÓ ·ÓÔÛÔÛÊ·ÈÚ›Ó˘ (ÎÂÊ·Ï·ÏÁ›·, ˘ÚÂÙfi˜, Ì˘·ÏÁ›Â˜, ·›ÛıËÌ· ÚÔοډȷ˜ ‰˘ÛÊÔÚ›·˜ Î.¿.) Â›Ó·È ‰˘Ó·Ùfi Ó· ·ÔÊ¢¯ıÔ‡Ó Ì ÙË ¯Ú‹ÛË Û΢·ÛÌ¿ÙˆÓ ÈÛÔˆÛ̈ÙÈÎÒÓ Ì ÙÔ Ï¿ÛÌ·5.
¶ÚˆÙfiÎÔÏÏ· Ï·ÛÌ·Ê·›ÚÂÛ˘ (ƒƒ/IVIg) ¶Ôχ ÈηÓÔÔÈËÙÈο ·ÔÙÂϤÛÌ·Ù· ÛÙËÓ ·Â˘·ÈÛıËÙÔÔ›ËÛË ·ÛıÂÓÒÓ ˘Ô„‹ÊÈˆÓ ÁÈ· ÌÂÙ·ÌfiÛ¯Â˘ÛË ÓÂÊÚÔ‡ Ê·›ÓÂÙ·È Ó· ˘fiÛ¯ÂÙ·È Ë ÂÓ‰ÔÊϤ‚È· ¯ÔÚ‹ÁËÛË ÌÈÎÚÒÓ ‰fiÛÂˆÓ ·ÓÔÛÔÛÊ·ÈÚ›Ó˘, ÛÂ Û˘Ó‰˘·ÛÌfi Ì ÙË ‰ÈÂÓ¤ÚÁÂÈ· Û˘Ó‰ÚÈÒÓ Ï·ÛÌ·Ê·›ÚÂÛ˘. π‰È·›ÙÂÚ· ÛÙȘ ÂÚÈÙÒÛÂȘ ÚÔÂÙÔÈÌ·Û›·˜ ÁÈ· ÌÂÙ·ÌfiÛ¯Â˘ÛË ÓÂÊÚÔ‡ ·fi ˙ˆÓÙ·Ófi ‰fiÙË, Ô ·Ú·¿Óˆ Û˘Ó‰˘·ÛÌfi˜ ÂÈÙÚ¤ÂÈ ÙËÓ Ï‹ÚË ·ÔÌ¿ÎÚ˘ÓÛË ÙˆÓ ÂȉÈÎÒÓ ÂÓ·ÓÙ›ÔÓ ÙÔ˘ ‰fiÙË ·ÓÙÈÛˆÌ¿ÙˆÓ (donor-specific antibodies, DSA) ÚÈÓ ÙË ÌÂÙ·ÌfiÛ¯Â˘ÛË. ™ÙȘ ÂÚÈÛÛfiÙÂÚ˜ ÌÂϤÙ˜, ¤¯Ô˘Ó ¯ÚËÛÈÌÔÔÈËı› Û΢¿ÛÌ·Ù· ·ÓÔÛÔÛÊ·ÈÚ›Ó˘ Ô˘ ÚÔ¤Ú¯ÂÙ·È ·fi ΢ÙÙ·ÚÔÌÂÁ·ÏÔ˚fi (CMV-Ig) Î·È ÙÔ‡ÙÔ ·ÔÙÂÏ› Û˘Ó‹ıˆ˜ ÂÈÏÔÁ‹ ÙÔ˘ ÌÂÙ·ÌÔÛ¯Â˘ÙÈÎÔ‡ ΤÓÙÚÔ˘. ΔÔ ÚˆÙfiÎÔÏÏÔ ÂÊ·ÚÌfi˙ÂÙ·È Î·Ù¿ ÙËÓ ÚÔÌÂÙ·ÌÔÛ¯Â˘ÙÈ΋ ÂÚ›Ô‰Ô Î·È ÂÚÈÏ·Ì‚¿ÓÂÈ ·Ú’ Ë̤ڷ Û˘Ó‰ڛ˜ ƒƒ Î·È ÂÓ‰ÔÊϤ‚È· ¯ÔÚ‹ÁËÛË ·ÓÔÛÔÛÊ·ÈÚ›Ó˘, Û ‰fiÛË 100mg/ Kg μ™, ÌÂÙ¿ ·fi οıÂ Û˘Ó‰ڛ·. O ·ÚÈıÌfi˜ ÙˆÓ Û˘Ó‰ÚÈÒÓ Ï·ÛÌ·Ê·›ÚÂÛ˘ Ô˘ ··ÈÙÔ‡ÓÙ·È ÂÍ·ÚÙ¿Ù·È ·fi ÙÔ ‡„Ô˜ ÙÔ˘ Ù›ÙÏÔ˘ ÙˆÓ ·ÓÙÈ-HLA ·ÓÙÈۈ̿وÓ. ∞̤ۈ˜ ÌÂÙ¿ ÙËÓ ÂÍ·Ê¿ÓÈÛË ÙˆÓ Î˘ÙÙ·ÚÔÙÔÍÈÎÒÓ ·ÓÙÈÛˆÌ¿ÙˆÓ Î·È ÙËÓ ·ÚÓËÙÈÎÔÔ›ËÛË ÙÔ˘ crossmatch, ÔÈ ·ÛıÂÓ›˜ ıˆÚÔ‡ÓÙ·È Ï¤ÔÓ ¤ÙÔÈÌÔÈ ÁÈ· ÌÂÙ·ÌfiÛ¯Â˘ÛË. ΔÔ ·Ú·¿Óˆ ıÂڷ¢ÙÈÎfi Û¯‹Ì· ÚÔÙ¿ıËΠ·fi ÙÔ˘˜ Montgomery Î·È Û˘Ó.6, ÔÈ ÔÔ›ÔÈ ‰ËÌÔÛ›Â˘Û·Ó Ù· ·ÔÙÂϤÛÌ·Ù· ÙˆÓ ÌÂÙ·ÌÔۯ‡ÛÂˆÓ ÓÂÊÚÔ‡ Û ÌÈ· ÌÈÎÚ‹ ÛÂÈÚ¿ ·ÛıÂÓÒÓ Ì ıÂÙÈÎfi crossmatch Ì ÙÔ˘˜ ˙ˆÓÙ·ÓÔ‡˜ ‰fiÙ˜ ÙÔ˘˜. ø˜ ıÂڷ›· ·ÁˆÁ‹˜ ¯ÚËÛÈÌÔÔÈ‹ıËÎÂ Ë daclizumab Î·È ˆ˜ ıÂڷ›· Û˘ÓÙ‹ÚËÛ˘ Ô Û˘Ó‰˘·ÛÌfi˜ MMF, ÎÔÚÙÈÎÔÛÙÂÚÔÂȉÒÓ Î·È tacrolimus. ΔÔ ÚˆÙfiÎÔÏÏÔ ·Â˘·ÈÛıËÙÔÔ›ËÛ˘ Û˘Ó¯›ÛıËÎÂ Î·È Î·Ù¿ ÙËÓ ÂÚ›Ô‰Ô ÌÂÙ¿ ÙË ÌÂÙ·ÌfiÛ¯Â˘ÛË Î·È Ë ¯ÚÔÓÈ΋ ÙÔ˘ ‰È¿ÚÎÂÈ· ÁÈ· οı ·ÛıÂÓ‹ ηıÔÚ›-
ÛÙËΠ·fi ÙÔ ‡„Ô˜ ÙÔ˘ Ù›ÙÏÔ˘ ÙˆÓ ·ÓÙÈ-HLA ·ÓÙÈÛˆÌ¿ÙˆÓ ÚÈÓ ÙËÓ Â¤Ì‚·ÛË. ™Â ÈÔ ÚfiÛÊ·ÙË ÌÂϤÙË ·Ú·ÎÔÏÔ‡ıËÛ˘7, ÔÈ ›‰ÈÔÈ ÂÚ¢ÓËÙ¤˜ ·Ó·Ê¤ÚÔ˘Ó Ï‹ÚË ÂÍ·Ê¿ÓÈÛË ÙˆÓ DSA Û ÔÛÔÛÙfi 89% ÙˆÓ ·ÛıÂÓÒÓ, ·ÔÙ¤ÏÂÛÌ· Ô˘ Ê¿ÓËΠӷ ¤¯ÂÈ ÌÂÁ¿ÏË ‰È¿ÚÎÂÈ·, ηıÒ˜ ‰È·ÙËÚ‹ıËΠÁÈ· ̤ÛÔ ¯ÚÔÓÈÎfi ‰È¿ÛÙËÌ· 13 ÌËÓÒÓ. ¶·ÚfiÌÔÈ· ‹Ù·Ó Ù· ·ÔÙÂϤÛÌ·Ù· ·fi ÙË ÌÂϤÙË ÙˆÓ Schweitzer Î·È Û˘Ó.8, ÛÙËÓ ÔÔ›· 11 ·fi ÙÔ˘˜ 15 ·ÛıÂÓ›˜ Ì ıÂÙÈÎfi crossmatch ˘Ô‚Ï‹ıËÎ·Ó Ì ÂÈÙ˘¯›· Û ÌÂÙ·ÌfiÛ¯Â˘ÛË ÓÂÊÚÔ‡ ·fi ˙ˆÓÙ·Ófi ‰fiÙË, ÌÂÙ¿ ·fi ÂÊ·ÚÌÔÁ‹ ÚˆÙÔÎfiÏÏÔ˘ ·Â˘·ÈÛıËÙÔÔ›ËÛ˘. ∞Í›˙ÂÈ Ó· ÛËÌÂȈı›, fiÙÈ ÔÈ ·ÛıÂÓ›˜ ·˘Ù‹˜ Ù˘ ÌÂϤÙ˘ ¤Ï·‚·Ó O∫Δ3 ÌÂÙ¿ ÙË ÌÂÙ·ÌfiÛ¯Â˘ÛË. ªÂÙ¿ ·fi ̤ÛÔ ¯ÚÔÓÈÎfi ‰È¿ÛÙËÌ· 13,3 ÌËÓÒÓ, Ë Ì¤ÛË ÙÈÌ‹ Ù˘ ÎÚ·ÙÈÓ›Ó˘ ÔÚÔ‡ ‹Ù·Ó 1,6mg/dl. ¶ÚfiÛÊ·Ù·, Ë ÔÌ¿‰· Ù˘ Mayo Clinic Û˘Ó¤ÎÚÈÓ ÙËÓ ·ÔÙÂÏÂÛÌ·ÙÈÎfiÙËÙ· ÛÙËÓ ·Â˘·ÈÛıËÙÔÔ›ËÛË ÙˆÓ ·ÛıÂÓÒÓ Ù˘ ¯ÔÚ‹ÁËÛ˘ ÌÂÁ¿ÏˆÓ ‰fiÛÂˆÓ IVIg Ì ÂΛÓË ÙˆÓ Û¯ËÌ¿ÙˆÓ Ô˘ ÂÚÈÏ·Ì‚¿ÓÔ˘Ó Û˘Ó‰ڛ˜ ƒƒ. ™ÙË ÌÔÓ·‰È΋ ·˘Ù‹ Û˘ÁÎÚÈÙÈ΋ ÌÂϤÙË9, ¯ÚËÛÈÌÔÔÈ‹ıËÎ·Ó Ù· ·Ú·Î¿Ùˆ ıÂڷ¢ÙÈο ÚˆÙfiÎÔÏÏ·: ñ ¶ÚˆÙfiÎÔÏÏÔ 1 –ªÂÁ¿Ï˜ ‰fiÛÂȘ IVIg (2g/ Kg μ™ x 1) (1-3 Ë̤Ú˜ ÚÈÓ ÙË ÌÂÙ·ÌfiÛ¯Â˘ÛË) ñ ¶ÚˆÙfiÎÔÏÏÔ 2 –∫·ıËÌÂÚÈÓ¤˜ Û˘Ó‰ڛ˜ ƒƒ + ÌÈÎÚ¤˜ ‰fiÛÂȘ IVIg (100mg/ Kg μ™) –Rituximab (375mg/m2 ∂™ x 1) (4-7 Ë̤Ú˜ ÚÈÓ ÙË ÌÂÙ·ÌfiÛ¯Â˘ÛË) ñ ¶ÚˆÙfiÎÔÏÏÔ 3 –∫·ıËÌÂÚÈÓ¤˜ Û˘Ó‰ڛ˜ ƒƒ + ÌÈÎÚ¤˜ ‰fiÛÂȘ IVIg (100mg/ Kg μ™) –Rituximab (375mg/m2 ∂™ x 1) (4-7 Ë̤Ú˜ ÚÈÓ ÙË ÌÂÙ·ÌfiÛ¯Â˘ÛË) –∞ÓÙÈı˘ÌÔ΢ÙÙ·ÚÈ΋ ÛÊ·ÈÚ›ÓË (1,5mg/ Kg μ™ ËÌÂÚËÛ›ˆ˜) (5-7 Ë̤Ú˜ ÚÈÓ ÙË ÌÂÙ·ÌfiÛ¯Â˘ÛË) –™˘¯Ófi˜ ¤ÏÂÁ¯Ô˜ ÙˆÓ DSA ÌÂÙ¿ ÙË ÌÂÙ·ÌfiÛ¯Â˘ÛË (ÂÊ·ÚÌÔÁ‹ Û¯‹Ì·ÙÔ˜ ƒƒ/IVIg, ÂÊfiÛÔÓ ÎÚÈÓfiÙ·Ó ·Ó·Áη›Ô, Û ÌÈ· ÚÔÛ¿ıÂÈ· ‰È·Ù‹ÚËÛ˘ ÙˆÓ ·ÓÙÈÛˆÌ¿ÙˆÓ Û ¯·ÌËÏfi Ù›ÙÏÔ). Δ· ·ÔÙÂϤÛÌ·Ù· ¤‰ÂÈÍ·Ó Û·Ê‹ ˘ÂÚÔ¯‹ ÙˆÓ ıÂڷ¢ÙÈÎÒÓ Û¯ËÌ¿ÙˆÓ ·Â˘·ÈÛıËÙÔÔ›ËÛ˘ Ô˘ ÂÚÈÏ·Ì‚¿ÓÔ˘Ó ÙË ‰ÈÂÓ¤ÚÁÂÈ· Û˘Ó‰ÚÈÒÓ ƒƒ, ÙfiÛÔ ˆ˜ ÚÔ˜ ÙËÓ Èı·ÓfiÙËÙ· ·ÚÓËÙÈÎÔÔ›ËÛ˘ ÙÔ˘ crossmatch (38%, 84% Î·È 88% ÛÙ· ÚˆÙfi-
METAMO™XEY™Eπ™ 2008
ÎÔÏÏ· 1,2 Î·È 3 ·ÓÙ›ÛÙÔȯ·) fiÛÔ Î·È ÚÔ˜ ÙË Û˘¯ÓfiÙËÙ· ÂÌÊ¿ÓÈÛ˘ ÂÂÈÛÔ‰›ˆÓ ·fiÚÚȄ˘ ¯˘ÌÈÎÔ‡ Ù‡Ô˘ ÌÂÙ¿ ÙË ÌÂÙ·ÌfiÛ¯Â˘ÛË (80%, 37% Î·È 29% ÛÙ· ÚˆÙfiÎÔÏÏ· 1,2 Î·È 3 ·ÓÙ›ÛÙÔȯ·).
Rituximab (ÌÔÓÔÎψÓÈÎfi ·ÓÙÈ-CD20 ·Óٛۈ̷) ΔÔ rituximab Â›Ó·È ¯ÈÌÂÚÈÎfi ÌÔÓÔÎψÓÈÎfi ·Óٛۈ̷ ¤Ó·ÓÙÈ ÙÔ˘ ·ÓÙÈÁfiÓÔ˘ ÂÈÊ¿ÓÂÈ·˜ CD20 ÙˆÓ Ê˘ÛÈÔÏÔÁÈÎÒÓ Î·È ÓÂÔÏ·ÛÌ·ÙÈÎÒÓ μ-ÏÂÌÊÔ΢ÙÙ¿ÚˆÓ. ∞ӷʤÚıËΠ‹‰Ë Ë ¯ÔÚ‹ÁËÛË rituximab Û 2 ·fi Ù· ÚˆÙfiÎÔÏÏ· ·Â˘·ÈÛıËÙÔÔ›ËÛ˘ Ô˘ ÂÊ·ÚÌfi˙ÔÓÙ·È ·fi ÙËÓ ÔÌ¿‰· Ù˘ Mayo Clinic9. ™ÙË ÌÂϤÙË ÙˆÓ Gloor Î·È Û˘Ó.10, 14 ·ÛıÂÓ›˜ Ì ıÂÙÈÎfi crossmatch Ì ÙÔ˘˜ ˘Ô„‹ÊÈÔ˘˜ ˙ˆÓÙ·ÓÔ‡˜ ‰fiÙ˜ ÙÔ˘˜ ˘Ô‚Ï‹ıËÎ·Ó Û 6 Û˘ÓÔÏÈο Û˘Ó‰ڛ˜ ƒƒ (ÙȘ Ë̤Ú˜ 4, 3 Î·È 1 ÚÈÓ ÙË ÌÂÙ·ÌfiÛ¯Â˘ÛË, ÙËÓ Ë̤ڷ Ù˘ ÌÂÙ·ÌfiÛ¯Â˘Û˘ Î·È ÙȘ Ë̤Ú˜ 1 Î·È 3 ÌÂÙ¿ ÙË ÌÂÙ·ÌfiÛ¯Â˘ÛË). ΔÔ ÚˆÙfiÎÔÏÏÔ ·Â˘·ÈÛıËÙÔÔ›ËÛ˘ Û˘ÌÏËÚˆÓfiÙ·Ó Ì ÙË ¯ÔÚ‹ÁËÛË IVIg, Û ‰fiÛË 100mg/ Kg μ™, ÌÂÙ¿ ·fi οıÂ Û˘Ó‰ڛ· ƒƒ, Î·È rituximab, Û ‰fiÛË 375mg/m2 ∂™, ÙËÓ Ë̤ڷ 4 ÌÂÙ¿ ÙË ÌÂÙ·ÌfiÛ¯Â˘ÛË. ∫·Ù¿ ÙË ‰È¿ÚÎÂÈ· Ù˘ ¤̂·Û˘, ÁÈÓfiÙ·Ó Ù·˘Ùfi¯ÚÔÓ· Î·È ÛÏËÓÂÎÙÔÌ‹. ø˜ ıÂڷ›· ·ÁˆÁ‹˜ ¯ÚËÛÈÌÔÔÈ‹ıËÎÂ Ë ÔÏ˘ÎψÓÈ΋ ·ÓÙÈı˘ÌÔ΢ÙÙ·ÚÈ΋ ÛÊ·ÈÚ›ÓË, ÂÓÒ Ë ıÂڷ›· Û˘ÓÙ‹ÚËÛ˘ ÂÚÈÂÏ¿Ì‚·Ó MMF, ÎÔÚÙÈÎÔÛÙÂÚÔÂȉ‹ Î·È tacrolimus. ŸÏÔÈ ÔÈ ·ÛıÂÓ›˜ ›¯·Ó ·ÚÓËÙÈÎfi crossmatch ÙËÓ Ë̤ڷ Ù˘ ÌÂÙ·ÌfiÛ¯Â˘Û˘. ªÂÙ¿ ·fi ̤ÛË ‰È¿ÚÎÂÈ· ·Ú·ÎÔÏÔ‡ıËÛ˘ 448±172 ËÌÂÚÒÓ, Ë ÂÈ‚›ˆÛË ÙˆÓ ·ÛıÂÓÒÓ Î·È ÙˆÓ ÌÔÛ¯Â˘Ì¿ÙˆÓ ¤Êı·Ó ÙÔ 87% Î·È 79% ·ÓÙ›ÛÙÔȯ· Î·È Ë Ì¤ÛË ÙÈÌ‹ Ù˘ ÎÚ·ÙÈÓ›Ó˘ ÔÚÔ‡ ‹Ù·Ó 1,4mg/dl. ™ÙÔ 86% ÙˆÓ ·ÛıÂÓÒÓ, ÙÔ crossmatch ·Ú¤ÌÂÈÓ ·ÚÓËÙÈÎfi Û fiÏË ÙË ‰È¿ÚÎÂÈ· Ù˘ ÂÚÈfi‰Ô˘ ·Ú·ÎÔÏÔ‡ıËÛ˘. ¢ÂÓ ·Ú·ÙËÚ‹ıËÎ·Ó ÂÂÈÛfi‰È· ˘ÂÚÔÍ›·˜ ·fiÚÚȄ˘, ÂÓÒ Ô Î›Ó‰˘ÓÔ˜ ÂÌÊ¿ÓÈÛ˘ ÔÍ›·˜ ·fiÚÚȄ˘ ¯˘ÌÈÎÔ‡ Ù‡Ô˘ Ê¿ÓËΠӷ Û˘Û¯ÂÙ›˙ÂÙ·È Ì ÙÔ ‡„Ô˜ ÙÔ˘ Ù›ÙÏÔ˘ ÙˆÓ ·ÓÙÈ-HLA ·ÓÙÈÛˆÌ¿ÙˆÓ ÚÈÓ ÙË ÌÂÙ·ÌfiÛ¯Â˘ÛË. ŒÓ· ¤ÙÔ˜ ·ÚÁfiÙÂÚ·, ÔÈ ›‰ÈÔÈ ÂÚ¢ÓËÙ¤˜ ·Ó·ÎÔ›ÓˆÛ·Ó ·ÚfiÌÔÈ· ·ÔÙÂϤÛÌ·Ù· Ì ÙÔ ›‰ÈÔ ÚˆÙfiÎÔÏÏÔ ·Â˘·ÈÛıËÙÔÔ›ËÛ˘, ¯ˆÚ›˜ fï˜ ÙË ‰ÈÂÓ¤ÚÁÂÈ· ÛÏËÓÂÎÙÔÌ‹˜ ηٿ ÙË ‰È¿ÚÎÂÈ· Ù˘ ÌÂÙ·ÌfiÛ¯Â˘Û˘11.
∞ÓÔÛÔÚÔÛÚfiÊËÛË (π∞) ΔÔ 1995, ÔÈ Reisaeter Î·È Û˘Ó.12 ‰ËÌÔÛ›Â˘Û·Ó Ù· ·ÔÙÂϤÛÌ·Ù· ÂÊ·ÚÌÔÁ‹˜ ÚˆÙÔÎfiÏÏÔ˘ ·Â˘·ÈÛıËÙÔÔ›ËÛ˘ Û ÌÈ· ÛÂÈÚ¿ 100 ˘Ô„‹ÊÈˆÓ ÏË-
33
ÙÒÓ ÓÂÊÚÈÎÔ‡ ÌÔۯ‡̷ÙÔ˜. ∞fi ÙÔ˘˜ ·ÛıÂÓ›˜ Ù˘ ÌÂϤÙ˘, 90 ˘Ô‚Ï‹ıËÎ·Ó ÚÔÂÁ¯ÂÈÚËÙÈο ÛÂ Û˘Ó‰ڛ˜ ƒƒ Î·È 10 ÛÂ Û˘Ó‰ڛ˜ π∞, ÛÂ Û˘Ó‰˘·ÛÌfi Ì ·ÓÔÛÔηٷÛÙÔÏ‹ Ì Ú‰ÓÈ˙ÔÏfiÓË Î·È Î˘ÎÏÔʈÛÊ·Ì›‰Ë. ΔÔ PRA Î·È Ô Ù›ÙÏÔ˜ ÙˆÓ HLA-·ÓÙÈÛˆÌ¿ÙˆÓ ÂÏ·ÙÙÒıËÎ·Ó ÌÂÙ¿ ÙÔ ¤Ú·˜ ÙˆÓ Û˘Ó‰ÚÈÒÓ ƒƒ ÛÙÔ 50% ÂÚ›Ô˘ ÙˆÓ ·ÛıÂÓÒÓ, ÂÓÒ ÌÂÙ¿ ÙÔ ¤Ú·˜ ÙˆÓ Û˘Ó‰ÚÈÒÓ π∞, ÙÔ PRA ÌÂÈÒıËΠ۠6 ·fi ÙÔ˘˜ 10 ·ÛıÂÓ›˜. ∞fi ÙÔ˘˜ 83 ·ÛıÂÓ›˜ Ô˘ ˘Ô‚Ï‹ıËÎ·Ó Û ÌÂÙ·ÌfiÛ¯Â˘ÛË ÓÂÊÚÔ‡, ÔÈ 17 ¤Ï·‚·Ó ÌfiÛ¯Â˘Ì· ·fi ˙ˆÓÙ·Ófi ‰fiÙË. ™ÙÔ ÚfiÁÚ·ÌÌ· Û˘ÌÂÚÈÂÏ‹ÊıËÛ·Ó Î·È ·ÛıÂÓ›˜ Ì ÚfiÛÊ·Ù· ıÂÙÈÎfi Î·È ¿ÌÂÛ· ÚÔÂÁ¯ÂÈÚËÙÈο ·ÚÓËÙÈÎfi crossmatch Ì ÙÔ˘˜ ‰fiÙ˜ ÙÔ˘˜. ∫·Ó¤Ó·˜ ·fi ÙÔ˘˜ ·Ú·¿Óˆ ·ÛıÂÓ›˜ ‰ÂÓ ·ÚÔ˘Û›·Û ÂÂÈÛfi‰ÈÔ ˘ÂÚÔÍ›·˜ ·fiÚÚȄ˘, ·ÏÏ¿ Ë ÂÈ‚›ˆÛË ÙˆÓ ÌÔÛ¯Â˘Ì¿ÙˆÓ ÌÂÙ¿ ·fi 1 Î·È 4 ¤ÙË ‹Ù·Ó 77% Î·È 64% ·ÓÙ›ÛÙÔȯ·, ÔÛÔÛÙ¿ Û·ÊÒ˜ ˘Ô‰Â¤ÛÙÂÚ· ·fi ÂΛӷ ÙˆÓ ÌË ˘ÂÚ¢·ÈÛıËÙÔÔÈËÌ¤ÓˆÓ ·ÛıÂÓÒÓ. ™ÙËÓ ÈÔ ÚfiÛÊ·ÙË ‚È‚ÏÈÔÁÚ·Ê›·, Ë ÂÊ·ÚÌÔÁ‹ Ù˘ ·ÓÔÛÔÚÔÛÚfiÊËÛ˘ Ì ∞ ÛÙ·Ê˘ÏÔÎÔÎÎÈ΋ ÚˆÙ½ÓË Ê·›ÓÂÙ·È Ó· ÂÚÈÔÚ›˙ÂÙ·È Û ÌÂÙ·ÌÔۯ‡ÛÂȘ ·fi ˙ˆÓÙ·Ófi ‰fiÙË Ì ∞μO ·Û˘Ì‚·ÙfiÙËÙ·13 Î·È Û و̷ÙÈΤ˜ ÌÂÙ·ÌÔۯ‡ÛÂȘ14. ∂Í¿ÏÏÔ˘, ÔÈ Goodyear Î·È Silverman15,16 ‰È·Ù‡ˆÛ·Ó ÙË ıˆڛ· fiÙÈ Ë ÚˆÙ½ÓË ∞ ·ÂÏ¢ıÂÚÒÓÂÙ·È Î·Ù¿ ÙË ‰È¿ÚÎÂÈ· Ù˘ Û˘Ó‰ڛ·˜ π∞ ÛÙÔ ·›Ì· ÙÔ˘ ·ÛıÂÓÔ‡˜ Î·È ¤¯ÂÈ Â˘ÂÚÁÂÙÈ΋ ‰Ú¿ÛË, ηıÒ˜ ÚÔηÏ› ÂÏ¿ÙÙˆÛË ÙˆÓ μ-ÏÂÌÊÔ΢ÙÙ¿ÚˆÓ. OÈ ›‰ÈÔÈ ÂÚ¢ÓËÙ¤˜ ÚÔÙ›ÓÔ˘Ó, Ì¿ÏÈÛÙ·, ÙËÓ ÂÓ‰ÔÊϤ‚È· ¯ÔÚ‹ÁËÛ‹ Ù˘ ˆ˜ ̤ıÔ‰Ô ·Â˘·ÈÛıËÙÔÔ›ËÛ˘15. ™‡Ìʈӷ Ì ٷ ·Ú·¿Óˆ ÛÙÔȯ›·, ˘¿Ú¯ÂÈ ‰˘Ó·ÙfiÙËÙ· ÂÈÙ˘¯Ô‡˜ ÌÂÙ·ÌfiÛ¯Â˘Û˘ ÓÂÊÚÔ‡ Û ÌÂÁ¿ÏÔ ·ÚÈıÌfi ˘ÂÚ¢·ÈÛıËÙÔÔÈËÌ¤ÓˆÓ ·ÛıÂÓÒÓ ·ÏÏ¿ ··ÈÙÂ›Ù·È Ì·ÎÚfi¯ÚÔÓË ·Ú·ÎÔÏÔ‡ıËÛ‹ ÙÔ˘˜, ÚÔÎÂÈ̤ÓÔ˘ Ó· ÂȂ‚·ÈˆıÔ‡Ó Ë ·ÔÙÂÏÂÛÌ·ÙÈÎfiÙËÙ· Î·È Ë ·ÛÊ¿ÏÂÈ· ÙˆÓ ıÂڷ¢ÙÈÎÒÓ Û¯ËÌ¿ÙˆÓ. ¶·Ú¿ ÙȘ Û‡Á¯ÚÔÓ˜ ÚÔfi‰Ô˘˜, Ë ·Â˘·ÈÛıËÙÔÔ›ËÛË ÙˆÓ ·ÛıÂÓÒÓ ı· Ú¤ÂÈ Ó· ıˆÚÂ›Ù·È ·ÎfiÌË ˆ˜ ÛÙÚ·ÙËÁÈ΋ ˘„ËÏÔ‡ ÎÈÓ‰‡ÓÔ˘ ÛÙË ÓÂÊÚÈ΋ ÌÂÙ·ÌfiÛ¯Â˘ÛË. °È’ ·˘ÙfiÓ ÙÔ ÏfiÁÔ, ··ÈÙÂ›Ù·È Ë ÏÂÙÔÌÂÚ‹˜ ÂÓË̤ڈÛË ÙˆÓ ·ÛıÂÓÒÓ ÁÈ· ÙËÓ Èı·ÓfiÙËÙ· ÂÌÊ¿ÓÈÛ˘ ÂÂÈÛÔ‰›ˆÓ ÔÍ›·˜ ·fiÚÚȄ˘ ηıÒ˜ Î·È ÁÈ· ÙȘ ‰˘ÓËÙÈΤ˜ ÂÈÏÔΤ˜ ·fi ÙË ¯ÔÚËÁÔ‡ÌÂÓË ·ÓÔÛÔηٷÛÙÔÏ‹, ȉȷ›ÙÂÚ· fiÙ·Ó ÚfiÎÂÈÙ·È Ó· Ï¿‚Ô˘Ó ÌfiÛ¯Â˘Ì· ·fi ˙ˆÓÙ·Ófi ‰fiÙË.
34
¢. ¶∞¶∞¢O¶OÀ§OÀ
μÈ‚ÏÈÔÁÚ·Ê›· 1. Glotz D, Haymann JP, Sansonetti N, et al. Suppression of HLA-specific alloantibodies by high-dose intravenous immunoglobulins (IVIg). A potential tool for transplantation of immunized patients. Transplantation 1993; 56:335. 2. Tyan DB, Li VA, Czer L, et al. Intravenous immunoglobulin suppresion of HLA alloantibody in highly sensitized transplant candidates and transplantation with a histoincompatible organ. Transplantation 1994; 57:553. 3. Glotz D, Antoine C, Julia P, et al. Desensitization and subsequent kidney transplantation of patients using intravenous immunoglobulins (IVIg).Am J Transplant 2002; 2:758. 4. Jordan SC, Vo A , Bunnapradist S, et al. Intravenous immunoglobulin treatment inhibits crossmatch positivity and allows for successful transplantation of incompatible organs in living-donor and cadaver recipients. Transplantation 2003; 76:331. 5. Jordan S, Cunningham-Rundles C, McEwan R. Utility of intravenous immune globulin in kidney transplantation: efficacy, safety, and cost implications. Am J Transplant 2003; 3:653. 6. Montgomery RA, Zachary AA, Racusen LC, et al. Plasmapheresis and intravenous immune globulin provides effective rescue therapy for refractory humoral rejection and allows kidneys to be successfully transplanted into cross-match-positive recipients. Transplantation 2000; 70:887. 7. Zachary AA, Montgomery RA, Ratner LE, et al. Specific and durable elimination of antibody to donor HLA antigens in renal-transplant patients. Transplantation 2003; 76:1519.
8. Schweitzer EJ, Wilson JS, Fernandez-Vina M, et al. A high panel-reactive antibody rescue protocol for crossmatch-positive live donor kidney transplants. Transplantation 2000; 70:1531. 9. Stegall MD, Gloor J,Winters JL, et al. A comparison of plasmapheresis versus high-dose IVIg desensitization in renal allograft recipients with high levels of donor specific alloantibody. Am J Tranplant 2006; 6:346. 10. Gloor JM, DeGoey SR, Pineda AA, et al. Overcoming a positive crossmatch in living-donor kidney transplantation. Am J Transplant 2003; 3:1017. 11. Gloor JM, DeGoey SR, Griffin MD, et al. Living donor kidney transplantation with and without splenectomy in positive crossmatch patients. American Transplant Congress, Boston, 2004 (abstract 364). 12. Reisaeter AV, Leivestad T, Albrechtsen D, et al. Pretranplant plasma exchange or immunoadsorption facilitates renal transplantation in immunized patients. Transplantation 1995; 60(3):242. 13. Squifflet JP, De Meyer M, Malaise J, et al. Lessons learned from ABO-incompatible living donor kidney transplantation: 20 years later. Exp Clin Transplant 2004; 2:208. 14. Lorenz M, Regele H, Schillinger M, et al. Peritransplant immunoadsorption: A strategy enabling transplantation in highly sensitized crossmatch-positive cadaveric kidney allograft recipients. Transplantation 2005; 79:696. 15. Goodyear CS, Silverman GJ. B cell superantigens: A microbe’s answer to innate-like B cells and natural antibodies. Springer Semin Immunopathol 2005; 26:463. 16. Goodyear CS, Silverman GJ. Staphylococcal toxin induced preferential and prolonged in vivo deletion of innate-like B lymphocytes. Proc Natl Acad Sci 2004; 101:11392.
A¢·ÈÛıËÙÔÔ›ËÛË ÓÂÊÚÔ·ıÔ‡˜ Û ηٿÏÔÁÔ ·Ó·ÌÔÓ‹˜ ÁÈ· و̷ÙÈ΋ ÌÂÙ·ÌfiÛ¯Â˘ÛË ∫. ºÔ˘ÚÙÔ‡Ó·˜
∂π™∞°ø°∏
Û· ÌÂÙ·ÌfiÛ¯Â˘ÛË, ·ÊÔ‡ Ù· ÌÔۯ‡̷ٷ Ôχ Û¿ÓÈ· ‰ÂÓ ·ÚÔ˘ÛÈ¿˙Ô˘Ó HLA ‰È·ÊÔÚ¤˜ (mismatches)7,8. ∏ Èı·ÓfiÙËÙ· ¢·ÈÛıËÙÔÔ›ËÛ˘ ·fi ¤Ó· ÌË ÏÂÈÙÔ˘ÚÁÈÎfi ÌfiÛ¯Â˘Ì· ÂÍ·ÚÙ¿Ù·È ·fi ÙÔÓ ·ÚÈıÌfi ÙˆÓ ÌË Û˘Ì‚·ÙÒÓ HLA: 20% (0-1 mismatches) ¤ˆ˜ 46-52% (5-6 mismatches)7,8. £· Ú¤ÂÈ Ó· ÙÔÓÈÛÙ› fiÙÈ Ë Â˘·ÈÛıËÙÔÔ›ËÛË Î·ı›ÛÙ·Ù·È ÂÓÙÔÓfiÙÂÚË Î·È ·ÚÔ˘ÛÈ¿˙ÂÈ ÈÔ Ì·ÎÚfi¯ÚÔÓË ‰È¿ÚÎÂÈ· Û ÂÚÈÙÒÛÂȘ fiÔ˘ ÂÚÈÛÛfiÙÂÚÔÈ ÙÔ˘ ÂÓfi˜ ·fi ÙÔ˘˜ ·Ú·¿Óˆ ·Ú¿ÁÔÓÙ˜ ‰ÚÔ˘Ó Ù·˘ÙÔ¯ÚfiÓˆ˜8: Û ÂÚ›ÙˆÛË ÌÂÙ¿ÁÁÈÛ˘ ·›Ì·ÙÔ˜ ηٿ ÙË ‰È¿ÚÎÂÈ· ÙÔ˘ ÙÔÎÂÙÔ‡ ÙÔ ÔÛÔÛÙfi ¢·ÈÛıËÙÔÔ›ËÛ˘ ·Ó‚·›ÓÂÈ ÛÙÔ 50%, ÂÓÒ Û ÂÚ›ÙˆÛË ÌÂÙ¿ÁÁÈÛ˘ ·›Ì·ÙÔ˜ ηٿ ÙËÓ ÓÂÊÚÂÎÙÔÌ‹ ÂÓfi˜ ÌË ÏÂÈÙÔ˘ÚÁÔ‡ÓÙÔ˜ ÌÔۯ‡̷ÙÔ˜ ·Ó¤Ú¯ÂÙ·È ÛÙÔ 80%! ∏ Ê˘ÛÈ΋ ÈÛÙÔÚ›· Ù˘ ·Ú¯È΋˜ ·˘Ù‹˜ ¢·ÈÛıËÙÔÔ›ËÛ˘ Ì ÙËÓ ¿ÚÔ‰Ô ÙˆÓ ÂÙÒÓ ÌÔÚ› Ó· ÂÚÈÏ·Ì‚¿ÓÂÈ ÙËÓ: – Ï‹ÚË ÂÍ¿ÏÂÈ„Ë Î·È Ì›ˆÛË ÙÔ˘ Ù›ÙÏÔ˘ ÙÔ˘˜ (<5%) ̤ۈ Ì˯·ÓÈÛÌÔ‡ ‰ËÌÈÔ˘ÚÁ›·˜ ·ÓÙÈ-ȉÈÔÙ˘ÈÎÒÓ ·ÓÙÈۈ̿وÓ. – ¶·Ú·ÌÔÓ‹ ÙÔ˘ ·Ú¯Èο ˘„ËÏÔ‡ Ù›ÙÏÔ˘. O ÔÚÈÛÌfi˜ Ù˘ ˘ÂÚ¢·ÈÛıËÙÔÔ›ËÛ˘ ‰È·Ê¤ÚÂÈ ÌÂٷ͇ ‰È·ÊfiÚˆÓ Î¤ÓÙÚˆÓ ·ÏÏ¿ ¿ÓÙˆ˜ ˘Ô‰ËÏÒÓÂÈ ÙËÓ ‡·ÚÍË ıÂÙÈÎÔ‡ crossmatch ¤Ó·ÓÙÈ ÂÓfi˜ ÌÂÁ¿ÏÔ˘ ·ÚÈıÌÔ‡ ‰˘ÓËÙÈÎÒÓ ‰ÔÙÒÓ (Panel Reactive Antibody (PRA) status). ∏ ÔÛÔÙÈÎÔÔ›ËÛË ÙÔ˘ Á›ÓÂÙ·È Ì ÙËÓ ·Ó›¯Ó¢ÛË ÙÔ˘ ÔÛÔÛÙÔ‡ ÙˆÓ Èı·ÓÒÓ ‰ÔÙÒÓ ¤Ó·ÓÙÈ ÙˆÓ ÔÔ›ˆÓ Ô ÔÚfi˜ ÂÓfi˜ ·ÛıÂÓÔ‡˜ ·ÓÙȉڿ (ıÂÙÈÎfi Δ-cell crossmatch), ÏfiÁˆ ÚÔÛ¯ËÌ·ÙÈÛÌ¤ÓˆÓ IgG ·ÓÙÈۈ̿وÓ. ¶¿ÓÙˆ˜, οÔÈÔ˜ ˘„ËÏfi˜ Ù›ÙÏÔ˜ PRA ‰ÂÓ ·ÓÙÈηÙÔÙÚ›˙ÂÈ ··Ú·›ÙËÙ· Î·È Î¿ÔÈÔ ÌÂÁ¿ÏÔ Â‡ÚÔ˜ ·ÓÙÈÛˆÌ¿ÙˆÓ ÛÙÔÓ ÔÚfi ÙÔ˘ ˘Ô„‹ÊÈÔ˘ Ï‹ÙË, ·ÏÏ¿ ·ÔÙÂÏ› Î·È ·ÓÙ·Ó¿ÎÏ·ÛË Ù˘ ηٷÓÔÌ‹˜ ÙˆÓ HLA Ê·ÈÓÔÙ‡ˆÓ ÛÙÔ ÁÂÓÈÎfi ÏËı˘ÛÌfi. °È· ·Ú¿‰ÂÈÁÌ· ·ÊÔ‡ ÙÔ HLA A2 ·Ó¢ڛÛÎÂÙ·È ÛÙÔ 28% ÙÔ˘ ÁÂÓÈÎÔ‡ ÏËı˘ÛÌÔ‡, Ë ‡·ÚÍË Î·È ÌfiÓÔÓ ÂÓfi˜ ·ÓÙÈÛÒÌ·ÙÔ˜ ¤Ó·ÓÙÈ ·˘-
∏ ÂÈÛ·ÁˆÁ‹ ÛÙËÓ Î·ıËÌÂÚÈÓ‹ ÎÏÈÓÈ΋ Ú¿ÍË ÙˆÓ ÌÂıfi‰ˆÓ ‰È·ÛÙ·‡ÚˆÛ˘ (cross-match) ·fi ÙÔ˘˜ Patel Î·È Terasaki1 Î·È Ô ·ÔÎÏÂÈÛÌfi˜ ˘Ô„ËÊ›ˆÓ ÏËÙÒÓ ÔÈ ÔÔ›ÔÈ ·ÚÔ˘ÛÈ¿˙Ô˘Ó ıÂÙÈ΋ ‰ÔÎÈÌ·Û›· cross-match ¤¯Ô˘Ó ÌÂÈÒÛÂÈ ‰Ú·Ì·ÙÈο Ù· ÂÂÈÛfi‰È· ˘ÂÚÔÍ›·˜ ·fiÚÚȄ˘. ¶·ÚfiÏ· ·˘Ù¿, Ô Ù‡Ô˜ ÙÔ˘ crossmatch Ô˘ ÂÊ·ÚÌfi˙ÂÙ·È Î·È Ù· ÎÚÈÙ‹ÚÈ· ÁÈ· ÙËÓ ·fi‰ÂÈÍË ÂÓfi˜ ıÂÙÈÎÔ‡ ·ÔÙÂϤÛÌ·ÙÔ˜ ‰È·Ê¤ÚÔ˘Ó ÌÂٷ͇ ÙˆÓ ·ÓÔÛÔÏÔÁÈÎÒÓ ÂÚÁ·ÛÙËÚ›ˆÓ, ÂÓÒ Ë ‡·ÚÍË ·˘ÙÔ·ÓÙÈÛˆÌ¿ÙˆÓ ·ÔÙÂÏ› ÙÔ Û˘¯ÓfiÙÂÚÔ ·›ÙÈÔ „¢‰Ò˜ ıÂÙÈÎÔ‡ crossmatch. ™ÙËÓ Û˘ÓÙÚÈÙÈ΋ ÏÂÈÔ„ËÊ›· ÙˆÓ ÂÚÈÙÒÛÂˆÓ ¿ÓÙˆ˜, Ë ·Ó›¯Ó¢ÛË ÂÓfi˜ ıÂÙÈÎÔ‡ crossmatch ˘Ô‰ËÏÒÓÂÈ ÙËÓ ·ÚÔ˘Û›· ÚÔÛ¯ËÌ·ÙÈÛÌ¤ÓˆÓ IgG ·ÓÙÈÛˆÌ¿ÙˆÓ ¤Ó·ÓÙÈ HLA ·ÓÙÈÁfiÓˆÓ Ù¿Í˘ π ÙÔ˘ ‰˘ÓËÙÈÎÔ‡ ‰fiÙË Î·È ·ÔÙÂÏ› ·ÓÙ¤Ó‰ÂÈÍË ÁÈ· ÌÂÙ·ÌfiÛ¯Â˘ÛË ÙÔ˘ ÔÚÁ¿ÓÔ˘. ∏ ¢·ÈÛıËÙÔÔ›ËÛË, ‰ËÏ·‰‹ Ë ‰ËÌÈÔ˘ÚÁ›· ·ÓÙÈHLA IgG ·ÓÙÈۈ̿وÓ, ÌÔÚ› Ó· Á›ÓÂÈ Ì ÙÚÂȘ ÙÚfiÔ˘˜2-7: ·) ÌÂÙ¿ÁÁÈÛË ÚÔ˚fiÓÙˆÓ ·›Ì·ÙÔ˜ ‚) ·ËÛË (Á˘Ó·›Î˜ ·ÛıÂÓ›˜) Á) ÚÔËÁËı›۷ ÌÂÙ·ÌfiÛ¯Â˘ÛË ΔÔ ÌÂÌÔӈ̤ÓÔ ÈÛÙÔÚÈÎfi ÌÂÙ·ÁÁ›ÛÂˆÓ ·›Ì·ÙÔ˜ ÌÔÚ› Ó· Ô‰ËÁ‹ÛÂÈ Û ¢·ÈÛıËÙÔÔ›ËÛË ÂÚ›Ô˘ ÛÙÔ 10% ÙˆÓ ·ÛıÂÓÒÓ. ∏ ¢Ú›· ÂÊ·ÚÌÔÁ‹ Ù˘ ·ÓÙÈÌÂÙÒÈÛ˘ Ù˘ ·Ó·ÈÌ›·˜ Ù˘ ¯ÚfiÓÈ·˜ ÓÂÊÚÈ΋˜ ÓfiÛÔ˘ Ì ·Ó·Û˘Ó‰È·Ṳ̂ÓË ·ÓıÚÒÈÓË ÂÚ˘ıÚÔÔÈËÙ›ÓË Î·Ù¿ ÙËÓ ÙÂÏÂ˘Ù·›· ÂÈÎÔÛ·ÂÙ›· ¤¯ÂÈ ÌÂÈÒÛÂÈ (·ÏÏ¿ fi¯È ÂÍ·Ï›„ÂÈ) ÙËÓ ·Ó¿ÁÎË ÌÂÙ·ÁÁ›ÛÂˆÓ ·›Ì·ÙÔ˜ ÛÙÔ˘˜ ÓÂÊÚÔ·ı›˜ ·ÛıÂÓ›˜ Î·È ¤¯ÂÈ ÌÂÈÒÛÂÈ ÙÔ ÔÛÔÛÙfi Ù˘ ¢·ÈÛıËÙÔÔ›ËÛ˘ Ì ·˘ÙfiÓ ÙÔÓ Ì˯·ÓÈÛÌfi. ª›· Èı·Ó‹ ·ËÛË ¤¯ÂÈ ÙÔÓ Î›Ó‰˘ÓÔ Â˘·ÈÛıËÙÔÔ›ËÛ˘ Ù˘ ÌËÙ¤Ú·˜ ηٿ 5-10%8. ∏ ΢ÚÈfiÙÂÚË Î·È Ë Û˘¯ÓfiÙÂÚË ¿ÓÙˆ˜ ·ÈÙ›· ¢·ÈÛıËÙÔÔ›ËÛ˘ Û‹ÌÂÚ· Â›Ó·È Î¿ÔÈ· ÚÔËÁËı›-
35
36
∫. ºOÀƒΔOÀ¡∞™
ÙÔ‡ ÙÔ˘ HLA, ¤¯ÂÈ ˆ˜ ·ÔÙ¤ÏÂÛÌ· ÙÔÓ ·ÔÎÏÂÈÛÌfi ÙÔ˘ 28% ÙˆÓ Èı·ÓÒÓ ‰ÔÙÒÓ3. ΔÔ ·Ú·¿Óˆ ·Ú¿‰ÂÈÁÌ· ·Ó·‰ÂÈÎÓ‡ÂÈ Î·È ÙÔ Úfi‚ÏËÌ· Ù˘ ÂȉÈÎfiÙËÙ·˜ Ù˘ ¢·ÈÛıËÙÔÔ›ËÛ˘. ™‹ÌÂÚ· Ì ÙË ‚ÂÏÙ›ˆÛË ÙˆÓ Ù¯ÓÈÎÒÓ Ù·˘ÙÔÔ›ËÛ˘ ·ÓÙÈÛˆÌ¿ÙˆÓ ıˆÚÂ›Ù·È Ôχ ÈÔ ÛËÌ·ÓÙÈ΋ Ë ·Ó›¯Ó¢ÛË Î·È ÛˆÛÙ‹ Ù·˘ÙÔÔ›ËÛË ÙˆÓ ÂȉÈÎÒÓ ÚÔÛ¯ËÌ·ÙÈÛÌ¤ÓˆÓ ·ÓÙÈÛˆÌ¿ÙˆÓ ÙÔ˘ ˘Ô„‹ÊÈÔ˘ Ï‹ÙË, ·Ú¿ Ô ·ÚÈıÌfi˜ Ô˘ ÂÎÊÚ¿˙ÂÈ ÙÔÓ Ù›ÙÏÔ ÙÔ˘ PRA. ∫¿ÔÈ· ΤÓÙÚ· ÔÚ›˙Ô˘Ó ˆ˜ ˘ÂÚ¢·ÈÛıËÙÔÔÈË̤ÓÔ ¤Ó·Ó ·ÛıÂÓ‹ fiÙ·Ó ÂÌÊ·Ó›˙ÂÈ Ù›ÙÏÔ PRA> 50%, ÂÓÒ ¿ÏÏ· ¯ÚËÛÈÌÔÔÈÔ‡Ó ˘„ËÏfiÙÂÚÔ˘˜ ·ÚÈıÌÔ‡˜ (∂urotranspant Registry> 85%)7. ™ÙË ¯ÒÚ· Ì·˜ ˆ˜ ˘ÂÚ¢·ÈÛıËÙÔÔÈË̤ÓÔ˜ ¯·Ú·ÎÙËÚ›˙ÂÙ·È Î¿ı ·ÛıÂÓ‹˜ Ô ÔÔ›Ô˜ ÂÌÊ·Ó›˙ÂÈ Ù›ÙÏÔ ·ÓÙÈÛˆÌ¿ÙˆÓ > 70% ¤Ó·ÓÙÈ ÙÔ˘ panel.
∂¶π¢∏ªπO§O°π∫∞ ¢∂¢Oª∂¡∞ ∫·Ù¿ ÙË ‰ÂηÂÙ›· 1994-2003 Ô ·ÚÈıÌfi˜ ÙˆÓ Â˘·ÈÛıËÙÔÔÈËÌ¤ÓˆÓ ·ÛıÂÓÒÓ Ô˘ ¢ڛÛÎÔÓÙ·Ó Û ϛÛÙ· ·Ó·ÌÔÓ‹˜ ÁÈ· و̷ÙÈ΋ ÌÂÙ·ÌfiÛ¯Â˘ÛË ÛÙȘ ∏¶∞ ·Ó‹Ïı ·fi ÙÔ˘˜ 12800 ÛÙÔ˘˜ 17814 ·ÛıÂÓ›˜. ΔÔ ¤ÙÔ˜ 2003 ÙÔ 32% ÙÔ˘ Û˘ÓfiÏÔ˘ ÙˆÓ ·ÛıÂÓÒÓ ·ÚÔ˘Û›·˙·Ó οÔÈÔ˘ ‚·ıÌÔ‡ HLA ¢·ÈÛıËÙÔÔ›ËÛË Î·È 13,7% ·fi ·˘ÙÔ‡˜ ›¯·Ó Ù›ÙÏÔ PRA>80%2. ΔÔ ›‰ÈÔ ¤ÙÔ˜ ÌfiÓÔÓ 6,3% ÙÔ˘ Û˘ÓfiÏÔ˘ ÙˆÓ ÓÂÊÚÈÎÒÓ ÌÂÙ·ÌÔۯ‡ÛÂˆÓ ÛÙȘ ∏¶∞ ·ÊÔÚÔ‡Û ˘ÂÚ¢·ÈÛıËÙÔÔÈË̤ÓÔ˘˜ ·ÛıÂÓ›˜, ·ÚfiÏÔ Ô˘ ·ÔÙÂÏÔ‡Û·Ó ÂÚ›Ô˘ ÙÔ 14% ÙˆÓ ˘Ô„ËÊ›ˆÓ ÏËÙÒÓ. Δ· ÛÙÔȯ›· ·˘Ù¿ ‰Â›¯ÓÔ˘Ó fiÙÈ Ë ÔÌ¿‰· ·˘Ù‹ ÙˆÓ ·ÛıÂÓÒÓ Â›Ó·È Î·Ù·‰ÈηṲ̂ÓË Û ̷ÎÚfi¯ÚÔÓË ·Ó·ÌÔÓ‹, ·Ú·Ì¤ÓÔÓÙ·˜ Û ıÂڷ›˜ ˘ÔηٿÛÙ·Û˘ Ù˘ ÓÂÊÚÈ΋˜ ÏÂÈÙÔ˘ÚÁ›·˜ Ì ·ÈÌÔοı·ÚÛË ‹ ÂÚÈÙÔÓ·˚΋ οı·ÚÛË. O ¯ÚfiÓÔ˜ ·Ú·ÌÔÓ‹˜ ÛÙȘ ıÂڷ›˜ ·˘Ù¤˜ ¤¯ÂÈ ·Ô‰Âȯı› fiÙÈ ·ÔÙÂÏ› ·ÓÂÍ¿ÚÙËÙÔ ·Ú¿ÁÔÓÙ· ÁÈ· ÌÂȈ̤ÓË ÂÈ‚›ˆÛË ·ÛıÂÓÒÓ Î·È ÌÔÛ¯Â˘Ì¿ÙˆÓ ÌÂÙ¿ ·fi ÙË ÓÂÊÚÈ΋ ÌÂÙ·ÌfiÛ¯Â˘ÛË. ∂›Û˘ Ë ÔÈfiÙËÙ· ˙ˆ‹˜ ÙˆÓ ·ÛıÂÓÒÓ ·˘ÙÒÓ Â›Ó·È Û›ÁÔ˘Ú· ηÙÒÙÂÚË Î·È Û¯ÂÙ›˙ÂÙ·È ¿ÌÂÛ· Ì ÙËÓ „˘¯ÔÏÔÁÈ΋ ‰ÔÎÈÌ·Û›· Ù˘ Ì·ÎÚfi¯ÚÔÓ˘ ·Ó·ÌÔÓ‹˜7-10. ™‡Ìʈӷ Ì ÚfiÛÊ·Ù· ÛÙÔȯ›· ÙÔ˘ ∂ıÓÈÎÔ‡ OÚÁ·ÓÈÛÌÔ‡ ªÂÙ·ÌÔۯ‡ÛÂˆÓ (OÎÙÒ‚ÚÈÔ˜ 2007) ·fi ÙÔ˘˜ 819 ·ÛıÂÓ›˜ Ô˘ Â›Ó·È ÂÓÂÚÁÔÔÈË̤ÓÔÈ ÛÙË Ï›ÛÙ· ÁÈ· و̷ÙÈ΋ ÓÂÊÚÈ΋ ÌÂÙ·ÌfiÛ¯Â˘ÛË, 79 ·ÛıÂÓ›˜ (9%) ·ÚÔ˘ÛÈ¿˙Ô˘Ó Ù›ÙÏÔ PRA>70% Î·È ıˆÚÔ‡ÓÙ·È ˘ÂÚ¢·ÈÛıËÙÔÔÈË̤ÓÔÈ. ΔÔ ÔÛÔÛÙfi ·˘Ùfi Â›Ó·È ÌÈÎÚfiÙÂÚÔ ·fi ¿ÏϘ ¯ÒÚ˜, ·Ï-
Ï¿ ÌÔÚ› Ó· ÂÍËÁËı› ‡ÎÔÏ· ÏfiÁˆ ÙÔ˘ ÌÈÎÚÔ‡ ·ÚÈıÌÔ‡ ÌÂÙ·ÌÔۯ‡ÛÂˆÓ ÛÙË ¯ÒÚ· Ì·˜ ηٿ Ù· ÚÔËÁÔ‡ÌÂÓ· ¤ÙË.
¶ƒO™∂°°π™∏ ΔOÀ ¶ƒOμ§∏ª∞ΔO™ ∏ ÚÔÛ¤ÁÁÈÛË ÙÔ˘ ÚÔ‚Ï‹Ì·ÙÔ˜ ÙˆÓ ˘ÂÚ¢·ÈÛıËÙÔÔÈËÌ¤ÓˆÓ ·ÛıÂÓÒÓ Á›ÓÂÙ·È ‰˘ÛÎÔÏfiÙÂÚË ·fi ÙÔ ÁÂÁÔÓfi˜, fiÙÈ ÔÈ ·ÛıÂÓ›˜ ·˘ÙÔ› ·ÚÔ˘ÛÈ¿˙Ô˘Ó ·˘ÍË̤ÓÔ ·ÓÔÛÔÏÔÁÈÎfi ΛӉ˘ÓÔ ÁÈ· ÂÌÊ¿ÓÈÛË ÔÍ›·˜ ·fiÚÚȄ˘ ̤ۈ ·ÓÙÈÛˆÌ¿ÙˆÓ Î·È Û·ÊÒ˜ ÂÏ·Ùو̤ÓË Ì·ÎÚfi¯ÚÔÓË ÂÈ‚›ˆÛË ÙˆÓ ÌÔÛ¯Â˘Ì¿ÙˆÓ. OÈ ‰‡Ô ÙÚfiÔÈ ÚÔÛ¤ÁÁÈÛ˘ ̤¯ÚÈ Û‹ÌÂÚ· ›ӷÈ: ·) Ë «‚ÈÔÏÔÁÈ΋» ÚÔÛ¤ÁÁÈÛË, fiÔ˘ Á›ÓÂÙ·È ÚÔÛ¿ıÂÈ· ·Ó‡ÚÂÛ˘ ηٿÏÏËÏˆÓ ‰ÔÙÒÓ Ì ÙÔ˘˜ ÔÔ›Ô˘˜ ÔÈ ·ÛıÂÓ›˜ ·˘ÙÔ› ‰ÂÓ ·ÚÔ˘ÛÈ¿˙Ô˘Ó ıÂÙÈΤ˜ ‰ÔÎÈ̷ۛ˜ crossmatch, ̤۷ ·fi ÌÂÁ¿Ï˜ ‰ÂÍ·ÌÂÓ¤˜ ‰ÔÙÒÓ Î·È ·˘ÍË̤ÓË ÚÔÙÂÚ·ÈfiÙËÙ· ÁÈ· ÙÔ˘˜ ·ÛıÂÓ›˜ ·˘ÙÔ‡˜ Ì ÔÈΛϷ ÚÔÁÚ¿ÌÌ·Ù· ÚÈÌÔ‰fiÙËÛ˘. ‚) Ë «Ê·ÚÌ·ÎÔÏÔÁÈ΋» ÚÔÛ¤ÁÁÈÛË, fiÔ˘ Á›ÓÂÙ·È ÚÔÛ¿ıÂÈ· ·ÔÌ¿ÎÚ˘ÓÛ˘ / ·‰Ú·ÓÔÔ›ËÛ˘ ÙˆÓ ÚÔÛ¯ËÌ·ÙÈÛÌ¤ÓˆÓ anti-HLA ·ÓÙÈÛˆÌ¿ÙˆÓ Ì ‰È¿ÊÔÚ˜ Ù¯ÓÈΤ˜.
«μπO§O°π∫∏» ¶ƒO™∂°°π™∏ Eurotransplant Acceptable Mismatching Program ΔÔ Acceptable Mismatching Program (AMP) Ù˘ Eurotransplant Â›Ó·È ¤Ó· ÔÏ˘ÎÂÓÙÚÈÎfi Î·È ÔÏ˘ÂıÓÈÎfi ÚfiÁÚ·ÌÌ· Ì ÛÎÔfi ÙˆÓ Î·ıÔÚÈÛÌfi ·ÓÙÈÁfiÓˆÓ HLA ÛÙ· ÔÔ›· Ô ˘ÂÚ¢·ÈÛıËÙÔÔÈË̤ÓÔ˜ ·ÛıÂÓ‹˜ ‰ÂÓ ¤¯ÂÈ ÚÔÛ¯ËÌ·ÙÈṲ̂ӷ ·ÓÙÈÛÒÌ·Ù· Î·È Û˘ÓÂÒ˜ Ó· ÚԂϤ„ÂÈ Èı·Ó¿ ÌÂÏÏÔÓÙÈο ·ÚÓËÙÈο crossmatch Ì ÂȉÈο HLA mismatches7. ΔÔ ÚfiÁÚ·ÌÌ· ¤¯ÂÈ ÂÚ·ÈÙ¤Úˆ ‚ÂÏÙȈı› ̤ۈ ÂÓfi˜ ·ÏÁÔÚ›ıÌÔ˘ ‚·ÛÈṲ̂ÓÔ˘ Û ËÏÂÎÙÚÔÓÈÎÔ‡˜ ˘ÔÏÔÁÈÛÙ¤˜ (HLA Match-maker) Ô˘ ÌÔÚ› Ó· ˘ÔÏÔÁ›˙ÂÈ Èı·Ó‹ Û˘Ì‚·ÙfiÙËÙ· Ì ˘ÂÚ¢·ÈÛıËÙÔÔÈË̤ÓÔ˘˜ ·ÛıÂÓ›˜. ™Â Ù¤ÙÔÈ· ÂÚ›ÙˆÛË ÙÔ ÓÂÊÚÈÎfi ÌfiÛ¯Â˘Ì· ÌÂٷʤÚÂÙ·È ÛÙÔ Î¤ÓÙÚÔ ÙÔ˘ ·ÛıÂÓÔ‡˜, fiÔ˘ Á›ÓÂÙ·È ÙÔ ÙÂÏÈÎfi crossmatch Î·È Â› ·ÚÓËÙÈÎÔ‡ ·ÔÙÂϤÛÌ·ÙÔ˜, Ô ·ÛıÂÓ‹˜ ˘Ô‚¿ÏÏÂÙ·È ÛÙË ÌÂÙ·ÌfiÛ¯Â˘ÛË. ∞fi ÙË ‰ËÌÈÔ˘ÚÁ›· ÙÔ˘ ÚÔÁÚ¿ÌÌ·ÙÔ˜, ÂÚ›Ô˘ 450 ˘ÂÚ¢·ÈÛıËÙÔÔÈË̤ÓÔÈ ·ÛıÂÓ›˜ ˆÊÂÏ‹ıËÎ·Ó Î·È ˘Ô‚Ï‹ıËÎ·Ó Û ÓÂÊÚÈ΋ ÌÂÙ·ÌfiÛ¯Â˘ÛË. ∂ÙËÛ›ˆ˜ ÂÚ›Ô˘ 45 ·ÛıÂÓ›˜ Ï·Ì‚¿ÓÔ˘Ó Û˘Ì‚·Ù¿ ÓÂÊÚÈο ÌÔۯ‡̷ٷ ·fi Ì›· ‰ÂÍ·ÌÂÓ‹ 3100 ÔÚÁ¿ÓˆÓ Ù˘
METAMO™XEY™Eπ™ 2008
Eurotransplant. O ·ÛıÂÓ‹˜ Ô˘ Ï·Ì‚¿ÓÂÈ Ì¤ÚÔ˜ ÛÙÔ ÚfiÁÚ·ÌÌ· ¤¯ÂÈ Èı·ÓfiÙËÙ· 43% Ó· Ï¿‚ÂÈ Û˘Ì‚·Ùfi ÌfiÛ¯Â˘Ì· ηٿ ÙÔ ·′ ¤ÙÔ˜ ·Ó·ÌÔÓ‹˜ Î·È 58% ̤۷ Û 21 Ì‹Ó˜. ∂›Û˘ Â›Ó·È ÛËÌ·ÓÙÈÎfi Ó· ÙÔÓÈÛÙ› fiÙÈ Ë ‰ÈÂÙ‹˜ ÂÈ‚›ˆÛË ÙˆÓ ÌÔÛ¯Â˘Ì¿ÙˆÓ Ì¤Ûˆ ÙÔ˘ AMP Â›Ó·È 87%, ·ÎÚÈ‚Ò˜ ·Ú·Ï‹ÛÈ· Ì ÙÔ˘˜ ÌË Â˘·ÈÛıËÙÔÔÈË̤ÓÔ˘˜ ·ÛıÂÓ›˜7.
¶ÚˆÙfiÎÔÏÏÔ ªÂÁ¿Ï˘ μÚÂÙ·Ó›·˜ (UK) ∏ ÂÈÏÔÁ‹ ÙÔ˘ ηٿÏÏËÏÔ˘ Ï‹ÙË ÓÂÊÚÈÎÔ‡ ÌÔۯ‡̷ÙÔ˜ ·fi ÙËÓ ÂıÓÈ΋ Ï›ÛÙ· ·Ó·ÌÔÓ‹˜ ÁÈ· و̷ÙÈ΋ ÌÂÙ·ÌfiÛ¯Â˘ÛË ‚·Û›˙ÂÙ·È ÛÙËÓ ·Ú¯‹ Ù˘ Ôχ ηϋ˜ ÈÛÙÔÛ˘Ì‚·ÙfiÙËÙ·˜ (ÌˉÂÓÈÎfi mismatching)9. OÈ ·È‰È·ÙÚÈÎÔ› ·ÛıÂÓ›˜ Î·È ÔÈ ˘ÂÚ¢·ÈÛıËÙÔÔÈË̤ÓÔÈ ·ÛıÂÓ›˜ ¤¯Ô˘Ó ÚÔÙÂÚ·ÈfiÙËÙ· ¤Ó·ÓÙÈ ÙˆÓ ˘ÔÏÔ›ˆÓ. ∞Ó·ÊÔÚÈο Ì ÙÔ˘˜ ˘ÂÚ¢·ÈÛıËÙÔÔÈË̤ÓÔ˘˜ ·ÛıÂÓ›˜ ÙÔ Û‡ÛÙËÌ· ‚·Û›˙ÂÙ·È ÛÙËÓ ·Ó›¯Ó¢ÛË Ù˘ ÂȉÈÎfiÙËÙ·˜ ÙˆÓ anti-HLA ·ÓÙÈÛˆÌ¿ÙˆÓ Ù· ÔÔ›· ·ÚÔ˘ÛÈ¿˙ÂÈ Ô ˘ÂÚ¢·ÈÛıËÙÔÔÈË̤ÓÔ˜ ·ÛıÂÓ‹˜ ηıÒ˜ Î·È ÂȉÈÎfiÙËÙ˜ Ô˘ ıˆÚÔ‡ÓÙ·È ÌË ·Ô‰ÂÎÙ¤˜ (HLA mismatches ·fi ÚÔËÁÔ‡ÌÂÓË ÌÂÙ·ÌfiÛ¯Â˘ÛË, ÔÏϷϤ˜ ΢‹ÛÂȘ). ªÂ ÙÔ ÚˆÙfiÎÔÏÏÔ ·˘Ùfi ηٿ ÙËÓ ÙÂÏÂ˘Ù·›· ‰ÂηÂÙ›· ¤¯ÂÈ ÙÚÈÏ·ÛÈ·ÛÙ› Ô ·ÚÈıÌfi˜ ÙˆÓ ÌÂÙ·ÌÔۯ‡ÛÂˆÓ Û ˘ÂÚ¢·ÈÛıËÙÔÔÈË̤ÓÔ˘˜ ·ÛıÂÓ›˜ ÛÙË ªÂÁ¿Ï˘ μÚÂÙ·Ó›· 9. ¶·ÚfiÌÔÈÔ ÚˆÙfiÎÔÏÏÔ ·ÎÔÏÔ˘ıÂ›Ù·È Ì ÂÈÙ˘¯›· Î·È ÛÙË ¯ÒÚ· Ì·˜.
¶ÚˆÙfiÎÔÏÏÔ ¶·ÓÂÈÛÙËÌ›Ô˘ Emory (∏¶∞)«∂ÈÎÔÓÈÎfi» crossmatch ΔÔ ∞ÌÂÚÈηÓÈÎfi ¶·ÓÂÈÛÙ‹ÌÈÔ ÙÔ˘ Emory ÛÙËÓ ∞ÙÏ¿ÓÙ· ¤¯ÂÈ ·ÚÔ˘ÛÈ¿ÛÂÈ ÚfiÛÊ·Ù· ÙËÓ ÂÌÂÈÚ›· ÙÔ˘ Û¯ÂÙÈο Ì ÙËÓ ÚÔÛÊÔÚ¿ ÓÂÊÚÈÎÒÓ ÌÔÛ¯Â˘Ì¿ÙˆÓ Û ¢·ÈÛıËÙÔÔÈË̤ÓÔ˘˜ Ï‹Ù˜ (PRA>30%)10. ΔÔ ÚˆÙfiÎÔÏÏÔ ·˘Ùfi Â›Ó·È ·ÚfiÌÔÈÔ Ì ÙÔ ÚˆÙfiÎÔÏÏÔ Ù˘ Eurotransplant ·ÏÏ¿ ‚·Û›˙ÂÙ·È Û ¿ÏϘ Ù¯ÓÈΤ˜ Ù·˘ÙÔÔ›ËÛ˘ ÌË ·Ô‰ÂÎÙÒÓ ‰ÔÙÒÓ. ∏ ‚·ÛÈ΋ ÙÔ˘ ·Ú¯‹ Â›Ó·È Ë Ù·˘ÙÔÔ›ËÛË ÂȉÈÎÒÓ ·ÓÙÈ-HLA ·ÓÙÈÛˆÌ¿ÙˆÓ ÛÙÔÓ ÔÚfi ÙÔ˘ ˘Ô„‹ÊÈÔ˘ Ï‹ÙË Ì ¢·›ÛıËÙ˜ ÌÂıfi‰Ô˘˜ (flow cytometry-based solid phase assay). ŸÙ·Ó Ô ÙˆÌ·ÙÈÎfi˜ ‰fiÙ˘ ʤÚÂÈ Ù· HLA ·ÓÙÈÁfiÓ· Ù· ÔÔ›· ·ÓȯÓ‡ıËÎ·Ó ÛÙÔÓ ÔÚfi ÙÔ˘ Èı·ÓÔ‡ Ï‹ÙË ·˘Ùfi˜ ÎÚ›ÓÂÙ·È ·Î·Ù¿ÏÏËÏÔ˜ (ÂÈÎÔÓÈÎfi crossmatch), ¯ˆÚ›˜ ÙË ‰ÈÂÓ¤ÚÁÂÈ· ·ÏËıÔ‡˜ crossmatch. OÈ ∞ÌÂÚÈηÓÔ› ÂÚ¢ÓËÙ¤˜ ·Ó·Ê¤ÚÔ˘Ó fiÙÈ Ì ÙÔ ÚˆÙfiÎÔÏÏÔ ·˘Ùfi ¤¯Ô˘Ó ·˘Í‹ÛÂÈ ÛËÌ·ÓÙÈο ÙˆÓ ·ÚÈıÌfi ÙˆÓ ÌÔÛ¯Â˘Ì¿ÙˆÓ Û ۯÂÙÈο ¢·ÈÛıË-
37
ÙÔÔÈË̤ÓÔ˘˜ ·ÛıÂÓ›˜ (30% Û ·ÛıÂÓ›˜ Ì PRA>30% Î·È 15% Û ·ÛıÂÓ›˜ Ì PRA>80%.
«º∞ƒª∞∫O§O°π∫∏» ¶ƒO™∂°°π™∏ ¶ÚˆÙfiÎÔÏÏ· ¯ÔÚ‹ÁËÛ˘ ÌÂÁ¿ÏˆÓ ‰fiÛÂˆÓ ·ÓÔÛÔÛÊ·ÈÚ›Ó˘ (IVIG) ¶ÚfiÎÂÈÙ·È ÁÈ· ÙËÓ ÂÓ‰ÔÊϤ‚È· ¯ÔÚ‹ÁËÛË ÌÂÁ¿ÏˆÓ ‰fiÛÂˆÓ (Û˘Ó‹ıˆ˜ 2gr/ ∫μ™) IgG ·ÓÔÛÔÛÊ·ÈÚ›Ó˘, Ë ÔÔ›· ·Ú¿ÁÂÙ·È ·fi ÌÈ· ÌÂÁ¿ÏË ‰ÂÍ·ÌÂÓ‹ ‰ÔÙÒÓ. À¿Ú¯ÂÈ Ì›· ÌÂÁ¿ÏË ÔÈÎÈÏ›· Û΢·ÛÌ¿ÙˆÓ Î·È ÙÔ ÈÔ ÛËÌ·ÓÙÈÎfi ÂÚÒÙËÌ· ·Ú·Ì¤ÓÂÈ Ë ·ÔÙÂÏÂÛÌ·ÙÈÎfiÙËÙ· ÙÔ˘ οı Û΢¿ÛÌ·ÙÔ˜ (fi¯È ÌfiÓÔ ÌÂٷ͇ ‰È·ÊÔÚÂÙÈÎÒÓ ÂÙ·ÈÚÈÒÓ ·ÏÏ¿ Î·È Û΢·ÛÌ¿ÙˆÓ Ù˘ ·˘Ù‹˜ ÂÙ·ÈÚ›·˜) ·Ó·ÊÔÚÈο Ì ÙËÓ ·Â˘·ÈÛıËÙÔÔ›ËÛË, ·ÊÔ‡ ‰ÂÓ ˘¿Ú¯Ô˘Ó Û˘ÁÎÚÈÙÈΤ˜ ÌÂϤÙ˜. OÈ Clark Î·È Û˘Ó Û˘ÁÎÚ›ÓÔÓÙ·˜ 22 ‰È·ÊÔÚÂÙÈο Û΢¿ÛÌ·Ù· ·fi 7 ‰È·ÊÔÚÂÙÈΤ˜ ÂÙ·ÈÚ›˜ ·Ú·Ù‹ÚËÛ·Ó ÌÈ· ÙÂÚ¿ÛÙÈ· ‰È·Î‡Ì·ÓÛË ÛÙËÓ ·ÔÙÂÏÂÛÌ·ÙÈÎfiÙËÙ· ÙÔ˘˜ ÛÙÔ ÂÚÁ·ÛÙ‹ÚÈÔ, Ó· ÌÂÈÒÛÔ˘Ó ÙÔÓ Ù›ÙÏÔ ÙÔ˘ PRA Ì ΢ÙÙ·ÚÔÌÂÙÚ›· ÚÔ‹˜ fiÙ·Ó ÚÔÛÙ¤ıËÎ·Ó ÛÙÔ crossmatch11. ∞Ó·ÊÔÚÈο Ì ÙÔ Ì˯·ÓÈÛÌfi ‰Ú¿Û˘ ¤¯Ô˘Ó ÚÔÙ·ı› ÔÈΛÏÔÈ Ì˯·ÓÈÛÌÔ› ̤ۈ ÙˆÓ ÔÔ›ˆÓ Ë ·ÓÔÛÔÛÊ·ÈÚ›ÓË ·ÚÔ˘ÛÈ¿˙ÂÈ ·ÓÔÛÔÙÚÔÔÔÈËÙÈΤ˜ ȉÈfiÙËÙ˜2: ·) ÌÂÙ·‚ÔÏ‹ ÙˆÓ ÂȤ‰ˆÓ ·˘Ùfi- Î·È ¿ÏÏÔ-·ÓÙÈÛˆÌ¿ÙˆÓ Ì¤Ûˆ ·ÓÙÈ-ȉÈÔÙ˘ÈÎÒÓ ·ÓÙÈۈ̿وÓ, ‚) ·Ó·ÛÙÔÏ‹ ÂÓÂÚÁÔÔ›ËÛ˘ ÁÔÓȉ›ˆÓ ΢ÙÙ·ÚÔÎÈÓÒÓ, Á) ‰Ú·ÛÙËÚÈfiÙËÙ· ¤Ó·ÓÙÈ ÙÔ˘ ˘Ô‰Ô¯¤· ÙÔ˘ Δ-ÏÂÌÊÔ΢ÙÙ¿ÚÔ˘, ‰) ·ÏÏËÏ›‰Ú·ÛË ·ÓÙÈÁÔÓÔ-·ÚÔ˘ÛÈ·ÛÙÈÎÒÓ Î˘ÙÙ¿ÚˆÓ Î·È Fc ˘Ô‰Ô¯¤·, Â) anti-CD4 ‰Ú·ÛÙÈÎfiÙËÙ·, ÛÙ) ÂÓÂÚÁÔÔ›ËÛË ·ÓÙ·ÁˆÓÈÛÙÒÓ ˘Ô‰Ô¯¤ˆÓ ΢ÙÙ·ÚÔÎÈÓÒÓ, ˙) ·Ó·ÛÙÔÏ‹ ÙÔ˘ Û˘ÌÏËÚÒÌ·ÙÔ˜. ∏ ÙÂÏÂ˘Ù·›· ‰Ú¿ÛË ·Ó·Ê¤ÚıËΠÚfiÛÊ·Ù· Î·È ·ÊÔÚ¿ ÙË Û‡Ó‰ÂÛË ÙÔ˘ Fc ÙÌ‹Ì·ÙÔ˜ Ù˘ ·ÓÔÛÔÛÊ·ÈÚ›Ó˘ Ì ÂÓÂÚÁÔÔÈË̤ӷ ÛÙÔȯ›· ÙÔ˘ Û˘ÌÏËÚÒÌ·ÙÔ˜ (C3b, C4b), ·ÏÏ¿ Î·È ·Ó·ÛÙÔÏ‹ Ù˘ ‰ËÌÈÔ˘ÚÁ›·˜ ÙÔ˘ Û˘ÌϤÁÌ·ÙÔ˜ C5bC9 MAC12. OÈ Glotz Î·È Û˘Ó ·ÚÔ˘Û›·Û·Ó ÙËÓ ÂÌÂÈÚ›· ÙÔ˘˜ ·fi 15 ·ÛıÂÓ›˜ Ì PRA>50% ‹ ıÂÙÈÎfi crossmatch Ì ˘Ô„‹ÊÈÔ˘˜ ˙ÒÓÙ˜ ‰fiÙ˜, ÌÂÙ¿ ·fi ¯ÔÚ‹ÁËÛË 2 mg/∫μ™ IVIG οı 4 ‚‰ÔÌ¿‰Â˜ ÁÈ· ÙÚ›˜ ÊÔÚ¤˜ ÂϤÁ¯ÔÓÙ·˜ ÙÔÓ Ù›ÙÏÔ ÙÔ˘ PRA Î·È ÌÂÏÂÙÒÓÙ·˜ ÙÔ crossmatch 3 ‚‰ÔÌ¿‰Â˜ ÌÂÙ¿ ·fi ÙËÓ Î¿ı ‰fiÛË IVIG13. ¢ÂηÙÚ›˜ (13) ·ÛıÂÓ›˜ ·ÚÔ˘Û›·Û·Ó ·ÍÈÔÛËÌ›ˆÙË ÙÒÛË ÙÔ˘ Ù›ÙÏÔ˘ ÙÔ˘ PRA Î·È ÌÂÙ·ÌÔۯ‡ıËÎ·Ó (2 ·fi ˙ÒÓÙ˜ ‰fiÙ˜).
38
∫. ºOÀƒΔOÀ¡∞™
OÈ ·ÛıÂÓ›˜ ¤Ï·‚·Ó ·ÁˆÁ‹ Ì thymoglobulin Î·È ÙÚÈÏfi Û¯‹Ì· Ì tacrolimus, MMF Î·È ÛÙÂÚÔÂȉ‹. ∂›Û˘ IVIG ¯ÔÚËÁ‹ıËΠÌÂÙ¿ ÙË ÌÂÙ·ÌfiÛ¯Â˘ÛË ÛÙËÓ ›‰È· ‰ÔÛÔÏÔÁ›· (2 mg/kg) ÌÂÙ¿ ·fi 3 Î·È 6 ‚‰ÔÌ¿‰Â˜. ŒÓ· ÓÂÊÚÈÎfi ÌfiÛ¯Â˘Ì· ¯¿ıËΠÙËÓ ÚÒÙË Ë̤ڷ ·fi ıÚfiÌ‚ˆÛË (Ë IVIG ·ÚÔ˘ÛÈ¿˙ÂÈ ÚÔıÚÔÌ‚ˆÙÈ΋ ‰Ú¿ÛË), ¤Ó· ·fi ÔÍ›· ·fiÚÚÈ„Ë, ¤Ó· ·fi Ïԛ̈ÍË Ì Èfi BK Î·È ‰‡Ô ÌÔۯ‡̷ٷ ÏfiÁˆ ı·Ó¿ÙÔ˘ ÙÔ˘ Ï‹ÙË. OÈ Jordan Î·È Û˘Ó ·Ó¤ÊÂÚ·Ó 48 ˘ÂÚ¢·ÈÛıËÙÔÔÈË̤ÓÔ˘˜ ·ÛıÂÓ›˜ ÔÈ ÔÔ›ÔÈ ¤Ï·‚·Ó 1-4 ‰fiÛÂȘ IVIG14. §fiÁˆ ÔÈÎÔÓÔÌÈÎÒÓ ÂÚÈÔÚÈÛÌÒÓ ÔÈ ·ÛıÂÓ›˜ ˘Â‚Ï‹ıËÛ·Ó ÚÈÓ ÙËÓ ¯ÔÚ‹ÁËÛË πVIG Û ÂÚÁ·ÛÙËÚÈ·Îfi ¤ÏÂÁ¯Ô ÁÈ· ÂÈÏÔÁ‹ ·˘ÙÒÓ Ô˘ Èı·ÓÒ˜ Ó· ˆÊÂÏÔ‡ÓÙ·Ó ÂÚÈÛÛfiÙÂÚÔ ·fi ÙË ıÂڷ›·. ∏ ÙÒÛË ÙÔ˘ Ù›ÙÏÔ˘ ÙÔ˘ PRA ÌÂÙ¿ ·fi ÚÔÛı‹ÎË IgG ıˆڋıËΠÂÓ‰ÂÈÎÙÈ΋ ηϋ˜ ·¿ÓÙËÛ˘ ÛÙË ¯ÔÚ‹ÁËÛË IVIG. ™Â ·ÓÙ›ıÂÙË ÂÚ›ÙˆÛË Ô ·ÛıÂÓ‹˜ ·ÔÎÏ›ÔÓÙ·Ó ·fi ÙË ıÂڷ›·. ™·Ú¿ÓÙ·-‰‡Ô (42) ·ÛıÂÓ›˜ ·ÚÔ˘Û›·Û·Ó ·ÚÓËÙÈÎfi crossmatch Ì IgG Î·È ÚÔ¯ÒÚËÛ·Ó Û ÌÂÙ·ÌfiÛ¯Â˘ÛË. OÈ Û˘ÁÁÚ·Ê›˜ ·Ó·Ê¤ÚÔ˘Ó ÔÛÔÛÙfi ÔÍ›·˜ ·fiÚÚȄ˘ 31% (3 ·ÒÏÂȘ ÌÔÛ¯Â˘Ì¿ÙˆÓ) Î·È 89% ‰ÈÂÙ‹ Û˘ÓÔÏÈ΋ ÂÈ‚›ˆÛË ÙˆÓ ÌÔÛ¯Â˘Ì¿ÙˆÓ. ∏ ÌÂϤÙË πG02 Â›Ó·È Ë ÌfiÓË ‰ÈÏ‹ Ù˘ÊÏ‹ Ù˘¯·ÈÔÔÈË̤ÓË ÌÂϤÙË Ì ÔÌ¿‰· ¤ÏÂÁ¯Ô˘ (placebo) ·Ó·ÊÔÚÈο Ì ÙË ‰Ú·ÛË Ù˘ IVIG Û ˘ÂÚ¢·ÈÛıËÙÔÔÈË̤ÓÔ˘˜ ·ÛıÂÓ›˜ (PRA >50%) Ô˘ ˘Ô‚¿ÏÏÔÓÙ·Ó Û ·ÈÌÔοı·ÚÛË Î·È ¯ÚËÌ·ÙÔ‰ÔÙ‹ıËΠ·fi ÙÔ ∂ıÓÈÎfi πÓÛÙÈÙÔ‡ÙÔ ÀÁ›·˜ ÙˆÓ ∏¶∞15. ¶ÚfiÎÂÈÙ·È ÁÈ· ÔÏ˘ÎÂÓÙÚÈ΋ ÌÂϤÙË 98 ·ÛıÂÓÒÓ Ì ¯ÔÚ‹ÁËÛË 2 mg/kg IVIG/ Ì‹Ó· ÁÈ· Û˘ÓÔÏÈο 4 Ì‹Ó˜ Î·È ¯ÚÔÓÈÎfi ‰È¿ÛÙËÌ· ·Ú·ÎÔÏÔ‡ıËÛ˘ ¿Óˆ ·fi 4 ¤ÙË. ¶·Ú·ÙËÚ‹ıËΠ̤ÙÚÈ· ·ÏÏ¿ ÛÙ·ÙÈÛÙÈο ÛËÌ·ÓÙÈ΋ ÙÒÛË ÙÔ˘ Ù›ÙÏÔ˘ ÙÔ˘ PRA Û¯ÂÙÈο Ì ÙÔ ÂÈÎÔÓÈÎfi Ê¿ÚÌ·ÎÔ Î·È Ë ¤Á¯˘ÛË Ù˘ ‹Ù·Ó ηϿ ·ÓÂÎÙ‹. 35% ÙˆÓ ·ÛıÂÓÒÓ Ù˘ ÔÌ¿‰·˜ Ù˘ IVIG ¤Ó·ÓÙÈ 17% Ù˘ ÔÌ¿‰·˜ ÙÔ˘ ÂÈÎÔÓÈÎÔ‡ Ê·ÚÌ¿ÎÔ˘ ηٿÊÂÚ ӷ ˘Ô‚ÏËı› Û ÓÂÊÚÈ΋ ÌÂÙ·ÌfiÛ¯Â˘ÛË. ∂ÂÈÛfi‰È· ÔÍ›·˜ ·fiÚÚȄ˘ ·ÚÔ˘Û›·Û·Ó 9/17 ·ÛıÂÓ›˜ Ù˘ ÔÌ¿‰·˜ Ù˘ IVIG Î·È 1/10 Ù˘ ÔÌ¿‰·˜ ÙÔ˘ ÂÈÎÔÓÈÎÔ‡ Ê·ÚÌ¿ÎÔ˘. ∏ ‰ÈÂÙ‹˜ ÂÈ‚›ˆÛË ÙˆÓ ÌÔÛ¯Â˘Ì¿ÙˆÓ ‹Ù·Ó 80% Î·È 75% ·ÓÙ›ÛÙÔȯ·. ∏ ÙÒÛË ÙˆÓ ÂȤ‰ˆÓ ÙÔ˘ PRA Û ۯ¤ÛË Ì ÙË ÌÂϤÙË ÙˆÓ Glotz Î·È Û˘Ó13 ‹Ù·Ó Û·ÊÒ˜ ÌÈÎÚfiÙÂÚË Î·È ·Ô‰fiıËΠÛÙ· ¯·Ú·ÎÙËÚÈÛÙÈο ÙˆÓ ·ÛıÂÓÒÓ (20% ·ÊÚÔ·ÌÂÚÈηÓÔ›) Î·È ÙÔ Û··ÛÌ· Ô˘ ¯ÚËÛÈÌÔÔÈ‹ıËÎÂ15.
∏ ıÂڷ›· ·Â˘·ÈÛıËÙÔÔ›ËÛ˘ Ì IVIG ıˆÚÂ›Ù·È ÂÍ·ÈÚÂÙÈο ‰··ÓËÚ‹. ™‡Ìʈӷ Ì ÌÈ· ÔÈÎÔÓÔÌÔÙ¯ÓÈ΋ ÌÂϤÙË ÛÙȘ ∏¶∞, ÙÔ ÎfiÛÙÔ˜ Ù˘ ıÂڷ›·˜ ÁÈ· ¤Ó· ·ÛıÂÓ‹ 70 kg Ì 4 ÂÁ¯‡ÛÂȘ Û ‰fiÛË 2 gr/kg Êı¿ÓÂÈ Ù· 30000 USD15. ∞Ó ÏËÊı› ˘fi„Ë ÙÔ ÎfiÛÙÔ˜ ·Ú·ÌÔÓ‹˜ ÛÙËÓ ·ÈÌÔοı·ÚÛË ÛÙȘ ∏¶∞, ÙfiÙ ۇÌʈӷ Ì ÙËÓ ›‰È· ÌÂϤÙË ı· ÂÍÔÈÎÔÓÔÌËıÔ‡Ó ÂÚ›Ô˘ 300.000 USD ÁÈ· οı ·ÛıÂÓ‹ Ô˘ ı· ·Ú¤ÌÂÓ ÛÙËÓ ·ÈÌÔοı·ÚÛË Â› Ì›· ÂÓÙ·ÂÙ›·2. ∏ ¯ÔÚ‹ÁËÛË ÌÂÁ¿ÏˆÓ ‰fiÛÂˆÓ IVIG ‰ÂÓ Â›Ó·È ¿ÌÔÈÚË ·ÚÂÓÂÚÁÂÈÒÓ. O Jordan ·Ó·Ê¤ÚÂÈ fiÙÈ Î·Ù¿ ÙËÓ ÌÂϤÙË IG02 ¤ÁÈÓ·Ó 300 ÂÁ¯‡ÛÂȘ IVIG Î·È 300 ÂÁ¯‡ÛÂȘ placebo2,15. ∫·ÙÂÁÚ¿ÊËÛ·Ó 24 ·ÓÂÈı‡ÌËÙ˜ ÂÓ¤ÚÁÂȘ ÛÙËÓ ÔÌ¿‰· Ù˘ IVIG Î·È 23 ÛÙËÓ ÔÌ¿‰· ÙÔ˘ ÂÈÎÔÓÈÎÔ‡ Ê·ÚÌ¿ÎÔ˘. ∏ ÈÔ Û˘¯Ó‹ ·ÓÂÈı‡ÌËÙË ÂÓ¤ÚÁÂÈ· ÛÙËÓ ÔÌ¿‰· Ù˘ IVIG ‹Ù·Ó Ë ÎÂÊ·Ï·ÏÁ›·, Ë ÔÔ›· ˘Ô¯ˆÚÔ‡Û Ì ÂÏ¿ÙÙˆÛË ÙÔ˘ Ú˘ıÌÔ‡ ¤Á¯˘Û˘ ÙÔ˘ Ê·ÚÌ¿ÎÔ˘ Î·È ¯ÔÚ‹ÁËÛË ·Ú·ÎÂÙ·ÌfiÏ˘. ÕÏϘ ·ÓÂÈı‡ÌËÙ˜ ÂÓ¤ÚÁÂȘ Ô˘ ¤¯Ô˘Ó ·Ó·ÊÂÚı› Â›Ó·È ˘ÚÂÙfi˜ Î·È Ú›ÁË Ô˘ ˘Ô¯ˆÚÔ‡Ó Ì ÙËÓ ·ÓˆÙ¤Úˆ Ú·ÎÙÈ΋, ·Ó·Ê˘Ï·Í›· Û ¿ÙÔÌ· ÌÂ Û˘ÁÁÂÓ‹ ·Ó¿ÚÎÂÈ· IgA, ıÚÔÌ‚ˆÙÈο ÂÂÈÛfi‰È· (Ù· ÂÚÈÛÛfiÙÂÚ· ΤÓÙÚ· Û‹ÌÂÚ· ¯ÚËÛÈÌÔÔÈÔ‡Ó ÚÔÊ˘Ï·ÎÙÈ΋ ·ÓÙÈıÚÔÌ‚ˆÙÈ΋ ·ÁˆÁ‹) Î·È ÔÍ›· ÓÂÊÚÈ΋ ·Ó¿ÚÎÂÈ· (ÔÊÂÈÏfiÌÂÓË Î‡ÚÈ· ÛÙË ÛÔ˘ÎÚfi˙Ë Ô˘ ÂÚȤ¯Ô˘Ó ÔÚÈṲ̂ӷ Û΢¿ÛÌ·Ù·) ·ÊÔ‡ ÔÈ ÂÁ¯‡ÛÂȘ Û˘Ó¯›˙ÔÓÙ·È Î·È ÌÂÙ¿ ÙË ÓÂÊÚÈ΋ ÌÂÙ·ÌfiÛ¯Â˘ÛË16.
¶ÚˆÙfiÎÔÏÏ· ¶Ï·ÛÌ·Ê·›ÚÂÛ˘ ¢È¿ÊÔÚ· ΤÓÙÚ· ¤¯Ô˘Ó ·Ó·Ê¤ÚÂÈ Ôχ ηϿ ·ÔÙÂϤÛÌ·Ù· Ì ڈÙfiÎÔÏÏ· ·Â˘·ÈÛıËÙÔÔÏ›ËÛ˘ ‚·ÛÈṲ̂ӷ ÛÙËÓ ‰ÈÂÓ¤ÚÁÂÈ· Ï·ÛÌ·Ê·›ÚÂÛ˘17-20. Δ· ÚˆÙfiÎÔÏÏ· ·˘Ù¿ ·ÊÔÚÔ‡Ó Î˘Ú›ˆ˜ ˘ÂÚ¢·ÈÛıËÙÔÔÈË̤ÓÔ˘˜ ·ÛıÂÓ›˜ Ì ˘Ô„‹ÊÈÔ˘˜ ˙ÒÓÙ˜ ‰fiÙ˜ Ì ÙÔ˘˜ ÔÔ›Ô˘˜ fï˜ ÂÌÊ·Ó›˙Ô˘Ó ıÂÙÈÎfi crossmatch. ∏ ‚·ÛÈ΋ ÙÔ˘˜ ·Ú¯‹ ÛÙËÚ›˙ÂÙ·È ÛÙËÓ ·ÔÌ¿ÎÚ˘ÓÛË ÙˆÓ ÚÔÛ¯ËÌ·ÙÈÛÌ¤ÓˆÓ anti-HLA IgG Ì ϷÛÌ·Ê·›ÚÂÛË Î·È ÙË ¯ÔÚ‹ÁËÛË ÌÈÎÚÒÓ ‰fiÛÂˆÓ IVIG Ë ÔÔ›· ¤¯ÂÈ ·ÓÔÛÔÙÚÔÔÔÈËÙÈΤ˜ ȉÈfiÙËÙ˜ ÙÚÂȘ ÊÔÚ¤˜ ÙËÓ Â‚‰ÔÌ¿‰·. ∏ ¯Ú‹ÛË Ù˘ Ï·ÛÌ·Ê·›ÚÂÛ˘ ÛÙÔ˘˜ ˘Ô„‹ÊÈÔ˘˜ Ï‹Ù˜ ÓÂÊÚÈÎÔ‡ ÌÔۯ‡̷ÙÔ˜ Û ηٷÏfiÁÔ˘˜ ·Ó·ÌÔÓ‹˜ ÁÈ· و̷ÙÈ΋ ÌÂÙ·ÌfiÛ¯Â˘ÛË ÎÚ›ÓÂÙ·È Ì¿ÏÏÔÓ ÂÚÈÔÚÈṲ̂ÓË, ·ÊÔ‡ ‰ÂÓ Â›Ó·È ‰˘Ó·ÙfiÓ Ó· ÚÔ‚ÏÂÊı› Ë È‰·ÓÈ΋ ¯ÚÔÓÈ΋ ÛÙÈÁÌ‹ Ù˘ ·Ó‡ÚÂÛ˘ ÙÔ˘ Û˘Ì‚·ÙÔ‡ ÌÔۯ‡̷ÙÔ˜, ÂÓÒ Ô Ù›ÙÏÔ˜ ÙˆÓ ·ÓÙÈ-HLA ·ÓÙÈÛˆÌ¿ÙˆÓ ·Ó‚·›ÓÂÈ (rebound) Û¯Â-
METAMO™XEY™Eπ™ 2008
ÙÈο ÁÚ‹ÁÔÚ· ÌÂÙ¿ ÙË ‰È·ÎÔ‹ ÙˆÓ Û˘Ó‰ÚÈÒÓ Ï·ÛÌ·Ê·›ÚÂÛ˘. ¶¿ÓÙˆ˜ Ë ¯Ú‹ÛË Ù˘ Ï·ÛÌ·Ê·›ÚÂÛ˘ ıˆÚÂ›Ù·È ÔχÙÈÌË ÛÙËÓ ·ÓÙÈÌÂÙÒÈÛË Ù˘ ÔÍ›·˜ ·fiÚÚȄ˘ ·fi ·ÓÙÈÛÒÌ·Ù· Ô˘ ·Ú·ÙËÚÂ›Ù·È Û˘¯Ó¿ ÛÙÔ˘˜ ·ÛıÂÓ›˜ Ô˘ ˘Ô‚¿ÏÏÔÓÙ·È Û ڈÙfiÎÔÏÏ· ·Â˘·ÈÛıËÙÔÔ›ËÛ˘2,8.
∞ÓÔÛÔÚÔÛÚfiÊËÛË ∏ ̤ıÔ‰Ô˜ Ù˘ ·ÓÔÛÔÚÔÛÚfiÊËÛ˘ ¤¯ÂÈ ÙÔ ÏÂÔÓ¤ÎÙËÌ· ¤Ó·ÓÙÈ Ù˘ ÎÏ·ÛÛÈ΋˜ Ï·ÛÌ·Ê·›ÚÂÛ˘, Ù˘ ÂÎÏÂÎÙÈ΋˜ ·ÔÌ¿ÎÚ˘ÓÛ˘ Ù˘ IgG, ¯ˆÚ›˜ ÙËÓ ·ÒÏÂÈ· ˆÊ¤ÏÈÌˆÓ ·Ú·ÁfiÓÙˆÓ fiˆ˜ ÔÈ ·Ú¿ÁÔÓÙ˜ ‹Í˘ ‹ ÙËÓ ·Ó¿ÁÎË ¯ÔÚ‹ÁËÛ˘ ˘ÁÚÒÓ ·Ó·Ï‹ÚˆÛ˘. OÈ Lorenz Î·È Û˘Ó ¯ÚËÛÈÌÔÔ›ËÛ·Ó ÙËÓ ·ÓÔÛÔÚÔÛÚfiÊËÛË ˆ˜ ıÂڷ›· ·Â˘·ÈÛıËÙÔÔ›ËÛ˘ Û ·ÛıÂÓ›˜ Ì ıÂÙÈÎfi crossmatch ¤Ó·ÓÙÈ ÙˆÌ·ÙÈÎÔ‡ ‰fiÙË21. ∂¿Ó ÌÂÙ¿ ·fi Ì›· Û˘Ó‰ڛ· ·ÓÔÛÔÚÔÛÚfiÊËÛ˘ ÙÔ crossmatch ÁÈÓfiÙ·Ó ·ÚÓËÙÈÎfi, Ô ·ÛıÂÓ‹˜ ÂÏ¿Ì‚·Ó ÙÔ ÌfiÛ¯Â˘Ì·. ∏ ‰ÈÂÓ¤ÚÁÂÈ· ÌfiÓÔÓ Ì›·˜ Î·È fi¯È ÂÚÈÛÛÔÙ¤ÚˆÓ Û˘Ó‰ÚÈÒÓ ·ÓÔÛÔÚÔÛÚfiÊËÛ˘ ÎÚ›ıËΠ·Ó·Áη›· ÁÈ· ÙËÓ ·ÔÊ˘Á‹ ÌÂÁ¿Ï˘ ·Ú¿Ù·Û˘ ÙÔ˘ ¯ÚfiÓÔ˘ „˘¯Ú‹˜ ÈÛ¯·ÈÌ›·˜. OÈ Û˘Ó‰ڛ˜ ·ÓÔÛÔÚÔÛÚfiÊËÛ˘ Û˘Ó¯›˙ÔÓÙ·Ó ÁÈ· ¤Ó· Ì‹Ó· ÌÂÙ¿ ÙË ÌÂÙ·ÌfiÛ¯Â˘ÛË. ∂ÓÓ¤· (9/14) ·ÛıÂÓ›˜ ÌÂÙ·ÌÔۯ‡ıËÎ·Ó Ì ·˘Ùfi ÙÔ ÚˆÙfiÎÔÏÏÔ Ì 78% ÙÚÈÂÙ‹ ÂÈ‚›ˆÛË ÌÔÛ¯Â˘Ì¿ÙˆÓ. ΔÔ ÌÂÈÔÓ¤ÎÙËÌ· ·˘ÙÔ‡ ÙÔ˘ ÚˆÙÔÎfiÏÏÔ˘ Â›Ó·È fiÙÈ ·Ó ‰ÂÓ ·ÚÓËÙÈÎÔÔÈËı› ÙÔ crossmatch, Ô ÂfiÌÂÓÔ˜ Ï‹Ù˘ ı· Ï¿‚ÂÈ ÓÂÊÚÈÎfi ÌfiÛ¯Â˘Ì· Ì ·˘ÍË̤ÓÔ ¯ÚfiÓÔ „˘¯Ú‹˜ ÈÛ¯·ÈÌ›·˜. ¶ÚfiÛÊ·Ù· ÔÈ Silverman Î·È Û˘Ó ‰È·Ù‡ˆÛ·Ó ÙË ıˆڛ· fiÙÈ Ë ÚˆÙ½ÓË ∞ Ô˘ ¯ÚËÛÈÌÔÔÈÂ›Ù·È ÛÙËÓ ·ÓÔÛÔÚÔÛÚfiÊËÛË ·ÂÏ¢ıÂÚÒÓÂÙ·È Î·Ù¿ ÙË Û˘Ó‰ڛ· Ù˘ ıÂڷ›·˜ ÛÙÔ ·›Ì· ÙÔ˘ ·ÛıÂÓÔ‡˜ Î·È ‰Ú· ¢ÂÚÁÂÙÈο ÚÔηÏÒÓÙ·˜ ÂÏ¿ÙÙˆÛË ÙˆÓ μ-ÏÂÌÊÔ΢ÙÙ¿ÚˆÓ22. OÈ ›‰ÈÔÈ ÂÚ¢ÓËÙ¤˜ ¤¯Ô˘Ó ·ÎfiÌË ÚoÙ›ÓÂÈ Î·È ÙËÓ ÂÓ‰ÔÊϤ‚È· ¯ÔÚ‹ÁËÛË Ù˘ ˆ˜ ̤ıÔ‰Ô ·Â˘·ÈÛıËÙÔÔ›ËÛ˘!
Rituximab To rituximab Â›Ó·È ¯ÈÌÂÚÈÎfi ÌÔÓÔÎψÓÈÎfi ·Óٛۈ̷ ¤Ó·ÓÙÈ ÙÔ˘ ·ÓÙÈÁfiÓÔ˘ ÂÈÊ·Ó›·˜ CD20, ÙÔ ÔÔ›Ô Â˘Ú›ÛÎÂÙ·È ÛÙËÓ ÂÈÊ¿ÓÂÈ· Ê˘ÛÈÔÏÔÁÈÎÒÓ Î·È ÓÂÔÏ·ÛÌ·ÙÈÎÒÓ μ-ÏÂÌÊÔ΢ÙÙ¿ÚˆÓ. ΔÔ Ê¿ÚÌ·ÎÔ ¤¯ÂÈ Ï¿‚ÂÈ Â›ÛËÌ· ¿‰ÂÈ· ¯Ú‹Û˘ ÁÈ· ÙË ıÂڷ›· non-Hodgkin ÏÂÌÊˆÌ¿ÙˆÓ (Û˘ÌÂÚÈÏ·Ì‚·ÓÔÌ¤ÓˆÓ Î·È ÙˆÓ ÏÂÌÊÔ-˘ÂÚÏ·ÛÙÈÎˆÓ ÓÔÛËÌ¿ÙˆÓ ÌÂÙ¿ ·fi ÙË ÌÂÙ·ÌfiÛ¯Â˘ÛË, PTLD), Î·È ÛÂ
39
ÂÚ¢ÓËÙÈο ÚˆÙfiÎÔÏÏ· ·˘ÙÔ¿ÓÔÛˆÓ ÓÔÛËÌ¿ÙˆÓ Ì ÂÌÏÔ΋ Ù˘ ¯˘ÌÈ΋˜ ·ÓÔÛ›·˜2. ∫¿ÔÈ· ÌÂÙ·ÌÔÛ¯Â˘ÙÈο ΤÓÙÚ· Û˘ÌÂÚÈÏ·Ì‚¿ÓÔ˘Ó ÙÔ rituximab ÛÙ· ÚˆÙfiÎÔÏÏ· ·Â˘·ÈÛıËÙÔÔ›ËÛ˘ ÁÈ· ÙËÓ ·ÔÊ˘Á‹ ·ӷ‰ËÌÈÔ˘ÚÁ›·˜ ÙˆÓ anti-HLA ·ÓÙÈۈ̿وÓ. £ÂˆÚËÙÈο ÙÔ ·ÓÙÈÁfiÓÔ CD20 ‰ÂÓ ÂÎÊÚ¿˙ÂÙ·È ÛÙ· Ï·ÛÌ·ÙÔ·ÙÙ·Ú· Ù· ÔÔ›· Â›Ó·È Ù· ·ÙÙ·Ú· ·Ú·ÁˆÁ‹˜ ÙˆÓ ·ÓˆÙ¤Úˆ ·ÓÙÈۈ̿وÓ, ·ÏÏ¿ ¤¯Ô˘Ó ÚÔÙ·ı› ‰‡Ô Ì˯·ÓÈÛÌÔ› Èı·Ó‹˜ ÂÌÏÔ΋˜ ÙÔ˘: ·) ̤ۈ ÂÍ·Ê¿ÓÈÛ˘ Úfi‰ÚÔÌˆÓ (precursor) μ-ÏÂÌÊÔ΢ÙÙ¿ÚˆÓ Î·È ‚) ̤ۈ ·Ó·ÛÙÔÏ‹˜ Ù˘ ·ÓÙÈÁÔÓÔ·ÚÔ˘Û›·Û˘ ̤ۈ μ-ÏÂÌÊÔ΢ÙÙ¿ÚˆÓ Î·È Û˘Ó‰È¤ÁÂÚÛ˘ ÙˆÓ Δ- ÏÂÌÊÔ΢ÙÙ¿ÚˆÓ. ΔÔ rituximab ‰ÔÎÈÌ¿ÛÙËΠ۠ÌÂϤÙË Ê¿Û˘ I Û 9 ˘ÂÚ-¢·ÈÛıËÙÔÔÈË̤ÓÔ˘˜ ·ÛıÂÓ›˜ ˘fi ·ÈÌÔοı·ÚÛË, ÚÔηÏÒÓÙ·˜ ·Ú·ÙÂٷ̤ÓË ÂÍ¿ÏÂÈ„Ë ÙˆÓ μ-ÏÂÌÊÔ΢ÙÙ¿ÚˆÓ23. ¶·ÚfiÏ· ·˘Ù¿ ·Ú·ÙËÚ‹ıËΠÌfiÓÔÓ ÌÈ· ÌÈÎÚ‹ ÙÒÛË ÙÔ˘ Ù›ÙÏÔ˘ ÙÔ˘ PRA Û ÌfiÓÔ Û ÌÂÚÈÎÔ‡˜ ·ÛıÂÓ›˜. ÃÚËÛÈÌÔÔÈÂ›Ù·È Ì ۯÂÙÈ΋ ÂÈÙ˘¯›· (off-label) ÛÙÔ ÚˆÙfiÎÔÏÏÔ ·Â˘·ÈÛıËÙÔÔ›ËÛ˘ ÙÔ˘ ÓÔÛÔÎÔÌ›Ԣ John Hopkins, Û ÌÂÙ·ÌÔۯ‡ÛÂȘ Ì ∞μO ·Û˘Ì‚·ÙfiÙËÙ· (ÙÂÏÂ˘Ù·›Â˜ ÌÂϤÙ˜ ·ÌÊÈÛ‚ËÙÔ‡Ó ÙË ¯ÚËÛÈÌfiÙËÙ· ÙÔ˘) Î·È Û ÂÚÈÙÒÛÂȘ ·ÓıÂÎÙÈ΋˜ ÛÙË ıÂڷ›· ÔÍ›·˜ ·fiÚÚȄ˘ ÔÊÂÈÏfiÌÂÓ˘ Û ·Óٛۈ̷. ∏ ıÂڷ›· Ì rituximab Â›Ó·È ÂÍ·ÈÚÂÙÈο ‰··ÓËÚ‹ Î·È ¯ÚÂÈ¿˙ÔÓÙ·È Ù˘¯·ÈÔÔÈË̤Ó˜ ÌÂϤÙ˜ Ì ÔÌ¿‰Â˜ ÂϤÁ¯Ô˘ ÁÈ· Ó· ·ÔÛ·ÊËÓÈÛÙÔ‡Ó Ï‹Úˆ˜ ÔÈ ÂӉ›ÍÂȘ Ù˘ ¯Ú‹Û˘ ÙÔ˘ ÛÙË ÓÂÊÚÈ΋ ÌÂÙ·ÌfiÛ¯Â˘ÛË2,3.
ÕÏϘ Δ¯ÓÈΤ˜ ∏ ÎÏÈÓÈ΋ ·Ú·Ù‹ÚËÛË fiÙÈ Ë ÂÌÊ¿ÓÈÛË ÔÍ›·˜ ·fiÚÚȄ˘ ·fi ·ÓÙÈÛÒÌ·Ù· Â›Ó·È ÂÍ·ÈÚÂÙÈο Û¿ÓÈ· Û ·ÛıÂÓ›˜ Ô˘ ¤¯Ô˘Ó ˘Ô‚ÏËı› Û ÌÂÙ·ÌfiÛ¯Â˘ÛË ‹·ÙÔ˜, ·ÎfiÌË Î·È Â› ·ÚÔ˘Û›·˜ ıÂÙÈÎÔ‡ crossmatch, Ô‰‹ÁËÛ ÛÙË ıˆڛ· Ù˘ ·ÔÚÚfiÊËÛ˘ ÙˆÓ ·ÓÙÈÛˆÌ¿ÙˆÓ ·fi ÙÔ ‹·Ú. OÈ Gutierrez Î·È Û˘Ó ·fi ÙËÓ πÛ·Ó›· ÚÒÙÔÈ ·Ó¤ÊÂÚ·Ó ÂÈÙ˘¯‹ ‰ÈÏ‹ ÌÂÙ·ÌfiÛ¯Â˘ÛË ‹·ÙÔ˜ Î·È ÓÂÊÚÔ‡ Û ˘ÂÚ¢·ÈÛıËÙÔÔÈË̤ÓÔ˘˜ ·ÛıÂÓ›˜ Ì ıÂÙÈÎfi crossmatch, ·ÏÏ¿ ÔÈ ·ÛıÂÓ›˜ ·˘ÙÔ› ·ÚÔ˘Û›·˙·Ó ¿ÌÂÛË ¤Ó‰ÂÈÍË ÁÈ· ‰ÈÏ‹ Ù·˘Ùfi¯ÚÔÓË ÌÂÙ·ÌfiÛ¯Â˘ÛË (·ÈÌÔηı·ÈÚfiÌÂÓÔÈ ·ÛıÂÓ›˜ Ì ˷ÙÈ΋ ΛÚÚˆÛË)24. OÈ Olausson Î·È Û˘Ó ·fi ÙË ™Ô˘Ë‰›· ˘¤‚·ÏÏ·Ó 7 ·ÛıÂÓ›˜ Ì ˘„ËÏfi Ù›ÙÏÔ PRA (50-99%) Û ٷ˘Ùfi¯ÚÔÓË ÌÂÙ·ÌfiÛ¯Â˘ÛË ÓÂÊÚÔ‡ Î·È ÙÌ‹Ì·ÙÔ˜ ‹·ÙÔ˜ (ÙÔ ¿ÏÏÔ ÙÌ‹Ì· ÙÔ˘
40
∫. ºOÀƒΔOÀ¡∞™
‹·ÙÔ˜ ›¯Â ¯ÚËÛÈÌÔÔÈËı› Û ·È‰È·ÙÚÈÎÔ‡˜ ·ÛıÂÓ›˜ - split liver) ·fi ‰fiÙ˜ Ì ıÂÙÈ΋ ‰ÔÎÈÌ·Û›· crossmatch, ¯ˆÚ›˜ ÔÈ ·ÛıÂÓ›˜ ·˘ÙÔ› Ó· ¤¯Ô˘Ó ¤Ó‰ÂÈÍË ÁÈ· ÌÂÙ·ÌfiÛ¯Â˘ÛË ‹·ÙÔ˜25. ¶¤ÓÙ ·ÛıÂÓ›˜ ·ÚÔ˘Û›·Û·Ó ¿ÚÈÛÙË ÓÂÊÚÈ΋ ÏÂÈÙÔ˘ÚÁ›· (¯ˆÚ›˜ ÂÂÈÛfi‰È· ÔÍ›·˜ ·fiÚÚȄ˘) ÁÈ· 20-60 Ì‹Ó˜ ÌÂÙ¿ ÙË ÌÂÙ·ÌfiÛ¯Â˘ÛË, ÂÓÒ ÙÔ crossmatch η٤ÛÙË ·ÚÓËÙÈÎfi ¿ÌÂÛ· ÌÂÙÂÁ¯ÂÈÚËÙÈο, ·ÏÏ¿ Î·È ÛÙË Û˘Ó¤¯ÂÈ· Ù˘ ·Ú·ÎÔÏÔ‡ıËÛ˘. ™Â ¤Ó· ·ÛıÂÓ‹ ÙÔ ÓÂÊÚÈÎfi ÌfiÛ¯Â˘Ì· ‰ÂÓ ÏÂÈÙÔ‡ÚÁËÛ (primary non function) Î·È Û ¤Ó· ·ÛıÂÓ‹ ·Ú·ÙËÚ‹ıËΠ‚·ÚÈ¿ ÔÍ›· ·fiÚÚÈ„Ë ·fi ·Óٛۈ̷ (C4d+) Ô˘ Ô‰‹ÁËÛ Û ·ÒÏÂÈ· ÙÔ˘ ÌÔۯ‡̷ÙÔ˜. ∞Ó Î·È Ù· ·ÔÙÂϤÛÌ·Ù· ·˘Ù¿ Â›Ó·È ÂÓı·ÚÚ˘ÓÙÈο ÂÁ›ÚÔ˘Ó ÔÈΛϷ ˙ËÙ‹Ì·Ù· ËıÈ΋˜ (·˘ÍË̤ÓÔ˜ ¯ÂÈÚÔ˘ÚÁÈÎfi˜ ΛӉ˘ÓÔ˜, ¯Ú‹ÛË Ë·ÙÈÎÒÓ ÌÔÛ¯Â˘Ì¿ÙˆÓ ÁÈ· ¿ÏÏÔ˘˜ ÏfiÁÔ˘˜ ÎÏ).
¶ƒøΔO∫O§§∞ ∞¡O™O∫∞Δ∞™ΔO§∏™ ª∂Δ∞ Δ∏ ª∂Δ∞ªO™Ã∂À™∏ §fiÁˆ ÙÔ˘ ·˘ÍË̤ÓÔ˘ ·ÓÔÛÔÏÔÁÈÎÔ‡ ÎÈÓ‰‡ÓÔ˘, Ù· ÂÚÈÛÛfiÙÂÚ· ÌÂÙ·ÌÔÛ¯Â˘ÙÈο ΤÓÙÚ· ÂÈϤÁÔ˘Ó ÈÛ¯˘Ú¿ ·ÓÔÛÔηٷÛÙ·ÏÙÈο Û¯‹Ì·Ù· Ì ıÂڷ›· ·ÁˆÁ‹˜ Ì ÔÏ˘ÎψÓÈ΋ ·ÓÙÈı˘ÌÔ΢ÙÙ·ÚÈ΋ ÛÊ·ÈÚ›ÓË (thymoglobulin) Î·È ÙÚÈÏ‹ ıÂڷ›· Ì tacrolimus, MMF Î·È ÛÙÂÚÔÂȉ‹. ªÂÚÈο ΤÓÙÚ· Û˘ÌÂÚÈÏ·Ì‚¿ÓÔ˘Ó ÛÙÔ ·ÓˆÙ¤Úˆ ÚˆÙfiÎÔÏÏ· Î·È rituximab. £ÂˆÚËÙÈο Ë ¯Ú‹ÛË thymoglobulin ˘ÂÚ¤¯ÂÈ ¤Ó·ÓÙÈ ÙˆÓ ÌÔÓÔÎψÓÈÎÒÓ ·ÓÙÈÛˆÌ¿ÙˆÓ ¤Ó·ÓÙÈ ÙˆÓ ˘Ô‰Ô¯¤ˆÓ Ù˘ ÈÓÙÂÚÏ¢ΛÓ˘-2 (basiliximab, daclizumab) ÛÙËÓ ÚfiÏË„Ë Ù˘ ÔÍ›·˜ ΢ÙÙ·ÚÈ΋˜ ·fiÚÚȄ˘. ¶·ÚfiÏ· ·˘Ù¿ Û ·Ó·‰ÚÔÌÈΤ˜ ÌÂϤÙ˜ ‚Ú¤ıËΠfiÙÈ Ë ¯Ú‹ÛË thymoglobulin Û¯ÂÙ›˙ÂÙ·È Ì ÌÈ· ·Ú¿‰ÔÍË ·‡ÍËÛË ÙˆÓ anti-HLA ·ÓÙÈÛˆÌ¿ÙˆÓ ÌÂÙ¿ ÙË ÌÂÙ·ÌfiÛ¯Â˘ÛË Î·È Ù· ÂÚÈÛÛfiÙÂÚ· ΤÓÙÚ· Û‹ÌÂÚ· ÚÔÙÈÌÔ‡Ó ıÂڷ›˜ ·ÁˆÁ‹˜ Ì basiliximab ‹ daclizumab. ∞Í›˙ÂÈ Ó· ÛËÌÂȈı› fiÙÈ ÙÔ ÌÔÓÔÎψÓÈÎfi ·Óٛۈ̷ ¤Ó·ÓÙÈ ÙÔ˘ ·ÓÙÈÁfiÓÔ˘ CD52 alemtuzumab (Campath 1H) ÙÔ ÔÔ›Ô ¯ÚËÛÈÌÔÔÈÂ›Ù·È Û‹ÌÂÚ· ¢ڤˆ˜ Û ڈÙfiÎÔÏÏ· ·ÔÊ˘Á‹˜ ·Ó·ÛÙÔϤˆÓ ηÏÛÈÓ¢ڛÓ˘ ‹ ÛÙÂÚÔÂȉÒÓ Û˘Óԉ‡ÙËΠ·fi ·˘ÍË̤ÓÔ Î›Ó‰˘ÓÔ ·fiÚÚȄ˘ ÔÊÂÈÏfiÌÂÓ˘ Û ·ÓÙÈÛÒÌ·Ù·3 Û ÌË Â˘·ÈÛıËÙÔÔÈË̤ÓÔ˘˜ ·ÛıÂÓ›˜. OÈ Vo Î·È Û˘Ó ÚfiÛÊ·Ù· ·Ó¤ÊÂÚ·Ó ÂÈÙ˘¯‹ ˘Ô‰fiÚÈ· ¯ÔÚ‹ÁËÛË alemtuzumab Û ˘ÂÚ¢·ÈÛıËÙÔÈË̤ÓÔ˘˜ ·ÛıÂÓ›˜, ÌË ÂȂ‚·ÈÒÓÔÓÙ·˜ ÙÔ˘˜ ·Ú¯ÈÎÔ‡˜ ÂÓ‰ÔÈ·ÛÌÔ‡˜26.
¶ƒOμ§∏ª∞Δπ™ªOπ - ¶ƒOO¶Δπ∫∂™ OÈ ÌÂϤÙ˜ Ì ‰È¿ÊÔÚÔ˘˜ Ê·ÚÌ·ÎÔÏÔÁÈÎÔ‡˜ ·Ú¿ÁÔÓÙ˜ Ô˘ ÚԷӷʤÚıËÎ·Ó ·ÚÔ˘ÛÈ¿˙Ô˘Ó ·ÍÈÔÛËÌ›ˆÙÔ˘˜ ÂÚÈÔÚÈÛÌÔ‡˜ ÔÈ ÔÔ›ÔÈ Î·È ı· Ú¤ÂÈ Ó· ÂÈÛËÌ·ÓıÔ‡Ó: – ∫·Ù·Ú¯‹Ó Ì ÌÔÓ·‰È΋ ÂÍ·›ÚÂÛË ÙË ÌÂϤÙË IG02, Ù· ÚˆÙfiÎÔÏÏ· ·˘Ù¿ ‰ÂÓ ¤¯Ô˘Ó ÌÂÏÂÙËı› ÛÂ Ù˘¯·ÈÔÔÈË̤Ó˜ ÌÂϤÙ˜ Ì ÔÌ¿‰· ÂϤÁ¯Ô˘. OÈ ˘ÔÛÙËÚÈÎÙ¤˜ ÙÔ˘˜ ÂÎÊÚ¿˙Ô˘Ó ÙËÓ ÂÔ›ıËÛË fiÙÈ Ù· ·ÔÙÂϤÛÌ·Ù· Â›Ó·È ·ÓÒÙÂÚ· ·fi ÙËÓ ÂÌÂÈÚ›· ·Ï·ÈfiÙÂÚˆÓ ÂÙÒÓ (historical controls), ·ÏÏ¿ ‰ÂÓ Ï·Ì‚¿ÓÔ˘Ó ˘fi„Ë ÙË ¯Ú‹ÛË Û‹ÌÂÚ· ÈÛ¯˘ÚfiÙÂÚˆÓ ·ÓÔÛÔηٷÛÙ·ÏÙÈÎÒÓ Ê·ÚÌ¿ÎˆÓ (tacrolimus, MMF, sirolimus, everolimus). – ΔÔ ÎfiÛÙÔ˜ ÙˆÓ ÚˆÙÔÎfiÏÏˆÓ ·˘ÙÒÓ Â›Ó·È ¿Ú· Ôχ ˘„ËÏfi. ∏ ÌÔÓ·‰È΋ ÔÈÎÔÓÔÌÔÙ¯ÓÈ΋ ÌÂϤÙË Ô˘ ¤ÁÈÓ ·fi ÙËÓ ÌÂϤÙË IG02 ‰Â›¯ÓÂÈ fiÙÈ Ë ¯ÔÚ‹ÁËÛË ÌÂÁ¿ÏˆÓ ‰fiÛÂˆÓ IVIG ·ÚÔ˘ÛÈ¿˙ÂÈ ıÂÙÈÎfi ÚfiÛËÌÔ ÎfiÛÙÔ˘˜/ˆÊ¤ÏÂÈ·˜ Û ۯ¤ÛË Ì ÙËÓ ·Ú·ÌÔÓ‹ ÙˆÓ ·ÛıÂÓÒÓ ÛÙËÓ ·ÈÌÔοı·ÚÛË, ·ÏÏ¿ Ù· ÔÈÎÔÓÔÌÈο ÌÂÁ¤ıË ·ÊÔÚÔ‡Ó ÌfiÓÔÓ ÙȘ ∏¶∞. – ∏ Ô˘Ì·ÓÈÛÙÈ΋/ÎÔÈÓˆÓÈ΋ ÚÔÛ¤ÁÁÈÛË ÙÔ˘ ı¤Ì·ÙÔ˜ ¤Ú¯ÂÙ·È Û ۷ʋ ·ÓÙ›ıÂÛË Ì ÙËÓ ÔÈÎÔÓÔÌÈ΋ ÚÔÛ¤ÁÁÈÛË ÙÔ˘, ·ÊÔ‡ Â›Ó·È ÁÓˆÛÙfi fiÙÈ Ë ÓÂÊÚÈ΋ ÌÂÙ·ÌfiÛ¯Â˘ÛË ˘ÂÚ¤¯ÂÈ ¤Ó·ÓÙÈ ÙˆÓ ıÂÚ·ÂÈÒÓ ˘ÔηٿÛÙ·Û˘ (·ÈÌÔοı·ÚÛË, ÂÚÈÙÔÓ·˚΋ οı·ÚÛË), ÙfiÛÔ ·Ó·ÊÔÚÈο Ì ÙËÓ ÂÈ‚›ˆÛË fiÛÔ Î·È Ì ÙËÓ ÔÈfiÙËÙ· ˙ˆ‹˜ ÙˆÓ ·ÛıÂÓÒÓ ·˘ÙÒÓ. ∂Ô̤ӈ˜ ıˆÚÂ›Ù·È Ì¿ÏÏÔÓ ·Ó‹ıÈÎÔ ÙÔ Ó· ÌËÓ ÚÔÛʤÚÂÙ·È Î¿ÔÈ· ÂÓ·ÏÏ·ÎÙÈ΋ χÛË, ¤ÛÙˆ Î·È Ì ÂÚÈÔÚÈṲ̂ÓË ÂÈÙ˘¯›·, ·ÊÔ‡ Á›ÓÔ˘Ó ÁÓˆÛÙ¿ ÛÙÔÓ ˘Ô„‹ÊÈÔ ·ÛıÂÓ‹ Ù· ‰ÈÂıÓ‹ ‰Â‰Ô̤ӷ, ·ÏÏ¿ Î·È Ù· ·ÔÙÂϤÛÌ·Ù· ÙÔ˘ οı ΤÓÙÚÔ˘. – ΔÔ ·ıÚÔÈÛÙÈÎfi ̤ÁÂıÔ˜ Ù˘ ¯ÔÚËÁÔ‡ÌÂÓ˘ ·ÓÔÛÔηٷÛÙÔÏ‹˜, ÙfiÛÔ Î·Ù¿ ÙËÓ ÚÔÂÙÔÈÌ·Û›· ÚÈÓ ÙË ÌÂÙ·ÌfiÛ¯Â˘ÛË, fiÛÔ Î·È ÌÂÙ¿ ·fi ·˘Ù‹Ó Û¯ÂÙ›˙ÂÙ·È ¿ÌÂÛ· Ì ÙÔÓ Î›Ó‰˘ÓÔ ÂÌÊ¿ÓÈÛ˘ Û˘ÛÙËÌ·ÙÈÎÒÓ ÏÔÈÌÒ͈Ó, ÈÔÁÂÓÒÓ ÏÔÈÌÒÍÂˆÓ ·fi CMV ‹ Èfi μ∫ Î·È ÓÂÔÏ·ÛÈÒÓ. ∂Ô̤ӈ˜, ÔÈ ˘Ô„‹ÊÈÔÈ ·ÛıÂÓ›˜ ÁÈ· ·ÚfiÌÔÈ· ÚˆÙfiÎÔÏÏ· ı· Ú¤ÂÈ Ó· Â›Ó·È Î·Ï¿ ÏËÚÔÊÔÚË̤ÓÔÈ ÁÈ· ÙȘ Èı·Ó¤˜ ÌÂÏÏÔÓÙÈΤ˜ ÂÈÏÔΤ˜. – ¢ÂÓ ˘¿Ú¯Ô˘Ó ·ÎfiÌË ·ÔÙÂϤÛÌ·Ù· Ì·ÎÚfi¯ÚÔÓ˘ ·Ú·ÎÔÏÔ‡ıËÛ˘. OÈ ÔϤÌÈÔÈ ÙˆÓ ÚˆÙÔÎfiÏÏˆÓ ·˘ÙÒÓ ÂÎÊÚ¿˙Ô˘Ó ¤ÓÙÔÓ˜ ÂÈÊ˘Ï¿ÍÂȘ ÁÈ· ÙËÓ Ì·ÎÚfi¯ÚÔÓË Û˘ÌÂÚÈÊÔÚ¿ ÙÔ˘ ·ÓÔÛÔÔÈËÙÈÎÔ‡ Û˘ÛÙ‹Ì·ÙÔ˜ ·Ó·ÊÔÚÈο Ì ÙË ÛÙ·‰È·Î‹ ·ӷ‰ËÌÈÔ˘ÚÁ›· anti-HLA ·ÓÙÈۈ̿وÓ
METAMO™XEY™Eπ™ 2008
–
–
–
–
Î·È ÙȘ Èı·Ó¤˜ ˘Ô-ÎÏÈÓÈΤ˜ ÌÔÚʤ˜ ÔÍ›·˜ ·fiÚÚȄ˘ ·fi ·ÓÙÈÛÒÌ·Ù·. ∏ ÚfiÏË„Ë Ù˘ Èı·Ó‹˜ ¢·ÈÛıËÙÔÔ›ËÛ˘ ÙˆÓ ·ÛıÂÓÒÓ ıˆÚÂ›Ù·È ıÂÌÂÏÈ҉˘. ∏ ¿ÛÎÔË ¯ÔÚ‹ÁËÛË ÚÔ˚fiÓÙˆÓ ·›Ì·ÙÔ˜ ı· Ú¤ÂÈ Ó· ·ÔʇÁÂÙ·È Î·È Ë Â˘Ú›· ¯Ú‹ÛË Ù˘ ·Ó·Û˘Ó‰È·Ṳ̂Ó˘ ÂÚ˘ıÚÔÔÈËÙ›Ó˘ ¤¯ÂÈ ÂÏ·ÙÙÒÛÂÈ ÛËÌ·ÓÙÈο ÙËÓ ·Ó¿ÁÎË ÌÂÙ·ÁÁ›ÛˆÓ. ∂›Û˘ ÂȉÈο ÛÙÔ˘˜ Ó¤Ô˘˜ ·ÛıÂÓ›˜ Ì ¯ÚfiÓÈ· ÓÂÊÚÈ΋ ÓfiÛÔ ÙÂÏÈÎÔ‡ ÛÙ·‰›Ô˘ Î·È Ì·ÎÚ‡ ÚÔÛ‰fiÎÈÌÔ ÂÈ‚›ˆÛ˘, Ë Î·Ù¿ÏÏËÏË ÂÈÏÔÁ‹ ÂÓfi˜ ÚÒÙÔ˘ ÌÔۯ‡̷ÙÔ˜, Ì ÙËÓ Î·Ï‡ÙÂÚË ‰˘Ó·Ù‹ ÈÛÙÔÛ˘Ì‚·ÙfiÙËÙ·, ıˆÚÂ›Ù·È ÛËÌ·ÓÙÈ΋ ÁÈ· ÙËÓ ·ÔÊ˘Á‹ ¢·ÈÛıËÙÔÔ›ËÛ˘ ÛÙÔ Ì¤ÏÏÔÓ. O ÚfiÏÔ˜ Ù˘ ·Ê·›ÚÂÛ˘ ÙÔ˘ ÓÂÊÚÈÎÔ‡ ÌÔۯ‡̷ÙÔ˜ ÌÂÙ¿ ÙËÓ Â·Ó¤ÓÙ·ÍË Û ıÂڷ›· ˘ÔηٿÛÙ·Û˘ ·Ú·Ì¤ÓÂÈ ·‰È¢ÎÚ›ÓÈÛÙÔ˜, ·ÊÔ‡ ˘¿Ú¯Ô˘Ó ‰Â‰Ô̤ӷ ·‡ÍËÛ˘ ÙÔ˘ Ù›ÙÏÔ˘ ÙÔ˘ PRA ÌÂÙ¿ ÙËÓ Â¤Ì‚·ÛË27. ΔËÓ ÙÂÏÂ˘Ù·›· ‰ÂηÂÙ›· ¤¯Ô˘Ó Á›ÓÂÈ ÌÂÁ¿Ï˜ ÚfiÔ‰ÔÈ ÛÙȘ Ù¯ÓÈΤ˜ Ù·˘ÙÔÔ›ËÛ˘ ÙˆÓ HLA ·ÓÙÈÁfiÓˆÓ Î·È ÙËÓ ·Ó›¯Ó¢ÛË ÙˆÓ ÂȉÈÎÒÓ antiHLA ·ÓÙÈۈ̿وÓ. ∏ ÂȉÈÎfiÙËÙ· Î·È Ë Â˘·ÈÛıËÛ›· ÙˆÓ ÌÂıfi‰ˆÓ ·˘ÙÒÓ, ·ÏÏ¿ Î·È Ë ÂÚ·ÈÙ¤Úˆ ‚ÂÏÙ›ˆÛË ÙÔ˘˜, ı· ÌÔÚÔ‡Ó ÛÙÔ Ì¤ÏÏÔÓ Ó· ÚԂϤ„Ô˘Ó Î·Ï‡ÙÂÚ· ÙËÓ ·ÓÔÛÔÏÔÁÈ΋ ·¿ÓÙËÛË ÙÔ˘ Ï‹ÙË ÛÙÔ ÓÂÊÚÈÎfi ÌfiÛ¯Â˘Ì· Î·È Ó· ‚ÂÏÙÈÒÛÔ˘Ó ÙËÓ Ì·ÎÚfi¯ÚÔÓË ÏÂÈÙÔ˘ÚÁ›· ÙÔ˘. ¶·ÚfiÏ· ·˘Ù¿, Û ÚfiÛÊ·ÙË ÌÂϤÙË ·fi ÙËÓ ª. μÚÂÙ·Ó›· Ê·›ÓÂÙ·È fiÙÈ Ë ¯Ú‹ÛË ÙˆÓ ÓÂÒÙÂÚˆÓ Î·È ÈÔ ÂÍÂȉÈÎÂ˘Ì¤ÓˆÓ Ù¯ÓÈÎÒÓ (fiˆ˜ ÔÈ solid phase assays) ›Ûˆ˜ ·ÔÎÏÂ›Ô˘Ó Î·ÎÒ˜ ·fi Èı·Ó‹ ÌÂÙ·ÌfiÛ¯Â˘ÛË Î¿ÔÈÔ˘˜ ¢·ÈÛıËÙÔÔÈË̤ÓÔ˘˜ ·ÛıÂÓ›˜28, ÂÁ›ÚÔÓÙ·˜ ÁÈ· Ì›· ·ÎfiÌË ÊÔÚ¿ ÙÔ ÂÚÒÙËÌ· ÁÈ· ÙÔÓ ·ÎÚÈ‚‹ Ù›ÙÏÔ ÙˆÓ ÂȉÈÎÒÓ ·ÓÙÈÛˆÌ¿ÙˆÓ Ô˘ ÎÚ›ÓÔÓÙ·È ··ÁÔÚ¢ÙÈο ÁÈ· ÙÔÓ Û˘ÁÎÂÎÚÈ̤ÓÔ ˘Ô„‹ÊÈÔ Ï‹ÙË29. ªÈ· ÚÔÛÂÎÙÈ΋ ÚÔÛ¤ÁÁÈÛË ÙˆÓ ·ÔÙÂÏÂÛÌ¿ÙˆÓ Ù˘ πG02 Ù˘ ÌÔÓ·‰È΋˜ Ù˘¯·ÈÔÔÈË̤Ó˘ ÌÂϤÙ˘ fiˆ˜ ÚԷӷʤÚıËÎÂ, ‰Â›¯ÓÂÈ Û·Ê‹ ˘ÂÚÔ¯‹ Ù˘ «‚ÈÔÏÔÁÈ΋˜» ÚÔÛ¤ÁÁÈÛ˘ ÙÔ˘ ÚÔ‚Ï‹Ì·ÙÔ˜ (·Ó‡ÚÂÛË Î·Ù¿ÏÏËÏÔ˘ ‰fiÙË) Û ۯ¤ÛË Ì ÙË Ê·ÚÌ·ÎÔÏÔÁÈ΋ (¯ÔÚ‹ÁËÛË IVIG) ·ÊÔ‡ Ù· ÂÂÈÛfi‰È· ÔÍ›·˜ ·fiÚÚȄ˘ ‹Ù·Ó Û˘ÓÙÚÈÙÈο ˘„ËÏfiÙÂÚ· ÛÙË ‰Â‡ÙÂÚË ÔÌ¿‰·. ∞ÎfiÌË Ù· ‰ÈÂÙ‹ ·ÔÙÂϤÛÌ·Ù· Ù˘ Eurotransplant, Ù· ÔÔ›· Â›Ó·È ·ÚfiÌÔÈ· Ì ·˘Ù¿ Û ÌË Â˘·ÈÛıËÙÔÔÈË̤ÓÔ˘˜ ·ÛıÂÓ›˜ ÂÈ΢ÚÒÓÔ˘Ó ·˘Ù‹Ó ÙËÓ ˘ÂÚÔ¯‹.
41
– ∂Ô̤ӈ˜ ÙÔ ÂӉȷʤÚÔÓ ı· Ú¤ÂÈ Ó· ÂÈÎÂÓÙÚˆı› ÛÙËÓ ·‡ÍËÛË Ù˘ ‰ÂÍ·ÌÂÓ‹˜ ÙˆÓ ‰ÔÙÒÓ Î·È ÌfiÓÔÓ Û ÂȉÈΤ˜ ÂÚÈÙÒÛÂȘ (Û¿ÓÈ· ∏LA ·ÓÙÈÁfiÓ·, Ôχ¯ÚÔÓË ·Ó·ÌÔÓ‹ ÎÏ) ı· Ú¤ÂÈ Ó· ÂÍÂÙ¿˙ÂÙ·È Ë ÂÚ›ÙˆÛË Ê·ÚÌ·ÎÔÏÔÁÈ΋˜ ÚÔÛ¤ÁÁÈÛ˘ ÙÔ˘ ÚÔ‚Ï‹Ì·ÙÔ˜. ∞˘Ù‹ ı· Ú¤ÂÈ Ó· Á›ÓÂÙ·È Û ÂÍÂȉÈÎÂ˘Ì¤Ó· ΤÓÙÚ· Ì ÂÌÂÈÚ›· ÛÙË ‰È¿ÁÓˆÛË Ù˘ ÔÍ›·˜ ·fiÚÚȄ˘ ·fi ·ÓÙÈÛÒÌ·Ù· (¿ÌÂÛË ÚfiÛ‚·ÛË Û ·ıÔÏÔÁÔ·Ó·ÙÔÌÈο ÂÚÁ·ÛÙ‹ÚÈ· Ì ‰˘Ó·ÙfiÙËÙ· ·Ó‡ÚÂÛ˘ C4d ÛÙÔ ˘ÏÈÎfi Ù˘ ‚ÈÔ„›·˜) Î·È Î·Ù¿ÏÏËÏ· ÂÍÔÏÈṲ̂ӷ ·ÓÔÛÔÏÔÁÈο ÂÚÁ·ÛÙ‹ÚÈ·, ·ÊÔ‡ ÔÈ ‰ÔÎÈ̷ۛ˜ crossmatch ÌÂÙ¿ ÙË ÌÂÙ·ÌfiÛ¯Â˘ÛË ÂËÚ¿˙ÔÓÙ·È ·fi ÙË ¯ÔÚ‹ÁËÛË IVIG, rituximab Î·È ¯ÚÂÈ¿˙ÔÓÙ·È ÈÔ ÂÍÂÏÈÁ̤Ó˜ ‰ÔÎÈ̷ۛ˜. – ™Â ÂÚ¢ÓËÙÈÎfi ·ÎfiÌË Â›Â‰Ô ÔÈ Rother Î·È Û˘Ó ·Ó·ÎÔ›ÓˆÛ·Ó ÚfiÛÊ·Ù·, fiÙÈ Ô ·ÔÎÏÂÈÛÌfi˜ ÙÔ˘ C5 ÛÙÔÈ¯Â›Ô˘ ÙÔ˘ Û˘ÌÏËÚÒÌ·ÙÔ˜ Ì ÙÔ ÌÔÓÔÎψÓÈÎfi ·Óٛۈ̷ eculizumab (ÂÁÎÂÎÚÈ̤ÓÔ Û··ÛÌ· ÁÈ· ÙË ıÂڷ›· Ù˘ Ó˘ÎÙÂÚÈÓ‹˜ ·ÚÔ͢ÓÙÈ΋˜ ·ÈÌÔÛÊ·ÈÚÈÓÔ˘Ú›·˜) Û ¢·ÈÛıËÙÔÔÈË̤ÓÔ˘˜ Â›Ì˘Â˜, ÌÔÚ› Ó· Ô‰ËÁ‹ÛÂÈ Û ̷ÎÚfi¯ÚÔÓË ÂÈ‚›ˆÛË ÙÔ˘ ÓÂÊÚÈÎÔ‡ ÌÔۯ‡̷ÙÔ˜ Ì ÙË ¯Ú‹ÛË ÂÏ¿¯ÈÛÙ˘ ·ÓÔÛÔηٷÛÙÔÏ‹˜30. ∏ ÎÏÈÓÈ΋ ÙÔ˘ ÂÊ·ÚÌÔÁ‹ Û ˘ÂÚ-¢·ÈÛıËÙÔÔÈË̤ÓÔ˘˜ ·ÛıÂÓ›˜ ·Ó·Ì¤ÓÂÙ·È Ì ÂӉȷʤÚÔÓ ÛÙÔ ÂÁÁ‡˜ ̤ÏÏÔÓ.
μπμ§πO°ƒ∞ºπ∞ 1. Patel R, Terasaki PI. Significance of the positive crossmatch test in kidney transplantation. N Engl J Med 1969; 280: 735-739. 2. Jordan SC, Pescovitz MD. Presensitization: the problem and its management. Clin J Am Soc Nephrol 2006; 1: 421-432. 3. Magee CC. Transplantation across previously incompatible immunological barriers. Transplant Int 2006; 19: 87-97. 4. Zachary AA, Montgomery RA, Leffell MS. Desensitization protocols improving access and outcome in transplantation. Clin Appl Immunol Reviews 2005; 5: 373-395. 5. Beimler JHM, Susal C, Zeier M. Desensitization strategies enabling successful renal transplantation in highly sensitized patients. Clin Transplant 2006; 20(Suppl 17): 7-12. 6. Crew RJ, Ratner LE. Overcoming immunologic incompatibility: Transplanting the difficult to transplant patient. Sem Dial 2005; 18: 474-481. 7. Doxiadis IIN, Duquesnoy RJ, Claas FHJ. Extending options for highly sensitized patients to receive a suitable kidney graft. Curr Opin Immunol 2005; 17: 536-540.
42
∫. ºOÀƒΔOÀ¡∞™
8. Glotz D, Antoine C, Julia P, ET AL. Intravenous immunoglobulins and transplantation for patients with anti-HLA antibodies. Transplant Int 2004; 17: 1-8. 9. Fuggle SV, Martin S. Towards performing transplantation in highly sensitized patients. Transplantation 2004; 78;186-189. 10. Bray RA, Nolen JDL, Larsen C et al. Transplanting the highly sensitized patient: The Emory algorithm. Am J Transplant 2006; 6: 2307-2315. 11. Clark B, Cole JY, Wortley A et al. Intravenous immunoglobulin-induced panel reactive antibody reduction: not all preparations are created equal. Transplantation 2003; 75: 242-245. 12. Watanabe J, Scornik JC. IVIG and HLA antibodies: Evidence for inhibition of complement activation but not for anti-idiotypic activity. Am J Transplant 2005; 5: 2786-2790. 13. Glotz D, Antoine C, Julia P et al. Desensitization and subsequent kidney transplantation of patients using intravenous immunoglobulins. Am J Transplant 2002; 2; 758-760. 14. Jordan SC, Cunnigham-Rundles C, McEwan R. Utility of intravenous immune globulin in kidney transplantation: efficacy, safety and cost implications. Am J Transplant 2003;3: 653-664. 15. Jordan SC, Tyan D, Stablein D et al. Evaluation of intravenous immunoglobulin as an agent to lower allo-sensitization and improve transplantation in highly sensitized adult patients with end-stage renal disease: Report of the NIH IG02 trial. J Am Soc Nephrol 2004; 15: 3256-3262. 16. Vo AA, Cam V, Toyoda M et al. Safety and adverse events profiles of intravenous immunoglobulin products used for immunomodulation: A single center experience. Clin J Am Soc Nephrol 2006; 1: 844-852. 17. Schweitzer EJ, Wilson JS, Fernandez-Vina M et al. A high panel reactive antibody rescue protocol for crossmatch positive live donor kidney transplants Transplantation 2000; 70: 1531-1536. 18. Gloor JM, DeGoey SR, Pineda AA et al. Overcoming a positive crossmatch in living donor kidney transplantation. Am J Transplant 2003; 3;1017-1021. 19. Montgomery RA, Zachary AA. Transplanting patients with a positive donor specific crossmatch: a single center’s perspective Pediatr Transplant 2004; 8:535
20. Stegall MD, Gloor J, Winters JL, Moore SB, DeGoey S. A comparison of plasmapheresis versus high dose IVIG desensitization in renal allograft recipients with high levels of donor specific alloantibody. Am J Transplant 2006; 6: 346-351. 21. Lorenz M, Regele H, Schillinger M et al. Peritransplant immunoabsorption: a strategy enabling transplantation in highly sensitized crossmatch positive cadaveric kidney allograft recipients. Transplantation 2005; 79: 696-701. 22. Silverman GJ, Goodyear CS, Siegel DL. On the mechanism of staphylococcal protein A immunomodulation. Transfusion 2005; 45: 274-280. 23. Viera CA, Agarwal A, Book BK et al. Rituximab for reduction of anti-HLA antibodies in patients awaiting renal transplantation: safety, pharmacodynamics and pharmacokinetics. Transplantation 2004; 77: 542-548. 24. Gutierrez A, Crespo M, Mila J, Torregrosa JV, Martorel J, Oppenheimer F. Outcome of simultaneous liver-kidney transplantation in highly sensitized crossmatch positive patients. Transpl Proc 2003; 35: 1861-1862. 25. Olausson M, Mjornstedt L, Norden G et al. Successful combined partial auxilliary liver and kidney transplantation in highly sensitized cross-match positive recipients. Am J Transplant 2007; 7; 130-136. 26. Vo AA, Wechsler EA, Wang J et al. Analysis of subcutaneous alemtuzumab induction therapy in highly sensitized patients desensitized with IVIG and rituximab. Am J Transpl 2008;8: 144-149. 27. Johnston O, Rose C, Landsberg D, Gourlay WA, Gill JS. Nephrectomy after transplant failure: current practice and outcomes. Am J Transpl 2007; 7: 1961-1967 28. Gupta A, Iverson V, Varagunam M et al. Pre-transplant donor-specific antibodies in cytotoxic negative crossmatch kidney transplants: Are they relevant? Transplantation 2008; 85: 1200-1204. 29. Vaughan R, Shaw O. How much donor human leukocyte antigen-specific antibody is too much for a renal transplant? Transplantation 2008; 85: 1081-1082. 30. Rother RP, Arp J, Jaing J et al. C5 blockade with conventional immunosuppresion induces long-term graft survival in presensitized recipients. Am J Transpl 2008; doi:10.1111/j.1600-6143.2008.02222.x (in press).
O ÚÔ¢·ÈÛıËÙÔÔÈË̤ÓÔ˜ Ï‹Ù˘ ÓÂÊÚÈÎÔ‡ ÌÔۯ‡̷ÙÔ˜ ª. ¢·ÚÂÌ¿, π.¡. ªÔϤÙ˘
Ô›ÔÈ ‰ÂÓ ¤¯Ô˘Ó ˘Ô‚ÏËı› Û ÌÂÙ·ÁÁ›ÛÂȘ ‹ Û ÚÔËÁÔ‡ÌÂÓË ÌÂÙ·ÌfiÛ¯Â˘ÛË, ·ÏÏ¿ ÂÌÊ·Ó›˙Ô˘Ó HLA ¢·ÈÛıËÙÔÔ›ËÛË. ∏ Èı·ÓfiÙËÙ· ¢·ÈÛıËÙÔÔ›ËÛ˘ ·fi ÂÚÈ‚·ÏÏÔÓÙÈÎÔ‡˜ ·Ú¿ÁÔÓÙ˜ ÂÓÈÛ¯‡ÂÙ·È ·fi ÙÔ ÁÂÁÔÓfi˜ Ù˘ ›‰È·˜ ·ÏÏËÏÔ˘¯›·˜ HLA Î·È ÌÈÎÚÔ‚È·ÎÒÓ ·Ú·ÁfiÓÙˆÓ, ÌÔÏÔÓfiÙÈ Ë Èı·ÓfiÙËÙ· ·˘ÙÒÓ ÙˆÓ ·Ú·ÁfiÓÙˆÓ Ó· ÚÔηÏÔ‡Ó Ì›· ÚˆÙ·Ú¯È΋ HLA ·¿ÓÙËÛË ‰ÂÓ ¤¯ÂÈ ·Ô‰Âȯı›7. ¶·Ú’fiÏ· ·˘Ù¿, Ë ÊÏÂÁÌÔÓ‹ Ô˘ ÚÔ·ÙÂÈ ·fi Ïԛ̈ÍË ‹ οÔÈÔ ÙÚ·‡Ì·, ÌÔÚ› Ó· Ô‰ËÁ‹ÛÂÈ Û ·ÓÂÓÂÚÁÔÔ›ËÛË Ì›·˜ ηı˘ÛÙÂÚË̤Ó˘ ·ÏÏÔ·¿ÓÙËÛ˘ ‹ ‰È·Ù‹ÚËÛË ÌÈ·˜ Û˘Ó¯È˙fiÌÂÓ˘ ·Ú·ÁˆÁ‹˜ ·ÓÙۈ̿وÓ8. ∞ÚÎÂÙ¤˜ ‰È·ÊÔÚÂÙÈΤ˜ ̤ıÔ‰ÔÈ ¯ÚËÛÈÌÔÔÈÔ‡ÓÙ·È, ÔÈ Ôԛ˜ ηıÔÚ›˙Ô˘Ó fiÛÔ Â˘·ÈÛıËÙÔÔÈË̤ÓÔ˜ Â›Ó·È ¤Ó·˜ ˘Ô„‹ÊÈÔ˜ Ï‹Ù˘ ÓÂÊÚÈÎÔ‡ ÌÔۯ‡̷ÙÔ˜ ÛÙ· HLA . OÈ Ì¤ıÔ‰ÔÈ ÔÈ Ôԛ˜ ηıÔÚ›˙Ô˘Ó ÙËÓ Â˘·ÈÛıËÙÔÔ›ËÛË ·ÓȯÓÂ‡Ô˘Ó ·ÓÙÈÛÒÌ·Ù· ¤Ó·ÓÙÈ ÂÓfi˜ ¢ڤˆ˜ Ê¿ÛÌ·ÙÔ˜ ΢ÙÙ¿ÚˆÓ (panel) ·fi Ì›· ‰ÂÍ·ÌÂÓ‹ ‰˘ÓËÙÈÎÒÓ ‰ÔÙÒÓ. ∏ ¢·ÈÛıËÙÔÔ›ËÛË ÙÔ˘ ·ÛıÂÓÔ‡˜ ηıÔÚ›˙ÂÙ·È Û·Ó ÙÔ ÔÛÔÛÙfi (%) ÙˆÓ ıÂÙÈÎÒÓ ·ÓÙȉڿÛÂˆÓ ÛÙÔ panel (panel reactive antibodies-PRA). ΔÔ crossmatch ·ÓȯÓ‡ÂÈ ·ÓÙÈÛÒÌ·Ù· ¤Ó·ÓÙÈ ÂÓfi˜ Û˘ÁÎÂÎÚÈ̤ÓÔ˘ ‰fiÙË. OÈ Ì¤ıÔ‰ÔÈ Ô˘ ¯ÚËÛÈÌÔÔÈÔ‡ÓÙ·È ÁÈ· ÙÔÓ ÚÔÛ‰ÈÔÚÈÛÌfi ÙˆÓ Î˘ÙÙ·ÚÔÙÔÍÈÎÒÓ ·ÓÙÈÛˆÌ¿ÙˆÓ Â›Ó·È Ë CDC (complement dependent cytotoxicity), Ë ÔÔ›· ·ÓȯÓ‡ÂÈ Ù· PRA fiÙ·Ó ÚÔÛı¤ÙÔÌ ÔÚfi ÙÔ˘ Ï‹ÙË Û ̛· ‰ÂÍ·ÌÂÓ‹ ÏÂÌÊÔ΢ÙÙ¿ÚˆÓ Ì ÁÓˆÛÙ¿ Ù·˘ÙÔÔÈË̤ӷ HLA Î·È ·ÎÔÏÔ˘ı› Ë ÚÔÛı‹ÎË Û˘ÌÏËÚÒÌ·ÙÔ˜ ·fi ÔÚfi ÔÓÙÈÎÔ‡.Δ· PRA ηıÔÚ›˙ÔÓÙ·È ·fi ÙÔ ÔÛÔÛÙfi ÙˆÓ Î˘ÙÙ·ÚÔÙÔÍÈÎÒÓ ·ÓÙȉڿÛÂˆÓ Ô˘ ·Ú·ÙËÚÔ‡ÓÙ·È. ÕÏϘ ̤ıÔ‰ÔÈ Â›Ó·È Ë Ì¤ıÔ‰Ô˜ ELISA, Ù·¯‡ÙÂÚË ·fi ÙËÓ CDC, ÛÙËÓ ÔÔ›· ÁÓˆÛÙ¿ HLA ·ÓÙȉÚÔ‡Ó Ì ÔÚfi ÙÔ˘ Ï‹ÙË Î·È Ë ÔÔ›· ¤¯ÂÈ ·ÓÙÈηٷÛÙ·ı› ·fi ÙË Ì¤ıÔ‰Ô Luminex, Ë ÔÔ›· ÛÙËÚ›˙ÂÙ·È ÛÙËÓ Î˘ÙÙ·ÚÔÌÂÙÚ›· ÚÔ‹˜ (flow cytometry). ∞Ó¿ÏÔÁ· Ì ÙË Ì¤ıÔ‰Ô Ô˘ ¯ÚËÛÈÌÔÔÈ›ٷÈ
∂˘·ÈÛıËÙÔÔÈË̤ÓÔÈ ˘Ô„‹ÊÈÔÈ Ï‹Ù˜ ÓÂÊÚÈÎÔ‡ ÌÔۯ‡̷ÙÔ˜ ıˆÚÔ‡ÓÙ·È ÔÈ ·ÛıÂÓ›˜ Ì ÚÔÛ¯ËÌ·ÙÈṲ̂ӷ ·ÓÙÈ-HLA ·ÓÙÈÛÒÌ·Ù· Ì ٛÙÏÔ, Ô˘ Û˘Ó‹ıˆ˜ Â›Ó·È ·˘ÍË̤ÓÔ˜ (PRA > 20%). ¶ÚfiÎÂÈÙ·È ÁÈ· ·ÛıÂÓ›˜ Ì ÓÂÊÚÈ΋ ÓfiÛÔ ÙÂÏÈÎÔ‡ ÛÙ·‰›Ô˘, ÔÈ ÔÔ›ÔÈ ¤¯Ô˘Ó ¢·ÈÛıËÙÔÔÈËı› Û HLA ÌÂÙ¿ ·fi οÔÈÔ ÁÂÁÔÓfi˜ ¢·ÈÛıËÙÔÔ›ËÛ˘,fiˆ˜ Â›Ó·È Ë Î‡ËÛË,ÔÈ ÌÂÙ·ÁÁ›ÛÂȘ ·›Ì·ÙÔ˜ ‹ ÚÔËÁÔ‡ÌÂÓË ÌÂÙ·ÌfiÛ¯Â˘ÛË1,2. ÀÂÚ¢·ÈÛıËÙÔÔÈË̤ÓÔÈ ıˆÚÔ‡ÓÙ·È ÔÈ ·ÛıÂÓ›˜ Ô˘ ¤¯Ô˘Ó PRA>80%. O ‚·ıÌfi˜ ·ÏÏ¿ Î·È Ë ‰È¿ÚÎÂÈ· Ù˘ ¢·ÈÛıËÙÔÔ›ËÛ˘ ÏfiÁˆ ·ËÛ˘ ‹ ÌÂÙ·ÁÁ›ÛÂˆÓ Û¯ÂÙ›˙ÂÙ·È ÙfiÛÔ Ì ÙÔÓ ·ÚÈıÌfi fiÛÔ Î·È Ì ÙË ¯ÚÔÓÈ΋ ÛÙÈÁÌ‹ ÂÌÊ¿ÓÈÛ˘ ·˘ÙÒÓ ÙˆÓ ÁÂÁÔÓfiÙˆÓ, ÂÓÒ Ë Â˘·ÈÛıËÙÔÔ›ËÛË ÌÂÙ¿ ·fi ÌÂÙ·ÌfiÛ¯Â˘ÛË ÂÌÊ·Ó›˙ÂÈ ÌÂÁ·Ï‡ÙÂÚË ‰È¿ÚÎÂÈ·3. ∏ ¯Ú‹ÛË Ù˘ ·ÓıÚÒÈÓ˘ ·Ó·Û˘Ó‰˘·Ṳ̂Ó˘ ÂÚ˘ıÚÔÔÈËÙ›Ó˘ ÙÔ 1989,›¯Â Û·Ó ·ÔÙ¤ÏÂÛÌ· ÙËÓ ÂÏ¿ÙÙˆÛË ÙÔ˘ ·ÚÈıÌÔ‡ ÙˆÓ ÌÂÙ·ÁÁ›ÛÂˆÓ Ô˘ ÂÏ¿Ì‚·Ó·Ó ÔÈ ·ÈÌÔηı·ÚfiÌÂÓÔÈ ·ÛıÂÓ›˜,Ì ·ÔÙ¤ÏÂÛÌ· ÙË Ì›ˆÛË Ù˘ Û˘¯ÓfiÙËÙ·˜ ÙˆÓ Â˘·ÈÛıËÙÔÔÈËÌ¤ÓˆÓ ·ÛıÂÓÒÓ ·ÏÏ¿ Î·È ÙÔ˘ ¯ÚfiÓÔ˘ ·Ó·ÌÔÓ‹˜ ÙÔ˘˜ ÁÈ· ÌÂÙ·ÌfiÛ¯Â˘ÛË4. øÛÙfiÛÔ, ÔÈ ·ÛıÂÓ›˜ Ì ¯ÚfiÓÈ· ÓÂÊÚÈ΋ ÓfiÛÔ ÂÍ·ÎÔÏÔ˘ıÔ‡Ó Ó· ÂÌÊ·Ó›˙Ô˘Ó ˘„ËÏfiÙÂÚË Û˘¯ÓfiÙËÙ· ¢·ÈÛıËÙÔÔ›ËÛ˘ Û ۇÁÎÚÈÛË Ì ·ÛıÂÓ›˜ ˘Ô„‹ÊÈÔ˘˜ ÁÈ· ÌÂÙ·ÌfiÛ¯Â˘ÛË ¿ÏÏˆÓ Û˘Ì·ÁÒÓ ÔÚÁ¿ÓˆÓ5. OÈ ∞ÊÚÔ·ÌÂÚÈηÓÔ› ÂÌÊ·Ó›˙Ô˘Ó ÌÂÁ·Ï‡ÙÂÚË Û˘¯ÓfiÙËÙ· ¢·ÈÛıËÙÔÔ›ËÛ˘ Û ۯ¤ÛË Ì ¿ÏϘ Ê˘Ï¤˜,ÁÂÁÔÓfi˜ Ô˘ ÔÊ›ÏÂÙ·È Û ÁÂÓÂÙÈ΋ ÚԉȿıÂÛË ÌÈ·˜ ÈÛ¯˘ÚfiÙÂÚ˘ ·ÓÔÛÔ·¿ÓÙËÛ˘, ·Ú¿ÏÏËÏ· Ì ÙËÓ ·˘ÍË̤ÓË Èı·ÓfiÙËÙ· ¤ÎıÂÛ˘ Û HLA, ·fi ÌÂÙ·ÁÁ›ÛÂȘ ·›Ì·ÙÔ˜ ·fi ‰fiÙ˜ ∫·˘Î¿ÛÈ·˜ Ê˘Ï‹˜6.OÈ Á˘Ó·›Î˜ ÏfiÁˆ Ù˘ ¤ÎıÂÛ‹˜ ÙÔ˘˜ Û ·ÙÚÈο HLA ηٿ ÙË ‰È¿ÚÎÂÈ· Ù˘ ·ËÛ˘, ÂÌÊ·Ó›˙Ô˘Ó ÙÚÂȘ ÊÔÚ¤˜ ÌÂÁ·Ï‡ÙÂÚË Èı·ÓfiÙËÙ· ·Ó¿Ù˘Í˘ ·ÓÙÈ-HLA ·ÓÙÈÛˆÌ¿ÙˆÓ Û˘ÁÎÚÈÙÈο Ì ¿Ó‰Ú˜ ˘Ô„‹ÊÈÔ˘˜ Ï‹Ù˜ ÓÂÊÚÈÎÔ‡ ÌÔۯ‡̷ÙÔ˜. øÛÙfiÛÔ ˘¿Ú¯Ô˘Ó ·Ó·ÊÔÚ¤˜ Û ¿Ó‰Ú˜, ÔÈ Ô-
43
44
ª. ¢∞ƒ∂ª∞, π.¡. ª¶O§∂Δ∏™
ÛÙÔÓ ¤ÏÂÁ¯Ô ¢·ÈÛıËÙÔÔ›ËÛ˘ Î·È crossmatch, ·ÓȯÓ‡ÔÓÙ·È ‰È·ÊÔÚÂÙÈÎÔ› Ù‡ÔÈ ·ÓÙÈۈ̿وÓ, ÙˆÓ ÔÔ›ˆÓ Ë ÎÏÈÓÈ΋ ÛËÌ·Û›· ÌÔÚ› Û ÔÚÈṲ̂Ó˜ ÂÚÈÙÒÛÂȘ Ó· ÌËÓ Â›Ó·È ·fiÏ˘Ù· Û·Ê‹˜. Δ· IgG ·ÓÙÈÛÒÌ·Ù· ÁÂÓÈο, ıˆÚÂ›Ù·È fiÙÈ ‰Â›¯ÓÔ˘Ó ·ÏËıÈÓ‹ ¢·ÈÛıËÙÔÔ›ËÛË ¤Ó·ÓÙÈ HLA, ÂÓÒ Ù· IgM ·ÓÙÈÛÒÌ·Ù· ‰ÂÓ ıˆÚÂ›Ù·È fiÙÈ ·ÓÙÈÚÔÛˆÂ‡Ô˘Ó Ì›· ·ÏËıÈÓ‹ ·ÓÙÈ-HLA ·¿ÓÙËÛË. ∞ÓÙÈÛÒÌ·Ù· Ô˘ ·ÓȯÓ‡ÔÓÙ·È ¤Ó·ÓÙÈ ÙˆÓ T΢ÙÙ¿ÚˆÓ ıˆÚÂ›Ù·È fiÙÈ ·ÓÙÚÔÛˆÂ‡Ô˘Ó Ú·ÁÌ·ÙÈ΋ ·ÓÙÈ-HLA ¢·ÈÛıËÙÔÔ›ËÛË ¤Ó·ÓÙÈ ÙˆÓ Ù¿Í˘ I ·ÓÙÈÁfiÓˆÓ. ™˘ÁÎÚÈÙÈο, ¤Ó· B (+) crossmatch ·ÓÙÈÚÔۈ‡ÂÈ Î˘Ú›ˆ˜ HLA Ù¿Í˘ II ·ÓÙÈÛÒÌ·Ù·, Ì ÌÈÎÚfiÙÂÚË ÎÏÈÓÈ΋ ÛËÌ·Û›·. Δ· ·ÓÙÈÁfiÓ· Ù¿Í˘ I ÂÎÊÚ¿˙ÔÓÙ·È ÙfiÛÔ ÛÙ· T fiÛÔ Î·È ÛÙ· μ ÏÂÌÊÔ·ÙÙ·Ú·. ∂ȉÈÎfiÙÂÚ·,Ù· ·ÓÙÈÛÒÌ·Ù· Ô˘ ¯·Ú·ÎÙËÚ›˙Ô˘Ó ¤Ó·Ó ·ÛıÂÓ‹ ˆ˜ ¢·ÈÛıËÙÔÔÈË̤ÓÔ Â›Ó·È fiÏ· Ù· IgG ·ÏÏÔ·ÓÙÈÛÒÌ·Ù· Ù¿Í˘ I Î·È Ù¿Í˘ II, Û˘Ó‰¤ÔÓÙ· Î·È ÌË Û˘Ó‰¤ÔÓÙ· in vitro ÙÔ Û˘Ìϋڈ̷,Ù· ÔÔ›· ·ÓȯÓ‡ıËÎ·Ó ÔÔÈ·‰‹ÔÙ ÛÙÈÁÌ‹ ÚÈÓ ÙË ÌÂÙ·ÌfiÛ¯Â˘ÛË, ηıÒ˜ Î·È IgM ·ÏÏÔ·ÓÙÈÛÒÌ·Ù· Ô˘ ·ÓȯÓ‡ÔÓÙ·È ÏÈÁfiÙÂÚÔ ·fi 6 Ì‹Ó˜ ÚÈÓ ÙË ÌÂÙ·ÌfiÛ¯Â˘ÛË. OÈ Â˘·ÈÛıËÙÔÔÈË̤ÓÔÈ ·ÛıÂÓ›˜ ÂÚÈ̤ÓÔ˘Ó ÌÂÁ·Ï‡ÙÂÚÔ ¯ÚÔÓÈÎfi ‰È¿ÛÙËÌ· ÁÈ· ÙËÓ Â͇ÚÂÛË ÌÔۯ‡̷ÙÔ˜ ÂÌÊ·Ó›˙Ô˘Ó ÂÚÈÛÛfiÙÂÚ· ÂÂÈÛfi‰È· ·fiÚÚȄ˘ Û˘ÁÎÚÈÙÈο Ì ÙÔ˘˜ ÌË Â˘·ÈÛıËÙÔÔÈË̤ÓÔ˘˜ ·ÛıÂÓ›˜. ∞fi Ùo 1985 Ë Eurotransplant ‰›ÓÂÈ ÚÔÙÂÚ·ÈfiÙËÙ· Û ·ÛıÂÓ›˜ Ì «acceptable missmatch» Î·È PRA >85%. ¶ÚfiÎÂÈÙ·È ÁÈ· ·ÛıÂÓ›˜ ÔÈ ÔÔ›ÔÈ ‰ÂÓ ÂÌÊ·Ó›˙Ô˘Ó Î˘ÎÏÔÊÔÚÔ‡ÓÙ· ·ÏÏÔ·ÓÙÈÛÒÌ·Ù· ¤Ó·ÓÙÈ ÙˆÓ ∏LA ÙÔ˘ Û˘ÁÎÂÎÚÈ̤ÓÔ˘ ‰fiÙË, ÌÔÏÔÓfiÙÈ Â›Ó·È ÔÏ˘Â˘·ÈÛıËÙÔÔÈË̤ÓÔÈ9. Δ· <acceptable missmatches> ηıÔÚ›˙ÔÓÙ·È ·fi ÙËÓ ·Ó¿Ï˘ÛË ÙˆÓ ·ÚÓËÙÈÎÒÓ Î˘ÙÙ·ÚÔÙÔÍÈÎÒÓ
·ÓÙȉڿÛÂˆÓ Û ̛· ¢Ú›· ‰ÂÍ·ÌÂÓ‹ ΢ÙÙ¿ÚˆÓ Ì Ôχ ηϿ ·Ó·ÁÓˆÚÈṲ̂ÓÔ˘˜ HLA Ê·ÈÓfiÙ˘Ô˘˜. OÈ ÚÔ˘Ôı¤ÛÂȘ ÁÈ· ÌÂÙ·ÌfiÛ¯Â˘ÛË ÂÓfi˜ ˘ÂÚ¢·ÈÛıËÙÔÔÈË̤ÓÔ˘ Ï‹ÙË Â›Ó·È Ë ·fiÏ˘ÙË Û˘Ì‚·ÙfiÙËÙ· ÔÌ¿‰ˆÓ ·›Ì·ÙÔ˜ ‰fiÙË-Ï‹ÙË, ÙÔ˘Ï¿¯ÈÛÙÔÓ ¤Ó· ÎÔÈÓfi HLA Ù¿Í˘ I (∞ ‹ μ) Î·È ¤Ó· ÎÔÈÓfi HLA Ù¿Í˘ II (DR), ·Ô‰ÂÎÙ‹ ·Û˘Ì‚·ÙfiÙËÙ· (acceptable mismatch), CDC ηıÒ˜ Î·È T- Î·È Bflow crossmatch ·ÚÓËÙÈο.
μÈ‚ÏÈÔÁÚ·Ê›· 1. Zachary AA, Montgomery RA, et al. 14th International HLA and Imunogenetics Workshop: Report on understanding andibodies in transplantation.Tissue Antigens 2007; 69: 160-173. 2. Cecka JM, Zhang Q et al. Performed cytotoxic antibodies in potential allograft recipients:recent data. Hum Immunol 2005; 66: 343-349. 3. Zachary AA and Hart JM. Relevance of antibody screening and crossmatch tests for organ transplantation. In: Handbook of Human Immunology. 4. Vella JP,O’Neill D et al. Sensitization to human leucocyte antigen before and after the introduction of erythropoietin.Nephrol Dial Transplant 1998; 13: 2027-2032. 5. Brand A. Immunological aspects of blood transfusions. Transpl Immunol 2002; 10: 183-190. 6. Young CJ and Gaston RS. Renal transplantation in black Americans.N Engl J Med 2000; 343: 1545-1552. 7. Massa MF Mazzoli P et al. Proinflammatory responses to self HLA epitopes are triggered by molecular mimicry to Epstein-Barr virus proteins in oligoarticular juvenile idiopathic arthritis.Arthritis Rheum 2002; 46: 2721-2729. 8. Bernasconi NL, Traggiai E et al. Maintenance of serological memory by polyclonal activation of human memory B cells. Science 2002; 298: 2199-2202. 9. Fuggle SV and Martin S. Toward performing transplantation in highly sensitized patient. Transplantation 2004; 78: 186-189.
Kidney Transplantation in Highly sensitized recipients G. Tsoulfas, Tatsuo Kawai
Introduction
AMR can be detectable by more sensitive assays using flow cytometry or Luminex.
The goal of this brief review is to introduce the topic of recipient sensitization in kidney transplantation, assess the risk it poses and discuss some of the different protocols used to address this most vexing problem in transplantation. Finally, some of the alternatives, such as ABO incompatible transplantation and a paired kidney exchange protocol1. Sensitization is defined as the presence of antibodies against Class I and/or Class II HLA molecules, specifically, HLA-A, HLA-B, HLADR, DQ. It may include sensitization against a single or multiple donors, leading to a positive donor-specific cross match. It represents a significant obstacle to transplantation, as it increases the waiting time. In the US nearly 30% of the 67,070 patients in the deceased donor waiting list are sensitized, with these patients having to wait three times longer than the nonsensitized ones for suitable match2. Ways that a patient can become sensitized include exposure to non-self HLA molecules (previous pregnancies, previous transplant or blood transfusions, or use of tissue allografts or “homografts” for vascular reconstruction in congenital heart surgery), viral infections (CMV), or noninfectious immune stimulation (vaccination, use of left ventricular assist devices). There are different levels of sensitization and these can be assessed by measuring the antibody level with different histocompatibility techniques. The combination of a high PRA (50-80%) and a positive crossmatch indicate a high level of donor-specific antibody resulting in a high risk of antibody mediated rejection (AMR). Even when a classic cytotoxicity crossmatch is negative, a low level of donorspecific antibody with a high-moderate risk of
Basic concepts in the management of HLAsensitized patients These include a) suppression of the T-cell response, b) elimination of pre-formed antibodies, c) inhibition of residual antibody and the complement system cascade, and d) depletion of antibody producing cells or their precursors (Naïve, memory and plasma B-cells). Efforts to suppress the T-cell response include the use of induction therapy with depleting and nondepleting antibodies, such as Thymoglobulin or IL-2 receptor blockers. These are effective in T-cell dependent B-cell responses, but ineffective in memory B-cell responses. Elimination of preformed antibody is done with plasma exchange (plasmapheresis, double filtration plasmapheresis, and immunoabsorption plasmapheresis), whereas inhibition of residual antibody and complement system is done with IVIG or CMV-Ig. Its methods of action include anti-idiotypic activity, inhibition of the complement system, FcÁRII ‚-mediated inhibition of antibody production, and enhanced catabolism of endogenous IgG3-5. Finally, depletion of B cells that eventually differentiate to antibody producing plasma cells is achieved primarily with Rituximab6. Rituximab is a genetically engineered chimeric murine/human monoclonal anti-CD20 antibody, the first of its type to be approved by the FDA for treatment of cancer (lymphoma). Its actions include antibody-dependent cell-mediated cytotoxicity, complement-dependent cytotoxicity and apoptosis. All of the above are part of the transplant physician’s armamentarium in bringing highlysensitized renal patients successfully to transplantation. The main modalities to achieve that include:
45
46
G. TSOULFAS, TATSUO KAWAI
–desensitization protocols –ABO-incompatible transplantation –transplantation across a positive donor specific crossmatch –Paired-kidney exchange program In this review we will discuss desensitization protocols in some more detail.
Desensitization protocols One of the more successful desensitization protocols is the one by the transplant team from the University of California Los Angeles CedarsSinai Medical Center (7). In the 1990s they developed the IVIg-PRA/CMX test to determine whether IVIg could inhibit PRA (Panel Reactive Antigen) or CMX (crossmatch) positivity of patients’ sera in vitro. Briefly, if the IVIg in vitro test shows any inhibition of the crossmatch test, then the highly-sensitized patients are treated with IVIg monthly x4 until a negative or acceptable CMX (living-donor) or deceased-donor transplant becomes available. Modification of antibody screens and antibody specificity by IVIg treatment can be monitored as usual and used to guide future therapy. If no inhibition is seen then the work-up stops and the patient is referred for plasma exchange therapy. These patients who fail in vitro IVIg inhibition or who have very high-titer anti-HLA antibody enter a protocol that includes five plasma exchange treatments followed by IVIg 2 g/kg x1 and Rituximab 375 mg/m 2 x1. These patients are usually awaiting living-donor renal transplantation, although this has also been used in patients with prolonged (more than 5 years) time on the deceased-donor waiting list. At the time of the transplant the patients receive IVIG 2gm/kg and Campath 30mg SQ, as well as steroids, Tacrolimus and MMF. Finally, a month posttransplant they receive another dose of IVIG. Of the 89 patients who were evaluated and treated with this protocol from July 2002 to October 2005, only 2 (2.2%) failed to respond to IVIg sufficiently to allow transplantation to be performed. The mean PRA for these recipients was 83%, and nearly all patients had antibodies specific to their donors that were eliminated or reduced b IVIg therapy. The incidence of allograft rejection is 28% with a 3year patient and graft
survival of 97.5% and 87.1% respectively. Five grafts were lost to rejection and the mean serum creatinine overall at 3 years was 1.4 mg/dl. Other protocols include the one from Johns Hopkins University where they used a combination of plasma exchange and CMV-Ig in 90 patients with patient and graft survivals at 3 years of 95% and 80.9% respectively. However, the rejection rate was higher at 62%, but the overall creatinine remained excellent at 1.2 mg/dl at 3 years8. Finally, the Mayo Clinic using a protocol of high dose IVIg and plasma exchange achieved patient and graft survival rates at 5 years of 97% and 80% respectively, with a rejection rate of 35%9.
Costs and Complications The complications of IVIg treatment were studied from 1997 to 2000 in the ICOG2 study of the National Institutes of Health, a controlled, clinical, multicenter, double-blinded trial of IVIg versus placebo in highly sensitized patients awaiting kidney transplantation10. Adverse events were similar in both arms of the study (24 IVIg versus 23placebo), with the most common adverse event in the IVIg arm being headache. This usually abated with reduction in the infusion rate and acetaminophen. Ten serious adverse events were noted, nine of these in the placebo group. Regarding cost, a four dose course of IVIg for a 70-kg person at 2 g/kg would cost $30,000. However, in the ICOG2 study the cost savings was approximately $300,000 per patient who received a kidney transplant versus those who remained on dialysis for the 5 years of the study. Thus a considerable cost savings are realized by being able to successfully bring these patients to transplantation.
Future perspectives Although Rituximab has been used as part of desensitization protocol, it does not delete plasma cells that actually produce antibodies. Therefore, there has been no clear evidence of antibody reduction reported by Rituximab alone. To improve the results of desensitization, treatments to block B cell maturation have been extensively studied. BAFF (B cell activation factor from the tumor necrosis factor family) and APRIL (A ProlifeRation Inducing Ligand) are members of
METAMO™XEY™Eπ™ 2008
the TNF family and interaction with their three ligands (BAFF-R, TACI and BCMA) is essential for B cell/Plasma cell survival, germinal center maintenance, T-dependent and independent antibody responses and T cell co-stimulation (11). BAFF and APRIL are secreted from various cells, such as T cell, dendritic cells and granulocytes, as a soluble form. BAFF binds to three receptors, BAFF-R, TACI (transmembrane activator and calcium-modulator and cyclophilin ligand interactor) and BCMA (B cell maturation antigens), whereas APRIL interacts with TACI, BCMA and proteoglycans. Three reagents (Belimumab, BR3 Fc and TACI-Ig) to block BAFF/APRIL are now under active investigation (12, 13). While Belimumab (anti-soluble BAFF mAb) and BR3-Fc only block BAFF, TACI-Ig is soluble receptor that block both BAFF and APRIL. In our preliminary studies in monkeys, TACI-Ig reduced splenic plasma cells and significantly decreased alloantibody titers without plasma exchange. With these reagents directly affect antibody production, better therapeutic interventions will be available for sensitized patients in near future.
References 1. Kaplan I, Houp JA, Leffell MS, Hart JM, Zachary AA. A computer match program for paired and unconventional kidney exchanges. Am J Transplant 2005; 5: 2306-2308. 2. Organ Procurement Transplantation Network/ Scientific Registry of Transplant Recipients: 2004 Annual Report: Transplant Data 1994-2003, Department of Health and Human Services, Health Resources and Services Administration, Healthcare Systems Bureau, Division of Transplantation; United Network of Organ Sharing; University Renal Research and Education Association, 2004. 3. US Renal Data System: USRDS 2003 Annual Data Report; Atlas of End-Stage Renal Diseases in the United States, Bethesda, National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, 2003.
47
4. Tyan D, Li VA, Czer L. Trento A, Jordan SC. Intravenous immunoglobulin suppression of HLA alloantibody in highly sensitized transplant candidates and transplantation with a histocompatible organ. Transplantation, 1994; 57: 553-562. 5. Kazatchkine MD, Kaveri SV. Immunomodulation of autoimmune and inflammatory diseases with intravenous immune globulin. N Engl J Med, 2001; 345: 747-755. 6. Pescovitz MD. The use of Rituximab, antiCD20 monoclonal antibody, in pediatric transplantation. Pediatr Transplant, 2005; 45: 274-280. 7. Vo AA, Toyoda M, Peng A, Bunnapradist S, Lukovsky M, Jordan SC. Effect of induction therapy protocols on transplant outcomes in crossmatch positive renal allograft recipients desensitized with IVIG. Am J Transplant, 2006; 6: 2384-2390. 8. Montgomery RA, Zachary AA, Racusen LC, et al. Plasmapheresis and intravenous immunoglobulin provides effective rescue therapy for refractory humoral rejection and allows kidneys to be successfully transplanted into crossmatch positive recipients. Transplantation, 2000; 70: 887-895. 9. Stegall MD, Gloor J, Winters JL, Moore SB, DeGoey S. A comparison of plasmapheresis versus high-dose IVIG desensitization in renal allograft recipients with high levels of donor specific antibody. AM J Transplant, 2006; 6: 346-351. 10. Jordan SC, Tyan D, Stablein D, et al. Evaluation of intravenous immunoglobulin as an agent to lower allosensitization and improve transplantation in highly sensitized adult patients with end stage renal disease: Report of the NIH ICOG2 trial. J Am Soc Nephrol, 2004; 15: 3256-3262. 11. Ye Q, Wang L, Wells AD. BAFF binding to T cell expressed BAFF-R costimulates T cell proliferation and alloresponses. Eur J of Immunology, 2004; 34: 2750-2759. 12. Bhat P, Rhadhakrishnan J. B lymphocytes and lupus nephritis: new insights into pathogenesis and targeted therapies. Kidney Intern, 2008; 73: 261-268. 13. Morimoto S, Nakano S, Watanabe T. Expression of the B-cell activating factor of the tumor necrosis factor family (BAFF) in T cells in active systemic lupus erythematosus: the role of BAFF in T-cell dependent B cell pathogenic autoantibody production. Rheumatology (Oxford), 2007; 46: 1083-1086.
OƒπA∫Oπ ¢OΔE™ ∫Aπ §∏¶ΔE™ ∏¶AΔπ∫ø¡ ªO™ÃEYªAΔø¡
ZÒÓÙ˜ Û˘ÁÁÂÓ›˜ ‰fiÙ˜ Ë·ÙÈÎÔ‡ ÌÔۯ‡̷ÙÔ˜ π. ºÔ‡˙·˜, ¢. Δ·ÎÔ‡‰·˜
Oƒπ™ªOπ – π™ΔOƒπ∫∏ ∞¡∞¢ƒOª∏
‰ÔÙÒÓ Û ÂÓ‹ÏÈΘ (adult to adult living donor liver transplantation, aLDLTx, Hashikura 1994)13,14.
H ÙÌËÌ·ÙÈ΋ ÌÂÙ·ÌfiÛ¯Â˘ÛË ‹·ÙÔ˜ Â›Ó·È Ì›· Ó¤· ¯ÂÈÚÔ˘ÚÁÈ΋ Ù¯ÓÈ΋ Ë ÔÔ›· Û˘Ó›ÛÙ·Ù·È ÛÙËÓ ÂÎÙÔÌ‹ ÙÌËÌ¿ÙˆÓ ÙÔ˘ ‹·ÙÔ˜ ·fi ˙ÒÓÙ˜ ‹ و̷ÙÈÎÔ‡˜ ‰fiÙ˜ Î·È ÙË ÌÂÙ·ÌfiÛ¯Â˘ÛË ÙÔ˘˜ ÛÙÔ˘˜ Ï‹Ù˜ (·È‰È¿ Î·È ÂÓ‹ÏÈΘ)1. B·Û›˙ÂÙ·È ÛÙË ÏÂÈÙÔ˘ÚÁÈ΋ ·Ó·ÙÔÌÈ΋ Î·È ÙËÓ ·Ó·ÁÂÓÓËÙÈ΋ ÈηÓfiÙËÙ· ÙÔ˘ ‹·ÙÔ˜, Ë ÔÔ›· ÂÈÙÚ¤ÂÈ ÙÔÓ ‰È·¯ˆÚÈÛÌfi ÙÔ˘ Û ÂÈ̤ÚÔ˘˜ ÙÌ‹Ì·Ù·, Ì ·˘ÙfiÓÔÌË ·ÁÁ›ˆÛË Î·È ·ÚÔ¯¤Ù¢ÛË Î·È Â·Ú΋ Ì¿˙· Ë·ÙÔ΢ÙÙ¿ÚˆÓ ÁÈ¿ Ó· ηχ„Ô˘Ó ÙȘ ÌÂÙ·‚ÔÏÈΤ˜ ·Ó¿ÁΘ ÙfiÛÔ ÙÔ˘ ‰fiÙË fiÛÔ Î·È ÙÔ˘ Ï‹ÙË, ÂÓÒ Ù·˘Ùfi¯ÚÔÓ· ·Ó·ÁÂÓÓÒÓÙ·È2,3. H ÙÌËÌ·ÙÈ΋ ÌÂÙ·ÌfiÛ¯Â˘ÛË ‹·ÙÔ˜ ÚÔ‹Ïı ·fi Ì›· ÛÂÈÚ¿ ÂÁ¯ÂÈÚËÙÈÎÒÓ ÂÈÓÔ‹ÛÂˆÓ ÔÈ Ôԛ˜ ›¯·Ó ˆ˜ ÛÙfi¯Ô ÙËÓ ·ÓÙÈÌÂÙÒÈÛË Ù˘ ‰Ú·Ì·ÙÈ΋˜ ·‡ÍËÛ˘ ÙˆÓ ÏËÙÒÓ Ë·ÙÈÎÒÓ ÌÔÛ¯Â˘Ì¿ÙˆÓ, Û ۯ¤ÛË Ì ÙÔ˘˜ ‰È·ı¤ÛÈÌÔ˘˜ و̷ÙÈÎÔ‡˜ ‰fiÙ˜4,5. ∂ȉÈÎfiÙÂÚ·, ÙÔ ·Ú¯ÈÎfi ΛÓËÙÚÔ ÁÈ¿ ÙËÓ ÙÚÔÔÔ›ËÛË Ù˘ ÎÏ·ÛÈ΋˜ Ù¯ÓÈ΋˜ Ù˘ ÔÚıÔÙÔÈ΋˜ ÌÂÙ·ÌfiÛ¯Â˘Û˘ ‹·ÙÔ˜ ‹Ù·Ó ¤ÏÏÂÈ„Ë ·È‰È·ÙÚÈÎÒÓ ÙˆÌ·ÙÈÎÒÓ ÌÔÛ¯Â˘Ì¿ÙˆÓ, Ì ·ÔÙ¤ÏÂÛÌ· Ë ıÓËÙfiÙËÙ· ÛÙȘ Ï›ÛÙ˜ ·Ó·ÌÔÓ‹˜ ·È‰È·ÙÚÈÎÒÓ ·ÛıÂÓÒÓ Ó· ÍÂÂÚÓ¿ ÙÔ 25%, Û ÔÚÈṲ̂ӷ ÌÂÙ·ÌÔÛ¯Â˘ÙÈο ΤÓÙÚ·6. ∏ ÚÔÛ¿ıÂÈ· ÁÈ· ÙËÓ ·ÓÙÈÌÂÙÒÈÛË ·˘ÙÔ‡ ÙÔ˘ ÚÔ‚Ï‹Ì·ÙÔ˜ Ô‰‹ÁËÛÂ, ·Ú¯Èο, ÛÙË ÌÂÙ·ÌfiÛ¯Â˘ÛË ÌÂȈ̤ÓÔ˘ ÌÂÁ¤ıÔ˘˜ و̷ÙÈÎÒÓ ÌÔÛ¯Â˘Ì¿ÙˆÓ ÂÓËÏ›ÎˆÓ (reduced-size liver transplantation, RLTx, Bismuth, 1984),7 ÂÓÒ ÛÙË Û˘Ó¤¯ÂÈ· ·Ó·Ù‡¯ıËÎ·Ó ÔÈ Ù¯ÓÈΤ˜ ÙÔ˘ ex vivo (Pichlmayr, 1988) Î·È ÙÔ˘ in situ (Rogiers Î·È Broelsch, 1995) ‰È·¯ˆÚÈÛÌÔ‡ ÙˆÓ Ë·ÙÈÎÒÓ ÌÔÛ¯Â˘Ì¿ÙˆÓ (split liver transplantation, SLTx),8-10 Ù˘ ÌÂÙ·ÌfiÛ¯Â˘Û˘ ÙÌ‹Ì·ÙÔ˜ ÙÔ˘ ‹·ÙÔ˜ ˙ÒÓÙˆÓ ÂÓËÏ›ÎˆÓ ‰ÔÙÒÓ Û ·È‰È¿ (adult-to-pediatric living donor liver transplantation, pLDLTx, Strong 1990 Î·È Broelsch 1991)11,12 Î·È ÙÂÏÈο Ù˘ ÌÂÙ·ÌfiÛ¯Â˘Û˘ ÙÌ‹Ì·ÙÔ˜ ÙÔ˘ ‹·ÙÔ˜ ˙ÒÓÙˆÓ ÂÓËϛΈÓ
ª∂Δ∞ªO™Ã∂À™∏ ∏¶∞ΔO™ ∞¶O ™À°°∂¡∂π™ ∑ø¡Δ∂™ ¢OΔ∂™ ∏ ÌÂÙ·ÌfiÛ¯Â˘ÛË ·fi Û˘ÁÁÂÓ›˜ ‰fiÙ˜ ¤¯ÂÈ ·Ó·‰Âȯı› Û ÛËÌ·ÓÙÈÎfi ·Ú¿ÁÔÓÙ· ·‡ÍËÛ˘ ÙÔ˘ ·ÚÈıÌÔ‡ ÙˆÓ Ë·ÙÈÎÒÓ ÌÔÛ¯Â˘Ì¿ÙˆÓ Î·È ¤¯ÂÈ ‰ÈÂÓÂÚÁËı› Û ÂÚÈÛÛfiÙÂÚ· ·fi 14000 ·È‰È¿ Î·È ÂÓ‹ÏÈΘ, ·fi ÙÔ 1989 ̤¯ÚÈ ÙÔ 200715. Δ· ÏÂÔÓÂÎÙ‹Ì·Ù· Ù˘ LDLTx, Û ۯ¤ÛË Ì ÙËÓ ÌÂÙ·ÌfiÛ¯Â˘ÛË ·fi و̷ÙÈÎfi ‰fiÙË, Â›Ó·È fiÙÈ ÌÔÚ› Ó· ÚÔÁÚ·ÌÌ·ÙÈÛı› ÚÈÓ Ë Î·Ù¿ÛÙ·ÛË ÙÔ˘ Ï‹ÙË ÂȉÂÈÓˆı› Û ÌË ·Ó·ÛÙÚ¤„ÈÌÔ ÛËÌ›Ô, Ó· ÂÈÏÂÁ› Ô Î·Ï‡ÙÂÚÔ˜ ‰˘Ó·Ùfi˜ ‰fiÙ˘, Ì ÌfiÛ¯Â˘Ì· Ì Ôχ ÌÈÎÚfi ¯ÚfiÓÔ „˘¯Ú‹˜ ÈÛ¯·ÈÌ›·˜, ÂÓÒ ÚÔÛʤÚÂÈ Î·È ÙËÓ ‰˘Ó·ÙfiÙËÙ· ¤ÎÙ·Û˘ ÙˆÓ ÎÚÈÙËÚ›ˆÓ ÂÈÏÔÁ‹˜ ÙˆÓ ÏËÙÒÓ Î·È ÙÂÏÈο ÌÂÈÒÓÂÈ ÙË ıÓËÙfiÙËÙ· Û ۯ¤ÛË Ì ÙËÓ ·Ú·ÌÔÓ‹ ÛÙË Ï›ÛÙ· ·Ó·ÌÔÓ‹˜16. ∞fi ÙËÓ ¿ÏÏË ÏÂ˘Ú¿, Ë Â¤Ì‚·ÛË ·ÚÔ˘ÛÈ¿˙ÂÈ ‰˘ÓËÙÈ΋ ÓÔÛËÚfiÙËÙ· Î·È ıÓËÙfiÙËÙ· 200% (100% ÁÈ· ÙÔÓ ‰fiÙË Î·È ÁÈ· ÙÔÓ Ï‹ÙË) Î·È Ú¤ÂÈ Ó· ·ÔÊ·Û›˙ÂÙ·È Î·È Ó· ‰ÈÂÓÂÚÁÂ›Ù·È Ì ÔÏÏ‹ ÚÔÛÔ¯‹, ·fi ÂÍÂȉÈÎÂ˘Ì¤Ó· ΤÓÙÚ·.
∂¶π§O°∏ ΔOÀ ¢OΔ∏ ™ÙËÓ ∂ÏÏ¿‰· Ë Ï‹„Ë ÔÚÁ¿ÓˆÓ ·fi ˙ÒÓÙ· ‰fiÙË Î·ıÔÚ›˙ÂÙ·È ·fi ÙÔ ÓfiÌÔ 2737/27.8.1999 Î·È ÂÈÙÚ¤ÂÙ·È ÌfiÓÔ ÌÂٷ͇ Û˘ÁÁÂÓÒÓ ÂÍ ·›Ì·ÙÔ˜, ̤¯ÚÈ Î·È ÙÔ ‰Â‡ÙÂÚÔ ‚·ıÌfi Û ¢ı›· ‹ Ï¿ÁÈ· ÁÚ·ÌÌ‹, ›Ù ÛÂ Û˘ÁÁÂÓ›˜ ÂÍ ·Á¯ÈÛÙ›·˜ (Û˘˙‡ÁÔ˘˜). ∂ÈϤÔÓ, ÙÔ ¿ÙÔÌÔ Ô˘ ÂÈϤÁÂÙ·È ÁÈ· ‰ˆÚ¿ ÙÌ‹Ì·ÙÔ˜ ÙÔ˘ ‹·ÙÔ˜ Ú¤ÂÈ Ó· ÂÓ‹ÏÈη˜, ÓÔËÙÈο ÈηÓfi˜, „˘¯Èο ˘ÁÈ‹˜ Î·È Ï‹Úˆ˜ ÂÓËÌÂڈ̤ÓÔ˜ ÁÈ· ÙÔ˘˜ ÎÈÓ‰‡ÓÔ˘˜ Ù˘ ÂÂÌ‚¿Ûˆ˜ Ô˘ ı· ˘ÔÛÙ› Î·È ÁÈ· ÙȘ ÂÓ·ÏÏ·ÎÙÈΤ˜ χÛÂȘ ÁÈ· ÙËÓ ıÂڷ›· ÙÔ˘ Ï‹ÙË. ¢ÂÓ Ú¤ÂÈ Ó· ˘¿Ú¯ÂÈ ÔÈÎÔÓÔÌÈ΋ Û˘Ó·ÏÏ·Á‹ ÌÂٷ͇ Ï‹ÙË Î·È ‰fiÙË Ô‡ÙÂ Î·È „˘¯ÔÏÔÁÈÎfi˜ Â΂ȷÛÌfi˜.
51
52
π. ºOÀ∑∞™, ¢. Δ∞∫OÀ¢∞™
Δ· ÎÚÈÙ‹ÚÈ· ÂÈÏÔÁ‹˜ ‰È·Ê¤ÚÔ˘Ó ÛÙȘ ‰È¿ÊÔÚ˜ ¯ÒÚ˜ ÙÔ˘ ÎfiÛÌÔ˘, ·Ó¿ÏÔÁ· Ì ÙȘ ÓÔÌÈΤ˜ Î·È ÔÏÈÙÈÛÙÈΤ˜ ȉȷÈÙÂÚfiÙËÙ˜. ∏ ËÏÈΛ· ÙÔ˘ ‰fiÙË, ÛÙȘ ÂÚÈÛÛfiÙÂÚ˜ ¯ÒÚ˜, Â›Ó·È ÌÂٷ͇ 18 Î·È 60 ÂÙÒÓ. OÈ ÌÂÁ·Ï‡ÙÂÚÔÈ Û ËÏÈΛ· ‰fiÙ˜ ·ÚÔ˘ÛÈ¿˙Ô˘Ó ·˘ÍË̤ÓÔ Î›Ó‰˘ÓÔ ÁÈ· ·‰È¿ÁÓˆÛÙ· ÚÔ‚Ï‹Ì·Ù· ˘Á›·˜. ∂ÈϤÔÓ, ÈÛÙ‡ÂÙ·È fiÙÈ Ë ËÏÈΛ· ÂËÚ¿˙ÂÈ ÙËÓ ·Ó·ÁÂÓÓËÙÈ΋ ÈηÓfiÙËÙ· ÙÔ˘ ‹·ÙÔ˜, ÌÂ Û˘Ó¤ÂȘ ÙfiÛÔ ÛÙÔÓ ‰fiÙË fiÛÔ Î·È ÛÙÔÓ Ï‹ÙË17. ∏ ÔÌ¿‰· ·›Ì·ÙÔ˜ ÙÔ˘ ‰fiÙË Ú¤ÂÈ Ó· Â›Ó·È Ù·˘ÙfiÛËÌË ‹ Û˘Ì‚·Ù‹ Ì ÂΛÓË ÙÔ˘ Ï‹ÙË. ™Â ÂȉÈΤ˜ ÂÚÈÙÒÛÂȘ ÌÔÚ› Ó· ‰ÈÂÓÂÚÁËı› ÌË Û˘Ì‚·Ù‹ ÌÂÙ·ÌfiÛ¯Â˘ÛË, fiˆ˜ Û ‚Ú¤ÊË ÌÈÎÚfiÙÂÚ· ÙÔ˘ ÂÓfi˜ ¤ÙÔ˘˜ Ô˘ ‰ÂÓ ¤¯Ô˘Ó ·Ó·Ù‡ÍÂÈ ·ÎfiÌË ·ÓÙÈÛÒÌ·Ù· ¤Ó·ÓÙÈ ÙˆÓ ÔÌ¿‰ˆÓ ·›Ì·ÙÔ˜ ‹ ۠›ÁÔ˘Û˜ ÂÚÈÙÒÛÂȘ ÛÙȘ Ôԛ˜ ‰ÂÓ ˘¿Ú¯ÂÈ Û˘Ì‚·Ùfi و̷ÙÈÎfi ÌfiÛ¯Â˘Ì·18,19. ¶ÚfiÛÊ·Ù·, ¤¯Ô˘Ó ‰ËÌÔÛÈ¢ı› ÌÈÎÚ¤˜ ÛÂÈÚ¤˜ Ì ÂÈÙ˘¯Â›˜ ÌË Û˘Ì‚·Ù¤˜ ÌÂÙ·ÌÔۯ‡ÛÂȘ ÌÂÙ¿ ·fi ¤ÓÙÔÓË ÂȉÈ΋ ÚÔÂÙÔÈÌ·Û›· ·Â˘·ÈÛıËÙÔÔ›ËÛ˘20.
¶ÚÔÂÁ¯ÂÈÚËÙÈÎfi˜ ¤ÏÂÁ¯Ô˜ ÙÔ˘ ‰fiÙË O ÚÔÂÁ¯ÂÈÚËÙÈÎfi˜ ¤ÏÂÁ¯Ô˜ Á›ÓÂÙ·È ÌÂ Û˘ÁÂÎÚÈ̤ÓÔ ÚˆÙfiÎÔÏÔ Î·È ·ÔÛÎÔ› ÙfiÛÔ ÛÙËÓ ·ÔÊ˘Á‹ ÂÈÏÔÎÒÓ ·fi ÙÔÓ ‰fiÙË, fiÛÔ Î·È ÛÙËÓ ÂÍ·ÛÊ¿ÏÈÛË ÙÔ˘ ηٷÏÏËÏfiÙÂÚÔ˘ ÌÔۯ‡̷ÙÔ˜ ÁÈ· ÙÔÓ Ï‹ÙË. O ¤ÏÂÁ¯Ô˜ Á›ÓÂÙ·È Î·Ù¿ ÛÙ¿‰È·, ·fi ÙȘ ÏÈÁfiÙÂÚÔ ÚÔ˜ ÙȘ ÂÚÈÛÛfiÙÂÚÔ ÂÂÌ‚·ÙÈΤ˜ ÂÍÂÙ¿ÛÂȘ, ·ÏÏ¿ Ù·˘Ùfi¯ÚÔÓ· Ú¤ÂÈ Ó· ·ÔÎÏ›ÂÈ ÙÔ˘˜ ·Î·Ù¿ÏÏËÏÔ˘˜ ‰fiÙ˜ fiÛÔ ÙÔ ‰˘Ó·ÙfiÓ ÓˆÚ›ÙÂÚ· (¶›Ó·Î·˜ 1)21. O ‰fiÙ˘ ‰ÂÓ Ú¤ÂÈ Ó· ¿Û¯ÂÈ ·fi ÔÔÈ·‰‹ÔÙ ÓfiÛÔ Ë ÔÔ›· ·˘Í¿ÓÂÈ ÙÔÓ ÂÚÈÂÁ¯ÂÈÚËÙÈÎfi ΛӉ˘ÓÔ Ù˘ Ë·ÙÂÎÙÔÌ‹˜, Ô‡Ù ӷ Â›Ó·È ˘¤Ú‚·ÚÔ˜ (μªπ >30 Kg/m2) (¶›Ó·Î·˜ 2)15. OÈ ·¯‡Û·ÚÎÔÈ ‰fiÙ˜ ·ÚÔ˘ÛÈ¿˙Ô˘Ó ÌÂÁ¿ÏË Èı·ÓfiÙËÙ· ÏÈÒ‰Ô˘˜ ‰ÈËı‹Ûˆ˜ ÙÔ˘ ‹·ÙÔ˜ ÌÂ Û˘Ó¤ÂÈ· ÙËÓ ·‡ÍËÛË ÙÔ˘ ÎÈÓ‰‡ÓÔ˘ ÌÂÙÂÁ¯ÂÈÚËÙÈ΋˜ Ë·ÙÈ΋˜ ·Ó¿ÚÎÂÈ·˜ ÙfiÛÔ ÛÙÔÓ ‰fiÙË fiÛÔ Î·È ÛÙÔÓ Ï‹ÙË15. OÚÈṲ̂ӷ ΤÓÙÚ· ··ÈÙÔ‡Ó ‚ÈÔ„›· ‹·ÙÔ˜ ÁÈ· ÙÔÓ ·ÔÎÏÂÈÛÌfi Ù˘ ÏÈÒ‰Ô˘˜ ‰ÈËı‹Ûˆ˜, ÂÓÒ ¿ÏÏ·
¶›Ó·Î·˜ 1. ¶ÚˆÙfiÎÔÏÔ ÚÔÂÁ¯ÂÈÚËÙÈÎÔ‡ ÂϤÁ¯Ô˘ / ÚÔÂÙÔÈÌ·Û›·˜ ‰ÔÙÒÓ22. ™Ù¿‰ÈÔ 1 ∫ÏÈÓÈ΋ ÂͤٷÛË, ÈÛÙÔÚÈÎfi, ÂÓË̤ڈÛË ÁÈ· ÙÔ˘˜ ÎÈÓ‰‡ÓÔ˘˜ Ù˘ ÂÂÌ‚¿Ûˆ˜ ∂ÚÁ·ÛÙËÚÈ·Îfi˜ ¤ÏÂÁ¯Ô˜: °ÂÓÈ΋ ·›Ì·ÙÔ˜, ‚ÈÔ¯ËÌÈÎfi˜ ¤ÏÂÁ¯Ô˜, ËÎÙÈÎfi˜ Ì˯·ÓÈÛÌfi˜, ÔÚÔÏÔÁÈÎfi˜ ¤ÏÂÁ¯Ô˜: HAV, HBV, HCV, EBV, CMV, HSV, HIV. ÀÔÁÚ·Ê‹ Ù˘ 1˘ ·Ô‰Ô¯‹˜ Ù˘ ÂÂÌ‚¿Ûˆ˜ ™Ù¿‰ÈÔ 2 ∞ÂÈÎÔÓÈÛÙÈΤ˜ ÂÍÂÙ¿ÛÂȘ: ∂ÏÈÎÔÂȉ‹˜ ·ÍÔÓÈ΋ ÙÔÌÔÁÚ·Ê›· ‹·ÙÔ˜ Ì ̤ÙÚËÛË ÙÔ˘ fiÁÎÔ˘ ÙÔ˘ ÌÔۯ‡̷ÙÔ˜, ·ÁÁÂÈÔÁÚ·Ê›· ·ÔÚÙ‹˜ Î·È Ë·ÙÈ΋˜ ·ÚÙËÚ›·˜, ˘Ï·›·˜ ÊϤ‚·˜, οو ÎÔ›Ï˘ Î·È Ë·ÙÈÎÒÓ ÊÏ‚ÒÓ Î·È ¯ÔÏ·ÁÁÂÈÔÁÚ·Ê›· ‹ Ì·ÁÓËÙÈ΋ ¯ÔÏ·ÁÁÂÈÔÁÚ·Ê›·. μÈÔ„›· ‹·ÙÔ˜, fiÙ·Ó ÂӉ›ÎÓ˘Ù·È23. 1Ë „˘¯È·ÙÚÈ΋ ÂÎÙ›ÌËÛË ™Ù¿‰ÈÔ 3 ∫·Ú‰ÈÔÏÔÁÈÎfi˜ ¤ÏÂÁ¯Ô˜ (∏∫°, ˘ÂÚ˯ÔηډÈÔÁÚ¿ÊËÌ·, test ÎÔÒÛˆ˜), Ó¢ÌÔÓÔÏÔÁÈÎfi˜ ¤ÏÂÁ¯Ô˜, ÂȉÈΤ˜ ‚ÈÔ¯ËÌÈΤ˜ ÂÍÂÙ¿ÛÂȘ (TSH, FT3, FT4, IgA, IgG, IgM, Fe, ÙÚ·ÓÛÊÂÚÚ›ÓË, ·1-·ÓÙÈıÚ˘„›ÓË, ÛÂÚÔ˘ÏÔÏ·ÛÌ›ÓË, ·Ú¿ÁÔÓÙ˜ ‹Íˆ˜ (V, VII, VIII, C, S, APC), ηÚÎÈÓÈÎÔ› ‰Â›ÎÙ˜ (CEA, AFP, Ca 19-9), Ô‡Ú· 24ÒÚÔ˘. 1Ë ·Ê·›Ì·ÍË ÁÈ· ·˘ÙfiÏÔÁË ÌÂÙ¿ÁÁÈÛË ·›Ì·ÙÔ˜ ™Ù¿‰ÈÔ 4 2Ë „˘¯È·ÙÚÈ΋ ÂÎÙ›ÌËÛË ∏·ÙÔÏÔÁÈÎfi meeting 2Ë ·Ê·›Ì·ÍË ÁÈ· ·˘ÙfiÏÔÁË ÌÂÙ¿ÁÁÈÛË ·›Ì·ÙÔ˜ ™Ù¿‰ÈÔ 5 ∞ÓÔÛÔÏÔÁÈÎfi˜ ¤ÏÂÁ¯Ô˜ [HLAs, ‰È·ÛÙ·˘ÚÔ‡ÌÂÓË ·ÓÙ›‰Ú·ÛË (cross match)] ∞Ó·ÈÛıËÛÈÔÏÔÁÈ΋ ÂÎÙ›ÌËÛË ŒÏÂÁ¯Ô˜ ÂÈÙÚÔ‹˜ μÈÔËıÈ΋˜ ÀÔÁÚ·Ê‹ Ù˘ ÙÂÏÈ΋˜ ·Ô‰Ô¯‹˜ Ù˘ ÂÂÌ‚¿Ûˆ˜
METAMO™XEY™Eπ™ 2008
53
¶›Ó·Î·˜ 2. ∞ÓÙÂӉ›ÍÂȘ ÂÈÏÔÁ‹˜ Û˘ÁÁÂÓÔ‡˜ ˙ÒÓÙÔ˜ ‰fiÙË Ë·ÙÈÎÔ‡ ÌÔۯ‡̷ÙÔ˜15. ¶·Ú¿ÌÂÙÚÔ˜
™ËÌÂÈÒÛÂȘ
∏ÏÈΛ·
> 60
¶·¯˘Û·ÚΛ·
μªπ > 30-35 Kg/m2
∂·ÓÂÎÙ›ÌËÛË ÌÂÙ¿ ·fi ‰›·ÈÙ·
∞ÏÎÔÔÏÈÛÌfi˜, Ó·ÚΈÙÈο ∫·Ú‰È·ÁÁÂÈ·Îfi
™ÙÂÊ·ÓÈ·›· ÓfiÛÔ˜, μ·ÚÂÈ¿ ˘¤ÚÙ·ÛË ÃÚÔÓ›· ηډȷ΋ ·Ó¿ÚÎÂÈ·
∞Ó·Ó¢ÛÙÈÎfi
ÃÚÔÓ›· ·ÔÊÚ·ÎÙÈ΋ Ó¢ÌÔÓÔ¿ıÂÈ· ¶Ó¢ÌÔÓÈ΋ ˘¤ÚÙ·ÛË
¶‹ÍË ·›Ì·ÙÔ˜
∞Ó¿ÚÎÂÈ· ÚˆÙÂ˚ÓÒÓ C ‹ S ∞ÓÙ›ÛÙ·ÛË ÛÙËÓ ÚˆÙ½ÓË C ∞ÈÌÔÚÚÔÊÈÏ›·
¡ÂÔÏ¿ÛÌ·Ù·
∫·ÎÔ‹ıË
Î·È ·‰¤ÓˆÌ· ‹·ÙÔ˜
§ÔÈÌÒÍÂȘ
HBV
HBsAg+
HCV
Anti-HCV+
EBV, CMV, HSV
IgM+
HIV ∫¿ı ÂÓÂÚÁfi˜ Ïԛ̈ÍË ¡Â˘ÚÈÎfi ™‡ÛÙËÌ·
∂ÈÏË„›·, ·ÔÌ˘ÂÏÈÓˆÙÈο ÓÔÛ‹Ì·Ù·
°∂™
∂ÏÎ҉˘ ÎÔÏ›Ùȉ· Î·È Crohn ÃÚÔÓ›· Î·È ÔÍ›· ·ÁÎÚ·ٛÙȉ·
∏¶∞ƒ
ªË ·ÏÎÔÔÏÈ΋ ÛÙ·ÙÔË·Ù›Ùȉ·
ª·ÎÚÔÊ˘ÛÛ·Ïȉ҉˘ > 10%
ÃÚÔÓ›· Ë·Ù›Ùȉ·, ›ÓˆÛË ªÂÙ·‚ÔÏÈο ÓÔÛ‹Ì·Ù·, ∂Ó‰ÔË·ÙÈ΋ ÏÈı›·ÛË ¶ÚÔËÁËı›۷ Ë·ÙÂÎÙÔÌ‹ ¡ÂÊÚÔ› ∂Ó‰ÔÎÚÈÓ›˜
ÃÚÔÓ›· ÓÂÊÚÈ΋ ·Ó¿ÚÎÂÈ· ™. ¢È·‚‹Ù˘ Ù‡Ô˘ 1 ÀÂÚ- / ˘Ôı˘ÚÂÔÂȉÈÛÌfi˜
·ÓıÂÎÙÈÎfi˜ Û ıÂڷ›·
∂ÈÓÂÊÚȉÈ΋ ·Ó¿ÚÎÂÈ· ∞ÓÔÛÔÔÈËÙÈÎfi
∞˘ÙÔ¿ÓÔÛ· Û˘ÛÙËÌ·ÙÈο ÓÔÛ‹Ì·Ù·
·ÚÎÔ‡ÓÙ·È ÛÙȘ ·ÂÈÎÔÓÈÛÙÈΤ˜ ÂÍÂÙ¿ÛÂȘ22. ™‡Ìʈӷ Ì ÙÔ Vancouver Forum,23 ‚ÈÔ„›· ‹·ÙÔ˜ Ú¤ÂÈ Ó· ‰ÈÂÓÂÚÁÂ›Ù·È ÌfiÓÔ fiÙ·Ó ˘¿Ú¯Ô˘Ó ÂӉ›ÍÂȘ ·fi ÙÔÓ ÂÚÁ·ÛÙËÚÈ·ÎÔ Î·È ÙÔÓ ·ÂÈÎÔÓÈÛÙÈÎfi ¤ÏÂÁ¯Ô ÁÈ· ÛÙ¿وÛË, fiÙ·Ó Ô ‰fiÙ˘ Â›Ó·È ·¯‡Û·ÚÎÔ˜ (μªπ >30 Kg/m2), ‹ fiÙ·Ó ÚfiÎÂÈÙ·È ÁÈ· Û˘ÁÁÂÓ‹ Ï‹ÙË Ì ·˘ÙÔ¿ÓÔÛÔ Ë·Ù›Ùȉ·, ÚˆÙÔ·ı‹ ¯ÔÏÈ΋ ΛÚÚˆÛË, ‹ ÚˆÙÔ·ı‹ ÛÎÏËÚ˘ÓÙÈ΋ ¯ÔÏ·ÁÁÂÈ›Ùȉ·. ∂ÈϤÔÓ, Ù· ÈÛÙÔÏÔÁÈο ÎÚÈÙ‹ÚÈ· ·ÔÎÏÂÈÛÌÔ‡ ˙ÒÓÙÔ˜ ‰fiÙË ‹·ÙÔ˜ ›ӷÈ: ·) ˘Ï·›· ‹ ÂÚÈÎÔÏÔÂȉÈ΋ ›ÓˆÛË, ‚) ÌË ·ÏÎÔÔÏÈ΋ ÛÙ·ÙÔË·Ù›Ùȉ·, Á) ÛÙ¿وÛË > 20% (Û ‰fiÙ˜ ‰ÂÍÈÔ‡ ‹·ÙÔ˜) Î·È ‰) ÊÏÂÁÌÔÓÒ‰Ë ‹ ÓÂÎÚˆÙÈο ÛÙÔȯ›· ÛÙȘ ˘Ï·›Â˜ ÙÚÈ¿‰Â˜23.
∞ÂÈÎÔÓÈÛÙÈÎfi˜ ¤ÏÂÁ¯Ô˜ O ÚÔÂÁ¯ÂÈÚËÙÈÎfi˜ ·ÂÈÎÔÓÈÛÙÈÎfi˜ ¤ÏÂÁ¯Ô˜ ·ÔÛÎÔ› ÛÙËÓ ÂÎÙ›ÌËÛË Ù˘ ¿ÚÎÂÈ·˜ ÙÔ˘ fiÁÎÔ˘
ÙÔ˘ Ë·ÙÈÎÔ‡ ·ÚÂÁ¯‡Ì·ÙÔ˜, ÛÙË ‰È·Ï‡ηÓÛË Ù˘ ·Ó·ÙÔÌÈ΋˜ ÙˆÓ ·ÁÁ›ˆÓ ÙÔ˘ ‹·ÙÔ˜ Î·È ÙˆÓ ¯ÔÏËÊfiÚˆÓ Î·È ÛÙÔÓ Û¯Â‰È·ÛÌfi Ù˘ ÂÂÌ‚¿Ûˆ˜.
ª¤ÙÚËÛË ÙÔ˘ fiÁÎÔ˘ ÙÔ˘ Ë·ÙÈÎÔ‡ ÌÔۯ‡̷ÙÔ˜ ∏ ÚÔÂÁ¯ÂÈÚËÙÈ΋ ÂÎÙ›ÌËÛË Ù˘ ¿ÚÎÂÈ·˜ ÙÔ˘ fiÁÎÔ˘ ÙÔ˘ Ë·ÙÈÎÔ‡ ·ÚÂÁ¯‡Ì·ÙÔ˜, ÙfiÛÔ ÁÈ· ÙÔÓ ‰fiÙË fiÛÔ Î·È ÁÈ· ÙÔÓ Ï‹ÙË, ‰ÈÂÓÂÚÁÂ›Ù·È Ì ‚¿ÛË Ì ‰‡Ô ÌÂıfi‰Ô˘˜: ·. ÙÔ Â› ÙÔȘ ÂηÙfi ÔÛÔÛÙfi Ô˘ ·ÔÙÂÏ› Ô fiÁÎÔ˜ ÙÔ˘ ÌÔۯ‡̷ÙÔ˜ Û ۯ¤ÛË Ì ÙÔÓ Î·Ù’ ÂÎÙ›ÌËÛË Ê˘ÛÈÔÏÔÁÈÎfi fiÁÎÔ ‹·ÙÔ˜ ÙÔ˘ Ï‹ÙË (standard liver volume, SLV), Ì ‚¿ÛË ÛˆÌ·ÙÔÌÂÙÚÈΤ˜ ÂÍÈÛÒÛÂȘ24-27 Î·È ∂ÈÊ¿ÓÂÈ· ÛÒÌ·ÙÔ˜ (BSA m2) (Du Bois)24 = 0.007184 á ⁄„Ô˜ (cm)0.725 á μ¿ÚÔ˜ (Kg)0.425 ÀÔÏÔÁÈÛÌfi˜ fiÁÎÔ˘ ‹·ÙÔ˜ ŸÁÎÔ˜ ‹·ÙÔ˜ (mL) (Urata)25 = 706.2 á BSA (m2) + 2.4
54
π. ºOÀ∑∞™, ¢. Δ∞∫OÀ¢∞™
ŸÁÎÔ˜ ‹·ÙÔ˜ (mL) (Heinemann)26 = 1072.8 á BSA (m2) – 345.7
ŸÁÎÔ˜ ‹·ÙÔ˜ (Vauthey)27 = –794.41 + 1,267.28 á BSA (m2)
‚. ÙÔ Â› ÙÔȘ ÂηÙfi ÔÛÔÛÙfi Ô˘ ·ÔÙÂÏ› ÙÔ ‚¿ÚÔ˜ ÙÔ˘ ÌÔۯ‡̷ÙÔ˜ Û ۯ¤ÛË Ì ÙÔ ‚¿ÚÔ˜ ÙÔ˘ ÛÒÌ·ÙÔ˜ ÙÔ˘ Ï‹ÙË (Graft Weight/Recipient Body Weight Ratio, GW/RBW)28. OÈ ·ÓˆÙ¤Úˆ ‰Â›ÎÙ˜ ·ÚÔ˘ÛÈ¿˙Ô˘Ó Ôχ ηϋ ÁÚ·ÌÌÈ΋ Û˘Û¯¤ÙÈÛË Î·È Ë ÙÈÌ‹ GW/RBW 1% ·ÓÙÈÛÙÔȯ›, ÂÚ›Ô˘, Û 50% ÙÔ˘ SLV29. AÓÙ›ıÂÙ·, Ë Û˘Û¯¤ÙÈÛË ÌÂٷ͇ ÙÔ˘ ‚¿ÚÔ˘˜ ÙÔ˘ ÛÒÌ·ÙÔ˜ ÙÔ˘ ‰fiÙË Î·È ÙÔ˘ ‚¿ÚÔ˘˜ ÙÔ˘ ÙÌËÌ·ÙÈÎÔ‡ ÌÔۯ‡̷ÙÔ˜ ‰ÂÓ Â›Ó·È È‰È·›ÙÂÚ· ÈÛ¯˘Ú‹ Î·È ÁÈ’ ·˘Ùfi, ÛÙÔ˘˜ Û˘ÁÁÂÓ›˜ ˙ÒÓÙ˜ ‰fiÙ˜, ··ÈÙÂ›Ù·È ÚÔÂÁ¯ÂÈÚËÙÈ΋ ̤ÙÚËÛË ÙÔ˘ fiÁÎÔ˘ ÙÔ˘ ÌÔۯ‡̷ÙÔ˜ Ì ·ÍÔÓÈ΋ ‹ Ì·ÁÓËÙÈ΋ ÙÔÌÔÁÚ·Ê›·,30 (∂ÈÎfiÓ˜ 1 Î·È 2). ∫·È Ë Ì¤ÙÚËÛË ·˘Ù‹, fï˜, ˘ÂÚÂÎÙÈÌ¿ ÙÔÓ fiÁÎÔ ÙÔ˘ ÌÔۯ‡̷ÙÔ˜ ηٿ 10%, Û ۯ¤ÛË Ì ÙÔ ‚¿ÚÔ˜ ÙÔ˘ ÌÂÙ¿ ÙËÓ ÂÎÙÔÌ‹31. ∏ ‰È·ÊÔÚ¿ ·˘Ù‹ ·Ô‰›‰ÂÙ·È ÛÙÔÓ fiÁÎÔ ÙÔ˘ ·›Ì·ÙÔ˜. ∏ ·ÛÊ¿ÏÂÈ· ÙÔ˘ ‰fiÙË ··ÈÙ› ‰È·Ù‹ÚËÛË ÙÔ˘ 30% ÙÔ˘ Ë·ÙÈÎÔ‡ ·ÚÂÁ¯‡Ì·ÙÔ˜ Ì ·Ú΋ ÊÏ‚È΋ ·ÚÔ¯¤Ù¢ÛË, ÂÓÒ ÛÙÔÓ Ï‹ÙË Ú¤ÂÈ Ó· ÌÂÙ·ÌÔÛ¯Â˘ı› ÙÔ˘Ï¿¯ÈÛÙÔÓ ÙÔ 0.8% ÙÔ˘ GW/RBW23. OÈ Ù‡ÔÈ ÙˆÓ Ë·ÙÈÎÒÓ ÌÔÛ¯Â˘Ì¿ÙˆÓ Ô˘ ¯ÚËÛÈÌÔÔÈÔ‡ÓÙ·È ÛÙȘ ÌÂÙ·ÌÔۯ‡ÛÂȘ ·Ô ˙ÒÓÙ· ‰fiÙË Â›Ó·È: 1. TÔ ‰ÂÍÈfi ‹·Ú (ÙÌ‹Ì·Ù· V-VIII, ∼ 800-1000 ml, ÁÈ· ÂÓ‹ÏÈη ‚¿ÚÔ˘˜ ∼ 80 Kgr), 2. TÔ ·ÚÈÛÙÂÚfi ‹·Ú (ÙÌ‹Ì·Ù· II-IV), Ì ‹ ¯ˆÚ›˜ ÙÔ
ÙÌ‹Ì· I, ∼ 400 ml ÁÈ· ÂÓ‹ÏÈη ‚¿ÚÔ˘˜ ∼ 60 Kgr), 3. O ·ÚÈÛÙÂÚfi˜ ÏÔ‚fi˜ ‹ ·ÚÈÛÙÂÚfi ¤Íˆ Ï¿ÁÈÔ ÙÌ‹Ì· (ÙÌ‹Ì·Ù· II Î·È III, ∼250 ml, ÁÈ· ¤Ó· ·È‰›), 4. O ‰ÂÍÈfi˜ ÏÔ‚fi˜ ‹ ‰ÂÍÈfi ÂÎÙÂٷ̤ÓÔ ÌfiÛ¯Â˘Ì· (ÙÌ‹Ì·Ù· I, IV, V-VIII, ∼ 1100 ml, ÁÈ· ÂÓ‹ÏÈη ‚¿ÚÔ˘˜ ≥ 80 Kgr) Î·È 5. O ‰ÂÍÈfi˜ Ô›ÛıÈÔ˜ ÙÔ̤·˜ (ÙÌ‹Ì·Ù· VI Î·È VII, ) ΔÔ ·ÚÈÛÙÂÚfi ¤Íˆ Ï¿ÁÈÔ ÙÌ‹Ì· ÌÔÚ› Ó· ‰È·¯ˆÚÈÛı› ÂÚ·ÈÙ¤Úˆ Î·È Ó· ¯ÚËÛÈÌÔÔÈËı› ÌfiÓÔ ÙÔ ÙÌ‹Ì· πππ ÁÈ· ÌÂÙ·ÌfiÛ¯Â˘ÛË Û ÌÈÎÚ¿ ‚Ú¤ÊË Î·È ÓÂÔÁÓ¿33-35.
∞ÂÈÎfiÓÈÛË ÙˆÓ ·ÁÁ›ˆÓ ÙÔ˘ ‹·ÙÔ˜ ∏ ÔχÏÔÎË ·Ó·ÙÔÌÈ΋ ÙˆÓ ·ÁÁ›ˆÓ ÙÔ˘ ‹·ÙÔ˜, ηıÒ˜ Î·È ÙÔ ˘„ËÏfi ÔÛÔÛÙfi ·Ú·ÏÏ·ÁÒÓ Î·ıÈÛÙ¿ ·Ó·Áη›· ÙËÓ ·ÎÚÈ‚‹ ÚÔÂÁ¯ÂÈÚËÙÈ΋ ·ÂÈÎfiÓÈÛË. ™Ù· ·Ú¯Èο ÛÙ¿‰È·, ÔÈ ˙ÒÓÙ˜ ‰fiÙ˜ ˘Ô‚¿ÏÏÔÓÙ·Ó Û ÂÂÌ‚·ÙÈΤ˜ ÌÂıfi‰Ô˘˜, fiˆ˜ Ë ·ÁÁÂÈÔÁÚ·Ê›· Ù˘ ·ÔÚÙ‹˜ Î·È Ù˘ Ë·ÙÈ΋˜ ·ÚÙËÚ›·˜, Ì fiÏÔ˘˜ ÙÔ˘˜ Û¯ÂÙÈÎÔ‡˜ ÎÈÓ‰‡ÓÔ˘˜ Î·È ÂÈÏÔΤ˜38. ™‹ÌÂÚ·, ÚÔÙÈÌÒÓÙ·È ÏÈÁfiÙÂÚÔ ÂÂÌ‚·ÙÈΤ˜, ·ÏÏ¿ ÙÔ ›‰ÈÔ ·ÍÈfiÈÛÙ˜ ̤ıÔ‰ÔÈ fiˆ˜ Ë ·ÚÙËÚÈÔÁÚ·Ê›· Ì ·ÍÔÓÈÎfi ÙÔÌÔÁÚ¿ÊÔ ÔÏÏ·ÏÒÓ ·ÓȯÓ¢ÙÒÓ (Multi-detector computer tomography, MDCT) ‹ Ì·ÁÓËÙÈ΋ ·ÚÙËÚÈÔÁÚ·Ê›·30,40.
ÃÔÏÏ·ÁÁÂÈÔÁÚ·Ê›· OÈ ÂÈÏÔΤ˜ ·fi Ù· ¯ÔÏËÊfiÚ·, fiˆ˜ Ë ‰È·Ê˘Á‹ ¯ÔÏ‹˜ Î·È ÔÈ ÛÙÂÓÒÛÂȘ, Â›Ó·È ÔÈ Û˘¯ÓfiÙÂÚ˜ ·Èٛ˜ ÓÔÛËÚfiÙËÙ·˜ ÌÂÙ¿ ·fi Ë·ÙÂÎÙÔÌ‹ Û ˙ÒÓÙ˜
EÈÎfiÓ· 1. ∞ÚÈÛÙÂÚ¿: ™‡ÁÎÚÈÛË ÌÂٷ͇ ÙÔ˘ ‚¿ÚÔ˘˜ ÙÔ˘ ÌÔۯ‡̷ÙÔ˜ ˆ˜ › ÙÔȘ ÂηÙfi ÔÛÔÛÙÔ‡ ÙÔ˘ ۈ̷ÙÈÎÔ‡ ‚¿ÚÔ˘˜ ÙÔ˘ ÏËÙË (Graft Weight/Recipient Body Weight Ratio, GW/RBW), Î·È ÙÔ˘ › ÙÔȘ ÂηÙfi ÔÛÔÛÙÔ‡ Ô˘ ·ÔÙÂÏ› Ô fiÁÎÔ˜ ÙÔ˘ ÌÔۯ‡̷ÙÔ˜ Û ۯ¤ÛË Ì ÙÔÓ Î·Ù’ ÂÎÙ›ÌËÛË Ê˘ÛÈÔÏÔÁÈÎfi fiÁÎÔ ‹·ÙÔ˜ ÙÔ˘ Ï‹ÙË (standard liver volume, SLV). ¢ÂÍÈ¿: ™‡ÁÎÚÈÛË ÌÂٷ͇ ÙÔ˘ ۈ̷ÙÈÎÔ‡ ‚¿ÚÔ˘˜ ÙÔ˘ Û˘ÁÁÂÓÔ‡˜ ˙ÒÓÙÔ˜ ‰fiÙË Î·È ÙÔ˘ ‚¿ÚÔ˘˜ ÙÔ˘ ÌÔۯ‡̷ÙÔ˜29.
METAMO™XEY™Eπ™ 2008
55
EÈÎfiÓ· 2. OÁÎÔÌÂÙÚÈ΋ ÌÂϤÙË ÙÔ˘ ‹·ÙÔ˜ Ì ̷ÁÓËÙÈ΋ ÙÔÌÔÁÚ·Ê›·. A. AÂÈÎfiÓÈÛË Ù˘ ÌÂıfi‰Ô˘ ÚÔÛ‰ÈÔÚÈÛÌÔ‡ ÙÔ˘ fiÁÎÔ˘ ÙÔ˘ ‹·ÙÔ˜ ·fi ‰È·‰Ô¯ÈΤ˜ ÙÔ̤˜30. B. M·ÁÓËÙÈ΋ ÙÔÌÔÁÚ·Ê›· ÛÙÔ ‡„Ô˜ ÙÔ˘ ıfiÏÔ˘ ÙÔ˘ ‹·ÙÔ˜ (ÂÈ‚¿Ú˘ÓÛË T1, Ì ηٷÛÙÔÏ‹ Ï›Ô˘˜ Î·È ¤Á¯˘ÛË ·Ú·Ì·ÁÓËÙÈ΋˜ Ô˘Û›·˜), ÛÙËÓ ÔÔ›· ·ÂÈÎÔÓ›˙ÂÙ·È Ë ‰ÂÍÈ¿ (‚¤ÏË) Î·È Ë Ì¤ÛË Ë·ÙÈ΋ ÊϤ‚· (ÎÂʷϤ˜ ‚ÂÏÒÓ). T· ËÏÂÎÙÚÔÓÈο ÂÚÈÁÚ¿ÌÌ·Ù· ·ÊÔÚ›˙Ô˘Ó Ù· fiÚÈ· ÙÔ˘ ‰ÂÍÈÔ‡ ‹·ÙÔ˜ (Rt), ÙÔ˘ ¤Ûˆ (Med) Î·È ÙÔ˘ ¤Íˆ ÙÌ‹Ì·ÙÔ˜ (Lat) ÙÔ˘ ·ÚÈÛÙÂÚÔ‡ ‹·ÙÔ˜, ηıÒ˜ Î·È ÙÔ˘ ÎÂÚÎÔÊfiÚÔ˘ ÏÔ‚Ô‡ ÙÔ˘ ‹·ÙÔ˜ (C), ·fi Ù· ÔÔ›· ˘ÔÏÔÁ›˙ÂÙ·È ÙÔ ÂÌ‚·‰fiÓ ÙÔ˘˜30. °. M·ÁÓËÙÈ΋ ÙÔÌÔÁÚ·Ê›· ÛÙÔ ‡„Ô˜ ÙÔ˘ ÛÙÂϤ¯Ô˘˜ Ù˘ ˘Ï·›·˜ ÊϤ‚·˜ (MPV) (ÂÈ‚¿Ú˘ÓÛË T1, Ì ηٷÛÙÔÏ‹ Ï›Ô˘˜ Î·È ¤Á¯˘ÛË ·Ú·Ì·ÁÓËÙÈ΋˜ Ô˘Û›·˜). T· ËÏÂÎÙÚÔÓÈο ÂÚÈÁÚ¿ÌÌ·Ù· ÙÔ˘ ‰ÂÍÈÔ‡ ‹·ÙÔ˜ (Rt), ÙÔ˘ ¤Ûˆ (Med) Î·È ÙÔ˘ ¤Íˆ ÙÌ‹Ì·ÙÔ˜ (Lat) ÙÔ˘ ·ÚÈÛÙÂÚÔ‡ ‹·ÙÔ˜, ÂÈÙÚ¤Ô˘Ó ÙÔÓ ÚÔÛ‰ÈÔÚÈÛÌfi ÙˆÓ ÂÌ‚·‰ÒÓ ÙÔ˘˜30. ΔÔ ¿ıÚÔÈÛÌ· ÙˆÓ ÂÌ‚·‰ÒÓ ÙˆÓ ÙÔÌÒÓ Â› ÙÔ ¿¯Ô˜ Ù˘ οı ÙÔÌ‹˜ ÂÈÙÚ¤ÂÈ ÙÔÓ ˘ÔÏÔÁÈÛÌfi ÙÔ˘ fiÁÎÔ˘ ÙÔ˘ οı ÙÌ‹Ì·ÙÔ˜ ÙÔ˘ ‹·ÙÔ˜. ¢. ¶ÚÔÂÁ¯ÂÈÚËÙÈ΋ Ì·ÁÓËÙÈ΋ ÙÔÌÔÁÚ·Ê›· ·fi Û˘ÁÁÂÓ‹ ‰fiÙË Ë·ÙÈÎÔ‡ ÌÔۯ‡̷ÙÔ˜. TÔ ËÏÂÎÙÚÔÓÈÎfi ÂÚ›ÁÚ·ÌÌ· ·ÊÔÚ›˙ÂÈ Ù· fiÚÈ· ÙÔ˘ ‰ÂÍÈÔ‡ ‹·ÙÔ˜. E. TÔ Ë·ÙÈÎfi ÎÔÏfi‚ˆÌ· ÛÙÔÓ ‰fiÙË 14 Ë̤Ú˜ ÌÂÙ¿ ÙËÓ Ë·ÙÂÎÙÔÌ‹. H ÛËÌ·ÓÙÈ΋ ·‡ÍËÛË ÙÔ˘ fiÁÎÔ˘ ÙÔ˘ ·ÚÈÛÙÂÚÔ‡ ‹·ÙÔ˜ Â›Ó·È ÂÌÊ·Ó‹˜ (110% ÙÔ˘ ·Ú¯ÈÎÔ‡ fiÁÎÔ˘). ™T. ΔÔ ‰ÂÍÈfi ‹·Ú ÙÔ˘ ‰fiÙË 30 Ë̤Ú˜ ÌÂÙ¿ ÙË ÌÂÙ·ÌfiÛ¯Â˘ÛË ÛÙÔ Ï‹ÙË ¤¯ÂÈ, ›Û˘, ·˘ÍËı› Ôχ ÛËÌ·ÓÙÈο (101% ÙÔ˘ ÙÔ˘ ·Ú¯ÈÎÔ‡ fiÁÎÔ˘)32.
56
π. ºOÀ∑∞™, ¢. Δ∞∫OÀ¢∞™
Αμερικανική βιβλιογραφία
Ευρωπαϊκή βιβλιογραφία (Couinaud)
∆εξιός λοβός
∆εξιό ήπαρ V, VI, VII, VII
Αριστερός λοβός
Αριστερό ήπαρ II, III, IV±I
Αριστερό έξω πλάγιο τμήμα
Αριστερός λοβός II, III
ÂÚÈÛÛfiÙÂÚ· ΤÓÙÚ· ‰ÈfiÙÈ Â›Ó·È ÂÂÌ‚·ÙÈ΋ Î·È ÌÔÚ› Ó· ·ÚÔ˘ÛÈ¿ÛÂÈ ÛÔ‚·Ú¤˜ ÂÈÏÔΤ˜, fiˆ˜ Ë ·ÁÎÚ·ٛÙȉ·. ∏ ¯ÔÏ·ÁÁÂÈÔÁÚ·Ê›· Ì ·ÍÔÓÈÎfi ÙÔÌÔÁÚ¿ÊÔ ÔÏÏ·ÏÒÓ ·ÓȯÓ¢ÙÒÓ (MDCT) ·ÚÔ˘ÛÈ¿˙ÂÈ Ôχ ˘„ËÏ‹ ‰È·ÎÚÈÙÈ΋ ÈηÓfiÙËÙ·, ·Ó·ÏÔÁË Î·Ù¿ 96% Ì ٷ ÂÁ¯ÂÈÚËÙÈο Â˘Ú‹Ì·Ù·, ÂÓÒ ·ÂÈÎÔÓ›˙ÂÈ ·ÎfiÌË Î·È Ù· ÌÈÎÚ¿ ¯ÔÏ·ÁÁ›· ·fi ÙÔÓ ‰ÂÍÈfi Ë·ÙÈÎfi fiÚÔ ÚÔ˜ ÙÔÓ ÎÂÚÎÔÊfiÚÔ ÏÔ‚fi28,40. ∏ Ì·ÁÓËÙÈ΋ ¯ÔÏ·ÁÁÂÈÔ-·ÁÎÚ·ÙÔÁÚ·Ê›· (MRCP) ·ÔÎÙ¿ fiÏÔ Î·È ÛËÌ·ÓÙÈÎfiÙÂÚÔ ÚfiÏÔ ÛÙËÓ ÚÔÂÁ¯ÂÈÚËÙÈ΋ ÂÎÙ›ÌËÛË ÙˆÓ ˙ÒÓÙˆÓ ‰ÔÙÒÓ ‰ÈfiÙÈ ÚÔÛÊ·Ù˜ ÌÂϤÙ˜ ·Ô‰ÂÈÎÓ‡Ô˘Ó fiÙÈ ‰È·ı¤ÙÂÈ ‰È·ÎÚÈÙÈ΋ ÈηÓfiÙËÙ· ·Ó¿ÏÔÁË Ì Ù˘ MDCT ¯ÔÏ·ÁÁÂÈÔÁÚ·Ê›·˜, Ì ÌÈÎÚfiÙÂÚÔ Î›Ó‰˘ÓÔ ·ÏÏÂÚÁÈÎÒÓ ·ÓÙȉڿÛÂˆÓ ·fi Ù· ÛÎÈ·ÛÙÈο ¯ÔÏËÊfiÚˆÓ41.
™˘Ó‰˘·Ṳ̂Ó˜ ·ÂÈÎÔÓÈÛÙÈΤ˜ ̤ıÔ‰ÔÈ ∆εξιό εκτεταμένο μόσχευμα
∆εξιός λοβός I, IV, V, VI, VII, VIII
EÈÎfiÓ· 3. ¢È·ÊÔÚ¤˜ ÌÂٷ͇ Ù˘ ·ÌÂÚÈηÓÈ΋˜ Î·È Ù˘ Â˘Úˆ·˚΋˜ ‚È‚ÏÈÔÁÚ·Ê›·˜ ˆ˜ ÚÔ˜ ÙËÓ ÔÓÔÌ·ÙÔÏÔÁ›· ÙˆÓ ÙÌËÌ·ÙÈÎÒÓ Ë·ÙÈÎÒÓ ÌÔÛ¯Â˘Ì¿ÙˆÓ. OÈ ‰È·ÊÔÚ¤˜ ·˘Ù¤˜ ÔÊ›ÏÔÓÙ·È ÛÙÔ fiÙÈ ‰ÂÓ ¤¯ÂÈ ˘¿ÚÍÂÈ ÔÌÔʈӛ· ˆ˜ ÚÔ˜ ÙËÓ ÏÂÈÙÔ˘ÚÁÈ΋ ·Ó·ÙÔÌÈ΋ ‰È·›ÚÂÛË ÙÔ˘ ‹·ÙÔ˜. H ÛËÌ·ÓÙÈÎfiÙÂÚË ‰È·ÊÔÚ¿ ÌÂٷ͇ ÙˆÓ ‰‡Ô Ù·ÍÈÓÔÌ‹ÛÂˆÓ ·ÊÔÚ¿ ÙÔ ÎÚÈÙ‹ÚÈÔ ÁÈ· ÙËÓ ‰È·›ÚÂÛË ÙÔ˘ ‹·ÙÔ˜. OÈ ∞ÌÂÚÈηÓÔ› Healey Î·È Schroy, ηıÒ˜ Î·È ÔÈ Goldsmith Î·È Woodburne,36,37 ¯ÚËÛÈÌÔÔ›ËÛ·Ó ÙÔ˘˜ ÎÏ¿‰Ô˘˜ ÙÔ˘ ¯ÔÏËÊfiÚÔ˘ ‰¤Ó‰ÚÔ˘ ˆ˜ Ô‰ËÁfi ÁÈ· ÙËÓ ‰È·›ÚÂÛË ÙÔ˘ ‹·ÙÔ˜, ÂÓÒ ÔÈ °¿ÏÏÔÈ Couinaud Î·È Bismuth2,3,37 ¯ÚËÛÈÌÔÔ›ËÛ·Ó ÙȘ ‰È·ÎÏ·‰ÒÛÂȘ Ù˘ ˘Ï·›·˜ ÊϤ‚·˜.
‰fiÙ˜31. ∫·Ù¿ Û˘Ó¤ÂÈ·, Ë ÏÂÙÔÌÂÚ‹˜ ·ÂÈÎfiÓÈÛË ÙˆÓ ·Ó·ÙÔÌÈÎÒÓ ·Ú·ÏÏ·ÁÒÓ ÙˆÓ ¯ÔÏËÊfiÚˆÓ ¤¯ÂÈ Î·ıÔÚÈÛÙÈ΋ ÛËÌ·Û›· ÁÈ· ÙËÓ ·ÛÊ·Ï‹ ‰ÈÂÓ¤ÚÁÂÈ· Ù˘ Ë·ÙÂÎÙÔÌ‹˜ ÛÙÔÓ ‰fiÙË ·ÏÏ¿ Î·È Ù˘ ·Ó·ÛÙÔÌÒÛˆ˜ ÛÙÔÓ Ï‹ÙË. ∏ ·ÂÈÎfiÓÈÛË Á›ÓÂÙ·È ÚÔÂÁ¯ÂÈÚËÙÈο Î·È ‰ÈÂÁ¯ÂÈÚËÙÈο. ∏ ‰ÈÂÁ¯ÂÈÚËÙÈ΋ ¯ÔÏ·ÁÁÂÈÔÁÚ·Ê›· Â›Ó·È Ë Û˘¯ÓfiÙÂÚ· ¯ÚËÛÈÌÔÔÈÔ‡ÌÂÓË Ì¤ıÔ‰Ô˜ ·ÂÈÎfiÓÈÛ˘ ÙˆÓ ¯ÔÏËÊfiÚˆÓ, ¤¯ÂÈ ¿ÚÈÛÙË ‰È·ÎÚÈÙÈ΋ ÈηÓfiÙËÙ· ·ÏÏ¿ ÚÔηÏ› ηı˘ÛÙ¤ÚËÛË ÛÙÔ ¯ÂÈÚÔ˘ÚÁÂ›Ô Î·È ‰ÂÓ ÂÈÙÚ¤ÂÈ ÙÔÓ ÚÔÂÁ¯ÂÈÚËÙÈÎfi ۯ‰ȷÛÌfi Ù˘ ÂÂÌ‚¿Ûˆ˜. ¶ÚÔÂÁ¯ÂÈÚËÙÈο, ÌÔÚ› Ó· ¯ÚËÛÈÌÔÔÈËı› Ë ÂÓ‰ÔÛÎÔÈ΋ ·Ï›Ó‰ÚÔÌË ¯ÔÏ·ÁÁÂÈÔ-·ÁÎÚ·ÙÔÁÚ·Ê›· (ERCP), Ë ÔÔ›· ¤¯ÂÈ ÂÁηٷÏÂÈÊı› ·fi Ù·
OÈ Û˘Ó‰˘·Ṳ̂Ó˜ ·ÂÈÎÔÓÈÛÙÈΤ˜ ̤ıÔ‰ÔÈ (‘All in one’ procedures), Ì ·ÍÔÓÈ΋ ‹ Ì·ÁÓËÙÈ΋ ÙÔÌÔÁÚ·Ê›·, ‰›ÓÔ˘Ó ÙËÓ ‰˘Ó·ÙfiÙËÙ· Ó· ÂÏ·ÙÙˆı› Ô ¯ÚfiÓÔ˜ Î·È ÙÔ ÎfiÛÙÔ˜ Ù˘ ÚÔÂÁ¯ÂÈÚËÙÈ΋˜ ÂÎÙ›ÌËÛ˘ ÙÔ˘ ‰fiÙË. ∏ MDCT ·ÍÔÓÈ΋ ÙÔÌÔÁÚ·Ê›· ·Ú¤¯ÂÈ ÙË ‰˘Ó·ÙfiÙËÙ· Ù˘ Ù·˘Ùfi¯ÚÔÓ˘ ÌÂϤÙ˘ Ù˘ ÌÔÚÊÔÏÔÁ›·˜ ÙÔ˘ Ë·ÙÈÎÔ‡ ·ÚÂÁ¯‡Ì·ÙÔ˜, ÔÁÎÔÌÂÙÚ›·˜ Î·È ·ÂÈÎÔÓ›Ûˆ˜, ̤¯ÚÈ ÙÔÓ ‰Â‡ÙÂÚÔ ÂÓ‰ÔË·ÙÈÎfi ‰È¯·ÛÌfi, Ù˘ Ë·ÙÈ΋˜ ·ÚÙËÚ›·˜, Ù˘ ˘Ï·›·˜ ÊϤ‚·˜ ÙˆÓ Ë·ÙÈÎÒÓ ÊÏ‚ÒÓ Î·È Ù˘ ηو ÎÔ›Ï˘ ÊϤ‚·˜, ηıÒ˜ Î·È ÙÔ˘ ¯ÔÏËÊfiÚÔ˘ ‰¤Ó‰ÚÔ˘ (∂ÈÎfiÓ· 4)42. ∏ Ì·ÁÓËÙÈ΋ ÙÔÌÔÁÚ·Ê›· ·Ú¤¯ÂÈ ·Ó¿ÏÔÁË ·ÎÚ›‚ÂÈ· ÛÙËÓ ·ÂÈÎfiÓÈÛË ÙˆÓ ·ÁÁ›ˆÓ ·ÏÏ¿ ˘ÛÙÂÚ› fiÛÔÓ ·ÊÔÚ¿ Ù· ¯ÔÏËÊfiÚ·42,43. ∞fi ÙËÓ ¿ÏÏË ÏÂ˘Ú¿, Ë MDCT ·ÍÔÓÈ΋ ÙÔÌÔÁÚ·Ê›· ÂÎı¤ÙÂÈ ÙÔÓ ‰fiÙË Û ·ÎÙÈÓÔ‚ÔÏ›· ÂÓÒ ··ÈÙ› ÙËÓ ¯ÔÚ‹ÁËÛË ÌÂÁ¿ÏˆÓ ‰fiÛÂˆÓ ·ÎÙÈÓÔÛÎÈÂÚÒÓ Ô˘ÛÈÒÓ.
™¯Â‰È·ÛÌfi˜ Ù˘ Ë·ÙÂÎÙÔÌ‹˜ Δ· ‰Â‰Ô̤ӷ ÙˆÓ Û˘Ó‰˘·ÛÌ¤ÓˆÓ ·ÂÈÎÔÓÈÛÙÈÎÒÓ Ù¯ÓÈÎÒÓ ÌÔÚÔ‡Ó Ó· ηÙÂÚÁ·ÛıÔ‡Ó Ì ÂȉÈÎfi ÏÔÁÈÛÌÈÎfi Î·È Ó· ·ÚÔ˘ÛÈ·ÛıÔ‡Ó Û ÙÚÈۉȿÛÙ·ÙË ÌÔÚÊ‹ ÁÈ· ÙÔÓ Û¯Â‰È·ÛÌfi Ù˘ Ë·ÙÂÎÙÔÌ‹˜ (MeVis Liver-Analyzer and Liver-Viewer, Bremen, Germany). ∂ÈϤÔÓ, Ë Î·ÙÂÚÁ·Û›· ÙˆÓ ·ÓˆÙ¤Úˆ ‰Â‰ÔÌ¤ÓˆÓ Ì ÙÔ ÏÔÁÈÛÌÈÎfi HepaVision (MeVis, Bremen, Germany) ÂÈÙÚ¤ÂÈ: ·. ÙËÓ ÙÚÈۉȿÛÙ·ÙË ÏÂÈÙÔ˘ÚÁÈ΋ ·ÂÈÎfiÓÈÛË Ù˘ ·ÁÁÂȷ΋˜ ·Ó·ÙÔÌÈ΋˜ ÙÔ˘ ‹·ÙÔ˜ Î·È ÙˆÓ ÂÚÈÔ¯ÒÓ Ô˘ ·ÈÌ·ÙÒÓÔÓÙ·È ‹ ·ÚÔ¯ÂÙ‡ÔÓÙ·È ·fi ÎÏ¿‰Ô˘˜ Ù˘ Ë·ÙÈ΋˜ ·ÚÙËÚÈ·˜, Ù˘ ˘Ï·›·˜ ÊϤ‚·˜ Î·È ÙˆÓ Ë·ÙÈÎÒÓ ÊÏ‚ÒÓ, ‚. ÙËÓ ÙÚÈۉȿÛÙ·ÙË ·ÂÈÎfiÓÈÛË ÙÔ˘ ¯ÔÏËÊfi-
METAMO™XEY™Eπ™ 2008
57
∂ÈÎfiÓ· 4. ªÂϤÙË ˘Ô„ËÊ›ˆÓ ˙ÒÓÙˆÓ ‰ÔÙÒÓ Ë·ÙÈÎÔ‡ ÌÔۯ‡̷ÙÔ˜ ÌÂ Û˘Ó‰˘·Ṳ̂ÓË (all in one) ÙÚÈۉȿÛÙ·ÙË ·ÍÔÓÈ΋ ÙÔÌÔÁÚ·Ê›· ÔÏÏ·ÏÒÓ ·ÓȯÓ¢ÙÒÓ, ÌÂÙ¿ ·fi ‰È·‰Ô¯È΋ ¯ÔÚ‹ÁËÛË ÛÎÈ·ÛÙÈÎÒÓ Ô˘ÛÈÒÓ ÁÈ· Ù· ¯ÔÏËÊfiÚ· Î·È Ù· ·ÁÁ›· ÙÔ˘ ‹·ÙÔ˜. ·. ∞ÚÙËÚÈÔÁÚ·Ê›· ÛÙËÓ ÔÔ›· ·ÂÈÎÔÓ›˙ÂÙ·È ·ÓÙÈηٷÛÙ·ı›۷ ‰ÂÍÈ¿ Ë·ÙÈ΋ ·ÚÙËÚ›· ·fi ÙËÓ ¿Óˆ ÌÂÛÂÓÙ¤ÚÈÔ (Ï¢Îfi ‚¤ÏÔ˜). μ. ¶˘Ï·ÈÔÁÚ·Ê›· Ì ¤ÎÙÔË ¤ÎÊ˘ÛË ÙÔ˘ ÚÔÛı›Ô˘ ÙÔÌ·ÎÔ‡ ÎÏ¿‰Ô˘ Ù˘ ‰ÂÍÈ¿˜ ˘Ï·›·˜ ÊϤ‚·˜ (¶∫¢¶º) ·fi ÙËÓ ·ÚÈÛÙÂÚ‹ ˘Ï·›· ÊϤ‚· (∞¶º). Á. ºÏ‚ÔÁÚ·Ê›· Ì ÌÂÁ¿ÏË ‰ÂÍÈ¿ Ë·ÙÈ΋ ÊϤ‚· (¢∏º) Ô˘ ·ÚÔ¯ÂÙ‡ÂÈ ÙÔÓ ‰ÂÍÈfi Ô›ÛıÈÔ ÙÔ̤·, ηıÒ˜ Î·È ÌÂÁ¿ÏÔ ÙÌ‹Ì· ÙÔ˘ ÚÔÛı›Ô˘ ÙÔ̤· ÙÔ˘ ‰ÂÍÈÔ‡ ‹·ÙÔ˜ (*ÂÈÚÔ‚ÔÏ‹ ÙˆÓ ¯ÔÏËÊfiÚˆÓ). ‰. ÃÔÏ·ÁÁÂÈÔÁÚ·Ê›· Ì Â΂ÔÏ‹ ÙÔ˘ ‰ÂÍÈÔ‡ ÔÈÛı›Ô˘ ÙÔÌ·ÎÔ‡ ÎÏ¿‰Ô˘ (O∫¢∏¶) ÛÙÔÓ ·ÚÈÛÙÂÚfi Ë·ÙÈÎfi fiÚÔ (∞∏¶)42.
ÚÔ˘ ‰¤Ó‰ÚÔ˘, Á. ÔÁÎÔÌÂÙÚ›· ÙˆÓ ÙÌËÌ¿ÙˆÓ ÙÔ˘ ‹·ÙÔ˜, ‰. ۯ‰ȷÛÌfi ÙÔ˘ ÂȤ‰Ô˘ ‰È·ÙÔÌ‹˜ ÙÔ˘ ‹·ÙÔ˜ Î·È ÂÎÙ›ÌËÛË ÙÔ˘ ÎÈÓ‰‡ÓÔ˘ (risk analysis) ÊÏ‚È΋˜ Û˘ÌÊÔÚ‹Ûˆ˜, ·Ó¿ÏÔÁ· Ì ÙËÓ Î·Ù·ÓÔÌ‹ ÙˆÓ Ë·ÙÈÎÒÓ ÊÏ‚ÒÓ (hepatic vein dominance)44-47.
∏·ÙÂÎÙÔÌ‹ ÙÔ˘ ‰fiÙË ŸÙ·Ó Ô ‰fiÙ˘ Êı¿ÛÂÈ Ì¤¯ÚÈ ÙÔ ¯ÂÈÚÔ˘ÚÁÂ›Ô ÌÂÙ·ÙÚ¤ÂÙ·È Û ·ÛıÂÓ‹ Î·È ··ÈÙ› ·fi ÙËÓ ¯ÂÈÚÔ˘ÚÁÈ΋ ÔÌ¿‰· ·fiÏ˘ÙË ·ÊȤڈÛË ÛÙËÓ ·ÔÊ˘-
Á‹ ÂÈÏÔÎÒÓ Î·È ÛÙËÓ ÂÍ·ÛÊ¿ÏÈÛË ÙÔ˘ ηχÙÂÚÔ˘ ‰˘Ó·ÙÔ‡ ·ÔÙÂϤÛÌ·ÙÔ˜ ÁÈ· ÙÔÓ Ï‹ÙË48. H Ù¯ÓÈ΋ Ù˘ Ë·ÙÂÎÙÔÌ‹˜ Û ˙ÒÓÙ˜ ‰fiÙ˜ ¤¯ÂÈ Î·ıÔÚÈÛÙÈ΋ ÛËÌ·Û›· ÁÈ· ÙËÓ ‚ȈÛÈÌfiÙËÙ· Î·È ÙËÓ ·Ó·ÁÂÓÓËÙÈ΋ ÈηÓfiÙËÙ· ÙfiÛÔ ÙÔ˘ Ë·ÙÈÎÔ‡ ÎÔÏÔ‚ÒÌ·ÙÔ˜ ÛÙÔ ‰fiÙË, fiÛÔ Î·È ÙÔ˘ ÌÔۯ‡̷ÙÔ˜. °È· Ó· ÂÈÙ¢¯ı› ·˘Ùfi Ú¤ÂÈ Ó· ÂÍ·ÛÊ·ÏÈÛı› Ë ·ÎÂÚ·ÈfiÙËÙ· Ù˘ ·ÚÔ¯‹˜ ·ÚÙËÚÈ·ÎÔ‡ Î·È ˘Ï·›Ô˘ ·›Ì·ÙÔ˜ Î·È Ù˘ ·ÚÔ¯¤Ù¢Û˘ ÙfiÛÔ ÙÔ˘ ÊÏ‚ÈÎÔ‡ ·›Ì·ÙÔ˜ fiÛÔ Î·È Ù˘ ¯ÔÏ‹˜.
58
π. ºOÀ∑∞™, ¢. Δ∞∫OÀ¢∞™
∂ÈÎfiÓ· 5. ΔÚÈۉȿÛÙ·ÙË ·ÂÈÎfiÓÈÛË ÙˆÓ ·ÁÁ›ˆÓ Î·È ÙˆÓ ¯ÔÏËÊfiÚˆÓ ÙÔ˘ ‹·ÙÔ˜ Î·È Û¯Â‰È·ÛÌfi˜ Ù˘ Ë·ÙÂÎÙÔÌ‹˜ Û ˙ÒÓÙ· ‰fiÙË Ì ÙÔ ÏÔÁÈÛÌÈÎfi HepaVision - MeVis43-47.
H ÚÔۤϷÛË Á›ÓÂÙ·È Ì ·ÌÊÔÙÂÚfiÏ¢ÚË ˘ÔχÚÈ· ÙÔÌ‹ Î·È Î¿ıÂÙË Â¤ÎÙ·ÛË Ù˘ ÚÔ˜ ÙÔ ÛÙ¤ÚÓÔ. AÎÔÏÔ˘ı› Ë ‰È·ÙÔÌ‹ ÙÔ˘ ÛÙÚÔÁÁ‡ÏÔ˘ Î·È ÙÔ˘ ‰Ú·ÓÔÂȉԇ˜ Û˘Ó‰¤ÛÌÔ˘ ÙÔ˘ ‹·ÙÔ˜ Î·È ·Ú·Û΢¿˙ÂÙ·È Ë ·‡Ï·Î· ÌÂٷ͇ Ù˘ ‰ÂÍÈ¿˜ Î·È Ù˘ ̤Û˘ Ë·ÙÈ΋˜ ÊϤ‚·˜. ™Â ‰ÂÍÈ¿ Ë·ÙÂÎÙÔÌ‹, ÔÈÛ‡Ó‰ÂÛÌÔÈ ÙÔ˘ ·ÚÈÛÙÂÚÔ‡ ÏÔ‚Ô‡ ‰ÂÓ ‰È·Ù¤ÌÓÔÓÙ·È ÁÈ· Ó· ·ÔÊ¢¯ı› Ë ·˘ÍË̤ÓË ÎÈÓËÙÈÎfiÙËÙ· Ë ÔÔ›· ÌÔÚ› Ó· ÚÔηϤÛÂÈ Î¿Ì„Ë ÙˆÓ Ë·ÙÈÎÒÓ ÊÏ‚ÒÓ Î·È Û˘ÌÊfiÚËÛË ÙÔ˘ ‹·ÙÔ˜. ∏ ÙÂÏÈ΋ ÂÈÏÔÁ‹ ÙÔ˘ ›‰Ô˘˜ Î·È Ù˘ ¤ÎÙ·Û˘ Ù˘ Ë·ÙÂÎÙÔÌ‹˜ Á›ÓÂÙ·È ‰ÈÂÁ¯ÂÈÚËÙÈο Ì ‚¿ÛË ÙȘ ·Ó¿ÁΘ ÙÔ˘ Ï‹ÙË ÁÈ· Ë·ÙÈÎfi ·Ú¤Á¯˘Ì·, Ù· ·Ó·ÙÔÌÈο Â˘Ú‹Ì·Ù·, ÙÔ ‰ÈÂÁ¯ÂÈÚËÙÈÎfi ˘ÂÚ˯ÔÁÚ¿ÊËÌ·, ÙËÓ ÚÔËÁÔ‡ÌÂÓË ·ÂÈÎfiÓÈÛË ÙˆÓ ¯ÔÏËÊfiÚˆÓ Î·È ÙËÓ ‰ÈÂÁ¯ÂÈÚËÙÈ΋ ¯ÔÏ·ÁÁÂÈÔÁÚ·Ê›· (∂ÈÎfiÓ· 6). ŸÛÔÓ ·ÊÔÚ¿ Ù· ¯ÔÏËÊfiÚ·, Ë ÁÂÓÈ΋ ÁÚ·ÌÌ‹ Â›Ó·È Ë ·ÔÊ˘Á‹ ÙˆÓ ÂÚÈÛÛÔÙ¤ÚˆÓ ·fi ‰‡Ô ¯ÔÏÔÂÙÈÎÒÓ ·Ó·ÛÙÔÌÒÛÂˆÓ ÁÈ· ÙÔÓ Ï‹ÙË, ¯ˆÚ›˜ Ó· ˘¿ÚÍÂÈ Î›Ó‰˘ÓÔ˜ ÛÙÂÓÒÛˆ˜ ÁÈ· ÙÔÓ ‰fiÙË48 (∂ÈÎfiÓ· 7). ∏ ‰È·ÙÔÌ‹ ÙÔ˘ ¯ÔÏˉfi¯Ô˘ fiÚÔ˘, ÛÙ· ÂÚÈÛÛfiÙÂÚ· ΤÓÙÚ·, ‰ÈÂÓÂÚÁÂ›Ù·È ÛÙÔ Ù¤ÏÔ˜ Ù˘ Ë·ÙÂÎÙÔÌ‹˜, ÂÓÒ Û ¿ÏÏ· ·fi ÙËÓ ·Ú¯‹, Ì ÙËÓ ÏÔÁÈ΋ fiÙÈ ¤ÙÛÈ ÂÈÙ˘Á¯¿ÓÂÙ·È Î·Ï‡ÙÂÚÔ˜ ηıÔÚÈÛÌfi˜ ÙÔ˘ ÂȤ‰Ô˘ ‰È·ÙÔÌ‹˜ ÙÔ˘ ¯ÔÏˉfi¯Ô˘ fiÚÔ˘ Î·È ·ÔÊ˘Á‹ ıÂÚÌÈ΋˜ ‚Ï¿‚˘ ·fi ÙËÓ ‰È·ıÂÚÌ›·49. AÎÔÏÔ˘ı› Ë ·Ú·Û΢‹ ÙˆÓ ˘ÏÒÓ ÙÔ˘ ‹·ÙÔ˜ Î·È Ë ·ÔÌfiÓˆÛË ÙÔ˘ ‰ÂÍÈÔ‡ ‹ ÙÔ˘ ·ÚÈÛÙÂÚÔ˘ ÎÏ¿‰Ô˘ Ù˘ Ë·ÙÈ΋˜ ·ÚÙËÚ›·˜, Ù˘ ˘Ï·›·˜ ÊϤ‚·˜ Î·È ÙÔ˘ ¯ÔÏˉfi¯Ô˘ fiÚÔ˘, ·Ó¿ÏÔÁ· Ì ÙÔ Â›‰Ô˜ Ù˘
Ë·ÙÂÎÙÔÌ‹˜. ™Â ‰ÂÍÈ¿ Ë·ÙÂÎÙÔÌ‹, O ‰ÂÍÈfi˜ ÎÏ¿‰Ô˜ Ù˘ Ë·ÙÈ΋˜ ·ÚÙËÚ›·˜, Û˘Ó‹ıˆ˜, ÔÚ‡ÂÙ·È ›Ûˆ ·fi ÙÔÓ ¯ÔÏˉfi¯Ô fiÚÔ Î·È ÛÙÔ ÛËÌÂ›Ô ÂΛÓÔ ¯ÔÚËÁ› ÎÏ¿‰Ô ÚÔ˜ ÙÔ Ï¤ÁÌ· ÙˆÓ ·ÁÁ›ˆÓ ÙÔ˘. H ‰È·ÙÔÌ‹ ÙÔ˘ ÎÏ¿‰Ô˘ ·˘ÙÔ‡ ÚÔηÏ› ÈÛ¯·ÈÌ›· Î·È ·ÒÙÂÚË ÛÙ¤ÓˆÛË ÙÔ˘ ¯ÔÏˉfi¯Ô˘ fiÚÔ˘ ÙÔ˘ ‰fiÙË50. °È· Ó· ·ÔÊ¢¯ı› ·˘Ùfi, Ë ÚÔۤϷÛË ÙÔ˘ ‰ÂÍÈÔ‡ ÎÏ¿‰Ô˘ Ù˘ Ë·ÙÈ΋˜ ·ÚÙËÚ›·˜ Á›ÓÂÙ·È ·fi Ù· ‰ÂÍÈ¿ ÙÔ˘ ÎÔÈÓÔ‡ Ë·ÙÈÎÔ‡ Î·È ÛÙËÓ Û˘Ó¤¯ÂÈ· ·Ú·Û΢¿˙ÂÙ·È ·fi ÙÔ ‰ÂÍÈfi ¯Â›ÏÔ˜ ÙÔ˘ ̤¯ÚÈ ÙÔ Ë·ÙÈÎfi ·Ú¤Á¯˘Ì·51. ™ÙË Û˘Ó¤¯ÂÈ· ·Ó¢ڛÛÎÂÙ·È Ô ‰ÂÍÈfi˜ ÎÏ¿‰Ô˜ Ù˘ ˘Ï·›·˜ ÊϤ‚·˜ Î·È ·Ú·Û΢¿˙ÂÙ·È ·fi ÙÔÓ ‰È¯·ÛÌfi ̤¯ÚÈ ÙÔ Ë·ÙÈÎfi ·Ú¤Á¯˘Ì·, ¤ÙÛÈ ÒÛÙÂ, ηٿ ÙËÓ ÂÎÙÔÌ‹ ÙÔ˘ ÌÔۯ‡̷ÙÔ˜, Ó· ÏËÊı› ÙÔ Ì¤ÁÈÛÙÔ ‰˘Ó·Ùfi Ì‹ÎÔ˜ ÙÔ˘. O ÚÔÛˆÚÈÓfi˜ ·ÔÎÏÂÈÛÌfi˜ ÙˆÓ ‰ÂÍÈÒÓ ÎÏ¿‰ˆÓ Ù˘ Ë·ÙÈ΋˜ ·ÚÙËÚ›·˜ Î·È Ù˘ ˘Ï·›·˜ ÊϤ‚·˜ Ì ·ÙÚ·˘Ì·ÙÈΤ˜ ·ÁÁÂÈÔÏ·‚›‰Â˜, › ¤Ó· ÏÂÙfi, ÚÔηÏ› ÈÛ¯·ÈÌ›· ÙÔ˘ ‰ÂÍÈÔ‡ ‹·ÙÔ˜ Î·È ÙËÓ ÂÌÊ¿ÓÈÛË ‰È·¯ˆÚÈÛÙÈ΋˜ ÁÚ·ÌÌ‹˜, Ë ÔÔ›· ˘Ô‚ÔËı¿ ÛÙÔÓ Î·ıÔÚÈÛÌfi ÙÔ˘ ÂȤ‰Ô˘ Ù˘ Ë·ÙÂÎÙÔÌ‹˜. I‰È·›ÙÂÚË ÚÔÛÔ¯‹ ‰›ÓÂÙ·È ÛÙËÓ ·ÁÁ›ˆÛË ÙÔ˘ ÙÌ‹Ì·ÙÔ˜ IV ÙÔ ÔÔ›Ô ·ÔÙÂÏ› ÙÔ 40% ÙÔ˘ ÌÂÙÂÁ¯ÂÈÚËÙÈÎÔ‡ fiÁÎÔ˘ ÙÔ˘ Ë·ÙÈÎÔ‡ ÎÔÏÔ‚ÒÌ·ÙÔ˜ ÙÔ˘ ‰fiÙË ‰ÂÍÈÔ‡ ‹·ÙÔ˜ Î·È Ë ·Ó·Á¤ÓÓËÛË ÙÔ˘ Â›Ó·È Î·ıÔÚÈÛÙÈ΋ ÁÈ· ÙËÓ ÂÈ‚›ˆÛË ÙÔ˘ . AÓ Ë ·ÚÙËÚȷ΋ ·ÈÌ¿ÙˆÛË ÙÔ˘ ÙÌ‹Ì·ÙÔ˜ IV ÚÔ¤Ú¯ÂÙ·È ·fi Ù· ‰ÂÍÈ¿, Ë ·Ú·Û΢‹ Ù˘ ‰ÂÍÈ¿˜ Ë·ÙÈ΋˜ ·ÚÙËÚ›·˜ (¢∏∞) ÚÔ¯ˆÚ› ̤¯ÚÈ ÙÔÓ ÎÏ¿‰Ô ÙÔ˘ ÙÌ‹Ì·ÙÔ˜ IV Î·È Ë ¢HA ‰È·Ù¤ÌÓÂÙ·È ÂÚÈÊÂÚÈÎfiÙÂÚ· (EÈÎfiÓ· 8). AÓ Ë ·ÚÙËÚȷ΋ ·ÈÌ¿ÙˆÛË ÙÔ˘ ÙÌ‹Ì·ÙÔ˜
METAMO™XEY™Eπ™ 2008
59
EÈÎfiÓ· 6.·. ¢ÈÂÁ¯ÂÈÚËÙÈ΋ ˘ÂÚ˯ÔÁÚ·ÊÈ΋ ÌÂϤÙË ÙÔ˘ ‹·ÙÔ˜ Ì ÙËÓ ÔÔ›· ηıÔÚ›˙ÂÙ·È Ë ÔÚ›· Ù˘ ̤Û˘ Ë·ÙÈ΋˜ ÊϤ‚·˜ (MHº), Û ‰fiÙË ‰ÂÍÈÔ‡ ‹·ÙÔ˜ ¯ˆÚ›˜ ÙË ª∏º. ‚. 1 cm ÚÔ˜ Ù· ‰ÂÍÈ¿ Ù˘ MHº ÛÎÈ·ÁÚ·ÊÂ›Ù·È Ì ÙÔ Argon laser ÙÔ Â›Â‰Ô Ù˘ Ë·ÙÂÎÙÔÌ‹˜. Á. AÂÈÎfiÓÈÛË Ù˘ ·ÎÔ˘ÛÙÈ΋˜ ÛÎÈ¿˜ ÙÔ˘ ÂȤ‰Ô˘ Ù˘ Ë·ÙÂÎÙÔÌ‹˜ (‚¤ÏÔ˜), Ì ‰ÈÂÁ¯ÂÈÚËÙÈÎfi ¤Á¯ÚˆÌÔ Doppler, ¤ÙÛÈ ÒÛÙ ӷ ‰È¤Ú¯ÂÙ·È ‰ÂÍÈ¿ Ù˘ ̤Û˘ Ë·ÙÈ΋˜ ÊϤ‚·˜ (middle hepatic vein, MHV) Î·È ‰. ‰È· ÙÔ˘ ‰ÂÍÈÔ‡ ÎÏ¿‰Ô˘ Ù˘ ˘Ï·›·˜ ÊϤ‚·˜ (ÎÂʷϤ˜ ‚ÂÏÒÓ), Ì Gray-scale US scan (‰ÂÍÈ¿).
IV ÚÔ¤Ú¯ÂÙ·È Â›Ù ·fi ÙËÓ AHA, ›ÙÂ Î·È ·fi ÙËÓ AHA Î·È ·fi ÙËÓ ¢HA, Ë ·Ú·Û΢‹ Ù˘ ¢HA ÚÔ¯ˆÚ› ̤¯ÚÈ ÙÔÓ ‰È¯·ÛÌfi Ù˘ ÎÔÈÓ‹˜ Ë·ÙÈ΋˜ ·ÚÙËÚ›·˜. M ·Ó¿ÏÔÁÔ ÙÚfiÔ Á›ÓÂÙ·È Î·È Ë ·Ú·Û΢‹ ÙÔ˘ ‰ÂÍÈÔ‡ ÎÏ¿‰Ô˘ Ù˘ ˘Ï·›·˜ ÊϤ‚·˜ (EÈÎfiÓ· 8)52,53. ∏ ÎÈÓËÙÔÔ›ËÛË ÙÔ˘ ‹·ÙÔ˜, Û ‰ÂÍÈ¿ Ë·ÙÂÎÙÔÌ‹, Á›ÓÂÙ·È Ì ‰È·ÙÔÌ‹ ÙÔ˘ ‰ÂÍÈÔ‡ ÛÙÂÊ·ÓÈ·›Ô˘ Î·È ÙÔ˘ ÙÚÈÁÒÓÔ˘ Û˘Ó‰¤ÛÌÔ˘, Ë ÛÙÚÔÊ‹ ÙÔ˘ ‹·ÙÔ˜ ÚÔ˜ Ù· ·ÚÈÛÙÂÚ¿. ∞ÎÔÏÔ˘ı› Ë ·Ú·Û΢‹ ÙÔ˘ ÔÈÛıÔË·ÙÈÎÔ‡ ÙÌ‹Ì·ÙÔ˜ Ù˘ οو ÎÔ›Ï˘ ÊϤ‚·˜ (KKº). OÈ ‚Ú·¯Â›Â˜ Ë·ÙÈΤ˜ ÊϤ‚˜ ·ÔÏÈÓÒÓÔÓÙ·È Ì¤¯ÚÈ ÙÔ ‡„Ô˜ Ù˘ ‰ÂÍÈ¿˜ Ë·ÙÈ΋˜
ÊϤ‚·˜ (¢Hº), ÚÔ˜ Ù· ¿Óˆ Î·È Ì¤¯ÚÈ ÙÔ Â›Â‰Ô Ù˘ Ë·ÙÂÎÙÔÌ‹˜, ÚÔ˜ Ù· ¤Ûˆ. H ·Ú·Û΢‹ Ù˘ ‰ÂÍÈ¿˜ Ë·ÙÈ΋˜ ÊϤ‚·˜ ··ÈÙ› Ó· ‰È·Ù·Ì› Ì›· ÈÓ҉˘ Ù·ÈÓ›· ÛÙÂÚÚÔ‡ Û˘Ó‰ÂÙÈÎÔ‡ ÈÛÙÔ‡, Ô Û‡Ó‰ÂÛÌÔ˜ Ù˘ KKº, Ô ÔÔ›Ô˜ ÂÎÙ›ÓÂÙ·È ÌÂٷ͇ ÙÔ˘ ÔÈÛı›Ô˘ ¯Â›ÏÔ˘˜ ÙÔ˘ ÎÂÚÎÔÊfiÚÔ˘ Î·È ÙÔ˘ ‰ÂÍÈÔ‡ ÏÔ‚Ô‡ ÙÔ˘ ‹·ÙÔ˜. K·Ù¿ ÙËÓ Ë ÛÙÚÔÊ‹ ÙÔ˘ ‹·ÙÔ˜ ÚÔ˜ Ù· ·ÚÈÛÙÂÚ¿, Ô Û‡Ó‰ÂÛÌÔ˜ Ù˘ KKº Û˘ÌȤ˙ÂÈ ÙËÓ ‰ÂÍÈ¿ Ë·ÙÈ΋ ÊϤ‚· Î·È ÌÔÚ› Ó· ÚÔηϤÛÂÈ ÊÏ‚È΋ Û˘ÌÊfiÚËÛË ÙÔ˘ ÌÔۯ‡̷ÙÔ˜. (EÈÎfiÓ· 9 ·-Á). ™ÙÔ 10% ÙˆÓ ‰ÔÙÒÓ ·Ó¢ڛÛÎÂÙ·È Ì›· ÂÈÎÔ˘ÚÈ΋ ‰ÂÍÈ¿ Ë·ÙÈ΋ ÊϤ‚·, Ì ‰È¿ÌÂÙÚÔ ÌÂÁ·Ï‡ÙÂ-
60
π. ºOÀ∑∞™, ¢. Δ∞∫OÀ¢∞™
EÈÎfiÓ· 7. ¢ÈÂÁ¯ÂÈÚËÙÈ΋ ¯ÔÏ·ÁÁÂÈÔÁÚ·Ê›· Û ‰fiÙË ‰ÂÍÈÔ‡ ÏÔ‚Ô‡ ‹·ÙÔ˜. · : O ¯ÔÏˉfi¯Ô˜ fiÚÔ˜ ÙÔ˘ ÙÌ‹Ì·ÙÔ˜ VII (Ï¢΋ ÎÂÊ·Ï‹ ‚¤ÏÔ˘˜) Â΂¿ÏÏÂÈ ÛÙÔÓ ·ÚÈÛÙÂÚfi ¯ÔÏˉfi¯Ô fiÚÔ, ‚: ÌÂÙ¿ ÙËÓ ‰È·ÙÔÌ‹ Î·È ·ÔϛӈÛË ÙÔ˘ ‰ÂÍÈÔ‡ Ë·ÙÈÎÔ‡ (‚¤ÏÔ˜), ÙÔ ÚÔ‚ÏÂfiÌÂÓÔ ÛËÌÂ›Ô ‰È·ÙÔÌ‹˜ ÙÔ˘ ÎÏ¿‰Ô˘ ÙÔ˘ ÙÌ‹Ì·ÙÔ˜ VII ÛËÌÂÈÒÓÂÙ·È Ì ·ÁÁÂÈÔÏ·‚›‰· (ÎÂÊ·Ï‹ ‚¤ÏÔ˘˜). ¢ÂÓ Ú¤ÂÈ Ó· Á›ÓÂÙ·È ÚÔÛ¿ıÂÈ· Ó· ÏËÊı› ÌÔÓ‹Ú˜ ÛÙfiÌÈÔ ÛÙÔÓ ‰ÂÍÈfi ¯ÔÏˉfi¯Ô fiÚÔ Û ‚¿ÚÔ˜ ÙˆÓ ¯ÔÏËÊfiÚˆÓ ÙÔ˘ ‰fiÙË. Á: º˘ÛÈÔÏÔÁÈ΋ ¯ÔÏ·ÁÁÂÈÔÁÚ·Ê›· ÙÔ˘ ‹·ÙÔ˜ ÙÔ˘ ‰fiÙË ÌÂÙ¿ ÙËÓ ÂÎÙÔÌ‹ ÙÔ˘ ÌÔۯ‡̷ÙÔ˜. ‰. ∂Ȃ‚·›ˆÛË ÙˆÓ Â˘ÚËÌ¿ÙˆÓ Ù˘ ¯ÔÏ·ÁÁÂÈÔÁÚ·Ê›·˜ ÌÂÙ¿ ÙËÓ ‰È·ÙÔÌ‹ ÎÏ¿‰ˆÓ ÙÔ˘ ‰ÂÍÈÔ‡ Ë·ÙÈÎÔ‡ fiÚÔ˘.
ÚË ·fi 5 mm, Ë ÔÔ›· ·ÚÔ¯ÂÙ‡ÂÈ ÙÔ Ô›ÛıÈÔ Î¿Ùˆ ÙÌ‹Ì· ÙÔ˘ ‰ÂÍÈÔ‡ ÏÔ‚Ô‡ ÚÔ˜ ÙËÓ ÔÈÛıÔË·ÙÈ΋ KKº. (EÈÎfiÓ· 9‰). TÔ ·ÁÁÂ›Ô ·˘Ùfi ÌÔÚ› Ó· Û˘ÓÂÈÛʤÚÂÈ ÛËÌ·ÓÙÈο ÛÙËÓ ÊÏ‚È΋ ·Ô¯¤Ù¢ÛË ÙÔ˘ ‰ÂÍÈÔ‡ ÏÔ‚Ô‡ Î·È Ë ·Ôϛӈۋ ÙÔ˘ ÌÔÚ› Ó· ÚÔηϤÛÂÈ ÊÏ‚È΋ Û˘ÌÊfiÚËÛË ÌÂÙ¿ ÙËÓ Â·ÓÂÌʇÙ¢ÛË. OÈ ÂÚÈÛÛfiÙÂÚÔÈ Û˘ÁÁÚ·Ê›˜ ·Ó·Ê¤ÚÔ˘Ó fiÙÈ fiÙ·Ó Ë ÂÈÎÔ˘ÚÈ΋ ‰ÂÍÈ¿ Ë·ÙÈ΋ ÊϤ‚·
¤¯ÂÈ ‰È¿ÌÂÙÚÔ ÌÂÁ·Ï‡ÙÂÚË ·fi 5 mm Ú¤ÂÈ Ó· ‰È·ÛÒ˙ÂÙ·È Î·È Ó· ·Ó·ÛÙÔÌÒÓÂÙ·È Ì ÙËÓ KKº ÙÔ˘ Ï‹ÙË. ΔÔ Â›Â‰Ô ‰È·ÙÔÌ‹˜ ÙÔ˘ Ë·ÙÈÎÔ‡ ·ÚÂÁ¯‡Ì·ÙÔ˜ Â›Ó·È ·Ó¿ÏÔÁÔ ÙÔ˘ Ù‡Ô˘ ÙÔ˘ ÌÔۯ‡̷ÙÔ˜ (∂ÈÎfiÓ· 3). ∏ ‚·ÛÈ΋ ·Ú¯‹ Â›Ó·È fiÙÈ ‰ÂÓ Ú¤ÂÈ ˘¿Ú¯ÂÈ ÓÂÎڈ̤ÓÔ Ë·ÙÈÎfi ·Ú¤Á¯˘Ì· ÛÙÔÓ ‰fiÙË ‹ ÛÙÔÓ Ï‹ÙË, ÙÔ ÔÔ›Ô ÌÔÚ› Ó· ÚÔηϤÛÂÈ Û˘-
METAMO™XEY™Eπ™ 2008
EÈÎfiÓ· 8. ™¯ËÌ·ÙÈ΋ ·ÂÈÎfiÓÈÛË ÙÔ˘ ÙÌ‹Ì·ÙÔ˜ IV ÙÔ˘ ‹·ÙÔ˜ Ì ÙËÓ ·ÚÙËÚȷ΋ ÊÏ‚È΋ ·ÈÌ¿ÙˆÛË ÙÔ˘ Ó· ÚÔ¤Ú¯ÂÙ·È ·fi Ù· ‰ÂÍÈ¿. TÔ ÛËÌÂ›Ô ‰È·ÙÔÌ‹˜ Ù˘ ‰ÂÍÈ¿˜ Ë·ÙÈ΋˜ ·ÚÙËÚ›·˜ ÌÂÙ·ÎÈÓÂ›Ù·È ·fi ÙÔ · ÛÙÔ ‚ fiÙ·Ó Ô Î‡ÚÈÔ˜ ·ÚÙËÚÈ·Îfi˜ ÎÏ¿‰Ô˜ (b) ÚÔ¤Ú¯ÂÙ·È ·fi Ù· ‰ÂÍÈ¿. TÔ ÛËÌÂ›Ô ‰È·ÙÔÌ‹˜ Ù˘ ‰ÂÍÈ¿˜ ˘Ï·›·˜ ÊϤ‚·˜ ÌÂÙ·ÎÈÓÂ›Ù·È ·fi ÙÔ Á ÛÙÔ ‰ ÁÈ· Ó· ‰È·ÙËÚËıÔ‡Ó ÛËÌ·ÓÙÈÎÔ› ÎÏ¿‰ÔÈ ÚÔ˜ ÙÔ ÙÌ‹Ì· IV (2).
ÛÙËÌ·ÙÈ΋ ÊÏÂÁÌÔÓÒ‰Ë ·ÓÙ›‰Ú·ÛË Î·È Û‹„Ë48. ™Â ·ÚÈÛÙÂÚ¿ ÏÔ‚ÂÎÙÔÌ‹ (ÙÌ‹Ì·Ù· ππ + πππ), ÙÔ Â›Â‰Ô ‰È·ÙÔÌ‹˜ ¢ڛÛÎÂÙ·È ÚÔ˜ Ù· ‰ÂÍÈ¿ ÙÔ˘ ‰Ú·ÓÔÂȉԇ˜ Û˘Ó‰¤ÛÌÔ˘. ∏ ÔÌÊ·ÏÈ΋ ÊϤ‚· ‰È·ÛÒ˙ÂÙ·È Î·Ù¿ ÙËÓ ·Ú·Û΢‹ ‰ÈfiÙÈ ˘Ô‚ÔËı¿ ÛÙËÓ ÊÏ‚È΋ ·ÚÔ¯¤Ù¢ÛË ÙÔ˘ ÙÌ‹Ì·ÙÔ˜ πππ55. ΔÔ ÙÌ‹Ì· IV ÛÙÔÓ ‰fiÙË ÌÔÚ› Ó· ·ÚÔ˘ÛÈ¿ÛÂÈ ÈÛ¯·ÈÌÈ΋ ¯ÚÔÈ¿, ·ÏÏ¿ Ë ·ÈÌ¿ÙˆÛË ÙÔ˘ ‰È·ÛÒ˙ÂÙ·È ·Ó ‰È·ÙËÚËıÔ‡Ó ÔÈ ·ÚÙËÚÈ·ÎÔ› Î·È ˘Ï·›ÔÈ ÎÏ¿‰ÔÈ (∂ÈÎfiÓ· 9‰). ™Â ‰ÂÍÈ¿ ‹ ·ÚÈÛÙÂÚ¿ Ë·ÙÂÎÙÔÌ‹ ÙÔ Â›Â‰Ô ‰È·ÙÔÌ‹˜ ¢ڛÛÎÂÙ·È ÛÙËÓ ÁÚ·ÌÌ‹ ÙÔ˘ Cantlie, fiˆ˜ ηıÔÚ›˙ÂÙ·È ·fi ÙËÓ ÚÔÛˆÚÈÓ‹ Û‡ÁÎÏÂÈÛË ÙÔ˘ ‰ÂÍÈÔ‡ ˘Ï·›Ô˘ Ì›Û¯Ô˘ Î·È ÙÔ ‰ÈÂÁ¯ÂÚËÙÈÎfi ˘ÂÚ˯ÔÁÚ¿ÊËÌ·. ΔÔ ·ÚÈÛÙÂÚfi Ë·ÙÈÎfi ÌfiÛ¯Â˘Ì· ÂÚÈÏ·Ì‚¿ÓÂÈ ¿ÓÙÔÙ ÙË Ì¤ÛË Ë·ÙÈ΋ ÊϤ‚·. ∏ ·Ó¿ÁÎË Ó· Û˘ÌÂÚÈÏËÊı› Ë Ì¤ÛË Ë·ÙÈ΋ ÊϤ‚· ÛÙÔ ‰ÂÍÈfi Ë·ÙÈÎfi ÌfiÛ¯Â˘Ì· Â›Ó·È ·ÌÊÈÏÂÁfiÌÂÓË ‰ÈfiÙÈ ÂÓÒ ÂÍ·ÛÊ·Ï›˙ÂÈ ¿ÚÈÛÙË ÊÏ‚È΋ ·Ô¯¤Ù¢-
61
ÛË ÛÙÔÓ Ï‹ÙË, ÌÔÚ› Ó· ¤¯ÂÈ ·ÚÓËÙÈΤ˜ Û˘Ó¤ÂȘ ÁÈ· ÙÔÓ ‰fiÙË. ∏ ÔÌ¿‰· ÙÔ˘ Hong Kong ÂÈÛ‹Á·Á ·˘Ù‹ ÙËÓ ¿Ô„Ë Î·È ·¤‰ÂÈÍ fiÙÈ Ë Ï‹„Ë Ù˘ ̤Û˘ Ë·ÙÈ΋˜ ÊϤ‚·˜ Ì ÙÔ ‰ÂÍÈfi Ë·ÙÈÎfi ÌfiÛ¯Â˘Ì· Â›Ó·È ·ÛÊ·Ï‹˜ ÁÈ· ÙÔÓ ‰fiÙË Î·È Î·ıÔÚÈÛÙÈ΋ ÁÈ· ÙËÓ ÏÂÈÙÔ˘ÚÁ›· ÙÔ˘ ÌÔۯ‡̷ÙÔ˜ Î·È ÙËÓ ÂÈ‚›ˆÛË ÙÔ˘ Ï‹ÙË56,57. Δ· Â˘Ú‹Ì·Ù· ·˘Ù¿ ÂȂ‚·ÈÒıËÎ·Ó Î·È ·fi ÙȘ ÔÌ¿‰Â˜ ÛÙÔ ΔÔÚfiÓÙÔ Î·È ÛÙÔ ¶·Ú›ÛÈ58,59. OÈ de Villa et al.,60 ‰ËÌÈÔ‡ÚÁËÛ·Ó ¤Ó· ·ÏÁfiÚÈıÌÔ, Ì ‚¿ÛË ÙË Û¯¤ÛË ÛˆÌ·ÙÈÎÔ‡ ‚¿ÚÔ˘˜ ‰fiÙË Î·È Ï‹ÙË, ÙËÓ Û¯¤ÛË ÙÔ˘ fiÁÎÔ˘ ÙÔ˘ ‰ÂÍÈÔ‡ ‹·ÙÔ˜ ÚÔ˜ ÙÔÓ Î·Ù’ ÂÎÙ›ÌËÛË Ê˘ÛÈÔÏÔÁÈÎfi fiÁÎÔ ‹·ÙÔ˜ ÙÔ˘ Ï‹ÙË (standard liver volume, SLV) Î·È ÙËÓ ·Ó·ÙÔÌÈ΋ ÙˆÓ Ë·ÙÈÎÒÓ ÊÏ‚ÒÓ ÙÔ˘ ‰fiÙË Î·È ¤‰ÂÈÍ·Ó fiÙÈ ÌÔÚ› Ó· ·ÔÊ·ÛÈÛı› Ë ¤ÎÙ·ÛË Ù˘ ‰ÂÍÈ¿˜ Ë·ÙÂÎÙÔÌ‹˜, Ì ‹ ¯ˆÚ›˜ ÙË Ì¤ÛË Ë·ÙÈ΋ ÊϤ‚·, Ì ÈηÓÔÔÈËÙÈο ·ÔÙÂϤÛÌ·Ù· Î·È ÁÈ· ÙÔÓ ‰fiÙË Î·È ÁÈ· ÙÔÓ Ï‹ÙË. ∏ ÔÌ¿‰· ÙÔ˘ Essen ÂȂ‚·›ˆÛ ٷ Â˘Ú‹Ì·Ù· ÙˆÓ de Villa et al.,60 ÙfiÛÔ Ì ÙËÓ ÚÔÂÁ¯ÂÈÚËÙÈ΋ ÂÎÙ›ÌËÛË Ì ÙÔ MeVis – HepaVision,45-47 fiÛÔ Î·È Ì ٷ ÂÁ¯ÂÈÚËÙÈο Â˘Ú‹Ì·Ù· Î·È ·ÔÙÂϤÛÌ·Ù·61. ∂ÈϤÔÓ, ¤‰ÂÈÍ fiÙÈ Ì ÙËÓ «Â΢ڋÓËÛË» (carving ) Ù˘ ̤Û˘ Ë·ÙÈ΋˜ ÊϤ‚·˜ ·fi ÙÔ ·ÚÈÛÙÂÚfi ‹·Ú ‰È·ÛÒ˙ÂÙ·È ÙÌ‹Ì· Ë·ÙÈÎÔ‡ ·ÚÂÁ¯‡Ì·ÙÔ˜62. H ‰È·ÙÔÌ‹ ÙÔ˘ Ë·ÙÈÎÔ‡ ·ÚÂÁ¯‡Ì·ÙÔ˜ ·Ú¯›˙ÂÈ ·fi ÙÔ ÚfiÛıÈÔ ¯Â›ÏÔ˜ ÙÔ˘ ‹·ÙÔ˜ Î·È ÚÔ¯ˆÚ› Ù·˘Ùfi¯ÚÔÓ· ÚÔ˜ ÙȘ ‡Ï˜ Î·È ÙËÓ Û˘Ì‚ÔÏ‹ ÙˆÓ Ë·ÙÈÎÒÓ ÊÏ‚ÒÓ. ™ÙȘ Ë·ÙÂÎÙÔ̤˜ ÁÈ¿ ÓÂÔÏ¿ÛÌ·Ù· Ë ‰È·ÙÔÌ‹ ÙÔ˘ Ë·ÙÈÎÔ‡ ·ÚÂÁ¯‡Ì·ÙÔ˜ Á›ÓÂÙ·È ÌÂÙ¿ ·fi Ï‹ÚË ·ÁÁÂÈ·Îfi ·ÔÎÏÂÈÛÌfi. H ̤ıÔ‰Ô˜ ·˘Ù‹ ‰ÂÓ ÌÔÚ› Ó· ÂÊ·ÚÌÔÛı› ÛÙËÓ Ë·ÙÂÎÙÔÌ‹ ÙÔ˘ ‰fiÙË ‰ÈfiÙÈ ÈÛÙ‡ÂÙ·È fiÙÈ Ë ÈÛ¯·ÈÌÈ΋ ‚Ï¿‚Ë ·˘Í¿ÓÂÈ ÙÔÓ Î›Ó‰˘ÓÔ ÚˆÙÔ·ıÔ‡˜ ÌË ÏÂÈÙÔ˘ÚÁ›·˜ ÙÔ˘ ÌÔۯ‡̷ÙÔ˜ Î·È ÂÏ·ÙÙÒÓÂÈ ÙËÓ ·Ó·ÁÂÓÓËÙÈ΋ ÙÔ˘ ÈηÓfiÙËÙ·. Afi ÙËÓ ¿ÏÏË ÏÂ˘Ú¿, Ú¤ÂÈ Ó· ÌÂȈı› ÛÙÔ ÂÏ¿¯ÈÛÙÔ Ë ·ÈÌÔÚÚ·Á›·. OÈ ÂÚÈÛÛfiÙÂÚÔÈ Û˘ÁÁÚ·Ê›˜ ÚÔÙ›ÓÔ˘Ó ÙËÓ ‰È·ÙÔÌ‹ Ì CUSA (Cavitron Ultrasonic Aspirator, Valley Lab, Boulder, CO). H Û˘Û΢‹ ·˘Ù‹ ‰È·ı¤ÙÂÈ Ì›· ÌÂÙ·ÏÏÈ΋ ·Î›‰· Ë ÔÔ›· ¿ÏÏÂÙ·È Ì ˘ÂÚ˯ËÙÈ΋ Û˘¯ÓfiÙËÙ· Î·È ÚÔηÏ› ÙËÓ Ú‹ÍË ÙÔ˘ Ë·ÙÈÎÔ‡ ·ÚÂÁ¯‡Ì·ÙÔ˜ Î·È ÙËÓ ·ÔÎfiÏÏËÛË ÙˆÓ Ë·ÙÔ΢ÙÙ¿ÚˆÓ. T·˘Ùfi¯ÚÔÓ·, ÙÔ ÂÁ¯ÂÈÚËÙÈÎfi ‰›Ô ÂÎϤÓÂÙ·È Î·È Ù· Ë·ÙÔ·ÙÙ·Ú· Ô˘ ·ÔÎÔÏÏ‹ıËÎ·Ó ·Ó·ÚÚÔÊÒÓÙ·È. TÔ ÙÂÏÈÎfi ·ÔÙ¤ÏÂÛÌ· Â›Ó·È fiÙÈ ·ÔÁ˘ÌÓÒÓÔÓÙ·È Ù· ·ÈÌÔÊfiÚ· ·ÁÁ›· Î·È Ù· ¯ÔÏ·ÁÁ›· ¯ˆÚ›˜ Ó· ÙÚ·˘Ì·ÙÈÛıÔ‡Ó. (EÈÎfiÓ· 10 · Î·È ‚) T· ÌÈÎÚfiÙÂÚ· ·ÁÁ›· ‰È·Ù¤ÌÓÔÓÙ·È
62
π. ºOÀ∑∞™, ¢. Δ∞∫OÀ¢∞™
EÈÎfiÓ· 9. ·. OÈÛı›· ÂÈÊ¿ÓÂÈ· ÙÔ˘ ‹·ÙÔ˜. O Û‡Ó‰ÂÛÌÔ˜ Ù˘ KKº ÂÎÙ›ÓÂÙ·È ÌÂٷ͇ ÙÔ˘ ÔÈÛı›Ô˘ ¯Â›ÏÔ˘˜ ÙÔ˘ ÎÂÚÎÔÊfiÚÔ˘ Î·È ÙÔ˘ ‰ÂÍÈÔ‡ ÏÔ‚Ô‡ ÙÔ˘ ‹·ÙÔ˜. ‚. EÁηÚÛ›· ·ÂÈÎfiÓÈÛË ÙÔ˘ Û˘Ó‰¤ÛÌÔ˘ Ù˘ KKº. Á. K·Ù¿ ÙËÓ ·Ú·Û΢‹ ÙÔ˘ ÙÔ˘ ÔÈÛıÔË·ÙÈÎÔ‡ ÙÌ‹Ì·ÙÔ˜ Ù˘ KKº Î·È ÙËÓ ÛÙÚÔÊ‹ ÙÔ˘ ‹·ÙÔ˜ ÚÔ˜ Ù· ·ÚÈÛÙÂÚ¿, Ô Û‡Ó‰ÂÛÌÔ˜ Ù˘ KKº Û˘ÌȤ˙ÂÈ ÙËÓ ‰ÂÍÈ¿ Ë·ÙÈ΋ ÊϤ‚·. ‰. AÂÈÎÔÓ›˙ÂÙ·È Î·È Ë ‰ÂÍÈ¿ Ë·ÙÈ΋ ÊϤ‚·, fiˆ˜ Î·È ÔÈ ‚Ú·¯Â›Â˜ Ë·ÙÈΤ˜ ÊϤ‚˜ Î·È ÂÈÎÔ˘ÚÈ΋ ‰ÂÍÈ¿ Ë·ÙÈ΋ ÊϤ‚·.
Ì ‰ÈÔÏÈ΋ ‰È·ıÂÚÌ›· Î·È Ù· ÌÂÁ·Ï‡ÙÂÚ· ·ÔÏÈÓÒÓÔÓÙ·È ‹ Û˘ÏÏ·Ì‚¿ÓÔÓÙ·È Ì ÂȉÈÎÔ‡˜ ÌÂÙ·ÏÏÈÎÔ‡˜ ·ÁÎÙ‹Ú˜ (clips). MÈÎÚfiÙÂÚ˜ ÂÛٛ˜ ·ÈÌÔÚÚ·Á›·˜ η˘ÙËÚÈ¿˙ÔÓÙ·È Ì Argon laser (Argon beam coagulator, Conmed, Utica, NY)51. OÙ·Ó Ë ‰È·ÙÔÌ‹ Êı¿ÛÂÈ ÛÙÔ Î·ÙÒÙÂÚÔ ÙÚÈÙËÌfiÚÈÔ Ù˘ οو ÂÈÊ·Ó›·˜ ÙÔ˘ ‹·ÙÔ˜, Ë Î·Ù‡ı˘ÓÛË Ù˘ ηıÔÚ›˙ÂÙ·È ·fi ÙËÓ ÔÚ›· ÙÔ˘ ‰ÂÍÈÔ‡ Ë·ÙÈÎÔ‡ fiÚÔ˘. ™ÙË Û˘Ó¤¯ÂÈ·, Ë ‰È·ÙÔÌ‹ ÙÔ˘ Ë·ÙÈÎÔ‡ ·ÚÂÁ¯‡Ì·ÙÔ˜ ÚÔ¯ˆÚ› ÚÔ˜ ÙËÓ ‰ÂÍÈ¿ Ë·ÙÈ΋ ÊϤ‚· Î·È ÙËÓ Î¿Ùˆ ÎÔ›ÏË ÊϤ‚·, Ì ηÙ‡ı˘ÓÛË ÚÔ˜ Ù· ·ÚÈÛÙÂÚ¿ ÙˆÓ ÂÈÎÔ˘ÚÈÎÒÓ Ë·ÙÈÎÒÓ ÊÏ‚ÒÓ, ·Ó ˘¿Ú¯Ô˘Ó. TÂÏÈο, ·Ú·Û΢¿˙ÂÙ·È Ë Â΂ÔÏ‹ Ù˘ ‰ÂÍÈ¿˜ Ë·ÙÈ΋˜ ÊϤ‚·˜, ‰È·Ù¤ÌÓÂÙ·È Ë Á¤Ê˘Ú· ÙÔ˘ Ë·ÙÈÎÔ‡ ·ÚÂÁ¯‡Ì·ÙÔ˜ ›Ûˆ ·fi ÙËÓ ˘Ï·›· ÊϤ‚·, ¤ÙÛÈ ÒÛÙÂ Ô ‰ÂÍÈfi˜ ÏÔ‚fi˜ Ó· ÎÚ¤ÌÂÙ·È ÌfiÓÔ ·fi Ù· ·ÁÁ›· ÙÔ˘. M ÙÔÓ Û˘Ó-
‰˘·ÛÌfi ÙˆÓ ·ÓˆÙ¤Úˆ Ù¯ÓÈÎÒÓ, Ë ‰È·ÙÔÌ‹ ÙÔ˘ Ë·ÙÈÎÔ‡ ·ÚÂÁ¯‡Ì·ÙÔ˜ ÔÏÔÎÏËÚÒÓÂÙ·È Û 1 – 2 ÒÚ˜, Ì ÂÏ¿¯ÈÛÙË ·ÒÏÂÈ· ·›Ì·ÙÔ˜ Î·È ¯ˆÚ›˜ ·ÁÁÂÈ·Îfi ·ÔÎÏÂÈÛÌfi. OÈ ‰ÂÍÈÔ› ÎÏ¿‰ÔÈ Ù˘ Ë·ÙÈ΋˜ ·ÚÙËÚ›·˜ Î·È Ù˘ ˘Ï·›·˜ ÊϤ‚·˜ Û˘Ï·Ì‚¿ÓÔÓÙ·È Ì ·ÁÁÂÈÔÏ·‚›‰Â˜ Î·È ‰È·Ù¤ÌÓÔÓÙ·È Û ·fiÛÙ·ÛË ·ÚÎÂÙ‹ ·fi ÙÔÓ ‰È¯·ÛÌfi ÒÛÙÂ, ηٿ ÙËÓ Û˘ÚÚ·Ê‹ ÙÔ˘ ÎÂÓÙÚÈÎÔ‡ ÎÔÏÔ‚ÒÌ·ÙÔ˜, Ó· ÌËÓ ÚÔÎÏËı› ÛÙ¤ÓˆÛË ÙˆÓ ·ÁÁ›ˆÓ ÙÔ˘ ‰fiÙË. ™ÙË Û˘Ó¤¯ÂÈ· ‰È·Ù¤ÌÓÔÓÙ·È Ù˘¯fiÓ ˘¿Ú¯Ô˘Û˜ ÂÈÎÔ˘ÚÈΤ˜ ‰ÂÍȤ˜ Ë·ÙÈΤ˜ ÊϤ‚˜ Î·È ÙÂÏÈο Ô ‰ÂÍÈfi˜ ÏÔ‚fi˜ ·Ó·Û¿Ù·È Î·È ‰È·Ù¤ÌÓÂÙ·È Ë ‰ÂÍÈ¿ Ë·ÙÈ΋ ÊϤ‚· (EÈÎfiÓ· 10Á). O ‰ÂÍÈfi˜ ÏÔ‚fi˜ ÌÂٷʤÚÂÙ·È Û ·ÔÛÙÂÈڈ̤ÓÔ ÙÚ·¤˙È Î·È ÂÎϤÓÂÙ·È Ì ‰È¿Ï˘Ì· ÙÔ˘ ¶·ÓÂÈÛÙËÌ›Ô˘ ÙÔ˘ Wisconsin. AÎÔÏÔ˘ı› ÂÈÌÂÏ‹˜ ·ÈÌfiÛÙ·ÛË Ù˘ ÂÈÊ·Ó›·˜ ‰È·ÙÔÌ‹˜ ÙÔ˘ ·ÚÈÛÙÂÚÔ‡ ÏÔ‚Ô‡, Ì ÙÔ Argon laser, ηıÒ˜
METAMO™XEY™Eπ™ 2008
63
EÈÎfiÓ· 10 · η ‚. ¢È·ÙÔÌ‹ ÙÔ˘ Ë·ÙÈÎÔ‡ ·ÚÂÁ¯‡Ì·ÙÔ˜ Ì CUSA (Cavitron Ultrasonic Aspirator, Valley Lab, Boulder, CO). AÔÁ˘ÌÓÒÓÔÓÙ·È Ù· ·ÈÌÔÊfiÚ· ·ÁÁ›· Î·È Ù· ¯ÔÏ·ÁÁ›· ¯ˆÚ›˜ Ó· ÙÚ·˘Ì·ÙÈÛıÔ‡Ó. Á. OÈ ‰ÂÍÈÔ› ÎÏ¿‰ÔÈ Ù˘ Ë·ÙÈ΋˜ ·ÚÙËÚ›·˜ (¢HA) Î·È Ù˘ ˘Ï·›·˜ ÊϤ‚·˜ (¢¶º), ηıÒ˜ Î·È Ù˘¯fiÓ ˘¿Ú¯Ô˘Û˜ ÂÈÎÔ˘ÚÈΤ˜ ‰ÂÍȤ˜ Ë·ÙÈΤ˜ ÊϤ‚˜ (E¢Hº) Û˘ÏÏ·Ì‚¿ÓÔÓÙ·È Ì ·ÁÁÂÈÔÏ·‚›‰Â˜ Î·È ‰È·Ù¤ÌÓÔÓÙ·È Î·È ÙÂÏÈο Ô ‰ÂÍÈfi˜ ÏÔ‚fi˜ ·Ó·Û¿Ù·È Î·È ‰È·Ù¤ÌÓÂÙ·È Ë ‰ÂÍÈ¿ Ë·ÙÈ΋ ÊϤ‚· (¢Hº).
Î·È Ù˘ ÎÔ›Ù˘ ÙÔ˘ ‰ÂÍÈÔ‡ ÏÔ‚Ô‡. TÔÔıÂÙÔ‡ÓÙ·È ·ÚÔ¯ÂÙ‡ÛÂȘ Î·È Ù· ÙÔȯÒÌ·Ù· Û˘ÁÎÏ›ÔÓÙ·È Î·Ù¿ ÛÙÚÒÌ·Ù·.
∂¶π¶§O∫E™ ∏ ·ÛÊ¿ÏÂÈ· ÙÔ˘ ‰fiÙË Â›Ó·È ÚˆÙ·Ú¯ÈÎfi˜ ÛÙfi¯Ô˜ ηٿ ÙË LDLTx. ∫·ıÒ˜ Ë ÂÊ·ÚÌÔÁ‹ Ù˘ LDLTx ÚÔ¯ÒÚËÛ ·fi ÙÔ˘˜ ÂÓ‹ÏÈΘ ÛÙ· ·È‰È¿
Î·È ·fi ÙÔ ·ÚÈÛÙÂÚfi ÛÙÔ ‰ÂÍÈfi Ë·ÙÈÎfi ÌfiÛ¯Â˘Ì·, ÙÔ ‰›ÏËÌ· ÌÂٷ͇ Ù˘ ÂÈÙ˘¯›·˜ ÛÙÔÓ Ï‹ÙË Î·È Ù˘ ·ÛÊ¿ÏÂÈ·˜ ÙÔ˘ ‰fiÙË ‹Ïı ÛÙÔ ÚÔÛ΋ÓÈÔ. ΔÔ ÔÛÔÛÙfi ÂÈÏÔÎÒÓ ÙÔ˘ ‰fiÙË Â›Ó·È ÂÚ›Ô˘ 20%, ·ÏÏ¿ Êı¿ÓÂÈ Ì¤¯ÚÈ ÙÔ 67% Û ̛· ·Ó·ÛÎfiËÛË63. ΔÔ Â‡ÚÔ˜ ·˘Ùfi ÈÛÙ‡ÂÙ·È fiÙÈ ı· ÌÂȈı› Ì ÙËÓ ÂÊ·ÚÌÔÁ‹ ÂÓfi˜ ÂÓÔÔÈË̤ÓÔ˘ Û˘ÛÙ‹Ì·ÙÔ˜ ·Ó·ÊÔÚ¿˜ ÙˆÓ ÌÂÙÂÁ¯ÂÈÚËÙÈÎÒÓ ÂÈÏÔÎÒÓ64. ∂ÈϤÔÓ,
64
π. ºOÀ∑∞™, ¢. Δ∞∫OÀ¢∞™
ÔÈΛÏÏÂÈ Î·È Ë ‚·Ú‡ÙËÙ· ÙˆÓ ·Ó·ÊÂÚÔÌ¤ÓˆÓ ÂÈÏÔÎÒÓ. ∏ ÏÂÈÔÓfiÙËÙ· ÙˆÓ ÂÈÏÔÎÒÓ ·ÊÔÚ¿ ÙËÓ ‰È·‡ËÛË ÙÔ˘ ÙÚ·‡Ì·ÙÔ˜ Î·È ·ÎÔÏÔ˘ı› Ô ÌÂÙÂÁ¯ÂÈÚËÙÈÎfi˜ ÂÈÏÂfi˜ Î·È Ë ‰È·Ê˘Á‹ ·fi Ù· ¯ÔÏËÊfiÚ·, Ë ÔÔ›· ÌÂÈÒÓÂÙ·È Î·ıÒ˜ ·˘Í¿ÓÂÙ·È Ë ÂÌÂÈÚ›· ÙÔ˘ ÌÂÙ·ÌÔÛ¯Â˘ÙÈÎÔ‡ ΤÓÙÚÔ˘65. O ı¿Ó·ÙÔ˜ ÙÔ˘ ‰fiÙË Â›Ó·È ‰Ú·Ì·ÙÈ΋ ÂÈÏÔ΋ Ù˘ LDLTx Î·È Ì¤¯ÚÈ ÙÔÓ πÔ‡ÓÈÔ ÙÔ˘ 2007 ¤¯Ô˘Ó ·Ó·ÎÔÈÓˆı› ›ÛËÌ· 12 ÂÚÈÙÒÛÂȘ ·fi Ù· ÌÂÙ·ÌÔÛ¯Â˘ÙÈο ΤÓÙÚ·66. ∂ÈϤÔÓ, ˘¿Ú¯Ô˘Ó ¤ÌÌÂÛ˜ ·ÓÂȂ‚·›ˆÙ˜ ·Ó·ÊÔÚ¤˜ Î·È ÁÈ· 21 ·ÎfiÌË ı·Ó¿ÙÔ˘˜ ˙ÒÓÙˆÓ ‰ÔÙÒÓ66. OÎÙÒ ı¿Ó·ÙÔÈ ‰ÔÙÒÓ ¤¯Ô˘Ó ·Ó·ÊÂÚı› ÛÙËÓ ∂˘ÚÒË, 8 ÛÙȘ ∏¶∞, 10 ÛÙËÓ ∞Û›· Î·È 2 ÛÙËÓ ¡fiÙÈ· ∞ÊÚÈ΋66. ∏ ıÓËÙfiÙËÙ· ÂÎÙÈÌ¿Ù·È fiÙÈ Â›Ó·È 0.1-0.3% ÛÙȘ 14000 Ë·ÙÂÎÙÔ̤˜ Û ˙ÒÓÙ˜ ‰fiÙ˜ Ô˘ ¤¯Ô˘Ó Á›ÓÂÈ Ì¤¯ÚÈ ÙÔÓ πÔ‡ÓÈÔ ÙÔ˘ 2007 Î·È ·Ó¤Ú¯ÂÙ·È ÛÙÔ 0.5% ÛÙÔ˘˜ ‰fiÙ˜ ‰ÂÍÈÔ‡ ‹·ÙÔ˜66. ªÂ ¿ÏÏ· ÏfiÁÈ·, ÁÈ· Ó· ÂÈÙ¢¯ı› ÂÓÙ·ÂÙ‹˜ ÂÈ‚›ˆÛË 80% ÛÙÔ˘˜ Ï‹Ù˜ ··ÈÙÂ›Ù·È Ë ˙ˆ‹ ÂÓfi˜ ‰fiÙË ÁÈ· Ó· ÛˆıÔ‡Ó 160 Ï‹Ù˜67.
μπμ§πO°ƒ∞ºπ∞ 1. Renz JF, Busuttil RW. Adult-to-adult living-donor liver transplantation: a critical analysis. Semin Liver Dis 2000; 20, 4 : 411. 2. Couinaud C. Le Foie, Etudes Anatomiques et Chirurgicales. Paris: Masson & Cie, 1957. 3. Couinaud C. Controlled hepatectomies and exposure of the intrahepatic bile ducts. Anatomical and technical studies. Paris: C Couinaud, 1981. 4. 2000 Annual Report of the U.S. Scientific Registry for Transplant Recipients and the Organ Procurement and Transplantation Network: Transplant Data: 1990-1999. U.S. Department of Health and Human Services, Health Resources and Services Administration, Office of Special Programs, Division of Transplantation, Rockville, MD; United Network for Organ Sharing, Richmond, VA. 5. Keeffe EB. Liver transplantation: current status and novel approaches to liver replacement. Gastroenterology 2001; 120:749. 6. Emond JC, Whitington PF, Thistlethwaite JR, et al. Reduced-size orthotopic liver transplantation: use in the management of children with chronic liver disease. Hepatology 1989; 10: 867. 7. Bismuth H, Houssin D. Reduced-sized orthotopic liver graft in hepatic transplantation in children. Surgery 1984; 95: 367. 8. Pichlmayr R, Ringe B, Gubernatis G, et al. Transplantation of a donor liver to 2 recipients (splitting transplantation)—a new method in the further development of segmental liver transplantation. Langenbecks Arch Chir 1988; 373: 127.
9. Rogiers X, Malago M, Habib N, et al. In situ splitting of the liver in the heart-beating cadaveric organ donor for transplantation in two recipients. Transplantation. 1995 Apr 27; 59:1081. 10. Azoulay D, Astarcioglu I, Bismuth H, et al. Split-liver transplantation. The Paul Brousse policy. Ann Surg 1996; 224: 737. 11. Strong RW, Lynch SV, Ong TH, et al. Successful liver transplantation from a living donor to her son. N Engl J Med 1990; 322: 1505. 12. Broelsch CE, Whitington PF, Emond JC, et al. Liver transplantation in children from living related donors. Surgical techniques and results. Ann Surg 1991; 214: 428. 13. Hashikura Y, Makuuchi M, Kawasaki S, et al. Successful living-related partial liver transplantation to an adult patient. Lancet 1994; 343: 1233. 14. Yamaoka Y, Washida M, Honda K, et al. Liver transplantation using a right lobe graft from a living related donor. Transplantation 1994; 57: 1127. 15. Nadalin S, Malago M, Radtke A, et al. Current trends in live liver donation. Transplant Int 2007; 20(4):312. 16. Berg CL, Gillespie BW, Merion RM, et al. A2ALL Study Group. Improvement in survival associated with adultto-adult living donor liver transplantation. Gastroenterology. 2007 Dec; 133(6):1806-13. 17. Hirata M, Harihara Y, Kitamura T et al. The influence of donor age to graft volume increase rate in living donor liver transplantation. Transplant Proc. 2001 FebMar; 33(1-2):1416. 18. Hwang S, Lee SG, Lee YJ, et al. Lessons learned from 1,000 living donor liver transplantations in a single center: how to make living donations safe. Liver Transpl 2006; 12: 920. 19. Heffron T, Welch D, Pillen T, et al. Successful ABOincompatible pediatric liver transplantation utilizing standard immunosuppression with selective postoperative plasmapheresis. Liver Transpl 2006; 12: 972. 20. Testa G, Vidanovic V, Chejfec G, et al. Adult livingdonor liver transplantation with ABO-incompatible grafts. Transplantation. 2008 Mar 15; 85(5):681. 21. Valentin-Gamazo C, Malago M, Karliova M, et al. Experience after the evaluation of 700 potential donors for living donor liver transplantation in a single center. Liver Transpl 2004; 10: 1087. 21. Brown RS Jr. Live donors in liver transplantation. Gastroenterology. 2008 May; 134(6):1802-13. 23. Barr ML, Belghiti J, Villamil FG, et al. A report of the Vancouver Forum on the care of the live organ donor: lung, liver, pancreas, and intestine data and medical guidelines. Transplantation 2006; 81: 1373. 24. DuBois D, DuBois EF. A formula to estimate the approximate surface area if height and weight be known. Arch Intern Med 1916; 17: 863. 25. Urata K, Kawasaki S, Matsunami H, et al. Calculation of child and adult standard liver volume for liver transplantation. Hepatology 1995; 21:1317.
METAMO™XEY™Eπ™ 2008
26. Heinemann A, Wischhusen F, Puschel K, Rogiers X. Standard liver volume in the Caucasian population. Liver Transpl Surg 1999; 5:366. 27. Vauthey JN, Abdalla EK, Doherty DA, et al. Body surface area and body weight predict total liver volume in Western adults. Liver Transpl 2002; 8: 233. 28. Kawasaki S, Makuuchi M, Ishizone S, et al. Liver regeneration in recipients and donors after transplantation. The Lancet 1992; 339 (Mar. 7) : 580. 29. Kiuchi T, Kasahara M, Uryuhara K., et al. Impact of graft size mismatching on graft prognosis in liver transplantation from living donors. Transplantation 1999; 67: 321. 30. Bassignani MJ, Fulcher AS, Szucs RA, et al. Use of imaging for living donor liver transplantation. RadioGraphics 2001; 21:39. 31. Itamoto T, Emoto K, Mitsuta H, et al. Safety of donor right hepatectomy for adult-to-adult living donor liver transplantation. Transpl Int 2006; 19: 177. 32. Marcos A. Right lobe living donor liver transplantation : a review. Liver Transplantation 2000; 6: 3. 33. Sugawara Y, Makuuchi M, Takayama T, et al. Right lateral sector graft in adult living-related liver transplantation. Transplantation 2002; 73: 111. 34. Kasahara M, Kaihara S, Oike F, et al. Living- donor liver transplantation with mono-segments. Transplantation 2003; 76: 694. 35. Kokudo N, Sugawara Y, Imamura H, et al. Tailoring the Type of Donor Hepatectomy for Adult Living Donor Liver Transplantation. Am J Transplant 2005; 5(7): 1694. 36. 6. Healey JE, Jr, Schroy PC. Anatomy of the biliary ducts within the human liver; analysis of the prevailing pattern of branchings and the major variations of the biliary ducts. Arch Surg 1953; 66: 599. 37. 11. Bismuth H. Surgical anatomy and anatomical surgery of the liver. World J Surg 1982; 6:3. 38. Kishi Y, Sugawara Y, Kaneko J, et al. Hepatic arterial anatomy for right liver procurement from living donors. Liver Transpl 2004; 10: 129. 39. Coskun M, Kayahan EM, Ozbek O, et al. Imaging of hepatic arterial anatomy for depicting vascular variations in living related liver transplant donor candidates with multi-detector computed tomography: comparison with conventional angiography. Transplant Proc 2005; 37: 1070. 39. Carr JC, Nemcek Jr AA, Abecassis M, et al. Preoperative evaluation of the entire hepatic vasculature in living liver donors with use of contrast-enhanced MR angiography and true fast imaging with steady-state precession. J Vasc Interv Radiol 2003; 14: 441. 40. Wang ZJ, Yeh BM, Roberts JP, et al. Living donor candidates for right hepatic lobe transplantation: evaluation at CT cholangiography – initial experience. Radiology 2005; 235: 899.
65
41. Kim RD, Sakamoto S, Haider MA, et al. Role of magnetic resonance cholangiography in assessing biliary anatomy in right lobe living donors. Transplantation 2005; 79: 1417. 42. Schroeder T, Radtke A, Kuehl H, et al. Evaluation of living liver donors with an allinclusive 3D multidetector row CT protocol. Radiology 2006; 238: 900. 43. Yeh BM, Breiman RS, Taouli B, et al. Biliary tract depiction in living potential liver donors: comparison of conventional MR, mangafodipir trisodium-enhanced excretory MR, and multi-detector row CT cholangiography – initial experience. Radiology 2004; 230: 645. 44. Radtke A, Schroeder T, Molmenti EP, et al. Anatomical and physiological comparison of liver volumes among three frequent types of parenchyma transection in live donor liver transplantation. Hepatogastroenterology 2005; 52: 333. 45. Malago M, Molmenti EP, Paul A, et al. Hepatic venous outflow reconstruction in right live donor liver transplantation. Liver Transpl 2005; 11: 364. 46. Radtke A, Schroeder T, Molmenti EP, et al. The “territorial belonging” of the middle hepatic vein: a troublesome dilemma in adult live donor liver transplantation—anatomical evidence based on virtual 3dimensional-computed tomography-imaging reconstructions. Eur J Med Res. 2006 Feb 21; 11(2):66-72. 47. Radtke A, Nadalin S, Sotiropoulos GC, et al. Computer assisted operative planning in adult living donor liver transplantation: a new way to resolve the dilemma of the middle hepatic vein. World J Surg. 2007; 31: 175. 48. Fan ST. Live Donor Liver Transplantation in Adults. Transplantation 2006; 82: 723. 49. Testa G, Malago M, Porubsky M, et al. Hilar early division of the hepatic duct in living donor right hepatectomy: the probe-and-clamp technique. Liver Transpl 2006; 12: 1337. 50. Imamura H, Makuuchi M, Sakamoto Y, et al. Anatomical keys and pitfalls in living donor liver transplantation. J Hepatobiliary Pancreat Surg 2000; 7: 380. 51. Grewal HP, M. Shokouh-Amir H, Vera S, et al. Surgical technique for right lobe adult living donor liver transplantation without venovenous bypass or portocaval shunting and with duct-to-duct biliary reconstruction. Ann Surg 2001; 233(4): 502. 52. Marcos A, Fisher RA, Ham JM, et al. Liver regeneration and function in donor and recipient after right lobe adult to adult living donor liver transplantation. Transplantation 2000; 69: 1375. 53. Pomfret EA, Pomposelli JJ, Lewis WD, et al. Live donor adult liver transplantation using right lobe grafts. Donor evaluation and surgical outcome. Arch Surg 2001; 136: 425. 54. Marcos A, Ham JM, Fisher RA, Olzinski AT, Posner MP. Surgical management of anatomical variations of the right lobe in living donor liver transplantation. Ann Surg 2000; 231 (6): 824. 55. Couinaud C. Liver anatomy: portal (and suprahepatic) or biliary segmentation. Dig Surg 1999; 16: 459.
66
π. ºOÀ∑∞™, ¢. Δ∞∫OÀ¢∞™
56. Fan ST, Lo CM, Liu CL, Wang WX, Wong J. Safety and necessity of including the middle hepatic vein in the right lobe graft in adult-to-adult live donor liver transplantation. Ann Surg 2003; 238: 137. 57. Liu CL, Lo CM, Fan ST. What is the best technique for right hemiliver living donor liver transplantation? With or without the middle hepatic vein? Duct-to-duct biliary anastomosis or Roux-en-Y hepaticojejunostomy? J Hepatol 2005; 43: 17. 58. Shah SA, Grant DR, Greig PD, et al. Analysis and outcomes of right lobe hepatectomy in 101 consecutive living donors. Am J Transplant 2005; 5: 2764.
62. Nadalin S, Boockhorn M, Malago M, et al. Living donor liver transplantation. HPB 2006; 8: 10. 63. Beavers KL, Sandler RS, Shrestha R. Donor morbidity associated with right lobectomy for living donor liver transplantation to adult recipients: a systematic review. Liver Transpl 2002; 8: 110-117. 64. Dindo D, Demartines N, Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg 2004; 240:205.
59. Scatton O, Belghiti J, Dondero F, et al. Harvesting the middle hepatic vein with a right hepatectomy does not increase the risk for the donor. Liver Transpl 2004; 10:71.
65. Chan SC, Fan ST, Lo CM, Liu CL, Wong J. Toward current standards of donor right hepatectomy for adult-to-adult live donor liver transplantation through the experience of 200 cases. Ann Surg 2007; 245: 110.
60. de Villa VH, Chen CL, Chen YS, et al. Right lobe living donor liver transplantation-addressing the middle hepaticÓ vein controversy. Ann Surg 2003; 238: 275.
66. Ringe B, Strong RW. The Dilemma of Living Liver Donor Death: to Report or not to Report? Transplantation 2008; 85: 790.
61. Broelsch CE, Frilling A, Testa G, et al. Early and late complications in the recipient of an adult living donor liver. Liver Transpl 2003; 9(Suppl. 2): S50.
67. Chan SC, Fan ST. Historical perspective of living donor liver transplantation. World J Gastroenterol. 2008 Jan 7; 14(1):15.
OÚÈ·ÎÔ› ‰fiÙ˜ ‹·ÙÔ˜ (¢fiÙ˜ Ì ‰È¢ڢṲ̂ӷ ÎÚÈÙ‹ÚÈ· ÂÈÏÔÁ‹˜) ¡. ∞ÓÙˆÓÈ¿‰Ë˜
ıÂÙÈÎÔ› ÔÚÔÏÔÁÈÎÔ› ‰Â›ÎÙ˜ Ë·Ù›Ùȉ·˜ HbsAg, anti-HBc Î·È anti-HCV, Û‹„Ë Ì ıÂÙÈ΋ ηÏÏȤÚÁÂÈ· ·›Ì·ÙÔ˜, ÌËÓÈÁÁ›Ùȉ·, ÈÛÙÔÚÈÎfi Â͈˷ÙÈ΋˜ ηÎÔ‹ıÂÈ·˜, ¯Ú‹ÛË ÂÓ‰ÔÊϤ‚ÈˆÓ Ó·ÚΈÙÈÎÒÓ Ô˘ÛÈÒÓ.4 ∞˘ÙÔ› ÔÈ ·Ú¿ÁÔÓÙ˜ Ê¿ÓËÎ·Ó Ó· ·˘Í¿ÓÔ˘Ó ÙÔÓ Î›Ó‰˘ÓÔ ÂÌÊ¿ÓÈÛ˘ ÌÂÙÂÁ¯ÂÈÚËÙÈ΋˜ ‰˘ÛÏÂÈÙÔ˘ÚÁ›·˜ ÌÔۯ‡̷ÙÔ˜ Î·È Ô Û˘Ó‰˘·ÛÌfi˜ ·˘ÙÒÓ ‰Ú· ·ıÚÔÈÛÙÈο ÛÙË ‚Ï¿‚Ë ÙÔ˘ ÌÔۯ‡̷ÙÔ˜.5-7 ™ÙË ‰ÈÂıÓ‹ ÌÂÙ·ÌÔÛ¯Â˘ÙÈ΋ ÎÔÈÓfiÙËÙ· ‰ÂÓ ¤¯ÂÈ ‰Ôı› ÔÚÈÛÙÈÎfi˜ ÔÚÈÛÌfi˜ ÙÔ˘ ÔÚÈ·ÎÔ‡ ‰fiÙË. ŸÌˆ˜, ·fi Ù· ΢ÚÈfiÙÂÚ· ¯·Ú·ÎÙËÚÈÛÙÈο ÙÔ˘ ‰fiÙË Ô˘ ÌÔÚÔ‡Ó Ó· ÂËÚ¿ÛÔ˘Ó ÂÚÈÛÛfiÙÂÚÔ ÙËÓ ÂÌÊ¿ÓÈÛË ÚÒÈÌ˘ ‰˘ÛÏÂÈÙÔ˘ÚÁ›·˜ ‹ ·Ó¿ÚÎÂÈ·˜ ÙÔ˘ ÌÔۯ‡̷ÙÔ˜ ·ÔÙÂÏÔ‡Ó Ë ÌÂÁ¿ÏË ËÏÈΛ·, Ë ·Ú·ÙÂٷ̤ÓË „˘¯Ú‹ ÈÛ¯·ÈÌ›·, Ë ·Ó¿ÁÎË ÁÈ· ˘ÔÛÙ‹ÚÈÍË Ì ÈÓfiÙÚÔ·, Ë ÏÈ҉˘ ‰È‹ıËÛË ÙÔ˘ ‹·ÙÔ˜ Î·È ·Ó ÚfiÎÂÈÙ·È ÁÈ· و̷ÙÈÎfi ‰fiÙË Ì ηډȷ΋ ·Û˘ÛÙÔÏ›· (non heart beating donor).8-13 ∂›Û˘, ηıÔÚÈÛÙÈÎÔ› ·Ú¿ÁÔÓÙ˜ ÁÈ· ÙËÓ Ì·ÎÚÔÚfiıÂÛÌË ÂÈ‚›ˆÛË ÙÔ˘ Ï‹ÙË ·ÔÙÂÏÔ‡Ó ÙÔ ÈÛÙÔÚÈÎfi ηÎÔ‹ıÂÈ·˜ ‹ ÈÔÁÂÓÔ‡˜ Ë·Ù›Ùȉ·˜ ÙÔ˘ ‰fiÙË.
ŒÓ·˜ ·fi ÙÔ˘˜ ÏfiÁÔ˘˜ Ù˘ ·‡ÍËÛ˘ ÙÔ˘ ·ÚÈıÌÔ‡ ÙˆÓ ÌÂÙ·ÌÔۯ‡ÛÂˆÓ ‹·ÙÔ˜ Ô˘ ‰ÈÂÓÂÚÁÔ‡ÓÙ·È ‰ÈÂıÓÒ˜ Ù· ÙÂÏÂ˘Ù·›· ¯ÚfiÓÈ· Â›Ó·È Ë ‰È‡ڢÓÛË ÙˆÓ ÎÚÈÙËÚ›ˆÓ ·Ô‰Ô¯‹˜ ÔÚÈ·ÎÒÓ ÌÔÛ¯Â˘Ì¿ÙˆÓ. OÚȷο ηıÔÚ›˙ÔÓÙ·È Ù· ÌÔۯ‡̷ٷ Ô˘ ¤¯Ô˘Ó ·˘ÍË̤ÓË Èı·ÓfiÙËÙ· Ó· ·ÚÔ˘ÛÈ¿ÛÔ˘Ó ÚÒÈÌË ‰˘ÛÏÂÈÙÔ˘ÚÁ›· ‹ ·Ó¿ÚÎÂÈ· ı¤ÙÔÓÙ·˜ ÙÔ Ï‹ÙË Û ·˘ÍË̤ÓÔ Î›Ó‰˘ÓÔ ÓÔÛËÚfiÙËÙ·˜ Î·È ıÓËÙfiÙËÙ·˜.1,2 ∏ ·˘ÍË̤ÓË ¯Ú‹ÛË ÙˆÓ ÔÚÈ·ÎÒÓ ÌÔÛ¯Â˘Ì¿ÙˆÓ ÚÔˆı‹ıËΠ΢ڛˆ˜ ·fi ‰‡Ô ·Ú¿ÁÔÓÙ˜: ÙËÓ ¤ÏÏÂÈ„Ë ÌÔÛ¯Â˘Ì¿ÙˆÓ ·fi و̷ÙÈÎÔ‡˜ ‰fiÙ˜ Î·È ·fi Ù· ‰Â‰Ô̤ӷ Ô˘ ‰Â›¯ÓÔ˘Ó fiÙÈ ÔÚȷο ÌÔۯ‡̷ٷ ÌÔÚÔ‡Ó Ó· ¯ÚËÛÈÌÔÔÈËıÔ‡Ó Ì ηϿ ·ÔÙÂϤÛÌ·Ù·.3 ∏ Ù¿ÛË Ù˘ ¯ÚËÛÈÌÔÔ›ËÛ˘ ÔÚÈ·ÎÒÓ ÌÔÛ¯Â˘Ì¿ÙˆÓ ‰È·Ê¤ÚÂÈ ·fi ΤÓÙÚÔ Û ΤÓÙÚÔ. ŒÓ· ÌfiÛ¯Â˘Ì· Ô˘, ‚¿ÛÂÈ Î¿ÔÈˆÓ ÎÚÈÙËÚ›ˆÓ, ·ÔÚÚ›ÙÂÙ·È ·fi ¤Ó· ΤÓÙÚÔ ÌÔÚ› Ó· ¯ÚËÛÈÌÔÔÈËı› ˆ˜ ÔÚÈ·Îfi ÌfiÛ¯Â˘Ì· ·fi οÔÈÔ ¿ÏÏÔ Î¤ÓÙÚÔ. ¢ÂÓ ˘¿Ú¯ÂÈ ÎÔÈÓ‹ ·Ô‰Ô¯‹ ÁÈ· ÙÔ ÔÈÔ› ·Ú¿ÁÔÓÙ˜ ÚÔÛ‰ÈÔÚ›˙Ô˘Ó ÙÔ ÌfiÛ¯Â˘Ì· ˆ˜ ÔÚÈ·Îfi ‹ ÔÈÔ› ·fi ·˘ÙÔ‡˜ ÙÔ˘˜ ·Ú¿ÁÔÓÙ˜ ‹ Û˘Ó‰˘·ÛÌfi˜ ·˘ÙÒÓ Ó· ·ÔÙÂÏÔ‡Ó ÎÚÈÙ‹ÚÈ· ÁÈ· Ó· ·ÔÎÏÂÈÛı› Ë ¯ÚËÛÈÌÔÔ›ËÛË ÂÓfi˜ Ë·ÙÈÎÔ‡ ÌÔۯ‡̷ÙÔ˜ ÏfiÁˆ ÙÔ˘ ·Ó›ÙÚÂÙ· ·˘ÍË̤ÓÔ˘ ÎÈÓ‰‡ÓÔ˘ ÁÈ· ÙÔÓ Ï‹ÙË. ∏ ·fiÊ·ÛË Ù˘ ÌÂÙ·ÌfiÛ¯Â˘Û˘ ÙÔ˘ Ë·ÙÈÎÔ‡ ÌÔۯ‡̷ÙÔ˜ ÂÍ·ÚÙ¿Ù·È ·fi ÙËÓ ÎÚ›ÛË ÙÔ˘ ¯ÂÈÚÔ˘ÚÁÔ‡ Ï·Ì‚¿ÓÔÓÙ·˜ ˘fi„Ë Ù· ȉȷ›ÙÂÚ· ÚÔ‚Ï‹Ì·Ù· ÙÔ˘ οı ϋÙË. Œ¯Ô˘Ó ·Ó·ÁÓˆÚÈÛÙ› οÔÈÔÈ ·Ú¿ÁÔÓÙ˜ Ô˘ ÌÔÚ› Ó· ¯·Ú·ÎÙËÚ›˙Ô˘Ó Î¿ÔÈÔÓ ‰fiÙË ˆ˜ ÔÚÈ·Îfi Î·È ·ÔÙÂÏÔ‡Ó ‰È¢ڢṲ̂ӷ ÎÚÈÙ‹ÚÈ· ÂÈÏÔÁ‹˜ ‰fiÙË: ËÏÈΛ· > 65 ¯ÚÔÓÒÓ, ·Ú·ÌÔÓ‹ ÛÙË ª.∂.£. ˘fi Ì˯·ÓÈÎfi ·ÂÚÈÛÌfi > 7 Ë̤Ú˜ (‹ > 4 Ë̤Ú˜ Û οÔȘ ÌÂϤÙ˜), ‰Â›ÎÙ˘ Ì¿˙·˜ ÛÒÌ·ÙÔ˜ > 30, ‚ÈÔ„›· Ì ÏÈÒ‰Ë ‰È‹ıËÛË ‹·ÙÔ˜ > 40%, ¡¿ÙÚÈÔ ·›Ì·ÙÔ˜ > 165 mmol/l, ÙÈ̤˜ Ë·ÙÈÎÒÓ ÂÓ˙‡ÌˆÓ SGOT (AST) Î·È SGPT (ALT) > ÙÚÈÏ¿ÛȘ ÙˆÓ Ê˘ÛÈÔÏÔÁÈÎÒÓ, ÔÏÈ΋ ¯ÔÏÂÚ˘ıÚ›ÓË > 3 mg/dl,
∏ÏÈΛ· ÙÔ˘ ‰fiÙË ¶·Ï·ÈfiÙÂÚ·, Ë ¯ÚËÛÈÌÔÔ›ËÛË Ë·ÙÈÎÔ‡ ÌÔۯ‡̷ÙÔ˜ ·fi ÚÔ¯ˆÚË̤Ó˘ ËÏÈΛ·˜ ‰fiÙ˜ (> 50 ¯ÚÔÓÒÓ) ıˆÚÔ‡Ù·Ó ·ÓÙ¤Ó‰ÂÈÍË ‰ÈfiÙÈ ˘‹Ú¯Â Êfi‚Ô˜ fiÙÈ ·˘Í¿ÓÂÈ ÙÔÓ Î›Ó‰˘ÓÔ ÏÂÈÙÔ˘ÚÁÈ΋˜ ·Ó¿ÚÎÂÈ·˜ ÙÔ˘ ÌÔۯ‡̷ÙÔ˜.14 ™ÙËÓ Ú·ÁÌ·ÙÈÎfiÙËÙ· fï˜, Ù· ·ÔÙÂϤÛÌ·Ù· ÙˆÓ ÌÂÙ·ÌÔۯ‡ÛÂˆÓ ¯ÚËÛÈÌÔÔÈÒÓÙ·˜ ‰fiÙ˜ ÚÔ¯ˆÚË̤Ó˘ ËÏÈΛ·˜, Ô˘ ‰ÂÓ ¤¯Ô˘Ó ¿ÏÏÔ˘˜ ÂÈ‚·Ú˘ÓÙÈÎÔ‡˜ ·Ú¿ÁÔÓÙ˜, Ê¿ÓËÎ·Ó Ó· Â›Ó·È ›‰È· Ì ٷ ·ÔÙÂϤÛÌ·Ù· fiÙ·Ó ¯ÚËÛÈÌÔÔÈÔ‡ÓÙ·È Û¯ÂÙÈο Ó·ÚfiÙÂÚ˘ ËÏÈΛ·˜ ‰fiÙ˜. 15,16 ™‡Ìʈӷ Ì ٷ ‰Â‰Ô̤ӷ ÙÔ˘ UNOS, ÙÔ ·ÓÒÙÂÚÔ fiÚÈÔ ÙˆÓ ÙˆÌ·ÙÈÎÒÓ ‰ÔÙÒÓ ‹·ÙÔ˜ ·˘Í‹ıËΠٷ ÙÂÏÂ˘Ù·›· ¯ÚfiÓÈ·. ΔÔ 1996, ÙÔ 25% ÙˆÓ Ë·ÙÈÎÒÓ ÌÔÛ¯Â˘Ì¿ÙˆÓ ÚÔ¤Ú¯ÔÓÙ·Ó ·fi و̷ÙÈÎÔ‡˜ ‰fiÙ˜ ËÏÈΛ·˜ ÌÂÁ·Ï‡ÙÂÚ˘ ÙˆÓ 50 ¯ÚfiÓˆÓ, ÂÓÒ ÙÔ 2006 ÙÔ 34% ÙˆÓ ÙˆÌ·ÙÈÎÒÓ
67
68
¡. ∞¡Δø¡π∞¢∏™
‰ÔÙÒÓ ‹Ù·Ó ËÏÈΛ·˜ ÌÂÁ·Ï‡ÙÂÚ˘ ÙˆÓ 50 ¯ÚfiÓˆÓ. ¶·ÚfiÌÔÈ· Ù¿ÛË ·Ú·ÙËÚÂ›Ù·È Î·È ÁÈ· ÙÔ˘˜ و̷ÙÈÎÔ‡˜ ‰fiÙ˜ ËÏÈΛ·˜ ÌÂÁ·Ï‡ÙÂÚ˘ ÙˆÓ 65 ¯ÚfiÓˆÓ: 6% ÙÔ 1996 ¤Ó·ÓÙÈ 10% ÙÔ 2006.17 ∞Ó Î·È, ·fi ÙËÓ ·Ó¿Ï˘ÛË ÙˆÓ ·ÔÙÂÏÂÛÌ¿ÙˆÓ ÙÔ˘ European Liver Transplant Registry, Ë ËÏÈΛ· ÙÔ˘ ‰fiÙË ÌÂÁ·Ï‡ÙÂÚË ·fi 60 ¯ÚÔÓÒÓ Û¯ÂÙ›˙ÂÙ·È Ì ·˘ÍË̤ÓË ıÓËÙfiÙËÙ· ÙÔ˘˜ ÚÒÙÔ˘˜ 3 Ì‹Ó˜ ÌÂÙ¿ ÙË ÌÂÙ·ÌfiÛ¯Â˘ÛË, Ô ·ÚÈıÌfi˜ ÙˆÓ ÌÔÛ¯Â˘Ì¿ÙˆÓ ·fi ‰fiÙ˜ ËÏÈΛ·˜ ¿Óˆ ·fi 60 ¯ÚÔÓÒÓ ·˘Í‹ıËΠÛËÌ·ÓÙÈο (·fi 2% ÙÔ 1991 ÛÙÔ 20% ÙÔ 2001).18,19 ∞˘Ù‹ Ë Î·ÙËÁÔÚ›· ‰ÔÙÒÓ ¤¯ÂÈ ·Ó·ÁÓˆÚÈÛÙ› ˆ˜ Ô ÛËÌ·ÓÙÈÎfiÙÂÚÔ˜ ·Ú¿ÁÔÓÙ·˜ ÁÈ· ÙËÓ ¿˘ÍËÛË ÙÔ˘ ·ÚÈıÌÔ‡ ÙˆÓ ÙˆÌ·ÙÈÎÒÓ Ë·ÙÈÎÒÓ ÌÂÙ·ÌÔۯ‡ÛÂˆÓ Î·È fiÙ·Ó ·Ô˘ÛÈ¿˙Ô˘Ó ¿ÏÏÔÈ ÂÈ‚·Ú˘ÓÙÈÎÔ› ·Ú¿ÁÔÓÙ˜ Ô Î›Ó‰˘ÓÔ˜ ·˘ÍË̤Ó˘ ıÓËÙfiÙËÙ·˜ ÂÏ·ÙÙÒÓÂÙ·È Û ÚÔÛÂÎÙÈο ÂÈÏÂÁ̤ÓÔ˘˜ Ï‹Ù˜.20 Δ· Û¯ÂÙÈο ηϿ ·ÔÙÂϤÛÌ·Ù· ·fi ÙË ¯ÚËÛÈÌÔÔ›ËÛË ÌÂÁ¿Ï˘ ËÏÈΛ·˜ Ë·ÙÈÎÒÓ ÌÔÛ¯Â˘Ì¿ÙˆÓ Èı·ÓÒ˜ Ó· ÔÊ›ÏÔÓÙ·È ÛÙȘ ·ÚΛ˜ ÏÂÈÙÔ˘ÚÁÈΤ˜ Âʉڛ˜, ÛÙËÓ ·Ó·ÁÂÓÓËÙÈ΋ ÈηÓfiÙËÙ· Î·È ÛÙË ‰ÈÏ‹ ·ÈÌ¿ÙˆÛË ÙÔ˘ ‹·ÙÔ˜ Ù· ÔÔ›· ˘ÂÚηχÙÔ˘Ó ÙȘ ÌÂÙ·‚ÔÏÈΤ˜ ·Ó¿ÁΘ ÙÔ˘.21,22 ŸÌˆ˜ ÁÂÓÈο, Ë ÌÂÁ¿Ï˘ ËÏÈΛ·˜ ‰fiÙ˜ ¤¯Ô˘Ó ·˘ÍË̤ӷ ÔÛÔÛÙ¿ ÂÌÊ¿ÓÈÛ˘ ‚·ÚÂÈ¿˜ ·ıËÚÔÛÎÏ‹ÚˆÛ˘ Î·È ÏÈÒ‰Ô˘˜ ‰È‹ıËÛ˘ ‹·ÙÔ˜. ¶Ú¤ÂÈ Ó· ‰›ÓÂÙ·È ÚÔÛÔ¯‹ ÛÙËÓ Èı·Ó‹ ‡·ÚÍË ·ıËÚÔÛÎÏËÚˆÙÈÎÒÓ ‚Ï·‚ÒÓ ÛÙ· ·ÁÁ›· ÙÔ˘ ÌÔۯ‡̷ÙÔ˜ ‰ÈfiÙÈ ÌÔÚ› Ó· Á›ÓÔ˘Ó ·ÈÙ›· ÛËÌ·ÓÙÈÎÒÓ ÌÂÙÂÁ¯ÂÈÚËÙÈÎÒÓ ÂÈÏÔÎÒÓ.16 ∂›Û˘, Ô Û˘Ó‰˘·ÛÌfi˜ ÌÂÁ¿Ï˘ ËÏÈΛ·˜ ‰fiÙË Î·È Ì¤ÙÚÈ·˜ ÚÔ˜ ‚·Ú›·˜ ÛÙ¿وÛ˘ ÂËÚ¿˙ÂÈ ‰˘ÛÌÂÓÒ˜ ÙËÓ ÂÈ‚›ˆÛË ÙÔ˘ ÌÔۯ‡̷ÙÔ˜ ÛÙËÓ ·Ú¯È΋ ÂÚ›Ô‰Ô.23 ∞ÎfiÌË ¤Ó· ı¤Ì· Ô˘ Ú¤ÂÈ Ó· Ï·Ì‚¿ÓÂÙ·È ˘fi„Ë Â›Ó·È fiÙÈ Ë ÌÂÁ¿Ï˘ ËÏÈΛ·˜ ‰fiÙ˜ ¤¯Ô˘Ó ·˘ÍË̤ÓË Èı·ÓfiÙËÙ· Ó· ¤¯Ô˘Ó οÔÈ· ·‰È¿ÁÓˆÛÙË Î·ÎÔ‹ıÂÈ· Ô˘ ÌÔÚ› Ó· ÙË ÌÂÙ·‰ÒÛÔ˘Ó ÛÙÔÓ ·ÓÙ›ÛÙÔÈ¯Ô Ï‹ÙË. ™ÙÔ˘˜ Ï‹Ù˜ Ì ˷ٛÙȉ· C (HCV +), Ë ÌÂÁ¿ÏË ËÏÈΛ· ÙÔ˘ ‰fiÙË Û¯ÂÙ›˙ÂÙ·È Ì ‚·Ú›·˜ ÌÔÚÊ‹˜ ˘ÔÙÚÔ‹ Ù˘ ÓfiÛÔ˘, ÓˆÚ›˜ ÌÂÙ¿ ÙË ÌÂÙ·ÌfiÛ¯Â˘ÛË. Œ¯ÂÈ Ê·Ó› fiÙÈ fiÙ·Ó Ô ‰fiÙ˘ Â›Ó·È ÌÂÁ·Ï‡ÙÂÚÔ˜ ·fi 60 ¯ÚÔÓÒÓ, Ô Ï‹Ù˘ Ù›ıÂÙ·È Û ·˘ÍË̤ÓÔ Î›Ó‰˘ÓÔ ÂÌÊ¿ÓÈÛ˘ ÛËÌ·ÓÙÈ΋˜ ÈÛÙÔÏÔÁÈ΋˜ ‚Ï¿‚˘ Î·È ·Ó¿ÚÎÂÈ·˜ ÙÔ˘ ÌÔۯ‡̷ÙÔ˜ ÏfiÁˆ Ù˘ ÁÚ‹ÁÔÚ· ÂÍÂÏÈÛÛfiÌÂÓ˘ ˘ÔÙÚÔ‹˜ Ù˘ HCV Ïԛ̈͢ ÛÙÔ ÌfiÛ¯Â˘Ì·.24,25 ŒÙÛÈ ÚÔÙ›ÓÂÙ·È, Ë ËÏÈΛ· ÙÔ˘ ‰fiÙË Ó· ·ÔÙÂÏ› ·Ú¿ÁÔÓÙ· Ô˘ Ï·Ì‚¿ÓÂÙ·È ˘’ fi„Ë ÛÙËÓ ÂÈÏÔÁ‹ Î·È ÛÙËÓ ÌÂÙ¿ ÙË ÌÂÙ·ÌfiÛ¯Â˘ÛË ÎÏÈÓÈ΋ ·Ú·ÎÔÏÔ‡ıËÛË Î¿ÔÈÔ˘ HCV+ Ï‹ÙË.
¶·Ú·ÙÂٷ̤ÓÔ˜ ¯ÚfiÓÔ˜ ÈÛ¯·ÈÌ›·˜ ∏ ÈÛ¯·ÈÌÈ΋ ‚Ï¿‚Ë ·ÔÙÂÏ› ·fi ÙȘ ΢ÚÈfiÙÂÚ˜ ·Èٛ˜ ÚÒÈÌ˘ ‰˘ÛÏÂÈÙÔ˘ÚÁ›·˜ ÙÔ˘ Ë·ÙÈÎÔ‡ ÌÔۯ‡̷ÙÔ˜. O ·Ú·ÙÂٷ̤ÓÔ˜ ¯ÚfiÓÔ˜ „˘¯Ú‹˜ ÈÛ¯·ÈÌ›·˜ Â›Ó·È ·Ú¿ÁÔÓÙ·˜ ÎÈÓ‰‡ÓÔ˘ ‰ËÌÈÔ˘ÚÁ›·˜ ‚Ï¿‚˘ Û˘ÓÙ‹ÚËÛ˘, ÛËÌ·ÓÙÈÎfiÙÂÚÔ˜ ·fi fiÙÈ Â›Ó·È Ë ËÏÈΛ· ÙÔ˘ ‰fiÙË.26 ÃÚfiÓÔ˜ „˘¯Ú‹˜ ÈÛ¯·ÈÌ›·˜ ÌÔۯ‡̷ÙÔ˜ ÂÚÈÛÛfiÙÂÚÔ˜ ·fi 14 ÒÚ˜ Û¯ÂÙ›˙ÂÙ·È Ì ‰ÈÏ¿ÛÈ· ·‡ÍËÛË Ù˘ ‚·Ú‡ÙËÙ·˜ Ù˘ ‚Ï¿‚˘ Û˘ÓÙ‹ÚËÛ˘, ¤¯ÔÓÙ·˜ ˆ˜ ·ÔÙ¤ÏÂÛÌ· ÙËÓ ÂÈÏÂÁ̤ÓË ÌÂÙÂÁ¯ÂÈÚËÙÈ΋ ÂÚ›Ô‰Ô, ÙÔÓ ·˘ÍË̤ÓÔ Î›Ó‰˘ÓÔ ÚÒÈÌ˘ ÌË ÏÂÈÙÔ˘ÚÁ›·˜ ÙÔ˘ ÌÔۯ‡̷ÙÔ˜, ÙËÓ ÂÌÊ¿ÓÈÛË ÛÙÂÓÒÛÂˆÓ ÛÙ· ¯ÔÏËÊfiÚ· Î·È ÙË ÌÂȈ̤ÓË ÂÈ‚›ˆÛË ÙÔ˘ ÌÔۯ‡̷ÙÔ˜.26-29 ∏ ·Ó¿Ï˘ÛË ÙˆÓ ‰Â‰ÔÌ¤ÓˆÓ Ù˘ ELTR ÚÔÛ‰ÈfiÚÈÛ fiÙÈ ¯ÚfiÓÔ˜ „˘¯Ú‹˜ ÈÛ¯·ÈÌ›·˜ > 13 ÒÚ˜ Û¯ÂÙ›˙ÂÙ·È Ì ·˘ÍË̤ÓË ıÓËÙfiÙËÙ· ÛÙÔ˘˜ 3 Î·È 12 Ì‹Ó˜ ÌÂÙ¿ ÙË ÌÂÙ·ÌfiÛ¯Â˘ÛË.18 ¶ÚÔÙ›ÓÂÙ·È Ô ¯ÚfiÓÔ˜ ÈÛ¯·ÈÌ›·˜ Ó· ·Ú·Ì¤ÓÂÈ Î¿Ùˆ ·fi 12 ÒÚ˜, ·Ó Î·È ·˘Ùfi ÙÔ ¯ÚÔÓÈÎfi fiÚÈÔ ‰ÂÓ Â›Ó·È ·fiÏ˘ÙÔ ·ÊÔ‡ ÁÈ· οı ÌfiÛ¯Â˘Ì· Ë Â˘¿ıÂÈ· ÛÙÔ ¯ÚfiÓÔ ÈÛ¯·ÈÌ›·˜ ÂÍ·ÚÙ¿Ù·È Î·È ·fi ¿ÏÏÔ˘˜ ·Ú¿ÁÔÓÙ˜.18 ™Ù· ÔÚȷο ÌÔۯ‡̷ٷ, Ì ÂÈÚfiÛıÂÙÔ˘˜ ÂÈ‚·Ú˘ÓÙÈÎÔ‡˜ ·Ú¿ÁÔÓÙ˜ fiˆ˜ ÏÈ҉˘ ‰È‹ıËÛË, ËÏÈΛ· ÙÔ˘ ‰fiÙË ÌÂÁ·Ï‡ÙÂÚË ÙˆÓ 50 ¯ÚfiÓˆÓ Î·È ÌÈÎÚfi ̤ÁÂıÔ˜ ÌÔۯ‡̷ÙÔ˜, Ô ¯ÚfiÓÔ˜ ÈÛ¯·ÈÌ›·˜ Ú¤ÂÈ Ó· ·Ú·Ì¤ÓÂÈ Î¿Ùˆ ·fi 12 ÒÚ˜. ∂ÓÒ, ÌÔۯ‡̷ٷ ·fi ‰fiÙ˜ ¯ˆÚ›˜ Î·Ó¤Ó·Ó ¿ÏÏÔ ÂÈ‚·Ú˘ÓÙÈÎfi ·Ú¿ÁÔÓÙ· ÌÔÚÔ‡Ó Ó· ·Ó¯ÙÔ‡Ó, ‰›¯ˆ˜ Ó· ·ÚÔ˘ÛÈ¿ÛÔ˘Ó ÌÂÙÂÁ¯ÂÈÚËÙÈο ÏÂÈÙÔ˘ÚÁÈο ÚÔ‚Ï‹Ì·Ù·, ·Ú·ÙÂٷ̤ÓÔ ¯ÚfiÓÔ ÈÛ¯·ÈÌ›·˜ > 12 ÒÚ˜ (¤ˆ˜ Î·È 16 ÒÚ˜).
¶·Ú·ÌÔÓ‹ ÛÙË ª∂£ Î·È ˘ÔÛÙ‹ÚÈÍË Ì ÈÓfiÙÚÔ· OÈ ‰fiÙ˜ Ì ·Ú·ÙÂٷ̤ÓË ·Ú·ÌÔÓ‹ ÛÙË ª∂£ ¤¯Ô˘Ó ·˘ÍË̤ÓÔ Î›Ó‰˘ÓÔ ÁÈ· ÏÔÈÌÒÍÂȘ. Œ¯ÂÈ Ê·Ó› fiÙÈ Ë ·Ú·ÌÔÓ‹ ÛÙË ª∂£ ≥ 3 Ë̤Ú˜ ·ÔÙÂÏ› ÙÔ ÌfiÓÔ ·fi Ù· ¯·Ú·ÎÙËÚÈÛÙÈο ÙÔ˘ ‰fiÙË Ô˘ ·˘Í¿ÓÔ˘Ó ÛËÌ·ÓÙÈο ÙËÓ Èı·ÓfiÙËÙ· Ïԛ̈͢ ÙÔ˘ ˘Ô„‹ÊÈÔ˘ ‰fiÙË.30 ∞fi ÌÂÁ¿Ï˜ ÛÂÈÚ¤˜ Ô˘ ÌÂϤÙËÛ·Ó ÙÔ˘˜ ‰fiÙ˜ Ì ÌÈÎÚÔ‚È·ÈÌ›· Û˘ÌÂÚ·›ÓÂÙ·È fiÙÈ ÌÔۯ‡̷ٷ ·fi Ù¤ÙÔÈÔ˘˜ ‰fiÙ˜ ÏÂÈÙÔ˘ÚÁÔ‡Ó ÈηÓÔÔÈËÙÈο, ¯ˆÚ›˜ Ó· ÚÔÛÙ›ıÂÙ·È ÛËÌ·ÓÙÈÎfi˜ ÂÈ‚·Ú˘ÓÙÈÎfi˜ ·Ú¿ÁÔÓÙ·˜ ÛÙÔÓ Ï‹ÙË, Ì ÙËÓ ÚÔ¸fiıÂÛË fiÙÈ ÛÙÔÓ Ï‹ÙË ı· ¯ÔÚËÁËı› Ë Î·Ù¿ÏÏËÏË ·ÓÙÈÌÈÎÚԂȷ΋ ·ÁˆÁ‹ ÁÈ· ÙÔ ÌÈÎÚfi‚ÈÔ Ô˘ ·ÔÌÔÓÒıËΠÛÙÔÓ ‰fiÙË.31-34 ∏ ·Ó¿Ï˘ÛË ÙˆÓ ‰Â‰ÔÌ¤ÓˆÓ ÙÔ˘ UNOS ¤‰ÂÈÍ fiÙÈ Ù· ÌÔۯ‡̷ٷ ·fi ‰fiÙ˜ Ô˘ Ì ·Ú·ÙÂٷ̤ÓË ˘fiÙ·ÛË ‰ÂÓ ·ÚÔ˘ÛÈ¿˙Ô˘Ó ·˘ÍË̤ÓÔ Î›Ó‰˘ÓÔ
METAMO™XEY™Eπ™ 2008
ÚÒÈÌ˘ ·Ó¿ÚÎÂÈ·˜ ÌÂÙ¿ ÙË ÌÂÙ·ÌfiÛ¯Â˘ÛË. ∏ Èı·ÓfiÙËÙ· ·Ó¿ÚÎÂÈ·˜ ÌÔۯ‡̷ÙÔ˜ ·˘Í¿ÓÂÙ·È fiÙ·Ó ÛÙÔ˘˜ ‰fiÙ˜ Â›Ó·È ·Ó·Áη›· Ë ¯ÔÚ‹ÁËÛË ÓÔÚ·‰ÚÂÓ·Ï›Ó˘.35 ™Â ¿ÏϘ ÌÂϤÙ˜, Ë ¯ÔÚ‹ÁËÛË ‰fiÛÂˆÓ ÓÙÔ·Ì›Ó˘ ≥ 10 Ìg/kg/min ‹ ≥ 6 Ìg/kg/min ›¯Â ÛËÌ·ÓÙÈ΋ ·ÚÓËÙÈ΋ ›وÛË ÛÙËÓ ·Ú¯È΋ ÏÂÈÙÔ˘ÚÁ›· ÙÔ˘ ÌÔۯ‡̷ÙÔ˜. ŸÌˆ˜, Ë ‡·ÚÍË Ë fi¯È ÚfiÛıÂÙˆÓ ÂÈ‚·Ú˘ÓÙÈÎÒÓ ·Ú·ÁfiÓÙˆÓ (¯. ËÏÈΛ·, ÏÈ҉˘ ‰È‹ıËÛË) ηıÔÚ›˙ÂÈ ÙÂÏÈο ÙÔÓ ‚·ıÌfi Ù˘ ›وÛ˘ Ù˘ ·Ú·ÙÂٷ̤Ó˘ ˘fiÙ·Û˘ ÛÙË ÌÂÙÂÁ¯ÂÈÚËÙÈ΋ ÏÂÈÙÔ˘ÚÁ›· ÙÔ˘ ÌÔۯ‡̷ÙÔ˜.36
§È҉˘ ‰È‹ıËÛË (ÛÙ¿وÛË) ΔÔ 13%-26% ÙˆÓ ‰ÔÙÒÓ ¤¯Ô˘Ó ÏÈÒ‰Ë ‰È‹ıËÛË ÙÔ˘ ‹·ÙÔ˜.37 OÈ Û˘Ó‹ıÂȘ ·Èٛ˜ Ù˘ ·ÔÙÂÏÔ‡Ó Ë ·¯˘Û·ÚΛ·, Ë ÚÔ¯ˆÚË̤ÓË ËÏÈΛ·, Ô ·ÏÎÔÔÏÈÛÌfi˜, Ô Û·Î¯·Ú҉˘ ‰È·‚‹Ù˘ Î·È ÔÈ ÂÈÙÒÛÂȘ ÙÔ˘ ÂÁÎÂÊ·ÏÈÎÔ‡ ı·Ó¿ÙÔ˘. ¢‡Ô ÈÛÙÔÏÔÁÈÎÔ› Ù‡ÔÈ ÏÈÒ‰Ô˘˜ ‰È‹ıËÛ˘ ÂÚÈÁÚ¿ÊÔÓÙ·È: Ë ÌÈÎÚÔÊ˘ÛÛ·Ïȉ҉˘, Î·È Ë ÌÂÁ·ÏÔÊ˘ÛÛ·Ïȉ҉˘. ∏ ÔÛÔÙÈ΋ ·ÍÈÔÏfiÁËÛË ÙÔ˘ ‚·ıÌÔ‡ Ù˘ ÏÈÒ‰Ô˘˜ ‰È‹ıËÛ˘ ‚·Û›˙ÂÙ·È ÛÙÔ ÔÛÔÛÙfi ÙˆÓ Ë·ÙÔ΢ÙÙ¿ÚˆÓ Ô˘ ·ÚÔ˘ÛÈ¿˙Ô˘Ó ÂÓ‰Ô΢ÙÙ·ÚÔÏ·ÛÌ·ÙÈΤ˜ Ê˘ÛÛ·Ï›‰Â˜ Ï›Ô˘˜. ∏ ‡·ÚÍË ÌÈÎÚÔÊ˘ÛÛ·ÏÈ‰Ò‰Ô˘˜ ÏÈÒ‰Ô˘˜ ‰È‹ıËÛ˘ Ê·›ÓÂÙ·È Ó· ÌËÓ ÂËÚ¿˙ÂÈ ÙËÓ ÏÂÈÙÔ˘ÚÁ›· ÙÔ˘ Ë·ÙÈÎÔ‡ ÌÔۯ‡̷ÙÔ˜ ÌÂÙ¿ ÙËÓ ÌÂÙ·ÌfiÛ¯Â˘ÛË.38,39 ∂›Û˘, Ù· ÌÔۯ‡̷ٷ Ì ‹È· ÌÂÁ·ÏÔÊ˘ÛÛ·ÏÈ‰Ò‰Ë ÏÈÒ‰Ë ‰È‹ıËÛË (< 30% ÙˆÓ Ë·ÙÔ΢ÙÙ¿ÚˆÓ) ÌÔÚÔ‡Ó Ó· ¯ÚËÛÈÌÔÔÈËıÔ‡Ó Ì ·ÛÊ¿ÏÂÈ·, ·ÊÔ‡ Ù· ·ÔÙÂϤÛÌ·Ù· fiÛÔÓ ·ÊÔÚ¿ ÙË ÏÂÈÙÔ˘ÚÁ›· ÙÔ˘˜ ÌÂÙ¿ ÙË ÌÂÙ·ÌfiÛ¯Â˘ÛË Â›Ó·È ›‰È· Ì ٷ ÌÔۯ‡̷ٷ ¯ˆÚ›˜ ÏÈÒ‰Ë ‰È‹ıËÛË.40 Δ· Ë·ÙÈο ÌÔۯ‡̷ٷ Ì ¤ÓÙÔÓË ÏÈÒ‰Ë ‰È‹ıËÛË (> 60% ÙˆÓ Ë·ÙÔ΢ÙÙ¿ÚˆÓ) ¤¯Ô˘Ó ÛËÌ·ÓÙÈο ·˘ÍË̤ÓÔ Î›Ó‰˘ÓÔ Ó· ·ÚÔ˘ÛÈ¿ÛÔ˘Ó ·Ó¿ÚÎÂÈ· ÏÂÈÙÔ˘ÚÁÈÎfiÙËÙ·˜ ÌÂÙ¿ ÙË ÌÂÙ·ÌfiÛ¯Â˘ÛË Î·È ‰ÂÓ Ú¤ÂÈ Ó· ¯ÚËÛÈÌÔÔÈÔ‡ÓÙ·È.41 ∏ ¯ÚËÛÈÌÔÔ›ËÛË Ë·ÙÈÎÒÓ ÌÔÛ¯Â˘Ì¿ÙˆÓ Ì ̤ÙÚÈÔ˘ ‚·ıÌÔ‡ ÏÈÒ‰Ë ‰È‹ıËÛË (30%-60%) Â›Ó·È Û¯ÂÙÈ΋ Î·È ·ÌÊÈÏÂÁfiÌÂÓË. ¶ÂÚÈÁÚ¿ÊÔÓÙ·È ·ÔÙÂϤÛÌ·Ù· ÏÂÈÙÔ˘ÚÁ›·˜ Ù¤ÙÔÈˆÓ ÌÔÛ¯Â˘Ì¿ÙˆÓ ·ÚfiÌÔÈ· Ì ·˘Ù¿ ÙˆÓ Ê˘ÛÈÔÏÔÁÈÎÒÓ ÌÔÛ¯Â˘Ì¿ÙˆÓ, ·ÏÏ¿ ÂÚÈÁÚ¿ÊÔÓÙ·È Î·È ·˘ÍË̤ӷ ÔÛÔÛÙ¿ ÚÒÈÌ˘ ·Ó¿ÚÎÂÈ·˜ (13% ¤Ó·ÓÙÈ ÙÔ˘ 3% ÁÈ· Ù· Ê˘ÛÈÔÏÔÁÈο ÌÔۯ‡̷ٷ).40 ∂›Ó·È ·Ô‰ÂÎÙfi fiÙÈ Ù· ÌÔۯ‡̷ٷ Ì ̤ÙÚÈÔ˘ ‚·ıÌÔ‡ ÏÈÒ‰Ë ‰È‹ıËÛË Â›Ó·È ÚÔÙÈÌfiÙÂÚÔ Ó· ¯ÚËÛÈÌÔÔÈÔ‡ÓÙ·È fiÙ·Ó ‰ÂÓ ˘¿Ú¯Ô˘Ó ¿ÏÏÔÈ ÂÈÚfiÛıÂÙÔÈ ÂÈ‚·Ú˘ÓÙÈÎÔ› ·Ú¿ÁÔÓÙ˜ ÎÈÓ‰‡ÓÔ˘ ÛÙÔÓ ‰fiÙË ·ÏÏ¿ Î·È ÛÙÔÓ Ï‹ÙË.
69
∏·Ù›Ùȉ· μ Î·È C ™ÙÔ ·ÚÂÏıfiÓ ‰ÂÓ ‹Ù·Ó ·Ô‰ÂÎÙ‹ Ë ÂÈÏÔÁ‹ ‰ÔÙÒÓ Ë·ÙÈÎÔ‡ ÌÔۯ‡̷ÙÔ˜ Ô˘ ‹Ù·Ó ÔÚÔıÂÙÈÎÔ› ÁÈ· ÙÔ˘˜ ÈÔ‡˜ Ù˘ Ë·Ù›Ùȉ·˜ μ Î·È C. O ΛӉ˘ÓÔ˜ ÌÂÙ¿‰ÔÛ˘ ÛÙÔÓ Ï‹ÙË ÙÔ˘ ÈÔ‡ Ù˘ Ë·Ù›Ùȉ·˜ μ (HBV) Ì ÙË ÌÂÙ·ÌfiÛ¯Â˘ÛË ‹·ÙÔ˜ Â›Ó·È ˘„ËÏfi˜.42 ¶ÂÚÈÁÚ¿ÊÂÙ·È fiÙÈ Ë·ÙÈο ÌÔۯ‡̷ٷ ·fi ‰fiÙ˜ ·ÚÓËÙÈÎÔ‡˜ ÛÙÔ ·ÓÙÈÁfiÓÔ ÂÈÊ·Ó›·˜ (HbsAg –) ·ÏÏ¿ ıÂÙÈÎÔ‡˜ Û ·ÓÙÈÛÒÌ·Ù· ¤Ó·ÓÙÈ ÙÔ˘ ·ÓÙÈÁfiÓÔ˘ ÙÔ˘ ˘Ú‹Ó· (anti-Hbc +) ÙÔ˘ ÈÔ‡ Ë·Ù›Ùȉ·˜ μ ¤¯Ô˘Ó ÌÂÙ·‰ÒÛÂÈ HBV Ïԛ̈ÍË Û ϋÙ˜ Ô˘ ‹Ù·Ó HbsAg (–) Û ÔÛÔÛÙfi 33% - 78%.43 O ΛӉ˘ÓÔ˜ ·˘Ùfi˜ ÌÂÈÒÓÂÙ·È ÛËÌ·ÓÙÈο (13%) ÛÙÔ˘˜ Ï‹Ù˜ Ô˘ ÚÔ¸¿Ú¯Ô˘Ó ·ÓÙÈÛÒÌ·Ù· ¤Ó·ÓÙÈ ÙÔ˘ ·ÓÙÈÁfiÓÔ˘ ÂÈÊ·Ó›·˜ (anti-HBs) ‹ ·ÓÙÈÛÒÌ·Ù· ¤Ó·ÓÙÈ ÙÔ˘ ·ÓÙÈÁfiÓÔ˘ ÙÔ˘ ˘Ú‹Ó· (anti-Hbc +).44 OÈ Ï‹Ù˜ Ë·ÙÈÎÒÓ ÌÔÛ¯Â˘Ì¿ÙˆÓ anti-Hbc(+) ¤¯Ô˘Ó ·˘ÍË̤ÓÔ Î›Ó‰˘ÓÔ HBV Ïԛ̈͢, ÂÓÒ ÔÈ Ï‹Ù˜ ÌÔÛ¯Â˘Ì¿ÙˆÓ anti-HBs(+) ¤¯Ô˘Ó ÂÏ¿¯ÈÛÙÔ Î›Ó‰˘ÓÔ Ó· ·ÔÎÙ‹ÛÔ˘Ó HBV Ïԛ̈ÍË. ∏ ÌÂÙ·ÌfiÛ¯Â˘ÛË ‹·ÙÔ˜ ·fi ‰fiÙ˜ anti-HBc ‰ÂÓ ÂËÚ¿˙ÂÈ ÙËÓ ÂÈ‚›ˆÛË ÙÔ˘ ÌÔۯ‡̷ÙÔ˜ ‹ ÙÔ˘ Ï‹ÙË, ·ÏÏ¿ ·˘Í¿ÓÂÙ·È Ë Èı·ÓfiÙËÙ· ηٿ 2,5 ÊÔÚ¤˜ Ó· ˘ÔÙÚÔÈ¿ÛÂÈ Ë HBV Ïԛ̈ÍË ÙÔ˘ Ï‹ÙË, ·Ó Î·È ˘ÔÙÚÔ‹ ‰ÂÓ ·ÚÔ˘ÛÈ¿˙ÂÙ·È ÛÙÔ˘˜ Ï‹Ù˜ Ô˘ Ï·Ì‚¿ÓÔ˘Ó ÚÔÊ˘Ï·ÎÙÈ΋ ıÂڷ›· Ì ·ÓÔÛÔÛÊ·ÈÚ›ÓË Ë·Ù›Ùȉ·˜ μ (HBIG) Î·È lamivudine.45 ªÔۯ‡̷ٷ ·fi ‰fiÙ˜ HBc(+) Ú¤ÂÈ ÂÈÏÂÎÙÈο Ó· ‰›ÓÔÓÙ·È Û HbsAg(+) Ï‹Ù˜, ·ÊÔ‡ Ô‡Ùˆ˜ ‹ ¿Ïψ˜ ÙÔ˘˜ ¯ÔÚËÁÂ›Ù·È ‰È· ‚›Ô˘ HBIG. ø˜ ‰Â‡ÙÂÚË ÂÈÏÔÁ‹, ·˘Ù¿ Ù· ÌÔۯ‡̷ٷ Ú¤ÂÈ Ó· ‰›ÓÔÓÙ·È Û anti-HBs(+) Ï‹Ù˜, ÛÙÔ˘˜ ÔÔ›Ô˘˜ Û˘Ó‹ıˆ˜ ‰ÂÓ ¯ÚÂÈ¿˙ÂÙ·È Ó· ¯ÔÚËÁÂ›Ù·È HBIG. ªÔۯ‡̷ٷ ·fi HBc(+) ‰fiÙ˜ ‰ÂÓ Ú¤ÂÈ Ó· ‰›ÓÔÓÙ·È Û HBV ÔÚÔ·ÚÓËÙÈÎÔ‡˜ Ï‹Ù˜, ·Ú¿ ÌfiÓÔ Â¿Ó ‚Ú›ÛÎÔÓÙ·È Û ÎÚ›ÛÈÌË Î·Ù¿ÛÙ·ÛË ¤¯ÔÓÙ·˜ ¿ÌÂÛË ·Ó¿ÁÎË ÁÈ· ÌfiÛ¯Â˘Ì·. ∏ ÌÂÙ·ÌfiÛ¯Â˘ÛË ‹·ÙÔ˜ ·fi ‰fiÙË ıÂÙÈÎfi Û ·ÓÙÈÛÒÌ·Ù· Ë·Ù›Ùȉ·˜ C (HCV+) ÌÂÙ·‰›‰ÂÈ ¿ÓÙÔÙ de novo Ïԛ̈ÍË Û ϋÙË Ô˘ ‰ÂÓ ¤¯ÂÈ ÂÎÙÂı› ÚÔËÁÔ˘Ì¤Óˆ˜ ÛÙÔÓ Èfi Ù˘ Ë·Ù›Ùȉ·˜ C (HCV–).46 ŸÌˆ˜, Ë ÌÂÙ·ÌfiÛ¯Â˘ÛË ·˘ÙÒÓ ÙˆÓ ÌÔÛ¯Â˘Ì¿ÙˆÓ Û HCV(+) Ï‹Ù˜ ‰ÂÓ Ê·›ÓÂÙ·È Ó· ÂËÚ¿˙ÂÈ ÙËÓ ÂÈ‚›ˆÛË ÙÔ˘ ÌÔۯ‡̷ÙÔ˜ ‹ ÙÔ˘ Ï‹ÙË. ∞ÚÎÂÙ¤˜ ÌÂϤÙ˜ ¤‰ÂÈÍ·Ó fiÙÈ Ë ÂÈ‚›ˆÛË ÙˆÓ ·ÛıÂÓÒÓ Ì ÌÔۯ‡̷ٷ ·fi HCV(+) ‰fiÙ˜ Â›Ó·È ›‰È·, Î·È Î¿ÔȘ ÊÔÚ¤˜ ηχÙÂÚË, ·fi ÙËÓ ÂÈ‚›ˆÛË ÙˆÓ ·ÛıÂÓÒÓ Ì ÌÔۯ‡̷ٷ ·fi HCV(–) ‰fiÙ˜.47-52 ¶Ú¤ÂÈ fï˜ Ó· ÛËÌÂȈı› fiÙÈ HCV(+) ÌÔۯ‡̷ٷ ·fi Û¯ÂÙÈο ÌÂÁ¿Ï˘ ËÏÈΛ·˜ ‰fiÙ˜
70
¡. ∞¡Δø¡π∞¢∏™
(≥ 50 ¯ÚÔÓÒÓ) ›¯·Ó ·˘ÍË̤ӷ ÔÛÔÛÙ¿ ·Ó¿ÚÎÂÈ·˜ ÌÔۯ‡̷ÙÔ˜ Û˘ÁÎÚÈÙÈο Ì ÙÔ˘˜ Ï‹Ù˜ HCV(–) ÌÔÛ¯Â˘Ì¿ÙˆÓ Ù˘ ›‰È·˜ ËÏÈÎȷ΋˜ ÔÌ¿‰·˜. μ¿ÛÂÈ ÙˆÓ ·Ú·¿Óˆ, Ù· ÂÚÈÛÛfiÙÂÚ· ΤÓÙÚ· ıˆÚÔ‡Ó ‰Â‰Ô̤ÓË ÙË ¯ÚËÛÈÌÔÔ›ËÛË Ë·ÙÈÎÒÓ ÌÔÛ¯Â˘Ì¿ÙˆÓ ·fi HCV(+) ‰fiÙ˜ Û ∏CV(+) Ï‹Ù˜, Ì ÙËÓ ÚÔ¸fiıÂÛË fiÙÈ Ë ‚ÈÔ„›· ÙÔ˘ ÌÔۯ‡̷ÙÔ˜ Ô˘ ÚÔËÁÂ›Ù·È ·ÔÎÏ›ÂÈ ÙËÓ ‡·ÚÍË ‚Ï¿‚˘ Ë·Ù›Ùȉ·˜.
∫·ÎÔ‹ıÂÈ· ∏ ‡·ÚÍË ÂÓÂÚÁÔ‡ ηÎÔ‹ıÂÈ·˜ Ì ٿÛË Ó· ÌÂı›ÛÙ·Ù·È ·ÔÙÂÏ› ·ÓÙ¤Ó‰ÂÈÍË ÂÈÏÔÁ‹˜ ‰fiÙË. ŸÌˆ˜, Ô ¯·ÌËÏ‹˜ ηÎÔ‹ıÂÈ·˜ ηÚΛÓÔ˜ ÙÔ˘ ‰¤ÚÌ·ÙÔ˜, fiˆ˜ ÙÔ ‚·ÛÈÎÔ΢ÙÙ·ÚÈÎfi ηÚΛӈ̷ Î·È Ù· ηÚÎÈÓÒÌ·Ù· ·fi Ï·ÎÒ‰Ë Î‡ÙÙ·Ú·, Ô in situ ηÚΛÓÔ˜ (Ù˘ Ì‹ÙÚ·˜ Î·È ÙÔ˘ ÙÚ·¯‹ÏÔ˘) Î·È ÔÈ ÚˆÙÔ·ı›˜ ηÚΛÓÔÈ ÙÔ˘ ÂÁÎÂÊ¿ÏÔ˘ ¯ˆÚ›˜ Â͈ÎÚ¿ÓȘ ÌÂÙ·ÛÙ¿ÛÂȘ ‰ÂÓ ·ÔÎÏÂ›Ô˘Ó ÙËÓ ÂÈÏÔÁ‹ οÔÈÔ˘ ‰fiÙË.53,54 ŸÛÔ ·Ó·ÊÔÚ¿ ÙÔ˘˜ ÂÁÎÂÊ·ÏÈÎÔ‡˜ fiÁÎÔ˘˜, οÔÈÔÈ ÈÛÙÔÏÔÁÈÎÔ› Ù‡ÔÈ, fiˆ˜ ÙÔ ÔχÌÔÚÊÔ ÁÏÔÈÔ‚Ï¿Ûو̷ Î·È ÙÔ Ì˘ÂÏÔ‚Ï¿Ûو̷, Î·È ÙÔ ÈÛÙÔÚÈÎfi ÎÚ·ÓÈÔÙÔÌ‹˜, ‰ÈÂÓ¤ÚÁÂÈ·˜ ·Ô¯ÂÙ¢ÙÈ΋˜ ·Ú¿Î·Ì„˘ ÙˆÓ ÂÁÎÂÊ·ÏÈÎÒÓ ÎÔÈÏÈÒÓ Î·È ıÂڷ¢ÙÈ΋˜ ·ÎÙÈÓÔ‚ÔÏ›·˜ ·˘Í¿ÓÔ˘Ó ÙÔÓ Î›Ó‰˘ÓÔ Èı·Ó‹˜ ÌÂÙ¿‰ÔÛ˘ ηÎÔ‹ıÂÈ·˜ ÛÙÔÓ Ï‹ÙË. ŸÙ·Ó ÚfiÎÂÈÙ·È ÁÈ· ‰fiÙË Ì ÚÔËÁÔ‡ÌÂÓÔ ÈÛÙÔÚÈÎfi ÓÂÔÏ·Û›·˜ Û˘Ì·ÁÔ‡˜ ÔÚÁ¿ÓÔ˘, Ú¤ÂÈ Ó· Ï·Ì‚¿ÓÂÙ·È ˘fi„Ë Ë ‚ÈÔÏÔÁÈ΋ Û˘ÌÂÚÈÊÔÚ¿ ÙÔ˘ Û˘ÁÎÂÎÚÈ̤ÓÔ˘ Ù‡Ô˘ Ù˘ ÓÂÔÏ·Û›·˜, Ù· ÈÛÙÔÏÔÁÈο Â˘Ú‹Ì·Ù· Î·È ÙÔ ÛÙ¿‰ÈÔ Î·Ù¿ ÙÔÓ ¯ÚfiÓÔ Ù˘ ‰È¿ÁÓˆÛ˘, Î·È ÙÔ ÂχıÂÚÔ ÓfiÛÔ˘ ¯ÚÔÓÈÎfi ‰È¿ÛÙËÌ· Ô˘ ÌÂÛÔÏ¿‚ËÛÂ. ∞ÛıÂÓ›˜ Ì ηÎÔ‹ıÂÈ· Ô˘ ·ÓÙÈÌÂÙˆ›ÛÙËΠÛÙÔ ·ÚÂÏıfiÓ ıˆÚÔ‡ÓÙ·È ıÂÚ·Â˘Ì¤ÓÔÈ ÌÂÙ¿ ·fi ¯ÚÔÓÈÎfi ‰È¿ÛÙËÌ· 5 ¯ÚfiÓˆÓ ÂχıÂÚÔ ÓfiÛÔ˘.55 ΔÔ ÌÂϿӈ̷, ÙÔ ¯ÔÚÈÔηÚΛӈ̷, Ô Î·ÚΛÓÔ˜ ÙÔ˘ Ó‡ÌÔÓ· Î·È ÙÔ˘ Ì·ÛÙÔ‡ ·ÔÙÂÏÔ‡Ó ·fiÏ˘Ù˜ ·ÓÙÂӉ›ÍÂȘ ÂÈÏÔÁ‹˜ ‰fiÙË ÂÂȉ‹ ·ÚÔ˘ÛÈ¿˙Ô˘Ó ·˘ÍË̤ÓË Èı·ÓfiÙËÙ· ÌÂÙ¿‰ÔÛ˘ ηÎÔ‹ıÂÈ·˜ ÛÙÔÓ Ï‹ÙË.56 °ÂÓÈο, ·fi ÙËÓ ·Ó¿Ï˘ÛË ‰Â‰ÔÌ¤ÓˆÓ ÙÔ˘ UNOS Ê·›ÓÂÙ·È fiÙÈ ÙÔ ÔÛÔÛÙfi Èı·Ó‹˜ ÌÂÙ¿‰ÔÛ˘ ηÎÔ‹ıÂÈ·˜ ·fi ÙÔÓ ‰fiÙË ÛÙÔÓ Ï‹ÙË Â›Ó·È Ôχ ¯·ÌËÏfi (0,02%).56
μÈ‚ÏÈÔÁÚ·Ê›· 1. Cameron A, Busuttil R. AASLD/ILTS transplant course: is there an extended donor suitable for everyone? Liver Transpl 2005; 11(11 Suppl 1): S2–5.
2. Renz J, Kin C, Kinkhabwala M, et al. Utilization of extended donor criteria liver allografts maximizes donor use and patient access to liver transplantation. Ann Surg 2005; 242:556–63. 3. The Organ Procurement and Transplant Network. Transplants by donor type; liver. Available at: www.optn.org. Accessed July 17, 2006. 4. Nickkholgh A, Weitz J, Encke J, Sauer P, Mehrabi A, Büchler MW, Schmidt J, Schemmer P. Utilization of extended donor criteria in liver transplantation: a comprehensive review of the literature. Nephrol Dial Transplant. 2007 Sep; 22 Suppl 8: viii29-viii36. 5. Briceno J, Solorzano G, Pera C. A proposal for scoring marginal liver grafts. Transpl Int 2000; 13 [Suppl 1]: S249–S252. 6. Pokorny H, Langer F, Herkner H et al. Influence of cumulative number of marginal donor criteria on primary organ dysfunction in liver recipients. Clin Transplant 2005; 19: 532–536. 7. Fischer-Fro hlich CL, Lauchart W. Expanded Criteria Liver Donors (ECD): Effect of Cumulative Risks. Ann Transplant 2006; 2: 52–56. 8. Seu P, Imagawa DK, Olthoff KM, Yersiz H, Rosenthal TJ, Sellers CA, et al. A prospective study on the reliability and cost effectiveness of preoperative ultrasound screening of the “marginal” liver donor. Transplantation 1996; 62:129-130. 9. Alexander JW, Vaughn WK. The use of “marginal” donors for organ transplantation. The influence of donor age on outcome. Transplantation 1991; 51:135-141. 10. Mor E, Klintmalm GB, Gonwa TA, Solomon H, Holman MJ, Gibbs JF, et al. The use of marginal donors for liver transplantation. A retrospective study of 365 liver donors. Transplantation 1992; 53:383-386. 11. Mirza DF, Gunson BK, Da Silva RF, Mayer AD, Buckels JA, McMaster P. Policies in Europe on “marginal quality” donor livers. Lancet 1994; 344:1480-1483. 12. De Carlis L, Sansalone CV, Rondinara GF, Colella G, Slim AO, Rossetti O, et al. Is the use of marginal donors justified in liver transplantation? Analysis of results and proposal of modern criteria. Transpl Int 1996; 9(suppl)1: S414-417. 13. Agnes S, Avolio AW, Magalini SC, Grieco G, Castagneto M. Marginal donors for patients on regular waiting lists for liver transplantation. Transpl Int 1996; 9(suppl 1): S469-S471. 14. Greig PD, Forster J, Superina RA, Strasberg SM, Mohamed M, Blendis LM, et al. Donor-specifi c factors predict graft function following liver transplantation. Transplant Proc 1990; 22: 2072–3. 15. Emre S, Schwartz ME, Altaca G, Sethi P, Fiel MI, Guy SR, et al. Safe use of hepatic allografts from donors older than 70 years. Transplantation 1996; 62:62–5. 16. Grazi GL, Cescon M, Ravaioli M, Ercolani G, Pierangeli F, D’Errico A, et al. A revised consideration on the use
METAMO™XEY™Eπ™ 2008
71
of very aged donors for liver transplantation. Am J Transplant 2001; 1: 61–8.
fungalpositive cultures in organ donors: clinical impact in liver transplantation. Liver Transpl 2006; 12: 1253-1259.
17. United Network for Organ Sharing website. Available at: http://www.unos.org.
31. Little D, Farell J, Cunningham P, Hickey DP. Donor sepsis is not a contraindication to cadaveric organ donation. Q J Med 1997; 90: 641-642.
18. Burroughs AK, Sabin CA, Rolles K, Delvart V, Karam V, Buckels J, O’Grady JG, Castaing D, Klempnauer J, Jamieson N, Neuhaus P, Lerut J, de Ville de Goyet J, Pollard S, Salizzoni M, Rogiers X, Muhlbacher F, Garcia Valdecasas JC, Broelsch C, Jaeck D, Berenguer J, Gonzalez EM, Adam R; European Liver Transplant Association. 3-month and 12-month mortality after first liver transplant in adults in Europe: predictive models for outcome. Lancet. 2006 Jan 21; 367(9506): 225-32. 19. Mutimer DJ, Gunson B, Chen J et al. Impact of donor age and year of transplantation on graft and patient survival following liver transplantation for hepatitis C virus. Transplantation 2006; 81: 7-14 20. Lopez-Navidad A, Caballero F. Extended criteria for organ acceptance. Strategies for achieving organ safety and for increasing organ pool. Clin Transplant 2003; 17: 308-324. 21. Popper H. Aging and the liver. Prog Liver Dis 1986; 8:659-83. 22. Serste T, Bourgeois N. Ageing and the liver. Acta Gastroenterol 2006; 69:296-8. 23. Verran D, Kusyk T, Painter D, Fisher J, Koorey D, Strasser S, et al. Clinical experience gained from the use of 120 steatotic donor livers for orthotopic liver transplantation. Liver Transpl 2003; 9:500-5. 24. Russo MW, Galanko JA, Zacks SL, Beavers KL, Fried MW, Shrestha R. Impact of donor age and year of transplant on graft survival in liver transplant recipients with chronic hepatitis C. Am J Transplant 2004; 4:1133-8. 25. Rayhill SC, Wu YM, Katz DA, Voigt MD, Labrecque DR, Kirby PA, et al. Older donor livers show early severe histological activity, fibrosis, and graft failure after liver transplantation for hepatitis C. Transplantation 2007; 84:331-9. 26. Briceno J, Marchal T, Padillo J, Solorzano G, Pera C. Influence of marginal donors on liver preservation injury. Transplantation 2002; 74:522-526. 27. Hoofnagle JH, Lombardero M, Zetterman RK, Lake J, Porayko M, Everhart J, et al. Donor age and outcome of liver transplantation. Hepatology 1996; 24:89-96. 28. Piratvisuth T, Tredger JM, Hayllar KA, Williams R. Contribution of true cold and rewarming ischemia times to factors determining outcome after orthotopic liver transplantation. Liver Transpl Surg 1995; 1:296-301. 29. Ploeg RJ, D’Alessandro AM, Knechtle SJ, Stegall MD, Pirsch JD, Hoffmann RM, et al. Risk factors for primary dysfunction after liver transplantation—a multivariate analysis. Transplantation 1993; 55:807-813. 30. Cerutti E, Stratta C, Romagnoli R et al. Bacterial- and
32. Lumbreras C, Sanz F, Gonzalez A et al. Clinical significance of donor-unrecognized bacteremia in the outcome of solid-organ transplant recipients. Clin Infect Dis 2001; 33: 722–726. 33. Freeman RB, Giatras I, Falagas ME et al. Outcome of transplantation of organs procured from bacteremic donors. Transplantation 1999; 68: 1107–1111. 34. Zibari G, Lipka J, Zizzi A, Abreo K, Jacobbi L, McDonald J. The use of contaminated donor organs in transplantation. Clin Transpl 2000; 14: 397-400. 35. Markmann JF, Markmann JW, Markmann DA, Bacquerizo A, Singer J, Holt CD, et al. Preoperative factors associated with outcome and their impact on resource use in 1148 consecutive primary liver transplants. Transplantation 2001; 72:1113-1122. 36. Mimeault R, Grant D, Ghent C, Duff J, Wall W. Analysis of donor and recipient variables and early graft function after orthotopic liver transplantation. Transplant Proc 1989; 21: 3355. 37. D’Alessandro AM, Kalayoglu M, Sollinger HW, Hoffmann RM, Reed A, Knechtle SJ, et al. The predictive value of donor liver biopsies on the development of primary nonfunction after orthotopic liver transplantation. Transplant Proc 1991; 23: 1536-7. 38. Fishbein TM, Fiel MI, Emre S, Cubukcu O, Guy SR, Schwartz ME, et al. Use of livers with microvesicular fat safely expands the donor pool. Transplantation 1997; 64:248-51. 39. Urena MA, Moreno Gonzalez E, Romero CJ, Ruiz-Delgado FC, Moreno Sanz C. An approach to the rational use of steatotic donor livers in liver transplantation. Hepatogastroenterology 1999; 46:1164–73. 40. Strasberg SM, Howard TK, Molmenti EP, Hertl M. Selecting the donor liver: risk factors for poor function after orthotopic liver transplantation. Hepatology 1994; 20:829–38. 41. Selzner M, Clavien PA. Fatty liver in liver transplantation and surgery. Semin Liver Dis. 2001; 21(1):105-13. 42. Feng S, Buell JF, Cherikh WS, Deng MC, Hanto DW, Kauffman HM, Leichtman AB, Lorber MI, Maters RG, McBride MA, Metzger RA, Nolte FS, O’Connor KJ, Roth D, Terrault NA, Henry ML. Organ donors with positive viral serology or malignancy: risk of disease transmission by transplantation. Transplantation. 2002 Dec 27; 74(12): 1657-63. 43. Dickson RC, Everhart JE, Lake JR, Wei Y, Seaberg EC, Wiesner RH, et al. Transmission of hepatitis B by transplantation of livers from donors positive for antibody to hepatitis B core antigen. The National Institute of Diabetes and Digestive Utility of Marginal Donors in
72
44.
45.
46.
47.
48.
49.
¡. ∞¡Δø¡π∞¢∏™
Liver Transplantation and Kidney Diseases Liver Transplantation Database. Gastroenterology 1997; 113: 1668-1674. Dodson SF, Issa S, Araya V, Gayowski T, Pinna A, Eghtesad B, et al. Infectivity of hepatic allografts with antibodies to hepatitis B virus. Transplantation 1997; 64:1582-4. Dodson SF, Bonham CA, Geller DA, Cacciarelli TV, Rakela J, Fung JJ. Prevention of de novo hepatitis B infection in recipients of hepatic allografts from anti-HBc positive donors. Transplantation 1999; 68:1058-1061. Pereira B, Milford E, Kirkman R, et al. Prevalence of hepatitis C virusRNAin organ donors positive for hepatitis Cantibody and in the recipients of their organs. N Engl J med 1992; 327: 910-5. Ghobrial R, Steadman R, Gornbein J, et al. A10-year experience of liver transplantation for hepatitis C: analysis of factors determining outcome in over 500 patients. Ann Surg 2001; 234: 384-94. Marroquin C, Marino G, Kuo P, et al. Transplantation of hepatitis c-positive livers in hepatitis C-positive patients is equivalent to transplanting hepatitis C-negative livers. Liver Transpl 2001; 7:762-8. Ricchiuti A, Brunati A, Mirabella S, et al. Use of hepatitis C virus-positive grafts in liver transplantation: a singlecentre experience. Transplant Proc 2005; 37:2569-70.
50. Vargas H, Laskus T, Wang L, et al. Outcome of liver transplantation in hepatitis C virusinfected patients who received hepatitis C virus-infected grafts. Gastroenterology 1999; 117:149-53. 51. Testa G, Goldstein R, Netto G, et al. Long-term outcome of patients transplanted with livers from hepatitis C-positive donors. Transplantation 1998; 65:925-9. 52. Velidedeoglu E, Desai N, Campos L, et al. The outcome of liver grafts procured from hepatitis C-positive donors. Transplantation 2002; 73:582-7. 53. Detry O, Honoré P, Hans MF, Delbouille MH, Jacquet N, Meurisse M. Organ donors with primary central nervous system tumor. Transplantation. 2000 Jul 15; 70(1):244-8. 54. Kauffman HM, McBride MA, Cherikh WS, Spain PC, Delmonico FL. Transplant tumor registry: donors with central nervous system tumors1. Transplantation. 2002 Feb 27; 73(4): 579-82. 55. Kauffman HM, McBride MA, Delmonico FL. First report of the United Network for Organ Sharing Transplant Tumor Registry: donors with a history of cancer. Transplantation. 2000 Dec 27; 70(12): 1747-51. 56. Feng S, Buell JF, Chari RS, DiMaio JM, Hanto DW. Tumors and transplantation: The 2003 Third Annual ASTS State-of-the- Art Winter Symposium. Am J Transplant 2003; 3: 1481–1467.
MÂÙ·ÌfiÛ¯Â˘ÛË ·fi ‰fiÙ˜ Ì ÈÛÙÔÚÈÎfi Ë·Ù›Ùȉ·˜ π.°. °Ô˘Ï‹˜
¤ÙË4. OÈ Wachs Î·È Û˘Ó ÙÔ 1995 ¤‰ÂÈÍ·Ó ÌÂÙ¿ ·fi ·Ó·‰ÚÔÌÈ΋ ·Ó¿Ï˘ÛË 25 ÂÚÈÛÙ·ÙÈÎÒÓ de novo Ë·Ù›Ùȉ·˜ μ ·fi anti-HBc ‰fiÙ˜ fiÙÈ Ô Î›Ó‰˘ÓÔ˜ Â›Ó·È Û·ÊÒ˜ ÌÂÁ·Ï‡ÙÂÚÔ˜ Î·È Ë Ë·Ù›Ùȉ· ‰È·ÙÚ¤¯ÂÈ ‚·Ú‡ÙÂÚË ÔÚ›· Û ·ÛıÂÓ›˜ Ì ÌÂÙ·ÌfiÛ¯Â˘ÛË ‹·ÙÔ˜ Û ۇÁÎÚÈÛË Ì ·ÛıÂÓ›˜ Ô˘ ˘Ô‚¿ÏÏÔÓÙ·È Û ÌÂÙ·ÌfiÛ¯Â˘ÛË ÓÂÊÚÔ‡ ‹ ηډȿ˜5. Ÿˆ˜ ‹Ù·Ó ¢ÓfiËÙÔ Û˘ÛÙ¿ıËΠÙfiÙÂ Ô ¤ÏÂÁ¯Ô˜ Î·È Ë ÂÍ·›ÚÂÛË ·fi ÌÂÙ·ÌfiÛ¯Â˘ÛË ÙˆÓ anti-HBc (+) ÌÔÛ¯Â˘Ì¿ÙˆÓ. ∞ÚÁfiÙÂÚ· fï˜ ‰È·ÈÛÙÒıËΠfiÙÈ Ë ÂÊ·ÚÌÔÁ‹ ÚÔʇϷ͢ Û ϋÙ˜ anti-HBc (+) ÌÔÛ¯Â˘Ì¿ÙˆÓ ÌÔÚ› Ó· ·ÔÙÚ¤„ÂÈ ÙËÓ ÂÌÊ¿ÓÈÛË de novo Ë·Ù›Ùȉ·˜ μ Î·È ÁÈ· ÙÔ ÏfiÁÔ ·˘Ùfi Ù· ÌÔۯ‡̷ٷ ·˘Ù¿ ‰ÂÓ ı· Ú¤ÂÈ Ó· ·ÔÚÚ›ÙÔÓÙ·È ÂÎ ÚÔÔÈÌ›Ô˘6.
ΔÔ ÌÂÁ¿ÏÔ ¯¿ÛÌ· Ô˘ ˘Ê›ÛÙ·Ù·È ÌÂٷ͇ ÙˆÓ ‰È·ı¤ÛÈÌˆÓ Ë·ÙÈÎÒÓ ÌÔÛ¯Â˘Ì¿ÙˆÓ Î·È ÙÔ˘ ÌÂÁ¿ÏÔ˘ ·ÚÈıÌÔ‡ ·ÛıÂÓÒÓ Û ϛÛÙ· ÌÂÙ·ÌfiÛ¯Â˘Û˘ ¤¯ÂÈ Ô‰ËÁ‹ÛÂÈ ÛÙË Â›Ù·ÛË ÙˆÓ ÚÔÛ·ıÂÈÒÓ ÁÈ· ÙËÓ ·Ó‡ÚÂÛË ÌÔÛ¯Â˘Ì¿ÙˆÓ ·fi ÏÈÁfiÙÂÚÔ ÂӉ‰ÂÈÁ̤ÓÔ˘˜ ‰fiÙ˜. ∂Ó·˜ ·fi ÙÔ˘˜ ÙÚfiÔ˘˜ ·‡ÍËÛ˘ Ù˘ ‰ÂÍ·ÌÂÓ‹˜ ÙˆÓ Ë·ÙÈÎÒÓ ÌÔÛ¯Â˘Ì¿ÙˆÓ Â›Ó·È Ë ¯Ú‹ÛË ÔÚÁ¿ÓˆÓ ·fi ‰fiÙ˜ Ô˘ ¤¯Ô˘Ó ÈÛÙÔÚÈÎfi ¤ÎıÂÛ˘ ÛÙÔÓ Èfi Ù˘ Ë·Ù›Ùȉ·˜ μ. øÛÙfiÛÔ Ë ÌÂÙ·ÌfiÛ¯Â˘ÛË ·ÓÙÈ-HBc (+) Ë·ÙÈÎÒÓ ÌÔÛ¯Â˘Ì¿ÙˆÓ ÂÓ¤¯ÂÈ ·˘ÍË̤ÓÔ Î›Ó‰˘ÓÔ ÌÂÙ¿‰ÔÛ˘ Ù˘ Ë·Ù›Ùȉ·˜ μ ÛÙÔ Ï‹ÙË, ÁÂÁÔÓfi˜ Ô˘ ÌÔÚ› Ó· Ô‰ËÁ‹ÛÂÈ Û ÔÚÈṲ̂Ó˜ ÂÚÈÙÒÛÂȘ Û ÛÔ‚·Ú‹ ÂÓÂÚÁÔÔ›ËÛË Ù˘ ÓfiÛÔ˘ ÛÙÔ Ï‹ÙË1,2. O ΛӉ˘ÓÔ˜ Ù˘ ÂÌÊ¿ÓÈÛ˘ de novo Ë·Ù›Ùȉ·˜ μ, Ô˘ ÔÚ›˙ÂÙ·È ˆ˜ Ë ·Ó›¯Ó¢ÛË HBsAg Û ·ÛıÂÓ›˜ Ì ·ÚÓËÙÈ΋ ‰ÔÎÈÌ·Û›· ÚÈÓ ÙËÓ ÌÂÙ·ÌfiÛ¯Â˘ÛË, ·˘Í¿ÓÂÈ Î·È ÂÍ·ÈÙ›·˜ Ù˘ ¯ÔÚ‹ÁËÛ˘ ·ÓÔÛÔηٷÛÙÔÏ‹˜.
¶·Ú¿ÁÔÓÙ˜ ÎÈÓ‰‡ÓÔ˘ ÁÈ· ÂÌÊ¿ÓÈÛË de novo Ë·Ù›Ùȉ·˜ μ O ΛӉ˘ÓÔ˜ ÂÌÊ¿ÓÈÛ˘ de novo Ë·Ù›Ùȉ·˜ μ Û ·ÛıÂÓ›˜ Ô˘ Ï·Ì‚¿ÓÔ˘Ó anti-HBc (–) ÌÔۯ‡̷ٷ Â›Ó·È Ôχ ¯·ÌËÏfi˜ Î·È Î˘Ì·›ÓÂÙ·È ÌÂٷ͇ 0%-1.5%. À¿Ú¯Ô˘Ó ÈÛ¯˘Ú¿ ‰Â‰Ô̤ӷ Û‡Ìʈӷ Ì ٷ ÔÔ›· ÔÈ ‰fiÙ˜ Ì ÌÂÌÔӈ̤ÓË ·Ó›¯Ó¢ÛË anti-HBs ‰ÂÓ ÌÂÙ·‰›‰Ô˘Ó ÙË ÓfiÛÔ. ∞ÓÙ›ıÂÙ· ÔÈ anti-HBc (+) ‰fiÙ˜ ·ÓÂÍ¿ÚÙËÙ· ·fi ÙËÓ ·Ó›¯Ó¢ÛË ‹ fi¯È anti-HBs ‰˘ÓËÙÈο ÌÔÚÔ‡Ó Ó· ÌÂÙ·‰ÒÛÔ˘Ó ÙË Ïԛ̈ÍË4. O ΛӉ˘ÓÔ˜ ·˘Í¿ÓÂÈ ·Ó¿ÏÔÁ· Ì ÙÔÓ ÂÈÔÏ·ÛÌfi Ù˘ Ë·Ù›Ùȉ·˜ μ ÛÙÔÓ ·ÓÙ›ÛÙÔÈ¯Ô ÁÂÓÈÎfi ÏËı˘ÛÌfi. Oˆ˜ Â›Ó·È ·Ó·ÌÂÓfiÌÂÓÔ ·˘Ùfi Û˘Ì‚·›ÓÂÈ Û ˘ËÏfiÙÂÚ· ÔÛÔÛÙ¿ ÛÙȘ ¯ÒÚ˜ Ù˘ ∞Û›·˜ Û ۇÁÎÚÈÛË Ì ∂˘ÚÒË – μ ∞ÌÂÚÈ΋. ∫·ıÔÚÈÛÙÈÎfi ÚfiÏÔ ÁÈ· ÙÔÓ Î›Ó‰˘ÓÔ ÂÌÊ¿ÓÈÛ˘ de novo Ë·Ù›Ùȉ·˜ μ ·ÔÙÂÏ› Ë ·Ó›¯Ó¢ÛË ÔÚÔÏÔÁÈÎÒÓ ‰ÂÈÎÙÒÓ ÛÙÔ ‰fiÙË. À¿Ú¯Ô˘Ó ÍÂοı·Ú· ‰Â‰Ô̤ӷ Û‡Ìʈӷ Ì ٷ ÔÔ›· ·ÛıÂÓ›˜ Ì ·ÚÓËÙÈÎÔ‡˜ fiÏÔ˘˜ ÙÔ˘˜ ‰Â›ÎÙ˜ Ù˘ Ë·Ù›Ùȉ·˜ μ ‚Ú›ÛÎÔÓÙ·È ÛÙÔ ÌÂÁ·Ï‡ÙÂÚÔ Î›Ó‰˘ÓÔ ·Ó¿Ù˘Í˘ de novo Ë·Ù›Ùȉ·˜ fiÙ·Ó Ï·Ì‚¿ÓÔ˘Ó anti-HBc (+) ÌfiÛ¯Â˘Ì·. O ΛӉ˘ÓÔ˜ ·˘Ùfi˜ ÚÔÛÂÁÁ›˙ÂÈ ÙÔ
∞Ó·ÁÓÒÚÈÛË ÙÔ˘ ÎÈÓ‰‡ÓÔ˘ ÌÂÙ¿‰ÔÛ˘ Ë·Ù›Ùȉ·˜ Ì ÌÂÙ·ÌfiÛ¯Â˘ÛË anti-HBc (+) ÌÔÛ¯Â˘Ì¿ÙˆÓ O ΛӉ˘ÓÔ˜ ÌÂÙ¿‰ÔÛ˘ Ë·Ù›Ùȉ·˜ μ ·fi antiHBc (+) & HBsAg (–) ‰fiÙ˜ ·Ó·ÁÓˆÚ›ÛıËΠÁÈ· ÚÒÙË ÊÔÚ· ηٿ ÙË ÌÂÙ¿ÁÁÈÛË ·›Ì·ÙÔ˜3. ¢È·ÈÛÙÒıËΠÙfiÙ fiÙÈ ¿ÙÔÌ· Ô˘ ¤¯Ô˘Ó ¤ÚıÂÈ Û ·ʋ Ì ÙÔÓ Èfi Ù˘ Ë·Ù›Ùȉ·˜ μ ÌÔÚ› Ó· ¤¯Ô˘Ó ÂÈÙ‡¯ÂÈ ÙËÓ Î¿ı·ÚÛË ÙÔ˘ HBsAg Î·È Ó¿ ¤¯Ô˘Ó ÔÚÔÏÔÁÈ΋ ¤Ó‰ÂÈÍË ·ÓÔÛ›·˜, ·ÏÏ¿ ‰È·ÙËÚÔ‡Ó ·ÎfiÌË ÙË ‰˘Ó·ÙfiÙËÙ· ÌÂÙ¿‰ÔÛ˘ Ù˘ ÓfiÛÔ˘. OÈ ÂÈÙÒÛÂȘ Ô˘ ¤¯ÂÈ Î¿ÙÈ Ù¤ÙÔÈÔ ÛÙË ÌÂÙ·ÌfiÛ¯Â˘ÛË ÔÚÁ¿ÓˆÓ Â›Ó·È ÂÌÊ·Ó‹˜. ΔÔ Úfi‚ÏËÌ· ·ÔÎÙ¿ Û·ÊÒ˜ ÌÂÁ·Ï‡ÙÂÚ˜ ‰È·ÛÙ¿ÛÂȘ ÛÙË ÌÂÙ·ÌfiÛ¯Â˘ÛË ‹·ÙÔ˜ fiÔ˘ Ë ÂÚ›ÙˆÛË Ï·Óı¿ÓÔ˘Û·˜ Ïԛ̈͢ ÙÔ˘ ÌÔۯ‡̷ÙÔ˜ Â›Ó·È ÌÂÁ·Ï‡ÙÂÚË ÏfiÁˆ Ù˘ ·˘ÍË̤Ó˘ Û˘ÁΤÓÙÚˆÛ˘ ÙÔ˘ ÈÔ‡ ÛÙÔ ‹·Ú. ∏ ÂÌÊ¿ÓÈÛË Ó¤·˜ Ïԛ̈͢ ·fi ÙÔÓ Èfi Ù˘ Ë·Ù›Ùȉ·˜ μ Û ÔÚÔ·ÚÓËÙÈÎÔ‡˜ Ï‹Ù˜ ̤ۈ ÌÂÙ·ÌfiÛ¯Â˘Û˘ ÔÚÁ¿ÓˆÓ ·fi HBsAg(–) anti-HBc (+) ‰fiÙ˜ ·Ó·ÁÓˆÚ›ÛıËΠÁÈ· ÚÒÙË ÊÔÚ¿ ÂÚ›Ô˘ ÚÈÓ ·fi 15
73
74
π. °√À§∏™
75%4. ∞ÛıÂÓ›˜ Ì ·ÓÙÈÛÒÌ·Ù· ¤Ó·ÓÙÈ ÙÔ˘ ÈÔ‡ ∏μV ÂÌÊ·Ó›˙Ô˘Ó ÌÈÎÚfiÙÂÚÔ Î›Ó‰˘ÓÔ. ∞˘Ùfi fï˜ ‰Â ÛËÌ·›ÓÂÈ fiÙÈ ·ÛıÂÓ›˜ Ì ÌÂÌÔӈ̤ÓË ·Ó›¯Ó¢ÛË anti-HBs ‰ÂÓ ¤¯Ô˘Ó ηӤӷ ΛӉ˘ÓÔ ÂÌÊ¿ÓÈÛ˘ de novo Ë·Ù›Ùȉ·˜ μ. ∏ ¤ÏÏÂÈ„Ë ÚÔÛÙ·Û›·˜ Èı·ÓÒ˜ Û¯ÂÙ›˙ÂÙ·È Ì ÙÔÓ Ù›ÙÏÔ ÙˆÓ Î˘ÎÏÔÊÔÚÔ‡ÓÙˆÓ ·ÓÙÈۈ̿وÓ. ™‹ÌÂÚ· Â›Ó·È ÁÂÓÈÎÒ˜ ·Ô‰ÂÎÙfi fiÙÈ ÛÙÔÓ ÚÔÌÂÙ·ÌÔÛ¯Â˘ÙÈÎfi ¤ÏÂÁ¯Ô ı· Ú¤ÂÈ Ó· ÂÚÈÏ·Ì‚¿ÓÂÙ·È ÔÛÔÙÈ΋ ̤ÙÚËÛË ÙˆÓ anti-HBs ·ÓÙÈÛˆÌ¿ÙˆÓ Î·È Ù· ÂÈı˘ÌËÙ¿ ›‰· Ú¤ÂÈ Ó· ˘ÂÚ‚·›ÓÔ˘Ó Ù· 100U/L, ÒÛÙ ӷ ıˆÚÔ‡ÓÙ·È ÚÔÊ˘Ï·ÎÙÈο. Δ¤ÏÔ˜ ȉȷ›ÙÂÚË ÚÔÛÔ¯‹ ¯ÚÂÈ¿˙ÂÙ·È ÛÙËÓ ·Ó¿Ï˘ÛË ÙˆÓ ÂÚÈÙÒÛÂˆÓ ÂÌÊ¿ÓÈÛ˘ de novo Ë·Ù›Ùȉ·˜ μ Û anti-HBc (+) Ï‹Ù˜ Ô˘ Ï·Ì‚¿ÓÔ˘Ó anti-HBc (+) ÌÔۯ‡̷ٷ. ™ÙÔ˘˜ ·ÛıÂÓ›˜ ·˘ÙÔ‡˜ ˘¿Ú¯ÂÈ ¿ÓÙ· Ô Î›Ó‰˘ÓÔ˜ ÂÓÂÚÁÔÔ›ËÛ˘ Ï·Óı¿ÓÔ˘Û·˜ HBV Ïԛ̈͢ ÌÂÙ¿ ¯ÔÚ‹ÁËÛË ·ÓÔÛÔηٷÛÙÔÏ‹˜. ªÂٷ͇ ÙˆÓ ˘ÔÏÔ›ˆÓ ·Ú·ÁfiÓÙˆÓ Ô˘ Û¯ÂÙ›˙ÔÓÙ·È Ì ÂÌÊ¿ÓÈÛË de novo Ë·Ù›Ùȉ·˜ μ Û ·ÛıÂÓ›˜ Ô˘ Ï·Ì‚¿ÓÔ˘Ó anti-HBc (+) ÌÔۯ‡̷ٷ ÂÚÈÏ·Ì‚¿ÓÔÓÙ·È ·ÎfiÌË ÙÔ ÈÈÎfi ÊÔÚÙ›Ô ÛÙÔ ÌfiÛ¯Â˘Ì·, Ë ÚÔÂÁ¯ÂÈÚËÙÈ΋ ÁÂÓÈ΋ ηٿÛÙ·ÛË ÙÔ˘ Ï‹ÙË (Child-Pugh score) Î·È Ô ‚·ıÌfi˜ ·ÓÔÛÔηٷÛÙÔÏ‹˜ ÌÂÙ¿ ÙË ÌÂÙ·ÌfiÛ¯Â˘ÛË4.
ÃÂÈÚÈÛÌfi˜ Ï‹ÙË anti-HBc (+) ÌÔۯ‡̷ÙÔ˜ ªÂ ‚¿ÛË Ù· ÚÔ·Ó·ÊÂÚı¤ÓÙ· ‰Â‰Ô̤ӷ antiHBc (+) ÌÔۯ‡̷ٷ ı· Ú¤ÂÈ Ó· ÚÔÛʤÚÔÓÙ·È Î·Ù¿ ÚÔÙÂÚ·ÈfiÙËÙ· Û ·ÛıÂÓ›˜ Ì HBsAg (+). ∏ ¯Ú‹ÛË ·˘ÙÒÓ ÙˆÓ ÌÔÛ¯Â˘Ì¿ÙˆÓ Û ·ÛıÂÓ›˜ Ì ÌË ·ÓÙÈÚÚÔÔ‡ÌÂÓË ∏μV ΛÚÚˆÛË ‹ ÎÂÚ·˘ÓÔ‚fiÏÔ HBV Ïԛ̈ÍË ·ÔÙÂÏ› ÌÈ· ÏÔÁÈ΋ ÚÒÙË ÂÈÏÔÁ‹, ηıÒ˜ ¤¯ÂÈ ‰Âȯı› fiÙÈ Ì ÙÔÓ ÙÚfiÔ ·˘Ùfi ‰ÂÓ ÂËÚ¿˙ÂÙ·È Ë ıÓËÙfiÙËÙ· ‹ Ô Î›Ó‰˘ÓÔ˜ ˘ÔÙÚÔ‹˜ HBV Ïԛ̈͢ ÛÙo ÌfiÛ¯Â˘Ì·7. ∂¿Ó ‰ÂÓ Â›Ó·È ‰È·ı¤ÛÈÌÔ˜ HBsAg (+) Ï‹Ù˘, Ùo anti-HBc (+) ÌfiÛ¯Â˘Ì· ı· Ú¤ÂÈ Ó· ÚÔÛʤÚÂÙ·È Û antiHBc (+) Ï‹ÙË, Ô ÔÔ›Ô˜ ηٿ ÚÔÙ›ÌËÛË ı· Ú¤ÂÈ Ó· ¤¯ÂÈ Î·È anti-HBs (+) ·ÓÙÈÛÒÌ·Ù·. ∞ÎfiÌË fï˜ Î·È Û ·˘Ù‹ ÙËÓ ÂÚ›ÙˆÛË Ô Î›Ó‰˘ÓÔ˜ ·Ó·˙ˆ‡ÚˆÛ˘ HBV Ïԛ̈͢ ÛÙÔ Ï‹ÙË Â›Ó·È ˘·ÚÎÙfi˜. OÈ ÂÚÈÛÛfiÙÂÚÔÈ Û˘ÌʈÓÔ‡Ó fiÙÈ ·˘Ù‹ Ë Î·ÙËÁÔÚ›· ·ÛıÂÓÒÓ ı· Ú¤ÂÈ Ó· Ï¿‚ÂÈ ÚÔÊ˘Ï·ÎÙÈ΋ ·ÁˆÁ‹1 ·Ó Î·È ÔÚÈṲ̂ÓÔÈ Û˘ÛÙ‹ÓÔ˘Ó ÌfiÓÔ Ù·ÎÙÈ΋ Î·È Û˘ÛÙËÌ·ÙÈ΋ ·Ú·ÎÔÏÔ‡ıËÛË Ì ÚÔÛ‰ÈÔÚÈÛÌfi ÛÙÔÓ ÔÚfi HBV DNA, HBsAg HBcAb Î·È HBsAb οı 3-6 Ì‹Ó˜.
Δ¤ÏÔ˜ ÛÙËÓ ÂÚ›ÙˆÛË Ô˘ ‰ÂÓ Â›Ó·È ‰È·ı¤ÛÈÌÔ˜ Ï‹Ù˘ anti-HBc (+), anti-HBs (+) Ùo antiHBc (+) ÌfiÛ¯Â˘Ì· ı· ÌÔÚÔ‡Û ӷ ÚÔÛÊÂÚı› Û ϋÙË ¯ˆÚ›˜ ηӤӷ ıÂÙÈÎfi ‰Â›ÎÙË Ë·Ù›Ùȉ·˜ μ, Ì ÙËÓ ÚÔ¸fiıÂÛË fiÙÈ ˘¿Ú¯ÂÈ ·ÈÙÈÔÏÔÁËÌÂÓË È·ÙÚÈ΋ ·Ó·ÁηÈfiÙËÙ· ÁÈ· Ó· Û˘Ì‚Â› οÙÈ Ù¤ÙÔÈÔ. OÏÔÈ ÔÈ Ï‹Ù˜ ·˘Ù‹˜ Ù˘ ηÙËÁÔÚ›·˜ ı· Ú¤ÂÈ Ó· Ï·Ì‚¿ÓÔ˘Ó ÚÔÊ˘Ï·ÎÙÈ΋ ·ÁˆÁ‹ Ì ÓÔ˘ÎÏÂÔÛȉÈο/ÓÔ˘ÎÏÂÔÙȉÈο ·Ó¿ÏÔÁ· ˆ˜ ÌÔÓÔıÂڷ›· ‹ Û ıÂڷ›· Û˘Ó‰˘·ÛÌÔ‡ Ì ·ÓÔÛÔÛÊ·ÈÚ›ÓË ¤Ó·ÓÙÈ Ë·Ù›Ùȉ·˜ μ (HBIg), fiˆ˜ ı· ·Ó·Ï˘ı› ÛÙË Û˘Ó¤¯ÂÈ·.
¶ÚÔʇϷÍË ¤Ó·ÓÙÈ ·Ó·˙ˆ‡ÚˆÛ˘ HBV Ïԛ̈͢ OÈ ÛÙÚ·ÙËÁÈΤ˜ Ô˘ ¯ÚËÛÈÌÔÔÈÔ‡ÓÙ·È ÛÙËÓ ÚÔʇϷÍË ·fi ÙËÓ ˘ÔÙÚÔ‹ Ù˘ HBV Ïԛ̈͢ ÛÙÔ ÌfiÛ¯Â˘Ì· ¤¯Ô˘Ó ¯ÚËÛÈÌÔÔÈËı› Î·È ÛÙËÓ ÚÔʇϷÍË ·Ó·˙ˆ‡ÚˆÛ˘ HBV Ïԛ̈͢ Û ϋÙ˜ anti-HBc (+) ÌÔÛ¯Â˘Ì¿ÙˆÓ. ∏ Û˘Ìʈӛ· Â›Ó·È ·fiÏ˘ÙË ÛÙË ¯ÔÚ‹ÁËÛË ÚÔʇϷ͢ Û ·ÛıÂÓ›˜ Ì ·ÚÓËÙÈÎÔ‡˜ ‰Â›ÎÙ˜ Ë·Ù›Ùȉ·˜ [(anti-HBc (–) & anti-HBs (–)]. OÌÔʈӛ· ÛÙË ‚È‚ÏÈÔÁÚ·Ê›· ‰ÂÓ ˘¿Ú¯ÂÈ ÁÈ· ÙËÓ ·Ó·ÁηÈfiÙËÙ· ÚÔʇϷ͢ ·ÛıÂÓÒÓ Ì anti-HBc (+) ηÈ/‹ anti-HBs (+). OÚÈṲ̂ÓÔÈ ÚÔÙ›ÓÔ˘Ó ÙË ÛÙÂÓ‹ ·Ú·ÎÔÏÔ‡ıËÛË ·˘ÙÒÓ ÙˆÓ ·ÛıÂÓÒÓ Ì ÔÚÔÏÔÁÈÎÔ‡˜ ‰Â›ÎÙ˜ HBV Î·È ÚÔÛ‰ÈÔÚÈÛÌfi HBV DNA, ÒÛÙ Ì ÙÔÓ ÙÚfiÔ ·˘Ùfi οÔÈÔÈ ·fi ÙÔ˘˜ ·ÛıÂÓ›˜ Ó· ·ÔʇÁÔ˘Ó ÙË Ì·ÎÚfi¯ÚÔÓË ¯ÔÚ‹ÁËÛË ÚÔÊ˘Ï·ÎÙÈÎÒÓ ·Ú·ÁfiÓÙˆÓ8. øÛÙfiÛÔ Ì¿ÏÏÔÓ ˘ÂÚÙÂÚÔ‡Ó ÔÈ ·fi„ÂȘ fiÙÈ fiÏÔÈ ÔÈ Ï‹Ù˜ anti-HBc (+) ÌÔÛ¯Â˘Ì¿ÙˆÓ ı· Ú¤ÂÈ Ó· Ï·Ì‚¿ÓÔ˘Ó ÚÔÊ˘Ï·ÎÙÈ΋ ·ÁˆÁ‹. OÈ ÛÙÚ·ÙËÁÈΤ˜ Ô˘ ¤¯Ô˘Ó ¯ÚËÛÈÌÔÔÈËı› Â›Ó·È ÔÈ ·ÎfiÏÔ˘ı˜: ¯ÔÚ‹ÁËÛË ÌÔÓÔÚÔʇϷ͢ Ì HBIg, Û˘Ó‰˘·ÛÌfi˜ HBIg Î·È Ï·ÌÈ‚Ô˘‰›Ó˘, ¯ÔÚ‹ÁËÛË ÌÔÓÔÚÔʇϷ͢ Ì ϷÌÈ‚Ô˘‰›ÓË Î·È ÂÌ‚ÔÏÈ·ÛÌfi˜ ¤Ó·ÓÙÈ HBV Ú›Ó ÙË ÌÂÙ·ÌfiÛ¯Â˘ÛË Î·È ÛÙË Û˘Ó¤¯ÂÈ· ¯ÔÚ‹ÁËÛË Ï·ÌÈ‚Ô˘‰›Ó˘ ÌÂÙ¿ ÙË ÌÂÙ·ÌfiÛ¯Â˘ÛË. ∏ ÌÔÓÔÚÔʇϷÍË Ì HBIg Ô˘ ÚÔÙ¿ıËΠ·Ú¯Èο ·fi ÙÔ˘˜ Uemoto Î·È Û˘Ó Â›¯Â ·ÔÙÂÏÂÛÌ·ÙÈÎfiÙËÙ· ·ÏÏ¿ ‰ÂÓ ÚÔʇϷÛÛ fiÏÔ˘˜ ÙÔ˘˜ ·ÛıÂÓ›˜ Î·È ÁÈ· ÙÔ ÏfiÁÔ ·˘Ùfi ¤¯ÂÈ ÂÁηٷÏËÊı›6,8,9. ∞ÓÙ›ıÂÙ· Ë ¯ÔÚ‹ÁËÛË Û˘Ó‰˘·ÛÌÔ‡ Ì HBIg Î·È Ï·ÌÈ‚Ô˘‰›ÓË ÚÔÊ˘Ï¿ÛÛÂÈ fiÏÔ˘˜ ÙÔ˘˜ Ï‹Ù˜ anti-∏μc (+) ÌÔÛ¯Â˘Ì¿ÙˆÓ10. øÛÙfiÛÔ Ë Ù·ÎÙÈ΋ ·˘Ù‹ Â›Ó·È ¤¯ÂÈ ˘„ËÏfi ÎfiÛÙÔ˜ Î·È ÂÌÊ·Ó›˙ÂÈ ‰˘ÛÎÔϛ˜ ÛÙË Ì·ÎÚÔ¯ÚfiÓÈ· ÂÊ·ÚÌÔÁ‹ Ù˘. °È· Ó·
METAMO™XEY™Eπ™ 2008
·ÔÊ¢¯ıÔ‡Ó Ù· ÚÔ‚Ï‹Ì·Ù· ·˘Ù¿ ÔÚÈṲ̂ӷ ΤÓÙÚ· ÚÔÙ›ÓÔ˘Ó ÙËÓ ‰È·ÎÔ‹ Ù˘ ¯ÔÚ‹ÁËÛ˘ HBIg ÌÂÙ¿ ·fi ¤Ó· ·Ú¯ÈÎfi ‰È¿ÛÙËÌ· ÌÂÙ¿ ÙË ÌÂÙ·ÌfiÛ¯Â˘ÛË Î·È ÙË Û˘Ó¤¯ÈÛË Ù˘ ÚÔʇϷ͢ ÌfiÓÔ Ì ϷÌÈ‚Ô˘‰›ÓË4. ¶ÚÔÙ¿ıËΠ·ÎfiÌË Ë ¯ÔÚ‹ÁËÛË ÌÔÓÔÚÔʇϷ͢ Ì ϷÌÈ‚Ô˘‰›ÓË ·fi ÙÔ˘˜ Yu Î·È Û˘Ó Ô˘ ‹Ù·Ó ÔÈ ÚÒÙÔÈ Ô˘ ¯ÔÚ‹ÁËÛ·Ó ·˘Ùfi ÙÔÓ ·Ú¿ÁÔÓÙ· Û 9 Ï‹Ù˜ anti-∏μc (+) ÌÔÛ¯Â˘Ì¿ÙˆÓ, 5 ·fi ÙÔ˘˜ ÔÔ›Ô˘˜ ‹Ù·Ó ·ÚÓËÙÈÎÔ› ÁÈ· anti-HBc & antiHBs11. ∫·Ó¤Ó·˜ ·fi ÙÔ˘˜ ·ÛıÂÓ›˜ ‰ÂÓ ÂÌÊ¿ÓÈÛ ·Ó·˙ˆ‡ÚˆÛË HBV Ïԛ̈͢ ·Ó Î·È ˘¿Ú¯ÂÈ ˘„ËÏfi ÔÛÔÛÙfi ÚÒÈÌ˘ ıÓËÙfiÙËÙ·˜ Î·È Ë ‰È¿ÚÎÂÈ· Ù˘ ·Ú·ÎÔÏÔ‡ıËÛ˘ ‹Ù·Ó ‚Ú·¯Â›·. ΔÔ Î‡ÚÈÔ ÌÂÈ·Ó¤ÎÙËÌ· ·˘Ù‹˜ Ù˘ ÛÙÚ·ÙËÁÈ΋˜ Â›Ó·È Ô Î›Ó‰˘ÓÔ˜ ÂÌÊ¿ÓÈÛ˘ YMDD ÌÂÙ·ÏÏ·Á‹˜ Î·È ÈÔÏÔÁÈ΋˜ ·ÓÙ›ÛÙ·Û˘ Ô˘ fiˆ˜ Â›Ó·È ÁÓˆÛÙfi Û˘Ì‚·›ÓÂÈ ÛÙËÓ ÏÂÈÔ„ËÊ›· ÙˆÓ ∏BsAg (+) ·ÛıÂÓÒÓ Ô˘ Ï·Ì‚¿ÓÂÈ Ï·ÌÈ‚Ô˘‰›ÓË ÚÈÓ ÙË ÌÂÙ·ÌfiÛ¯Â˘ÛË. ¶ÂÚÈÛÙ·ÙÈο Ì ·Ó¿Ù˘ÍË ÈÔÏÔÁÈ΋˜ ·ÓÙ›ÛÙ·Û˘ Û ·˘Ù‹ ÙËÓ ÂȉÈ΋ ÔÌ¿‰· ·ÛıÂÓÒÓ ¿Ú¯ÈÛ·Ó Ó· ÂÌÊ·Ó›˙ÔÓÙ·È ÛÙË ‚È‚ÏÈÔÁÚ·Ê›·12. ¡ÂfiÙÂÚ· ÓÔ˘ÎÏÂÔÛȉ›Î¿/ÓÔ˘ÎÏÂÔÙȉÈο ·Ó¿ÏÔÁ· Ô˘ ‚Ú›ÛÎÔÓÙ·È ‹‰Ë ÛÙËÓ Î˘ÎÏÔÊÔÚ›· Î·È ÂÌÊ·Ó›˙Ô˘Ó Ôχ ¯·ÌËÏfiÙÂÚ· ÔÛÔÙ¿ ·Ó¿Ù˘Í˘ ÈÔÏÔÁÈ΋˜ ·ÓÙ›ÛÙ·Û˘ fiˆ˜ Â›Ó·È ‹ ÂÓÙÂη‚›ÚË Èı·ÓÒ˜ Ó· ·Ô‰ÂȯıÔ‡Ó Ôχ ¯Ú‹ÛÈÌ· ÛÙÔÓ ÙÔ̤· ·˘Ùfi. Δ¤ÏÔ˜ ÌÈ· ·ÎfiÌË ÂӉȷʤÚÔ˘Û· ÛÙÚ·ÙËÁÈ΋ Ô˘ ¤¯ÂÈ ÚÔÙ·ı› Â›Ó·È Ë ÂÓÂÚÁËÙÈ΋ ·ÓÔÛÔÔ›ËÛË (ÂÊ·ÚÌÔÁ‹ ÂÌ‚ÔÏÈ·ÛÌÔ‡) ·ÛıÂÓÒÓ Ì ·ÚÓËÙÈÎÔ‡˜ ‰Â›ÎÙ˜ ÚÈÓ ÙË ÌÂÙ¿ÌfiÛ¯Â˘ÛË Î·È Ë ¯ÔÚ‹ÁËÛË ÛÙË Û˘Ó¤¯ÂÈ· ıÂڷ›·˜ Ì ϷÌÈ‚Ô˘‰›ÓË13. H ÛÙÚ·ÙËÁÈ΋ ·˘Ù‹ ¤¯ÂÈ ÂÊ·ÚÌÔÛı› ÂÈÙ˘¯Ò˜ Û ÌÂϤÙË 16 ·ÛıÂÓÒÓ ·fi ÙËÓ Δ·È‚¿Ó, Ô˘ ¤Ï·‚·Ó anti-HBc (+) ÌÔۯ‡̷ٷ ·fi ˙ÒÓÙ· ‰fiÙË. OÈ 15 ·fi ÙÔ˘˜ 16 ·ÛıÂÓ›˜ ÂÌÊ¿ÓÈÛ·Ó anti-HBs Ì ÂÌ‚ÔÏÈ·ÛÌfi ÚÈÓ ÙË ÌÂÙ·ÌfiÛ¯Â˘ÛË Î·È Î·Ó¤Ó·˜ ‰ÂÓ ÂÌÊ¿ÓÈÛ ·Ó·˙ˆ‡ÚˆÛË HBV Ïԛ̈͢ ηٿ ÙË ‰È¿ÚÎÂÈ· ·Ú·ÎÔÏÔ‡ıËÛ˘ 14-40 ÌËÓÒÓ.
ÃÚ‹ÛË anti-HCV (+) ÌÔÛ¯Â˘Ì¿ÙˆÓ ∏ ¯Ú‹ÛË anti-HCV (+) ÌÔÛ¯Â˘Ì¿ÙˆÓ ÁÈ· ·ÛıÂÓ›˜ Ì ¯ÚfiÓÈ· Ë·Ù›Ùȉ· C ¤¯ÂÈ ÚÔÙ·ı› ˆ˜ ¤Ó· ÂÈϤÔÓ Ì¤ÙÚÔ Ô˘ ÌÔÚ› Ó· ‚ÔËı‹ÛÂÈ ÛÙËÓ ·‡ÍËÛË ÙÔ˘ ·ÚÈıÌÔ‡ ÙˆÓ ÌÔÛ¯Â˘¿ÙˆÓ Î·È ÙË Ì›ˆÛË ÙÔ˘ ·ÚÈıÌÔ‡ ÙˆÓ ·ÛıÂÓÒÓ Û ϛÛÙ· ÌÂÙ·ÌfiÛ¯Â˘Û˘. OÈ Vargas Î·È Û˘Ó ‰ÂÓ ‚Ú‹Î·Ó ÛÙ·ÙÈÛÙÈο ÛËÌ·ÓÙÈ΋ ‰È·ÊÔÚ¿ ÛÙËÓ ˘ÔÙÚÔ‹ Ù˘ Ë·Ù›Ùȉ·˜ C ÛÙÔ ÌfiÛ¯Â˘Ì·, ηıÒ˜ Î·È ÛÙËÓ ÂÈ‚›ˆÛË
75
ÌÔۯ‡̷ÙÔ˜ Î·È ·ÛıÂÓÒÓ Î·Ù¿ ÙË Û‡ÁÎÚÈÛË 23 ·ÛıÂÓÒÓ Ì ¯ÚfiÓÈ· Ë·Ù›Ùȉ· C Ô˘ ¤Ï·‚·Ó antiHCV (+) ÌfiÛ¯Â˘Ì· Ì 169 ·ÛıÂÓ›˜ Ô˘ ¤Ï·‚·Ó anti-HCV(–) ÌfiÛ¯Â˘Ì·14. ∞Ó¿ÏÔÁ· ‹Ù·Ó Î·È Ù· ·ÔÙÂϤÛÌ·Ù· ÈÔ ÚfiÛÊ·Ù˘ ÌÂϤÙ˘ ÙˆÓ Saab Î·È Û˘Ó Ô˘ Û˘Ó¤ÎÚÈÓ·Ó 59 ·ÛıÂÓ›˜ Ô˘ ¤Ï·‚·Ó anti-HCV (+) ÌfiÛ¯Â˘Ì· Ì ›‰ÈÔ ·ÚÈıÌfi ·ÛıÂÓÒÓ Ô˘ ¤Ï·‚·Ó anti-HCV (–) ÌfiÛ¯Â˘Ì·15. OÈ ·ÛıÂÓ›˜ ÂÈϤ¯ıËÎ·Ó ÒÛÙ ӷ ¤¯Ô˘Ó ·ÚfiÌÔÈ· ¯·Ú·ÎÙËÚÈÛÙÈο fiÛÔÓ ·ÊÔÚ¿ ÛÙÔ MELD status, ÛÙË ÓÂÊÚÈ΋ ÏÂÈÙÔ˘ÚÁ›·, ÛÙËÓ ËÏÈΛ· ‰fiÙË Î·È Ï‹ÙË, ÛÙÔ ¯ÚfiÓÔ ıÂÚÌ‹˜ ÈÛ¯·ÈÌ›·˜ Î·È ÛÙÔ ¤ÙÔ˜ ÌÂÙ·ÌfiÛ¯Â˘Û˘. OÈ Û˘ÁÁÚ·Ê›˜ ‰ÂÓ ‰È·›ÛÙˆÛ·Ó ÛÙ·ÙÈÛÙÈο ÛËÌ·ÓÙÈ΋ ‰È·ÊÔÚ¿ ÛÙËÓ ÂÈ‚›ˆÛË ·ÛıÂÓÔ‡˜, ÌÔۯ‡̷ÙÔ˜ ηıÒ˜ Î·È ÛÙËÓ ÂÈ‚›ˆÛË ¯ˆÚ›˜ ˘ÔÙÚÔ‹ Ù˘ HCV Ïԛ̈͢ ÌÂٷ͇ ·ÛıÂÓÒÓ Ô˘ ¤Ï·‚·Ó anti-HCV (+) ÌfiÛ¯Â˘Ì· Î·È ·ÛıÂÓÒÓ Ô˘ ¤Ï·‚·Ó anti-HCV (–) ÌfiÛ¯Â˘Ì·. ªÂÙ¿ ·fi ÙȘ ÌÂϤÙ˜ ·˘Ù¤˜ Ë ¯Ú‹ÛË anti-HCV (+) ÌÔÛ¯Â˘Ì¿ÙˆÓ ÁÈ· ·ÛıÂÓ›˜ Ì ¯ÚfiÓÈ· Ë·Ù›Ùȉ· C ¤¯ÂÈ ÁÂÓÈ΢ٛ ÛÙ· ÂÚÈÛÛfiÙÂÚ· ΤÓÙÚ· ÌÂÙ·ÌfiÛ¯Â˘Û˘ Û fiÏÔ ÙÔÓ ÎfiÛÌÔ. ∂Ó·˜ ÂÚÈÔÚÈÛÌfi˜ Ù˘ ¯Ú‹Û˘ ·Ó¿ÏÔÁˆÓ ÌÔÛ¯Â˘Ì¿ÙˆÓ ·ÏÏ¿ ·fi ËÏÈÎȈ̤ÓÔ˘˜ ‰fiÙ˜ ÚÔÙ¿ıËΠ۠ÚfiÛÊ·ÙË ÌÂϤÙË ÙˆÓ Khapra Î·È Û˘Ó16. OÈ Û˘ÁÁÚ·Ê›˜ ‰ÂÓ ‰È·›ÛÙˆÛ·Ó ‰È·ÊÔÚ¿ ÛÙËÓ Û˘ÓÔÏÈ΋ ÂÈ‚›ˆÛË ÌÂٷ͇ ·ÛıÂÓÒÓ Ô˘ ¤Ï·‚·Ó anti-HCV (+) ÌfiÛ¯Â˘Ì· Î·È ·ÛıÂÓÒÓ Ô˘ ¤Ï·‚·Ó anti-HCV (–) ÌfiÛ¯Â˘Ì·, fiˆ˜ ¤¯ÂÈ ÂÚÈÁÚ·Ê› Î·È Û ÚÔËÁÔ‡ÌÂÓ˜ ÌÂϤÙ˜. ∞ӷʤÚÔ˘Ó fï˜ fiÙÈ ·ÛıÂÓ›˜ Ô˘ ¤Ï·‚·Ó anti-HCV (+) ÌfiÛ¯Â˘Ì· ·fi ËÏÈÎȈ̤ÓÔ˘˜ ‰fiÙ˜ (>50 ÂÙÒÓ) ÂÌÊ¿ÓÈÛ·Ó ˘„ËÏfiÙÂÚ· ÔÛÔÛÙ¿ ·ÒÏÂÈ·˜ ÌÔۯ‡̷ÙÔ˜ (hazard ratio 2.74) Î·È ıÓËÙfiÙËÙ·˜ (hazard ratio 2.63) Û ۇÁÎÚÈÛË Ì ÙÔ˘˜ ·ÛıÂÓ›˜ Ô˘ ¤Ï·‚·Ó anti-HCV (-) ÌfiÛ¯Â˘Ì·. ∏ ·Ó¿Ï˘ÛË ¤‰ÂÈÍ ›Û˘ fiÙÈ ·ÛıÂÓ›˜ Ô˘ ¤Ï·‚·Ó anti-HCV (+) ÌfiÛ¯Â˘Ì· ÂÌÊ¿ÓÈ˙·Ó ÛÔ‚·ÚfiÙÂÚË ›ÓˆÛË ÌÂÙ¿ ÙË ÌÂÙ·ÌfiÛ¯Â˘ÛË Û ۯ¤ÛË Ì fiÛÔ˘˜ ¤Ï·‚·Ó antiHCV (–) ÌfiÛ¯Â˘Ì·. ∞ÎfiÌË ·ÛıÂÓ›˜ Ô˘ ¤Ï·‚·Ó anti-HCV (+) ÌfiÛ¯Â˘Ì· ·fi ËÏÈÎȈ̤ÓÔ˘˜ ‰fiÙ˜ ÂÌÊ¿ÓÈÛ·Ó ÈÔ ÚÔ¯ˆÚË̤ÓË ›ÓˆÛË Û ۯ¤ÛË Ì ·˘ÙÔ‡˜ ·ÛıÂÓ›˜ Ô˘ ¤Ï·‚·Ó anti-HCV (+) ÌfiÛ¯Â˘Ì· ·fi ÓÂfiÙÂÚÔ˘˜ ‰fiÙ˜. Δ¤ÏÔ˜ ·fi ÙË ÌÂϤÙË ‰È·ÈÛÙÒıËΠfiÙÈ Ë ·ÚÔ˘Û›· ‹È·˜ ›ÓˆÛ˘, ÊÏÂÁÌÔÓ‹˜ Î·È ÛÙ¿وÛ˘ ÛÙÔ anti-HCV (+) ÌfiÛ¯Â˘Ì· ‰ÂÓ ÂËÚ¿˙ÂÈ ÙÔ Ú˘ıÌfi ÚfiÔ‰Ô˘ Ù˘ ›ÓˆÛ˘ ÌÂÙ¿ ÙË ÌÂÙ·ÌfiÛ¯Â˘ÛË.
76
π. °√À§∏™
μπμ§πO°ƒ∞ºπ∞ 1. Chung RT, Feng S, Delmonico FL. Approach to the management of allograft recipients following the detection of hepatitis B virus in the prospective organ donor. Am J Transpl 2001; 1: 185-191. 2. Prieto M, Gomez MD, Berenguer M, et al. De novo hepatitis B after liver transplantation from hepatitis B core antibody-positive donors in an area with high prevalence of anti-HBc positivity in the donor population. Liver Transpl 2001; 7: 51-58. 3. Hoofnagle JH, Seefe LB, Bales ZB, et al. Type B hepatitis after transfusion with blood containing antibody to hepatitis B core antigen. N Engl J Med 1978; 298: 1379. 4. De Villa V, Chen YS, Chen CL. Hepatitis B core antibody positive grafts: recipient’s risk. Transplantation 2003; 75: S49-S53. 5. Wachs ME, Amend WJ, Ascher NL, et al. The risk of transmission of hepatitis B from HBsAg (–), HBcAb (+) HBIgM (–) organ donors. Transplantation 1995; 59: 230. 6. Uemoto S, Sugiyama K, Marusawa H, et al. Transmission of hepatitis B virus from hepatitis B core antibody-positive donors in living related liver transplants. Transplantation 1998; 6: 494. 7. Han S, Swenson K, Seu J, et al. Use of hepatitis B virus (HBV) core antibody positive donors does not increase the risk of recurrent HBV in recipients undergoing OLT for HBV. Hepatology 1998; 28: 348. 8. Munoz SJ. Use of hepatitis B core antibody-positive donors for liver transplantation. Liver Transplantation 2002; 8(Suppl 1): S82-S87.
9. Radomski J, Moritz M, Armenti V, et al. Hepatitis B transmission from a liver donor who tested negative for hepatitis B surface antigen and positive for hepatitis B core antibody. Liver Transpl Surg 1996; 2: 130-131. 10. Holt D, Thomas R, Van Thiel D, Berms J. Use of hepatitis B core antibody-positive donors in orthotopic liver transplantation. Arch Surg 2002; 137: 572-575. 11. Yu AS, Vierling J, Colquhoun SD et al. Transmission of hepatitis B virus infection from hepatitis B core antibody-positive liver allografts is prevented by lamivudine therapy. Liver Transpl 2001; 7: 513-517. 12. Yen RD, Bonnati H, Mendez J. Case report of lamivudine-resistant hepatitis B virus infection post liver transplantation from a hepatitis B core antibody positive donor. Am J Transpl 2006; 6: 1077-1083. 13. Chen YS, Wang CC, de Villa V, et al. Prevention of de novo hepatitis B virus infection in living donor liver transplantation using hepatitis B core antibody positive donors. Clin Transplant 2002; 16: 405. 14. Vargas HE, Laskus T, Wang LF et al. Outcome of liver transplantation in hepatitis C virus-infected patients who received hepatitis C virus-infected grafts. Gastroenterology 1999; 117: 149-153. 15. Saab S, Ghobrial RM, Ibrahim AB, et al. Hepatitis C positive grafts may be used in orthotopic liver transplantation: a matched analysis. Am J Transpl 2003; 3: 1167-1172. 16. Khapra AP, Agarwal K, Fiel MI, et al. Impact of donor age on survival and fibrosis progression in poatients with hepatitis C undergoing liver transplantation using HCV+ allografts. Liver Transpl 2006; 12;1496-1503.
OÚÈ·ÎÔ› Ï‹Ù˜ ¢.∂. °È·ÎÔ˘ÛÙ›‰Ë˜
∂π™∞°ø°∏
‹ fi¯È ÈÎÙ¤ÚÔ˘. ΔÔ ·ÔÙ¤ÏÂÛÌ· Â›Ó·È fiÙÈ ÏÈÁfiÙÂÚÔÈ ·fi 50% ÙˆÓ ·ÛıÂÓÒÓ Ô˘ ÂÌÊ·Ó›˙Ô˘Ó ·˘ÙfiÌ·ÙË ‚·ÎÙËÚȷ΋ ÂÚÈÙÔÓ›Ùȉ· ‹ ·ÔÊÚ·ÎÙÈÎfi ·ÛΛÙË ÂÈ‚ÈÒÓÔ˘Ó ÂÚÈÛÛfiÙÂÚÔ ·fi 1 ¯ÚfiÓÔ. ∏ ‡·ÚÍË Ë·ÙÔÓÂÊÚÈÎÔ‡ Û˘Ó‰ÚfiÌÔ˘ Â›Ó·È Û˘Ó‰Â‰Â̤ÓË Ì ·ÎfiÌË ¯ÂÈÚfiÙÂÚË ÚfiÁÓˆÛË. ∞ÓÙ›ıÂÙ· Ë ‡·ÚÍË ÂÂÈÛÔ‰›Ô˘ ·ÈÌÔÚÚ·Á›·˜ ÎÈÚÛÒÓ ¤¯ÂÈ Û‹ÌÂÚ· ÌÈÎÚfiÙÂÚÔ ·ÓÙ›ÎÙ˘Ô ÏfiÁˆ Ù˘ ·Ó¿Ù˘Í˘ Ôχ ·ÔÙÂÏÂÛÌ·ÙÈÎÒÓ ÙÚfiˆÓ ·ÓÙÈÌÂÙÒÈÛ˘ ·˘ÙÒÓ.
∏ ÌÂÙ·ÌfiÛ¯Â˘ÛË ‹·ÙÔ˜ ·ÔÙÂÏ› ÙËÓ ÌÔÓ·‰È΋ ÂÈÏÔÁ‹ ÁÈ· ÙËÓ ·Ó·ÛÙÚÔÊ‹ Ù˘ Ë·ÙÈ΋˜ ·Ó¿ÚÎÂÈ·˜ Î·È ÙËÓ ·ÓÙÈÌÂÙÒÈÛË ÙˆÓ ÂÈÏÔÎÒÓ ÛÙÔ˘˜ ·ÛıÂÓ›˜ Ì ΛÚÚˆÛË ÙÂÏÈÎÔ‡ ÛÙ·‰›Ô˘. ∞Ó Î·È Ë ÌÂÙ·ÌfiÛ¯Â˘ÛË ‹·ÙÔ˜ ·ÔÙÂÏ› Ì›· ÂÈ‚·Ú˘ÓÙÈ΋ Î·È ··ÈÙËÙÈ΋ ¤̂·ÛË, ÔÈ ·ÛıÂÓ›˜ ÌÔÚÔ‡Ó Û˘Ó‹ıˆ˜ Ó· ÂÈÛÙÚ¤„Ô˘Ó ÛÙË Ê˘ÛÈÔÏÔÁÈ΋ ‹ ۯ‰fiÓ Ê˘ÛÈÔÏÔÁÈ΋ ˙ˆ‹ ̤۷ Û 3-6 Ì‹Ó˜. ¢˘ÛÙ˘¯Ò˜ ÏfiÁˆ Ù˘ ÌÂÁ¿Ï˘ ·Ó¿ÚÎÂÈ·˜ ÚÔÛÊÂÚfiÌÂÓˆÓ ÔÚÁ¿ÓˆÓ Î·È Ù˘ Ôχ ÌÂÁ¿Ï˘ Î·È ·˘Í·ÓfiÌÂÓ˘ ˙‹ÙËÛ˘ Â›Ó·È ··Ú·›ÙËÙË Ë ‡·ÚÍË Ôχ Û˘ÁÎÂÎÚÈÌ¤ÓˆÓ ÎÚÈÙËÚ›ˆÓ ÁÈ· ÙËÓ ÂÈÏÔÁ‹ ÙˆÓ ÏËÙÒÓ Î·È ÙËÓ Î·Ù·ÓÔÌ‹ ÙˆÓ ÌÔÛ¯Â˘Ì¿ÙˆÓ. ™‹ÌÂÚ· Ë Î·Ù·ÓÔÌ‹ ÙˆÓ ÙˆÌ·ÙÈÎÒÓ Ë·ÙÈÎÒÓ ÌÔÛ¯Â˘Ì¿ÙˆÓ Á›ÓÂÙ·È Ì ‚¿ÛË ÙËÓ ‚·Ú‡ÙËÙ· ÙÔ˘ ˘Ô„‹ÊÈÔ˘ Ï‹ÙË ·ÏÏ¿ Î·È ÛÙÔ ·Ó·ÌÂÓfiÌÂÓÔ fiÊÂÏÔ˜ ÙÔ˘ Ï‹ÙË ·fi ÙËÓ ÌÂÙ·ÌfiÛ¯Â˘ÛË. ∂›Ó·È ÎÔÈÓ¿ ·Ô‰ÂÎÙfi fiÙÈ ÌfiÓÔ ‰˘ÓËÙÈÎÔ› ˘Ô„‹ÊÈÔÈ ÙˆÓ ÔÔ›ˆÓ Ë ·Ó·ÌÂÓfiÌÂÓË ÂÈ‚›ˆÛË 1 ¯ÚfiÓÔ˘ ÌÂÙ¿ ·fi ÌÂÙ·ÌfiÛ¯Â˘ÛË ‹·ÙÔ˜ ı· Â›Ó·È ÌÂÁ·Ï‡ÙÂÚË ·fi 50% Ú¤ÂÈ Ó· Ù›ıÂÓÙ·È ˘fi„Ë. ∞ÓÙ›ÛÙÔȯ· ·ÛıÂÓ›˜ Ì ȉȷ›ÙÂÚ· ˘„ËÏfi ¯ÂÈÚÔ˘ÚÁÈÎfi ΛӉ˘ÓÔ fiˆ˜ ›Û˘ Î·È ·ÛıÂÓ›˜ ÙˆÓ ÔÔ›ˆÓ Ë ÓfiÛÔ˜ ·Ó·Ì¤ÓÂÙ·È Ó· ˘ÔÙÚÔÈ¿ÛÂÈ ¿ÌÂÛ· Î·È ÂÈÙ·¯˘ÓfiÌÂÓ·, ›Ûˆ˜ ‰ÂÓ ı· ¤Ú ӷ Û˘ÌÂÚÈÏ·Ì‚¿ÓÔÓÙ·È ÛÙË Ï›ÛÙ· ÚÔ˜ ÌÂÙ·ÌfiÛ¯Â˘ÛË.
∫ƒπΔ∏ƒπ∞ ∂¶π§O°∏™ ∞¡∞§O°∞ ∞πΔπO ∫πƒƒø™∏™ ∞ÏÎÔÔÏÈ΋ ∫›ÚÚˆÛË ∏ ηٿ¯ÚËÛË ·ÏÎÔfiÏ ·ÔÙÂÏ› Ì›· ·fi ÙȘ ÈÔ Û˘¯Ó¤˜ ·Èٛ˜ ΛÚÚˆÛ˘ ÛÙË ¢˘ÙÈ΋ ∂˘ÚÒË Î·È μfiÚÂÈ· ∞ÌÂÚÈ΋ Î·È ·ÔÙÂÏ› ·˘Í·ÓfiÌÂÓË ¤Ó‰ÂÈÍË ÁÈ· ÌÂÙ·ÌfiÛ¯Â˘ÛË ‹·ÙÔ˜ ÛÙËÓ ∂ÏÏ¿‰·. ∞fi ÌÂϤÙ˜ ¤¯ÂÈ ·Ô‰ÂȯÙ› fiÙÈ ÂÈÏÂÁ̤ÓÔÈ ·ÛıÂÓ›˜ Ì ·ÏÎÔÔÏÈ΋ ÓfiÛÔ ‹·ÙÔ˜ (alcoholic liver disease, ALD) ¤¯Ô˘Ó ·ÚfiÌÔÈ· ÂÈ‚›ˆÛË ÌÂÙ¿ ·fi ÌÂÙ·ÌfiÛ¯Â˘ÛË ‹·ÙÔ˜ Ì ·ÛıÂÓ›˜ Ì ÌË-·ÏÎÔÔÏÈ΋˜ ·ÈÙÈÔÏÔÁ›·˜ ΛÚÚˆÛË ‹·ÙÔ˜. ™·Ó Û˘Ó¤ÂÈ· Ë ALD Â›Ó·È ·Ô‰ÂÎÙ‹ Û·Ó ¤Ó‰ÂÈÍË ÁÈ· ÌÂÙ·ÌfiÛ¯Â˘ÛË ‹·ÙÔ˜ Ì ÂÈ‚›ˆÛË 1 ¯ÚfiÓÔ˘ Ó· ÍÂÂÚÓ¿ÂÈ Î·Ù¿ ̤ÛÔ fiÚÔ ÙÔ 80%.
∫›ÚÚˆÛË ·fi ∏·Ù›Ùȉ· C ∏ ΛÚÚˆÛË ‹·ÙÔ˜ ÏfiÁˆ Ïԛ̈͢ ·fi ÙÔÓ Èfi Ù˘ Ë·Ù›Ùȉ·˜ C ·ÔÙÂÏ› ÙÔ 30-40% ÙˆÓ ·ÛıÂÓÒÓ Ô˘ ˘Ô‚¿ÏÏÔÓÙ·È Û ÌÂÙ·ÌfiÛ¯Â˘ÛË ‹·ÙÔ˜ ÛÙȘ ¢˘ÙÈΤ˜ ¯ÒÚ˜. ™ÙËÓ ∂ÏÏ¿‰· ·ÔÙÂÏ› Ì›· Ù·¯¤ˆ˜ ·Ó·Ù˘ÛÛfiÌÂÓË ¤Ó‰ÂÈÍË ÁÈ· ÌÂÙ·ÌfiÛ¯Â˘ÛË ‹·ÙÔ˜. ÀÔÏÔÁ›˙ÂÙ·È fiÙÈ ÂÚ›Ô˘ 20% ÙˆÓ ·ÛıÂÓÒÓ Ì Ã∏C (¯ÚfiÓÈ· Ë·Ù›Ùȉ· C, XHC) ı· ·Ó·Ù‡ÍÔ˘Ó Î›ÚÚˆÛË ÙÔ˘ ‹·ÙÔ˜ ̤۷ Û ̛· 20ÂÙ›·. ∏ ÏÂÈÔ„ËÊ›· ÙˆÓ ·ÛıÂÓÒÓ Ì Ã∏C ı· ÌÂÙ·ÌÔÛ¯Â˘ÙÔ‡Ó Ì ıÂÙÈÎfi HCV-RNA ·Ú¿ ÙËÓ ·ÓÙÈ-ÈÈ΋ ıÂڷ›· ¯ˆÚ›˜ ·˘Ùfi Ó· ·ÔÙÂÏ› ·ÓÙ¤Ó‰ÂÈÍË ÁÈ·
ª∏-∞¡ΔπƒO¶OÀª∂¡∏ ∫πƒƒø™∏ ∏ ¤Ó‰ÂÈÍË ÁÈ· ÌÂÙ·ÌfiÛ¯Â˘ÛË ‹·ÙÔ˜ Ù›ıÂÙ·È Û˘Ó‹ıˆ˜ fiÙ·Ó ÂÌÊ·Ó›˙ÂÙ·È ÁÈ· ÚÒÙË ÊÔÚ¿ ÌË-·ÓÙÈÚÚfiËÛË Ù˘ ΛÚÚˆÛ˘. ∏ ÂÌÊ¿ÓÈÛË ·ÛΛÙË, ·˘ÙfiÌ·Ù˘ ‚·ÎÙËÚȷ΋˜ ÂÚÈÙÔÓ›Ùȉ·˜ Î·È ÂÁÎÂÊ·ÏÔ¿ıÂÈ·˜ Â›Ó·È Û˘Ó‰Â‰Â̤Ó˜ Ì ÛËÌ·ÓÙÈ΋ Ì›ˆÛË Ù˘ ÂÈ‚›ˆÛ˘. OÈ ·ÛıÂÓ›˜ Ô˘ ˘fiÎÂÈÓÙ·È ÛÙȘ ·Ú·¿Óˆ ÂÈÏÔΤ˜ ¤¯Ô˘Ó 20-50% ÌÂȈ̤ÓÔ ÚÔÛ‰fiÎÈÌÔ ÂÈ‚›ˆÛ˘ Û ۯ¤ÛË Ì ·˘ÙÔ‡˜ Ì ·ÓÙÈÚÚÔÔ‡ÌÂÓË Î›ÚÚˆÛË ·ÓÂÍ¿ÚÙËÙ· Ù˘ ‡·Ú͢
77
78
¢. °π∞∫OÀ™Δπ¢∏™
ÌÂÙ·ÌfiÛ¯Â˘ÛË. ∂ÈϤÔÓ ·Ó Î·È Ë ˘ÔÙÚÔ‹ Ù˘ ÓfiÛÔ˘ ÌÂÙ¿ ÙË ÌÂÙ·ÌfiÛ¯Â˘ÛË Â›Ó·È Û¯Â‰fiÓ ‚¤‚·ÈË Ë ÂͤÏÈÍË Û ¯ÚfiÓÈ· Ë·Ù›Ùȉ· Â›Ó·È Û˘Ó‹ıˆ˜ ·ÚÁ‹ Î·È Ë ÌÂÙ·ÌfiÛ¯Â˘ÛË Û ·ÛıÂÓ›˜ Ì ÌË-·ÓÙÈÚÚÔÔ‡ÌÂÓË Î›ÚÚˆÛË ÏfiÁˆ XHC ˘ÂÚ¤¯ÂÈ Ù˘ Û˘ÓÙËÚËÙÈ΋˜ ıÂڷ›·˜.
∫›ÚÚˆÛË ·fi ∏·Ù›Ùȉ· μ ∂›Ó·È ÁÂÓÈο ·Ô‰ÂÎÙfi fiÙÈ Ú¤ÂÈ Ó· ÂÚÈÏ·Ì‚¿ÓÔÓÙ·È ÛÙȘ Ï›ÛÙ˜ ÁÈ· ÌÂÙ·ÌfiÛ¯Â˘ÛË ÔÈ ·ÛıÂÓ›˜ Ì ¯ÚfiÓÈ· Ïԛ̈ÍË ·fi ÙÔÓ Èfi Ë·Ù›Ùȉ·˜ μ ·˘ÙÔ› Ô˘ ¤¯Ô˘Ó «ÌË-ÔÏÏ·Ï·ÛÈ·ÛÙÈ΋» Ïԛ̈ÍË. ∏ ÌÂÙ·ÌfiÛ¯Â˘ÛË ‹·ÙÔ˜ Û ·ÛıÂÓ›˜ Ì «ÔÏÏ·Ï·ÛÈ·ÛÙÈ΋ ÓfiÛÔ» ÂÌÊ·Ó›˙ÂÈ ÚÒÈÌË ˘ÔÙÚÔ‹ Û ¿Óˆ ·fi 80% Î·È ·Ó·Ù‡ÛÛÂÙ·È ÂÎÙÂٷ̤ÓË ›ÓˆÛË Î·È ·Ó¿ÚÎÂÈ· ÙÔ˘ ÌÔۯ‡̷ÙÔ˜ ̤۷ Û ̋Ó˜ ¯ˆÚ›˜ ÚÒÈÌË ·ÓÙÈÈ΋ ıÂڷ›·. ∏ ¯Ú‹ÛË ·ÓÙÈÈÎÒÓ Ê·ÚÌ¿ÎˆÓ fiˆ˜ Â›Ó·È Ë lamivudine, ÙÔ adefovir dipivoxil ¤¯ÂÈ Ô‰ËÁ‹ÛÂÈ Û Ì›ˆÛË ÙˆÓ ˘ÔÙÚÔÒÓ Î·È Â›Ó·È Î·Ï¿ ·ÓÂÎÙ‹ Û ΛÚÚˆÛË Ì ÌÔÓ·‰È΋ ·ÚÂÓ¤ÚÁÂÈ· ÙË ÓÂÊÚÔÙÔÍÈÎfiÙËÙ·.
¢È¿ÊÔÚ· ·›ÙÈ· ∏ ÚˆÙÔ·ı‹˜ ¯ÔÏÈ΋ ΛÚÚˆÛË (PBC) ·ÔÙ¤ÏÂÛ ̛· ·fi ÙȘ ÚÒÙ˜ ·ı‹ÛÂȘ ÙÔ˘ ‹·ÙÔ˜ Ì ηÙ¢ı˘ÓÙ‹ÚȘ Ô‰ËÁ›Â˜ ˆ˜ ÚÔ˜ ÙËÓ ÌÂÙ·ÌfiÛ¯Â˘ÛË ‹·ÙÔ˜. ∏ ÌË-·ÓÙÈÚÚÔÔ‡ÌÂÓË Î›ÚÚˆÛË Î·È Ë ˘„ËÏ‹ ¯ÔÏÂÚ˘ıÚ›ÓË ·ÔÙÂÏÔ‡Ó ·Ú¿ÁÔÓÙ˜ ÊÙˆ¯‹˜ ÚfiÁÓˆÛ˘ Ô˘ ‰ÈηÈÔÏÔÁÔ‡Ó ÙËÓ ÌÂÙ·ÌfiÛ¯Â˘ÛË. ∏ ¯Ú‹ÛË Ô˘ÚÛÔ‰ÂÔ͢¯ÔÏÈÎÔ‡ ÔͤԘ ‚ÂÏÙÈÒÓÂÈ ÙËÓ ÂÈ‚›ˆÛË Î·È ·Ó Ë ¯ÔÚ‹ÁËÛË ÙÔ˘ ·Ú¯›ÛÂÈ ÚÒÈÌ· ÌÔÚ› Ó· ηı˘ÛÙÂÚ‹ÛÂÈ ÛËÌ·ÓÙÈο ÙËÓ ÂͤÏÈÍË Ù˘ ÓfiÛÔ˘. ∏ ·ÍÈÔÏfiÁËÛË Ù˘ ÚfiÁÓˆÛ˘ Ù˘ ÚˆÙÔ·ıÔ‡˜ ÛÎÏËÚ˘ÓÙÈ΋˜ ¯ÔÏÏ·ÁÁÂÈ›Ùȉ·˜ (PSC) Â›Ó·È ‰‡ÛÎÔÏË. O ΛӉ˘ÓÔ˜ ÂÌÊ¿ÓÈÛ˘ de novo ¯ÔÏ·ÁÁÈÔηÚÎÈÓÒÌ·ÙÔ˜ Â›Ó·È 1% ·Ó¿ ¤ÙÔ˜. ∏ ÌË-·ÓÙÈÚÚÔÔ‡ÌÂÓË Î›ÚÚˆÛË Â›Ó·È ·›ÙÈÔ ÌÂÙ·ÌfiÛ¯Â˘Û˘ ·ÏÏ¿ Û˘Ó‹ıˆ˜ ·˘Ù‹ Á›ÓÂÙ·È ÂÍ·ÈÙ›·˜ ÈÎÙ¤ÚÔ˘ ‹ ¯ÔÏ·ÁÁÂÈ›ÙȉԘ. ∏ ‡·ÚÍË ¯ÔÏ·ÁÁÂÈÔηÚÎÈÓÒÌ·ÙÔ˜ ÛÙÔ Èı·ÁÂÓ¤˜ ‹·Ú Ô‰ËÁÔ‡Ó Û Ôχ ˘„ËÏ‹ ˘ÔÙÚÔ‹ ÌÂÙ¿ ÙË ÌÂÙ·ÌfiÛ¯Â˘ÛË. ∏ ·˘ÙÔ¿ÓÔÛË Ë·Ù›Ùȉ·, Ë ·ÈÌԯڈ̿وÛË, Ë ÓfiÛÔ˜ ÙÔ˘ Wilson Î·È Ë ¤ÏÏÂÈ„Ë Ù˘ ·1-·ÓÙÈıÚ˘„›Ó˘ ¤¯Ô˘Ó Û·Ó Î‡ÚÈ· ¤Ó‰ÂÈÍË ÌÂÙ·ÌfiÛ¯Â˘Û˘ ÙË ÌË-·ÓÙÈÚÚÔÔ‡ÌÂÓË Î›ÚÚˆÛË.
∏¶∞ΔO∫ÀΔΔ∞ƒπ∫O™ ∫∞ƒ∫π¡O™ (HCC) O Û˘ÛÙËÌ·ÙÈÎfi˜ ¤ÏÂÁ¯Ô˜ ÁÈ· HCC ¯ÚËÛÈÌÔÔÈÒÓÙ·˜ ÙÔ˘˜ ˘ÂÚ‹¯Ô˘˜ Î·È ÙËÓ aFP ÂÊ·ÚÌfi˙ÂÙ·È Â˘Ú¤ˆ˜ Ì ·ÔÙ¤ÏÂÛÌ· ÙËÓ ÚÒÈÌË ÂÓÙfiÈÛË HCC. ∏ ·ÓÙÈÌÂÙÒÈÛË ÙˆÓ HCC fiÁÎˆÓ ÛÙÔ˘˜ ·ÛıÂÓ›˜ Ì ·ÓÙÈÚÚÔÔ‡ÌÂÓË Î›ÚÚˆÛË ÂÚÈÏ·Ì‚¿ÓÂÈ ÔÏϤ˜ ÂÈÏÔÁ¤˜ fiˆ˜ Â›Ó·È Ô TACE (Trans arterial chemembolization), ÙÔ radiofrequency ablation, Ë ¯ÂÈÚÔ˘ÚÁÈ΋ ÂÎÙÔÌ‹ Î·È Ë ÌÂÙ·ÌfiÛ¯Â˘ÛË. ∏ ÌÂÙ·ÌfiÛ¯Â˘ÛË ·Ó Î·È ÈÔ ··ÈÙËÙÈ΋ ·fi ÙȘ ¿ÏϘ ÌÂıfi‰Ô˘˜ ¤¯ÂÈ Ù· ηχÙÂÚ· Ì·ÎÚÔ¯ÚfiÓÈ· ·ÔÙÂϤÛÌ·Ù· Î·È ÌÂÈÒÓÂÈ ÙÔÓ Î›Ó‰˘ÓÔ Ù˘ ˘ÔÙÚÔ‹˜. ∏ ¯Ú‹ÛË ÙˆÓ ÎÚÈÙËÚ›ˆÓ ÙÔ˘ ªÈÏ¿ÓÔ˘ ·ÏÏ¿ Î·È ÙˆÓ ÈÔ ÂÏ·ÛÙÈÎÒÓ ÎÚÈÙËÚ›ˆÓ ÙÔ˘ UCSF ¤¯Ô˘Ó Ô‰ËÁ‹ÛÂÈ Û 5ÂÙ‹ ÂÈ‚›ˆÛË ÂÚÈÛÛfiÙÂÚÔ ·fi 75%. ∏ ÌÂÙ·ÌfiÛ¯Â˘ÛË Û ·ÛıÂÓ›˜ Ì fiÁÎÔ˘˜ Ô˘ ˘ÂÚ‚·›ÓÔ˘Ó Ù· ÎÚÈÙ‹ÚÈ· ÙÔ˘ UCSF Û¿ÓÈ· ÂÌÊ·Ó›˙ÂÈ 3ÂÙ‹ ÂÈ‚›ˆÛË ¿Óˆ ·fi 50% Î·È ‰ÂÓ ‰ÈηÈÔÏÔÁ› ÙËÓ Û·Ù¿ÏË ÔÚÁ¿ÓˆÓ ȉ›ˆ˜ Û ¤Ó· ÂÚÈ‚¿ÏÏÔÓ ¤ÏÏÂȄ˘ ·˘ÙÒÓ. ∏ ¯Ú‹ÛË ‰È·ÊfiÚˆÓ ÌÂıfi‰ˆÓ ÁÈ· ˘ÔÛÙ·‰ÈÔÔ›ËÛË (downstaging) ÙˆÓ ·ÛıÂÓÒÓ Î·È ÙˆÓ fiÁÎˆÓ ÙÔ˘˜ (downsizing) ¯ÚËÛÈÌÔÔÈÂ›Ù·È ÁÈ· ·ӷÊÔÚ¿ ÙˆÓ ·ÛıÂÓÒÓ Ì¤Û· ÛÙ· ÎÚÈÙ‹ÚÈ· ÙÔ˘ ªÈÏ¿ÓÔ˘. ¶ÚfiÛÊ·ÙË ÌÂϤÙË ¤¯ÂÈ ‰Â›ÍÂÈ fiÙÈ Ù· ·ÔÙÂϤÛÌ·Ù· Â›Ó·È Û˘ÁÎÚ›ÛÈÌ· Ì ÙÔ˘˜ ·ÛıÂÓ›˜ Ô˘ ÏËÚÔ‡Û·Ó ÂÍ’·Ú¯‹˜ Ù· ÎÚÈÙ‹ÚÈ· ÙÔ˘ ªÈÏ¿ÓÔ˘, ·ÏÏ¿ ·ÚÎÂÙ¤˜ ÂÚÈÛÛfiÙÂÚ˜ ÌÂϤÙ˜ ı· ¯ÚÂÈ·ÛÙÔ‡Ó ÁÈ· Ó· Á›ÓÂÈ Â˘Ú¤ˆ˜ ·Ô‰ÂÎÙfi.
∂¶π¶§O∫∂™ ∞¶O ΔOÀ™ ¡∂ºƒOÀ™ OÍ›· ¡ÂÊÚÈ΋ ∞Ó¿ÚÎÂÈ· ∏ ÔÍ›· ÓÂÊÚÈ΋ ·Ó¿ÚÎÂÈ· (O¡∞) Û ·ÛıÂÓ›˜ Ì ΛÚÚˆÛË Â›Ó·È ·ÚÎÂÙ¿ Û˘ÓËıÈṲ̂ÓË, Ì ¿ÁÓˆÛÙË fï˜ ÙËÓ ·ÎÚÈ‚‹ ÂÌÊ¿ÓÈÛË Ù˘. ∏ ·Ó¿Ù˘ÍË O¡∞ Û ·ÛıÂÓ›˜ Ì ΛÚÚˆÛË ¤¯ÂÈ ÌÂÁ¿ÏË ÚÔÁÓˆÛÙÈ΋ ÛËÌ·Û›· Î·È ·ÔÙÂÏ› ·ÓÂÍ¿ÚÙËÙÔ ÚÔÁÓˆÛÙÈÎfi ·Ú¿ÁÔÓÙ· ı·Ó¿ÙÔ˘. ∏ ·Ó¿Ù˘ÍË OÍ›·˜ ™ˆÏËÓ·Úȷ΋˜ ¡¤ÎÚˆÛ˘ (O™¡) ÔÊ›ÏÂÙ·È Û˘¯Ó¿ Û OÍ›· ∏·ÙÈ΋ ∞Ó¿ÚÎÂÈ· (O∏∞). O™¡ Ì ·ÔÙ¤ÏÂÛÌ· O¡∞ Û ·ÛıÂÓ›˜ Ì ÛÙ·ıÂÚ‹ Ë·ÙÈ΋ ÓfiÛÔ Â›Ó·È Û˘Ó‹ıˆ˜ ·ÔÙ¤ÏÂÛÌ· ˘Ô‚ÔÏ·ÈÌÈÎÔ‡ shock, ÌÂÁ¿Ï˘ ¯ÂÈÚÔ˘ÚÁÈ΋˜ ¤̂·Û˘, ¯Ú‹Û˘ ÓÂÊÚÔÙÔÍÈÎÒÓ Ê·ÚÌ¿ÎˆÓ Î·È ÛÎÈ·ÁÚ·ÊÈÎÒÓ Ô˘ÛÈÒÓ.
∏·ÙÔÓÂÊÚÈÎfi ™‡Ó‰ÚÔÌÔ ΔÔ Ë·ÙÔÓÂÊÚÈÎfi ™‡Ó‰ÚÔÌÔ (∏¡™) Â›Ó·È Ì›·
METAMO™XEY™Eπ™ 2008
ÌÔÓ·‰È΋ ÌÔÚÊ‹ ÏÂÈÙÔ˘ÚÁÈ΋˜ ÓÂÊÚÈ΋˜ ·Ó¿ÚÎÂÈ·˜ Ô˘ ÂÈϤÎÂÈ ÚÔ¯ˆÚË̤ÓË ÓfiÛÔ ÙÔ˘ ‹·ÙÔ˜, Ë·ÙÈ΋ ·Ó¿ÚÎÂÈ· Î·È ˘Ï·›· ˘¤ÚÙ·ÛË. ∏ Û˘¯ÓfiÙËÙ· ÂÌÊ¿ÓÈÛ˘ ∏¡™ Û ·ÛıÂÓ›˜ Ì ΛÚÚˆÛË Ô˘ ÓÔÛËχÔÓÙ·È Â›Ó·È ÂÚ›Ô˘ 10%. ΔÔ Û‡Ó‰ÚÔÌÔ ¯·Ú·ÎÙËÚ›˙ÂÙ·È ·fi ¤ÓÙÔÓË ÂÓ‰ÔÓÂÊÚÈ΋ ·ÁÁÂÈÔÛ‡Û·ÛË Û ‡·ÚÍË ·ÁÁÂÈԉȷÛÙÔÏ‹˜ Ù˘ Û˘ÛÙËÌ·ÙÈ΋˜ Î·È Ù˘ ÛÏ·Á¯ÓÈ΋˜ ΢ÎÏÔÊÔÚ›·˜, Ô˘ ‰›ÓÂÈ ¤Ó·˘ÛÌ· Û Ì›ˆÛË ÙˆÓ ÂÚÈÊÂÚÈÎÒÓ ·ÁÁÂÈ·ÎÒÓ ·ÓÙÈÛÙ¿ÛÂˆÓ Î·È Ì›ˆÛË ÛÙÔÓ ·ÔÙÂÏÂÛÌ·ÙÈÎfi Û˘ÛÙËÌ·ÙÈÎfi ΢ÎÏÔÊÔÚÔ‡ÓÙ· fiÁÎÔ ·Ú¿ ÙÔÓ ·˘ÍË̤ÓÔ Û˘ÓÔÏÈÎfi ÂÍˆÎ˘ÙÙ¿ÚÈÔ fiÁÎÔ ˘ÁÚÒÓ. ¢‡Ô ÌÔÚʤ˜ ∏¡™ ·Ó·ÁÓˆÚ›˙ÔÓÙ·È. ΔÔ Ù‡Ô˘ 1 ∏¡™, ÙÔ ÔÔ›Ô ¯·Ú·ÎÙËÚ›˙ÂÙ·È ·fi Ì›· Ù·¯¤ˆ˜ ÂÍÂÏÈÛÛfiÌÂÓË Ì›ˆÛË Ù˘ ÓÂÊÚÈ΋˜ ÏÂÈÙÔ˘ÚÁ›·˜, Ë ÔÔ›· ÔÚ›˙ÂÙ·È Â›Ù Ì ÙÔÓ ‰ÈÏ·ÛÈ·ÛÌfi Ù˘ ÎÚ·ÙÈÓ›Ó˘ ÔÚÔ‡ Ì ÙÈ̤˜ >2,5 mg/dl ‹ 50% Ì›ˆÛË Ù˘ GFR Ì ÙÈÌ‹ <20% ̤۷ Û 2 ‚‰ÔÌ¿‰Â˜. ™ÙÔ˘˜ ÂÎÏ˘ÙÈÎÔ‡˜ ·Ú¿ÁÔÓÙ˜ ÂÚÈÏ·Ì‚¿ÓÔÓÙ·È Ë ·˘ÙfiÌ·ÙË ‚·ÎÙËÚȷ΋ ÂÚÈÙÔÓ›Ùȉ·, ÌÂÁ¿ÏË ¯ÂÈÚÔ˘ÚÁÈ΋ ¤̂·ÛË Î·È ÔÍ›· ·ÏÎÔÔÏÈ΋ Ë·Ù›Ùȉ·. ∏ ÔÚ›· ÙÔ˘ ∏¡™ Ù‡Ô˘ 1 Â›Ó·È ÔÍ›· Ì ·Ó¿Ù˘ÍË ÔÏÈÁÔ˘Ú›·˜, ÂÁÎÂÊ·ÏÔ¿ıÂÈ·˜ Î·È ˘„ËÏ‹˜ ˘ÂÚ¯ÔÏÂÚ˘ıÚÈÓ·ÈÌ›·˜ Ì Ôχ ˘„ËÏ‹ ıÓËÙfiÙËÙ·. ΔÔ Ù‡Ô˘ 2 ∏¡™ ¯·Ú·ÎÙËÚ›˙ÂÙ·È ·fi Ôχ ÈÔ ‹È· ÂÈÎfiÓ·, Ì ÛÙ·ıÂÚ‹ Ì›ˆÛË Ù˘ GFR ̤۷ Û ‚‰ÔÌ¿‰Â˜ ‹ Ì‹Ó˜ Ô˘ Û˘Óԉ‡ÂÈ ·ÓıÂÎÙÈÎfi ÛÙ· ‰ÈÔ˘ÚËÙÈο ·ÛΛÙË Î·È ÛËÌ·ÓÙÈ΋ ¤Ó‰ÂÈ· Ó·ÙÚ›Ô˘.
∂¶π¶§O∫∂™ ∞¶O ΔOÀ™ ¶¡∂ÀªO¡∂™ ∏·ÙÔÓ¢ÌÔÓÈÎfi ™‡Ó‰ÚÔÌÔ ΔÔ Ë·ÙÔÓ¢ÌÔÓÈÎfi Û‡Ó‰ÚÔÌÔ Â›Ó·È Ì›· Û¿ÓÈ· ηٿÛÙ·ÛË Ë ÔÔ›· ¯·Ú·ÎÙËÚ›˙ÂÙ·È ·fi ÙËÓ ÂÌÊ¿ÓÈÛË ‚·ÚÈ¿˜ ˘ÔÍ·ÈÌ›·˜ Û·Ó ·ÔÙ¤ÏÂÛÌ· ÙˆÓ ‰È¿¯˘ÙˆÓ ÂÓ‰ÔÓ¢ÌÔÓÈÎÒÓ ·ÁÁÂÈ·ÎÒÓ shunt. ΔÔ Ë·ÙÔÓ¢ÌÔÓÈÎfi Û‡Ó‰ÚÔÌÔ ÔÚ›˙ÂÙ·È Ì ÙËÓ ‡·ÚÍË ¯ÚfiÓÈ·˜ ¿ıËÛ˘ ÙÔ˘ ‹·ÙÔ˜ Ì ˘Ï·›· ˘¤ÚÙ·ÛË, PaO2 ÌÈÎÚfiÙÂÚÔ ÙˆÓ 70mmHg ÛÂ Ê˘ÛÈÔÏÔÁÈÎfi ·¤Ú· Î·È ÂӉ›ÍÂȘ ÂÓ‰ÔÓ¢ÌÔÓÈ΋˜ ·ÁÁÂÈԉȷÛÙÔÏ‹˜. ∏ ·ÓÙÈÌÂÙÒÈÛË Á›ÓÂÙ·È Ì ÙËÓ ¯ÔÚ‹ÁËÛË Ô͢ÁfiÓÔ˘ Î·È ‰ÂÓ ˘¿Ú¯ÂÈ Î¿ÔÈ· ÂȉÈ΋ ·ÓÙÈÌÂÙÒÈÛË. ∏ ÌÂÙ·ÌfiÛ¯Â˘ÛË ‹·ÙÔ˜ ·Ó·ÛÙÚ¤ÊÂÈ ÙËÓ ÂÓ‰ÔÓ¢ÌÔÓÈ΋ ·ÁÁÂÈԉȷÛÙÔÏ‹ Î·È ‚ÂÏÙÈÒÓÂÈ ÙËÓ ˘ÔÍ›· ·ÎfiÌ· Î·È ÛÙÔ˘˜ ·ÛıÂÓ›˜ Ì ÛËÌ·ÓÙÈ΋ ˘ÔÍ·ÈÌ›· ÛÙËÓ ·Ú¯È΋ ÙÔ˘˜ ÂÎÙ›ÌËÛË. ø˜ ·ÔÙ¤ÏÂÛÌ· Ë ‡·ÚÍË Ë·ÙÔÓ¢ÌÔÓÈÎÔ‡ Û˘Ó‰ÚfiÌÔ˘ ‰ÂÓ ·ÔÙÂÏ› ·ÓÙ¤Ó‰ÂÈÍË ÁÈ· ÌÂÙ·ÌfiÛ¯Â˘ÛË ‹·ÙÔ˜ Û ·ÛıÂÓ›˜ Ì ÌË-·ÓÙÈÚÔÔ‡ÌÂÓÔ ·ÛΛÙË.
79
¶˘Ï·ÈÔÓ¢ÌÔÓÈ΋ À¤ÚÙ·ÛË ∏ ˘Ï·ÈÔÓ¢ÌÔÓÈ΋ ˘¤ÚÙ·ÛË ·ÔÙÂÏ› ¤Ó· ·ÚÎÂÙ¿ ·Û˘Ó‹ıÈÛÙÔ Û‡Ó‰ÚÔÌÔ ÙÔ ÔÔ›Ô ÔÚ›˙ÂÙ·È ·fi ¯ÚfiÓÈ· ¿ıËÛË ÙÔ˘ ‹·ÙÔ˜, ̤ÛË ›ÂÛË Ó¢ÌÔÓÈ΋˜ ·ÚÙËÚ›·˜ 25mmHg Î·È Ó¢ÌÔÓÈ΋ ÙÚȯÔÂȉÈ΋ ›ÂÛË ÂÓÛÊ‹ÓˆÛ˘ ÏÈÁfiÙÂÚÔ ·fi 15mmHg. ¢ÂÓ ÂÌÊ·Ó›˙ÂÙ·È Û˘Ó‹ıˆ˜ ˘ÔÍ·ÈÌ›· ‹ ·Ó ÂÌÊ·Ó›˙ÂÙ·È Â›Ó·È Ôχ ‹È·. ∏ ˘Ï·ÈÔÓ¢ÌÔÓÈ΋ ˘¤ÚÙ·ÛË ·ÔÙÂÏ› ·Ú¿ÁÔÓÙ· Ôχ ˘„ËÏÔ‡ ÎÈÓ‰‡ÓÔ˘ Î·È ÔÈ ÂÚÈÛÛfiÙÂÚÔÈ ·ÛıÂÓ›˜ Âı·›ÓÔ˘Ó ·fi οډÈÔ-΢ÎÏÔÊÔÚÈΤ˜ ÂÈÏÔΤ˜ ·ÓÙ› ·fi ÂÈÏÔΤ˜ Ù˘ ΛÚÚˆÛ˘. ∏ ¯Ú‹ÛË Û˘Ó¯ԇ˜ ÂÓ‰ÔÊϤ‚È·˜ ¯ÔÚ‹ÁËÛ˘ ÂÓfi˜ ·Ó¿ÏÔÁÔ˘ Ù˘ ÚÔÛÙ·Î˘ÎÏ›Ó˘, Ù˘ ÂÔÚÔÛÙÂÓfiÏ˘, ÌÂÈÒÓÂÈ ÙËÓ Ó¢ÌÔÓÈ΋ ˘¤ÚÙ·ÛË ÛÙȘ ÂÚÈÛÛfiÙÂÚ˜ ÂÚÈÙÒÛÂȘ. OÈ ÂӉ›ÍÂȘ ÁÈ· ÌÂÙ·ÌfiÛ¯Â˘ÛË ‹·ÙÔ˜ ‰ÂÓ Â›Ó·È ÍÂοı·Ú˜ ÛÙËÓ ‡·ÚÍË ˘Ï·ÈÔÓ¢ÌÔÓÈ΋˜ ˘¤ÚÙ·Û˘ ÁÈ·Ù› ·ÔÙÂÏ› ÈÛ¯˘Úfi ·Ú¿ÁÔÓÙ· ÎÈÓ‰‡ÓÔ˘ ȉ›ˆ˜ fiÙ·Ó Ë Ì¤ÛË ·ÚÙËÚȷ΋ ›ÂÛË ÍÂÂÚÓ¿ Ù· 35mmHg.
∫∞ƒ¢πO§O°π∫∂™ ∂¶π¶§O∫∂™ ∫·Ú‰ÈÔÌ˘Ô¿ıÂÈ· Ù˘ ∫›ÚÚˆÛ˘ ∞ÚÎÂÙ¤˜ Ï¢ڤ˜ Ù˘ ηډȷ΋˜ ÏÂÈÙÔ˘ÚÁ›·˜ ¤¯ÂÈ ‚ÚÂı› Ó· ÌËÓ Â›Ó·È Ê˘ÛÈÔÏÔÁÈΤ˜ ÛÙËÓ Î›ÚÚˆÛË. ™Â ·˘Ù¿ ÂÚÈÏ·Ì‚¿ÓÔÓÙ·È Ë ÈÛÙÔÏÔÁÈ΋ ÂÈÎfiÓ·, Ë ÌÔÚÊÔÏÔÁ›·, ¯ÚÔÓfiÙÚÔ˜, Û˘ÛÙÔÏÈΤ˜ Î·È ‰È·ÛÙÔÏÈΤ˜ ÏÂÈÙÔ˘ÚÁ›Â˜ Î·È ËÏÂÎÙÚÔÊ˘ÛÈÔÏÔÁÈΤ˜ ÌÂÙ·‚ÔϤ˜. §ÂÈÙÔ˘ÚÁÈΤ˜ Î·È ‰ÔÌÈΤ˜ ·ÏÏ·Á¤˜ ¤¯Ô˘Ó ·Ú·ÙËÚËı› ΢ڛˆ˜ ÛÙËÓ ·ÚÈÛÙÂÚ‹ ·Ú¿ ÛÙË ‰ÂÍÈ¿ ηډȿ. OÈ ÂÚÈÛÛfiÙÂÚ˜ ÌÂϤÙ˜ ¤¯Ô˘Ó ‰Â›ÍÂÈ ‰È·ÛÙÔÏ‹ ÙÔ˘ ·ÚÈÛÙÂÚÔ‡ ÎfiÏÔ˘ Î·È ˘ÂÚÙÚÔÊ›· Ù˘ ·ÚÈÛÙÂÚ¿˜ ÎÔÈÏ›·˜. O ‰ÂÍÈfi˜ ÎfiÏÔ˜ Î·È Ë ‰ÂÍÈ¿ ÎÔÈÏ›· ¤¯Ô˘Ó Û˘Ó‹ıˆ˜ Ê˘ÛÈÔÏÔÁÈΤ˜ ‰È·ÛÙ¿ÛÂȘ Î·È ¿¯Ô˜ ÙÔȯÒÌ·ÙÔ˜ Û ·Ô˘Û›· ˘Ï·ÈÔÓ¢ÌÔÓÈ΋˜ ˘¤ÚÙ·Û˘. ªÂÙ¿ ·fi ÌÂÙ·ÌfiÛ¯Â˘ÛË ‹·ÙÔ˜ ·Ó Î·È ÙÔ ¿ÌÂÛÔ ‰ÈÂÁ¯ÂÈÚËÙÈÎfi stress Î·È È‰›ˆ˜ Ë ·˘ÍË̤ÓË ·ÚÙËÚȷ΋ ›ÂÛË Î·È ÙÔ ·˘ÍË̤ÓÔ ÌÂÙ·ÊÔÚÙ›Ô ÌÔÚÔ‡Ó Ó· ·Ôηχ„Ô˘Ó Ì›· Ï·Óı¿ÓÔ˘Û· ηډÈÔÌ˘Ô¿ıÂÈ·, Ì ÙÔÓ Î·ÈÚfi Ë Î·Ú‰È¿ ı· ÚÔÛ·ÚÌÔÛÙ› ÛÙÔ ·˘ÍË̤ÓÔ ÌÂÙ·ÊÔÚÙ›Ô. Œ¯ÂÈ ‚ÚÂı› fiÙÈ Ë ÌÂÙ·ÌfiÛ¯Â˘ÛË ‹·ÙÔ˜ ‚ÂÏÙÈÒÓÂÈ ÛËÌ·ÓÙÈο fiϘ ÙȘ ηډȷΤ˜ ·Ú·Ì¤ÙÚÔ˘˜ Ì ·ÔÙ¤ÏÂÛÌ· Ë ˘ÂÚ‰˘Ó·ÌÈ΋ ηٿÛÙ·ÛË Ó· ÂÍ·Ê·ÓÈÛÙ›, Ì›ˆÛË ÙÔ˘ ¿¯Ô˘˜ Ù˘ ·ÚÈÛÙÂÚ¿˜ ÎÔÈÏ›·˜ Î·È Ì›ˆÛË Ù˘ ‰È·Ì¤ÙÚÔ˘ ÙÔ˘ ·ÚÈÛÙÂÚÔ‡ ÎfiÏÔ˘.
80
¢. °π∞∫OÀ™Δπ¢∏™
∞¡Δ∂¡¢∂π•∂π™ °π∞ ª∂Δ∞ªO™Ã∂À™∏ °ÂÓÈΤ˜ ·ÓÙÂӉ›ÍÂȘ ÁÈ· ÌÂÙ·ÌfiÛ¯Â˘ÛË ‹·ÙÔ˜ ·ÔÙÂÏÔ‡Ó Ë ·Ó·Ú΋˜ Û˘ÌÌfiÚʈÛË, ·Ó·Ú΋ ΛÓËÙÚ· Î·È ‚·Ú›˜ Â͈˷ÙÈΤ˜ Û˘Ó˘¿Ú¯Ô˘Û˜ ·ı‹ÛÂȘ. ∞fi ÙȘ ÈÔ ÛËÌ·ÓÙÈΤ˜ Â›Ó·È Ë ¯ÚfiÓÈ· ·ÔÊÚ·ÎÙÈ΋ ÓfiÛÔ˜, ÈÛÙÔÚÈÎfi Â͈˷ÙÈ΋˜ ηÎÔ‹ıÂÈ·˜ Ì Èı·ÓfiÙËÙ· ˘ÔÙÚÔ‹˜, ÌÂÁ¿ÏË ËÏÈΛ· (¿Óˆ ·fi 65 ÂÙÒÓ) Î·È ÙÔ ·˘ÍË̤ÓÔ ÛˆÌ·ÙÈÎfi ‚¿ÚÔ˜ (μªπ >35).
μπμ§πO°ƒ∞ºπ∞ 1. Francoz C, Belghiti J, Durand F. Indications of liver transplantation in patients with complication of cirrhosis. Best Practise & Research Clinical Gastroenterology 21:175-190, 2007. 2. Merion RM, Schaubel DE, Dykstra DM et al. The survival benefit of liver transplantation Am J Transplant 5:307-313, 2005. 3. Poynard T, Naveu S, Doffoel M et al. Evaluation of efficacy of liver transplantation in alcoholic cirrhosis using mathed and simulated controls: 5-year survival. Multi-centre group. J Hepatol 30:1130-1137, 1999. 4. Feray C, Caccamo L, Alexander GJ et al. European collaborative study on factors influencing outcome after liver transplantation for hepatitis C.European Concerted Action on Viral Hepatitis (EUROHEP) Group Gastroenterology 117:619-625, 1999. 5. Terrault N, Roche B, Samuel D. Management of the hepatitis B virus in the liver transplantation setting: a European and an American perspective Liver Transpl 11:716-732, 2005.
6. Marcellin P, Chang TT, Lin SG et al. Adefovir dipivoxil for the treatment of hepatitis B e antigen-positive chronic hepatitis B N Engl J Med 348:808-816, 2003. 7. Mazzaferro V, Regalia E, Doci R et al. Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis. N Engl J Med 334:693-699, 1996. 8. Betrosian AP, Agarwal B, Douzinas EE. Acute renal dysfunction in liver diseases World J Gastroenterol 13:5552-5559, 2007. 9. Moreau R, Lebrec D. Acute renal failure in patients with cirrhosis: perspectives in the age of MELD Hepatology 37:233-243, 2003. 10. Cardenas A. Hepatorenal syndrome: a dreaded complication of end-stage liver disease Am J Gastroenterol 100:460-467, 2005. 11. Swanson KL, Wiesner RH, Krowka MJ. Natural history of hepatopulmonary syndrome: Impact of liver transplantation Hepatology 41:1122-1129, 2005. 12. Colle IO, Moreau R, Godinho E et al. Diagnosis of portopulmonary hypertension in candidates for liver transplantation: a prospective study Hepatology 37:401-409, 2003. 13. Baik SK, Fouad TR, Lee SS. Cirrhotic cardiomyopathy Orphanet J Rare Dises 2:15-23, 2007. 14. Menon NKV, Nyberg SL, Harmsen WS et al. MELD and other factors associated with survival after liver transplantation Am J Transpl 4:819-825, 2004. 15. Kim WR, Therneau TM, Benson JT et al. Deaths on the liver transplant waiting list: an analysis of competing risks Hepatology 43:345-351, 2006.
EӉ›ÍÂȘ Î·È ÎÚÈÙ‹ÚÈ· ÌÂÙ·ÌfiÛ¯Â˘Û˘ ‹·ÙÔ˜ ÛÙÔÓ Ë·ÙÔ΢ÙÙ·ÚÈÎfi ηÚΛÓÔ ¢. μÚÔ¯›‰Ë˜, ¢. Δ·ÎÔ‡‰·˜
1. πÛÙÔÚÈ΋ ·Ó·‰ÚÔÌ‹
¯ËÌÂÈÔÂÌ‚ÔÏÈÛÌfi˜, Ë ¤Á¯˘ÛË ·Èı·ÓfiÏ˘, Ë ÎÚ˘Ô¯ÂÈÚÔ˘ÚÁÈ΋ Î·È Ë ıÂÚÌÈ΋ ηٷÛÙÚÔÊ‹ Ì ڷ‰ÈÔ·̷ٷ (RFA). ∂ÈϤÔÓ, Ì ÙË ‚Ô‹ıÂÈ· ÂȉÈÎÒÓ ÌÔÓÙ¤ÏˆÓ Î·Ù·ÓÔÌ‹˜ Ë·ÙÈÎÒÓ ÌÔÛ¯Â˘Ì¿ÙˆÓ, Ô ¯ÚfiÓÔ˜ ·Ó·ÌÔÓ‹˜ ÛÙË Ï›ÛÙ· ÙÔ˘ ·ÚÚÒÛÙÔ˘ Ì ∏∫∫ ÌÂÈÒıËΠÛÙȘ 90 Ë̤Ú˜7. ªÂ ‚¿ÛË ÏÔÈfiÓ Ù· ÓÂfiÙÂÚ· ‚È‚ÏÈÔÁÚ·ÊÈο ‰Â‰Ô̤ӷ, ı· ·ÎÔÏÔ˘ı‹ÛÂÈ ÚÔÛ¿ıÂÈ· ·ÔÛ·Ê‹ÓÈÛ˘ ÙˆÓ ÂӉ›ÍÂˆÓ Î·È ÙˆÓ ÎÚÈÙËÚ›ˆÓ ÌÂÙ·ÌfiÛ¯Â˘Û˘ ‹·ÙÔ˜ ÛÙÔÓ ·ÛıÂÓ‹ Ô˘ ¤¯ÂÈ ‰È·ÁÓˆÛı› Ì ∏∫∫.
ΔÔÓ πÔ‡ÏÈÔ ÙÔ˘ 1967 Ú·ÁÌ·ÙÔÔÈ‹ıËΠÌÂÙ·ÌfiÛ¯Â˘ÛË ‹·ÙÔ˜ Û ¤Ó· ÎÔÚÈÙÛ¿ÎÈ Ì ∏∫∫, ËÏÈΛ·˜ 19 ÌËÓÒÓ. ◊Ù·Ó Ô ‰¤Î·ÙÔ˜ Ï‹Ù˘ Ë·ÙÈÎÔ‡ ÌÔۯ‡̷ÙÔ˜ ÛÙÔÓ ÎfiÛÌÔ, Ô ÚÒÙÔ˜ Ô˘ ÂÈ‚›ˆÛ Ù˘ ¿ÌÂÛ˘ ÌÂÙÂÁ¯ÂÈÚËÙÈ΋˜ ÂÚÈfi‰Ô˘. ∏ ·ÛıÂÓ‹˜ ÂÌÊ¿ÓÈÛ ˘ÔÙÚÔ‹ ÙÔ˘ ∏∫∫ 3 Ì‹Ó˜ ÌÂÙ¿ ÙË ÌÂÙ·ÌfiÛ¯Â˘ÛË, ÁÈ· Ó· ηٷϋÍÂÈ ÙÂÏÈο ·fi ÔÏ˘ÌÂÙ·ÛÙ·ÙÈ΋ ÓfiÛÔ 400 Ë̤Ú˜ ÌÂÙ¿ ÙËÓ Â¤Ì‚·ÛË1. O ÂÓıÔ˘ÛÈ·ÛÌfi˜ ÁÈ· ÙË ıÂڷ›· ÙÔ˘ ∏∫∫ Ì ÙË ‚Ô‹ıÂÈ· Ù˘ Ë·ÙÈ΋˜ ÌÂÙ·ÌfiÛ¯Â˘Û˘ ›¯Â ÔÏϤ˜ ·˘ÍÔÌÂÈÒÛÂȘ Ù· ÙÂÏÂ˘Ù·›· 40 ¯ÚfiÓÈ·. ∞Ó Î·È Ù· ÂÚÈÛÛfiÙÂÚ· ÌÂÙ·ÌÔÛ¯Â˘ÙÈο ΤÓÙÚ· ·Ó¤ÊÂÚ·Ó ÛÔÚ·‰ÈΤ˜ Ì·ÎÚfi¯ÚÔÓ˜ ÂÈ‚ÈÒÛÂȘ ‡ÛÙÂÚ· ·fi ÌÂÙ·ÌfiÛ¯Â˘ÛË ÁÈ· ∏∫∫, ·˘Ùfi ·ÔÙÂÏÔ‡Û ̿ÏÏÔÓ ÙËÓ ÂÍ·›ÚÂÛË ·Ú¿ ÙÔÓ Î·ÓfiÓ·2. ∞˘Ùfi ÁÈ·Ù› ÛÙȘ ÂÚÈÛÛfiÙÂÚ˜ ÂÚÈÙÒÛÂȘ ·Ú·ÙËÚÔ‡ÓÙ·Ó ˘ÔÙÚÔ‹ Ù˘ ÚˆÙÔ·ıÔ‡˜ ÓfiÛÔ˘ ÛÙÔ ÌfiÛ¯Â˘Ì·. ∏ ˘ÔÙÚÔ‹ ÂÌÊ·Ó›˙ÔÓÙ·Ó Ì¤Û· ÛÙ· ‰‡Ô ÚÒÙ· ¯ÚfiÓÈ· ÌÂÙ¿ ÙËÓ Â¤Ì‚·ÛË. ∞˘Ù‹ Ë ÂÌÂÈÚ›· Û˘¯Ó¿ Ô‰ËÁÔ‡Û Û ·ÚÓËÙÈ΋ ÛÙ¿ÛË Ù˘ È·ÙÚÈ΋˜ ÎÔÈÓfiÙËÙ·˜ Û ۯ¤ÛË Ì ÙË ¯Ú‹ÛË ÙˆÓ “ÔχÙÈ̈Ӕ Ë·ÙÈÎÒÓ ÌÔÛ¯Â˘Ì¿ÙˆÓ ÁÈ· ÙË ıÂڷ›· ÙÔ˘ ∏∫∫3. ΔÂÏÈο, ÙÔ 1989, ÙÔ ÀÔ˘ÚÁÂ›Ô ÀÁ›·˜ ÙˆÓ ∏¶∞ (Department of Health and Human Services) ·ÔÊ¿ÓıËΠˆ˜ Ë ‡·ÚÍË ∏∫∫ ·ÔÙÂÏÔ‡Û ·fiÏ˘ÙË ·ÓÙ¤Ó‰ÂÈÍË ÁÈ· ÙËÓ Ú·ÁÌ·ÙÔÔ›ËÛË Ë·ÙÈ΋˜ ÌÂÙ·ÌfiÛ¯Â˘Û˘. ™ÙÔ Ù¤ÏÔ˜ Ù˘ ‰ÂηÂÙ›·˜ ÙÔ˘ 1990 ·ӋÏıÂ Ô ÂÓıÔ˘ÛÈ·ÛÌfi˜ ÁÈ· ÙË ¯Ú‹ÛË Ù˘ Ë·ÙÈ΋˜ ÌÂÙ·ÌfiÛ¯Â˘Û˘ ˆ˜ ̤ÛÔ ıÂڷ›·˜ ÙÔ˘ ∏∫∫, ηıÒ˜ ·Ô‰Â›¯ıËΠfiÙÈ ‹Ù·Ó ‰˘Ó·Ù‹ Ë Â›Ù¢ÍË ÂÍ·ÈÚÂÙÈÎÒÓ ÂÈ‚ÈÒÛˆÓ, ·ÚΛ Ó· ÂÈϤÁÔÓÙ·Ó Î·Ù¿ÏÏËÏ· ÔÈ Ï‹Ù˜4. ™ÙÔ ÌÂٷ͇ ›¯Â ·Ó·Ù˘¯ı› Ï‹ıÔ˜ ıÂڷ¢ÙÈÎÒÓ ·ÚÂÌ‚¿ÛÂˆÓ Ì ÙË ‚Ô‹ıÂÈ· ÙˆÓ ÔÔ›ˆÓ ·˘Í¿ÓÔÓÙ·Ó ÙÔ ÚÔÛ‰fiÎÈÌÔ ÂÈ‚›ˆÛ˘ (Î·È ÂÔ̤ӈ˜ Ë ‰˘Ó·ÙfiÙËÙ· ·Ó·ÌÔÓ‹˜ Û ϛÛÙ· ÌÂÙ·ÌfiÛ¯Â˘Û˘) ÙˆÓ ·ÛıÂÓÒÓ Ì ∏∫∫. ™ÙȘ ·ÚÂÌ‚¿ÛÂȘ ·˘Ù¤˜5,6 Û˘ÌÂÚÈÏ·Ì‚¿ÓÔÓÙ·È Ô ·ÚÙËÚÈ·Îfi˜
2. OÚÈÛÌÔ› ∏ ¤Ó‰ÂÈÍË ÁÈ· ÌÂÙ·ÌfiÛ¯Â˘ÛË ‹·ÙÔ˜ ÛÙÔÓ ·ÛıÂÓ‹ Ì ∏∫∫ Ù›ıÂÙ·È ÂÊfiÛÔÓ ÈÛ¯‡ÂÈ Ì›· Î·È ÌfiÓË Û˘Óı‹ÎË: ∏ ·Ó·ÌÂÓfiÌÂÓË ÂÈ‚›ˆÛË ‡ÛÙÂÚ· ·fi ÙË ÌÂÙ·ÌfiÛ¯Â˘ÛË Ú¤ÂÈ Ó· ˘ÂÚ‚·›ÓÂÈ ÙËÓ ÂÈ‚›ˆÛË Ô˘ ÌÔÚ› Ó· ÂÈÙ¢¯ı› ‡ÛÙÂÚ· ·fi ÙË Ì¤ÁÈÛÙË ¯Ú‹ÛË ¿ÏψÓ, ÏËÓ Ù˘ ÌÂÙ·ÌfiÛ¯Â˘Û˘, ıÂÚ·ÂÈÒÓ (Ë·ÙÂÎÙÔÌ‹, ¯ËÌÂÈÔÂÌ‚ÔÏÈÛÌfi˜, RFA, Û˘ÛÙËÌ·ÙÈ΋ ¯ËÌÂÈÔıÂڷ›·, Î.Ù.Ï.). Δ· ÎÚÈÙ‹ÚÈ·, fï˜, ÁÈ· ÌÂÙ·ÌfiÛ¯Â˘ÛË ‹·ÙÔ˜ ÛÙÔÓ ·ÛıÂÓ‹ Ì ˷ÙÔ΢ÙÙ·ÚÈÎfi ηÚΛÓÔ ÏËÚÔ‡ÓÙ·È ÂÊfiÛÔÓ ÈÛ¯‡ÂÈ, ÂÎÙfi˜ ·fi ÙËÓ ÚÔ·Ó·ÊÂÚfiÌÂÓË, Î·È Ì›· ‰Â‡ÙÂÚË Û˘Óı‹ÎË: ∏ ·Ó·ÌÂÓfiÌÂÓË ÂÈ‚›ˆÛË ‡ÛÙÂÚ· ·fi ÌÂÙ·ÌfiÛ¯Â˘ÛË ÁÈ· ∏∫∫ Ú¤ÂÈ Ó· ˘ÂÚ‚·›ÓÂÈ ÙËÓ ÂÈ‚›ˆÛË Ô˘ ÂÈÙ˘Á¯¿ÓÂÙ·È ‡ÛÙÂÚ· ·fi ÌÂÙ·ÌfiÛ¯Â˘ÛË ÁÈ· ¿ÏÏÔ˘˜, ÂÎÙfi˜ ·fi ∏∫∫, ÏfiÁÔ˘˜. ¢ËÏ·‰‹, Ë ·Ó¿ÁÎË ı¤ÛÈÛ˘ ÎÚÈÙËÚ›ˆÓ ÚÔ·ÙÂÈ ·fi ÙËÓ ¤ÏÏÂÈ„Ë ÌÔÛ¯Â˘Ì¿ÙˆÓ Î·È Â͢ËÚÂÙ› ÛÙË ÌÂÁÈÛÙÔÔ›ËÛË Ù˘ ·fi‰ÔÛ‹˜ ÙÔ˘˜ (¯ÚfiÓÈ· ÏÂÈÙÔ˘ÚÁ›·˜). ¡· ÛËÌÂȈı› fiÙÈ ¤Ó·˜ ÎÈÚÚˆÙÈÎfi˜ ıˆÚÂ›Ù·È fiÙÈ ¤¯ÂÈ ∏∫∫ fiÙ·Ó ·ÓȯÓ‡ÂÙ·È ÛÙÔ ‹·Ú ÙÔ˘ Ì›· Ì¿˙· ÌÂÁ·Ï‡ÙÂÚË ÙÔ˘ ÂÓfi˜ ÂηÙÔÛÙÔ‡ Ì ‰‡Ô ‰È·ÊÔÚÂÙÈÎÔ‡ ›‰Ô˘˜ ·ÂÈÎÔÓÈÛÙÈΤ˜ ÂÍÂÙ¿ÛÂȘ Î·È fiÙ·Ó ÈÛ¯‡ÂÈ ÙÔ˘Ï¿Á¯ÈÛÙÔÓ ¤Ó· ·fi Ù· ·ÎfiÏÔ˘ı·: ·) ·F-p > 200 ng/ml, ‚) Ì¿˙· Ì ¤ÓÙÔÓË ·ÚÙËÚȷ΋ ÚfiÛÏË„Ë, Á) ÈÛÙÔÏÔÁÈ΋ ÂȂ‚·›ˆÛË Ì ‚ÈÔ„›·8.
81
¢. μƒOÃπ¢∏™, ¢. Δ∞∫OÀ¢∞™
82
3. ∏ Úfi‚ÏÂ„Ë Ù˘ Ê˘ÛÈ΋˜ ÈÛÙÔÚ›·˜ ÙÔ˘ ∏∫∫ °›ÓÂÙ·È ÏÔÈfiÓ Î·Ù·ÓÔËÙfi fiÙÈ ÁÈ· ÙËÓ ·fiÊ·ÛË Ú·ÁÌ·ÙÔÔ›ËÛ˘ ÌÂÙ·ÌfiÛ¯Â˘Û˘ ÛÙÔÓ ·ÛıÂÓ‹ Ì ∏∫∫ ··ÈÙÂ›Ù·È Ë ÁÓÒÛË Ù˘ Ê˘ÛÈ΋˜ ÈÛÙÔÚ›·˜ Ù˘ ÓfiÛÔ˘ (ÚÔ‚ÏÂfiÌÂÓË ÂÈ‚›ˆÛË), ηıÒ˜ Î·È ÙÔ ˆ˜ ·˘Ù‹ ÂËÚ¿˙ÂÙ·È ·fi Ù· ‰È¿ÊÔÚ· ›‰Ë ıÂÚ·ÂÈÒÓ. O ∏∫∫ Û˘Ó‹ıˆ˜ ·Ó·Ù‡ÛÛÂÙ·È Û ¤‰·ÊÔ˜ ΛÚÚˆÛ˘. ™ÙÔ ‰˘ÙÈÎfi ËÌÈÛÊ·›ÚÈÔ, ÙÔ ÔÛÔÛÙfi Û˘Ó‡·Ú͢ ∏∫∫ Î·È Î›ÚÚˆÛ˘ ÔÔÈ·Û‰‹ÔÙ ·ÈÙÈÔÏÔÁ›·˜ (HBV, HCV, ·ÏÎÔÔÏÈ΋˜, Î.Ù.Ï.) ˘ÂÚ‚·›ÓÂÈ ÙÔ 80%9. ∂Ô̤ӈ˜, Ë ÎÏÈÓÈ΋ ÂÈÎfiÓ· ÙÔ˘ ·ÚÚÒÛÙÔ˘ Â›Ó·È Û˘Ó‰˘·ÛÌfi˜ Î·È ÙˆÓ ‰‡Ô ·˘ÙÒÓ ÓÔÛËÌ¿ÙˆÓ. O ı¿Ó·ÙÔ˜ ÙÔ˘ ·ÛıÂÓÔ‡˜ ÌÔÚ› Ó· ¤ÏıÂÈ Â›Ù ÂÍ·ÈÙ›·˜ ÙÔ˘ ∏∫∫ (·‡ÍËÛË ÙÔ˘ ηÚÎÈÓÈÎÔ‡ ÊÔÚÙ›Ô˘, ηÚÎÈÓÈ΋ η¯ÂÍ›·, Î.Ù.Ï.), ›Ù ÂÍ·ÈÙ›·˜ Ù˘ Ë·ÙÈ΋˜ ·Ó¿ÚÎÂÈ·˜ (ÎÈÚÚÛÔÚ·Á›·, Ë·ÙÈÎfi ÎÒÌ·, Î.Ù.Ï.). ÕÚ·, Ë Ê˘ÛÈ΋ ÈÛÙÔÚ›· ÙÔ˘ ∏∫∫ ÂÍ·ÚÙ¿Ù·È Î·È ·fi ÙË Û˘Ó‡·ÚÍË ‹ fi¯È ÎÈÚÚˆÙÈÎÔ‡ ˘ÔÛÙÚÒÌ·ÙÔ˜. À¿Ú¯Ô˘Ó ˘ÔÏÔÁÈÛÙÈο ÂÚÁ·Ï›· Ô˘ ‚ÔËıÔ‡Ó ÛÙËÓ Úfi‚ÏÂ„Ë Ù˘ Ê˘ÛÈ΋˜ ÈÛÙÔÚ›·˜ Ù˘ ΛÚÚˆÛ˘ (CTP, MELD, Î.Ù.Ï.), Ù˘ ÂͤÏÈ͢ Ù˘ ΛÚÚˆÛ˘ Î·È ÙÔ˘ ∏∫∫ Ù·˘Ùfi¯ÚÔÓ· (CLIP, AJCC, Î.Ù.Ï.) Î·È ÙÔ˘ ·ÔÙÂϤÛÌ·ÙÔ˜ Ù˘ Ë·ÙÈ΋˜ ÌÂÙ·ÌfiÛ¯Â˘Û˘ (ªilan, UCSF, Î.Ù.Ï.). ªÂ ÙË ¯Ú‹ÛË ÙˆÓ ˘ÔÏÔÁÈÛÙÈÎÒÓ ÂÚÁ·Ï›ˆÓ Á›ÓÂÙ·È ÚfiÁÓˆÛË Ù˘ Ê˘ÛÈ΋˜ ÈÛÙÔÚ›·˜ Ù˘ ÓfiÛÔ˘ ÁÈ· ¤Ó· Û˘ÁÎÂÎÚÈ̤ÓÔ ¿ÚÚˆÛÙÔ Ì ∏∫∫ Î·È ¤ÙÛÈ, ·ÊÂÓfi˜ Ù›ıÂÙ·È Ë ¤Ó‰ÂÈÍË, ·ÊÂÙ¤ÚÔ˘ ‰È·ÈÛÙÒÓÂÙ·È ·Ó ÙËÚÔ‡ÓÙ·È Ù· ÎÚÈÙ‹ÚÈ· ÁÈ· ÙËÓ Ú·ÁÌ·ÙÔÔ›ËÛË Ë·ÙÈ΋˜ ÌÂÙ·ÌfiÛ¯Â˘Û˘. ¡· ÛËÌÂȈı› fiÙÈ fiÙ·Ó Ë ¯Ú‹ÛË ÙˆÓ ˘ÔÏÔÁÈÛÙÈÎÒÓ ÂÚÁ·Ï›ˆÓ ‰ÂÈÎÓ‡ÂÈ fiÙÈ
‰ÂÓ ÙËÚÔ‡ÓÙ·È Ù· ÎÚÈÙ‹ÚÈ· ÌÂÙ·ÌfiÛ¯Â˘Û˘, ÙfiÙÂ, Ì ÙË ¯Ú‹ÛË ‰È·ÊfiÚˆÓ ¿ÏÏˆÓ ıÂÚ·ÂÈÒÓ (Ë·ÙÂÎÙÔÌ‹, ¯ËÌÂÈÔÂÌ‚ÔÏÈÛÌfi˜, RFA, Û˘ÛÙËÌ·ÙÈ΋ ¯ËÌÂÈÔıÂڷ›·, Î.Ù.Ï.), ÂȯÂÈÚÂ›Ù·È ˘ÔÛÙ·‰ÈÔÔ›ËÛË ÙÔ˘ ∏∫∫, Ì ÙÂÏÈÎfi ÛÙfi¯Ô ÙËÓ ¤ÓÙ·ÍË ÛÙË Ï›ÛÙ· ·Ó·ÌÔÓ‹˜ ÂÓfi˜ Ë·ÙÈÎÔ‡ ÌÔۯ‡̷ÙÔ˜.
4. Δ· ˘ÔÏÔÁÈÛÙÈο ÂÚÁ·Ï›· Δ· ˘ÔÏÔÁÈÛÙÈο ÂÚÁ·Ï›· (›Ó·Î·˜ 1) Â›Ó·È Û˘Ó¿ıÚoÈÛË ‰ÂÈÎÙÒÓ Ô˘ Û¯ÂÙ›˙ÔÓÙ·È ÙfiÛÔ Ì ÙË ‚·Ú‡ÙËÙ· Ù˘ ΛÚÚˆÛ˘, fiÛÔ Î·È Ì ÙËÓ ÂÈıÂÙÈÎfiÙËÙ· ÙÔ˘ ∏∫∫ (ÔÏÈ΋ ¯ÔÏÂÚ˘ıÚ›ÓË ÔÚÔ‡, ·Ï‚Ô˘Ì›ÓË ÔÚÔ‡, ̤ÁÂıÔ˜ ∏∫∫, ·F-p oÚÔ‡, Î.Ù.Ï.) ··ÚÙ›˙Ô˘Ó ‰Â ›Ù ‚·ıÌÔÏÔÁ›Â˜ (CTP, MELD, CLIP Î·È CUPI), ›ÙÂ Û˘ÛÙ‹Ì·Ù· Ù·ÍÈÓfiÌËÛ˘ (AJCC, Okuda, JISS Î·È BCLC), ›Ù ÚÔ¸Ôı¤ÛÂȘ ‰ÈÂÓ¤ÚÁÂÈ·˜ ÌÂÙ·ÌfiÛ¯Â˘Û˘ (Milan, UCSF Î·È Barcelona). Δ¤ÏÔ˜, ˘¿Ú¯Ô˘Ó Î·È ÌÂÚÈÎÔ› ‰Â›ÎÙ˜ ÔÈ ÔÔ›ÔÈ ÚÔÛʤÚÔ˘Ó ÚÔÁÓˆÛÙÈΤ˜ ÏËÚÔÊÔڛ˜ ·ÎfiÌ· Î·È ÌÂÌÔӈ̤ÓÔÈ (DCP, VEGF-P Î·È FAL), ¯ˆÚ›˜ ‰ËÏ·‰‹ Ó· ÂÓÙ¿ÛÛÔÓÙ·È ÛÙ· Ï·›ÛÈ· οÔÈÔ˘ ˘ÔÏÔÁÈÛÙÈÎÔ‡ ÂÚÁ·Ï›Ԣ10.
i. μ·ıÌÔÏÔÁ›Â˜ (scores) Ÿˆ˜ ¤¯ÂÈ ‹‰Ë ·Ó·ÊÂÚı›, Ù· ˘ÔÏÔÁÈÛÙÈο ÂÚÁ·Ï›· CTP, MELD, CLIP Î·È CUPI ·Ó‹ÎÔ˘Ó ÛÙȘ ‚·ıÌÔÏÔÁ›Â˜. H ‚·ıÌÔÏÔÁ›· CTP ÂÎÙÈÌ¿ ÙË ‚·Ú‡ÙËÙ· Ù˘ ΛÚÚˆÛ˘, ‰ÂÓ ¤¯ÂÈ Û¯¤ÛË Ì ÙËÓ ‡·ÚÍË ∏∫∫ Î·È ÚԂϤÂÈ ÙË ıÓËÙfiÙËÙ· ÙÔ˘ Ë·ÙÔ·ıÔ‡˜ ‡ÛÙÂÚ· ·fi ¯ÔÚ‹ÁËÛË ·Ó·ÈÛıËÛ›·˜ ÁÈ· ̤ÙÚÈ·˜ ‚·Ú‡ÙËÙ·˜ ¯ÂÈÚÔ˘ÚÁÈ΋ ¤̂·ÛË11. ∏ ‚·ıÌÔÏÔÁ›· Î˘Ì·›ÓÂÙ·È ·fi 5 ¤ˆ˜ Î·È 15 ‚·ıÌÔ‡˜ Î·È ·ÓÙÈÛÙÔȯ›˙ÂÙ·È
¶›Ó·Î·˜ 1. ™˘ÁÎÂÓÙÚˆÙÈÎfi˜ ›Ó·Î·˜ ÙˆÓ ·Ú·Ì¤ÙÚˆÓ Ô˘ ··ÚÙ›˙Ô˘Ó Ù· ˘ÔÏÔÁÈÛÙÈο ÂÚÁ·Ï›· Ù· ÔÔ›· Û¯ÂÙ›˙ÔÓÙ·È Ì ÙÔÓ ∏∫∫ (‚·ıÌÔÏÔÁ›Â˜, Û˘ÛÙ‹Ì·Ù· Ù·ÍÈÓfiÌËÛ˘, ÚÔ¸Ôı¤ÛÂȘ ‰ÈÂÓ¤ÚÁÂÈ·˜ ÌÂÙ·ÌfiÛ¯Â˘Û˘). ÀÔÏÔÁÈÛÙÈÎfi ∂ÚÁ·Ï›Ô
∞ÚÈıÌfi˜ ŸÁΈÓ
ª¤ÁÂıÔ˜ ŸÁÎÔ˘
CLIP
ñ
ñ
ñ
CUPI
ñ
ñ
ñ
ñ
AJCC
ñ
ñ
ñ
ñ
ñ
Okuda JISS
ñ
BCLC Milan
∞ÁÁÂȷ΋ μ·ıÌfi˜ ∏·ÙÈ΋ ∂¤ÎÙ·ÛË ∫·ÎÔ‹ıÂÈ·˜ ∂¿ÚÎÂÈ·
ñ
ªÂÙ·ÛÙ¿ÛÂȘ ™˘ÌÙÒÌ·Ù· μÈ‚ÏÈÔÁÚ·Ê›·
14
ñ ñ
15
ñ
16
ñ
18
ñ
ñ
19
ñ
ñ
ñ
ñ
ñ
ñ
ñ ñ
ñ
20 4
UCSF
ñ
ñ
ñ
ñ
21
Barcelona
ñ
ñ
ñ
ñ
23
METAMO™XEY™Eπ™ 2008
Ì ٷ ÛÙ¿‰È· ηٿ Child (5-6: ÛÙ¿‰ÈÔ ∞, 7-9: ÛÙ¿‰ÈÔ μ, 10-15: ÛÙ¿‰ÈÔ C). ÃÚËÛÈÌÔÔÈÂ›Ù·È Ôχ Û¿ÓÈ· ηٿ ÙËÓ ÂÎÙ›ÌËÛË ÙÔ˘ ·ÛıÂÓ‹ Ì ∏∫∫. ∏ ‚·ıÌÔÏÔÁ›· MELD ÂÎÙÈÌ¿ ÙË ‚·Ú‡ÙËÙ· Ù˘ ΛÚÚˆÛ˘12. ∫·È ·˘Ù‹ ‰ÂÓ ¤¯ÂÈ Û¯¤ÛË Ì ÙËÓ ‡·ÚÍË ∏∫∫. O ˘ÔÏÔÁÈÛÌfi˜ Ù˘ Á›ÓÂÙ·È Ì ‚¿ÛË ÙÔÓ ·ÏÁfiÚÈıÌÔ: 0.957 á Loge(ÎÚ·ÙÈÓ›ÓË) + 0. 378 á Loge(¯ÔÏÂÚ˘ıÚ›ÓË) + 1.120 á Loge (INR) + 0.643 ∫˘Ì·›ÓÂÙ·È ·fi 6 ¤ˆ˜ Î·È 40 ‚·ıÌÔ‡˜. ∏ ‚·ıÌÔÏÔÁ›· ÚÔÛ‰ÈÔÚ›˙ÂÈ ÙËÓ ÚÔ‚ÏÂfiÌÂÓË ıÓËÙfiÙËÙ· ÙÔ˘ Ë·ÙÔ·ıÔ‡˜ ̤۷ ÛÙÔ˘˜ ÂfiÌÂÓÔ˘˜ ÙÚÂȘ Ì‹Ó˜. ¶·Ú·‰Â›ÁÌ·ÙÔ˜ ¯¿ÚÈÓ, ·Ó ÙÔ MELD ÂÓfi˜ ÎÈÚÚˆÙÈÎÔ‡ Â›Ó·È 22, ÙfiÙÂ Ë Èı·ÓfiÙËÙ· ı·Ó¿ÙÔ˘ ÙÔ˘ ηٿ ÙÔ˘˜ ÂfiÌÂÓÔ˘˜ 3 Ì‹Ó˜ Â›Ó·È 15%. ΔÔ MELD Ú¤ÂÈ Ó· ·ӢÔÏÔÁ›˙ÂÙ·È Î¿ı ÙÚÂȘ Ì‹Ó˜. ΔÔ MELD ‰ÂÓ ÌÔÚ› Ó· ¯ÚËÛÈÌÔÔÈËı› ÁÈ· ÙËÓ ÚfiÁÓˆÛË Ù˘ ·Ó·ÏÔÁÈÛÙÈ΋˜ ÂÈ‚›ˆÛ˘ ÙÔ˘ Ë·ÙÔ·ıÔ‡˜ Ì ∏∫∫. ∞˘Ùfi Û˘Ì‚·›ÓÂÈ ÁÈ·Ù› Ë Ë·ÙÈ΋ ·Ó¿ÚÎÂÈ· ÔÏÏÒÓ ·ÛıÂÓÒÓ Ì ∏∫∫ ‰ÂÓ Â›Ó·È ÛÔ‚·Ú‹, ÔfiÙÂ Ô ¿ÚÚˆÛÙÔ˜ ηٷϋÁÂÈ ·fi ÙËÓ Â¤ÎÙ·ÛË ÙÔ˘ ηÚΛÓÔ˘ Î·È fi¯È ·fi ÙË ‚·Ú‡ÙËÙ· Ù˘ ΛÚÚˆÛ˘. °È· ÙÔ ÏfiÁÔ ·˘Ùfi, fiÙ·Ó Ë Î·Ù·ÓÔÌ‹ ÙˆÓ ÌÔÛ¯Â˘Ì¿ÙˆÓ Á›ÓÂÙ·È Ì ‚¿ÛË ÙÔ MELD (fiˆ˜ ÏfiÁÔ˘ ¯¿ÚÈÓ ÛÙȘ ∏ӈ̤Ó˜ ¶ÔÏÈÙ›˜ Ù˘ ∞ÌÂÚÈ΋˜) Ô ·ÛıÂÓ‹˜ Ì ∏∫∫ ÚÈÌÔ‰ÔÙÂ›Ù·È Ì ÂÈϤÔÓ ‚·ıÌÔ‡˜, ÁÈ·Ù› Ë Î›ÚÚˆÛ‹ ÙÔ˘ Â›Ó·È ÙȘ ÂÚÈÛÛfiÙÂÚ˜ ÊÔÚ¤˜ Û ·Ú¯ÈÎfi ÛÙ¿‰ÈÔ. ™˘ÁÎÂÎÚÈ̤ӷ, οı ·ÛıÂÓ‹˜ Ì ∏∫∫ ÛÙ·‰›Ô˘ Δ2 ‹ ÌÂÁ·Ï‡ÙÂÚÔ˘ (ηٿ AJCC, ‚Ϥ ·Ú·Î¿Ùˆ) Î·È ¯ˆÚ›˜ ÌÂÙ·ÛÙ¿ÛÂȘ Ï·Ì‚¿ÓÂÈ 22 ‚·ıÌÔ‡˜. ∂ÈϤÔÓ, οı ÙÚÂȘ Ì‹Ó˜ ·Ú·ÌÔÓ‹˜ ÛÙË Ï›ÛÙ· ÌÂÙ·ÌfiÛ¯Â˘Û˘ Ï·Ì‚¿ÓÂÈ ¿ÏÏÔ˘˜ ‰‡Ô ‚·ıÌÔ‡˜13. ∏ ‚·ıÌÔÏÔÁ›· CLIP (›Ó·Î·˜ 2) ÂÎÙÈÌ¿ ÙfiÛÔ ÙË ‚·Ú‡ÙËÙ· Ù˘ ΛÚÚˆÛ˘ fiÛÔ Î·È ÙËÓ ¤ÎÙ·ÛË ÙÔ˘ ∏∫∫14. ∫˘Ì·›ÓÂÙ·È ·fi 0 ¤ˆ˜ Î·È 6 ‚·ıÌÔ‡˜. ∏ ‚·ıÌÔÏÔÁ›· ÚÔÛ‰ÈÔÚ›˙ÂÈ ÙËÓ ÚÔ‚ÏÂfiÌÂÓË ıÓËÙfiÙËÙ· ÙÔ˘ Ë·ÙÔ·ıÔ‡˜ ̤۷ ÛÙÔÓ ÂfiÌÂÓÔ ¯ÚfiÓÔ. ™˘ÁÎÂÎÚÈ̤ӷ, ÔÈ ·ÛıÂÓ›˜ Ì ‚·ıÌÔÏÔÁ›Â˜ 0, 1, 2, 3, Î·È 4-6 ¤¯Ô˘Ó ÂÙ‹ÛȘ ÚÔ‚ÏÂfiÌÂÓ˜ ÂÈ‚ÈÒÛÂȘ 84%, 66%, 45%, 36% Î·È 9% ·ÓÙ›ÛÙÔȯ·. ∏ ‚·ıÌÔÏÔÁ›· CLIP ‚·Û›ÛÙËΠ۠‰Â‰Ô̤ӷ ·fi ·ÛıÂÓ›˜ Ô˘ ·Ó¤Ù˘Í·Ó ∏∫∫ Û ¤‰·ÊÔ˜ ΢ڛˆ˜ ·ÏÎÔÔÏÈ΋˜ ‹ HCV ΛÚÚˆÛ˘. ∏ ‚·ıÌÔÏÔÁ›· CUPI (›Ó·Î·˜ 3) ÂÎÙÈÌ¿ ÙfiÛÔ ÙË ‚·Ú‡ÙËÙ· Ù˘ ΛÚÚˆÛ˘ fiÛÔ Î·È ÙËÓ ¤ÎÙ·ÛË ÙÔ˘ ∏∫∫15. ∫˘Ì·›ÓÂÙ·È ·fi -7 ¤ˆ˜ Î·È 12 ‚·ıÌÔ‡˜. ∏ ‚·ıÌÔÏÔÁ›· ÚÔÛ‰ÈÔÚ›˙ÂÈ ÙËÓ ÚÔ‚ÏÂfiÌÂÓË ıÓË-
83
¶›Ó·Î·˜ 2. ∏ ÙÂÏÈ΋ ‚·ıÌÔÏÔÁ›· CLIP ÚÔ·ÙÂÈ ·fi ÙËÓ ÚfiÛıÂÛË ÙˆÓ ‚·ıÌÒÓ Ô˘ ·ÓÙÈÛÙÔÈ¯Ô‡Ó ÛÙÔ˘˜ ÂÈ̤ÚÔ˘˜ Ù¤ÛÛÂÚÂȘ ‰Â›ÎÙ˜. ¢Â›ÎÙ˜
μ·ıÌÔ› 0
1
2
™Ù¿‰ÈÔ Child
∞
μ
C
ªÔÚÊÔÏÔÁ›· fiÁÎÔ˘
ªÔÓ‹Ú˘
¶ÔÏÏ·Ïfi˜, ≤ 50% ÙÔ˘ ‹·ÙÔ˜
¶ÔÏÏ·Ïfi˜, > 50% ÙÔ˘ ‹·ÙÔ˜
·F-p (ng/ml)
< 400
¢È‹ıËÛË ˘Ï·›·˜ Ÿ¯È
≥ 400
–
¡·›
–
ÙfiÙËÙ· ÙÔ˘ Ë·ÙÔ·ıÔ‡˜ ̤۷ ÛÙÔ˘˜ ÂfiÌÂÓÔ˘˜ ÙÚÂȘ Ì‹Ó˜. ™˘ÁÎÂÎÚÈ̤ӷ, ÔÈ ·ÛıÂÓ›˜ Ì ‚·ıÌÔÏÔÁ›Â˜ < 2, 2-7 Î·È >7, ¤¯Ô˘Ó ÚÔ‚ÏÂfiÌÂÓ˜ ÂÈ‚ÈÒÛÂȘ ÙÚÈÌ‹ÓÔ˘ 86%, 56% Î·È 20% ·ÓÙ›ÛÙÔȯ·. ∏ ‚·ıÌÔÏÔÁ›· CUPI ‚·Û›ÛÙËΠ۠‰Â‰Ô̤ӷ ·fi ·ÛıÂÓ›˜ Ô˘ ·Ó¤Ù˘Í·Ó ∏∫∫ Û ¤‰·ÊÔ˜ ΢ڛˆ˜ HBV ΛÚÚˆÛ˘.
ii. ™˘ÛÙ‹Ì·Ù· Ù·ÍÈÓfiÌËÛ˘ (staging systems) Ÿˆ˜ ¤¯ÂÈ ‹‰Ë ·Ó·ÊÂÚı›, Ù· ˘ÔÏÔÁÈÛÙÈο ÂÚÁ·Ï›· AJCC, Okuda, JISS Î·È BCLC ·Ó‹ÎÔ˘Ó ÛÙ· Û˘ÛÙ‹Ì·Ù· Ù·ÍÈÓfiÌËÛ˘. ΔÔ Û‡ÛÙËÌ· Ù·ÍÈÓfiÌËÛ˘ AJCC (›Ó·Î·˜ 4) ÂÎÙÈÌ¿ ΢ڛˆ˜ ÙËÓ ¤ÎÙ·ÛË ÙÔ˘ ∏∫∫ Î·È ÏÈÁfiÙÂÚÔ ÙË ‚·Ú‡ÙËÙ· Ù˘ ΛÚÚˆÛ˘16. ¶ÂÚÈÏ·Ì‚¿ÓÂÈ Ù¤ÛÛÂÚ· ‰È·ÎÚÈÙ¿ ÛÙ¿‰È· (I-IV). ΔÔ AJCC ‰ÂÈÎÓ‡ÂÈ ÙËÓ Èı·ÓfiÙËÙ· ÂÈ‚›ˆÛ˘ ÙÔ˘ ·ÛıÂÓÔ‡˜ ÁÈ· ÂÚÈÛÛfiÙÂÚÔ ·fi ¤ÓÙ ¯ÚfiÓÈ·, ‡ÛÙÂÚ· ·fi R0 Ë·ÙÂÎÙÔÌ‹. ™˘ÁÎÂÎÚÈ̤ӷ, ÔÈ ·ÛıÂÓ›˜ ÛÙ·‰›Ô˘ π ¤¯Ô˘Ó ÂÓÙ·ÂÙ‹ ÂÈ‚›ˆÛË 64% ·Ó Ô ∏∫∫ ‰Â Û˘Ó˘¿Ú¯ÂÈ Ì ›ÓˆÛË/ΛÚÚˆÛË Î·È 49% ·Ó Û˘Ó˘¿Ú¯ÂÈ. OÈ ·ÛıÂÓ›˜ ÛÙ·‰›Ô˘ ππ ¤¯Ô˘Ó ÂÓÙ·ÂÙ‹ ÂÈ‚›ˆÛË 46% ·Ó Ô ∏∫∫ ‰Â Û˘Ó˘¿Ú¯ÂÈ Ì ›ÓˆÛË/ΛÚÚˆÛË Î·È 30% ·Ó Û˘Ó˘¿Ú¯ÂÈ. OÈ ·ÛıÂÓ›˜ ÛÙ·‰›Ô˘ πππ∞ ¤¯Ô˘Ó ÂÓÙ·ÂÙ‹ ÂÈ‚›ˆÛË 17% ·Ó Ô ∏∫∫ ‰Â Û˘Ó˘¿Ú¯ÂÈ Ì ›ÓˆÛË/ΛÚÚˆÛË Î·È 9% ·Ó Û˘Ó˘¿Ú¯ÂÈ. ΔÔ Û‡ÛÙËÌ· Ù·ÍÈÓfiÌËÛ˘ AJCC ‚·Û›ÛÙËΠ۠‰Â‰Ô̤ӷ ·fi ·ÛıÂÓ›˜ Ô˘ ·Ó¤Ù˘Í·Ó ∏∫∫ Û ¤‰·ÊÔ˜ ΢ڛˆ˜ HCV ΛÚÚˆÛ˘ ·ÏÏ¿ Ë ÚÔÁÓˆÛÙÈ΋ ÙÔ˘ ·Í›· ¤¯ÂÈ ÂȂ‚·Èˆı› Î·È Û ·ÚÚÒÛÙÔ˘˜ Ì HBV17. ΔÔ Û‡ÛÙËÌ· Ù·ÍÈÓfiÌËÛ˘ Okuda (›Ó·Î·˜ 5) ÂÎÙÈÌ¿ ÙfiÛÔ ÙËÓ ¤ÎÙ·ÛË ÙÔ˘ ∏∫∫ fiÛÔ Î·È ÙË ‚·Ú‡ÙËÙ· Ù˘ ΛÚÚˆÛ˘18. ¶ÂÚÈÏ·Ì‚¿ÓÂÈ ÙÚ›· ‰È·ÎÚÈÙ¿ ÛÙ¿‰È· (I-Iππ). ΔÔ Û‡ÛÙËÌ· Okuda ÚÔ‚¤ÂÈ ÙË ‰È¿ÌÂÛÔ ÙÈÌ‹ ÂÈ‚›ˆÛ˘ ÙÔ˘ ·ÛıÂÓÔ‡˜ (Û ̋-
¢. μƒOÃπ¢∏™, ¢. Δ∞∫OÀ¢∞™
84
¶›Ó·Î·˜ 3. ∏ ÙÂÏÈ΋ ‚·ıÌÔÏÔÁ›· CUPI ÚÔ·ÙÂÈ ·fi ÙËÓ ÚfiÛıÂÛË ÙˆÓ ‚·ıÌÒÓ Ô˘ ·ÓÙÈÛÙÔÈ¯Ô‡Ó ÛÙÔ˘˜ ÂÈ̤ÚÔ˘˜ ¤ÍÈ ‰Â›ÎÙ˜. ¢Â›ÎÙ˜ -3
-1
μ·ıÌÔ› 0
I / II
IIIa / IIIb
IVa / IVb
-4 ™Ù¿‰ÈÔ AJCC Ÿ¯È
™˘ÌÙÒÌ·Ù·
2
3
4
¡·› Ÿ¯È
∞ÛΛÙ˘
¡·›
< 500
·F-p (ng/ml)
<2
2-3
< 200
≥ 200
ÃÔÏÂÚ˘ıÚ›ÓË (mgdl) AÏÎ. ºˆÛÊ·Ù¿ÛË (U/L)
≥ 500 >3
¶›Ó·Î·˜ 4. ∞ÏÔÔÈË̤ÓÔ Û‡ÛÙËÌ· Ù·ÍÈÓfiÌËÛ˘ AJCC. ΔÔ ÛÙ¿‰ÈÔ ÙÔ˘ ∏∫∫ ÚÔ·ÙÂÈ ·Ó¿ÏÔÁ· Ì ÙÔ ‚·ıÌfi ‚·Ú‡ÙËÙ·˜ ÙˆÓ ÂÈ̤ÚÔ˘˜ ÛÙÔȯ›ˆÓ ÙÔ˘ Û˘ÛÙ‹Ì·ÙÔ˜. ŸÔ˘ i, ÙÔÔıÂÙÂ›Ù·È ÔÔÈ·‰‹ÔÙ ÙÈÌ‹ ·fi 0 ¤ˆ˜ 4. ™ÙÔȯ›·
μ·Ú‡ÙËÙ· 1
2
3
4
ŸÁÎÔ˜ (T)
ªÔÓ‹Ú˘
ªÔÓ‹Ú˘ > 5 cm
¶ÔÏÏ·ÏÔ› > 5 cm
‹ ¶ÔÏÏ·ÏÔ›
ÔÚÁ¿ÓˆÓ
§ÂÌÊ·‰¤Ó˜ (N)
¡·È
–
–
–
MÂÙ·ÛÙ¿ÛÂȘ (M)
¡·È
–
–
–
πÛÙÔÏÔÁ›· (G)
∫·Ï‹ ‰È·ÊÔÚÔÔ›ËÛË
ª¤ÙÚÈ· ‰È·ÊÔÚÔÔ›ËÛË ∫·Î‹ ‰È·ÊÔÚÔÔ›ËÛË
∞‰È·ÊÔÚÔÔ›ËÙÔ˜ fiÁÎÔ˜
ÿÓˆÛË (F)
™Ô‚·ÚÔ‡ ‚·ıÌÔ‡ ›ÓˆÛË –
–
‹ ∫ ›ÚÚˆÛË
¢È‹ıËÛË ¿ÏψÓ
– ™Ù·‰ÈÔÔ›ËÛË
™Ù¿‰ÈÔ I
T1 N0 M0
™Ù¿‰ÈÔ II
T2 N0 M0
™Ù¿‰ÈÔ IIIA
T3 N0 M0
™Ù¿‰ÈÔ IIIB
T4 N0 M0
™Ù¿‰ÈÔ IIIC
Ti N1 M0
™Ù¿‰ÈÔ IV
Ti Ni M1
¶›Ó·Î·˜ 5. ™‡ÛÙËÌ· Ù·ÍÈÓfiÌËÛ˘ Okuda. ΔÔ ÛÙ¿‰ÈÔ ÙÔ˘ ∏∫∫ ÚÔ·ÙÂÈ ·Ó¿ÏÔÁ· Ì ÙÔÓ ·ÚÈıÌfi ÙˆÓ ıÂÙÈÎÒÓ Â˘ÚËÌ¿ÙˆÓ ÙÔ˘ Û˘ÛÙ‹Ì·ÙÔ˜. ∂˘Ú‹Ì·Ù·
÷ڷÎÙËÚÈÛÌfi˜ ∞ÚÓËÙÈÎfi
£ÂÙÈÎfi
ª¤ÁÂıÔ˜ fiÁÎÔ˘
< 50%
≥ 50%
∞ÛΛÙ˘
Ÿ¯È
¡·È
∞Ï‚Ô˘Ì›ÓË ÔÚÔ‡
> 3 mg/dl
≤ 3 mg/dl
ÃÔÏÂÚ˘ıÚ›ÓË ÔÚÔ‡
< 3 mg/dl
≥ 3 mg/dl
™Ù·‰ÈÔÔ›ËÛË ™Ù¿‰ÈÔ I
∫·Ó¤Ó· ıÂÙÈÎfi
™Ù¿‰ÈÔ II
Œˆ˜ Î·È ‰‡Ô ıÂÙÈο Â˘Ú‹Ì·Ù·
™Ù¿‰ÈÔ III
¶¿Óˆ ·fi ‰‡Ô ıÂÙÈο Â˘Ú‹Ì·Ù·
METAMO™XEY™Eπ™ 2008
Ó˜) ¯ˆÚ›˜ Î·È ‡ÛÙÂÚ· ·fi R0 Ë·ÙÂÎÙÔÌ‹. ™˘ÁÎÂÎÚÈ̤ӷ, Ë ‰È¿ÌÂÛË ÂÈ‚›ˆÛË ÙˆÓ ·ÛıÂÓÒÓ ÛÙ·‰›Ô˘ π Â›Ó·È 8,3 Ì‹Ó˜ ¯ˆÚ›˜ η̛· ıÂڷ›· Î·È 25,6 Ì‹Ó˜ ‡ÛÙÂÚ· ·fi R0 Ë·ÙÂÎÙÔÌ‹. ∏ ‰È¿ÌÂÛË ÂÈ‚›ˆÛË ÙˆÓ ·ÛıÂÓÒÓ ÛÙ·‰›Ô˘ ππ Â›Ó·È 2 Ì‹Ó˜ ¯ˆÚ›˜ η̛· ıÂڷ›· Î·È 12,2 Ì‹Ó˜ ‡ÛÙÂÚ· ·fi R0 Ë·ÙÂÎÙÔÌ‹. ∏ ‰È¿ÌÂÛË ÂÈ‚›ˆÛË ÙˆÓ ·ÛıÂÓÒÓ ÛÙ·‰›Ô˘ πππ Â›Ó·È 0,7 Ì‹Ó˜ ¯ˆÚ›˜ η̛· ıÂڷ›·, ÂÓÒ ÔÈ ¿ÚÚˆÛÙÔÈ ·˘ÙÔ› Û˘Ó‹ıˆ˜ ‰ÂÓ ˘Ô‚¿ÏÔÓÙ·È Û ˷ÙÂÎÙÔÌ‹. Δ· Û˘ÛÙ‹Ì·Ù· Ù·ÍÈÓfiÌËÛ˘ JISS19 Î·È BCLC20 ΢ڛˆ˜ ·ÔÙÂÏÔ‡Ó ·ÏÁfiÚÈıÌÔ˘˜ ıÂڷ›·˜ ÁÈ· ÙÔÓ ∞ÛÈ¿ÙË Î·È ÙÔÓ ∂˘Úˆ·›Ô ·ÓÙ›ÛÙÔȯ· ·ÛıÂÓ‹ Ì ∏∫∫. OÈ ·ÏÁfiÚÈıÌÔÈ ·˘ÙÔ› ¤¯Ô˘Ó ηٷÛÙÚˆı› ‡ÛÙÂÚ· ·fi ÂÎÙÂÙ·Ì̤ÓË ·Ó·ÛÎfiËÛË Ù˘ ‚È‚ÏÈÔÁÚ·Ê›·˜ ÛÂ Û˘Ó‰˘·ÛÌfi Ì ÂÓۈ̿وÛË Ù˘ ÂÌÂÈÚ›·˜ ÙˆÓ ÌÂÁ¿ÏˆÓ ΤÓÙÚˆÓ ·fi Ù· ÔÔ›· ÚÔ¤Ú¯ÔÓÙ·È. ™ÙÔ Û‡ÛÙËÌ· JISS Û˘Ó˘ÔÏÔÁ›˙ÔÓÙ·È Ô ·ÚÈıÌfi˜ ÙˆÓ fiÁΈÓ, Ë ‰È¿ÌÂÙÚÔ˜ ÙÔ˘ ÌÂÁ·Ï‡ÙÂÚÔ˘ fiÁÎÔ˘ Î·È Ë Â¿ÚÎÂÈ· ÙÔ˘ ‹·ÙÔ˜. ™ÙÔ Û‡ÛÙËÌ· BCLC Û˘Ó˘ÔÏÔÁ›˙ÔÓÙ·È Ô ·ÚÈıÌfi˜ ÙˆÓ fiÁΈÓ, Ë Ì·ÎÚÔÛÎÔÈ΋ ·ÁÁÂȷ΋ ¤ÎÙ·ÛË, Ë Â¿ÚÎÂÈ· ÙÔ˘ ‹·ÙÔ˜, Ë ‡·ÚÍË ÌÂÙ·ÛÙ¿ÛÂˆÓ Î·È Ë ·ÚÔ˘Û›· Û˘ÌÙˆÌ¿ÙˆÓ ·fi ÙÔÓ ∏∫∫. OÈ ·ÛıÂÓ›˜ ηٷٿÛÔÓÙ·È Û Ôχ ÚÒÈÌÔ (0), ÚÒÈÌÔ (∞), ‰È¿ÌÂÛÔ (B), ÚÔ¯ˆÚË̤ÓÔ (C) ÙÂÏÈÎfi (D) ÛÙ¿‰ÈÔ. ™Â ÁÂÓÈΤ˜ ÁÚ·Ì̤˜ ÔÈ ¿ÚÚˆÛÙÔÈ ·˘ÙÔ› Ô‰ËÁÔ‡ÓÙ·È Û ˷ÙÂÎÙÔÌ‹ (ÛÙ¿‰ÈÔ 0), ÌÂÙ·ÌfiÛ¯Â˘ÛË (ÛÙ¿‰ÈÔ A), ˘ÔÛÙ·‰ÈÔÔ›ËÛË (ÛÙ¿‰ÈÔ B), ·ÁˆÁ¤˜ ÚˆÙÔÎfiÏÏÔ˘ (ÛÙ¿‰ÈÔ C) Î·È ·ÚËÁÔÚÈ΋ ıÂڷ›· (ÛÙ¿‰ÈÔ D).
iii. ¶ÚÔ¸Ôı¤ÛÂȘ ‰ÈÂÓ¤ÚÁÂÈ·˜ ÌÂÙ·ÌfiÛ¯Â˘Û˘ (criteria - provisions) Ÿˆ˜ ¤¯ÂÈ ‹‰Ë ·Ó·ÊÂÚı›, Ù· ˘ÔÏÔÁÈÛÙÈο ÂÚÁ·Ï›· Milan, UCSF, Î·È Barcelona ·Ó‹ÎÔ˘Ó ÛÙȘ ÚÔ¸Ôı¤ÛÂȘ ‰ÈÂÓ¤ÚÁÂÈ·˜ Ë·ÙÈ΋˜ ÌÂÙ·ÌfiÛ¯Â˘Û˘. OÈ ÚÔ¸Ôı¤ÛÂȘ ‰ÈÂÓ¤ÚÁÂÈ·˜ ÌÂÙ·ÌfiÛ¯Â˘Û˘ ηٿ Milan ‰ÂÈÎÓ‡Ô˘Ó ÙËÓ Èı·ÓfiÙËÙ· ÂÈ‚›ˆÛ˘ ÙÔ˘ ·ÛıÂÓÔ‡˜ Ì ∏∫∫ ÁÈ· ÂÚÈÛÛfiÙÂÚÔ ·fi ¤ÓÙ ¯ÚfiÓÈ· ‡ÛÙÂÚ· ·fi ÌÂÙ·ÌfiÛ¯Â˘ÛË ‹·ÙÔ˜, Ì ‹ ¯ˆÚ›˜ ÚÔÌÂÙ·ÌÔÛ¯Â˘ÙÈÎfi ¯ËÌÂÈÔÂÌ‚ÔÏÈÛÌfi4. ™ÙȘ ÚÔ¸Ôı¤ÛÂȘ ηٿ Milan ·Ó‹ÎÔ˘Ó: ·) ∏ ‡·ÚÍË ÌÔÓ‹ÚÔ˘˜ fiÁÎÔ˘ ̤ÁÈÛÙ˘ ‰È·Ì¤ÙÚÔ˘ ≤ 5 ÂηÙÔÛÙ¿ ‹ Ë ‡·ÚÍË ¤ˆ˜ Î·È 3 fiÁÎˆÓ ÂÎ ÙˆÓ ÔÔ›ˆÓ Ë ‰È¿ÌÂÙÚÔ˜ ÙÔ˘ ÌÂÁ·Ï‡ÙÂÚÔ˘ ‰ÂÓ Ú¤ÂÈ Ó· ˘ÂÚ‚·›ÓÂÈ Ù· 3 ÂηÙÔÛÙ¿. ‚) ∏ ·Ô˘Û›· ·ÁÁÂÈ·ÎÒÓ ‰ÈËı‹ÛˆÓ. Á) ∏ ·Ô˘Û›· ÏÂÌÊ·‰ÂÓÈÎÒÓ ‹ ·ÈÌ·ÙÔÁÂÓÒÓ ÌÂÙ·-
85
ÛÙ¿ÛˆÓ. ŸÙ·Ó ÙËÚÔ‡ÓÙ·È ÔÈ ÚÔ¸Ôı¤ÛÂȘ ηٿ Milan, Ë ÚÔ‚ÏÂfiÌÂÓË ÂÙ‹ÛÈ· ÂÈ‚›ˆÛË ·Ó¤Ú¯ÂÙ·È ÛÙÔ 90%, ÂÓÒ Ë ÚÔ‚ÏÂfiÌÂÓË ÂÓÙ·ÂÙ‹˜ ÂÈ‚›ˆÛË ˘ÂÚ‚·›ÓÂÈ ÙÔ 70% (75% ÙÂÙÚ·ÂÙ‹˜ ÂÈ‚›ˆÛË). OÈ ÚÔ¸Ôı¤ÛÂȘ ‰ÈÂÓ¤ÚÁÂÈ·˜ ÌÂÙ·ÌfiÛ¯Â˘Û˘ ηٿ UCSF ‰ÂÈÎÓ‡Ô˘Ó ÙËÓ Èı·ÓfiÙËÙ· ÂÈ‚›ˆÛ˘ ÙÔ˘ ·ÛıÂÓÔ‡˜ Ì ∏∫∫ ÁÈ· ÂÚÈÛÛfiÙÂÚÔ ·fi ¤ÓÙ ¯ÚfiÓÈ· ‡ÛÙÂÚ· ·fi ÌÂÙ·ÌfiÛ¯Â˘ÛË ‹·ÙÔ˜, Ì ‹ ¯ˆÚ›˜ ÚÔÌÂÙ·ÌÔÛ¯Â˘ÙÈÎfi ¯ËÌÂÈÔÂÌ‚ÔÏÈÛÌfi21. ™ÙȘ ÚÔ¸Ôı¤ÛÂȘ ηٿ UCSF ·Ó‹ÎÔ˘Ó: ·) ∏ ‡·ÚÍË ÌÔÓ‹ÚÔ˘˜ fiÁÎÔ˘ ̤ÁÈÛÙ˘ ‰È·Ì¤ÙÚÔ˘ ≤ 6,5 ÂηÙÔÛÙ¿ ‹ Ë ‡·ÚÍË ¤ˆ˜ Î·È 3 fiÁÎˆÓ ÂÎ ÙˆÓ ÔÔ›ˆÓ Ë ‰È¿ÌÂÙÚÔ˜ ÙÔ˘ ÌÂÁ·Ï‡ÙÂÚÔ˘ ‰ÂÓ Ú¤ÂÈ Ó· ˘ÂÚ‚·›ÓÂÈ Ù· 4,5 ÂηÙÔÛÙ¿ Î·È Ë Û˘ÓÔÏÈ΋ ÙÔ˘˜ ‰È¿ÌÂÙÚÔ˜ ‰ÂÓ Ú¤ÂÈ Ó· ˘ÂÚ‚·›ÓÂÈ Ù· 8 ÂηÙÔÛÙ¿. ‚) ∏ ·Ô˘Û›· ·ÁÁÂÈ·ÎÒÓ ‰ÈËı‹ÛˆÓ. Á) ∏ ·Ô˘Û›· ÏÂÌÊ·‰ÂÓÈÎÒÓ ‹ ·ÈÌ·ÙÔÁÂÓÒÓ ÌÂÙ·ÛÙ¿ÛˆÓ. ŸÙ·Ó ÙËÚÔ‡ÓÙ·È ÔÈ ÚÔ¸Ôı¤ÛÂȘ ηٿ UCSF, Ë ÚÔ‚ÏÂfiÌÂÓË ÂÙ‹ÛÈ· ÂÈ‚›ˆÛË ·Ó¤Ú¯ÂÙ·È ÛÙÔ 91%, ÂÓÒ Ë ÚÔ‚ÏÂfiÌÂÓË ÂÓÙ·ÂÙ‹˜ ÊÙ¿ÓÂÈ ÛÙÔ 72%. ΔÔ ÔÛÔÛÙfi ÙˆÓ ·ÛıÂÓÒÓ Ô˘ ·Ú·¤ÌÂÙ·È Û ÌÂÙ·ÌfiÛ¯Â˘ÛË Ì ÙȘ ‰ÈÂ˘Ú˘Ì¤Ó˜ ·˘Ù¤˜ ÚÔ¸Ôı¤ÛÂȘ ‰ÂÓ ˘ÂÚ‚·›ÓÂÈ ÙÔ 5% ÂÎÂ›ÓˆÓ Ô˘ ÂÈϤÁÔÓÙ·È Ì ‚¿ÛË ÙȘ ÚÔ¸Ôı¤ÛÂȘ ηٿ Milan22. OÈ ÚÔ¸Ôı¤ÛÂȘ ‰ÈÂÓ¤ÚÁÂÈ·˜ ÌÂÙ·ÌfiÛ¯Â˘Û˘ ηٿ Barcelona ‰ÂÈÎÓ‡Ô˘Ó ÙËÓ Èı·ÓfiÙËÙ· ÂÈ‚›ˆÛ˘ ÙÔ˘ ·ÛıÂÓÔ‡˜ Ì ∏∫∫ ÁÈ· ÂÚÈÛÛfiÙÂÚÔ ·fi ¤ÓÙ ¯ÚfiÓÈ· ‡ÛÙÂÚ· ·fi ÌÂÙ·ÌfiÛ¯Â˘ÛË ‹·ÙÔ˜, Ì ÚÔÌÂÙ·ÌÔÛ¯Â˘ÙÈÎfi ¯ËÌÂÈÔÂÌ‚ÔÏÈÛÌfi23. ™ÙȘ ÚÔ¸Ôı¤ÛÂȘ ηٿ Barcelona ·Ó‹ÎÔ˘Ó: ·) ∏ ‡·ÚÍË ÌÔÓ‹ÚÔ˘˜ fiÁÎÔ˘ ̤ÁÈÛÙ˘ ‰È·Ì¤ÙÚÔ˘ ≤ 7 ÂηÙÔÛÙ¿ ‹ Ë ‡·ÚÍË ¤ˆ˜ Î·È 3 fiÁÎˆÓ ÂÎ ÙˆÓ ÔÔ›ˆÓ Ë ‰È¿ÌÂÙÚÔ˜ ÙÔ˘ ÌÂÁ·Ï‡ÙÂÚÔ˘ ‰ÂÓ Ú¤ÂÈ Ó· ˘ÂÚ‚·›ÓÂÈ Ù· 5 ÂηÙÔÛÙ¿ ‹ Ë ‡·ÚÍË ¤ˆ˜ Î·È 5 fiÁÎˆÓ ÂÎ ÙˆÓ ÔÔ›ˆÓ Ë ‰È¿ÌÂÙÚÔ˜ ÙÔ˘ ÌÂÁ·Ï‡ÙÂÚÔ˘ ‰ÂÓ Ú¤ÂÈ Ó· ˘ÂÚ‚·›ÓÂÈ Ù· 3 ÂηÙÔÛÙ¿. ‚) ∏ ·Ô˘Û›· ·ÁÁÂÈ·ÎÒÓ ‰ÈËı‹ÛˆÓ. Á) ∏ ·Ô˘Û›· ÏÂÌÊ·‰ÂÓÈÎÒÓ ‹ ·ÈÌ·ÙÔÁÂÓÒÓ ÌÂÙ·ÛÙ¿ÛˆÓ. ŸÙ·Ó ÙËÚÔ‡ÓÙ·È ÔÈ ÚÔ¸Ôı¤ÛÂȘ ηٿ Barcelona, Ë ÚÔ‚ÏÂfiÌÂÓË ÂÓÙ·ÂÙ‹˜ ÂÈ‚›ˆÛË ÊÙ¿ÓÂÈ ÛÙÔ 50%.
iv. ªÂÌÔӈ̤ÓÔÈ ‰Â›ÎÙ˜ Ÿˆ˜ ¤¯ÂÈ ‹‰Ë ·Ó·ÊÂÚı›, ÛÙÔ˘˜ ÌÂÌÔӈ̤ÓÔ˘˜ ‰Â›ÎÙ˜ ·Ó‹ÎÔ˘Ó ÔÈ DCP, VEGF-P Î·È FAL. ™‡Ìʈӷ Ì ÙÔ ‰Â›ÎÙË DCP24, ÔÈ ·ÛıÂÓ›˜ Ì ∏∫∫ Ô˘ ˘Ô‚Ï‹ıËÎ·Ó Û ˷ÙÂÎÙÔÌ‹ ¯ˆÚ›˙ÔÓÙ·È Û ÙÚÂȘ ÔÌ¿‰Â˜: ·) DCP < 40 mU/ml. ‚) DCP ≥ 40 mU/ml Î·È ·Ó·ÏÔÁ›· ªU-3:19B7 < 3. Á) DCP ≥ 40 mU/ml Î·È ·Ó·ÏÔÁ›· ªU-3:19B7 ≥
86
¢. μƒOÃπ¢∏™, ¢. Δ∞∫OÀ¢∞™
3. ∫·Ï‡ÙÂÚË ÂÈ‚›ˆÛË ·ÚÔ˘ÛÈ¿˙Ô˘Ó ÔÈ ·ÛıÂÓ›˜ Ù˘ ÚÒÙ˘ ÔÌ¿‰·˜. ∏ Èı·ÓfiÙËÙ· ı·Ó¿ÙÔ˘ ÁÈ· ÙÔ˘˜ ·ÚÚÒÛÙÔ˘˜ Ù˘ ‰Â‡ÙÂÚ˘ ÔÌ¿‰·˜ Â›Ó·È ·˘ÍË̤ÓË Î·Ù¿ 2,87 ÊÔÚ¤˜ (p = 0.012). Δ¤ÏÔ˜, Ë Èı·ÓfiÙËÙ· ı·Ó¿ÙÔ˘ ÁÈ· ÙÔ˘˜ ·ÛıÂÓ›˜ Ù˘ ÙÚ›Ù˘ ÔÌ¿‰·˜ Â›Ó·È ·˘ÍË̤ÓË Î·Ù¿ 12,3 ÊÔÚ¤˜ (p < 0.0001). O VEGF-P ·Ó‹ÎÂÈ ÛÙËÓ Î·ÙËÁÔÚ›· ÙˆÓ ÌÔÚÈ·ÎÒÓ ÁÂÓÂÙÈÎÒÓ ‰ÂÈÎÙÒÓ. ™¯ÂÙ›˙ÂÙ·È Ì ÙËÓ ·Ó›¯Ó¢ÛË Û˘ÁÎÂÎÚÈÌ¤ÓˆÓ ÔÏ˘ÌÔÚÊÈÛÌÒÓ ÙÔ˘ ÁÔÓȉ›Ô˘ ÙÔ˘ VEGF. ™‡Ìʈӷ Ì ÙÔ ‰Â›ÎÙË VEGF-P25, ÔÈ ·ÛıÂÓ›˜ Ì ∏∫∫ Ô˘ ˘Ô‚Ï‹ıËÎ·Ó Û ηٿÏÏËÏË ıÂڷ›· ¤¯Ô˘Ó ¯ÂÈÚfiÙÂÚÔÈ ÚfiÁÓˆÛË ·Ó: ·) ¤¯Ô˘Ó ÙÔ ÁÔÓfiÙ˘Ô -634CC (HRs 0,67, 95%CI: 0,46-0,99). ‚) ¤¯Ô˘Ó ÙÔÓ ·ÏfiÙ˘Ô 1 (HRs 0,57, 95%CI: 0,36-0,92). ª¤¯ÚÈ Û‹ÌÂÚ· ¤¯Ô˘Ó Û˘ÓÔÏÔο ·ÓȯÓ¢ı› 19 ÁÔÓfiÙ˘ÔÈ Î·È 36 ·ÏfiÙ˘ÔÈ ÙÔ˘ ÁÔÓȉ›Ô˘ ÙÔ˘ VEGF. O FAL ·Ó‹ÎÂÈ ÛÙËÓ Î·ÙËÁÔÚ›· ÙˆÓ ÌÔÚÈ·ÎÒÓ ÁÂÓÂÙÈÎÒÓ ‰ÂÈÎÙÒÓ (26). ∞·ÈÙ› ‚ÈÔ„›· ÙÔ˘ Ë·ÙÈÎÔ‡ fiÁÎÔ˘. ™¯ÂÙ›˙ÂÙ·È Ì ÙËÓ ·Ó›¯Ó¢ÛË ÙˆÓ ÁÔÓȉ›ˆÓ Û 9 ¯ÚˆÌÔۈ̷ÙÈÎÔ‡˜ ÌÈÎÚÔ‰ÔÚ˘ÊfiÚÔ˘˜. ∞Ó¿ÏÔÁ· Ì ÙÔ ÔÛÔÛÙfi ÙˆÓ 9 ¯ÚˆÌÔۈ̷ÙÈÎÒÓ ‰ÔÚ˘ÊfiÚˆÓ Ô˘ ¤¯Ô˘Ó ˘ÔÛÙ› FAL, ÔÈ ·ÛıÂÓ›˜ Ì ∏∫∫ Ô˘ ¤¯Ô˘Ó ˘Ô‚ÏËı› Û ÌÂÙ·ÌfiÛ¯Â˘ÛË ‹·ÙÔ˜ ¯ˆÚ›˙ÔÓÙ·È Û ÙÚÂȘ ÔÌ¿‰Â˜: ·) ∞ÛıÂÓ›˜ Ì FAL ≤ 20%. ‚) ∞ÛıÂÓ›˜ Ì FAL 21% - 40%. Á) ∞ÛıÂÓ›˜ Ì FAL ≥ 40%. O ̤ÛÔ˜ ¯ÚfiÓÔ˜ ÂÈ‚›ˆÛ˘ Â›Ó·È 15,2 ¯ÚfiÓÈ· ÁÈ· ÙËÓ ÚÒÙË ÔÌ¿‰·, 8,5 ¯ÚfiÓÈ· ÁÈ· ÙË ‰Â‡ÙÂÚË ÔÌ¿‰· (ÂÓÙ·ÂÙ‹˜ ÂÈ‚›ˆÛË: 60%) Î·È 3,7 ¯ÚfiÓÈ· ÁÈ· ÙËÓ ÙÚ›ÙË ÔÌ¿‰·. ΔÔ ÔÛÔÛÙfi ÙˆÓ ·ÛıÂÓÒÓ Ô˘ ·Ú·¤ÌÂÙ·È Û ÌÂÙ·ÌfiÛ¯Â˘ÛË, ·Ó ÛÙÔ˘˜ Ï‹Ù˜ Û˘ÌÂÚÈÏËÊıÔ‡Ó ¿ÚÚˆÛÙÔÈ Ù˘ ÚÒÙ˘ Î·È ‰Â‡ÙÂÚ˘ ÔÌ¿‰·˜, ˘ÂÚ‚·›ÓÂÈ ÙÔ 20% (21.6%) ÂÎÂ›ÓˆÓ Ô˘ ÂÈϤÁÔÓÙ·È Ì ‚¿ÛË ÙȘ ÚÔ¸Ôı¤ÛÂȘ ηٿ Milan.
5. ∏ Ê˘ÛÈ΋ ÈÛÙÔÚ›· ÙÔ˘ ∏∫∫ i. ∏ Ê˘ÛÈ΋ ÈÛÙÔÚ›· ÙÔ˘ ∏∫∫ ¯ˆÚ›˜ ıÂڷ›· ∏ ÂÈ‚›ˆÛË ÂÓfi˜ ·ÛıÂÓÔ‡˜ Ì ∏∫∫ ¯ˆÚ›˜ ΛÚÚˆÛË ÂÍ·ÚÙ¿Ù·È ‚¤‚·È· ·fi ÙÔ Î·ÚÎÈÓÈÎfi ÊÔÚÙ›Ô, fiˆ˜ ·˘Ùfi ηıÔÚ›˙ÂÙ·È ·fi ÙÔ Û‡ÛÙËÌ· AJCC16. ∂Ó‰ÂÈÎÙÈο ·Ó·Ê¤ÚÂÙ·È fiÙÈ Ô ·ÛıÂÓ‹˜ Ô˘ ¤¯ÂÈ ‰È·ÁÓˆÛı› Ì ∏∫∫ < 5cm ¤¯ÂÈ, ¯ˆÚ›˜ ıÂڷ›·, ÂÙ‹ÛÈ· ÂÈ‚›ˆÛË 90%, ÂÊfiÛÔÓ ‰ÂÓ Â›Ó·È ÎÈÚÚˆÙÈÎfi˜. º˘ÛÈο, Ë ‡·ÚÍË Î›ÚÚˆÛ˘ ÂÏ·ÙÙÒÓÂÈ ÙËÓ ÂÈ‚›ˆÛË ÙÔ˘ ·ÚÚÒÛÙÔ˘, ÌÔÚ› ‰Â Ó· ˘ÔÏÔÁÈÛÙ› ηٿ ÚÔÛ¤ÁÁÈÛË Ì ÙË ¯Ú‹ÛË Ù˘ ‚·ıÌÔÏÔÁ›·˜ MELD12. ŒÙÛÈ, Ô ·ÓÙ›ÛÙÔȯԘ ·ÛıÂÓ‹˜ ¤¯ÂÈ, ¯ˆÚ›˜ ıÂڷ›·, ÂÙ‹ÛÈ· ÂÈ‚›ˆÛË 80%, ÂÊfiÛÔÓ Â›Ó·È
ÎÈÚÚˆÙÈÎfi˜ ÛÙ·‰›Ô˘ ∞ ηٿ Child. O ›‰ÈÔ˜ ·ÛıÂÓ‹˜ ¤¯ÂÈ, ¯ˆÚ›˜ ıÂڷ›·, ÂÙ‹ÛÈ· ÂÈ‚›ˆÛË 20%, ÂÊfiÛÔÓ Â›Ó·È ÎÈÚÚˆÙÈÎfi˜ ÛÙ·‰›Ô˘ μ ηٿ Child27. ∏ ÚÔ‚ÏÂfiÌÂÓË ÂÈ‚›ˆÛË ÂÓfi˜ ·ÛıÂÓÔ‡˜ Ì ∏∫∫ Î·È Î›ÚÚˆÛË ÌÔÚ› Ó· ˘ÔÏÔÁÈÛÙ› Ì ÙË ¯Ú‹ÛË Î¿ÔÈˆÓ ·fi Ù· ÚÔ·Ó·ÊÂÚfiÌÂÓ· ˘ÔÏÔÁÈÛÙÈο ÂÚÁ·Ï›· (.¯. CLIP, CUPI, ÎÙÏ).
ii. ∏ Ê˘ÛÈ΋ ÈÛÙÔÚ›· ÙÔ˘ ∏∫∫ ‡ÛÙÂÚ· ·fi Ë·ÙÂÎÙÔÌ‹ ∏ Ê˘ÛÈ΋ ÈÛÙÔÚ›· ÙÔ˘ ∏∫∫ ‡ÛÙÂÚ· ·fi Ë·ÙÂÎÙÔÌ‹ ÂÍ·ÚÙ¿Ù·È Î˘Ú›ˆ˜ ·fi Ù· ¯·Ú·ÎÙËÚÈÛÙÈο ÙÔ˘ fiÁÎÔ˘ Î·È fi¯È ·fi ÙË ‚·Ú‡ÙËÙ· Ù˘ ΛÚÚˆÛ˘ (fiÙ·Ó ·˘Ù‹ Û˘Ó˘¿Ú¯ÂÈ). ∞˘Ùfi Û˘Ì‚·›ÓÂÈ ÁÈ·Ù› ÔÙ¤ ۯ‰fiÓ ‰Â ‰ÈÂÓÂÚÁÔ‡ÓÙ·È Ë·ÙÂÎÙÔ̤˜ Û ·ÛıÂÓ›˜ Ô˘ ˘ÂÚ‚·›ÓÔ˘Ó ÙÔ ÛÙ¿‰ÈÔ ∞ ηٿ Child. Ÿˆ˜ ÚԷӷʤÚıËÎÂ, Ë ÚfiÁÓˆÛË Ù˘ ÂÈ‚›ˆÛ˘ ‡ÛÙÂÚ· ·fi ÙËÓ ¯ÂÈÚÔ˘ÚÁÈ΋ ¤̂·ÛË Á›ÓÂÙ·È Ì ÙË ¯Ú‹ÛË ˘ÔÏÔÁÈÛÙÈÎÒÓ ÂÚÁ·Ï›ˆÓ (AJCC, Okuda, ÎÙÏ). ŒÙÛÈ, ·Ó¿ÏÔÁ· Ì ÙÔ Ì¤ÁÂıÔ˜ ÙÔ˘ fiÁÎÔ˘, Ë ÂÓÙ·ÂÙ‹˜ ÂÈ‚›ˆÛË ‡ÛÙÂÚ· ·fi Ë·ÙÂÎÙÔÌ‹ ÛÙÔ ÌË ÎÈÚÚˆÙÈÎfi ·ÛıÂÓ‹ Ì ∏∫∫ Î˘Ì·›ÓÂÙ·È ·fi 64% (ÛÙ¿‰ÈÔ π) ¤ˆ˜ 17% ÛÙ¿‰ÈÔ (πππ∞). ∞ÓÙ›ÛÙÔȯ·, Ë ÂÓÙ·ÂÙ‹˜ ÂÈ‚›ˆÛË ‡ÛÙÂÚ· ·fi Ë·ÙÂÎÙÔÌ‹ ÛÙÔÓ ÎÈÚÚˆÙÈÎfi ·ÛıÂÓ‹ Ì ∏∫∫ Î˘Ì·›ÓÂÙ·È ·fi 49% (ÛÙ¿‰ÈÔ π) ¤ˆ˜ 9% ÛÙ¿‰ÈÔ (πππ∞).
iii. ∏ Ê˘ÛÈ΋ ÈÛÙÔÚ›· ÙÔ˘ ∏∫∫ ‡ÛÙÂÚ· ·fi ÂÚÔ¯ÈΤ˜, ÌË ¯ÂÈÚÔ˘ÚÁÈΤ˜ ıÂڷ›˜ ™ÙȘ ÂÚÈÔ¯ÈΤ˜, ÌË ¯ÂÈÚÔ˘ÚÁÈΤ˜ ıÂڷ›˜ ÙÔ˘ ∏∫∫ Û˘ÌÂÚÈÏ·Ì‚¿ÓÔÓÙ·È Ë ¤Á¯˘ÛË ·Èı·ÓfiÏ˘, Ë ÎÚ˘Ô¯ÂÈÚÔ˘ÚÁÈ΋, Ë ıÂÚÌÈ΋ ηٷÛÙÚÔÊ‹ Ì ڷ‰ÈÔ·̷ٷ, Ô ·ÚÙËÚÈ·Îfi˜ ÂÌ‚ÔÏÈÛÌfi˜ Î·È Ô ·ÚÙËÚÈ·Îfi˜ ¯ËÌÂÈÔÂÌ‚ÔÏÈÛÌfi˜. ™˘¯ÓfiÙÂÚ· ¯ÚËÛÈÌÔÔÈÔ‡ÓÙ·È Ë ıÂÚÌÈ΋ ηٷÛÙÚÔÊ‹ Î·È Ô ·ÚÙËÚÈ·Îfi˜ ¯ËÌÂÈÔÂÌ‚ÔÏÈÛÌfi˜. ªË ÎÈÚÚˆÙÈÎÔ› ·ÛıÂÓ›˜ ‹ ·ÛıÂÓ›˜ Ì ΛÚÚˆÛË ÛÙ·‰›Ô˘ ∞ ηٿ Child Û¿ÓÈ· ‰ÂÓ Î·Ù·Ï‹ÁÔ˘Ó ÛÙÔ ¯ÂÈÚÔ˘ÚÁ›Ô. ∞fi ·˘ÙÔ‡˜ Ô˘ ‰ÂÓ Ô‰ËÁÔ‡ÓÙ·È Û ˷ÙÂÎÙÔÌ‹ ‹ Û ÌÂÙ·ÌfiÛ¯Â˘ÛË (Û˘Ó‹ıˆ˜ ÏfiÁˆ ¿ÚÓËÛ˘ ÙÔ˘ ·ÚÚÒÛÙÔ˘), fiÛÔÈ ˘Ô‚¿ÏÔÓÙ·È Û ıÂÚÌÈ΋ ηٷÛÙÚÔÊ‹ Ì ڷ‰ÈÔ·̷ٷ, ÂȉÂÈÎÓ‡Ô˘Ó ÂÙ‹ÛÈ· Î·È ÙÚÈÂÙ‹ ÂÈ‚›ˆÛË 100% Î·È 72.7% ·ÓÙ›ÛÙÔȯ· 28. ∂ÈϤÔÓ, ·ÛıÂÓ›˜ Ì ΛÚÚˆÛË ÛÙ·‰›Ô˘ μ ηٿ Child, ÔÈ ÔÔ›ÔÈ ‰ÂÓ Ô‰ËÁÔ‡ÓÙ·È Û ˷ÙÈ΋ ÌÂÙ·ÌfiÛ¯Â˘ÛË ·ÏÏ¿ ˘Ô‚¿ÏÔÓÙ·È Û ηٷÛÙÚÔÊ‹ Ì ڷ‰ÈÔ·̷ٷ, ¤¯Ô˘Ó ÂÙ‹ÛÈ· Î·È ÙÚÈÂÙ‹ ÂÈ‚›ˆÛË 60% Î·È 20% ·ÓÙ›ÛÙÔȯ·29. ¡·
METAMO™XEY™Eπ™ 2008
ÛËÌÂȈı› fiÙÈ Ë Ì¤ÁÈÛÙË ‰È¿ÌÂÙÚÔ˜ ÙÔ˘ ∏∫∫ ÛÙȘ ÌÂϤÙ˜ Ô˘ ·Ô‰›‰Ô˘Ó Ù· Û˘ÁÎÂÎÚÈ̤ӷ ÔÛÔÛÙ¿ ÂÈ‚›ˆÛ˘ Â›Ó·È 4 ÂηÙÔÛÙ¿. ∞ÛıÂÓ›˜ Ì ΛÚÚˆÛË ÛÙ·‰›Ô˘ ∞ ηٿ Child, ÔÈ ÔÔ›ÔÈ ‰ÂÓ Ô‰ËÁÔ‡ÓÙ·È Û ˷ÙÂÎÙÔÌ‹ ‹ Û ÌÂÙ·ÌfiÛ¯Â˘ÛË ·ÏÏ¿ ˘Ô‚¿ÏÔÓÙ·È Û ·ÚÙËÚÈ·Îfi ¯ËÌÂÈÔÂÌ‚ÔÏÈÛÌfi, ÂȉÂÈÎÓ‡Ô˘Ó ÂÙ‹ÛÈ· Î·È ‰ÈÂÙ‹ ÂÈ‚›ˆÛË 82% Î·È 63% ·ÓÙ›ÛÙÔȯ· 30 . ∂ÈϤÔÓ, ·ÛıÂÓ›˜ Ì ΛÚÚˆÛË ÛÙ·‰›Ô˘ μ ηٿ Child, ÔÈ ÔÔ›ÔÈ ‰ÂÓ Ô‰ËÁÔ‡ÓÙ·È Û ˷ÙÈ΋ ÌÂÙ·ÌfiÛ¯Â˘ÛË ·ÏÏ¿ ˘Ô‚¿ÏÔÓÙ·È Û ·ÚÙËÚÈ·Îfi ¯ËÌÂÈÔÂÌ‚ÔÏÈÛÌfi, ¤¯Ô˘Ó ÂÙ‹ÛÈ· Î·È ÙÚÈÂÙ‹ ÂÈ‚›ˆÛË 57% Î·È 31% ·ÓÙ›ÛÙÔȯ·31. ¡· ÛËÌÂȈı› fiÙÈ ‰ÂÓ ˘¿Ú¯ÂÈ ÂÚÈÔÚÈÛÌfi˜ ̤ÁÈÛÙ˘ ‰È·Ì¤ÙÚÔ˘ ÙÔ˘ ∏∫∫ ÛÙȘ ÌÂϤÙ˜ Ô˘ ·Ô‰›‰Ô˘Ó Ù· Û˘ÁÎÂÎÚÈ̤ӷ ÔÛÔÛÙ¿ ÂÈ‚›ˆÛ˘.
iv. ∏ Ê˘ÛÈ΋ ÈÛÙÔÚ›· ÙÔ˘ ∏∫∫ ‡ÛÙÂÚ· ·fi Û˘ÛÙËÌ·ÙÈΤ˜ ıÂڷ›˜ ∏ ÌÔÓ·‰È΋ Û˘ÛÙËÌ·ÙÈ΋ ıÂڷ›· Ô˘ ·Ô‰Â‰ÂÈÁ̤ӷ ·˘Í¿ÓÂÈ ÙËÓ ÂÈ‚›ˆÛË ÙˆÓ ÎÈÚÚˆÙÈÎÒÓ ·ÛıÂÓÒÓ Ì ∏∫∫ Â›Ó·È Ë ¯Ú‹ÛË Ù˘ ÛÔÚ·ÊÂÓ›‰Ë˜ (sorafenib). ™˘ÁÎÂÎÚÈ̤ӷ, Ë ÂÈ‚›ˆÛË ·ÛıÂÓÒÓ Ì ΛÚÚˆÛË ÛÙ·‰›Ô˘ ∞ ηٿ Child Î·È ∏∫∫, ÔÈ ÔÔ›ÔÈ ‰ÂÓ Âȉ¤¯ÔÓÙ·È Ë·ÙÂÎÙÔÌ‹ ‹ ÌÂÙ·ÌfiÛ¯Â˘ÛË (Û˘Ó‹ıˆ˜ ÏfiÁˆ ÔÏÏ·ÏfiÙËÙ·˜ ÙˆÓ fiÁÎˆÓ ‹ ·ÁÁÂȷ΋˜ ‰È‹ıËÛ˘), ·˘Í¿ÓÂÈ Î·Ù¿ 44%, fiÙ·Ó Û˘ÁÎÚ›ÓÂÙ·È Ì ÙËÓ ÂÈ‚›ˆÛË ·ÓÙ›ÛÙÔȯˆÓ Ë·ÙÔ·ıÒÓ Ô˘ Ï·Ì‚¿ÓÔ˘Ó ·ÚËÁÔÚÈ΋ ÌfiÓÔ ıÂڷ›·32.
v. ∏ Ê˘ÛÈ΋ ÈÛÙÔÚ›· ÙÔ˘ ∏∫∫ ‡ÛÙÂÚ· ·fi ÌÂÙ·ÌfiÛ¯Â˘ÛË ‹·ÙÔ˜ ∏ ÌÂÁ·Ï‡ÙÂÚË ÛÂÈÚ¿ ·ÛıÂÓÒÓ Ì ∏∫∫ ‡ÛÙÂÚ· ·fi ÌÂÙ·ÌfiÛ¯Â˘ÛË ‹·ÙÔ˜ (n = 985) ‚Ú›ÛÎÂÙ·È ÛÙË ‚¿ÛË ‰Â‰ÔÌ¤ÓˆÓ ÙÔ˘ UNOS33. ∞fi ·Ó¿Ï˘ÛË ÙˆÓ Û¯ÂÙÈÎÒÓ ÛÙÔȯ›ˆÓ ÚÔ·ÙÂÈ fiÙÈ Ë ÂÓÙ·ÂÙ‹˜ ÂÈ‚›ˆÛË ÙˆÓ ·ÚÚÒÛÙˆÓ ·˘ÙÒÓ ·Ó¤Ú¯ÂÙ·È ÛÙÔ 61%. ™ÙËÓ ›‰È· ‚¿ÛË ‰Â‰Ô̤ӈÓ, Ë ÂÓÙ·ÂÙ‹˜ ÂÈ‚›ˆÛË ÙˆÓ ·ÛıÂÓÒÓ Ô˘ ˘Ô‚Ï‹ıËÎ·Ó Û ÌÂÙ·ÌfiÛ¯Â˘ÛË ‹·ÙÔ˜ ÁÈ· ¿ÏÏË ·ÈÙ›· (n = 33339) ·Ó¤Ú¯ÂÙ·È ÛÙÔ 75%. Ÿˆ˜ ·Ó·Ê¤ÚıËΠ·Ú·¿Óˆ, Â›Ó·È ‰˘Ó·Ùfi Ó· ÂÈϤÁÔÓÙ·È ·ÛıÂÓ›˜ Ì ‚¿ÛË Û˘ÁÎÂÎÚÈ̤ӷ ˘ÔÏÔÁÈÛÙÈο ÂÚÁ·Ï›·, ¤ÙÛÈ ÒÛÙ ӷ ÂÈÙ˘Á¯¿ÓÂÙ·È Ë ÂÈı˘ÌËÙ‹ ÂÓÙ·ÂÙ‹˜ ÂÈ‚›ˆÛË. O˘ÛÈ·ÛÙÈο ‰ËÏ·‰‹, ·ÔÎÏ›ÔÓÙ·˜ ÔÚÈṲ̂ÓÔ˘˜ ·ÛıÂÓ›˜ ·fi ÙË Ï›ÛÙ· ·Ó·ÌÔÓ‹˜, “ηٷÛ΢¿˙Ô˘Ì” ÙËÓ ÂÈı˘ÌËÙ‹ η̇ÏË Ê˘ÛÈ΋˜ ÈÛÙÔÚ›·˜ ÙÔ˘ ·ÚÚÒÛÙÔ˘ Ì ∏∫∫ ‡ÛÙÂÚ· ·fi ÌÂÙ·ÌfiÛ¯Â˘ÛË ‹·ÙÔ˜. ™˘ÁÎÂ-
87
ÎÚÈ̤ӷ, fiÙ·Ó ÙËÚÔ‡ÓÙ·È ÔÈ ÚÔ¸Ôı¤ÛÂȘ ÌÂÙ·ÌfiÛ¯Â˘Û˘ ηٿ Milan ‹ ηٿ UCSF, Ë ÚÔ‚ÏÂfiÌÂÓË ÂÓÙ·ÂÙ‹˜ ÂÈ‚›ˆÛË ˘ÂÚ‚·›ÓÂÈ ÙÔ 70%. ŸÙ·Ó ÙËÚÔ‡ÓÙ·È ÔÈ ÚÔ¸Ôı¤ÛÂȘ ηٿ Barcelona, Ë ÚÔ‚ÏÂfiÌÂÓË ÂÓÙ·ÂÙ‹˜ ÂÈ‚›ˆÛË ÊÙ¿ÓÂÈ ÛÙÔ 50%. ŸÙ·Ó ‰ÂÓ Ù›ıÔÓÙ·È Î¿ÔȘ ÚÔ¸Ôı¤ÛÂȘ ÌÂÙ·ÌfiÛ¯Â˘Û˘, Ë ÚÔ‚ÏÂfiÌÂÓË ÂÓÙ·ÂÙ‹˜ ÂÈ‚›ˆÛË Â›Ó·È 11,2%, ÂÓÒ Ë ÏÂÈÔ„ËÊ›· ÙˆÓ ˘ÔÙÚÔÒÓ ÙÔ˘ ∏∫∫ (75%) ·ÚÔ˘ÛÈ¿˙ÔÓÙ·È Ì¤Û· ÛÙËÓ ÚÒÙË ‰ÈÂÙ›· ÌÂÙ¿ ÙËÓ ÌÂÙ·ÌfiÛ¯Â˘ÛË34.
6. ∏ ¿Ì‚Ï˘ÓÛË ÙˆÓ ÚÔ¸Ôı¤ÛÂˆÓ ÌÂÙ·ÌfiÛ¯Â˘Û˘ ÁÈ· ∏∫∫ ŸÙ·Ó ÂÊ·ÚÌfi˙ÔÓÙ·È ÚÔ¸Ôı¤ÛÂȘ ÌÂÙ·ÌfiÛ¯Â˘Û˘ Û ·ÛıÂÓ›˜ Ì ∏∫∫ (Milan, UCSF, ÎÙÏ), ÔÏÏÔ› ¿ÚÚˆÛÙÔÈ ‰ÂÓ ÚfiÎÂÈÙ·È Ó· ˘Ô‚ÏËıÔ‡Ó ÛÙË ÛˆÙ‹ÚÈ· ·˘Ù‹ ¤̂·ÛË ÁÈ·Ù›, ·Ó Î·È ¤¯Ô˘Ó ¤Ó‰ÂÈÍË (‚ÂÏÙ›ˆÛË ÂÈ‚›ˆÛ˘), ‰ÂÓ ÏËÚÔ‡Ó Ù· ÎÚÈÙ‹ÚÈ· (ÂÈ‚›ˆÛË ÙÔ˘Ï¿Á¯ÈÛÙÔÓ ›ÛË Ì ·˘Ù‹ ÙˆÓ ÌÂÙ·ÌÔÛ¯Â˘Ì¤ÓˆÓ ÁÈ· ¿ÏÏÔ˘˜, ÂÎÙfi˜ ∏∫∫, ÏfiÁÔ˘˜). ™˘ÁÎÂÎÚÈ̤ӷ, ۯ‰fiÓ ÔÈ ÌÈÛÔ› ÎÈÚÚˆÙÈÎÔ› Ì ∏∫∫ ‚Ú›ÛÎÔÓÙ·È ‹‰Ë ¤Ú·Ó ÙˆÓ ÚÔ¸Ôı¤ÛÂˆÓ Î·Ù¿ Milan ÙË ¯ÚÔÓÈ΋ ÛÙÈÁÌ‹ Ù˘ ‰È¿ÁÓˆÛ˘. ∂ÈϤÔÓ, ·ÎfiÌ· Î·È ·˘ÙÔ› Ô˘ Â›Ó·È ÂÓÙfi˜ ÙˆÓ ÚÔ¸Ôı¤ÛÂˆÓ Î·Ù¿ Milan, ÂΛÙÔ˘Ó ·˘ÙÒÓ Ì ڢıÌfi 4% ÙÔ Ì‹Ó·35. ŸÏÔÈ ·˘ÙÔ› ÔÈ ·ÛıÂÓ›˜ ÌÔÚÔ‡Ó Ó· ÌÂÙ·ÌÔÛ¯Â˘ıÔ‡Ó ·Ó ·Ì‚Ï˘ÓıÔ‡Ó ÔÈ Û¯ÂÙÈΤ˜ ÚÔ¸Ôı¤ÛÂȘ. ∏ ¿Ì‚Ï˘ÓÛË ÙˆÓ ÚÔ¸Ôı¤ÛÂˆÓ Á›ÓÂÙ·È Â›Ù Ì ˘ÔÛÙ·‰ÈÔÔ›ËÛË ÙˆÓ fiÁÎˆÓ (downstaging) ›Ù Ì ¯Ú‹ÛË ÔÚÈ·ÎÒÓ ÌÔÛ¯Â˘Ì¿ÙˆÓ Â›Ù Ì ¯Ú‹ÛË ÌÔÛ¯Â˘Ì¿ÙˆÓ ·fi ˙ÒÓÙ· ‰fiÙË Â›Ù Ì ¯Ú‹ÛË ÓÔÌÔÁÚ·ÌÌ¿ÙˆÓ Â˘¤ÏÈÎÙˆÓ ÎÚÈÙËÚ›ˆÓ. ∏ ˘ÔÛÙ·‰ÈÔÔ›ËÛË ÙˆÓ fiÁÎˆÓ Ô˘ ÍÂÂÚÓÔ‡Ó ÙȘ ‰Â‰Ô̤Ó˜ ÁÈ· ÙÔ ÂοÛÙÔÙ ΤÓÙÚÔ Ú¸Ôı¤ÛÂȘ ÌÂÙ·ÌfiÛ¯Â˘Û˘ (Milan, UCSF, ÎÙÏ) ÂÈÙ˘Á¯¿ÓÂÙ·È Ì ÙË ¯Ú‹ÛË ÂÚÈÔ¯ÈÎÒÓ ıÂÚ·ÂÈÒÓ, Û˘Ó‹ıˆ˜ TACE ‹ RFA (‹ Î·È Û˘Ó‰˘·ÛÌfi ·˘ÙÒÓ) Î·È Û·ÓÈfiÙÂÚ· Ë·ÙÂÎÙÔÌ‹˜. ™‡Ìʈӷ Ì ٷ ‰Â‰Ô̤ӷ ÙÔ˘ ¢ÈÂıÓÔ‡˜ ∫¤ÓÙÚÔ˘ ∞Ó·ÊÔÚ¿˜ ∏·ÙÈÎÒÓ ªÂÙ·ÌÔۯ‡ÛÂˆÓ ÁÈ· ∫·ÎÔ‹ıÂȘ ÙÔ˘ ◊·ÙÔ˜ (International Registry of Hepatic Tumors in Liver Transplantation) Ë ÂÓÙ·ÂÙ‹˜ ÂÈ‚›ˆÛË ·ÛıÂÓÒÓ ‡ÛÙÂÚ· ·fi ÌÂÙ·ÌfiÛ¯Â˘ÛË ‹·ÙÔ˜ Ô˘ ·ÎÔÏÔ‡ıËÛ ˘ÔÛÙ·‰ÈÔÔ›ËÛË Ì TACE, RFA ‹ Û˘Ó‰˘·ÛÌfi ÙÔ˘˜ ·Ó‹Ïı ÛÙÔ 69%, ÛËÌ·ÓÙÈο ˘„ËÏfiÙÂÚÔ ·fi ÙÔ 31% ÙˆÓ ·ÛıÂÓÒÓ ¯ˆÚ›˜ ˘ÔÛÙ·‰ÈÔÔ›ËÛË. ΔÔ fiÊÂÏÔ˜ ÛÙËÓ ÂÈ‚›ˆÛË ·fi ÙËÓ ˘ÔÛÙ·‰ÈÔÔ›ËÛË ‹Ù·Ó ÌÂÁ·Ï‡ÙÂÚÔ ÛÙÔ˘˜ ·ÚÚÒ-
88
¢. μƒOÃπ¢∏™, ¢. Δ∞∫OÀ¢∞™
ÛÙÔ˘˜ ÂÎÙfi˜ ÚÔ¸Ôı¤ÛÂˆÓ Î·Ù¿ Milan36. ∂ÈϤÔÓ, ˘ÔÛÙ·‰ÈÔÔ›ËÛË Ì ˷ÙÂÎÙÔÌ‹ (·Ó Â›Ó·È Ú·ÁÌ·ÙÔÔÈ‹ÛÈÌË) Û˘ÓÈÛÙ¿Ù·È ÌfiÓÔÓ ÂÊfiÛÔÓ Ë Èı·ÓfiÙËÙ· ·Ú·ÌÔÓ‹˜ ÛÙË Ï›ÛÙ· ˘ÂÚ‚·›ÓÂÈ ÙÔ˘˜ 18 Ì‹Ó˜37. ™Â οı ÂÚ›ÙˆÛË, ÌÂÙ¿ ÙËÓ ˘ÔÛÙ·‰ÈÔÔ›ËÛË Û˘ÁηÏÂ›Ù·È È·ÙÚÈÎfi Û˘Ì‚Ô‡ÏÈÔ ÁÈ· ÙËÓ ÙÂÏÈ΋ ·fiÊ·ÛË ÂÁÁÚ·Ê‹˜ ‹ fi¯È ÙÔ˘ ·ÛıÂÓÔ‡˜ ÛÙË Ï›ÛÙ· Ù˘ Ë·ÙÈ΋˜ ÌÂÙ·ÌfiÛ¯Â˘Û˘. H ¯Ú‹ÛË ÔÚÈ·ÎÒÓ ÌÔÛ¯Â˘Ì¿ÙˆÓ (ÌÔۯ‡̷ٷ Ô˘ ‰Â ı· ¯ÚËÛÈÌÔÔÈËıÔ‡Ó ·ÏÏÔ‡) Û ·ÛıÂÓ›˜ Ô˘ ÍÂÂÚÓÔ‡Ó ÙȘ ‰Â‰Ô̤Ó˜ ÁÈ· ÙÔ ÂοÛÙÔÙ ΤÓÙÚÔ Ú¸Ôı¤ÛÂȘ ÌÂÙ·ÌfiÛ¯Â˘Û˘ (Milan, UCSF, ÎÙÏ) Á›ÓÂÙ·È ÌfiÓÔÓ ‡ÛÙÂÚ· ·fi È·ÙÚÈÎfi Û˘Ì‚Ô‡ÏÈÔ Î·È ÌfiÓÔÓ ÂÊfiÛÔÓ ÂÓËÌÂÚˆı› Ï‹Úˆ˜ Ô ¿ÚÚˆÛÙÔ˜ Î·È Ë ÔÈÎÔÁ¤ÓÂÈ¿ ÙÔ˘. ¡· ÛËÌÂȈı› fiÙÈ ·Ó Ô Ï‹Ù˘ ÂÓfi˜ ÔÚÈ·ÎÔ‡ ÌÔۯ‡̷ÙÔ˜ ÍÂÂÚ¿ÛÂÈ ÙËÓ ¿ÌÂÛË ÌÂÙÂÁ¯ÂÈÚËÙÈ΋ ÂÚ›Ô‰Ô (30 Ë̤Ú˜), ÙfiÙÂ Ë ÂÓÙ·ÂÙ‹˜ ÂÈ‚›ˆÛË Â›Ó·È Û˘ÁÎÚ›ÛÈÌË Ì ·˘Ù‹ ÙˆÓ ÏËÙÒÓ ÌË ÔÚÈ·ÎÒÓ ÌÔÛ¯Â˘Ì¿ÙˆÓ. H ¯Ú‹ÛË ÌÔÛ¯Â˘Ì¿ÙˆÓ ·fi Û˘ÁÁÂÓ‹ ˙ÒÓÙ· ‰fiÙË Û ·ÛıÂÓ›˜ Ô˘ ÍÂÂÚÓÔ‡Ó ÙȘ ‰Â‰Ô̤Ó˜ ÁÈ· ÙÔ ÂοÛÙÔÙ ΤÓÙÚÔ Ú¸Ôı¤ÛÂȘ ÌÂÙ·ÌfiÛ¯Â˘Û˘ (Milan, UCSF, ÎÙÏ) Á›ÓÂÙ·È ‡ÛÙÂÚ· ·fi È·ÙÚÈÎfi Û˘Ì‚Ô‡ÏÈÔ Î·È ÌfiÓÔÓ ÂÊfiÛÔÓ ÂÓËÌÂÚˆı› Ï‹Úˆ˜ Ô ¿ÚÚˆÛÙÔ˜ Î·È Ô ˘Ô„‹ÊÈÔ˜ ‰fiÙ˘. ™Â ÁÂÓÈΤ˜ ÁÚ·Ì̤˜, Û˘ÓÈÛÙ¿Ù·È ¿Ì‚Ï˘ÓÛË ÙˆÓ ÚÔ¸Ôı¤ÛÂˆÓ ÌÂÙ·ÌfiÛ¯Â˘Û˘ Ì ÙË ¯Ú‹ÛË ÌÔۯ‡̷ÙÔ˜ ·fi ˙ÒÓÙ· ‰fiÙË, ÂÊfiÛÔÓ Ë ÚÔ‚ÏÂfiÌÂÓË ÂÓÙ·ÂÙ‹˜ ÂÈ‚›ˆÛË ·Ó¤Ú¯ÂÙ·È ÙÔ˘Ï¿Á¯ÈÛÙÔÓ ÛÙÔ 50% 26 . øÛÙfiÛÔ, ηϿ ÂÓËÌÂڈ̤ÓÔÈ ‰fiÙ˜ Ô˘ ·ÓÙÈÏ·Ì‚¿ÓÔÓÙ·È Ï‹Úˆ˜ ÙȘ Èı·Ó¤˜ ÂÈÏÔΤ˜ Ù˘ ¤̂·Û˘ ÛÙËÓ ÔÔ›· ı· ˘Ô‚ÏËıÔ‡Ó, ÌÔÚÔ‡Ó Ó· ÚÔÛʤÚÔ˘Ó ÌfiÛ¯Â˘Ì·, ·ÎfiÌ· Î·È ·Ó Â›Ó·È ¯·ÌËÏfiÙÂÚË Ë ÚÔ‚ÏÂfiÌÂÓË ÂÈ‚›ˆÛË ÙÔ˘ Ï‹ÙË38. H ¯Ú‹ÛË ÓÔÌÔÁÚ·ÌÌ¿ÙˆÓ Â˘¤ÏÈÎÙˆÓ ÎÚÈÙËÚ›ˆÓ Û ·ÛıÂÓ›˜ Ô˘ ÍÂÂÚÓÔ‡Ó ÙȘ ‰Â‰Ô̤Ó˜ ÁÈ· ÙÔ ÂοÛÙÔÙ ΤÓÙÚÔ Ú¸Ôı¤ÛÂȘ ÌÂÙ·ÌfiÛ¯Â˘Û˘ (Milan, UCSF, ÎÙÏ) Á›ÓÂÙ·È ‡ÛÙÂÚ· ·fi È·ÙÚÈÎfi Û˘Ì‚Ô‡ÏÈÔ. ™˘ÁÎÂÎÚÈ̤ӷ, οı ÌÂÙ·ÌÔÛ¯Â˘ÙÈÎfi ΤÓÙÚÔ ÌÔÚ› ·fi ÙË ‚¿ÛË ‰Â‰ÔÌ¤ÓˆÓ Ô˘ ‰È·ı¤ÙÂÈ Ó· ·ÓȯÓ‡ÛÂÈ ÂΛӘ ÙȘ ÚÔÌÂÙ·ÌÔÛ¯Â˘ÙÈΤ˜ ·Ú·Ì¤ÙÚÔ˘˜ (Î·È ÙÔ˘˜ Û˘ÓÙÂÏÂÛÙ¤˜ Û˘ÌÌÂÙÔ¯‹˜ ·˘ÙÒÓ) Ô˘ ÂËÚ¿˙Ô˘Ó ÙËÓ ¤Î‚·ÛË Ù˘ ÌÂÙ·ÌfiÛ¯Â˘Û˘ Î·È Ó· ηٷÛÙÚÒÛÂÈ ÓÔÌÔÁÚ¿ÌÌ·Ù· ÂÓÙ·ÂÙÔ‡˜ ÂÈ‚›ˆÛ˘ ÁÈ· οı ÌÈ· ·fi ·˘Ù¤˜. ΔÔ È·ÙÚÈÎfi Û˘Ì‚Ô‡ÏÈÔ, ˘ÔÏÔÁ›˙ÔÓÙ·˜ ·fi Ù· ÓÔÌÔÁÚ¿ÌÌ·Ù· ÙËÓ ÚÔ‚ÏÂfiÌÂÓË ÂÓÙ·ÂÙ‹ ÂÈ‚›ˆÛË ÁÈ· ÙÔ Û˘ÁÎÂÎÚÈ̤ÓÔ ·ÛıÂÓ‹ Î·È Û˘ÁÎÚ›ÓÔÓÙ¿˜ ÙËÓ Ì ÙË Ì¤ÛË ÂÓÙ·ÂÙ‹ ÂÈ‚›ˆÛË fiÏˆÓ ÙˆÓ ·ÛıÂ-
ÓÒÓ ÙÔ˘ ÂÓ ÏfiÁˆ ΤÓÙÚÔ˘, ·ÔÊ·›ÓÂÙ·È ÁÈ· ÙËÓ ¤ÓÙ·Í‹ ÙÔ˘ ‹ ÌË ÛÙË Ï›ÛÙ· Ù˘ Ë·ÙÈ΋˜ ÌÂÙ·ÌfiÛ¯Â˘Û˘39.
7. ∞ÏÁfiÚÈıÌÔ˜ ÌÂÙ·ÌfiÛ¯Â˘Û˘ Û ·ÛıÂÓ‹ Ì ∏∫∫ ÛÙËÓ ∂ÏÏËÓÈ΋ Ú·ÁÌ·ÙÈÎfiÙËÙ· ™ÙÔÓ ·ÛıÂÓ‹ Ô˘ ¤¯ÂÈ ‰È·ÁÓˆÛı› Ì ∏∫∫ Ú¤ÂÈ Ó· ˘ÔÏÔÁ›˙ÔÓÙ·È, Ì ÙË ‚Ô‹ıÂÈ· ÙˆÓ ˘ÔÏÔÁÈÛÙÈÎÒÓ ÂÚÁ·Ï›ˆÓ, ÔÈ ·ÎfiÏÔ˘ı˜ ÚÔ‚ÏÂfiÌÂÓ˜ ÂÈ‚ÈÒÛÂȘ: ·) Èڛ˜ ıÂڷ¢ÙÈ΋ ·Ú¤Ì‚·ÛË. ‚) ⁄ÛÙÂÚ· ·fi Ë·ÙÂÎÙÔÌ‹ (·Ó ·˘Ù‹ Â›Ó·È ÂÊÈÎÙ‹) Î·È Á) ⁄ÛÙÂÚ· ·fi Ë·ÙÈ΋ ÌÂÙ·ÌfiÛ¯Â˘ÛË. ∞Ó Ë ÚÔ‚ÏÂfiÌÂÓË ÂÈ‚›ˆÛË ‡ÛÙÂÚ· ·fi Ë·ÙÈ΋ ÌÂÙ·ÌfiÛ¯Â˘ÛË Â›Ó·È ÌÂÁ·Ï‡ÙÂÚË ·fi ÙȘ ¿ÏϘ ‰‡Ô, ÙfiÙ ٛıÂÙ·È Ë Û¯ÂÙÈ΋ ¤Ó‰ÂÈÍË. ∫·ÙfiÈÓ Û˘ÁÎÚ›ÓÔÓÙ·È Ë ÚÔ‚ÏÂfiÌÂÓË ÂÈ‚›ˆÛË ‡ÛÙÂÚ· ·fi Ë·ÙÈ΋ ÌÂÙ·ÌfiÛ¯Â˘ÛË ÁÈ· ∏∫∫ Ì ÙËÓ ÂÈ‚›ˆÛË ‡ÛÙÂÚ· ·fi Ë·ÙÈ΋ ÌÂÙ·ÌfiÛ¯Â˘ÛË ÁÈ· ¿ÏÏÔ˘˜ ÏfiÁÔ˘˜. ∞Ó Ë ÚÒÙË Â›Ó·È ÌÂÁ·Ï‡ÙÂÚË ·fi ÙË ‰Â‡ÙÂÚË, ÙfiÙ ÏËÚÔ‡ÓÙ·È Ù· Û¯ÂÙÈο ÎÚÈÙ‹ÚÈ· Î·È ÚÔ¯ˆÚԇ̠ÛÙË ÌÂÙ·ÌfiÛ¯Â˘ÛË. ∞Ó fï˜ Ë ÚÒÙË Â›Ó·È ÌÈÎÚfiÙÂÚË ·fi ÙË ‰Â‡ÙÂÚË, ÙfiÙ ‰ÂÓ ÏËÚÔ‡ÓÙ·È Ù· ÎÚÈÙ‹ÚÈ·. ™ÙËÓ ÂÚ›ÙˆÛË ÌË Ï‹ÚˆÛ˘ ÙˆÓ ÎÚÈÙËÚ›ˆÓ ÚÔ¯ˆÚԇ̠۠˘ÔÛÙ·‰ÈÔÔ›ËÛË, Û˘Ó‹ıˆ˜ Ì ¯ËÌÂÈÔÂÌ‚ÔÏÈÛÌfi. ∞Ó, ‡ÛÙÂÚ· ·fi ¢ڇ È·ÙÚÈÎfi Û˘Ì‚Ô‡ÏÈÔ, ·ÔÊ·ÛÈÛı› fiÙÈ Ë ˘ÔÛÙ·‰ÈÔÔ›ËÛË Ô‰‹ÁËÛ Û ÛËÌ·ÓÙÈ΋ ·‡ÍËÛË Ù˘ ÚÔ‚ÏÂfiÌÂÓ˘ ÂÈ‚›ˆÛ˘ ‡ÛÙÂÚ· ·fi ÌÂÙ·ÌfiÛ¯Â˘ÛË ÁÈ· ∏∫∫ (ÌÂÁ·Ï‡ÙÂÚË ·fi ÙËÓ ÂÈ‚›ˆÛË ‡ÛÙÂÚ· ·fi ÌÂÙ·ÌfiÛ¯Â˘ÛË ÁÈ· ¿ÏÏÔ˘˜ ÏfiÁÔ˘˜), ÙfiÙ ÏËÚÔ‡ÓÙ·È Ù· Û¯ÂÙÈο ÎÚÈÙ‹ÚÈ· Î·È ÚÔ¯ˆÚԇ̠ÛÙË ÌÂÙ·ÌfiÛ¯Â˘ÛË. ∞Ó ·Ú¿ ÙËÓ ˘ÔÛÙ·‰ÈÔÔ›ËÛË Ù· ÎÚÈÙ‹ÚÈ· ÂÍ·ÎÔÏÔ˘ıÔ‡Ó Ó· ÌËÓ ÏËÚÔ‡ÓÙ·È, ÙfiÙÂ, ‹ ÚÔ¯ˆÚԇ̠۠ÌÂÙ·ÌfiÛ¯Â˘ÛË Ì ÔÚȷο ÌÔۯ‡̷ٷ ‹ ηٷϋÁÔ˘Ì Û ·ÚËÁÔÚÈ΋ ÌfiÓÔ ıÂڷ›·.
μπμ§πO°ƒ∞ºπ∞ 1. Starzl TE. The Puzzle People. 1 st ed. Pittsburgh: University of Pittsburg; 1992, pp. 166-167. 2. Starzl TE, Demetris AJ, Van Thiel D. Liver Transplantation. N Engl J Med 1989; 321: 1014-1022. 3. Olthoff KM, Millis JM, Rosove MH, et al. Is liver transplantation justified for the treatment of hepatic malignancies? Arch Surg 1990; 125: 1261-1268. 4. Mazzafero V, Regalia E, Doci R, et al. Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis. N Engl J Med 1996; 334: 693-699. 5. Lo CM, Ngan H, Tso WK, et al. Randomized controlled trial of transarterial lipoidal chemoembolization for
METAMO™XEY™Eπ™ 2008
89
unresectable hepatocellular carcinoma. Hepatology 2002; 35: 1164-1171.
guidelines from Japan. World J Gastroenterol 2006; 12: 828-829.
6. Fong Y, Venook AP, Lawrence T. Hepatocellular cancer: Clinical management. In: Kelsen DP, Daly JM, Levin B, et al, editors. Gastrointestinal Oncology Principles and Practice. Philadelphia: Lippincot Williams and Wilkins, 2002, pp. 579-600.
20. Llovet JM, Burroughs A, Bruix J. Hepatocellular carcinoma. Lancet 2003; 362: 1907-1917.
7. Fink SA, Brown RS Jr. Current indications, contraindications, delisting criteria and timing for liver transplantation. In: Busuttil RW, Klintmalm GB, editors. Transplantation of the Liver. 2 nd ed. Philadelphia: Elsevier Saunders, 2006, pp. 95-114. 8. Bruix J, Sherman M. Management of hepatocellular carcinoma. Hepatology 2005; 42: 1208-1236. 9. Zaman SN, Melia WM, Johnson RD, et al. Risk factors in development of hepatocellular carcinoma in cirrhosis: prospective study of 613 patients. Lancet 1985; 1: 1357-1360. 10. Stone MJ, Fulmer JM, Klintmalm GB. Transplantation for primary hepatic malignancy. In: Busuttil RW, Klintmalm GB, editors. Transplantation of the Liver. 2nd ed. Philadelphia: Elsevier Saunders, 2006, pp. 95-114. 11. Choi EA, Rodgers SE, Ahmad SA, Abdalla EK. Hepatobiliary cancers. In: Feig BW, Berger DH, Fuhrman GM, editors. The MD Anderson Surgical Oncology Handbook. 4th ed. Philadelphia: Lippincot Williams and Wilkins, 2006, pp. 320-338. 12. Kamath PS, Wiesner RH, Malinchoc M, et al. A model to predict survival in patients with end-stage liver disease. Hepatology 2001; 33: 464-470. 13. Policy 3.6.4.4 on organ allocation. UNOS website (www.unos.org). 14. The Cancer of the Liver Italian Program (CLIP) Investigators. A new prognostic system for hepatocellular carcinoma: A retrospective study of 435 patients. Hepatology 1998; 28: 751-755. 15. Leung T, Tang A, Zee B, et al. Construction of the Chinese University prognostic index for hepatocellular carcinoma and comparison with the TNM staging system, the Okuda staging system and the cancer of the liver Italian program staging system. Cancer 2002; 94: 1760-1769. 16. Greene FL, Balch CM, Page DL, et al. American Joint Committee on Cancer Staging Manual. 6th ed. New York: Springer-Verlag; 2002, pp. 131-138. 17. Poon RT, Fan ST. Evaluation of the new AJCC/UICC staging system for hepatocellular carcinoma after hepatic resection in Chinese patients. Surg Oncol Clin N Am 2003; 12: 35-50. 18. Okuda K, Ohtsuki T, Obata H, et al. Natural history of hepatocellular carcinoma and prognosis in relation to treatment: Study of 850 patients. Cancer 1985; 56: 918928. 19. Makuuchi M, Kokudo M. Clinical practice guidelines for hepatocellular carcinoma: the first evidence based
21. Yao FY, Ferrell L, Bass NM, et al. Liver transplantation for hepatocellular carcinoma: expansion of the tumor size limits does not adversely impact survival. Hepatology 2001; 33: 1394-1403. 22. Shetty K, Timmins K, Brensinger C, et al. Liver transplantation for hepatocellular carcinoma validation of present selection criteria in predicting outcome. Liver Transpl 2004; 10: 911-918. 23. Llovet JM. Expanding HCC criteria for liver transplantation: the urgent need for prospective robust data. Liver Transpl 2006; 12: 1741-1743. 24. Nagaoka S, Yatsuhashi H, Hamada H, et al. The des-Ácarboxy prothrombin index is a new prognostic indicator for hepatocellular carcinoma. Cancer 2003; 98: 2671-2677. 25. Kong SY, Park JW, Lee JA, et al. Association between vascular endothelial growth factor gene polymorphisms and survival in hepatocellular carcinoma patients. Hepatology 2007; 46: 446-455. 26. Marsh JW, Holtzman MP, Dvorchik I. Living donor liver transplantation for hepatocellular carcinoma. In: Tan HP, Marcos A, Shapiro R, editors. Living Donor Transplantation. 1st ed. New York: Informa Healthcare, 2007, pp. 227-233. 27. NÙÔ˘Ú¿Î˘ ™. ™ÙÔ: Δ·ÎÔ‡‰·˜ ¢, ¶··ÓÈÎÔÏ¿Ô˘ μ, ÿÌ‚ÚÈÔ˜ °, ÂΉfiÙ˜. ªÂÙ·ÌÔۯ‡ÛÂȘ 2007: ™‡Á¯ÚÔÓ˜ ··ÓÙ‹ÛÂȘ Û ·Ï·È¿ ÂÚˆÙ‹Ì·Ù·. 1Ë ¤Î. £ÂÛÛ·ÏÔÓ›ÎË: University Studio Press, 2007, ÛÛ. 238-252. 28. Hong SN, Lee SY, Choi MS, et al. Comparing the outcomes of radiofrequency ablation and surgery in patients with a single small hepatocellular carcinoma and well-preserved hepatic function. J Clin Gastroenterol 2005; 39: 247-252. 29. Vivarelli M, Guglielmi A, Ruzzenente A, et al. Surgical resection versus percutaneous radiofrequency ablation in the treatment of hepatocellular carcinoma on cirrhotic liver. Ann Surg 2004; 240: 102-107. 30. Bruix J, Sala M, Llovet JM. Chemoembolization for hepatocellular carcinoma. Gastroenterology 2004; 127(5 Suppl 1): S179-S188. 31. Lo CM, Ngan H, Tso WK, et al. Randomized controlled trial of transarterial lipiodol chemoembolization for unresectable hepatocellular carcinoma. Hepatology; 35: 1164-1171. 32. Lang L. FDA approves sorafenib for patients with inoperable liver cancer. Gastroenterology 2008; 134: 379. 33. Yoo HY, Patt CH, Geschwind JF, et al. The outcome of liver transplantation in patients with hepatocellular carcinoma in the United States between 1987 and 2001: 5-year survival has improved significantly with time. J Clin Oncol 2003; 21: 4329-4335.
90
¢. μƒOÃπ¢∏™, ¢. Δ∞∫OÀ¢∞™
34. Houben KW, McCall JL. Liver transplantation for hepatocellular carcinoma in patients without underlying liver disease. A systematic review. Liver Transpl Surg 1999; 5: 91-95.
37. Kassahun WT, Fangmann J, Harms J, et al. Liver resection and transplantation in the management of hepatocellular carcinoma: a review. Experiment Clin Transplantation 2006; 4: 549-558.
35. Cheng SJ, Pratt DS, Freeman RB Jr, et al. Living-donor versus cadaveric liver transplantation for non-resectable small hepatocellular carcinoma and compensated cirrhosis: A decision analysis. Transplantation 2001; 72: 861-868.
38. Steinmuller T, Pascher A, Sauer I, et al. Living-donation liver transplantation for hepatocellular carcinoma: time to drop the limitations? Transplant Proc 2002; 34: 2263-2264.
36. Molmenti EP, Klintmalm GB, et al. Liver transplantation in association with hepatocellular carcinoma: An update of the International Tumor Registry. Liver Transpl 2002; 8: 736-748.
39. Vrochides D, Hassanain M, Barkun J, et al. Selection of liver transplant recipients for the treatment of HCC based on adjustable preoperative criteria with a predetermined, center specific, five-year patient survival target. Am J Transpl 2008; 8 (6 Suppl 1): ahead of print.
MÂÙ·ÌfiÛ¯Â˘ÛË ‹·ÙÔ˜ ÁÈ· ÎÈÚÚˆÙÈÎÔ‡˜ ·ÛıÂÓ›˜ Ì ˷ÙÔ΢ÙÙ·ÚÈÎfi ηÚΛÓÔ ÂÎÙfi˜ ÎÚÈÙËÚ›ˆÓ MÈÏ¿ÓÔ˘ °.Ã. ™ˆÙËÚfiÔ˘ÏÔ˜
∂ÈÛ·ÁˆÁ‹
ÎÒÓ Û¯ÂÙÈÎÒÓ Ì ÙËÓ ÂÊ·ÚÌÔÁ‹ ·˘Ù‹˜ Ù˘ Ù¯ÓÈ΋˜8-9. ∏ ·Ô‰Ô¯‹ ÔÚÈ·ÎÒÓ ÔÚÁ¿ÓˆÓ ÁÈ· ÛÙ·ıÂÚÔ‡˜ ·ÛıÂÓ›˜ Ì ˷ÙÔ΢ÙÙ·ÚÈÎfi ηÚΛÓÔ ·ÂÙ¤ÏÂÛ ̛· ÂÚ·ÈÙ¤Úˆ ‰˘ÓËÙÈ΋ χÛË. ∏ ÂÊ·ÚÌÔÁ‹ Ù˘ fï˜ ·Ú·Ì¤ÓÂÈ ÂÊÈÎÙ‹ ۯ‰fiÓ ÌfiÓÔ Û ÌÂÁ¿Ï· ÌÂÙ·ÌÔÛ¯Â˘ÙÈο ΤÓÙÚ· Î·È ÂÚÈÔÚ›˙ÂÙ·È ÂÚ·ÈÙ¤Úˆ ·fi ÙÔÈÎÔ‡˜ ηÓfiÓ˜ ηٷÓÔÌ‹˜ ÔÚÁ¿ÓˆÓ10. ™˘Ó¤ÂÈ· ÙˆÓ ·ÓˆÙ¤Úˆ Â›Ó·È fiÙÈ Ë ÌÂÙ·ÌfiÛ¯Â˘ÛË ‹·ÙÔ˜ ·fi ˙ÒÓÙ· ‰fiÙË ·ÔÙÂÏ› ÙËÓ ÂÚÈÛÛfiÙÂÚÔ ÂÊÈÎÙ‹ ‰˘Ó·ÙfiÙËÙ· ÁÈ· ÙË ‰È‡ڢÓÛË Ù˘ ÙÚ¿Â˙·˜ ÔÚÁ¿ÓˆÓ ÁÈ· ·ÛıÂÓ›˜ Ì ˷ÙÔ΢ÙÙ·ÚÈÎfi ηÚΛÓÔ Î·È Î›ÚÚˆÛË ÙÂÏÈÎÔ‡ ÛÙ·‰›Ô˘11-12. ∂ÓÒ ÛÙȘ ·Ó·ÙÔÏÈΤ˜ ¯ÒÚ˜ Ë ÌÂÙ·ÌfiÛ¯Â˘ÛË ‹·ÙÔ˜ ·fi ˙ÒÓÙ· ‰fiÙË ÁÈ· Ë·ÙÔ΢ÙÙ·ÚÈÎfi ηÚΛÓÔ ÂÚÈÔÚ›˙ÂÙ·È Û˘Ó‹ıˆ˜ Û ·ÛıÂÓ›˜ Ô˘ ÏËÚÔ‡Ó Ù· ÎÚÈÙ‹ÚÈ· ÙÔ˘ ªÈÏ¿ÓÔ˘, ÛÙȘ ‰˘ÙÈΤ˜ ¯ÒÚ˜ Û˘Ó‹ıˆ˜ Û˘Óԉ‡ÂÙ·È Ì ̛· Ù¿ÛË ÌÂÙ·ÌfiÛ¯Â˘Û˘ ·ÛıÂÓÒÓ Ô˘ ‰ÂÓ ÏËÚÔ‡Ó Ù· ÎÚÈÙ‹ÚÈ· ÙÔ˘ ªÈÏ¿ÓÔ˘13-18. ™Â ·˘Ù¤˜ ÙȘ ÂÚÈÙÒÛÂȘ Ë ¤ÓÙÔÓË ‰È¿ıÂÛË ÚÔÛÊÔÚ¿˜ ÙÌ‹Ì·ÙÔ˜ ÙÔ˘ ‹·ÙÔ˜ ÌÂٷ͇ Û˘ÁÁÂÓÒÓ ·›˙ÂÈ ¤Ó·Ó ÛËÌ·ÓÙÈÎfi ÚfiÏÔ ÛÙËÓ ÙÂÏÈ΋ Ï‹„Ë Ù˘ ·fiÊ·Û˘19. ™ÎÔfi˜ Ù˘ ·ÚÔ‡Û˘ ÌÂϤÙ˘ Â›Ó·È Ë ·Ó·ÛÎfiËÛË ·ÔÙÂÏÂÛÌ¿ÙˆÓ ÌÂÙ·ÌfiÛ¯Â˘Û˘ ‹·ÙÔ˜ Û ·ÛıÂÓ›˜ Ì ˷ÙÔ΢ÙÙ·ÚÈÎfi ηÚΛÓÔ ÂÎÙfi˜ ÎÚÈÙËÚ›ˆÓ ªÈÏ¿ÓÔ˘. ∏ ·Ó·ÛÎfiËÛË ·˘Ù‹ ‚·Û›˙ÂÙ·È Î˘Ú›ˆ˜ ÛÙ· ÌÂÙ·ÌÔÛ¯Â˘ÙÈο ·ÔÙÂϤÛÌ·Ù· Ù˘ ∫ÏÈÓÈ΋˜ °ÂÓÈ΋˜ ÃÂÈÚÔ˘ÚÁÈ΋˜ Î·È ÃÂÈÚÔ˘ÚÁÈ΋˜ ÙˆÓ ªÂÙ·ÌÔۯ‡ÛÂˆÓ ÙÔ˘ ¶·ÓÂÈÛÙËÌÈ·ÎÔ‡ ¡ÔÛÔÎÔÌ›Ԣ Essen °ÂÚÌ·Ó›·˜, ·ÏÏ¿ Î·È Û ‰ËÌÔÛÈÂ˘Ì¤Ó˜ ÌÂϤÙ˜ ·fi ¿ÏÏ· ΤÓÙÚ·.
O Ë·ÙÔ΢ÙÙ·ÚÈÎfi˜ ηÚΛÓÔ˜ Â›Ó·È Ô Û˘¯ÓfiÙÂÚÔ˜ ÚˆÙÔ·ı‹˜ ηÎÔ‹ı˘ fiÁÎÔ˜ ÙÔ˘ ‹·ÙÔ˜ Î·È Ì›· ·fi ÙȘ ·ÚȘ ·Èٛ˜ ı·Ó¿ÙÔ˘ Û ·ÁÎfiÛÌÈ· Îϛ̷η1. ¶·Ú¿ ÙÔ ÁÂÁÔÓfi˜ fiÙÈ Ô Ë·ÙÔ΢ÙÙ·ÚÈÎfi˜ ηÚΛÓÔ˜ ·ÔÙÂÏÔ‡Û › ÛÂÈÚ¿ ÂÙÒÓ ¤Ó· È·ÙÚÈÎfi Úfi‚ÏËÌ· Ô˘ ··Û¯ÔÏÔ‡Û ΢ڛˆ˜ ÙȘ ·ÛÈ·ÙÈΤ˜ Î·È ·ÊÚÈηÓÈΤ˜ ¯ÒÚ˜, Ë ‚·ıÌÈ·›· ·‡ÍËÛË ÙˆÓ ÂÚÈÛÙ·ÙÈÎÒÓ Î›ÚÚˆÛ˘ ÏfiÁˆ ÈÔÁÂÓÔ‡˜ Ë·Ù›Ùȉ·˜ C Ô‰‹ÁËÛ Û ̛· ηٷÎfiÚ˘ÊË ·‡ÍËÛË Ù˘ ›وÛ˘ ÙÔ˘ Ë·ÙÔ΢ÙÙ·ÚÈÎÔ‡ ηÚΛÓÔ˘ ·ÎfiÌË Î·È ÛÙȘ ‰˘ÙÈΤ˜ ¯ÒÚ˜2. ∏ ÌÂÙ·ÌfiÛ¯Â˘ÛË ‹·ÙÔ˜ ¤¯ÂÈ Ï¤ÔÓ Â˘Ú¤ˆ˜ ·Ó·ÁÓˆÚÈÛÙ› ˆ˜ Ë Î·Ï‡ÙÂÚË ıÂڷ¢ÙÈ΋ ‰˘Ó·ÙfiÙËÙ· ÁÈ· ·ÛıÂÓ›˜ Ì ÚÒÈÌÔ Ë·ÙÔ΢ÙÙ·ÚÈÎfi ηÚΛÓÔ Î·È Î›ÚÚˆÛË ÙÂÏÈÎÔ‡ ÛÙ·‰›Ô˘3. ∏ ÂÈÛ·ÁˆÁ‹ ÙˆÓ ÎÚÈÙËÚ›ˆÓ ÙÔ˘ ªÈÏ¿ÓÔ˘ (ÌÔÓ‹Ú˘ fiÁÎÔ˜≤5cm, 2-3 fiÁÎÔÈ ÂÎ ÙˆÓ ÔÔ›ˆÓ ηÓ›˜>3cm, ·Ô˘Û›· ·ÁÁÂȷ΋˜ ‰È‹ıËÛ˘) ·fi ÙÔ˘˜ Mazzafero Î·È Û˘ÓÂÚÁ¿Ù˜ ÙÔ 19964 Û˘ÓÂÙ¤ÏÂÛ Û ÔÛÔÛÙ¿ 5ÂÙÔ‡˜ ÂÈ‚›ˆÛ˘ ÌÂٷ͇ ÙˆÓ ·ÛıÂÓÒÓ Ì ˷ÙÔ΢ÙÙ·ÚÈÎfi ηÚΛÓÔ Ô˘ ÏËÚÔ‡Ó Ù· ÎÚÈÙ‹ÚÈ· ÙÔ˘ ªÈÏ¿ÓÔ˘ ۯ‰fiÓ Û˘ÁÎÚ›ÛÈÌ· Ì ÂΛӷ ÎÈÚÚˆÙÈÎÒÓ ·ÛıÂÓÒÓ Ô˘ ÌÂÙ·ÌÔۯ‡ÙËÎ·Ó Û ·Ô˘Û›· ηÎÔ‹ıÂÈ·˜5-7. ∞˘Ùfi ÙÔ ·ÔÙ¤ÏÂÛÌ· ÛÂ Û˘Ó‰˘·ÛÌfi Ì ÙËÓ ¤ÏÏÂÈ„Ë ÔÚÁ¿ÓˆÓ Ô‰‹ÁËÛ Û ÚÔÛ¿ıÂȘ Ó· “‰È¢ڢÓı›” Ë ÙÚ¿Â˙· ‰ÔÙÒÓ ÔÚÁ¿ÓˆÓ, ¤ÙÛÈ ÒÛÙ ӷ Â›Ó·È ‰˘Ó·Ù‹ Ë ‰ÈÂÓ¤ÚÁÂÈ· ÌÂÙ·ÌfiÛ¯Â˘Û˘ ‹·ÙÔ˜ Û ÂÚÈÛÛfiÙÂÚÔ˘˜ ·ÛıÂÓ›˜ Ì ˷ÙÔ΢ÙÙ·ÚÈÎfi ηÚΛÓÔ. ∏ ÂÊ·ÚÌÔÁ‹ Ù˘ ÙÌËÌ·ÙÈ΋˜ ÌÂÙ·ÌfiÛ¯Â˘Û˘ ‹·ÙÔ˜ ·fi و̷ÙÈÎfi ‰fiÙË Û ÂÓ‹ÏÈΘ ·ÛıÂÓ›˜ Ì ˷ÙÔ΢ÙÙ·ÚÈÎfi ηÚΛÓÔ, ÛÂ Û˘Ó‰˘·ÛÌfi Ì ·È‰È·ÙÚÈ΋ ÌÂÙ·ÌfiÛ¯Â˘ÛË ‹·ÙÔ˜, ·¤Ù˘¯Â ÛÙËÓ ·ÔÛÙÔÏ‹ Ù˘ ‰È‡ڢÓÛ˘ Ù˘ ÙÚ¿Â˙·˜ ‰ÔÙÒÓ ÔÚÁ¿ÓˆÓ, ΢ڛˆ˜ ÂÍ·ÈÙ›·˜ ÏÔÁÈÛÙÈÎÒÓ/ÔÚÁ·ÓˆÙÈÎÒÓ ÚÔ‚ÏËÌ¿ÙˆÓ Ô˘ ¤ÙÚ„·Ó ÙËÓ Ú·ÁÌ·ÙÔÔ›ËÛ‹ Ù˘ ÌfiÓÔ Û ÌÂÁ¿Ï· ÌÂÙ·ÌÔÛ¯Â˘ÙÈο ΤÓÙÚ· Ì ÙÚ¤¯ÔÓ ·È‰È·ÙÚÈÎfi ÚfiÁÚ·ÌÌ· ÌÂÙ·ÌfiÛ¯Â˘Û˘ ‹·ÙÔ˜, ηıÒ˜ Î·È ÏfiÁˆ ÌÂÙÂÁ¯ÂÈÚËÙÈÎÒÓ ÂÈÏÔ-
ªÂÙ·ÌfiÛ¯Â˘ÛË ‹·ÙÔ˜ ˆ˜ ıÂڷ›· ÂÎÏÔÁ‹˜ Û ÎÈÚÚˆÙÈÎÔ‡˜ ·ÛıÂÓ›˜ Ì ˷ÙÔ΢ÙÙ·ÚÈÎfi ηÚΛÓÔ Ÿˆ˜ ÚԷӷʤÚıËÎÂ, Ë ÌÂÙ·ÌfiÛ¯Â˘ÛË ‹·ÙÔ˜ ¤¯ÂÈ Ï¤ÔÓ Â˘Ú¤ˆ˜ ·Ó·ÁÓˆÚÈÛÙ› ˆ˜ Ë Î·Ï‡ÙÂÚË ıÂڷ¢ÙÈ΋ ‰˘Ó·ÙfiÙËÙ· ÁÈ· ·ÛıÂÓ›˜ Ì ÚÒÈÌÔ Ë·ÙÔ΢ÙÙ·ÚÈÎfi ηÚΛÓÔ Î·È Î›ÚÚˆÛË ÙÂÏÈÎÔ‡
91
°. ™øΔ∏ƒO¶OÀ§O™
92
ÛÙ·‰›Ô˘. O ηÏÔ‡ÌÂÓÔ˜ ˆ˜ ÚÒÈÌÔ˜ Ë·ÙÔ΢ÙÙ·ÚÈÎfi˜ ηÚΛÓÔ˜ ¤¯ÂÈ Û¯Â‰fiÓ Ù·˘ÙÈÛÙ› Ì ÂΛÓÔÓ Ô˘ ÏËÚ› Ù· ÎÚÈÙ‹ÚÈ· ÙÔ˘ ªÈÏ¿ÓÔ˘. ™Â Ì›· ÚÔÔÙÈ΋ ÌÂϤÙË Ô˘ ‰ÈÂÓÂÚÁ‹ıËΠÛÙÔ ªÂÙ·ÌÔÛ¯Â˘ÙÈÎfi Ì·˜ ∫¤ÓÙÚÔ Û ·ÛıÂÓ›˜ Ì ˷ÙÔ΢ÙÙ·ÚÈÎfi ηÚΛÓÔ Û ¤‰·ÊÔ˜ ΛÚÚˆÛ˘ ÂÚÂ˘Ó‹Û·ÌÂ Û˘ÁÎÚÈÙÈο Ù· ·ÔÙÂϤÛÌ·Ù· ÙÚÈÒÓ ıÂڷ¢ÙÈÎÒÓ ÌÂıfi‰ˆÓ ˆ˜ «ÌÔÓÔıÂڷ›·˜», Ù˘ ÌÂÙ·ÌfiÛ¯Â˘Û˘ ‹·ÙÔ˜, Ù˘ Ë·ÙÂÎÙÔÌ‹˜ Î·È ÙÔ˘ ·ÚÙËÚÈ·ÎÔ‡ ¯ËÌÂÈÔÂÌ‚ÔÏÈÛÌÔ‡. ∏ ÌÂϤÙË ÂÚȤϷ‚Â Û˘ÓÔÏÈο 185 ÎÈÚÚˆÙÈÎÔ‡˜ ·ÛıÂÓ›˜, 60 ÛÙËÓ ÔÌ¿‰· Ù˘ ÌÂÙ·ÌfiÛ¯Â˘Û˘, 61 ÛÙËÓ ÔÌ¿‰· Ù˘ Ë·ÙÂÎÙÔÌ‹˜ Î·È 64 ÛÙËÓ ÔÌ¿‰· ÙÔ˘ ·ÚÙËÚÈ·ÎÔ‡ ¯ËÌÂÈÔÂÌ‚ÔÏÈÛÌÔ‡. Ÿˆ˜ Ê·›ÓÂÙ·È ÛÙËÓ ∂ÈÎfiÓ· 1, ÔÈ Î·Ì‡Ï˜ ÂÈ‚›ˆÛ˘ Ô˘ ˘ÔÏÔÁ›ÛÙËÎ·Ó Ì ÙË Ì¤ıÔ‰Ô Kaplan-Meier Î·È Û˘ÁÎÚ›ıËÎ·Ó Ì ÙË ‰ÔÎÈÌ·Û›· log-rank, ¤‰ˆÛ·Ó ÛÙ·ÙÈÛÙÈο ηχÙÂÚ· ·ÔÙÂϤÛÌ·Ù· ÛÙËÓ ÔÌ¿‰· ÙˆÓ ·ÛıÂÓÒÓ Ô˘ ˘¤ÛÙËÛ·Ó ÌÂÙ·ÌfiÛ¯Â˘ÛË ‹·ÙÔ˜ (p=0.001). ΔÔ ·ÔÙ¤ÏÂÛÌ· ·˘Ùfi ‰Â›¯ÓÂÈ fiÙÈ Ë ÌÂÙ·ÌfiÛ¯Â˘ÛË ‹·ÙÔ˜ ·Ú¤¯ÂÈ Ù· ηχÙÂÚ· ÔÛÔÛÙ¿ ÂÈ‚›ˆÛ˘, fiÛÔÓ ·ÊÔÚ¿ ÛÙÔÓ Ë·ÙÔ΢ÙÙ·ÚÈÎfi ηÚΛÓÔ, ·ÓÂÍ¿ÚÙËÙ· ÙÔ˘ Â¿Ó Â›Ó·È «ÚÒÈÌÔ˜» ‹ Î·È ÈÔ ÚÔ¯ˆÚË̤ÓÔ˜. ¶ÂÚ·ÈÙ¤Úˆ ÚÔÛÂÎÙÈ΋ ·Ó¿Ï˘ÛË ÙˆÓ ·ÓˆÙ¤Úˆ ·ÔÙÂÏÂÛÌ¿ÙˆÓ Û ·Ó·ÊÔÚ¿ Ì ٷ ÎÚÈÙ‹ÚÈ· ÙÔ˘ ªÈÏ¿ÓÔ˘ (∂ÈÎfiÓ· 2), ‰Â›¯ÓÂÈ fiÙÈ ÔÈ ÌÂÙ·ÌÔÛ¯Â˘Ì¤ÓÔÈ ·ÛıÂÓ›˜ Ô˘ ‰ÂÓ ÏËÚÔ‡Ó Ù· ÎÚÈÙ‹ÚÈ· ÙÔ˘ ªÈÏ¿ÓÔ˘ ¤¯Ô˘Ó ηÏÏ›ÙÂÚË 5ÂÙ‹ ÂÈ‚›ˆÛË (50%) ·ÎfiÌË Î·È ·fi ÙÔ˘˜ ·ÛıÂÓ›˜ Ô˘ ÏËÚÔ‡Ó Ù· ÎÚÈÙ‹ÚÈ· ÙÔ˘ ªÈÏ¿ÓÔ˘ ÛÙËÓ ÔÌ¿‰· Ù˘ Ë·ÙÂÎÙÔÌ‹˜ (28%) ‹ ÙÔ˘ ·ÚÙËÚÈ·ÎÔ‡ ¯ËÌÂÈÔÂÌ‚ÔÏÈÛÌÔ‡ (32%). Δ· ·Cumulative Proportion Surviving (Kaplan-Meier) (p=0.001) Resection
Cumutative Proportion Surviving
1,0
TACE
Transplantation Complete
0,9
Censored
0,8 0,7 0,6 0,5 0,4 0,3 0,2 0,1 0,0 0
12
24
36
48
60
72
84
96
108
Time (months)
∂ÈÎfiÓ· 1. ∫·Ì‡Ï˜ ÂÈ‚›ˆÛ˘ (ηٿ Kaplan-Meier) ·Ó¿ ÔÌ¿‰· ÌÂϤÙ˘.
ÓˆÙ¤Úˆ ·ÔÙÂϤÛÌ·Ù· 3 ‰È·ÊÔÚÂÙÈÎÒÓ ÌÂıfi‰ˆÓ «ÌÔÓÔıÂڷ›·˜» Û ÎÈÚÚˆÙÈÎÔ‡˜ ·ÛıÂÓ›˜, ‰Â›¯ÓÔ˘Ó Î·ı·Ú¿ fiÙÈ Ë ÌÂÙ·ÌfiÛ¯Â˘ÛË ‹·ÙÔ˜ ·ÔÙÂÏ› ÙËÓ Î·Ï‡ÙÂÚË ıÂڷ›· ÁÈ· ÙÔÓ Ë·ÙÔ΢ÙÙ·ÚÈÎfi ηÚΛÓÔ ·fi ÔÁÎÔÏÔÁÈ΋ ¿Ô„Ë. ∞fi ÌÂÙ·ÌÔÛ¯Â˘ÙÈ΋ ¿Ô„Ë, ÂÂȉ‹ ÙÔ Úfi‚ÏËÌ· Ù˘ ¿ÚÎÂÈ·˜ ÔÚÁ¿ÓˆÓ ÚÔ˜ ÌÂÙ·ÌfiÛ¯Â˘ÛË ÂȉÂÈÓÒÓÂÙ·È Û˘Ó¯Ҙ, Â›Ó·È ·Ó·Áη›· Ë ‡·ÚÍË Î¿ÔÈˆÓ ÎÚÈÙËÚ›ˆÓ, ¤ÙÛÈ ÒÛÙ ӷ ÌË ‰ÈÂÓÂÚÁÂ›Ù·È Ë ÌÂÙ·ÌfiÛ¯Â˘ÛË ‹·ÙÔ˜ ÁÈ· Ë·ÙÔ΢ÙÙ·ÚÈÎfi ηÚΛÓÔ ÂȘ ‚¿ÚÔ˜ ÙˆÓ ˘fiÏÔȈÓ, ÌË Î·ÚÎÈÓÔ·ıÒÓ, ÎÈÚÚˆÙÈÎÒÓ ·ÛıÂÓÒÓ.
∂Ê·ÚÌÔÛÈÌfiÙËÙ· ÙˆÓ ÎÚÈÙËÚ›ˆÓ ÙÔ˘ ªÈÏ¿ÓÔ˘: ∞ÎÙÈÓÔÏÔÁÈ΋ Î·È ·ıÔÏÔÁÔ·Ó·ÙÔÌÈ΋ ·Ó·ÛÎfiËÛË ŒÓ· ÂÚÒÙËÌ· Ô˘ ‡ÏÔÁ· ÁÂÓÓ¿Ù·È ÛÙÔÓ ¤ÌÂÈÚÔ ÎÏÈÓÈÎfi È·ÙÚfi, Â›Ó·È ÙÔ Î·Ù¿ fiÛÔ Ù· ¢ڤˆ˜ ·Ô‰ÂÎÙ¿ ÎÚÈÙ‹ÚÈ· ÙÔ˘ ªÈÏ¿ÓÔ˘ Â›Ó·È ÂÊ·ÚÌfiÛÈÌ·, Î·È ‰Ë fiÛÔ Â‡ÎÔÏË ‹ ‰‡ÛÎÔÏË Â›Ó·È Ë ÌÂϤÙË Î·È Ë Ù·ÍÈÓfiÌËÛË ÙˆÓ ¯·Ú·ÎÙËÚÈÛÙÈÎÒÓ ÙÔ˘ Ë·ÙÔ΢ÙÙ·ÚÈÎÔ‡ ηÚΛÓÔ˘ (̤ÁÂıÔ˜, ·ÎÚÈ‚‹˜ ·ÚÈıÌfi˜ fiÁΈÓ) ÚÔÂÁ¯ÂÈÚËÙÈο, Û ¤Ó· ÎÈÚÚˆÙÈÎfi ‹·Ú ÙÂÏÈÎÔ‡ ÛÙ·‰›Ô˘, fiÔ˘ Ë ‰È·ÊÔÚÈ΋ ‰È¿ÁÓˆÛË ·Ó¿ÌÂÛ· Û ˷ÙÔ΢ÙÙ·ÚÈÎfi ηÚΛÓÔ Î·È ·Ó·ÁÂÓÓËÙÈÎfi fi˙Ô ·ÔÙÂÏ› ÚfiÎÏËÛË ·ÎfiÌË Î·È ÁÈ· ÙÔÓ ¤ÌÂÈÚÔ ·ÎÙÈÓÔÏfiÁÔ. ¶ÔÏ˘¿ÚÈı̘ ·ÎÙÈÓÔÏÔÁÈΤ˜ ÌÂϤÙ˜ ‹‰Ë ·fi ÙÔ 1998 ÙfiÓÈÛ·Ó ÙÔ Úfi‚ÏËÌ· Ù˘ ·Û˘Ìʈӛ·˜ ÙˆÓ ·ÔÙÂÏÂÛÌ¿ÙˆÓ Ù·ÍÈÓfiÌËÛ˘ ÙÔ˘ Ë·ÙÔ΢ÙÙ·ÚÈÎÔ‡ ηÚΛÓÔ˘, fiÙ·Ó Û˘ÁÎÚ›ÓÔÓÙ·È Ù· ·ÎÙÈÓÔÏÔÁÈο Ì ٷ ·ıÔÏÔÁÔ·Ó·ÙÔÌÈο Â˘Ú‹Ì·Ù· ÌÂÙ¿ ·fi ÌÂÙ·ÌfiÛ¯Â˘ÛË, ·ÎfiÌË Î·È ÌÂÙ¿ ·fi ÂÊ·ÚÌÔÁ‹ ÚÔËÁËÌ¤ÓˆÓ ·ÎÙÈÓÔÏÔÁÈÎÒÓ Ì‰fi‰ˆÓ (˘ÂÚ˯ÔÁÚ·Ê‹Ì·ÙÔ˜ Ì ÛÎÈ·ÁÚ·ÊÈÎfi, ·ÍÔÓÈ΋˜ Ì Ôχ ÏÂÙ¤˜ ÙÔ̤˜, Ì·ÁÓËÙÈ΋˜ ÙÔÌÔÁÚ·Ê›·˜ Ì ‰È¿ÊÔÚ˜ Ù¯ÓÈΤ˜ Î·È ÛÎÈ·ÁÚ·ÊÈο). ∂Ó‰ÂÈÎÙÈο, ÔÈ Lopez Hanninen Î·È Û˘ÓÂÚÁ¿Ù˜ ÌÂÏÂÙÒÓÙ·˜ ÙËÓ Â˘·ÈÛıËÛ›· Ù˘ ·ÍÔÓÈ΋˜ ·Ó¤ÊÂÚ·Ó Ì›· Ôχ ¯·ÌËÏ‹ ¢·ÈÛıËÛ›· Ù˘ ٿ͈˜ ÙÔ˘ 20% ÌfiÓÔ ÁÈ· ÌÈÎÚÔ‡˜ fiÁÎÔ˘˜ ÌÂٷ͇ ÂÓfi˜ Î·È ‰‡Ô ÂηÙÔÛÙÒÓ. Krinsky Î·È Û˘ÓÂÚÁ¿Ù˜21 ÌÂÏÂÙÒÓÙ·˜ ÙËÓ Â˘·ÈÛıËÛ›· Ù˘ Ì·ÁÓËÙÈ΋˜ ÙÔÌÔÁÚ·Ê›·˜ ·Ó¤ÊÂÚ·Ó Ì›· Û˘ÓÔÏÈ΋ ¢·ÈÛıËÛ›· Ù˘ ٿ͈˜ ÙÔ˘ 33%, ÂÚÈÁÚ¿ÊÔÓÙ·˜ ÌfiÓÔ 39 fiÁÎÔ˘˜ ÛÙ· ·ÎÙÈÓÔÏÔÁÈο Â˘Ú‹Ì·Ù·, ÂÓÒ ÛÙ· ·ıÔÏÔÁÈο ·Ó¢ڤıËÛ·Ó 118! ∏ ·Ó‡ÚÂÛË ÌÈÎÚÒÓ fiÁÎˆÓ ‹Ù·Ó ·Ó·Ú΋˜, Ì ÌfiÓÔ 11 ·fi ÙÔ˘˜ 21 fiÁÎÔ˘˜ ÌÂٷ͇ ÂÓfi˜ Î·È ‰‡Ô ÂηÙÔÛÙÒÓ (51%) Î·È 3 ·fi ÙÔ˘˜ 72 fiÁÎÔ˘˜ ÌÈÎÚfiÙÂÚÔ˘˜ ÙÔ˘ ÂÓfi˜ ÂηÙÔÛÙÔ‡ (4%).
METAMO™XEY™Eπ™ 2008
Milan Criteria Meeting Exceeding
Cumulative Proportion Surviving (Kaplan-Meier) (p=0.03524) Complete
0,8
Censored
0,7 0,6 0,5 0,4 0,3 0,2 0,1 0
12
24
36
48 60 72 Time (months)
84
96
Censored
Cumutative Proportion Surviving
Cumutative Proportion Surviving
Complete
0,8 0,7 0,6 0,5 0,4 0,3 0,2 0,1 0
12
24
36 48 Time (months)
60
72
Complete
0,8
Censored
0,7 0,6 0,5 0,4 0,3 0,2 0,1 0
12
24 38 48 Time (months)
60
Cumulative Proportion Surviving (Kaplan-Meier) (Transplantation group p=0.72512) 1,0
1,0 0,9
0,9
0,0
108
Cumulative Proportion Surviving (Kaplan-Meier) (TACE group p=0.04105)
0,0
Cumulative Proportion Surviving (Kaplan-Meier) (Resection group p=0.72512) 1,0
0,9
Cumutative Proportion Surviving
Cumutative Proportion Surviving
1,0
0,0
93
84
0,9
Complete
0,8
Censored
0,7 0,6 0,5 0,4 0,3 0,2 0,1 0,0
0
12
24
36 48 60 Time (months)
72
84
69
∂ÈÎfiÓ· 2. ∫·Ì‡Ï˜ ÂÈ‚›ˆÛ˘ (ηٿ Kaplan-Meier) ·Ó¿ ÔÌ¿‰· ÌÂϤÙ˘ Û‡Ìʈӷ Ì ٷ ÎÚÈÙ‹ÚÈ· ÙÔ˘ ªÈÏ¿ÓÔ˘ ÁÈ· ÙË Û˘ÓÔÏÈ΋ ÔÌ¿‰· ÌÂϤÙ˘ (a), ÙËÓ ÔÌ¿‰· ÙˆÓ Ë·ÙÂÎÙÔÌÒÓ (b), ÙÔ˘ ·ÚÙËÚÈ·ÎÔ‡ ¯ËÌÂÈÔÂÌ‚ÔÏÈÛÌÔ‡ (c) Î·È Ù˘ ÌÂÙ·ÌfiÛ¯Â˘Û˘ ‹·ÙÔ˜ (d).
¶·ÚfiÌÔÈ· Â˘Ú‹Ì·Ù· ·Ó¤ÊÂÚ·Ó Î·È ÔÈ Bhartia Î·È Û˘ÓÂÚÁ¿Ù˜, ηٷϋÁÔÓÙ·˜ fiÙÈ Ë ·ÎÙÈÓÔÏÔÁÈ΋ ·Ó·ÁÓÒÚËÛË fiÁÎˆÓ ÌÈÎÚfiÙÂÚˆÓ ÙÔ˘ ÂÓfi˜ ÂηÙÔÛÙÔ‡ Â›Ó·È ·ÎfiÌË ÂÚÈÔÚÈṲ̂ÓË22. ™Â Ì›· ‰È΋ Ì·˜ ÌÂϤÙË ‚·ÛÈṲ̂ÓË Û 70 ÌÂÙ·ÌÔÛ¯Â˘Ì¤ÓÔ˘˜ ·ÛıÂÓ›˜ Ì ˷ÙÔ΢ÙÙ·ÚÈÎfi ηÚΛÓÔ (35 ·fi ˙ÒÓÙ· Î·È 35 ·fi و̷ÙÈÎfi ‰fiÙË) Ë Â˘·ÈÛıËÛ›· Ù˘ ·ÎÙÈÓÔÏÔÁÈ΋˜ ÌÂıfi‰Ô˘ ‹Ù·Ó Ôχ ¯·ÌËÏ‹, Î·È Û˘ÁÎÂÎÚÈ̤ӷ 0% ÁÈ· fiÁÎÔ˘˜ ÌÈÎÚfiÙÂÚÔ˘˜ ÙÔ˘ ÂÓfi˜ ÂηÙÔÛÙÔ‡, Î·È 21% ÁÈ· fiÁÎÔ˘˜ ÌÂٷ͇ ÂÓfi˜ Î·È ‰‡Ô ÂηÙÔÛÙÒÓ23. ™¯ÂÙÈο Ì ÙËÓ ·ÎÙÈÓÔÏÔÁÈ΋ Ù·ÍÈÓfiÌËÛË ÙÔ˘ Ë·ÙÔ΢ÙÙ·ÚÈÎÔ‡ ηÚΛÓÔ˘, ÌfiÓÔ 10 ·fi ÙÔ˘˜ 70 ·ÛıÂÓ›˜ Ì·˜ (14.3%) ›¯·Ó ÂÎÙÈÌËı› ÛˆÛÙ¿,fiÛÔÓ ·ÊÔÚ¿ ÛÙË ‰È¿ÌÂÙÚÔ ÙÔ˘ fiÁÎÔ˘, Î·È 24 ·fi ÙÔ˘˜ 70 (34.2%) fiÛÔÓ ·ÊÔÚ¿ ÛÙÔÓ ·ÚÈıÌfi ÙˆÓ fiÁΈÓ. ¶ÂÓ‹ÓÙ· ·ÛıÂÓ›˜ (71.4%) ›¯·Ó Ì›· ·fiÎÏÈÛË ÛÙË ‰È¿ÌÂÙÚÔ
ÙÔ˘ fiÁÎÔ˘ ÌÂÁ·Ï‡ÙÂÚË ÙÔ˘ ÂÓfi˜ ÂηÙÔÛÙÔ‡ ÛÙÔ ·ıÔÏÔÁÔ·Ó·ÙÔÌÈÎfi ·Ú·Û··ÛÌ· Û ۯ¤ÛË Ì ÙÔ ·ÎÙÈÓÔÏÔÁÈÎfi ‡ÚËÌ·, ÂÓÒ 26 ·ÛıÂÓ›˜ (37.1%) ›¯·Ó ÂÚÈÛÛfiÙÂÚÔ˘˜ fiÁÎÔ˘˜ ·fi fiÛÔ˘˜ ÂÚÈÂÁÚ¿ÊËÛ·Ó ÛÙ· ·ÎÙÈÓÔÏÔÁÈο Â˘Ú‹Ì·Ù·. ™‡Ìʈӷ Ì ٷ ÎÚÈÙ‹ÚÈ· ÙÔ˘ ªÈÏ¿ÓÔ˘, ÌfiÓÔ 60% ÙˆÓ ·ÛıÂÓÒÓ Â›¯·Ó ÂÎÙÈÌËı› ÛˆÛÙ¿ ÚÔÂÁ¯ÂÈÚËÙÈο23. ∞ÎfiÌË Î·È ÔÈ Mazzaferro Î·È Û˘ÓÂÚÁ¿Ù˜ ÛÙËÓ ÚˆÙfiÙ˘Ë ‰ËÌÔÛ›Â˘Û‹ ÙÔ˘˜4, ÂÓÒ ·Ú¯Èο ÂÚȤϷ‚·Ó Û˘ÓÔÏÈο 48 ·ÛıÂÓ›˜ Ô˘ ÏËÚÔ‡Û·Ó fiÏÔÈ Ù· ÎÚÈÙ‹ÚÈ¿ ÙÔ˘˜ Û‡Ìʈӷ Ì ٷ ·ÎÙÈÓÔÏÔÁÈο ÎÚÈÙ‹ÚÈ·, ‰È›ÛÙˆÛ·Ó fiÙÈ 35 ÌfiÓÔ ·ÛıÂÓ›˜ (73%) ÏËÚÔ‡Û·Ó ÂÓ Ù¤ÏÂÈ Ù· ÎÚÈÙ‹ÚÈ· ·˘Ù¿, Û‡Ìʈӷ Ì ٷ ·ıÔÏÔÁÔ·Ó·ÙÔÌÈο Â˘Ú‹Ì·Ù·, ÂÓÒ 13 ·ÛıÂÓ›˜ (27%) ‹Ù·Ó ÂÎÙfi˜ ÎÚÈÙËÚ›ˆÓ! ∞fi ÙȘ ·Ú·¿Óˆ ·Ó·ÊÔÚ¤˜ Â›Ó·È Ï¤ÔÓ ÚÔÊ·Ó¤˜ fiÙÈ Ë ÎÏÈÓÈ΋-ÚÔÌÂÙ·ÌÔÛ¯Â˘ÙÈ΋ Ù·ÍÈÓfiÌË-
94
°. ™øΔ∏ƒO¶OÀ§O™
ÛË ÙÔ˘ Ë·ÙÔ΢ÙÙ·ÚÈÎÔ‡ ηÚΛÓÔ˘ ÛÙÔ ÎÈÚÚˆÙÈÎfi ‹·Ú ÙÂÏÈÎÔ‡ ÛÙ·‰›Ô˘, Î·È Ë Î·Ù’ ¤ÎÙ·ÛË Î·Ù¿Ù·ÍË ·ÛıÂÓÒÓ Û‡Ìʈӷ Ì ٷ ÎÚÈÙ‹ÚÈ· ÙÔ˘ ªÈÏ¿ÓÔ˘, Ô˘ Â›Ó·È Î·ıÔÚÈÛÙÈ΋˜ ÛËÌ·Û›·˜ ÁÈ· ÙËÓ ·Ô‰Ô¯‹ ÙˆÓ ·ÛıÂÓÒÓ ÛÙÔ ÌÂÙ·ÌÔÛ¯Â˘ÙÈÎfi ηٿÏÔÁÔ ·Ó·ÌÔÓ‹˜, Â›Ó·È ÂÈÚÚ‹˜ Û ÔÏÏ¿ ÛÊ¿ÏÌ·Ù· ÂÎÙ›ÌËÛ˘, ÁÈ’ ·˘Ùfi Î·È Ë «·fiÏ˘ÙË» ·Ô‰Ô¯‹ ÙˆÓ ·Ú·¿Óˆ ÎÚÈÙËÚ›ˆÓ Â›Ó·È Î·Ù¿ ÚÒÙÔÓ Ô˘ÙÔÈ΋ Î·È Î·Ù¿ ‰Â‡ÙÂÚÔÓ ‰ÂÔÓÙÔÏÔÁÈο ÂÏÂÁ¯fiÌÂÓË.
∞ÔÙÂϤÛÌ·Ù· Ù˘ ÌÂÙ·ÌfiÛ¯Â˘Û˘ ‹·ÙÔ˜ Û ÎÈÚÚˆÙÈÎÔ‡˜ ·ÛıÂÓ›˜ Ì ˷ÙÔ΢ÙÙ·ÚÈÎfi ηÚΛÓÔ ÂÎÙfi˜ ÎÚÈÙËÚ›ˆÓ ªÈÏ¿ÓÔ˘ ∞Ó¿Ï˘ÛË ÙˆÓ ÚÒÙˆÓ 100 ÌÂÙ·ÌÔÛ¯Â˘Ì¤ÓˆÓ ÎÈÚÚˆÙÈÎÒÓ ·ÛıÂÓÒÓ Ì ˷ÙÔ΢ÙÙ·ÚÈÎfi ηÚΛÓÔ ÛÙÔ ¶·ÓÂÈÛÙËÌÈ·Îfi ¡ÔÛÔÎÔÌÂ›Ô ÙÔ˘ Essen, ¤‰ˆÛ ٷ οوıÈ ·ÔÙÂϤÛÌ·Ù· fiÛÔÓ ·ÊÔÚ¿ ÛÙ· ÎÚÈÙ‹ÚÈ· ÙÔ˘ ªÈÏ¿ÓÔ˘, ÛÙËÚÈÁ̤ӷ ÛÙ· ·ıÔÏÔÁÔ·Ó·ÙÔÌÈο Â˘Ú‹Ì·Ù·. ∏ ÛÂÈÚ¿ ‹Ù·Ó ηϿ ÈÛÔÏÔÁÈṲ̂ÓË fiÛÔÓ ·ÊÔÚ¿ ÛÙ· ÎÚÈÙ‹ÚÈ· ÂÈÏÔÁ‹˜ Î·È ÛÙË Ì¤ıÔ‰Ô ÌÂÙ·ÌfiÛ¯Â˘Û˘, ÂÚÈÏ·Ì‚¿ÓÔ˘Û· 48 ·ÛıÂÓ›˜ ÂÓÙfi˜ ÎÚÈÙËÚ›ˆÓ Î·È 52 ·ÛıÂÓ›˜ ÂÎÙfi˜, 55 ·ÛıÂÓ›˜ ÌÂÙ·ÌÔÛ¯Â˘Ì¤ÓÔ˘˜ ·fi و̷ÙÈÎfi Î·È 45 ·fi ˙ÒÓÙ· ‰fiÙË24. OÈ ·ÛıÂÓ›˜ ÂÎÙfi˜ ÎÚÈÙËÚ›ˆÓ ªÈÏ¿ÓÔ˘ ›¯·Ó ÂÈ‚›ˆÛË ÛÙÔ ¯ÚfiÓÔ Î·È ÛÙËÓ 5ÂÙ›· 76% Î·È 54% ·ÓÙ›ÛÙÔȯ·, Û ۇÁÎÚÈÛË Ì ÂÈ‚›ˆÛË ÛÙÔ ¯ÚfiÓÔ Î·È ÛÙËÓ 5ÂÙ›· 77% Î·È 66% ÁÈ· ·ÛıÂÓ›˜ ÂÓÙfi˜ ÎÚÈÙËÚ›ˆÓ, ·ÓÙ›ÛÙÔȯ· (p=0.22). ªÂٷ͇ ·ÛıÂÓÒÓ Ô˘ ‹Ù·Ó ÂÎÙfi˜ ÎÚÈÙËÚ›ˆÓ ªÈÏ¿ÓÔ˘ 12 ·ÛıÂÓ›˜ (23%) ·ÚÔ˘Û›·Û·Ó ˘ÔÙÚÔ‹ ÓfiÛÔ˘ ÛÙËÓ ÂÚ›Ô‰Ô ·Ú·ÎÔÏÔ‡ıËÛ˘ ÙˆÓ 38.4±24.3 ÌËÓÒÓ, ÂÓÒ Û ·ÓÙ›ıÂÛË ÌfiÓÔ 2 ·ÛıÂÓ›˜ (4%) ˘¤ÛÙËÛ·Ó ˘ÔÙÚÔ‹ Ë·ÙÔ΢ÙÙ·ÚÈÎÔ‡ ÌÂٷ͇ ÙˆÓ ·ÛıÂÓÒÓ Ô˘ ›¯·Ó ¯·Ú·ÎÙËÚÈÛÙÈο ÂÓÙfi˜ ÎÚÈÙËÚ›ˆÓ ÙÔ˘ ªÈÏ¿ÓÔ˘ (p=0.0148). ™˘ÓÔ„›˙ÔÓÙ·˜, ÔÈ ·ÛıÂÓ›˜ ÂÎÙfi˜ ·ıÔÏÔÁÔ·Ó·ÙÔÌÈÎÒÓ ÎÚÈÙËÚ›ˆÓ ªÈÏ¿ÓÔ˘ ›¯·Ó ¯ÂÈÚfiÙÂÚË ÂÈ‚›ˆÛË ·fi ÙÔ˘˜ ·ÛıÂÓ›˜ Ô˘ Ï‹ÚˆÓ·Ó ·˘Ù¿ Ù· ÎÚÈÙ‹ÚÈ·, ¯ˆÚ›˜ fï˜ Ë ‰È·ÊÔÚ¿ ÛÙËÓ ÂÈ‚›ˆÛË Ó· Â›Ó·È ÛÙ·ÙÈÛÙÈο ÛËÌ·ÓÙÈ΋. ™Â ·ÓÙ›ıÂÛË, ÔÈ ·ÛıÂÓ›˜ ÂÎÙfi˜ ·ıÔÏÔÁÔ·Ó·ÙÔÌÈÎÒÓ ÎÚÈÙËÚ›ˆÓ ªÈÏ¿ÓÔ˘ ·ÚÔ˘Û›·Û·Ó ÛÙ·ÙÈÛÙÈο ÌÂÁ·Ï‡ÙÂÚÔ ÔÛÔÛÙfi ˘ÔÙÚÔ‹˜ ÙÔ˘ fiÁÎÔ˘.
μÈ‚ÏÈÔÁÚ·ÊÈ΋ ·Ó·ÛÎfiËÛË Ù˘ ÛËÌ·Û›·˜ ÙˆÓ ÎÚÈÙËÚ›ˆÓ ÙÔ˘ ªÈÏ¿ÓÔ˘ ˆ˜ ÚÔÁÓˆÛÙÈÎÔ‡ ‰Â›ÎÙË ™Â Ì›· Û˘ÛÙËÌ·ÙÈ΋ ‚È‚ÏÈÔÁÚ·ÊÈ΋ ·Ó·ÛÎfiËÛË ÙˆÓ ‰ËÌÔÛȇÛÂˆÓ Ù˘ ÙÂÏÂ˘Ù·›·˜ 15ÂÙ›·˜ ÂÚ›
ÌÂÙ·ÌfiÛ¯Â˘Û˘ ‹·ÙÔ˜ ÁÈ· Ë·ÙÔ΢ÙÙ·ÚÈÎfi ηÚΛÓÔ ÌÂÏÂÙ‹Û·Ì Ì ÌÂıfi‰Ô˘˜ ̤ٷ-·Ó¿Ï˘Û˘ 8 ‰˘ÓËÙÈÎÔ‡˜ ÚÔÁÓˆÛÙÈÎÔ‡˜ ·Ú¿ÁÔÓÙ˜ ÁÈ· Û˘ÓÔÏÈ΋ ÂÈ‚›ˆÛË Î·È ˘ÔÙÚÔ‹ ÓfiÛÔ˘ ÌÂÙ¿ ·fi ÌÂÙ·ÌfiÛ¯Â˘ÛË24. ∏ ̤ٷ-·Ó¿Ï˘ÛË ÂÚȤϷ‚ 92 ÎÏÈÓÈΤ˜ ÌÂϤÙ˜. ªÂÏÂÙ‹ıËÎ·Ó Í¯ˆÚÈÛÙ¿ Ù· ·ÔÙÂϤÛÌ·Ù· ÙˆÓ ÌÔÓÔ·Ú·ÁÔÓÙÈÎÒÓ Î·È ÔÏ˘·Ú·ÁÔÓÙÈÎÒÓ ·Ó·Ï‡ÛÂˆÓ Ô˘ ·ÊÔÚÔ‡Û·Ó Û ÂÈ‚›ˆÛË ‹ ˘ÔÙÚÔ‹ fiÁÎÔ˘. Δ· ·ÔÙÂϤÛÌ·Ù· ·˘Ù‹˜ Ù˘ ̤ٷ-·Ó¿Ï˘Û˘, fiÛÔÓ ·ÊÔÚ¿ ÛÙ· ÎÚÈÙ‹ÚÈ· ÙÔ˘ ªÈÏ¿ÓÔ˘, ‹Ù·Ó Ù· ÂÍ‹˜:
ªÔÓÔ·Ú·ÁÔÓÙÈΤ˜ ÌÂϤÙ˜ ÁÈ· ÂÈ‚›ˆÛË ∞fi ÙȘ 92 ÌÂϤÙ˜ Ô˘ Û˘ÌÂÚÈÏ‹ÊıËÎ·Ó ÛÙËÓ ·Ó¿Ï˘ÛË, ÌfiÓÔ 12 ·Ó¤ÊÂÚ·Ó ÙÈ̤˜ ÛÙ·ÙÈÛÙÈ΋˜ ÛËÌ·ÓÙÈÎfiÙËÙ·˜ (p-values), Ô˘ ·ÊÔÚÔ‡Û·Ó ÛÙË ÌÂϤÙË Ù˘ ÂÈ‚›ˆÛ˘ ÁÈ· ·ÛıÂÓ›˜ ÂÓÙfi˜ Î·È ÂÎÙfi˜ ÎÚÈÙËÚ›ˆÓ ªÈÏ¿ÓÔ˘. ∂ÓÓ¤· ÂÍ ·˘ÙÒÓ ‹Ù·Ó ÌË ÛÙ·ÙÈÛÙÈο ÛËÌ·ÓÙÈΤ˜, ÂÓÒ ÔÈ ˘fiÏÔȘ ÙÚÂȘ ‹Ù·Ó ÛÙ·ÙÈÛÙÈο ÛËÌ·ÓÙÈΤ˜ (p<0.05). O Û˘ÁÎÂÓÙÚˆÙÈÎfi˜ ˘ÔÏÔÁÈÛÌfi˜ Ù˘ ÛÙ·ÙÈÛÙÈ΋˜ ÛËÌ·ÓÙÈÎfiÙËÙ·˜ Û‡Ìʈӷ Ì ÙËÓ truncated product ̤ıÔ‰Ô ÁÈ· ÙËÓ ÂÈ‚›ˆÛË ·Ó¤‰ÂÈÍ ÛÙ·ÙÈÛÙÈο ηχÙÂÚË ÂÈ‚›ˆÛË ÁÈ· ÙÔ˘˜ ·ÛıÂÓ›˜ ÂÓÙfi˜ ÙˆÓ ÎÚÈÙËÚ›ˆÓ ÙÔ˘ ªÈÏ¿ÓÔ˘ (p=0.0023).
ªÔÓÔ·Ú·ÁÔÓÙÈΤ˜ ÌÂϤÙ˜ ÁÈ· ˘ÔÙÚÔ‹ ÙÔ˘ fiÁÎÔ˘ ∞fi ÙȘ 92 ÌÂϤÙ˜ Ô˘ Û˘ÌÂÚÈÏ‹ÊıËÎ·Ó ÛÙËÓ ·Ó¿Ï˘ÛË, ÌfiÓÔ 13 ·Ó¤ÊÂÚ·Ó ÙÈ̤˜ ÛÙ·ÙÈÛÙÈ΋˜ ÛËÌ·ÓÙÈÎfiÙËÙ·˜, Ô˘ ·ÊÔÚÔ‡Û·Ó ÛÙË ÌÂϤÙË Ù˘ ˘ÔÙÚÔ‹˜ ÙÔ˘ fiÁÎÔ˘ ÁÈ· ·ÛıÂÓ›˜ ÂÓÙfi˜ Î·È ÂÎÙfi˜ ÎÚÈÙËÚ›ˆÓ ªÈÏ¿ÓÔ˘. ¶¤ÓÙ ÂÍ ·˘ÙÒÓ ‹Ù·Ó ÌË ÛÙ·ÙÈÛÙÈο ÛËÌ·ÓÙÈΤ˜, ÂÓÒ ÔÈ ˘fiÏÔȘ ÂÙ¿ ‹Ù·Ó ÛÙ·ÙÈÛÙÈο ÛËÌ·ÓÙÈΤ˜. O Û˘ÁÎÂÓÙÚˆÙÈÎfi˜ ˘ÔÏÔÁÈÛÌfi˜ Ù˘ ÛÙ·ÙÈÛÙÈ΋˜ ÛËÌ·ÓÙÈÎfiÙËÙ·˜ Û‡Ìʈӷ Ì ÙËÓ truncated product ̤ıÔ‰Ô ÁÈ· ÙËÓ ˘ÔÙÚÔ‹ ÙÔ˘ fiÁÎÔ˘ ·Ó¤‰ÂÈÍ ÛÙ·ÙÈÛÙÈο ¯·ÌËÏfiÙÂÚÔ ÔÛÔÛÙfi ˘ÔÙÚÔ‹˜ ÁÈ· ÙÔ˘˜ ·ÛıÂÓ›˜ ÂÓÙfi˜ ÙˆÓ ÎÚÈÙËÚ›ˆÓ ÙÔ˘ ªÈÏ¿ÓÔ˘ (p<0.0001).
¶ÔÏ˘·Ú·ÁÔÓÙÈΤ˜ ÌÂϤÙ˜ ÁÈ· ÂÈ‚›ˆÛË ∞fi ÙȘ 92 ÌÂϤÙ˜ Ô˘ Û˘ÌÂÚÈÏ‹ÊıËÎ·Ó ÛÙËÓ ·Ó¿Ï˘ÛË, ÌfiÓÔ 4 ·Ó¤ÊÂÚ·Ó ÙÈ̤˜ ÛÙ·ÙÈÛÙÈ΋˜ ÛËÌ·ÓÙÈÎfiÙËÙ·˜ ÛÙËÓ ÔÏ˘·Ú·ÁÔÓÙÈ΋ ·Ó¿Ï˘ÛË, Ô˘ ·ÊÔÚÔ‡Û·Ó ÛÙË ÌÂϤÙË Ù˘ ÂÈ‚›ˆÛ˘ ÁÈ· ·ÛıÂÓ›˜ ÂÓÙfi˜ Î·È ÂÎÙfi˜ ÎÚÈÙËÚ›ˆÓ ªÈÏ¿ÓÔ˘. ŸÏ˜ ‹Ù·Ó ÌË ÛÙ·ÙÈÛÙÈο ÛËÌ·ÓÙÈΤ˜. O Û˘ÁÎÂÓÙÚˆÙÈÎfi˜ ˘ÔÏÔÁÈÛÌfi˜ Ù˘ ÛÙ·ÙÈÛÙÈ΋˜ ÛËÌ·ÓÙÈ-
METAMO™XEY™Eπ™ 2008
ÎfiÙËÙ·˜ ÁÈ· ÙËÓ ÂÈ‚›ˆÛË Û‡Ìʈӷ Ì ÙË Ì¤ıÔ‰Ô ÙÔ˘ Tippet ‰ÂÓ ·Ó¤‰ÂÈÍ ÛÙ·ÙÈÛÙÈο ÛËÌ·ÓÙÈΤ˜ ‰È·ÊÔÚ¤˜ ÛÙËÓ ÂÈ‚›ˆÛË ÁÈ· ·ÛıÂÓ›˜ ÂÓÙfi˜ ‹ ÂÎÙfi˜ ÎÚÈÙËÚ›ˆÓ ªÈÏ¿ÓÔ˘ (p>0.05).
¶ÔÏ˘·Ú·ÁÔÓÙÈΤ˜ ÌÂϤÙ˜ ÁÈ· ˘ÔÙÚÔ‹ ÙÔ˘ fiÁÎÔ˘ ∞fi ÙȘ 92 ÌÂϤÙ˜ Ô˘ Û˘ÌÂÚÈÏ‹ÊıËÎ·Ó ÛÙËÓ ·Ó¿Ï˘ÛË, ÌfiÓÔ 4 ·Ó¤ÊÂÚ·Ó ÙÈ̤˜ ÛÙ·ÙÈÛÙÈ΋˜ ÛËÌ·ÓÙÈÎfiÙËÙ·˜ ÛÙËÓ ÔÏ˘·Ú·ÁÔÓÙÈ΋ ·Ó¿Ï˘ÛË, Ô˘ ·ÊÔÚÔ‡Û·Ó ÛÙË ÌÂϤÙË Ù˘ ˘ÔÙÚÔ‹˜ ÙÔ˘ fiÁÎÔ˘ ÁÈ· ·ÛıÂÓ›˜ ÂÓÙfi˜ Î·È ÂÎÙfi˜ ÎÚÈÙËÚ›ˆÓ ªÈÏ¿ÓÔ˘. ŸÏ˜ ‹Ù·Ó ÌË ÛÙ·ÙÈÛÙÈο ÛËÌ·ÓÙÈΤ˜. O Û˘ÁÎÂÓÙÚˆÙÈÎfi˜ ˘ÔÏÔÁÈÛÌfi˜ Ù˘ ÛÙ·ÙÈÛÙÈ΋˜ ÛËÌ·ÓÙÈÎfiÙËÙ·˜ ÁÈ· ÙËÓ ˘ÔÙÚÔ‹ ÙÔ˘ fiÁÎÔ˘ Û‡Ìʈӷ Ì ÙË Ì¤ıÔ‰Ô ÙÔ˘ Tippet ‰ÂÓ ·Ó¤‰ÂÈÍ ÛÙ·ÙÈÛÙÈο ÛËÌ·ÓÙÈΤ˜ ‰È·ÊÔÚ¤˜ ÛÙËÓ ˘ÔÙÚÔ‹ ÙÔ˘ fiÁÎÔ˘ ÁÈ· ·ÛıÂÓ›˜ ÂÓÙfi˜ ‹ ÂÎÙfi˜ ÎÚÈÙËÚ›ˆÓ ªÈÏ¿ÓÔ˘ (p>0.05). ™˘ÌÂÚ·ÛÌ·ÙÈο, ÂÓÒ ˘ÔÏÔÁ›ÛÙËΠÚÔÁÓˆÛÙÈ΋ ÛËÌ·ÓÙÈÎfiÙËÙ· ÙˆÓ ÎÚÈÙËÚ›ˆÓ ÙÔ˘ ªÈÏ¿ÓÔ˘ ÛÙË Ì¤Ù·-·Ó¿Ï˘ÛË ÙˆÓ ÌÔÓÔ·Ú·ÁÔÓÙÈÎÒÓ ÌÂÏÂÙÒÓ ÙfiÛÔ ÁÈ· ÂÈ‚›ˆÛË, fiÛÔ Î·È ÁÈ· ˘ÔÙÚÔ‹ ÙÔ˘ fiÁÎÔ˘, ‰ÂÓ ÂȂ‚·ÈÒıËΠÛÙË Ì¤Ù·-·Ó¿Ï˘ÛË ÙˆÓ ÔÏ˘·Ú·ÁÔÓÙÈÎÒÓ ÌÂÏÂÙÒÓ, Ô‡Ù ÁÈ· ÙËÓ ÂÈ‚›ˆÛË, Ô‡Ù ÁÈ· ÙËÓ ˘ÔÙÚÔ‹ ÙÔ˘ fiÁÎÔ˘, ÎÏÔÓ›˙ÔÓÙ·˜ ÙËÓ ÚÔÁÓˆÛÙÈ΋ ÛËÌ·Û›· ÙˆÓ ÎÚÈÙËÚ›ˆÓ ·˘ÙÒÓ ÛÙËÓ ÎÏÈÓÈ΋ ÙÔ˘˜ ÂÊ·ÚÌÔÁ‹.
™˘ÌÂÚ¿ÛÌ·Ù· ∏ ÌÂÙ·ÌfiÛ¯Â˘ÛË ‹·ÙÔ˜ ·ÔÙÂÏ› ÙËÓ Î·Ï‡ÙÂÚË ıÂڷ›· ÙÔ˘ Ë·ÙÔ΢ÙÙ·ÚÈÎÔ‡ ηÚΛÓÔ˘ ÛÙÔ ÎÈÚÚˆÙÈÎfi ‹·Ú, ·ÓÂÍ·Úًو˜ ÎÚÈÙËÚ›ˆÓ. Δ· ÎÚÈÙ‹ÚÈ· ÙÔ˘ ªÈÏ¿ÓÔ˘ ·ÚÔ˘ÛÈ¿˙Ô˘Ó ÔÏÏ¿ ·ÛıÂÓ‹ ÛËÌ›· ÛÙËÓ ÎÏÈÓÈ΋ ÙÔ˘˜ ÂÊ·ÚÌÔÁ‹. ∞fi ÙË ÛÙÈÁÌ‹ Ô˘ Û‡Á¯ÚÔÓ˜ ÌÂϤÙ˜ ·Ô‰ÂÈÎÓ‡Ô˘Ó ÛËÌ·ÓÙÈ΋ ·fiÎÏÈÛË ÙˆÓ ·ıÔÏÔÁÔ·Ó·ÙÔÌÈÎÒÓ Â˘ÚËÌ¿ÙˆÓ Û ۯ¤ÛË Ì ٷ ·ÎÙÈÓÔÏÔÁÈο Â˘Ú‹Ì·Ù·, ÔÈ ·ÎÙÈÓÔÏÔÁÈΤ˜ ̤ıÔ‰ÔÈ Ô˘ Â›Ó·È ‰È·ı¤ÛÈ̘ ·‰˘Ó·ÙÔ‡Ó Ó· ÂÎÙÈÌ‹ÛÔ˘Ó Â·ÚÎÒ˜ ÂÛٛ˜ Ë·ÙÔ΢ÙÙ·ÚÈÎÔ‡ ηÚΛÓÔ˘ ÌÈÎÚfiÙÂÚ˜ ÙˆÓ 2 ÂηÙÔÛÙÒÓ Î·È È‰È·›ÙÂÚ· ÌÈÎÚfiÙÂÚ˜ ÙÔ˘ 1 ÂηÙÔÛÙÔ‡, Î·È Ë ÌÈÎÚÔ·ÁÁÂȷ΋ ‰È‹ıËÛË, ÛËÌ·ÓÙÈÎfi˜ ÚÔÁÓˆÛÙÈÎfi˜ ·Ú¿ÁÔÓÙ·˜ ÛÙËÓ ÔÚ›· Ù˘ ÓfiÛÔ˘, ‰ÂÓ Â›Ó·È ·ÎfiÌË ‰˘Ó·ÙfiÓ Ó· ÂÎÙÈÌËı› ÚÔÂÁ¯ÂÈÚËÙÈο, Â›Ó·È ‰ÈηÈÔÏÔÁË̤ÓË Ë ÌÂÙ·ÌfiÛ¯Â˘ÛË Î·È ·ÛıÂÓÒÓ ÂÎÙfi˜ ÙˆÓ Â˘Ú¤ˆ˜ ÂÊ·ÚÌÔ˙fiÌÂÓˆÓ ÎÚÈÙËÚ›ˆÓ ªÈÏ¿ÓÔ˘. OˆÛ‰‹ÔÙÂ, ÏfiÁˆ Ù˘ ‰Ú·Ì·ÙÈ΋˜ ¤ÏÏÂȄ˘ ÔÚÁ¿ÓˆÓ, Ë ‰È‡ڢÓÛË ÙˆÓ ÎÚÈÙËÚ›ˆÓ ÙÔ˘ ªÈÏ¿ÓÔ˘ ‰ÂÓ Ú¤ÂÈ Ó·
95
˘ÂÚ‚·›ÓÂÈ Î¿ÔÈ· fiÚÈ·. Δ· ÚÔÙÂÈÓfiÌÂÓ· ÎÚÈÙ‹ÚÈ· ·fi ÙÔ ¶·ÓÂÈÛÙ‹ÌÈÔ Ù˘ ∫·ÏÈÊfiÚÓÈ·˜/San Fransisco (UCSF, ÌÔÓ‹Ú˘ fiÁÎÔ˜≤6.5cm, 2-3 fiÁÎÔÈ ÂÎ ÙˆÓ ÔÔ›ˆÓ ηÓ›˜ >4.5cm ‹ ÔÏÈ΋ ‰È¿ÌÂÙÚÔ˜ ≤8cm, ·Ô˘Û›· ·ÁÁÂȷ΋˜ ‰È‹ıËÛ˘) ·ÔÙÂÏÔ‡Ó Û›ÁÔ˘Ú· Ì›· ηϋ Î·È Û¯ÂÙÈο Û˘ÁÎÚ·ÙË̤ÓË ·ÏÏ¿ ‹‰Ë ·ÚÎÂÙ¿ ·Ô‰ÂÎÙ‹ ÂͤÏÈÍË ÛÙËÓ ÚÔÛ¿ıÂÈ· ‰È‡ڢÓÛ˘ ÙˆÓ ÎÚÈÙËÚ›ˆÓ25. ¶ÂÚ·ÈÙ¤Úˆ ÎÏÈÓÈÎÔ› ‰Â›ÎÙ˜, fiˆ˜ Ô ‚·ıÌfi˜ Ù˘ ‰È·ÊÔÚÔÔ›ËÛ˘ ÙÔ˘ fiÁÎÔ˘, ÌÔÚÔ‡Ó Ó· ¯ÚËÛÈÌÔÔÈËıÔ‡Ó ÛÙË ‰È·ÏÔÁ‹ ÙˆÓ ·ÛıÂÓÒÓ26. ∏ ÌÂÙ·ÌfiÛ¯Â˘ÛË ‹·ÙÔ˜ ·fi ˙ÒÓÙ· ‰fiÙË ·ÔÙÂÏ› ·ÎfiÌË ÙËÓ Â˘Ú‡ÙÂÚ· ·Ô‰ÂÎÙ‹ ̤ıÔ‰Ô ÎÏÈÓÈ΋˜ ÚÔÛ¿ıÂÈ·˜ ÛÙÔÓ ·ÁÒÓ· ‰È‡ڢÓÛ˘ ÙˆÓ ÂÊ·ÚÌÔ˙fiÌÂÓˆÓ ÎÚÈÙËÚ›ˆÓ Î·È ÂÈÛ·ÁˆÁ‹˜ Ó¤ˆÓ.
∞Ó·ÊÔÚ¤˜ 1. Kim WR, Gores G J, Benson J T, et al. Mortality and hospital utilization for hepatocellular carcinoma in the United States. Gastroenterology 2005; 129: 486-493. 2. Hayashi PH, Di Bisceglie AM. The progression of hepatitis B- and C-infections to chronic liver disease and hepatocellular carcinoma: presentation, diagnosis, screening, prevention, and treatment of hepatocellular carcinoma. Med Clin North Am 2005; 89: 345-369. 3. Bigourdan JM, Jaeck D, Meyer N et al. Small hepatocellular carcinoma in Child A cirrhotic patients: hepatic resection versus transplantation. Liver Transpl 2003; 9: 513-520. 4. Mazzaferro V, Regalia E, Doci R et al. Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis. N Engl J Med 1996; 334: 693-699. 5. Llovet JM, Bruix J, Fuster J et al. Liver transplantation for small hepatocellular carcinoma: the tumor-nodemetastasis classification does not have prognostic power. Hepatology 1998; 27: 1572-1577. 6. Bismuth H, Majno PE, Adam R. Liver transplantation for hepatocellular carcinoma. Semin Liver Dis 1999; 19: 311-322. 7. De Carlis L, Giacomoni A, Lauterio A et al. Liver transplantation for hepatocellular cancer: should the current indication criteria be changed? Transpl Int 2003; 16: 115-122. 8. Malago M, Hertl M, Testa G et al. Split-liver transplantation: future use of scarce donor organs. World J Surg 2002; 26: 275-282. 9. Sotiropoulos GC, Lang H, Fruhauf NR et al. In situ splitting of deceased donor livers: an additional option for patients with hepatocellular carcinoma in cirrhosis. Surgery 2006; 139: 452. 10. Sotiropoulos GC, Paul A, Molmenti E et al. Liver transplantation for hepatocellular carcinoma in cirrhosis within the Eurotransplant area: an additional option
96
°. ™øΔ∏ƒO¶OÀ§O™
with “livers that nobody wants”. Transplantation 2005; 80: 897-902. 11. Miller CM, Gondolesi GE, Florman S et al. One hundred nine living donor liver transplants in adults and children: a single-center experience. Ann Surg 2001; 234: 301-311; discussion 311-302. 12. Malago M, Testa G, Frilling A et al. Right living donor liver transplantation: an option for adult patients: single institution experience with 74 patients. Ann Surg 2003; 238: 853-862; discussion 862-853. 13. Kaihara S, Kiuchi T, Ueda M et al. Living-donor liver transplantation for hepatocellular carcinoma. Transplantation 2003; 75: S37-40. 14. Gondolesi GE, Roayaie S, Munoz L et al. Adult living donor liver transplantation for patients with hepatocellular carcinoma: extending UNOS priority criteria. Ann Surg 2004; 239: 142-149. 15. Lo CM, Fan ST, Liu CL et al. The role and limitation of living donor liver transplantation for hepatocellular carcinoma. Liver Transpl 2004; 10: 440-447.
19. Malago M, Testa G, Marcos A et al. Ethical considerations and rationale of adult-to-adult living donor liver transplantation. Liver Transpl 2001; 7: 921-927. 20. Lopez Hanninen E, Vogl TJ, Bechstein WO, et al. Biphasic spiral computed tomography for detection of hepatocellular carcinoma before resection or orthotopic liver transplantation. Invest Radiol 1998; 33: 216-221. 21. Krinsky GA, Lee VS, Theise ND et al. Transplantation for hepatocellular carcinoma and cirrhosis: sensitivity of magnetic resonance imaging. Liver Transpl 2002; 8: 1156-1164. 22. Bhartia B, Ward J, Guthrie JA et al. Hepatocellular carcinoma in cirrhotic livers: Double-contrast thinsection MR imaging with pathologic correlation of explanted tissue. Am J Roentgenol 2003; 180: 577-584. 23. Sotiropoulos GC, Malag_ M, Molmenti E et al. Liver transplantation for hepatocellular carcinoma in cirrhosis: is clinical tumor classification before transplantation realistic? Transplantation.2005; 79: 483-487.
16. Todo S, Furukawa H. Living donor liver transplantation for adult patients with hepatocellular carcinoma: experience in Japan. Ann Surg 2004; 240: 451-459; discussion 459-461.
24. Sotiropoulos GC, Lang H, Nadalin S et al. Liver transplantation for hepatocellular carcinoma: University Hospital Essen experience and metaanalysis of prognostic factors. J Am Coll Surg 2007; 205: 661-675.
17. Hwang S, Lee SG, Joh JW et al. Liver transplantation for adult patients with hepatocellular carcinoma in Korea: comparison between cadaveric donor and living donor liver transplantations. Liver Transpl 2005; 11: 1265-1272.
25. Yao FY, Ferrell L, Bass NM et al. Liver transplantation for hepatocellular carcinoma: expansion of the tumor size limits does not adversely impact survival. Hepatology 2001; 33: 1394-1403.
18. Malago M, Sotiropoulos GC, Nadalin S et al. Living donor liver transplantation for hepatocellular carcinoma: a single-center preliminary report. Liver Transpl 2006; 12: 934-940.
26. Sotiropoulos GC, Molmenti EP, Lösch C et al. Metaanalysis of tumor recurrence after liver transplantation for hepatocellular carcinoma based on 1,198 cases. Eur J Med Res 2007; 12:527-534.
A¡Aπ™£∏™πA KAI ENTATIKH £EƒA¶EIA ™Δ∏ ªETAMO™XEY™H H¶ATO™
¶Ó¢ÌÔÓÈ΋ ˘¤ÚÙ·ÛË Î·È ÌÂÙ·ÌfiÛ¯Â˘ÛË ‹·ÙÔ˜ °.π. ªÔ‡ÙÛÈ·ÓÔ˜
Û˘Ó‹ıˆ˜ ¯ÚËÛÈÌÔÔÈÔ‡ÌÂÓÔÈ Ê·Ú̷΢ÙÈÎÔ› ·Ú¿ÁÔÓÙ˜ Â›Ó·È Î˘Ú›ˆ˜ Ë ÂÓ‰ÔÊϤ‚È· ¯ÔÚ‹ÁËÛË ÚÔÛÙ·Î˘ÎÏ›Ó˘ fiˆ˜ Î·È Ë ¯Ú‹ÛË ·ÓÙ·ÁˆÓÈÛÙÒÓ ÙˆÓ ˘Ô‰Ô¯¤ˆÓ Ù˘ ÂÓ‰ÔıËÏ›Ó˘ Î·È ÙˆÓ ·Ó·ÛÙÔϤˆÓ Ù˘ 5-ʈÛÊÔ‰ÈÂÛÙÂÚ¿Û˘. ¶Ú¤ÂÈ Ó· ÛËÌÂȈı› fiÙÈ ·Ú¿ ÙË ıÂڷ›· Ë ÂÚÈÂÁ¯ÂÈÚËÙÈ΋ ıÓËÙfiÙËÙ· ÛÙÔ˘˜ ·ÛıÂÓ›˜ ·˘ÙÔ‡˜ Â›Ó·È ˘„ËÏfiÙÂÚË Î·È fiÙÈ Ë ˘Ï·ÈÔÓ¢ÌÔÓÈ΋ ˘¤ÚÙ·ÛË ÌÔÚ› Ó· ·Ú·Ì›ÓÂÈ Ë Ó· ÚˆÙÔÂÌÊ·ÓÈÛÙ› ·ÎfiÌË Î·È ÌÂÙ¿ ÙË ÌÂÙ·ÌfiÛ¯Â˘ÛË Î¿ÓÔÓÙ·˜ ÂÈÙ·ÎÙÈ΋ ÙËÓ Â·ÁÚ‡ÓËÛË Î·È ÙÔÓ Ì·ÎÚÔ¯ÚfiÓÈÔ ¤ÏÂÁ¯Ô ÙˆÓ ·ÛıÂÓÒÓ ·˘ÙÒÓ.
H Ó¢ÌÔÓÈ΋ ˘¤ÚÙ·ÛË Û ·ÛıÂÓ›˜ Ì ˷ÙÈ΋ ·Ó¿ÚÎÂÈ· ÙÂÏÈÎÔ‡ ÛÙ·‰›Ô˘ ‹ ·ÏÏÈÒ˜ ˘Ï·ÈÔÓ¢ÌÔÓÈ΋ ˘¤ÚÙ·ÛË (portopulmonary hypertension – PPHT) ÔÚ›˙ÂÙ·È ˆ˜ ÚÔÙÚȯÔÂȉÈ΋ Ó¢ÌÔÓÈ΋ ˘¤ÚÙ·ÛË Û˘Óԉ¢fiÌÂÓË ·fi Ë·ÙÈ΋ ÓfiÛÔ ‹ ˘Ï·›· ˘¤ÚÙ·ÛË. ¶ÚÔηÏÂ›Ù·È ·fi ˘ÂÚ‚ÔÏÈ΋ Î·È ÌË Ê˘ÛÈÔÏÔÁÈ΋ ·Ó¿Ù˘ÍË (remodeling) ÙÔ˘ Ó¢ÌÔÓÈÎÔ‡ ·ÁÁÂÈ·ÎÔ‡ ‰ÈÎÙ‡Ô˘ Î·È ·ÁÁÂÈÔÛ‡Û·ÛË, ÌÂÙ·‚ÔϤ˜ Ô˘ Â›Ó·È fiÌÔȘ Î·È ÛÙȘ ¿ÏϘ ÌÔÚʤ˜ Ó¢ÌÔÓÈ΋˜ ˘¤ÚÙ·Û˘. ™ÙÔ˘˜ ·Ú¿ÁÔÓÙ˜ Ô˘ ÂÌϤÎÔÓÙ·È ÛÙËÓ ·ıÔÁ¤ÓÂÛË Ù˘, ÂÚÈÏ·Ì‚¿ÓÔÓÙ·È Ë ˘ÂÚÊfiÚÙˆÛË fiÁÎÔ˘, Ë ˘ÂÚ‰˘Ó·ÌÈ΋ ΢ÎÏÔÊÔÚ›· Î·È Î˘ÎÏÔÊÔÚÔ‡ÓÙ˜ ·ÁÁÂÈÔ‰Ú·ÛÙÈÎÔ› ‰È·‚È‚·ÛÙ¤˜. ◊È· ÂÒ˜ ̤ÙÚÈ· Ó¢ÌÔÓÈ΋ ˘¤ÚÙ·ÛË (̤ÛË < 35 mm Hg) ‰ÂÓ ·ÔÙÂÏ› ·ÓÙ¤Ó‰ÂÈÍË ÁÈ· ÌÂÙ·ÌfiÛ¯Â˘ÛË ˆÛÙfiÛÔ Ë ıÓËÛÈÌfiÙËÙ· ·˘Í¿ÓÂÙ·È Û ÂÚ›Ô˘ 100% Û ‚·ÚÈ¿ Ó¢ÌÔÓÈ΋ ˘ÂÚÙ·ÛË (̤ÛË > 50 mm Hg). °È· Ó· ıˆÚËı› ÏÔÈfiÓ Î¿ÔÈÔ˜ ·ÛıÂÓ‹˜ Ì Ó¢ÌÔÓÈ΋ ˘¤ÚÙ·ÛË ˘Ô„‹ÊÈÔ˜ ÁÈ· ÌÂÙ·ÌfiÛ¯Â˘ÛË ·ÏÏ¿ Î·È ÚÈÓ ·fi ÙË ÌÂÙ·ÌfiÛ¯Â˘ÛË ··ÈÙÂ›Ù·È ÚÔÛ¿ıÂÈ· ÁÈ· ÙÔÓ fiÛÔ ÙÔ ‰˘Ó·Ùfi Î·Ï˘ÙÂÚÔ ¤ÏÂÁ¯Ô Ù˘ Ó¢ÌÔÓÈ΋˜ ˘¤ÚÙ·Û˘ Ì ÛÙfi¯Ô ÌÈ· ̤ÛË ›ÂÛË ÙÔ˘Ï¿¯ÈÛÙÔÓ <35-40 mm Hg. ∏ ÚÔÛ¿ıÂÈ· ·˘Ù‹ Ú·ÁÌ·ÙÔÔÈÂ›Ù·È Ì ÙË ¯Ú‹ÛË Î·Ù¿ÏÏËÏÔ˘ ηډÈÔÏÔÁÈÎÔ‡ ‰È·ÁÓˆÛÙÈÎÔ‡ ÂϤÁ¯Ô˘ Î·È ·ÈÌÔ‰˘Ó·ÌÈÎÔ‡ monitoring ÂÓÒ ÔÈ
μÈ‚ÏÈÔÁÚ·Ê›· 1. Fabbroni D., Bellamy M. Anaesthesia for hepatic transplantation. Continuing Education in Anaesthesia, Critical Care & Pain, Volume 6 Number 5 2006 171-175. 2. Manley J., Plotkin J. et al. Controversies in anaesthetic management of liver transplantation. HPB, 2005; 7: 183-185. 3. Halank M., Ewert R. et al. Portopulmonary hypertension. J Gastroenterol. 2006 Sep;41(9):837-47. 4. Hedrickse A., Azam F, Mandell MS. Hepatopulmonary syndrome and portopulmonary hypertension. Curr Treat Options Cardiovasc Med. 2007 Apr;9(2):127-36. 5. Tam NL, He XS. Clinical management of portopulmonary hypertension. Herpatobiliary Pancrea Dis Int. 2007 Oct;6(5):464-9.
99
¢ÈÂÁ¯ÂÈÚËÙÈ΋ ÓÂÊÚÈ΋ ‰˘ÛÏÂÈÙÔ˘ÚÁ›· ÛÙË ÌÂÙ·ÌfiÛ¯Â˘ÛË ‹·ÙÔ˜ ∞. §·Ì·‰·Ú›Ô˘
∞. ∂π™∞°ø°∏
ÎÙËÚ›˙ÂÙ·È ·fi ÓÂÊÚÈ΋ ·Ó¿ÚÎÂÈ· – ÏÂÈÙÔ˘ÚÁÈ΋˜ ·ÈÙÈÔÏÔÁ›·˜ – Î·È ÛÔ‚·Ú¤˜ ‰È·Ù·Ú·¯¤˜ Ù˘ Û˘ÛÙËÌ·ÙÈ΋˜ ΢ÎÏÔÊÔÚ›·˜, ÔÈ Ôԛ˜ ıˆÚÂ›Ù·È fiÙÈ ˘ÚÔ‰ÔÙÔ‡Ó ÌÈ· ÛÂÈÚ¿ ·ıÔÁÂÓÂÙÈÎÒÓ Ì˯·ÓÈÛÌÒÓ, Ô˘ Ô‰ËÁÔ‡Ó ÌÂٷ͇ ¿ÏÏˆÓ Î·È ÛÙËÓ ÂΉ‹ÏˆÛ‹ ÙÔ˘2,3. OÈ ÂÚÈÛÛfiÙÂÚÔÈ ·ÛıÂÓ›˜ Ô˘ ÂΉËÏÒÓÔ˘Ó ∏.¡.™., Û˘Ó‹ıˆ˜ ¿Û¯Ô˘Ó ·fi ÚÔ¯ˆÚË̤ÓË Î›ÚÚˆÛË Î·È ÛÔ‚·Ú‹ ˘Ï·›· ˘¤ÚÙ·ÛË, ›ÎÙÂÚÔ, ‰È·Ù·Ú·¯¤˜ ËÎÙÈÎfiÙËÙ·˜, η¯ÂÍ›· Î·È ÂÁÎÂÊ·ÏÈ΋ ÂÁÎÂÊ·ÏÔ¿ıÂÈ·. ΔÔ ∏.¡.™. ÌÔÚ› Ó· ÂΉËψı› ¯ˆÚ›˜ ÚÔÊ·Ó‹ ·ÈÙ›·, Û˘Ó‹ıˆ˜ fï˜ ˘ÚÔ‰ÔÙÂ›Ù·È ·fi ÔÚÈṲ̂ÓÔ˘˜ ·Ú¿ÁÔÓÙ˜, fiˆ˜ Ë ·ÚÔ¯¤Ù¢ÛË Ì·˙ÈÎÒÓ ÔÛÔÙ‹ÙˆÓ (> 5 lt) ·ÛÎÈÙÈÎÔ‡ ˘ÁÚÔ‡ ¯ˆÚ›˜ ·Ó¿ÏÔÁË ·ÔηٿÛÙ·ÛË ÙÔ˘ Ï¿ÛÌ·ÙÔ˜, Ë ‚·ÎÙËÚȷ΋ ÂÚÈÙÔÓ›Ùȉ· Î·È Ë ·ÈÌÔÚÚ·Á›· ÂÙÈÎÔ‡3,4. ∏ ‰È¿ÁÓˆÛË Ù›ıÂÙ·È Ì ·ÔÎÏÂÈÛÌfi fiÏˆÓ ÙˆÓ ¿ÏÏˆÓ ·ÈÙ›ˆÓ Ô˘ ÚÔηÏÔ‡Ó ÓÂÊÚÈ΋ ·Ó¿ÚÎÂÈ·. ∏ ¯·ÌËÏ‹ Û˘ÁΤÓÙÚˆÛË ÙÔ˘ Ó·ÙÚ›Ô˘ ÙˆÓ Ô‡ÚˆÓ, Ë Ùˆ¯‹ ·¿ÓÙËÛË Ù˘ ‰ÈÔ‡ÚËÛ˘ ÛÙË ¯ÔÚ‹ÁËÛË ÎÔÏÏÔÂȉÒÓ Î·È Ë „¢‰‹˜ ˘ÔÓ·ÙÚÈ·ÈÌ›·, Û˘ÓËÁÔÚÔ‡Ó ˘¤Ú Ù˘ ‰È¿ÁÓˆÛ˘ ∏.¡.™.3. ΔÔ ∏.¡.™. ‰È·ÎÚ›ÓÂÙ·È Û ‰‡Ô Ù‡Ô˘˜. O Ù‡Ô˜ -1, ¯·Ú·ÎÙËÚ›˙ÂÙ·È ·fi 100 % ·‡ÍËÛË Ù˘ ÎÚ·ÙÈÓ›Ó˘ ÙÔ˘ ÔÚÔ‡ Û ÙÈ̤˜ > 2.5 mg/dl Î·È Ì›ˆÛË ÙÔ˘ GFR < 20 ml/min, Û ÂÚ›Ô‰Ô ÌÈÎÚfiÙÂÚË ÙˆÓ 2 ‚‰ÔÌ¿‰ˆÓ. OÈ ·ÛıÂÓ›˜ ·˘ÙÔ› Û˘Ó‹ıˆ˜ ¤¯Ô˘Ó ÔÏÈÁÔ·ÓÔ˘·Ú›· Î·È ¯ÚÂÈ¿˙ÔÓÙ·È ·ÈÌÔ‰È¿Ï˘ÛË ÂÓÒ Ë ÚfiÁÓˆÛË Â›Ó·È Ôχ Ùˆ¯‹ (̤ÛÔ˜ fiÚÔ˜ ÂÈ‚›ˆÛ˘ 15 Ë̤Ú˜). ΔÔ ∏.¡.™. Ù‡Ô˘ – 2, Â›Ó·È ÈÔ Î·ÏfiËı˜ (̤ÛÔ˜ fiÚÔ˜ ÂÈ‚›ˆÛ˘ 6 Ì‹Ó˜), ¯·Ú·ÎÙËÚ›˙ÂÙ·È ·fi ˘ÔÙÚÔÈ¿˙ÔÓÙ· ·ÛΛÙË Ô˘ ‰ÂÓ ·ÓÙ·ÔÎÚ›ÓÂÙ·È ÛÙË ‰ÈÔ˘ÚËÙÈ΋ ·ÁˆÁ‹ Î·È ÌÔÚ› ÔÔÙ‰‹ÔÙ ӷ ÌÂÙ·¤ÛÂÈ ÛÂ Ù‡Ô˘ – 13,4. Δ· ÙÂÏÂ˘Ù·›· ¯ÚfiÓÈ·, ¤¯Ô˘Ó ‰ÔÎÈÌ·ÛÙ› Ì ηϿ ·ÔÙÂϤÛÌ·Ù· ‰È¿ÊÔÚ˜ ıÂڷ›˜ (·ÁÁÂÈÔÛ˘Û·ÛÙÈο Ê¿Ú̷η ·Ó¿ÏÔÁ· Ù˘ ‚·ÛÔÚÂÛÛ›Ó˘, TIPS, MARS), Ô˘ ‚ÂÏÙÈÒÓÔ˘Ó ÙË ÓÂÊÚÈ΋ ÏÂÈ-
∏ ÓÂÊÚÈ΋ ·Ó¿ÚÎÂÈ· Â›Ó·È Û˘¯Ó‹ ÂÈÏÔ΋ ÙˆÓ ·ÛıÂÓÒÓ Ì ÙÂÏÈÎÔ‡ ÛÙ·‰›Ô˘ Ë·ÙÈ΋ ÓfiÛÔ (Δ.™.∏.¡.), Ô˘ ˘Ô‚¿ÏÏÔÓÙ·È Û ÔÚıÔÙÔÈ΋ ÌÂÙ·ÌfiÛ¯Â˘ÛË ‹·ÙÔ˜ (O.ª.∏.). ŸÏ˜ ÔÈ ÌÂϤÙ˜ ‰Â›¯ÓÔ˘Ó fiÙÈ ÙfiÛÔ Ë ÔÍ›· ÓÂÊÚÈ΋ ·Ó¿ÚÎÂÈ· (O.¡.∞.) Ô˘ ÌÔÚ› Ó· ÂΉËψı› ηٿ ÙËÓ ÂÚÈÂÁ¯ÂÈÚËÙÈ΋ ÂÚ›Ô‰Ô Ù˘ ÌÂÙ·ÌfiÛ¯Â˘Û˘ fiÛÔ Î·È Ë ¯ÚfiÓÈ· ÓÂÊÚÈ΋ ·Ó¿ÚÎÂÈ· (Ã.¡.∞.) Ô˘ ·Ó·Ù‡ÛÛÂÙ·È Ì·ÎÚÔÚfiıÂÛÌ· – ΢ڛˆ˜ ·fi ÙË ¯Ú‹ÛË ÙˆÓ ·Ó·ÛÙÔϤˆÓ Ù˘ ηÏÛÈÓ¢ڛÓ˘ – ÂËÚ¿˙Ô˘Ó ÛÔ‚·Ú¿ ÙË ÓÔÛËÚfiÙËÙ· Î·È ÙËÓ ÙÂÏÈ΋ ¤Î‚·ÛË ÙˆÓ ·ÛıÂÓÒÓ ·˘ÙÒÓ1.
μ. ¡∂ºƒπ∫∏ ∞¡∂¶∞ƒ∫∂π∞ ∫∞π Δ∂§π∫OÀ ™Δ∞¢πOÀ ∏¶∞Δπ∫∏ ¡O™O™ ™Â ÔÏÏÔ‡˜ ·ÛıÂÓ›˜ Ì Δ.™.∏.¡. Ô˘ Â›Ó·È ˘Ô„‹ÊÈÔÈ ÁÈ· ÌÂÙ·ÌfiÛ¯Â˘ÛË ‹·ÙÔ˜, Û˘Ó˘¿Ú¯ÂÈ Û˘¯Ó¿ ‰È·ÊfiÚÔ˘ ‚·ıÌÔ‡ ÓÂÊÚÈ΋ ‰˘ÛÏÂÈÙÔ˘ÚÁ›·, Ô˘ ÌÔÚ› Ó· ÚÔÎÏËı› ·fi ÔÏϤ˜ ÓfiÛÔ˘˜ ‹ ηٷÛÙ¿ÛÂȘ, Ô˘ ÂËÚ¿˙Ô˘Ó ¿ÌÂÛ· ‹ ¤ÌÌÂÛ· ÙË ÓÂÊÚÈ΋ ÏÂÈÙÔ˘ÚÁ›·.
1. ™˘Ó˘¿Ú¯Ô˘Û˜ ÓfiÛÔÈ ¶ÔÏϤ˜ Û˘ÛÙËÌ·ÙÈΤ˜ ÓfiÛÔÈ ÚÔÛ‚¿ÏÏÔ˘Ó ÙfiÛÔ ÙÔ ‹·Ú fiÛÔ Î·È ÙÔ˘˜ ÓÂÊÚÔ‡˜, fiˆ˜ Ë ÔÏ˘Î˘ÛÙÈ΋ ÓfiÛÔ˜, Ë ·Ì˘ÏÔ›‰ˆÛË, Ë ·ÈÌԯڈ̿وÛË, Ë ·˘ÙÔ¿ÓÔÛË Ë·Ù›Ùȉ·, Ë ˘ÂÚÔÍ·ÏÔ˘Ú›·, Ë ÓfiÛÔ˜ ÙÔ˘ Wilson, ÙÔ Û‡Ó‰ÚÔÌÔ Sjogren’s, Î.·. ™ÙÔ˘˜ ·ÛıÂÓ›˜ Ì ˷ٛÙȉ· μ, ÌÔÚ› Ó· ÂΉËψı› ÌÂÌ‚Ú·Ó҉˘ ˘ÂÚÏ·ÛÙÈ΋ ÛÂÈÚ·Ì·ÙÔÓÂÊÚ›Ùȉ· Î·È Ô˙҉˘ ÔÏ˘·ÚÙËÚ›Ùȉ· ÂÓÒ Ë Ë·Ù›Ùȉ· C, Û˘Ó‰¤ÂÙ·È Ì ÂÌÊ¿ÓÈÛË ÎÚ˘ÔÛÊ·ÈÚÈÓ·ÈÌ›·˜. ∂›Û˘, Ë Û˘Ó‡·ÚÍË Ë·ÙÈ΋˜ ÓfiÛÔ˘ Ì ÛÔ‚·Ú‹˜ ÌÔÚÊ‹˜ ۷ί·ÚÒ‰Ë ‰È·‚‹ÙË ‹ ˘¤ÚÙ·ÛË, ÂËÚ¿˙ÂÈ ÛËÌ·ÓÙÈο ÙË ÓÂÊÚÈ΋ ÏÂÈÙÔ˘ÚÁ›·2.
2. ∏·ÙÔÓÂÊÚÈÎfi Û‡Ó‰ÚÔÌÔ ΔÔ Ë·ÙÔÓÂÊÚÈÎfi Û‡Ó‰ÚÔÌÔ (∏.¡.™.) ¯·Ú·-
100
METAMO™XEY™Eπ™ 2008
ÙÔ˘ÚÁ›· ·ÏÏ¿ η̛· ‰ÂÓ Â›Ó·È ÈηӋ Ó· ·Ó·ÛÙÚ¤„ÂÈ ÔÚÈÛÙÈο ÙÔ ∏.¡.™. ÂÎÙfi˜ ·fi ÙËÓ ÂÈÙ˘¯‹ ÌÂÙ·ÌfiÛ¯Â˘ÛË ‹·ÙÔ˜2-4. ™‡Ìʈӷ Ì ‰È¿ÊÔÚ˜ ÌÂϤÙ˜, Ô ¯ÚfiÓÔ˜ χÛ˘ ÙÔ˘ ∏.¡.™. ÌÂÙ¿ ·fi ÂÈÙ˘¯‹ O.ª.∏., Î˘Ì·›ÓÂÙ·È ·fi 4 ¤ˆ˜ 110 Ë̤Ú˜ Ì ̤ÛÔ fiÚÔ ÙȘ 21+ 27 Ë̤Ú˜ ÂÓÒ ÙÔ ÔÛÔÛÙfi ÙˆÓ ·ÛıÂÓÒÓ Ì ∏.¡.™. Ô˘ ÂÈ‚›ˆÛ ̷ÎÚÔÚfiıÂÛÌ· ¯ˆÚ›˜ ıÂڷ›· ÓÂÊÚÈ΋˜ ˘ÔηٿÛÙ·Û˘ ÌÂÙ¿ ÙËÓ O.ª.∏., Î˘Ì·›ÓÂÙ·È ·fi 58 % ¤ˆ˜ 77 %4,5.
3. OÍ›· ÓÂÊÚÈ΋ ·Ó¿ÚÎÂÈ· ∏ O.¡.∞., ˘fi ÙËÓ ¤ÓÓÔÈ· Ù˘ ÔÍ›·˜ Ì›ˆÛ˘ ÙÔ˘ Ú˘ıÌÔ‡ ÛÂÈÚ·Ì·ÙÈ΋˜ ‰È‹ıËÛ˘ (GFR) Ô˘ ÌÔÚ› Ó· ÚÔηϤÛÂÈ ·˙ˆı·ÈÌ›·, Û˘Ó‰¤ÂÙ·È Ì ıÓËÙfiÙËÙ· ¿Óˆ ·fi 60 % Î·È Â›Ó·È Û˘¯Ó‹ ÂÈÏÔ΋ ÙˆÓ ·ÛıÂÓÒÓ Ì Δ.™.∏.¡. ™˘Ó‹ıˆ˜ Ë O.¡.∞. Ô˘ Û˘Ì‚·›ÓÂÈ ÛÙÔ˘˜ ·ÛıÂÓ›˜ Ô˘ ‰ÂÓ ¿Û¯Ô˘Ó ·fi ¿ÏÏË Û˘ÛÙËÌ·ÙÈ΋ ÓfiÛÔ, ¤¯ÂÈ Î·Ï‡ÙÂÚË ÚfiÁÓˆÛË Î·È Û˘Ó‰¤ÂÙ·È Ì ÌÈÎÚfiÙÂÚ· ÔÛÔÛÙ¿ ıÓËÙfiÙËÙ·˜2. Δ· ·›ÙÈ· Ô˘ ÙËÓ ÚÔηÏÔ‡Ó Â›Ó·È Û˘Ó‹ıˆ˜ ÔÏ˘·Ú·ÁÔÓÙÈο. OÈ ·ÛıÂÓ›˜ Ì ·ÛΛÙË, Ï·Ì‚¿ÓÔ˘Ó Û˘Ó‹ıˆ˜ ¤ÓÙÔÓË ‰ÈÔ˘ÚËÙÈ΋ ·ÁˆÁ‹ Î·È ˘Ô‚¿ÏÏÔÓÙ·È Û ÂÎÎÂÓˆÙÈΤ˜ ·Ú·ÎÂÓÙ‹ÛÂȘ, Ô˘ ÚÔηÏÔ‡Ó ‚·ÚÈ¿ ·Ê˘‰¿ÙˆÛË Î·È ÚÔÓÂÊÚÈ΋˜ ·ÈÙÈÔÏÔÁ›·˜ ·˙ˆı·ÈÌ›·. ∏ O.¡.∞. ÌÔÚ› Ó· ÚÔÎÏËı› Î·È È·ÙÚÔÁÂÓÒ˜, ·fi ÂÓ‰ÔÊϤ‚È· ¯ÔÚ‹ÁËÛË ÛÎÈ·ÁÚ·ÊÈÎÒÓ Ô˘ÛÈÒÓ ÁÈ· ·ÎÙÈÓԉȷÁÓˆÛÙÈΤ˜ ÂÍÂÙ¿ÛÂȘ ‹ ·ÓÙÈ‚ÈÔÙÈÎÒÓ ÁÈ· ÙËÓ ·ÓÙÈÌÂÙÒÈÛË ÏÔÈÌÒÍÂˆÓ fiˆ˜ ÔÈ ·ÌÈÓÔÁÏ˘ÎÔÛ›‰Â˜, Ë ·ÌÊÔÙÂÚÈΛÓË μ, ÔÈ ÂÓÈÎÈÏϛӘ, ÔÈ ÎÂÊ·ÏÔÛÔÚ›Ó˜, ÔÈ ÛÔ˘ÏÊÔÓ·Ì›‰Â˜ Î·È Ë ÚÈÊ·ÌÈΛÓË. ∂›Û˘, ÂÓÔ¯ÔÔÈÂ›Ù·È Ë ¯ÔÚ‹ÁËÛË ÙˆÓ ·Ó·ÛÙÔϤˆÓ ÙÔ˘ ÌÂÙ·ÙÚÂÙÈÎÔ‡ ÂÓ˙‡ÌÔ˘ Ù˘ ·ÁÁÂÈÔÙÂÓÛ›Ó˘, ÙˆÓ ÌË ÛÙÂÚÔÂȉÒÓ ·ÓÙÈÊÏÂÁÌÔÓˆ‰ÒÓ Ê·ÚÌ¿ÎˆÓ Û˘ÌÂÚÈÏ·Ì‚·ÓÔÌ¤ÓˆÓ Î·È ÙˆÓ ·Ó·ÛÙÔϤˆÓ Ù˘ COX-2, Ù˘ ÈÓÙÂÚÊÂÚfiÓ˘ Î·È Ù˘ ÈÓÙÂÚÏ¢ΛÓ˘ 2. ∏ O.¡.∞. ÌÔÚ› ·ÛÊ·ÏÒ˜ Ó· ÂΉËψı› Î·È ÛÙ· Ï·›ÛÈ· ¤Ó·Ú͢ ‹ Âȉ›ӈÛ˘ Ë·ÙÔÓÂÊÚÈÎÔ‡ Û˘Ó‰ÚfiÌÔ˘. ªÂ ‚¿ÛË Ù· ·ÓˆÙ¤Úˆ, Â›Ó·È ÚÔÊ·Ó¤˜ fiÙÈ ÔÈ Èı·ÓfiÙËÙ˜ ÂΉ‹ÏˆÛ˘ O.¡.∞. ÔÔÈ·‰‹ÔÙ ÛÙÈÁÌ‹ ηٿ ÙËÓ ÂÚÈÂÁ¯ÂÈÚËÙÈ΋ ÂÚ›Ô‰Ô Ù˘ O.ª.∏. Â›Ó·È ÌÂÁ¿Ï˜, ·˘Í¿ÓÔÓÙ·˜ ÛËÌ·ÓÙÈο ÙË ÓÔÛËÚfiÙËÙ· Î·È ıÓËÙfiÙËÙ·. ¶·ÚfiÙÈ Û οı ÂÚ›ÙˆÛË Ú¤ÂÈ Ó· ·ÔÎÏ›ÂÙ·È Ë ·ÔÊÚ·ÎÙÈ΋ Ô˘ÚÔ¿ıÂÈ· ˆ˜ ·ÈÙ›· O.¡.∞., Û ÔÛÔÛÙfi ¿Óˆ ·fi 50 % ·˘Ù‹ ÔÊ›ÏÂÙ·È Û ÔÍ›· ÛˆÏËÓ·Úȷ΋ Ó¤ÎÚˆÛË (O.™.¡.)1,2.
101
°. O•∂π∞ ¡∂ºƒπ∫∏ ∞¡∂¶∞ƒ∫∂π∞ ™Δ∏¡ ∏¶∞Δπ∫∏ ª∂Δ∞ªO™Ã∂À™∏ 1. ∂›ÙˆÛË, ·Èٛ˜ Î·È ·Ú¿ÁÔÓÙ˜ ÎÈÓ‰‡ÓÔ˘ ÚfiÎÏËÛ˘ ÂÚÈÂÁ¯ÂÈÚËÙÈ΋˜ O.¡.∞. ∏ ›وÛË Ù˘ O.¡.∞ ÛÙÔ˘˜ ·ÛıÂÓ›˜ Ô˘ ˘Ô‚¿ÏÏÔÓÙ·È Û ÌÂÙ·ÌfiÛ¯Â˘ÛË ‹·ÙÔ˜, Î˘Ì·›ÓÂÙ·È ·fi 20 % - 90 %6. ¶ÂÚÈÛÛfiÙÂÚÔ ·fi ÙÔ 80 % ÙˆÓ ÂÂÈÛÔ‰›ˆÓ ÓÂÊÚÈ΋˜ ‰˘ÛÏÂÈÙÔ˘ÚÁ›·˜, ÛËÌÂÈÒÓÂÙ·È ÙȘ ÚÒÙ˜ ‰‡Ô ÌÂÙÂÁ¯ÂÈÚËÙÈΤ˜ Ë̤Ú˜ Î·È ÔÊ›ÏÂÙ·È Û ÔÍ›· ÛˆÏËÓ·Úȷ΋ Ó¤ÎÚˆÛË ·fi ·Ú·ÙÂٷ̤ÓË ÈÛ¯·ÈÌ›·. ∏ ıÓËÙfiÙËÙ· ÛÙȘ 30 Ë̤Ú˜ ·Ó¤Ú¯ÂÙ·È ÛÙÔ 50 % ÛÙÔ˘˜ ·ÛıÂÓ›˜ Ì O.¡.∞. Î·È ÛÙÔ 29 % Û ·˘ÙÔ‡˜ Ô˘ ‰ÂÓ ÂΉËÏÒÓÔ˘Ó O.¡.∞7. ∞fi ÙÔ˘˜ ·ÛıÂÓ›˜ Ô˘ ÂΉËÏÒÓÔ˘Ó O.¡.∞. ÌÂÙ¿ ÙËÓ O.ª.∏., ÔÛÔÛÙfi 8 %-17 %, ¯ÚÂÈ¿˙ÂÙ·È ıÂڷ›· ˘ÔηٿÛÙ·Û˘ Î·È ÂÌÊ·Ó›˙ÂÈ ıÓËÙfiÙËÙ· Ô˘ Î˘Ì·›ÓÂÙ·È 55 % 90 %8-10. Δ· ÛËÌ·ÓÙÈÎfiÙÂÚ· ·›ÙÈ· ÚfiÎÏËÛ˘ O.¡.∞. ηٿ ÙËÓ ÂÚÈÂÁ¯ÂÈÚËÙÈ΋ ÂÚ›Ô‰Ô, Â›Ó·È ÔÏÏ¿ ·fi ·˘Ù¿ Ô˘ ÚԷӷʤÚıËÎ·Ó Î·È ÂÈϤÔÓ, Ë ÛÔ‚·Ú‹ ÚÔÂÁ¯ÂÈÚËÙÈ΋ Î·È ‰ÈÂÁ¯ÂÈÚËÙÈ΋ ˘fiÙ·ÛË, Ë ˘ÔÁηÈÌ›·, Ë Û‹„Ë, ÙÔ Û‡Ó‰ÚÔÌÔ ÂÓ‰ÔÎÔÈÏÈ·ÎÔ‡ ‰È·ÌÂÚ›ÛÌ·ÙÔ˜ Î·È Ë ¤Ó·ÚÍË ¯ÔÚ‹ÁËÛ˘ ÙˆÓ ÓÂÊÚÔÙÔÍÈÎÒÓ ·ÓÔÛÔηٷÛÙ·ÏÙÈÎÒÓ Ê·ÚÌ¿ÎˆÓ – ·Ó·ÛÙÔϤˆÓ Ù˘ ηÏÛÈÓ¢ڛÓ˘ (΢ÎÏÔÛÔÚ›ÓË ∞, tacrolimus)2,11,12. ¶ÔÏϤ˜ ÌÂϤÙ˜ ¤¯Ô˘Ó ÚÔÛ‰ÈÔÚ›ÛÂÈ ‰È¿ÊÔÚÔ˘˜ ·Ú¿ÁÔÓÙ˜ ÎÈÓ‰‡ÓÔ˘, Ô˘ Û¯ÂÙ›˙ÔÓÙ·È Ì ÙËÓ ÂÌÊ¿ÓÈÛË O.¡.∞.ηٿ ÙËÓ ÂÚÈÂÁ¯ÂÈÚËÙÈ΋ ÂÚ›Ô‰Ô Ù˘ O.ª.∏. ™ËÌ·ÓÙÈÎfiÙÂÚÔÈ ıˆÚÔ‡ÓÙ·È Ë ÚÔÂÁ¯ÂÈÚËÙÈ΋ ÓÂÊÚÈ΋ ‰˘ÛÏÂÈÙÔ˘ÚÁ›· (ÎÚ·ÙÈÓ›ÓË ÔÚÔ‡ > 1.5 mg/dl), Ë ÚÔÂÁ¯ÂÈÚËÙÈ΋ ÂÁÎÂÊ·ÏÔ¿ıÂÈ·, Ô ·ÛΛÙ˘, ÔÈ ÌÂÁ¿Ï˜ ‰ÈÂÁ¯ÂÈÚËÙÈΤ˜ ·Ó¿ÁΘ Û ÌÂÙ¿ÁÁÈÛË ·›Ì·ÙÔ˜ Î·È ·Ú·ÁÒÁˆÓ, Ô ¯ÚfiÓÔ˜ ÈÛ¯·ÈÌ›·˜ ÙÔ˘ ÌÔۯ‡̷ÙÔ˜ > 8 ÒÚ˜, Ë ‰˘ÛÏÂÈÙÔ˘ÚÁ›· ÙÔ˘ Ë·ÙÈÎÔ‡ ÌÔۯ‡̷ÙÔ˜ ¿Óˆ ·fi 4 Ë̤Ú˜ ÌÂÙÂÁ¯ÂÈÚËÙÈο, Ë Â·ÓÂÁ¯Â›ÚËÛË Î·È Ë ‚·ÎÙËÚȷ΋ Û‹„Ë11-13.
2. ¢ÈÂÁ¯ÂÈÚËÙÈ΋ ·ÓÙÈÌÂÙÒÈÛË Î·È ÂÈÏÔΤ˜ ∂Âȉ‹ ÔÏÏ¿ ·fi Ù· ·›ÙÈ· Î·È ÙÔ˘˜ ·Ú¿ÁÔÓÙ˜ ÎÈÓ‰‡ÓÔ˘ ÚfiÎÏËÛ˘ O.¡.∞. ÂȉÚÔ‡Ó ‹ ÂȉÂÈÓÒÓÔÓÙ·È ‰ÈÂÁ¯ÂÈÚËÙÈο, ¤¯Ô˘Ó ‰ÔÎÈÌ·ÛÙ› Î·È ÌÂÏÂÙËı› ‰È¿ÊÔÚ· ıÂڷ¢ÙÈο Û¯‹Ì·Ù· Ì ÛÙfi¯Ô ÙËÓ ÚfiÏË„Ë Î·È ‚ÂÏÙ›ˆÛË Ù˘ ÌÂÙÂÁ¯ÂÈÚËÙÈ΋˜ ÓÂÊÚÈ΋˜ ‰˘ÛÏÂÈÙÔ˘ÚÁ›·˜.
102
∞. §∞ª¶∞¢∞ƒπ√À
2.1. ™‡ÛÙËÌ· ÊÏ‚Ô-ÊÏ‚È΋˜ ·Ú¿Î·Ì„˘ (Veno-venous Bypass, V-VB) ΔÔ Û‡ÛÙËÌ· V-VB, ÂÈÛ‹¯ıË ÛÙËÓ O.ª.∏. ÙË ‰ÂηÂÙ›· ÙÔ˘ ’80. ∫·Ù¿ ÙËÓ ·ÓË·ÙÈ΋ Ê¿ÛË Ù˘ ¤̂·Û˘, Ú·ÁÌ·ÙÔÔÈÂ›Ù·È ˘Ô¯ÚˆÙÈÎfi˜, ÚÔÛˆÚÈÓfi˜ ·ÔÎÏÂÈÛÌfi˜ Ù˘ ˘Ï·›·˜ Î·È Ù˘ οو ÎÔ›Ï˘ ÊϤ‚·˜. O ¯ÂÈÚÈÛÌfi˜ ·˘Ùfi˜ ÂÌÔ‰›˙ÂÈ ÙËÓ ·Ô¯¤Ù¢ÛË Ù˘ ÛÏ·¯ÓÈ΋˜ Î·È Û˘ÛÙËÌ·ÙÈ΋˜ ÊÏ‚È΋˜ ΢ÎÏÔÊÔÚ›·˜ (ÙÔ˘ οو ̤ÚÔ˘˜ ÙÔ˘ ÛÒÌ·ÙÔ˜ Î·È ÙˆÓ Î¿Ùˆ ¿ÎÚˆÓ). ∞˘Ùfi ¤¯ÂÈ ˆ˜ Û˘Ó¤ÂȘ, ÙÔ ‰È¿¯˘ÙÔ Ô›‰ËÌ· Î·È ÙË ‰˘ÛÚ·Á›· ÙÔ˘ Á·ÛÙÚÂÓÙÂÚÈÎÔ‡ ۈϋӷ, ÙË ÓÂÊÚÈ΋ ÊÏ‚È΋ Û˘ÌÊfiÚËÛË Î·È ÙË ÓÂÊÚÈ΋ ‰˘ÛÏÂÈÙÔ˘ÚÁ›·, ÙËÓ ·ÈÌÔ‰˘Ó·ÌÈ΋ ·ÛÙ¿ıÂÈ· Î·È ÙȘ ‚·ÚȤ˜ ‰È·Ù·Ú·¯¤˜ Ù˘ ÔÍÂÔ‚·ÛÈ΋˜ ÈÛÔÚÚÔ›·˜ Î·È ÙÔ˘ Î·Ï›Ô˘14. ªÂ ÙËÓ Ù¯ÓÈ΋ ÙÔ˘ Û˘ÛÙ‹Ì·ÙÔ˜ V-VB, ÙÔ ÊÏ‚ÈÎfi ·›Ì· ·fi ÙËÓ ·ÔÎÏÂÈṲ̂ÓË ˘Ï·›· Î·È Î¿Ùˆ ÎÔ›ÏË ÊϤ‚· ‰ÈÔ¯ÂÙ‡ÂÙ·È Ì ÙË ‚Ô‹ıÂÈ· ·ÓÙÏ›·˜ ÛÙË Ì·Û¯·ÏÈ·›· ÊϤ‚·, ÂÍ·ÛÊ·Ï›˙ÔÓÙ·˜ ¿Óˆ ·fi ÙÔ 40 % Ù˘ ηډȷ΋˜ ·ÚÔ¯‹˜ Î·È ·ÔÙÚ¤ÔÓÙ·˜ ÙË ÊÏ‚È΋ ÛÙ¿ÛË. ªÂ ·˘Ùfi ÙÔÓ ÙÚfiÔ, ÙÔ V-VB ıˆڋıËΠfiÙÈ ‚ÂÏÙÈÒÓÂÈ ÙË ÓÂÊÚÈ΋ ÏÂÈÙÔ˘ÚÁ›· Î·È ÚÔÛٷهÂÈ ·fi ÙËÓ ÂΉ‹ÏˆÛË O.¡.∞. ∏ ¯Ú‹ÛË ÙÔ˘ fï˜ ¤¯ÂÈ ÂÁηٷÏÂÈÊı› Ù· ÙÂÏÂ˘Ù·›· ¯ÚfiÓÈ· ·fi Ù· ÂÚÈÛÛfiÙÂÚ· ΤÓÙÚ·, ÏfiÁˆ ÙˆÓ ÛÔ‚·ÚÒÓ ÌÂÈÔÓÂÎÙËÌ¿ÙˆÓ ÙÔ˘ Î·È Ù˘ ·Ó¿Ù˘Í˘ ÓÂfiÙÂÚˆÓ ÙÚÔÔÔÈËÌ¤ÓˆÓ ¯ÂÈÚÔ˘ÚÁÈÎÒÓ Ù¯ÓÈÎÒÓ, Ô˘ ‰ÂÓ Î·ıÈÛÙÔ‡Ó Ï¤ÔÓ ·Ó·Áη›· ÙË ¯Ú‹ÛË ÙÔ˘. ∂›Û˘, ÔÈ ÌÂϤÙ˜ ‰ÂÓ ˘ÔÛÙËÚ›˙Ô˘Ó ÙËÓ Â˘ÓÔ˚΋ ›‰Ú·ÛË Ù˘ ¯Ú‹Û˘ ÙÔ˘ V-VB ÛÙË ÓÂÊÚÈ΋ ÏÂÈÙÔ˘ÚÁ›·2.
2.2. ª·ÓÓÈÙfiÏË ∏ Ì·ÓÓÈÙfiÏË Â›Ó·È Â˘Ú¤ˆ˜ ¯ÚËÛÈÌÔÔÈË̤ÓÔ ˆÛ̈ÙÈÎfi ‰ÈÔ˘ÚËÙÈÎfi, ÁÈ· ÙËÓ ÚfiÏË„Ë Ù˘ O.¡.∞. ¶ÂÈÚ·Ì·ÙÈΤ˜ ÌÂϤÙ˜ ˘ÔÛÙËÚ›˙Ô˘Ó ˆ˜ fiÙ·Ó Ë ˘¤ÚÙÔÓË Ì·ÓÓÈÙfiÏË ¯ÔÚËÁÂ›Ù·È ÚÈÓ ÙËÓ ÚfiÎÏËÛË Ù˘ ‚Ï¿‚˘, ÚÔÛٷهÂÈ ÙË ÓÂÊÚÈ΋ ÏÂÈÙÔ˘ÚÁ›·15. Œ¯Ô˘Ó ÚÔÙ·ı› ‰È¿ÊÔÚÔÈ Ì˯·ÓÈÛÌÔ› ÁÈ· ·˘Ùfi ÙÔ ·ÔÙ¤ÏÂÛÌ·. ∏ Ì·ÓÓÈÙfiÏË ıˆÚÂ›Ù·È fiÙÈ ·˘Í¿ÓÂÈ ÙËÓ ¤ÎÎÚÈÛË ¡a+ Î·È ÓÂÚÔ‡ ÛÙÔ ¿ˆ ÂÛÂÈڷ̤ÓÔ ÛˆÏËÓ¿ÚÈÔ Î·È Ì ·˘Ùfi ÙÔÓ ÙÚfiÔ Ù· ÍÂϤÓÂÈ ·fi Ù· ÓÂÎÚ¿ ·ÙÙ·Ú· Î·È Ù· ¿¯ÚËÛÙ· ˘ÔÏ›ÌÌ·Ù· Ô˘ ‰ËÌÈÔ˘ÚÁ› Ë ‚Ï¿‚Ë. ∞ÎfiÌË, ·Ú·ÈÒÓÂÈ ÙË Û˘ÁΤÓÙÚˆÛË ÙˆÓ ÓÂÊÚÔÙÔÍÈÎÒÓ Ô˘ÛÈÒÓ Ì¤Û· ÛÙ· ÛˆÏËÓ¿ÚÈ·, ÌÂÈÒÓÔÓÙ·˜ ¤ÙÛÈ ÙË ‚Ï·ÙÈ΋ ÙÔ˘˜ ›‰Ú·ÛË. ∏ ˘ÂÚˆÛ̈ÙÈ΋ ηٿÛÙ·ÛË Ô˘ ‰ËÌÈÔ˘ÚÁ›, Èı·ÓfiÓ ÂÏ·ÙÙÒÓÂÈ ÙÔ Ô›‰ËÌ· ÙˆÓ ÂÓ‰ÔıËÏÈ·ÎÒÓ Î˘ÙÙ¿ÚˆÓ. ∂›Û˘, ıˆÚÂ›Ù·È fiÙÈ ‰ÂÛ̇ÂÈ ÙȘ ÂχıÂÚ˜ Ú›˙˜.
¶·ÚfiÏ· ·˘Ù¿, ÌÂϤÙ˜ Û ·ÛıÂÓ›˜ Ô˘ ˘Ô‚Ï‹ıËÎ·Ó Û ·ÔηٿÛÙ·ÛË ·Ó¢ڇÛÌ·ÙÔ˜ ÎÔÈÏȷ΋˜ ·ÔÚÙ‹˜ Î·È ˘¤ÛÙËÛ·Ó ·ÔÎÏÂÈÛÌfi Ù˘ ÎÔÈÏȷ΋˜ ·ÔÚÙ‹˜ οو ·fi ÙȘ ÓÂÊÚÈΤ˜ ·ÚÙËڛ˜, ‰ÂÓ ˘ÔÛÙËÚ›˙Ô˘Ó ÙË ÓÂÊÚÔÚÔÛٷ٢ÙÈ΋ Ù˘ ‰Ú¿ÛË15. ¶·ÚfiÌÔÈ· Î·È Û ·ÛıÂÓ›˜ Ô˘ ÂΉ‹ÏˆÛ·Ó ·ÓÙ›‰Ú·ÛË ÛÙË ÌÂÙ¿ÁÁÈÛË, Ë ¯ÔÚ‹ÁËÛ‹ Ù˘ ‰ÂÓ ÚÔÛٿ٢۠·fi ÙË ÓÂÊÚÈ΋ ‚Ï¿‚Ë16. ∏ ¯ÔÚ‹ÁËÛË Ù˘ Ì·ÓÓÈÙfiÏ˘ ÂÓ¤¯ÂÈ ÙÔÓ Î›Ó‰˘ÓÔ ÚfiÎÏËÛ˘ Ó¢ÌÔÓÈÎÔ‡ Ôȉ‹Ì·ÙÔ˜ Û ÔÏÈÁÔ˘ÚÈÎÔ‡˜ ·ÛıÂÓ›˜ Ì ηډȷ΋ ·Ó¿ÚÎÂÈ·, ÁÈ·Ù› ÚÔηÏ› ·fiÙÔÌË ·‡ÍËÛË ÙÔ˘ ÂÓ‰·ÁÁÂÈ·ÎÔ‡ fiÁÎÔ˘. ∂›Û˘, Ë ¯ÔÚ‹ÁËÛ‹ Ù˘ ÌÔÚ› Ó· Ô‰ËÁ‹ÛÂÈ Û ˘ÔÁηÈÌ›· ÏfiÁˆ ÌÂÁ¿Ï˘ ·ÒÏÂÈ·˜ Ó·ÙÚ›Ô˘ Î·È ÓÂÚÔ‡.
2.3. ¡ÙÔ·Ì›ÓË ∏ ÓÙÔ·Ì›ÓË ¯ÔÚËÁÂ›Ù·È ‰ÈÂÁ¯ÂÈÚËÙÈο Û ÔÏÈÁÔ˘ÚÈÎÔ‡˜ ·ÛıÂÓ›˜ Ì ÛÎÔfi ÙËÓ ·‡ÍËÛË Ù˘ ‰ÈÔ‡ÚËÛ˘. ∏ ‰Ú¿ÛË Ù˘ Û¯ÂÙ›˙ÂÙ·È Ì ÂÎÏÂÎÙÈ΋ ‰È¤ÁÂÚÛË ÙˆÓ ÓÂÊÚÈÎÒÓ ÓÙÔ·ÌÈÓÂÚÁÈÎÒÓ ˘Ô‰Ô¯¤ˆÓ, Ô˘ ÚÔηÏ› ·ÁÁÂÈԉȷÛÙÔÏ‹ ÙˆÓ ÓÂÊÚÈÎÒÓ ·ÚÙËÚȉ›ˆÓ Î·È ·‡ÍËÛË Ù˘ ÓÂÊÚÈ΋˜ ·ÈÌ·ÙÈ΋˜ ÚÔ‹˜. ∞ÓÂÍ¿ÚÙËÙ· ·fi ·˘Ùfi, ·Ó·ÛÙ¤ÏÏÂÈ ÙËÓ Â·Ó·ÚÚfiÊËÛË ÙˆÓ ÓÂÊÚÈÎÒÓ ÛˆÏËÓ·Ú›ˆÓ ÚÔ¿ÁÔÓÙ·˜ ÙËÓ ·‡ÍËÛË Ù˘ ·Ô‚ÔÏ‹˜ Ó·ÙÚ›Ô˘ Î·È ÓÂÚÔ‡17. OÈ ·fi„ÂȘ Û¯ÂÙÈο Ì ÙË ¯ÚËÛÈÌfiÙËÙ· Ù˘ ‰ÈÂÁ¯ÂÈÚËÙÈ΋˜ ¯ÔÚ‹ÁËÛ˘ ‰ÈÔ˘ÚËÙÈÎÒÓ ‰fiÛÂˆÓ ÓÙÔ·Ì›Ó˘ ( < 3 Ìg/kg/min) ÛÙËÓ O.ª.∏., ‰È˝ÛÙ·ÓÙ·È. ∞˘Ùfi ÁÈ·Ù› ÔÈ ÌÂϤÙ˜ Ô˘ ˘ÔÛÙËÚ›˙Ô˘Ó ÙË ¯ÚËÛÈÌfiÙËÙ¿ Ù˘, ·ÊÔÚÔ‡Ó Û ·ÛıÂÓ›˜ Ô˘ ‰ÂÓ Â›¯·Ó ÛÔ‚·ÚÔ‡˜ ÂÈ‚·Ú˘ÓÙÈÎÔ‡˜ ·Ú¿ÁÔÓÙ˜ ÎÈÓ‰‡ÓÔ˘ ÚfiÎÏËÛ˘ O.¡.∞. (Ì·˙È΋ ·ÈÌÔÚÚ·Á›·, ÌÂÁ¿Ï˘ ¯ÚÔÓÈ΋˜ ‰È¿ÚÎÂÈ·˜ ˘fiÙ·ÛË, ÛÔ‚·Ú¤˜ ·ÚÚ˘ı̛˜, Î.·.). ∂ÈϤÔÓ ÛÙȘ ÌÂϤÙ˜ ·˘Ù¤˜, Ë ¯ÔÚ‹ÁËÛË Ù˘ ÓÙÔ·Ì›Ó˘ Û˘Óԉ¢fiÙ·Ó ·fi ÙË Û˘Á¯ÔÚ‹ÁËÛË Î·È ¿ÏÏˆÓ ‰˘ÓËÙÈο ÓÂÊÚÔÚÔÛٷ٢ÙÈÎÒÓ ·Ú·ÁfiÓÙˆÓ (Ì·ÓÓÈÙfiÏ˘ ‹ /Î·È ÊÔ˘ÚÔÛÂÌ›‰Ë˜) ‹ ÂÊ·ÚÌÔÁ‹ ÙÔ˘ Û˘ÛÙ‹Ì·ÙÔ˜ V-VB18,19. ™˘ÓÂÒ˜, Ë Â›‰Ú·ÛË Ù˘ Û˘ÛÙËÌ·ÙÈ΋˜ ¯ÔÚ‹ÁËÛ˘ ‰ÈÔ˘ÚËÙÈÎÒÓ ‰fiÛÂˆÓ ÓÙÔ·Ì›Ó˘ ¤¯ÂÈ ÂÏ¿¯ÈÛÙË ·Í›· ÛÙÔ ÌË ·ÓÔ˘ÚÈÎfi ·ÛıÂÓ‹ Ô˘ ˘Ô‚¿ÏÏÂÙ·È Û O.ª.∏.
2.4. ºÔ˘ÚÔÛÂÌ›‰Ë ∏ ÊÔ˘ÚÔÛÂÌ›‰Ë Â›Ó·È ‰ÈÔ˘ÚËÙÈÎfi Ù˘ ·Á·Ï˘, Ô˘ ·Ó·ÛÙ¤ÏÏÂÈ ÙËÓ Â·Ó·ÚÚfiÊËÛË Na+ Î·È Cl-, ΢ڛˆ˜ ÛÙË Ì˘ÂÏÒ‰Ë ÌÔ›Ú· ÙÔ˘ ·ÓÈfiÓÙÔ˜ ÛΤÏÔ˘˜ Ù˘ ·Á·Ï˘ ÙÔ˘ Henle20. ∏ ÂÓ‰ÔÊϤ‚È· ¯ÔÚ‹ÁËÛË ÊÔ˘ÚÔÛÂÌ›‰Ë˜ ‰ÈÂÁ›ÚÂÈ ÙË ‰ÈÔ‡ÚËÛË ÂÓÙfi˜ 2-10
METAMO™XEY™Eπ™ 2008
min Î·È Ë ·ÓÙ·fiÎÚÈÛË Â›Ó·È Â˘ı¤ˆ˜ ·Ó¿ÏÔÁË Ì ÙÔ GFR ÁÈ· ¤Ó· ÌÂÁ¿ÏÔ Â‡ÚÔ˜ ÙÈÌÒÓ21. ∂Âȉ‹ Ë ‰Ú¿ÛË Ù˘ ÊÔ˘ÚÔÛÂÌ›‰Ë˜ ·ÛÎÂ›Ù·È Ì¤Ûˆ ·Ó·ÛÙÔÏ‹˜ Ù˘ ‰Ú¿Û˘ Ù˘ ·ÓÙÏ›·˜ Na+, K+, ÌÂÈÒÓÂÙ·È Ë Î·Ù·Ó¿ÏˆÛË Ô͢ÁfiÓÔ˘ ÛÙÔ ÓÂÊÚfi. ∏ ÂÓ‰ÔÊϤ‚È· ¯ÔÚ‹ÁËÛ‹ Ù˘ Û ‰fiÛÂȘ 0.1-1 mg/kg, Ì ÙËÓ ¤ÓÙÔÓË ‰ÈÔ‡ÚËÛË Ô˘ ÚÔηÏ› ÌÂÈÒÓÂÈ ÙÔ Ô›‰ËÌ· Ô˘ ÚÔηÏ› ÓÂÊÚÈ΋, Ë·ÙÈ΋ ‹ ηډȷ΋ ‰˘ÛÏÂÈÙÔ˘ÚÁ›·. ∏ ¤Ó·ÚÍË Ù˘ ‰ÈÔ‡ÚËÛ˘ ÚÔ·Ó·ÁÁ¤ÏÂÙ·È Ì ÙËÓ ÂÚÈÊÂÚÈ΋ ·ÁÁÂÈԉȷÛÙÔÏ‹ Î·È ÙË Ì›ˆÛË Ù˘ ÊÏ‚È΋˜ ÂÈÛÙÚÔÊ‹˜, Ô˘ ·ÔÙÂÏÔ‡Ó ÛËÌ·ÓÙÈο ÏÂÔÓÂÎÙ‹Ì·Ù· ÛÙËÓ ¿ÌÂÛË Î·È ·ÔÙÂÏÂÛÌ·ÙÈ΋ ·ÓÙÈÌÂÙÒÈÛË ÙÔ˘ Ó¢ÌÔÓÈÎÔ‡ Ôȉ‹Ì·ÙÔ˜. ∏ ÊÔ˘ÚÔÛÂÌ›‰Ë ÚÔ¿ÁÂÈ Â›Û˘, ÙË ÏÂÌÊÈ΋ ÚÔ‹ ÙÔ˘ ıˆÚ·ÎÈÎÔ‡ fiÚÔ˘22. ™Â ·Ó·‰ÚÔÌÈ΋ ÌÂϤÙË 22 ·ÛıÂÓÒÓ Ì ÌÂÙ·ÌfiÛ¯Â˘ÛË ‹·ÙÔ˜, Ô˘ Ï¿Ì‚·Ó·Ó ΢ÎÏÔÛÔÚ›ÓË ∞, ¤¯ÂÈ ‰Âȯı› Ë ÓÂÊÚÔÚÔÛٷ٢ÙÈ΋ ‰Ú¿ÛË Ù˘ ÊÔ˘ÚÔÛÂÌ›‰Ë˜ ηٿ ÙËÓ ÚÒ˚ÌË ÌÂÙÂÁ¯ÂÈÚËÙÈ΋ ÂÚ›Ô‰Ô. ∂Âȉ‹ Ë ÓÂÊÚÔÙÔÍÈÎfiÙËÙ· Ù˘ ΢ÎÏÔÛÔÚ›Ó˘ ∞, ÂÓÈÛ¯‡ÂÙ·È ·fi ÙËÓ ·Ú·ÁˆÁ‹ ıÚÔÌ‚ÔÍ¿Ó˘ ∞2 Î·È Ë ÊÔ˘ÚÔÛÂÌ›‰Ë ÌÂÈÒÓÂÈ ÙËÓ ·Ú·ÁˆÁ‹ Ù˘, ıˆÚÂ›Ù·È fiÙÈ ¤¯ÂÈ Â˘ÓÔ˚΋ ›‰Ú·ÛË ÛÙË ‚ÂÏÙ›ˆÛË Ù˘ ÓÂÊÚÈ΋˜ ·ÈÌ·ÙÈ΋˜ ÚÔ‹˜23.
2.5. ™˘Ó‰˘·Ṳ̂ÓË ıÂڷ›· (Ì·ÓÓÈÙfiÏË – ÓÙÔ·Ì›ÓË –ÊÔ˘ÚÔÛÂÌ›‰Ë) ∫¿ı ¤Ó·˜ ·fi ÙÔ˘˜ ·ÓˆÙ¤Úˆ ·Ú¿ÁÔÓÙ˜ ÚÔ¿ÁÂÈ Ì ‰È·ÊÔÚÂÙÈÎÔ‡˜ Ì˯·ÓÈÛÌÔ‡˜ ÙË ‰ÈÔ‡ÚËÛË, fï˜ Ë ÓÂÊÚÔÚÔÛٷ٢ÙÈ΋ ‰Ú¿ÛË ÙÔ˘ ηıÂÓfi˜ ÌÂÌÔӈ̤ӷ Â›Ó·È ÂÏ¿¯ÈÛÙË ÛÙÔ˘˜ ·ÛıÂÓ›˜ Ô˘ ˘Ô‚¿ÏÏÔÓÙ·È Û O.ª.∏. ∏ Ì·ÓÓÈÙfiÏË ÍÂϤÓÂÈ Ù· ÓÂÊÚÈο ÛˆÏËÓ¿ÚÈ· ·fi ÙÔÍÈΤ˜ Ô˘Û›Â˜ Î·È ‰ÂÛ̇ÂÈ ÙȘ ÂχıÂÚ˜ Ú›˙˜, Ë ÓÙÔ·Ì›ÓË ·˘Í¿ÓÂÈ ÙË ÓÂÊÚÈ΋ ·ÈÌ·ÙÈ΋ ÚÔ‹ Î·È Ë ÊÔ˘ÚÔÛÂÌ›‰Ë ÌÂÈÒÓÂÈ ÙË ÓÂÊÚÈ΋ ηٷӿψÛË Ô͢ÁfiÓÔ˘. ™˘ÓÂÒ˜, Ë Û˘Ó‰˘·Ṳ̂ÓË ¯ÔÚ‹ÁËÛË Î·È ÙˆÓ ÙÚÈÒÓ Ê·ÚÌ¿ÎˆÓ Â›Ó·È Èı·ÓfiÓ Ó· ¤¯ÂÈ ¤Ó· ηχÙÂÚÔ ·ıÚÔÈÛÙÈÎfi, ÓÂÊÚÔÚÔÛٷ٢ÙÈÎfi ·ÔÙ¤ÏÂÛÌ·. OÈ Planinsic Î·È Û˘ÓÂÚÁ¿Ù˜, ÌÂϤÙËÛ·Ó Û 79 ·ÛıÂÓ›˜ ÙÔ ·ÔÙ¤ÏÂÛÌ· ÙÔ˘ Û˘Ó‰˘·ÛÌÔ‡ ÙˆÓ ÙÚÈÒÓ ·Ú·ÁfiÓÙˆÓ ÛÙËÓ ÚÔÛÙ·Û›· ÙˆÓ ÓÂÊÚÒÓ ÙËÓ ÂÚÈÂÁ¯ÂÈÚËÙÈ΋ ÂÚ›Ô‰Ô Ù˘ O.ª.∏.. OÈ 40 ·ÛıÂÓ›˜ ¤Ï·‚·Ó Ê˘ÛÈÔÏÔÁÈÎfi ÔÚfi Î·È ÔÈ 39 Û˘Ó‰˘·ÛÌfi Ì·ÓÓÈÙfiÏ˘, ÓÙÔ·Ì›Ó˘ Î·È ÊÔ˘ÚÔÛÂÌ›‰Ë˜. ∞Ó Î·È Ë ‰ÈÔ‡ÚËÛË ‹Ù·Ó Ôχ ÈÔ ·˘ÍË̤ÓË ÛÙËÓ ÔÌ¿‰· ÙˆÓ ·ÛıÂÓÒÓ Ô˘ ¤Ï·‚ ÙËÓ ÙÚÈÏ‹ ·ÁˆÁ‹, Ù· ÌÂÙÂÁ¯ÂÈÚËÙÈο ›‰· ÙˆÓ ÙÈÌÒÓ Ù˘ ÎÚ·ÙÈÓ›Ó˘ ÙÔ˘ ÔÚÔ‡ fi¯È ÌfiÓÔ Î˘Ì¿ÓıËÎ·Ó ÛÙȘ ›-
103
‰È˜ ÙÈ̤˜ ·ÏÏ¿ Î·È ÂÌÊ¿ÓÈÛ·Ó ·Ó¿ÏÔÁË ·‡ÍËÛË Î·È ÛÙȘ ‰‡Ô ÔÌ¿‰Â˜. ∂›Ó·È ÂӉȷʤÚÔÓ, fiÙÈ ÔÈ ÙÈ̤˜ Ù˘ ÎÚ·ÙÈÓ›Ó˘ ÙÔ˘ ÔÚÔ‡ ÙˆÓ ·ÛıÂÓÒÓ Ô˘ ¤Ï·‚·Ó ÙÔ Û˘Ó‰˘·ÛÌfi ÙˆÓ ÙÚÈÒÓ Ê·Ú̿ΈÓ, ·ӋÏı·Ó ÛÙȘ ‚·ÛÈΤ˜ ÙÈ̤˜ ÂÚ› ÙËÓ ¤‚‰ÔÌË ÌÂÙÂÁ¯ÂÈÚËÙÈ΋ Ë̤ڷ24. ™˘ÓÂÒ˜, Ù· ·ÔÙÂϤÛÌ·Ù· ·˘Ù¿ ‰Â›¯ÓÔ˘Ó fiÙÈ Î·È Ô ÙÚÈÏfi˜ Û˘Ó‰˘·ÛÌfi˜ – Ì·ÓÓÈÙfiÏË, ÓÙÔ·Ì›ÓË, ÊÔ˘ÚÔÛÂÌ›‰Ë – ·ÛΛ ÂÏ¿¯ÈÛÙË ÓÂÊÚÔÚÔÛÙ·Û›· ÛÙÔ˘˜ ·ÛıÂÓ›˜ Ô˘ ˘Ô‚¿ÏÏÔÓÙ·È Û ÌÂÙ·ÌfiÛ¯Â˘ÛË ‹·ÙÔ˜24,25.
2.6. ÕÏÏÔÈ ·Ú¿ÁÔÓÙ˜ ÕÏÏÔÈ ·Ú¿ÁÔÓÙ˜ Ô˘ ¤¯Ô˘Ó ¯ÔÚËÁËı› ‰ÈÂÁ¯ÂÈÚËÙÈο Ì ÛÎÔfi ÙËÓ ÚfiÏË„Ë Ù˘ ÌÂÙÂÁ¯ÂÈÚËÙÈ΋˜ ÓÂÊÚÈ΋˜ ‰˘ÛÏÂÈÙÔ˘ÚÁ›·˜ ÛÙËÓ O.ª.∏., Â›Ó·È Ë ÊÂÓÔÏÓÙÔ¿ÌË Î·È Ë ¡-·ÎÂÙ˘ÏÔ΢ÛÙ½ÓË. ºÂÓÔÏÓÙÔ¿ÌË: Â›Ó·È ÂȉÈÎfi˜ ·ÁˆÓÈÛÙ‹˜ ÙˆÓ D∞1 (ÓÙÔ·ÌÈÓÂÚÁÈÎÒÓ 1) – ˘Ô‰Ô¯¤ˆÓ. ™Â ÌÈÎÚ¤˜ ‰fiÛÂȘ 0.03 Ìg/kg/min ÚÔηÏ› ‰ÔÛÔÂÍ·ÚÙÒÌÂÓË ·‡ÍËÛË Ù˘ ÓÂÊÚÈ΋˜ ·ÈÌ·ÙÈ΋˜ ÚÔ‹˜, ÚÔ¿ÁÔÓÙ·˜ ÙË ‰ÈÔ‡ÚËÛË Î·È ÙËÓ ·Ô‚ÔÏ‹ Ó·ÙÚ›Ô˘ 26. O ÚfiÏÔ˜ Ù˘ ÊÂÓÔÏÓÙÔ¿Ì˘ ˆ˜ ‰È·ÛÙ·ÏÙÈÎfi Ù˘ ÓÂÊÚÈ΋˜ ΢ÎÏÔÊÔÚ›·˜ ÛÙËÓ ÚfiÏË„Ë Ù˘ ÌÂÙÂÁ¯ÂÈÚËÙÈ΋˜ O.¡.∞. ÛÙËÓ O.ª.∏., Â›Ó·È ·ÎfiÌË ·Û·Ê‹˜. ¢È¿ÊÔÚ˜ ÌÂϤÙ˜ Û ηÙËÁÔڛ˜ ·ÛıÂÓÒÓ ˘„ËÏÔ‡ ÎÈÓ‰‡ÓÔ˘ ÁÈ· ·Ó¿Ù˘ÍË ÓÂÊÚÈ΋˜ ‰˘ÛÏÂÈÙÔ˘ÚÁ›·˜, ‰ÂÓ ‰ÂÈÎÓ‡Ô˘Ó Ô˘ÛÈ·ÛÙÈ΋ ÓÂÊÚÔÚÔÛٷ٢ÙÈ΋ ‰Ú¿ÛË Ù˘ ÊÂÓÔÏÓÙÔ¿Ì˘. ™Â Ì›· ÌÂϤÙË Û ·ÛıÂÓ›˜ Ì ÌÂÙ·ÌfiÛ¯Â˘ÛË ÓÂÊÚÔ‡, ¯ÔÚËÁ‹ıËΠÊÂÓÔÏÓÙÔ¿ÌË Î·È ‰ÈÔ˘ÚËÙÈΤ˜ ‰fiÛÂȘ ÓÙÔ·Ì›Ó˘ Ì ÛÎÔfi ÙË Û‡ÁÎÚÈÛË ÙˆÓ ‰‡Ô ·Ú·ÁfiÓÙˆÓ ÛÙËÓ ÚfiÏË„Ë Ù˘ ‚Ï¿‚˘ ·fi ÙËÓ ÈÛ¯·ÈÌ›· – ·ӷÈÌ¿ÙˆÛË. Δ· ·ÔÙÂϤÛÌ·Ù· ‹Ù·Ó ¢ÓÔ˚ÎfiÙÂÚ· ÁÈ· ÙËÓ ÊÂÓÔÏÓÙÔ¿ÌË ·ÏÏ¿ ‰ÂÓ ¤‰ÂÈÍ·Ó Û·Ê‹ ÏÂÔÓÂÎÙ‹Ì·Ù· Û ۯ¤ÛË Ì ÙË ÓÙÔ·Ì›ÓË27. ÕÏÏË ÌÂϤÙË Û ‚·ÚÈ¿ ¿Û¯ÔÓÙ˜ ·ÛıÂÓ›˜, ‰ÂÓ ¤‰ÂÈÍ fiÙÈ Ë ÊÂÓÔÏÓÙÔ¿ÌË ÌÔÚ› Ó· ÌÂÈÒÛÂÈ Ù· ÔÛÔÛÙ¿ ÂΉ‹ÏˆÛ˘ ÚÒ˚Ì˘ O.¡.∞28. ∂›Û˘, ÌÂϤÙË Û ˘„ËÏÔ‡ ÎÈÓ‰‡ÓÔ˘ ·ÛıÂÓ›˜ Ô˘ ˘Ô‚Ï‹ıËÎ·Ó Û ηډÈÔ¯ÂÈÚÔ˘ÚÁÈ΋ ¤̂·ÛË ‰ÂÓ ¤‰ÂÈÍ ÙË ÓÂÊÚÔÚÔÛٷ٢ÙÈ΋ ‰Ú¿ÛË Ù˘ ÊÂÓÔÏÓÙÔ¿Ì˘29. ¡-·ÎÂÙ˘Ï΢ÛÙ½ÓË (NAC): Â›Ó·È Ì›· ·ÎÂÙ˘ÏȈ̤ÓË ÌÔÚÊ‹ ÙÔ˘ ·ÌÈÓÔͤԘ L-΢ÛÙ½ÓË, ÏÔ‡ÛÈ· Û ˘‰ÚÔÁÔÓÔıÂÈ˚Τ˜ ÔÌ¿‰Â˜ (SH). ™ÙÔÓ ¿ÓıÚˆÔ, ÌÂÙ·ÙÚ¤ÂÙ·È Û ÌÂÙ·‚Ôϛ٘ Ô˘ ÌÔÚÔ‡Ó Ó· ‰ÈÂÁ›ÚÔ˘Ó ÙË Û‡ÓıÂÛË ÁÏÔ˘Ù·ıÂÈfiÓ˘, Ô˘
104
∞. §∞ª¶∞¢∞ƒπ√À
ÚÔ¿ÁÂÈ ÙËÓ ·ÔÙÔ͛ӈÛË Î·È ÙË ‰¤ÛÌ¢ÛË ÙˆÓ ÂχıÂÚˆÓ ÚÈ˙ÒÓ. ∏ ¯ÔÚ‹ÁËÛË Ù˘ ¡-·ÎÂÙ˘Ï΢ÛÙ½Ó˘ Ê·›ÓÂÙ·È fiÙÈ ¤¯ÂÈ Ôχ ηϿ ·ÔÙÂϤÛÌ·Ù· Û ηٷÛÙ¿ÛÂȘ, Ô˘ ¯·Ú·ÎÙËÚ›˙ÔÓÙ·È ·fi ÌÂȈ̤ÓË Û‡ÓıÂÛË ÁÏÔ˘Ù·ıÂÈfiÓ˘ ‹ ·fi ·˘ÍË̤ÓÔ ÔÍÂȉˆÙÈÎfi stress fiˆ˜ Ë ‚Ï¿‚Ë ÈÛ¯·ÈÌ›·˜ – ·ӷÈÌ¿ÙˆÛ˘, fiˆ˜ Û˘Ì‚·›ÓÂÈ Î·Ù¿ ÙËÓ Ë·ÙÈ΋ ÌÂÙ·ÌfiÛ¯Â˘ÛË. ∏ ¡-·ÎÂÙ˘Ï΢ÛÙ½ÓË ·Ú·Ì¤ÓÂÈ Ë Î‡ÚÈ· ıÂڷ›· ÛÙËÓ ·ÓÙÈÌÂÙÒÈÛË Ù˘ Ë·ÙÔÙÔÍÈÎfiÙËÙ·˜ Ô˘ ÚÔηÏ› Ë ·Ú·ÎÂÙ·ÌfiÏË. §fiÁˆ Ù˘ Ë·ÙÔÚÔÛٷ٢ÙÈ΋˜ Ù˘ ‰Ú¿Û˘, ¤¯ÂÈ ¯ÔÚËÁËı› Û ·ÚÎÂÙ¤˜ ÎÏÈÓÈΤ˜ ÌÂϤÙ˜ Û ·ÛıÂÓ›˜ Ì Δ.™.∏.¡., Ô˘ ˘Ô‚¿ÏÏÔÓÙ·È Û ˷ÙÈ΋ ÌÂÙ·ÌfiÛ¯Â˘ÛË Ì ÛÎÔfi ÙË ‚ÂÏÙ›ˆÛË Ù˘ ÏÂÈÙÔ˘ÚÁ›·˜ ÙÔ˘ Ó¤Ô˘ ‹·ÙÔ˜30-33. ΔÂÏÂ˘Ù·›·, ¤¯ÂÈ ‰ÔÎÈÌ·Ûı› Ì ÂÓı·ÚÚ˘ÓÙÈο ·ÔÙÂϤÛÌ·Ù· ÛÙËÓ ÚÔÛÙ·Û›· ÙˆÓ ÓÂÊÚÒÓ, Û ·ÛıÂÓ›˜ Ô˘ Ï·Ì‚¿ÓÔ˘Ó ÂÓ‰ÔÊϤ‚È· ÈηӤ˜ ÔÛfiÙËÙ˜ ÛÎÈ·ÁÚ·ÊÈÎÒÓ Ô˘ÛÈÒÓ ÁÈ· ÙËÓ ÂÎÙ¤ÏÂÛË ÂÂÌ‚·ÙÈÎÒÓ ·ÎÙÈÓÔÏÔÁÈÎÒÓ Ù¯ÓÈÎÒÓ34. ∏ Û˘Ó‰˘·Ṳ̂ÓË ‰Ú¿ÛË Ô˘ Ê·›ÓÂÙ·È fiÙÈ ·ÛΛ Ë ¡-·ÎÂÙ˘Ï΢ÛÙ½ÓË Û ‹·Ú Î·È ÓÂÊÚÔ‡˜, Èı·ÓfiÓ Ó· ÙËÓ Î·ıÈÛÙ¿ ÛËÌ·ÓÙÈÎfi Ë·ÙÔÓÂÊÚÈÎfi, ÚÔÛٷ٢ÙÈÎfi ·Ú¿ÁÔÓÙ· ÛÙËÓ O.ª.∏. ΔÂÏÈο, Ù· ·ÔÙÂϤÛÌ·Ù· ·Ï·ÈfiÙÂÚˆÓ Î·È ÓÂfiÙÂÚˆÓ ÌÂÏÂÙÒÓ, ηٷϋÁÔ˘Ó fiÙÈ Ë ¿ÚÈÛÙË ÂÚÈÂÁ¯ÂÈÚËÙÈ΋ ÓÂÊÚÔÚÔÛÙ·Û›· ‰ÂÓ ÂÈÙ˘Á¯¿ÓÂÙ·È ÚÔ˜ ÙÔ ·ÚfiÓ Ì ÙË ¯ÔÚ‹ÁËÛË Î¿ÔÈÔ˘ Ê·Ú̷΢ÙÈÎÔ‡ ·Ú¿ÁÔÓÙ·, ·Ú¿ ÌfiÓÔ Ì ÙË ‰È·Ù‹ÚËÛË Â·ÚÎÔ‡˜ ÂÓ‰·ÁÁÂÈ·ÎÔ‡ fiÁÎÔ˘ Î·È ÈηӋ˜ ›ÂÛ˘ ‰È‹ıËÛ˘ ÙˆÓ ÓÂÊÚÒÓ.
3. O ÚfiÏÔ˜ ÙˆÓ ‚ÈÔ‰ÂÈÎÙÒÓ ÛÙËÓ ÚÒ˚ÌË ‰È¿ÁÓˆÛË Ù˘ O.¡.∞. ¶ÚÔ˜ ÙÔ ·ÚfiÓ, ‰ÂÓ ˘¿Ú¯Ô˘Ó ÂȉÈÎÔ› ‰Â›ÎÙ˜ ÚÒ˚Ì˘ ‰È¿ÁÓˆÛ˘ Ù˘ ÓÂÊÚÈ΋˜ ‰˘ÛÏÂÈÙÔ˘ÚÁ›·˜ ÌÂÙ¿ ÙËÓ O.ª.∏. ∏ Â͇ÚÂÛË Ù¤ÙÔÈˆÓ ‰ÂÈÎÙÒÓ Â›Ó·È ÂÍ·ÈÚÂÙÈο ÂÈı˘ÌËÙ‹, ‰ÈfiÙÈ ı· ‚ÔËı‹ÛÂÈ ÙË ÛˆÛÙ‹ ·ÓÙÈÌÂÙÒÈÛË ·˘ÙÒÓ ÙˆÓ ·ÛıÂÓÒÓ Û ÔÏϤ˜ ηÙ¢ı‡ÓÛÂȘ, fiˆ˜ Ë ‰È·¯Â›ÚÈÛË Ù˘ ıÂڷ›·˜ ˘ÔηٿÛÙ·Û˘ Ù˘ ÓÂÊÚÈ΋˜ ÏÂÈÙÔ˘ÚÁ›·˜, Ë ÙÚÔÔÔ›ËÛË ÙÔ˘ ›‰Ô˘˜ Î·È Ù˘ ‰fiÛ˘ ÙˆÓ ·ÓÔÛÔηٷÛÙ·ÏÙÈÎÒÓ Ê·ÚÌ¿ÎˆÓ Î·È Ë ÂÎÙ›ÌËÛË Ù˘ ·ÔÙÂÏÂÛÌ·ÙÈÎfiÙËÙ·˜ ÌÂÏÏÔÓÙÈÎÒÓ ıÂÚ·ÂÈÒÓ1. ∏ neutrophil gelatinase-associated lipocalin (NGAL) Î·È Ë ÈÓÙÂÚÏ¢ΛÓË-18 (IL-18), ¤¯Ô˘Ó ÌÂÙÚËı› ÛÙ· Ô‡Ú· ηډÈÔ¯ÂÈÚÔ˘ÚÁÈÎÒÓ ·ÛıÂÓÒÓ 2 Ì 4 ÒÚ˜ ÌÂÙ¿ ÙËÓ Î·Ú‰ÈÔÓ¢ÌÔÓÈ΋ ·Ú¿Î·Ì-
„Ë. ™ÙÔ˘˜ ·ÛıÂÓ›˜ Ô˘ Ù· ›‰· ÙˆÓ ‚ÈÔ‰ÂÈÎÙÒÓ ·˘ÙÒÓ ‚Ú¤ıËÎ·Ó ·˘ÍË̤ӷ, ÂΉËÏÒıËΠÔÍ›· ÓÂÊÚÈ΋ ‚Ï¿‚Ë – ÔÚÈ˙fiÌÂÓË ˆ˜ ¿Óˆ ·fi 50% ·‡ÍËÛË ÙˆÓ ÂȤ‰ˆÓ Ù˘ ÎÚ·ÙÈÓ›Ó˘ ÙÔ˘ ÔÚÔ‡ – ÌÂÙ¿ ·fi 48-72 ÒÚ˜35. ∏ ¯ÚËÛÈÌfiÙËÙ· ÙˆÓ ‚ÈÔ‰ÂÈÎÙÒÓ ·˘ÙÒÓ ‹ Î·È ¿ÏÏˆÓ Ú¤ÂÈ Ó· ÌÂÏÂÙËı› Î·È ÛÙËÓ O.ª.∏.
∂. ™Àª¶∂ƒ∞™ª∞Δ∞ ∂›Ó·È Ê·ÓÂÚfi fiÙÈ Ë ÂÌÊ¿ÓÈÛË O.¡.∞. ηٿ ÙËÓ ÂÚÈÂÁ¯ÂÈÚËÙÈ΋ ÂÚ›Ô‰Ô Ù˘ O.ª.∏., ·˘Í¿ÓÂÈ ÙË ÓÔÛËÚfiÙËÙ·, ÙȘ Ë̤Ú˜ ÂÓ‰ÔÓÔÛÔÎÔÌÂȷ΋˜ ÓÔÛËÏ›·˜, ÙÔ ÎfiÛÙÔ˜ Î·È ÙË ıÓËÙfiÙËÙ·36,37. ∂›Û˘, ÙÔ 18 % Î·È ÙÔ 25 % ÙˆÓ ÌÂÙ·ÌÔÛ¯Â˘Ì¤ÓˆÓ Ì ‹·Ú ·ÛıÂÓÒÓ, ÎÈÓ‰˘Ó‡ÂÈ Ó· ÂÌÊ·Ó›ÛÂÈ Ã.¡.∞. (ÔÚÈ˙fiÌÂÓË ˆ˜ GFR < 29 ml/min/1.73 m2) ÛÙ· 5 Î·È 10 ¯ÚfiÓÈ· ·ÓÙ›ÛÙÔȯ·, Ì ·ÔÙ¤ÏÂÛÌ· ÙËÓ ·‡ÍËÛË Ù˘ ÓÔÛËÚfiÙËÙ·˜ Î·È ıÓËÙfiÙËÙ·˜38. ∏ ·ÚÈ· ·ÈÙ›· ÁÈ· ·˘Ùfi, Â›Ó·È Ë ·ÓÔÛÔηٷÛÙ·ÏÙÈ΋ ıÂڷ›· Ì ·Ó·ÛÙÔÏ›˜ Ù˘ ηÏÛÈÓ¢ڛÓ˘ (΢ÎÏÔÛÔÚ›ÓË ∞, tacrolimus). ªÂ ‰Â‰Ô̤ÓÔ fiÙÈ Ë ·ÓÙÈÌÂÙÒÈÛË Ù˘ ÓÂÊÚÈ΋˜ ·Ó¿ÚÎÂÈ·˜ – ÔÍ›·˜ ‹ ¯ÚfiÓÈ·˜ – ·Ú·Ì¤ÓÂÈ ˘ÔÛÙËÚÈÎÙÈ΋ Î·È fi¯È ıÂڷ¢ÙÈ΋ (ÂÎÙfi˜ Î·È ·Ó Ô ·ÛıÂÓ‹˜ ˘Ô‚ÏËı› Û ÂÈÙ˘¯‹ ÓÂÊÚÈ΋ ÌÂÙ·ÌfiÛ¯Â˘ÛË), Â›Ó·È ÛËÌ·ÓÙÈÎfi Ë ¤Ú¢ӷ Ó· ÂÛÙÈ¿ÛÂÈ Û ‰‡Ô ·ÚÈ· ‰›·: ÛÙËÓ Â͇ÚÂÛË ÓÂÊÚÔÚÔÛٷ٢ÙÈÎÒÓ ·Ú·ÁfiÓÙˆÓ, ·ÊÔ‡ ̤¯ÚÈ Û‹ÌÂÚ· ÌfiÓÔ Ë ‰È·Ù‹ÚËÛË Â·ÚÎÔ‡˜ ÂÓ‰·ÁÁÂÈ·ÎÔ‡ fiÁÎÔ˘ Î·È ÈηӋ˜ ›ÂÛ˘ ‰È‹ıËÛ˘ ÙˆÓ ÓÂÊÚÒÓ ÚÔÏ·Ì‚¿ÓÔ˘Ó Ô˘ÛÈ·ÛÙÈο ÙË ÓÂÊÚÈ΋ ·Ó¿ÚÎÂÈ· Î·È ·˘Ùfi ‰ÂÓ Â›Ó·È ¿ÓÙ· ÂÊÈÎÙfi Û ÂÂÌ‚¿ÛÂȘ fiˆ˜ Ë O.ª.∏. Î·È ÛÙËÓ Â͇ÚÂÛË ·ÍÈfiÈÛÙˆÓ ‚ÈÔ‰ÂÈÎÙÒÓ, Ô˘ Ó· ÚÔ‚Ï¤Ô˘Ó ¤ÁηÈÚ· ÙËÓ ÂÌÊ¿ÓÈÛË Ù˘ ÓÂÊÚÈ΋˜ ‰˘ÛÏÂÈÙÔ˘ÚÁ›·˜ ηıÒ˜ Î·È Ù· ¿ÙÔÌ· Ì ÙË ÌÂÁ·Ï‡ÙÂÚË ÚԉȿıÂÛË, ÒÛÙ ӷ ·ÔʇÁÔÓÙ·È ‹ Ó· ÂÏ·¯ÈÛÙÔÔÈÔ‡ÓÙ·È ÔÈ ·Ú¿ÁÔÓÙ˜ Ô˘ ÙËÓ ÚÔηÏÔ‡Ó.
μπμ§πO°ƒ∞ºπ∞ 1. Yalavarthy R, et al. Acute renal failure and chronic kidney disease following liver transplantation. Hemodialysis International 2007; 11: S7-S12. 2. Planinsic MR, Lebowitz JJ. Renal failure in end-stage liver disease and liver transplantation. International Anesthesiology Clinics 2006; vol 44; number 3; 35-48. 3. Gines P, et al. Hepatorenal syndrome. Lancet 2003; 362: 1819-1827.
METAMO™XEY™Eπ™ 2008
4. Marik EP, et al. The course of type 1 hepato-renal syndrome post liver transplantation. Nerhrol Dial Transplant. 2006; 21: 478-482. 5. Gonwa TA, et al. Long-term survival and renal function following liver transplantation in patients with and without hepatorenal syndrome – experience in 300 patients.Tranplantation 1991; 51: 428-430. 6. McCauley J, et al. Acute and chronic renal failure in liver transplantation. Nephron. 1990; 55: 121-128. 7. Pascual ∂, et al. Incidence and risk factors of early acute renal failure in liver transplant patients. Transplant Proc. 1993; 25:1827. 8. Ishitani M, et al. Outcome of patients requiring hemodialysis after liver transplantation. Transplant Proc. 1993; 25: 1762-1763. 9. Sanchez EQ, et al. Preoperative and perioperative predictors of the need for renal replacement therapy after orthotopic liver transplantation. Transplantation 2004; 78: 1048-1054. 10. Gonwa TA, et al. Renal replacement therapy and orthotopic liver transplantation: The role of continuous venovenous hemodialysis. Transplantation 2001; 71: 1424-1428. 11. Cabezuelo JB, et al. Risk factors of acute renal failure after liver transplantation. Kidney Int. 2006; 69: 10731080. 12. Nuno J, et al. Renal failure after liver transplantation: Analysis of risk factors in 139 liver transplant recipients. Transplant Proc. 1995; 27: 2319-2320. 13. Bilbao I, et al. Risk factors for acute renal failure requiring dialysis after liver transplantation. Clin Tranplant. 1998; 12: 123-129. 14. Kang YG. Liver Trasplantation. In: Anesthesia and Organ Transplantation (eds). International Anesthesiology Clinics 1991; 59-81. 15. Byrick RJ, Rose DK. Pathophysiology and prevention of acute renal failure: the role of the anaesthetist. Can J Anaesth. 1990; 37(4 Part 1):456–467. 16. Goldfinger D. Acute hemolytic transfusion reactions—a fresh look at pathogenesis and considerations regarding therapy. Transfusion. 1977; 17:85–98. 17. Hilberman M, et al. The diuretic properties of dopamine in patients after open heart operation. Anesthesiology. 1984; 61:489–494. 18. Polson RJ, et al. The prevention of renal impairment in patients undergoing orthotopic liver grafting by infusion of low dose dopamine. Anaesthesia. 1987; 42:15-19. 19. Swygert TH, et al. Effect of introperative low-dose dopamine on renal function in liver transplant recipients. Anesthesiology. 1991; 75:571–576. 20. Merin RG, Bastron RD. Diuretics. In: Smith NT, Miller RD, Corbascio AN, eds. Drug Interactions in Anesthesia. Philadelphia: Lea and Febiger; 1986: 206-224. 21. Tonnesen AS. Clinical pharmacology and use of diuretics. In: Hershey BJ, Bamforth BJ, Zauder HS, eds. Review Courses in Anesthesiology. Philadelphia: JB Lippincott Co; 1983:217–226.
105
22. Szwed JJ, Kleit SA, Hamburger RJ. Effect of furosemide and chlorthiazide on the thoracic duct lymph flow in the dog. J Lab Clin Med. 1972; 79:693–700. 23. Driscoll DF, et al. Potential protective effects of furosemide against early cyclosporine-induced renal injury in hepatic transplant recipients. Transplant Proc. 1989; 21:3549–3550. 24. Planinsic RM, et al. Dopamine, furosemide and mannitol infusions and the incidence of renal dysfunction after orthotopic liver transplantation. Anesthesiology. 1996; 85(3A):A247. 25. Planinsic RM, et al. Dopamine, furosemide and mannitol infusions and changes in serum creatinines after liver transplantation. Liver Transpl Surg. 1997; 3:C40. 26. Dlewati A, Lokhandwala MF. Dose response analysis of the effects of fenoldopam, a dopamine-1 receptor agonist on renal function. Drug Dev Res. 1991; 22:59–68. 27. Fontana I, et al. Dopamine “renal dose” versus fenoldopam mesylate to prevent ischemia-reperfusion injury in renal transplantation. Transplant Proc. 2005; 37: 2474–2475. 28. Tumlin JA, et al. Fenoldopam mesylate in early acute tubular necrosis: a randomized, double-blind, placebocontrolled clinical trial. Am J Kidney Dis. 2005; 46:26-34. 29. Bove T, et al. Renoprotective action of fenoldopam in high-risk patients undergoing cardiac surgery: a prospective, double-blind, randomized clinical trial. Circulation. 2005; 111:3230–3235. 30. Bromley PN, et al. Effects of intraoperative N-acetylcysteine in orthotopic liver transplantation. BJA. 1995; 75:352–354. 31. Thies JC, et al. Efficacy of N-acetylcysteine as hepatoprotective agent in liver transplantation; an experimental study. Transplant Proc. 1997; 29: 1326-1327. 32. Suleyman D, Mine JE. Pentoxifyline and N-acetylcysreine in hepatic ischemia reperfusion injury. Clin Chim Acta.1998; 275:127–135. 33. Thies JC, et al. The efficacy of NAC as a hepatoprotective agent in liver transplantation. Transplant Int. 1998; 11(Suppl 1): S390–S392. 34. Tepel M, Van der Giet M, Schwarzfeld C, et al. Prevention of radiographic-contrast-agent-induced reduction in renal dysfunction by N-acetylcysteine. N Engl J Med. 2000; 343:180–184. 35. Parikh CR, et al. Urinary IL-18 is an early predictive biomarker of acute kidney injury after cardiac surgery. Kidney Int. 2006; 70: 199-203. 36. Fraley DS, et al. Impact of acute renal failure on mortality in end-stage liver disease with or without transplantation. Kidney Int. 1998; 54: 518-524. 37. Chertow GM, et al. Acute kidney injury, mortality, length of stay, and costs in hospitalized patients. J Am Soc ¡ephrol. 2005; 16: 3365-3370. 38. Ojo AO, et al. Chronic renal failure after transplantation of a nonrenal organ. N Engl J Med. 2003; 349: 931-940.
AÈÌÔÚÚ·Á›· – H ı¤ÛË ÙÔ˘ ÂÓÂÚÁÔÔÈË̤ÓÔ˘ ·Ú¿ÁÔÓÙ· VII ÛÙËÓ ÌÂÙ·ÌfiÛ¯Â˘ÛË ‹·ÙÔ˜ Ã. ¶··ÁˆÚÁ›Ô˘
∂π™∞°ø°H
Î·È ·ÈÌÔÂÙ¿ÏÈ· ·ÏÏ¿ Î·È Ì ·ÓÙÈÈÓˆ‰ÔÏ˘ÙÈο Ê¿Ú̷η fiˆ˜ Â›Ó·È Ë ·ÚÔÙÈÓ›ÓË, ÙÔ ∂- ·ÌÈÓÔηÚÔ˚Îfi Î·È ÙÔ ÙÚ·ÓÍÂÓ·ÌÈÎfi Ô͇ ηıÒ˜ Î·È Ì ʿÚ̷η Ô˘ ·Ú·Î¿ÌÙÔ˘Ó ÙÔ ¤ÏÏÂÈÌÌ· ÙˆÓ ·Ú·ÁfiÓÙˆÓ ‹Í˘, fiˆ˜ Â›Ó·È Ô ·Ó·Û˘Ó‰˘·Ṳ̂ÓÔ˜ ·Ú¿ÁÔÓÙ·˜ VIIa (recombinant factor VII activated, rFVIIa). EÈϤÔÓ, ÔÈ ‚ÂÏÙȈ̤Ó˜ ¯ÂÈÚÔ˘ÚÁÈΤ˜ Ù¯ÓÈΤ˜ (piggyback Ù¯ÓÈ΋)8, Ù· ÂÍÂÏÈÁ̤ӷ ‰È·Ï‡Ì·Ù· Û˘ÓÙ‹ÚËÛ˘ ÙÔ˘ ÌÔۯ‡̷ÙÔ˜ (‰È¿Ï˘Ì· Wisconsin)9 Î·È Ë Î·Ï‡ÙÂÚË ‰ÈÂÁ¯ÂÈÚËÙÈ΋ ·Ó·ÈÛıËÛÈÔÏÔÁÈ΋ ·Ú·ÎÔÏÔ‡ıËÛË ÙfiÛÔ Ù˘ ·ÈÌfiÛÙ·Û˘ (¯Ú‹ÛË ‰ÈÂÁ¯ÂÈÚËÙÈο ıÚÔÌ‚ÔÂÏ·ÛÙÔÁÚ¿ÊÔ˘)10 fiÛÔ Î·È Ù˘ ˘fiÏÔÈ˘ ηٿÛÙ·Û˘ ÙÔ˘ ·ÛıÂÓÔ‡˜ Û˘Ó¤ÚÁËÛ·Ó ÛÙË Ì›ˆÛË ÙˆÓ ·Ó·ÁÎÒÓ ÁÈ· ÌÂÙ·ÁÁ›ÛÂȘ ηٿ ÙËÓ O.ª.∏. ¶·ÚfiÏ· ·˘Ù¿, Ë ‰ÈÂ- Î·È ÌÂÙÂÁ¯ÂÈÚËÙÈ΋ ·ÈÌÔÚÚ·Á›· ÂÍ·ÎÔÏÔ˘ı› Ó· ·ÔÙÂÏ› Ì›˙ÔÓ· ÂÈÏÔ΋ Ù˘ ÌÂÙ·ÌfiÛ¯Â˘Û˘ Î·È Û˘Ó¯‹˜ ¤Ú¢ӷ ‰ÈÂÓÂÚÁÂ›Ù·È ÛÙÔÓ ÙÔ̤· ·˘Ùfi ÚÔÎÂÈ̤ÓÔ˘ Ó· ÌÂȈı› Ë Û˘¯ÓfiÙËÙ¿ Ù˘. ™ÙÔ Î›ÌÂÓÔ Ô˘ ·ÎÔÏÔ˘ı› ı· ·ÚÔ˘ÛÈ·ÛÙ› Ë ·ıÔÊ˘ÛÈÔÏÔÁ›· Ù˘ ·ÈÌÔÚÚ·Á›·˜ ÛÙËÓ O.ª.∏. Î·È ÛÙË Û˘Ó¤¯ÂÈ· ı· ·Ó·Ï˘ı› Ô ÚfiÏÔ˜ ÙÔ˘ rFVIIa ÛÙËÓ ıÂڷ›· Ù˘. O ÂÓÂÚÁÔÔÈË̤ÓÔ˜ VIIa Â›Ó·È ·ÔÙÂÏÂÛÌ·ÙÈÎfi˜ ÛÙËÓ Â›Û¯ÂÛË Ì›˙ÔÓˆÓ ·ÈÌÔÚÚ·ÁÈÒÓ ‹ ·ÂÈÏËÙÈÎÒÓ ÁÈ· ÙËÓ ˙ˆ‹ ·ÈÌÔÚÚ·ÁÈÒÓ Û ‰È¿ÊÔÚ˜ ·ıÔÏÔÁÈΤ˜ ηٷÛÙ¿ÛÂȘ (ıÚÔÌ‚ÔÊÈÏ›· Ì ·Ó·ÛÙ·ÏÙ¤˜, ›ÎÙËÙË ıÚÔÌ‚ÔÊÈÏ›·, ‚·ÚÂÈ¿ ıÚÔÌ‚ÔÂÓ›·, ·ÛıÂÓ›˜ Ì ˷ÙÈ΋ ·Ó¿ÚÎÂÈ· ÙÂÏÈÎÔ‡ ÛÙ·‰›Ô˘ Î·È ·ÈÌÔÚÚ·Á›· ÙÔ˘ ·ÓÒÙÂÚÔ˘ Á·ÛÙÚÂÓÙÂÚÈÎÔ‡ ۈϋӷ ÎÙÏ.).
∏ ÔÚıÔÙÔÈ΋ ÌÂÙ·ÌfiÛ¯Â˘ÛË ‹·ÙÔ˜ (O.ª.∏.) ·ÔÙÂÏ› ÙËÓ ıÂڷ›· ÂÎÏÔÁ‹˜ Û ·ÛıÂÓ›˜ Ì ÔÍ›· ‹ ¯ÚfiÓÈ· Ë·ÙÈ΋ ·Ó¿ÚÎÂÈ· ÙÂÏÈÎÔ‡ ÛÙ·‰›Ô˘. ∂›Ó·È ÌÈ· ÛÔ‚·Ú‹ ¯ÂÈÚÔ˘ÚÁÈ΋ ¤̂·ÛË Ô˘ ¤¯ÂÈ ÂÍÂÏȯı› ÛËÌ·ÓÙÈο ·fi ÙËÓ ÚÒÙË ª.∏. Û ¿ÓıÚˆÔ ÙÔ 1963 ·fi ÙÔÓ Starzl1. ¢˘ÛÙ˘¯Ò˜, Ô ÚÒÙÔ˜ ·˘Ùfi˜ ·ÛıÂÓ‹˜ η٤ÏËÍ ·fi ·Î·Ù¿Û¯ÂÙË ·ÈÌÔÚÚ·Á›·, ÁÂÁÔÓfi˜ Ô˘ ¤‰ÂÈÍ fiÙÈ Ë ÂÈÏÔ΋ ·˘Ù‹ ı· ·ÔÙÂÏÔ‡Û ÛËÌ·ÓÙÈÎfi ·›ÙÈÔ ÓÔÛËÚfiÙËÙ·˜ Î·È ıÓËÙfiÙËÙ·˜ Ù· ÂfiÌÂÓ· ¯ÚfiÓÈ·. H O.M.H. Û¯ÂÙ›˙ÂÙ·È Ì ·˘ÍË̤Ó˜ ·ÒÏÂȘ ·›Ì·ÙÔ˜ ÙfiÛÔ ‰ÈÂÁ¯ÂÈÚËÙÈο fiÛÔ Î·È ¿ÌÂÛ· ÌÂÙÂÁ¯ÂÈÚËÙÈο. ∏ ¿ÌÂÛË ÌÂÙÂÁ¯ÂÈÚËÙÈ΋ ·ÈÌÔÚÚ·Á›· Û˘Ì‚·›ÓÂÈ ÛÙÔ 8.4% ÙˆÓ ÌÂÙ·ÌÔÛ¯Â˘Ì¤ÓˆÓ ·ÛıÂÓÒÓ2 Ì ·ÔÙ¤ÏÂÛÌ· ÙËÓ ·Ó¿ÁÎË ÌÂÙ·ÁÁ›ÛÂˆÓ ÌÂ Û˘Ì˘Îӈ̤ӷ ÂÚ˘ıÚ¿ ‹/Î·È Ì ÊÚ¤ÛÎÔ Î·Ù„˘Á̤ÓÔ Ï¿ÛÌ·. OÈ ÌÂÙ·ÁÁ›ÛÂȘ ·˘Ù¤˜ Ô‰ËÁÔ‡Ó Û ÂÏ¿ÙÙˆÛË Ù˘ ‚ȈÛÈÌfiÙËÙ·˜ ÙÔ˘ Ë·ÙÈÎÔ‡ ÌÔۯ‡̷ÙÔ˜3, ·˘ÍË̤ÓË Û˘¯ÓfiÙËÙ· ÛËÙÈÎÒÓ ÂÂÈÛÔ‰›ˆÓ 4 , ÌÂÁ·Ï‡ÙÂÚË ‰È¿ÚÎÂÈ· ÓÔÛËÏ›·˜ ÛÙËÓ ª.∂.£.4, ·˘ÍË̤ÓË ÓÔÛËÚfiÙËÙ· Î·È ıÓËÙfiÙËÙ·5,6. Δ· ÙÂÏÂ˘Ù·›· 15 ¯ÚfiÓÈ· ¤¯ÂÈ ·Ú·ÙËÚËı› ÌÈ· ÛÙ·‰È·Î‹ ÂÏ¿ÙÙˆÛË Ù˘ ‰ÈÂ- Î·È ÌÂÙÂÁ¯ÂÈÚËÙÈ΋˜ ·ÒÏÂÈ·˜ ·›Ì·ÙÔ˜ Î·È ÙˆÓ ·Ó·ÁÎÒÓ Û ÌÂÙ·ÁÁ›ÛÂȘ ÛÙ· ÂÚÈÛÛfiÙÂÚ· ÂÍÂȉÈÎÂ˘Ì¤Ó· ÌÂÙ·ÌÔÛ¯Â˘ÙÈο ΤÓÙÚ·. ∂ÈϤÔÓ, ÙËÓ ÙÂÏÂ˘Ù·›· ÂÓÙ·ÂÙ›· Ô ·ÚÈıÌfi˜ ÙˆÓ ÌÂÙ·ÌÔÛ¯Â˘Ì¤ÓˆÓ ·ÛıÂÓÒÓ Ô˘ ‰ÂÓ ··ÈÙ‹ıËΠӷ ÌÂÙ·ÁÁÈÛıÔ‡Ó ‰ÈÂ- Î·È ÌÂÙÂÁ¯ÂÈÚËÙÈο ¤¯ÂÈ ·˘ÍËı› ÛËÌ·ÓÙÈο7. ∏ ÂÚÌËÓ›· ·˘ÙÔ‡ ÙÔ˘ ÁÂÁÔÓfiÙÔ˜ Â›Ó·È ÔÏ˘·Ú·ÁÔÓÙÈ΋. ∏ ¤Ú¢ӷ ÛÙȘ ÂÚÈÂÁ¯ÂÈÚËÙÈΤ˜ ·ÏÏ·Á¤˜ Ù˘ ·ÈÌfiÛÙ·Û˘ Î·È Ù˘ ÈÓˆ‰fiÏ˘Û˘ ‚Ô‹ıËÛ ÛÙËÓ Î·Ù·ÓfiËÛË ÙˆÓ ‰È·Ù·Ú·¯ÒÓ Ù˘ ‹Í˘ Ô˘ Û¯ÂÙ›˙ÔÓÙ·È Ì ÙËÓ ÌÂÙ·ÌfiÛ¯Â˘ÛË ‹·ÙÔ˜. ∏ ·ÔηٿÛÙ·ÛË ÙˆÓ ‰È·Ù·Ú·¯ÒÓ ·ÈÌfiÛÙ·Û˘ Á›ÓÂÙ·È Ï¤ÔÓ fi¯È ÌfiÓÔ Ì ÙȘ ÎÏ·ÛÛÈΤ˜ ıÂڷ›˜ ˘ÔηٿÛÙ·Û˘ Ì ÊÚ¤ÛÎÔ Î·Ù„˘Á̤ÓÔ Ï¿ÛÌ·
ª∂Δ∞ªO™Ã∂À™∏ ∏¶∞ΔO™ ∏ ·ÈÌÔÚÚ·Á›· ·ÔÙÂÏ› Ì›˙ÔÓ· ÂÈÏÔ΋ Ù˘ O.ª.∏. ÙfiÛÔ ‰ÈÂÁ¯ÂÈÚËÙÈο fiÛÔ Î·È ÌÂÙÂÁ¯ÂÈÚËÙÈο. ∏ ÛÔ‚·Ú‹, ·ÓÂͤÏÂÁÎÙË ·ÈÌÔÚÚ·Á›· ÌÔÚ› Ó· ·˘Í‹ÛÂÈ ÙËÓ ıÓËÙfiÙËÙ· ·fi ÙÔ <1% ÛÙÔ 20% fiˆ˜ ηıÔÚ›˙ÂÙ·È Î·È ·fi Ù· Û˘ÛÙ‹Ì·Ù· ‚·ıÌÔÓfiÌËÛ˘ Ù˘ ¤Î‚·Û˘ ÙˆÓ ¯ÂÈÚÔ˘ÚÁÈÎÒÓ ·ÛıÂÓÒÓ
106
METAMO™XEY™Eπ™ 2008
POSSUM11 Î·È TRISS12. Δ· ·›ÙÈ· Ù˘ ·ÈÌÔÚÚ·Á›·˜ ›ӷÈ: ñ OÈ ÚÔÌÂÙ·ÌÔÛ¯Â˘ÙÈΤ˜ ‰È·Ù·Ú·¯¤˜ ÙÔ˘ Ì˯·ÓÈÛÌÔ‡ Ù˘ ‹Í˘ ÏfiÁˆ Ù˘ Èı·Ó‹˜ Ë·ÙÈ΋˜ ·Ó¿ÚÎÂÈ·˜ ñ OÈ ‰ÈÂÁ¯ÂÈÚËÙÈΤ˜ ‰È·Ù·Ú·¯¤˜ Ù˘ ‹Í˘ Î·È Ù˘ ÈÓˆ‰fiÏ˘Û˘ ñ ∏ ¯ÂÈÚÔ˘ÚÁÈ΋ Ù¯ÓÈ΋ ñ ∏ ÂÏÏÂÈ‹˜ ·Ó·ÈÛıËÛÈÔÏÔÁÈ΋ ·Ú·ÎÔÏÔ‡ıËÛË (˘ÔıÂÚÌ›·, ÌÂÙ·‚ÔÏÈ΋ ÔͤˆÛË, ˘ÂÚÊfiÚÙˆÛË ÙÔ˘ ·ÛıÂÓÔ‡˜ Ì ˘ÁÚ¿).
¶ÚÔÌÂÙ·ÌÔÛ¯Â˘ÙÈΤ˜ ‰È·Ù·Ú·¯¤˜ Ù˘ ·ÈÌfiÛÙ·Û˘ H ·ÈÌfiÛÙ·ÛË ·ÔÙÂÏ› ÌÈ· ¢·›ÛıËÙË ÈÛÔÚÚÔ›· ·Ó¿ÌÂÛ· ÛÙȘ ÚÔıÚÔÌ‚ˆÙÈΤ˜ Î·È ·ÓÙÈıÚÔÌ‚ˆÙÈΤ˜ ‰˘Ó¿ÌÂȘ. ™ÎÔfi˜ Ù˘ Â›Ó·È Ë ‰È·Ù‹ÚËÛË Ù˘ ÚÔ‹˜ ÙÔ˘ ·›Ì·ÙÔ˜ Î·È Ë ¤ÁηÈÚË ‰È·ÎÔ‹ Ù˘ ·ÈÌÔÚÚ·Á›·˜ ÛÙËÓ ÂÚÈÔ¯‹ Ù˘ ‚Ï¿‚˘ ÙÔ˘ ·ÁÁ›Ԣ. ΔÔ ‹·Ú ‰È·‰Ú·Ì·Ù›˙ÂÈ ÎÔÌ‚ÈÎfi ÚfiÏÔ ÛÙËÓ ‹ÍË ÙÔ˘ ·›Ì·ÙÔ˜13 ÌÈ· Î·È ÂΛ Û˘ÓÙ›ıÂÓÙ·È: 1) ÔÈ ·Ú¿ÁÔÓÙ˜ ‹Í˘ ÏËÓ ÙÔ˘ VIII Î·È ÙÔ˘ ·Ú¿ÁÔÓÙ· von Willebrand (vWF)14, 2) ÔÈ Ê˘ÛÈÎÔ› ·Ó·ÛÙÔÏ›˜ Ù˘ ‹Í˘ (ÚˆÙ›ÓË C Î·È S) Î·È 3) ÔÈ ·Ú¿ÁÔÓÙ˜ Ù˘ ÈÓˆ‰fiÏ˘Û˘ [Ï·ÛÌÈÓÔÁfiÓÔ˘ 15 , Δ∞FI (thrombin activable fibrinolysis inhibitor)15]. ∏ Ë·ÙÈ΋ ·Ó¿ÚÎÂÈ· Û˘Óԉ‡ÂÙ·È ·fi ÛËÌ·ÓÙÈΤ˜ ·ÏÏ·Á¤˜ ÛÙÔÓ ·ÈÌÔÛÙ·ÙÈÎfi Ì˯·ÓÈÛÌfi ÏfiÁˆ Ù˘ ÂÏ·Ùو̤Ó˘ Û˘ÁΤÓÙÚˆÛ˘ ÛÙÔ Ï¿ÛÌ· ÚÔËÎÙÈÎÒÓ Î·È ·ÓÙÈËÎÙÈÎÒÓ ·Ú·ÁfiÓÙˆÓ ‹Í˘ Ô˘ Û˘ÓÙ›ıÂÓÙ·È ·fi Ù· Ë·ÙÔ·ÙÙ·Ú·16. ∂›Û˘ Ë Û˘Ó˘¿Ú¯Ô˘Û· ¤ÏÏÂÈ„Ë ‚ÈÙ·Ì›Ó˘ ∫ Ô‰ËÁ› Û ۇÓıÂÛË ÌË ÏÂÈÙÔ˘ÚÁÈÎÒÓ ·Ú·ÁfiÓÙˆÓ ‹Í˘ ÏfiÁˆ ·‰˘Ó·Ì›·˜ Á-ηڂÔÍ˘Ï›ˆÛ˘ ÙÔ˘˜ ÛÙÔ Ë·ÙÔ·ÙÙ·ÚÔ. ∏ ÈÔ Û˘¯Ó‹ ÂÚÁ·ÛÙËÚȷ΋ ‰È·Ù·Ú·¯‹ Ù˘ ‹Í˘ ÛÙÔ˘˜ ·ÛıÂÓ›˜ ·˘ÙÔ‡˜ Â›Ó·È Ë ·Ú¿Ù·ÛË ÙÔ˘ ¯ÚfiÓÔ˘ ÚÔıÚÔÌ‚›Ó˘ (Prothrombin Time, ƒΔ) ÏfiÁˆ Ù˘ ÂÏ·Ùو̤Ó˘ Û‡ÓıÂÛ˘ ÙˆÓ ∫-ÂÍ·ÚÙÒÌÂÓˆÓ ·Ú·ÁfiÓÙˆÓ Ù˘ ‹Í˘17. ∂ÈϤÔÓ, ÙÔ ·Ó·ÚΤ˜ ‹·Ú ¤¯ÂÈ ÂÏ·Ùو̤ÓË ÈηÓfiÙËÙ· οı·ÚÛ˘ ÙˆÓ ÂÓÂÚÁÔÔÈËÌ¤ÓˆÓ ·Ú¿ÁÔÓÙˆÓ Ù˘ ‹Í˘ Î·È ÙˆÓ ·Ó·ÛÙ·ÏÙÒÓ ÙÔ˘˜ ·fi ÙË Î˘ÎÏÔÊÔÚ›· ÙÔ˘ ·›Ì·ÙÔ˜. ΔÔ ·ÔÙ¤ÏÂÛÌ· Â›Ó·È ÔÈ ·ÛıÂÓ›˜ Ì ˷ÙÈ΋ ·Ó¿ÚÎÂÈ· ÙÂÏÈÎÔ‡ ÛÙ·‰›Ô˘ Ó· ÂÌÊ·Ó›˙Ô˘Ó ·˘ÍË̤ÓÔ Î›Ó‰˘ÓÔ ·ÈÌÔÚÚ·Á›·˜ Î·È ıÚfiÌ‚ˆÛ˘. Δ¤ÏÔ˜, Ë ÂÎÛÂÛËÌ·Ṳ̂ÓË ˘Ï·›· ˘¤ÚÙ·ÛË Ì ·Ú¿Ï¢ÚË Î˘ÎÏÔÊÔÚ›· Ô‰ËÁ› Û ‰Â˘ÙÂÚÔ·ı‹ ÛÏËÓÔÌÂÁ·Ï›· Ì ·ÔÙ¤ÏÂÛÌ· ηٷÛÙÚÔÊ‹ ÙˆÓ ·ÈÌÔÂÙ·Ï›ˆÓ ÛÙÔÓ ÛÏ‹Ó·. ∏ η-
107
Ù·ÛÙÚÔÊ‹ ·˘Ù‹ fiÛÔ Î·È Ë ÂÏ·Ùو̤ÓË Û‡ÓıÂÛË ıÚÔÌ‚ÔÔÈËÙ›Ó˘ ·fi ÙÔ ·Ó·ÚΤ˜ ‹·Ú ÚÔηÏÔ‡Ó ıÚÔÌ‚ÔÂÓ›·. ŸÏ˜ ÔÈ ‰È·Ù·Ú·¯¤˜ Ô˘ ÂÚÈÁÚ¿ÊÙËÎ·Ó Ê·›ÓÔÓÙ·È Û˘ÓÔÙÈο ÛÙÔÓ ›Ó·Î· 1. ¶›Ó·Î·˜ 1. ¢È·Ù·Ú·¯¤˜ Ù˘ ‹Í˘ Î·È Ù˘ ÈÓˆ‰fiÏ˘Û˘ ÛÙËÓ Ë·ÙÈ΋ ·Ó¿ÚÎÂÈ· ÙÂÏÈÎÔ‡ ÛÙ·‰›Ô˘. ÀÔËÎÙÈ΋ ηٿÛÙ·ÛË
ÀÂÚËÎÙÈ΋ ηٿÛÙ·ÛË
∂Ï·Ùو̤ÓÔ˜ ·ÚÈıÌfi˜ ·ÈÌÔÂÙ·Ï›ˆÓ
∞˘ÍË̤ӷ ›‰· ·Ú·ÁfiÓÙˆÓ VIII Î·È vWf
∂ËÚ·Ṳ̂ÓË ÏÂÈÙÔ˘ÚÁÈ- ∂Ï·Ùو̤ӷ ›‰· ÚˆÙ½ÎfiÙËÙ· ÙˆÓ ·ÈÌÔÂÙ·Ï›ˆÓ Ó˘ C, ÚˆÙ½Ó˘ S Î·È ·ÓÙÈıÚÔÌ‚›Ó˘ ∞˘ÍË̤ÓË ·Ó·ÛÙÔÏ‹ ∂Ï·Ùو̤ӷ ›‰· Ï·ÛÌÈ·ÈÌÔÂÙ·Ï›ˆÓ ·fi ÙÔ ÓÔÁfiÓÔ˘ ÓÈÙÚÈÎfi ÔÍ›‰ÈÔ, ÙËÓ ÚÔÛÙ·Î˘ÎÏ›ÓË πππ Î·È ÙËÓ ·2-·ÓÙÈÏ·ÛÌ›ÓË ∂Ï·Ùو̤ÓË Û˘ÁΤÓÙÚˆÛË ∞˘ÍË̤ӷ ›‰· Û˘Ì·Ú¿ÙˆÓ ·Ú·ÁfiÓÙˆÓ ‹Í˘ ÁÔÓÙ· ππ Ë·Ú›Ó˘ (ππ,V,VII,IX,X,XI) ¶ÔÛÔÙÈ΋ Î·È ÔÈÔÙÈ΋ ‰È·Ù·Ú·¯‹ ÙÔ˘ ÈÓˆ‰ÔÁfiÓÔ˘ ÷ÌËÏ¿ ›‰· ·2-·ÓÙÈÏ·ÛÌ›Ó˘,Δ∞FI
¢ÈÂÁ¯ÂÈÚËÙÈΤ˜ ‰È·Ù·Ú·¯¤˜ Ù˘ ·ÈÌfiÛÙ·Û˘ OÈ ‰È·Ù·Ú·¯¤˜ Ù˘ ·ÈÌfiÛÙ·Û˘ ηٿ ÙË ‰È¿ÚÎÂÈ· Ù˘ ÌÂÙ·ÌfiÛ¯Â˘Û˘ ‹·ÙÔ˜ ‰È·ÎÚ›ÓÔÓÙ·È ·Ó¿ÏÔÁ· Ì ÙȘ ¯ÂÈÚÔ˘ÚÁÈΤ˜ Ê¿ÛÂȘ Ù˘ ÌÂÙ·ÌfiÛ¯Â˘Û˘: ÚÔ-·ÓË·ÙÈ΋ Ê¿ÛË, ·ÓË·ÙÈ΋ Ê¿ÛË, ÌÂÙ¿ ÙËÓ Â·Ó·ÈÌ¿ÙˆÛË ÙÔ˘ ÌÔۯ‡̷ÙÔ˜ Î·È ¿ÌÂÛË ÌÂÙÂÁ¯ÂÈÚËÙÈ΋ Ê¿ÛË.
1) ¶ÚÔ·ÓË·ÙÈ΋ Ê¿ÛË ΔÔ ÚÒÙÔ ·˘Ùfi ÛÙ¿‰ÈÔ Ù˘ ª.∏. ¯·Ú·ÎÙËÚ›˙ÂÙ·È ·fi ÂÎÙÂٷ̤ÓË ‚Ï¿‚Ë ÙˆÓ ÈÛÙÒÓ ÏfiÁˆ Ù˘ χÛ˘ ÙˆÓ Û˘ÌʇÛÂˆÓ ÛÙËÓ ÂÚÈÙÔÓ·˚΋ ÎÔÈÏfiÙËÙ· Î·È ÙËÓ ‰È·ÙÔÌ‹ ÔÏÏÒÓ ·ÁÁ›ˆÓ. ™˘Ó‹ıˆ˜ Û ·˘Ù‹Ó ÙËÓ Ê¿ÛË ˘¿Ú¯Ô˘Ó ‹È˜ ‰È·Ù·Ú·¯¤˜ ÙÔ˘ ËÎÙÈÎÔ‡ Ì˯·ÓÈÛÌÔ‡ Î·È ÔÈ ·ÒÏÂȘ ·›Ì·ÙÔ˜ Û¯ÂÙ›˙ÔÓÙ·È Ì ÙËÓ ¯ÂÈÚÔ˘ÚÁÈ΋ Ù¯ÓÈ΋ Î·È ÙËÓ ÚÔ¸¿Ú¯Ô˘Û· ˘ÔËÎÙÈ΋ ηٿÛÙ·ÛË18,19. ¶Ú¤ÂÈ Ó· ÛËÌÂȈı› fiÙÈ ÔÈ ·ÛıÂÓ›˜ Ì ˷ÙÔ΢ÙÙ·ÚÈÎfi ηÚΛÓÔ Î·È ¯ÔÏÔÛÙ·ÙÈ΋ ΛÚÚˆÛË ‚Ú›ÛÎÔÓÙ·È Û ˘ÂÚËÎÙÈ΋ ηٿÛÙ·ÛË (fiˆ˜ ·Ô‰ÂÈÎÓ‡ÂÙ·È ·fi ÙËÓ ıÚÔÌ‚ÔÂÏ·ÛÙÔÁÚ·Ê›·20) Î·È Ë ÈÓˆ‰fiÏ˘ÛË Û ·˘ÙÔ‡˜ ÙÔ˘˜ ·ÛıÂÓ›˜ Â›Ó·È ÂÏ·Ùو̤ÓË Î·Ù¿ ÙËÓ ‰È¿ÚÎÂÈ· Ù˘ ¤̂·Û˘ Ì ·ÔÙ¤ÏÂÛÌ· Ë ¯Ú‹ÛË ·ÓÙÈÈÓˆ‰ÔÏ˘ÙÈÎÒÓ Ê·ÚÌ¿ÎˆÓ Ó· ·ÓÙ‰›ÎÓ˘Ù·È.
108
X. ¶∞¶∞°∂øƒ°π√À
™ÙÔ˘˜ ·ÛıÂÓ›˜ Ì ˷ÙÈ΋ ·Ó¿ÚÎÂÈ· ÙÂÏÈÎÔ‡ ÛÙ·‰›Ô˘ ¯ˆÚ›˜ Ë·ÙÔ΢ÙÙ·ÚÈÎfi ηÚΛÓÔ Ô˘ ˘Ô‚¿ÏÏÔÓÙ·È Û ª.∏. Ë ·˘ÍË̤ÓË ÈÓˆ‰fiÏ˘ÛË Â˘ı‡ÓÂÙ·È ÁÈ· ·˘ÍË̤Ó˜ ·ÒÏÂȘ ·›Ì·ÙÔ˜ ÛÙËÓ ÚÔ-·ÓË·ÙÈ΋ Ê¿ÛË ÌfiÓÔ ÛÙÔ 10-20% ÙˆÓ ·ÛıÂÓÒÓ21.
2) ∞ÓË·ÙÈ΋ Ê¿ÛË ∫·Ù¿ ÙË ‰È¿ÚÎÂÈ· Ù˘ Ê¿Û˘ ·˘Ù‹˜ ‰ÂÓ ·Ú·ÙËÚÂ›Ù·È ·ÒÏÂÈ· ·›Ì·ÙÔ˜ ÏfiÁˆ ¯ÂÈÚÔ˘ÚÁÈÎÒÓ ¯ÂÈÚÈÛÌÒÓ ÌÈ· Î·È Ù· ·ÁÁ›· Ù˘ ÂÚÈÔ¯‹˜ Â›Ó·È ·ÔÎÏÂÈṲ̂ӷ. ™ÙËÓ Ê¿ÛË fï˜ ·˘Ù‹ Û˘Ì‚·›ÓÔ˘Ó ÛËÌ·ÓÙÈΤ˜ ·ÈÌÔÛÙ·ÙÈΤ˜ ·ÏÏ·Á¤˜ Ô˘ Ô‰ËÁÔ‡Ó Û ·ÈÌÔÚÚ·ÁÈ΋ ‰È¿ıÂÛË. ∏ ·ÚÈ· ‰È·Ù·Ú·¯‹ Ô˘ ·Ú·ÙËÚÂ›Ù·È Â›Ó·È Ë ·˘ÍË̤ÓË ÈÓˆ‰fiÏ˘ÛË Ô˘ ÚÔηÏÂ›Ù·È ·fi Ù· ·˘ÍË̤ӷ ›‰· ÙÔ˘ ÂÓÂÚÁÔÔÈËÙ‹ ÙÔ˘ Ï·ÛÌÈÓÔÁfiÓÔ˘ (tissue – plasminogen activator t-PA)18,19. O t-PA ÂÓÂÚÁÔÔÈ› ÙËÓ ÌÂÙ·ÙÚÔ‹ ÙÔ˘ Ï·ÛÌÈÓÔÁfiÓÔ˘ Û ϷÛÌ›ÓË Ô˘ Ì ÙËÓ ÛÂÈÚ¿ Ù˘ ηٷχÂÈ ÙËÓ ·Ô‰fiÌËÛË Ù˘ ÈÓÈ΋˜ ÙÔ˘ ıÚfiÌ‚Ô˘ ÛÙ· ÚÔÈfiÓÙ· ‰È¿Û·Û‹˜ Ù˘. Δ· ·˘ÍË̤ӷ ›‰· ÙÔ˘ t-PA ÔÊ›ÏÔÓÙ·È Î˘Ú›ˆ˜ ÛÙËÓ ·‰˘Ó·Ì›· Ë·ÙÈ΋˜ οı·ÚÛ˘ ÙÔ˘22. ∂ÈϤÔÓ, Ë ·‡ÍËÛË ·˘Ù‹ ÙÔ˘ t-PA ÚÔηÏ› Î·È Î·Ù·Ó¿ÏˆÛË ÙÔ˘ Ê˘ÛÈÎÔ‡ ·Ó·ÛÙ·ÏÙ‹ ÙÔ˘ (plasminogen activator inhibitor -1), ÚÔηÏÒÓÙ·˜ ‰È·Ù·Ú·¯‹ ÛÙËÓ ÈÛÔÚÚÔ›· Ù˘ ÈÓˆ‰ÔÏ˘ÙÈ΋˜ ‰È·‰Èηۛ·˜ Î·È ÚÒÈÌË Ï‡ÛË ÙˆÓ ıÚfiÌ‚ˆÓ. ∏ ‡·ÚÍË ÂÓÂÚÁÔ‡˜ ÈÓˆ‰fiÏ˘Û˘ ηٿ ÙËÓ ·ÓË·ÙÈÎË Ê¿ÛË Ê·›ÓÂÙ·È ·fi ÙËÓ ÂÏ¿ÙÙˆÛË Ù˘ ·2-·ÓÙÈÏ·ÛÌ›Ó˘ Î·È Ù· ·˘ÍË̤ӷ ›‰· ÈÓÈ΋˜ Î·È ÙˆÓ ÚÔ˚fiÓÙˆÓ ·Ô‰fiÌËÛ˘ Ù˘ (Fibrin Degradation Products)
3) º¿ÛË Â·Ó·ÈÌ¿ÙˆÛ˘ ∏ Ê¿ÛË ·˘Ù‹ ·ÔÙÂÏ› ÙÔ ÎÔÌ‚ÈÎfi ÛËÌÂ›Ô Ù˘ ¤̂·Û˘ Î·È ÚÔηÏ› ÛÔ‚·Ú¤˜ ‰È·Ù·Ú·¯¤˜ Ù˘ ·ÈÌfiÛÙ·Û˘. ª¤Û· Û ÌÂÚÈο ÏÂÙ¿ ·Ì¤Ûˆ˜ ÌÂÙ¿ ÙËÓ Â·Ó·ÈÌ¿ÙˆÛË ÙÔ˘ Ó¤Ô˘ ‹·ÙÔ˜ Ô Î›Ó‰˘ÓÔ˜ ÌË ÂÏÂÁ¯fiÌÂÓ˘ Ì›˙ÔÓÔ˜ ·ÈÌÔÚÚ·Á›·˜ ‹ ‰È¿¯˘Ù˘ ·ÈÌÔÚÚ·ÁÈ΋˜ ‰È¿ıÂÛ˘ Â›Ó·È ÛËÌ·ÓÙÈÎfi˜. O ÂÁÎψ‚ÈÛÌfi˜ ÙˆÓ ·ÈÌÔÂÙ·Ï›ˆÓ ̤۷ ÛÙÔ ÌfiÛ¯Â˘Ì· ·›˙ÂÈ ÛËÌ·ÓÙÈÎfi ÚfiÏÔ ÛÙËÓ ÂΉ‹ÏˆÛË ÙˆÓ ·ÈÌÔÚÚ·ÁÈÒÓ. ¶ÂÈÚ·Ì·ÙÈΤ˜ ÌÂϤÙ˜ ·¤‰ÂÈÍ·Ó fiÙÈ ˘¿Ú¯ÂÈ ‰È·ÊÔÚ¿ ÂÒ˜ 55% ÛÙÔÓ ·ÚÈıÌfi ÙˆÓ ·ÈÌÔÂÙ·Ï›ˆÓ ÌÂٷ͇ Ù˘ ·ÚÙËÚȷ΋˜ Î·È ÊÏ‚È΋˜ ΢ÎÏÔÊÔÚ›·˜ ÛÙÔ Ó¤Ô ‹·Ú23. O ‚·ıÌfi˜ Ù˘ ÂÏ¿ÙÙˆÛ˘ ÙˆÓ ·ÈÌÔÂÙ·Ï›ˆÓ Ê·›ÓÂÙ·È Ó· Û¯ÂÙ›˙ÂÙ·È Ì ÙËÓ ‚·Ú‡ÙËÙ· Ù˘ ‚Ï¿‚˘ ·fi ÙËÓ ÈÛ¯·ÈÌ›· – ·ӷÈÌ¿ÙˆÛË ÙÔ˘ ‹·ÙÔ˜. Δ· ·ÈÌÔÂÙ¿ÏÈ· ÚÔÛÎÔÏÏÒÓÙ·È ÛÙÔ ÂÓ‰Ôı‹ÏÈÔ ÙˆÓ ÂÓ‰ÔË-
·ÙÈÎÒÓ ·ÁÁ›ˆÓ Î·È ÂÈÙ›ÓÔ˘Ó ÙËÓ ‚Ï¿‚Ë ·˘Ù‹ ̤ۈ Ù˘ ÚfiÎÏËÛ˘ ·fiÙˆÛ˘ ÙˆÓ ÂÓ‰ÔıËÏÈ·ÎÒÓ Î˘ÙÙ¿ÚˆÓ 24. ∏ ÂÓ‰ÔË·ÙÈ΋ ηٷÎÚ¿ÙËÛË ÙˆÓ ·ÈÌÔÂÙ·Ï›ˆÓ, Ë Á¤ÓÂÛË ıÚÔÌ‚›Ó˘ ÛÙÔ ÂÓÂÚÁÔÔÈË̤ÓÔ ÂÓ‰Ôı‹ÏÈÔ ÙÔ˘ ÌÔۯ‡̷ÙÔ˜, Ë ÂÍ·ÁÁ›ˆÛË ·ÈÌÔÂÙ·Ï›ˆÓ ÛÙÔ˘˜ ¯ÒÚÔ˘˜ ÙÔ˘ Disse Î·È Ë ·˘ÍË̤ÓË Ê·ÁÔ΢ÙÙ¿ÚˆÛË ÙÔ˘˜ ·fi Ù· ·ÙÙ·Ú· Kuppfer ¤¯Ô˘Ó ÂÓÔ¯ÔÔÈËı› ÁÈ· ÙË ıÚÔÌ‚ÔÂÓ›·. ∂ÈϤÔÓ, ηٿ ÙËÓ Ê¿ÛË ·˘Ù‹ ·Ú·ÙËÚÂ›Ù·È ·˘ÍË̤ÓË ÈÓˆ‰fiÏ˘ÛË ÏfiÁˆ ÙˆÓ ·˘ÍËÌ¤ÓˆÓ ÂȤ‰ˆÓ t-PA ÙÔ˘ Ï‹ÙË Î·ıÒ˜ Î·È ÙËÓ ¤ÎÎÚÈÛË t-PA ·fi ÙÔ ÈÛ¯·ÈÌÈÎfi ÂÓ‰Ôı‹ÏÈÔ ÙÔ˘ ÌÔۯ‡̷ÙÔ˜ ·Ì¤Ûˆ˜ ÌÂÙ¿ ÙËÓ Â·Ó·ÈÌ¿ÙˆÛË. ∏ ·˘ÍË̤ÓË ·˘Ù‹ ÈÓˆ‰fiÏ˘ÛË ˘Ô¯ˆÚ› 60 min ÌÂÙ¿ ÙËÓ Â·Ó·ÈÌ¿ÙˆÛË ÙÔ˘ ÌÔۯ‡̷ÙÔ˜ ÏfiÁˆ Ù˘ ¤Ó·Ú͢ οı·ÚÛ˘ ÙÔ˘ t-PA ·fi ÙÔ ÌfiÛ¯Â˘Ì· ηıÒ˜ Î·È Ù˘ ·‡ÍËÛ˘ Ù˘ ‰Ú·ÛÙÈÎfiÙËÙ·˜ ÙÔ˘ ·Ó·ÛÙÔϤ· ÙÔ˘ t-PA. ™Ù· ÌÔۯ‡̷ٷ Ô˘ ‰˘ÛÚ·ÁÔ‡Ó ·Ú·ÙËÚÂ›Ù·È ÌÈ· ÂÌ̤ÓÔ˘Û· ·˘ÍË̤ÓË ÈÓˆ‰ÔÏ˘ÙÈ΋ ‰Ú·ÛÙËÚÈfiÙËÙ·. ªÂÙ¿ ÙËÓ Â·Ó·ÈÌ¿ÙˆÛË, ¤¯ÂÈ ·Ú·ÙËÚËı› ¤ÎÏ˘ÛË Ë·Ú›Ó˘ ·fi ÙÔ ÌfiÛ¯Â˘Ì· ÌÂÙ¿ ÙÔÓ Ë·ÚÈÓÈÛÌfi ÙÔ˘ ‹ ÂÓ‰ÔÁÂÓÒÓ Ô˘ÛÈÒÓ Ô˘ ÌÔÈ¿˙Ô˘Ó Ì ˷ڛÓË ·fi ÙÔ ÈÛ¯·ÈÌÈÎfi ÂÓ‰Ôı‹ÏÈÔ ÙÔ˘ ÌÔۯ‡̷ÙÔ˜, ÛÙÔ 25-95% ÙˆÓ ÂÚÈÙÒÛˆÓ25. ∞˘Ùfi ÙÔ Ê·ÈÓfiÌÂÓÔ ‰È·ÚΛ Ï›ÁÔ ·ÏÏ¿ Û ÌÂÚÈÎÔ‡˜ ·ÛıÂÓ›˜ ·Ú·ÙËÚÂ›Ù·È ·‰˘Ó·Ì›· οı·ÚÛ˘ ·˘ÙÒÓ ÙˆÓ Ô˘ÛÈÒÓ. ™ÙȘ ÂÚÈÙÒÛÂȘ ·˘Ù¤˜ ¤¯ÂÈ ¯ÚËÛÈÌÔÔÈËı› Ë ÚˆÙ·Ì›ÓË ˆ˜ ·Ó·ÛÙÚÔʤ·˜ Ù˘ ‰Ú¿Û˘ Ù˘ Ë·Ú›Ó˘. ¶Ú¤ÂÈ Ó· ÙÔÓÈÛÙ› fiÙÈ Î·È ¿ÏÏÔÈ ·Ú¿ÁÔÓÙ˜ fiˆ˜ Ë ÌÂÙ·‚ÔÏÈ΋ ÔͤˆÛË, Ë ˘ÔıÂÚÌ›·, Ë ¯·ÌËÏ‹ Û˘ÁΤÓÙÚˆÛË ÈÔÓÈṲ̂ÓÔ˘ Ca Û˘ÓÂÈÎÔ˘ÚÔ‡Ó ÛÙȘ ‰È·Ù·Ú·¯¤˜ ËÎÙÈÎÔ‡ Ì˯·ÓÈÛÌÔ‡ ÛÙËÓ Ê¿ÛË ·˘Ù‹.
4) ªÂÙÂÁ¯ÂÈÚËÙÈ΋ Ê¿ÛË ∏ ıÚÔÌ‚ÔÂÓ›· ÛÙËÓ ¿ÌÂÛË ÌÂÙÂÁ¯ÂÈÚËÙÈ΋ ÂÚ›Ô‰Ô Â›Ó·È ÙÔ Î‡ÚÈÔ ¯·Ú·ÎÙËÚÈÛÙÈÎfi ÙˆÓ ÌÂÙ·ÌÔÛ¯Â˘Ì¤ÓˆÓ ·ÛıÂÓÒÓ. OÊ›ÏÂÙ·È ÛÙËÓ Î·Ù·Ó¿ÏˆÛË ÙˆÓ ·ÈÌÔÂÙ·Ï›ˆÓ ÌÂÙ¿ ÙËÓ Â·Ó·ÈÌ¿ÙˆÛË, ÊÙ¿ÓÂÈ ÛÙÔ Ó·‰›Ú 2 Ì 3 Ë̤Ú˜ ÌÂÙ¿ (ÛÔ‚·Ú‹ ıÚÔÌ‚ÔÂÓ›· < 20.000 x109/lt) Î·È ÛÙËÓ Û˘Ó¤¯ÂÈ· ·Ôηı›ÛÙ·Ù·È ÛÙ·‰È·Î¿ Ô ·ÚÈıÌfi˜ ÙÔ˘˜ 18,19 . ∂ÊfiÛÔÓ ÙÔ ÌfiÛ¯Â˘Ì· ÏÂÈÙÔ˘ÚÁ›, Ù· ›‰· ıÚÔÌ‚ÔÔÈËÙ›Ó˘ ·˘Í¿ÓÔ˘Ó ·fi ÙËÓ ÚÒÙË Ì¤Ú· Î·È ÙËÓ 5Ë Ì¤Ú· ·Ú¯›˙Ô˘Ó Ó· ΢ÎÏÔÊÔÚÔ‡Ó Ó¤· ·ÈÌÔÂÙ¿ÏÈ·. ∏ Û˘ÁΤÓÙÚˆÛ‹ ÙÔ˘˜ ÊÙ¿ÓÂÈ ÛÂ Ê˘ÛÈÔÏÔÁÈο ›‰· ÌÂÙ¿ 14 Ë̤Ú˜26.
∏ ¯ÂÈÚÔ˘ÚÁÈ΋ Ù¯ÓÈ΋ ∏ ÓÂfiÙÂÚË piggyback Ù¯ÓÈ΋ ¤¯ÂÈ ·Ô‰Âȯı› fi-
METAMO™XEY™Eπ™ 2008
ÙÈ ÂÏ·ÙÙÒÓÂÈ ÙȘ ‰ÈÂÁ¯ÂÈÚËÙÈΤ˜ ·ÒÏÂȘ ·›Ì·ÙÔ˜ ÏfiÁˆ 1) Ù˘ ·ÔÊ˘Á‹˜ Ù˘ ‰È·ÙÔÌ‹˜ ÙˆÓ ÔÏÏ·ÏÒÓ ÊÏ‚ÈÎÒÓ ÙÚȯÔÂȉÒÓ ÛÙËÓ ÂÚÈÔ¯‹ ÙÔ˘ ÔÈÛıÔÂÚÈÙÔÓ·›Ô˘ Î·È 2) ÙÔ˘ ÌÈÎÚfiÙÂÚÔ˘ ¯ÚfiÓÔ˘ «ıÂÚÌ‹˜» ÈÛ¯·ÈÌ›·˜ ÙÔ˘ ÌÔۯ‡̷ÙÔ˜, ‰ËÏ. ÙÔ˘ ¯ÚfiÓÔ˘ ·fi ÙËÓ ¤ÍÔ‰Ô ÙÔ˘ ÌÔۯ‡̷ÙÔ˜ ·fi ÙÔ ‰È¿Ï˘Ì· Û˘ÓÙ‹ÚËÛ˘ ̤¯ÚÈ ÙËÓ Â·Ó·ÈÌ¿ÙˆÛ‹ ÙÔ˘9.
∞Ó·ÈÛıËÛÈÔÏÔÁÈ΋ ·Ú·ÎÔÏÔ‡ıËÛË OÈ ‰È·Ù·Ú·¯¤˜ ËÎÙÈÎfiÙËÙ·˜ ÂȉÂÈÓÒÓÔÓÙ·È ‰ÈÂÁ¯ÂÈÚËÙÈο Ì ÙËÓ ˘ÔıÂÚÌ›· Î·È ÙËÓ ÌÂÙ·‚ÔÏÈ΋ ÔͤˆÛË. ∏ ˘ÔıÂÚÌ›·, ˆ˜ ·ÔÙ¤ÏÂÛÌ· ¯ÔÚ‹ÁËÛ˘ ˘ÁÚÒÓ ‹ ·›Ì·ÙÔ˜ ‹ ·Ú·ÁfiÓÙˆÓ ¯ˆÚ›˜ ÚÔËÁÔ‡ÌÂÓË ı¤ÚÌ·ÓÛË, Ô‰ËÁ› Û ·Ú¿Ù·ÛË ÙˆÓ ¯ÚfiÓˆÓ ‹Í˘27. EÈϤÔÓ, Ë ÌÂÙ·‚ÔÏÈ΋ ÔͤˆÛË Ô˘ Û˘Ó·ÓÙ¿Ù·È ÛÙÔ˘˜ ·ÛıÂÓ›˜ ·˘ÙÔ‡˜ ÙfiÛÔ Î·Ù¿ ÙËÓ ·ÓË·ÙÈ΋ fiÛÔ Î·È ÙËÓ ¿ÌÂÛË ÌÂÙ¿ ÙËÓ Â·Ó·ÈÌ¿ÙˆÛË Ê¿ÛË Èı·ÓfiÓ Ó· ÚÔηÏ› ·Ó·ÛÙÔÏ‹ Ù˘ ÏÂÈÙÔ˘ÚÁÈÎfiÙËÙ·˜ ÙˆÓ ·ÈÌÔÂÙ·Ï›ˆÓ28. T¤ÏÔ˜, ¤¯ÂÈ ‰È·ÈÛÙˆı› ÌÈ· ÁÚ·ÌÌÈ΋ Û‡Ó‰ÂÛË ·Ó¿ÌÂÛ· ÛÙËÓ ‰ÈÂÁ¯ÂÈÚËÙÈ΋ ·ÒÏÂÈ· ·›Ì·ÙÔ˜ Î·È ÙËÓ ÎÂÓÙÚÈ΋ ÊÏ‚È΋ ›ÂÛË (∫.º.∫.). ¢È·Ù‹ÚËÛË Ù˘ ∫.º.∫. < 5mmHg ¤¯ÂÈ ·Ú·ÙËÚËı› fiÙÈ Û¯ÂÙ›˙ÂÙ·È Ì ÌÂȈ̤Ó˜ ·ÒÏÂȘ ·›Ì·ÙÔ˜ (·ÒÏÂÈ· ÌÈÎÚfiÙÂÚË ·fi 200 cc Ô˘ ‰ÂÓ ¯Ú‹˙ÂÈ ÌÂÙ¿ÁÁÈÛ˘ ·›Ì·ÙÔ˜)29. ∏ ¤ÁηÈÚË ·ÓÙÈÌÂÙÒÈÛË ÙˆÓ ÛÔ‚·ÚÒÓ ·ÈÌÔÚÚ·ÁÈÒÓ Î·Ù¿ ÙË ‰È¿ÚÎÂÈ· Ù˘ O.ª.∏. fiˆ˜ Î·È ¿ÌÂÛ· ÌÂÙÂÁ¯ÂÈÚËÙÈο ·ÔÙÂÏ› ·ÎÚÔÁˆÓÈ·›Ô Ï›ıÔ ÁÈ· ÙËÓ ÏÂÈÙÔ˘ÚÁÈÎfiÙËÙ· ÙÔ˘ ÌÔۯ‡̷ÙÔ˜ Î·È ÙËÓ ÂÏ¿ÙÙˆÛË Ù˘ ÓÔÛËÚfiÙËÙ·˜ ÙÔ˘ ·ÛıÂÓÔ‡˜. °È· ÙËÓ ıÂڷ›· ÙˆÓ ‰È·Ù·Ú·¯ÒÓ Ù˘ ·ÈÌfiÛÙ·Û˘ ¤¯Ô˘Ó ¯ÚËÛÈÌÔÔÈËı› ÔÈ ÎÏ·ÛÛÈΤ˜ Ù¯ÓÈΤ˜ ˘ÔηٿÛÙ·Û˘ ÙˆÓ ·Ú·ÁfiÓÙˆÓ (ÊÚ¤ÛÎÔ Î·Ù„˘Á̤ÓÔ Ï¿ÛÌ· FFP, ÎÚ˘ÔηıÈ˙‹Ì·Ù·), ·ÈÌÔÂÙ·Ï›ˆÓ ηıÒ˜ Î·È ·Ó·ÛÙÔÏ‹˜ Ù˘ ÈÓˆ‰fiÏ˘Û˘ Ì ·ÓÙÈ-ÈÓˆ‰ÔÏ˘ÙÈÎÔ‡˜ ·Ú¿ÁÔÓÙ˜ (Â-·ÌÈÓÔηÚÔ˚Îfi Ô͇, ·ÚÔÙÈÓ›ÓË, ÙÚ·ÓÍÂÓ·ÌÈÎfi Ô͇). ΔËÓ ÙÂÏÂ˘Ù·›· ÂÙ·ÂÙ›· ÌÂÏÂÙ¿Ù·È Î·È Ë ¯Ú‹ÛË ÙÔ˘ rFVIIa ÌÈ· Î·È Ë ¯ÔÚ‹ÁËÛË ÙÔ˘ Û ¿ÏϘ ηÙËÁÔڛ˜ ·ÛıÂÓÒÓ Ì ÛÔ‚·Ú‹ ·ÈÌÔÚÚ·Á›· ¤¯ÂÈ ·Ô‰Âȯı› fiÙÈ ÂÚÈÔÚ›˙ÂÈ ÙËÓ ·ÈÌÔÚÚ·Á›·.
AÓ·Û˘Ó‰˘·Ṳ̂ÓÔ˜ ·Ú¿ÁÔÓÙ·˜ VII O ·Ú¿ÁÔÓÙ·˜ VII Â›Ó·È ¤Ó·˜ ‚ÈÙ·ÌÈÓÔ- ∫ ÂÍ·ÚÙÒÌÂÓÔ˜ Ù˘ ‹Í˘ Ô˘ ‚Ú›ÛÎÂÙ·È Û ÂÓÂÚÁÔÔÈË̤ÓË ÌÔÚÊ‹ ÛÙÔ ·›Ì· (ÂÚ›Ô˘ ÙÔ 1% Ù˘ Û˘ÓÔÏÈ΋˜ ÔÛfiÙËÙ·˜ ÙÔ˘ FVII). OÈ ‰Ú¿ÛÂȘ ÙÔ˘ FVIIa ›ӷÈ: ·) Û‡Ó‰ÂÛË Ì ÙÔÓ ÈÛÙÈÎfi ·Ú¿ÁÔÓÙ· (Tissue
109
Factor, TF ) Î·È ÂÓÂÚÁÔÔ›ËÛË ÙÔ˘ Û¯ËÌ·ÙÈÛÌÔ‡ Ù˘ ıÚÔÌ‚›Ó˘. O TF ÂÎÙ›ıÂÙ·È ÚÔ˜ ÙËÓ ·ÈÌ·ÙÈ΋ ΢ÎÏÔÊÔÚ›· fiÙ·Ó Û˘Ì‚Â› ‚Ï¿‚Ë ÙÔ˘ ÂÓ‰ÔıËÏ›Ô˘ ÙˆÓ ·ÁÁ›ˆÓ Î·È Û˘Ó‰ÂfiÌÂÓÔ˜ Ì ÙÔÓ FVIIa ˘ÚÔ‰ÔÙ› ÙËÓ ‰È·‰Èηۛ· Á¤ÓÂÛ˘ ıÚÔÌ‚›Ó˘ Î·È Û¯ËÌ·ÙÈÛÌÔ‡ ÙÔ˘ ıÚfiÌ‚Ô˘ ÛÙÔ ÛËÌÂ›Ô Ù˘ ·ÈÌÔÚÚ·Á›·˜. ΔÔ Û‡ÌÏÔÎÔ FVIIa – ÈÛÙÈÎÔ‡ ·Ú¿ÁÔÓÙ· Ô˘ Û¯ËÌ·Ù›˙ÂÙ·È ÂÓÂÚÁÔÔÈ› Ì ÙËÓ ÛÂÈÚ¿ ÙÔ˘ ÙÔÓ ·Ú¿ÁÔÓÙ· Ã Ô ÔÔ›Ô˜ ÂÓÂÚÁÔÔÈ› ·ÚÁ¿ ÙËÓ ÚÔıÚÔÌ‚›ÓË Î·È ·Ú¿ÁÔÓÙ·È Ù· ÚÒÙ· ÌfiÚÈ· ıÚÔÌ‚›Ó˘. H ıÚÔÌ‚›ÓË Â›Ó·È ˘Â‡ı˘ÓË ÁÈ· ÙËÓ ÌÂÁÈÛÙÔÔ›ËÛË Ù˘ ÂÓÂÚÁÔÔ›ËÛ˘ Ù˘ ‹Í˘, ÙÔÓ Û¯ËÌ·ÙÈÛÌfi Ù˘ ÈÓÈ΋˜ Î·È ÁÈ· ÙËÓ ÛÙ·ıÂÚÔÔÈ‹Û˘ Ù˘ ÈÓÈ΋˜ ̤۷ ÛÙÔ ıÚfiÌ‚Ô. O Ì˯·ÓÈÛÌfi˜ ·˘Ùfi˜ Á¤ÓÂÛ˘ Ù˘ ıÚÔÌ‚›Ó˘ Â›Ó·È ÂÍ·ÚÙÒÌÂÓÔ˜ ·fi ÙÔ ÔÛfi ÙÔ˘ ÈÛÙÈÎÔ‡ ·Ú¿ÁÔÓÙ· Ô˘ ı· ÂÎÏ˘ı› ·fi Ù· ÂÓ‰ÔıËÏȷο ·ÙÙ·Ú· Ô˘ ¤¯Ô˘Ó ‚Ï·Êı›. ΔÔ ›‰ÈÔ Û‡ÌÏÔÎÔ FVIIa – ÈÛÙÈÎÔ‡ ·Ú¿ÁÔÓÙ·, ÂÓÂÚÁÔÔÈ› ÙÔÓ ·Ú¿ÁÔÓÙ· IX Ô ÔÔ›Ô˜ Ì ÙËÓ ÛÂÈÚ¿ ÙÔ˘, ·ÚÔ˘Û›· ÂÓÂÚÁÔÔÈËÌ¤ÓˆÓ ·ÈÌÔÂÙ·Ï›ˆÓ, ÚÔηÏ› ·Ú·ÁˆÁ‹ ıÚÔÌ‚›Ó˘. ‚) Û‡Ó‰ÂÛË Ì ٷ ÂÓÂÚÁÔÔÈË̤ӷ ·ÈÌÔÂÙ¿ÏÈ· Î·È ÂÓÂÚÁÔÔ›ËÛË ÙÔ˘ ·Ú¿ÁÔÓÙ· Ã. O rFVIIa ÌÔÚ› Ó· ÂÓÂÚÁÔÔÈ‹ÛÂÈ ÙÔÓ ·Ú¿ÁÔÓÙ· à ̤ۈ ÂÓfi˜ Ì˯·ÓÈÛÌÔ‡ ·ÓÂÍ·ÚÙ‹ÙÔ˘ ·fi ÙÔÓ ÈÛÙÈÎfi ·Ú¿ÁÔÓÙ·. ™Â ˘„ËϤ˜ Û˘ÁÎÂÓÙÚÒÛÂȘ (80-100Ìg/kg) Ô rFVIIa ÌÔÚ› Ó· Û˘Ó‰Âı› ¿ÌÂÛ· Ì ٷ ÂÓÂÚÁÔÔÈË̤ӷ ·ÈÌÔÂÙ¿ÏÈ· Î·È Ó· ÂÓÂÚÁÔÔÈ‹ÛÂÈ ÙÔÓ ·Ú¿ÁÔÓÙ· Ã Ô ÔÔ›Ô˜ Ì ÙËÓ ÛÂÈÚ¿ ÙÔ˘ ı· ÚÔηϤÛÂÈ Á¤ÓÂÛË ıÚÔÌ‚›Ó˘ ¯ˆÚ›˜ ÙËÓ ‰È·ÌÂÛÔÏ¿‚ËÛË ÙÔ˘ ÈÛÙÈÎÔ‡ ·Ú¿ÁÔÓÙ·30,31. ™ÙÔ˘˜ ·ÛıÂÓ›˜ Ì ‚·ÚÂÈ¿ ıÚÔÌ‚ÔÂÓ›· Ô˘ ·ÈÌÔÚÚ·ÁÔ˘Ó Ô rFVIIa Â›Ó·È ·ÔÙÂÏÂÛÌ·ÙÈÎfi˜ ÛÙËÓ ÂÏ¿ÙÙˆÛË Ù˘ ·ÈÌÔÚÚ·Á›·˜32,33. ™Â ÌÈ· ÚfiÛÊ·ÙË ÌÂϤÙË, ·Ô‰Â›¯ıËΠfiÙÈ Ô rFVIIa ÛÙÔ˘˜ ıÚÔÌ‚ÔÂÓÈÎÔ‡˜ ·ÛıÂÓ›˜ ÂÈÙ·¯‡ÓÂÈ ÙËÓ Á¤ÓÂÛË ıÚÔÌ‚›Ó˘, ÙËÓ ÂÓÂÚÁÔÔ›ËÛË ÙˆÓ ·ÈÌÔÂÙ·Ï›ˆÓ Î·È ÙÔÓ Û¯ËÌ·ÙÈÛÌfi ıÚfiÌ‚Ô˘ ·ÚÔ˘Û›· ÌÈÎÚ‹˜ ÌfiÓÔ ÔÛfiÙËÙ·˜ ÈÛÙÈÎÔ‡ ·Ú¿ÁÔÓÙ·34. ŸÌˆ˜ ÛÙË ›‰È· ÌÂϤÙË ·Ú·ÙËÚ‹ıËΠfiÙÈ Û ·ÛıÂÓ›˜ Ì ‚·ÚÂÈ¿ ıÚÔÌ‚ÔÂÓ›· (·ÚÈıÌfi ·ÈÌoÂÙ·Ï›ˆÓ < 20 x 109/lt) , o rFVIIa ‰ÂÓ ‚ÂÏÙ›ˆÛ ÙËÓ ÛÙ·ıÂÚfiÙËÙ· ÙÔ˘ ıÚfiÌ‚Ô˘ ÂÓÒ Û ÌÂÁ·Ï‡ÙÂÚ˜ ÙÈ̤˜ ·ÈÌÔÂÙ·Ï›ˆÓ Ë ÛÙ·ıÂÚfiÙËÙ· ÙÔ˘ ıÚfiÌ‚Ô˘ ‹Ù·Ó Ê˘ÛÈÔÏÔÁÈ΋. ∏ ·Ú·Ù‹ÚËÛË ·˘Ù‹ ¤¯ÂÈ ÛËÌ·Û›· ÁÈ· ÙÔ˘˜ ÎÈÚÚˆÙÈÎÔ‡˜ ıÚÔÌ‚ÔÂÓÈÎÔ‡˜ ·ÛıÂÓ›˜ ÌÈ· Î·È Ë ¯ÔÚ‹ÁËÛË rFVIIa ı· Ô‰ËÁ‹ÛÂÈ ÛÙËÓ ‰ËÌÈÔ˘ÚÁ›· ÛÙ·ıÂÚÒÓ ıÚfiÌ‚ˆÓ Î·È ÂÔ̤ӈ˜ Û ÂÚÈÔÚÈÛÌfi ÙˆÓ ·ÈÌÔÚÚ·ÁÈÒÓ ÛÙÔ˘˜ ·ÛıÂÓ›˜ Ì > 20 x 109/lt ·ÈÌÔÂÙ¿ÏÈ·.
110
X. ¶∞¶∞°∂øƒ°π√À
∫ÏÈÓÈΤ˜ ÂÊ·ÚÌÔÁ¤˜ ÙÔ˘ rFVIIa ŒÓ‰ÂÈÍË ÁÈ· ¯Ú‹ÛË ÙÔ˘ rFVIIa ·ÔÙÂÏ› Ë ·˘ÙfiÌ·ÙË ·ÈÌÔÚÚ·Á›· Û ·ÛıÂÓ›˜ Ô˘ ¿Û¯Ô˘Ó ·fi ·ÈÌÔÚÚÔÊÈÏ›· Î·È ¤¯Ô˘Ó ·Ó·Ù‡ÍÂÈ ·ÓÙ›ÛÙ·ÛË (·Ó·ÛÙÔÏ›˜) ÛÙÔÓ ·Ú¿ÁÔÓÙ· VIII Î·È πÃ35. ¶ÚfiÛÊ·Ù·, ÛÙËÓ ∂˘Úˆ·È΋ ŒÓˆÛË ÂÁÎÚ›ıËÎÂ Ë ¯Ú‹ÛË ÙÔ˘ rFVIIa Û ·ÛıÂÓ›˜ Ì ÎÏËÚÔÓÔÌÈ΋ ‹ ›ÎÙËÙË ·ÈÌÔÚÚÔÊÈÏ›· Î·È ·Ó·ÛÙ·ÏÙ¤˜ ÙÔ˘ ·Ú¿ÁÔÓÙ· VIII, Û ·ÛıÂÓ›˜ Ì ÁÂÓÂÙÈ΋ ¤ÏÏÂÈ„Ë FVII Ô˘ ˘Ô‚¿ÏÏÔÓÙ·È Û ¯ÂÈÚÔ˘ÚÁÈΤ˜ ÂÂÌ‚¿ÛÂȘ Î·È Û ·ÛıÂÓ›˜ Ì Glanzmann’s ıÚÔÌ‚·Ûı¤ÓÂÈ·36. ¶·ÚfiÏ· ·˘Ù¿, ·fi ÙÔ 1995 Ô˘ Ô rFVIIa ‹Ú ¿‰ÂÈ· ¯ÔÚ‹ÁËÛ˘ Û ·ÓıÚÒÔ˘˜, ¤Ó·˜ ÌÂÁ¿ÏÔ˜ ·ÚÈıÌfi˜ ÌÂÏÂÙÒÓ Ì ÌÈÎÚfi ·ÚÈıÌfi ·ÛıÂÓÒÓ ¤¯Ô˘Ó ·Ó·Ê¤ÚÂÈ ÈηÓÔÔÈËÙÈ΋, ·ÔÙÂÏÂÛÌ·ÙÈ΋ Î·È ·ÛÊ·Ï‹ ¯Ú‹ÛË ÙÔ˘ rFVIIa Û ‰È¿ÊÔÚ˜ ÎÏÈÓÈΤ˜ ηٷÛÙ¿ÛÂȘ Ì ÌÂÁ¿Ï˜ ·ÒÏÂȘ ·›Ì·ÙÔ˜ fiˆ˜ Û ·ÛıÂÓ›˜ Ì ˷ÙÈ΋ ·Ó¿ÚÎÂÈ· ÙÂÏÈÎÔ‡ ÛÙ·‰›Ô˘ Î·È ·ÈÌÔÚÚ·Á›· ·fi ÙÔ ·ÓÒÙÂÚÔ Á·ÛÙÚÂÓÂÙÂÚÈÎfi 37, Û ÔÏ˘ÙÚ·˘Ì·Ù›Â˜ Ì ÛÔ‚·Ú¿ Î·È ‰È·ÙÈÙÚ·›ÓÔÓÙ· ÙÚ·‡Ì·Ù·38, Û ·ÛıÂÓ›˜ Ì ÛÔ‚·Ú¤˜ ÂÁÎÂÊ·ÏÈΤ˜ ·ÈÌÔÚÚ·Á›Â˜39 Î·È Û ·ÛıÂÓ›˜ Ô˘ ˘Ô‚¿ÏÏÔÓÙ·È Û ÚÈ˙È΋ ÚÔÛÙ·ÙÂÎÙÔÌ‹40.
ÃÔÚ‹ÁËÛË rFVIIa ÛÙËÓ ÌÂÙ·ÌfiÛ¯Â˘ÛË ‹·ÙÔ˜ OÈ ·ÛıÂÓ›˜ Ô˘ ˘Ô‚¿ÏÏÔÓÙ·È Û O.ª.∏. ·ÔÙÂÏÔ‡Ó Ì›· ÔÌ¿‰· fiÔ˘ Ë ¯Ú‹ÛË ÙÔ˘ rFVIIa Èı·ÓÒ˜ Ó· ÌÔÚÔ‡Û ӷ ÂÏ·ÙÙÒÛÂÈ ÙȘ ·ÒÏÂȘ ·›Ì·ÙÔ˜. ¶Úfi‰ÚÔ̘ ÎÏÈÓÈΤ˜ ÌÂϤÙ˜ ¤‰ÂÈÍ·Ó fiÙÈ Ë ¯ÔÚ‹ÁËÛË rFVIIa ‰ÈÔÚıÒÓÂÈ ÙÔÓ ·Ú·ÙÂٷ̤ÓÔ ¯ÚfiÓÔ ÚÔıÚÔÌ‚›Ó˘ Û ÎÈÚÚˆÙÈÎÔ‡˜ ·ÛıÂÓ›˜ Ô˘ ‰ÂÓ ·ÈÌÔÚÚ·ÁÔ‡Ó41. Δ· ·ÔÙÂϤÛÌ·Ù· Ù˘ ÚÒÙ˘ ÎÏÈÓÈ΋˜ ¯Ú‹Û˘ ÙÔ˘ rFVIIa Û ÂÓ‹ÏÈΘ ÎÈÚÚˆÙÈÎÔ‡˜ ·ÛıÂÓ›˜ Ô˘ ˘Ô‚¿ÏÏÔÓÙ·È Û O.ª.∏. ·Ó·ÎÔÈÓÒıËÎ·Ó ÙÔ 2001 ·fi ÙÔÓ Hedriks Î·È Û˘ÓÂÚÁ¿Ù˜42. ™ÙËÓ ÈÏÔÙÈ΋ ·˘Ù‹ ÌÂϤÙË, Ô˘ ÂÚÈÂÏ¿Ì‚·Ó ÌfiÓÔ 6 ·ÛıÂÓ›˜ ÔÈ ÔÔ›ÔÈ ¤Ï·‚·Ó rFVIIa Û ‰fiÛË 80Ìg/kg ÚÈÓ ÙËÓ ¤Ó·ÚÍË Ù˘ ¤̂·Û˘, ·Ú·ÙËÚ‹ıËΠÛÙ·ÙÈÛÙÈο ÛËÌ·ÓÙÈ΋ Ì›ˆÛË ÙˆÓ ·Ó·ÁÎÒÓ ÁÈ· ÌÂÙ¿ÁÁÈÛË ÂÚ˘ıÚÒÓ ·ÈÌÔÛÊ·ÈÚ›ˆÓ (67% ÂÏ¿ÙÙˆÛË, p=0.002). OÈ ÂÚ¢ÓËÙ¤˜ ›Û˘ ·Ú·Ù‹ÚËÛ·Ó, Ì ÙË ¯Ú‹ÛË Ù˘ ıÚÔÌ‚ÔÂÏ·ÛÙÔÁÚ·Ê›·˜ (thromboelastography, TEG), fiÙÈ Ë ¯ÔÚ‹ÁËÛË ÙÔ˘ rFVIIa ÂÈÙ¿¯˘Ó ÙËÓ ‰È·‰Èηۛ· Û¯ËÌ·ÙÈÛÌÔ‡ ÙÔ˘ ıÚfiÌ‚Ô˘ Î·È ‚ÂÏÙ›ˆÛ ÙËÓ ÛÙ·ıÂÚfiÙËÙ· Î·È Ù· Ê˘ÛÈο ¯·Ú·ÎÙËÚÈÛÙÈο ÙÔ˘43 (›Ó·Î·˜ 2). H ÌÂϤÙË ·˘Ù‹ ·ÔÙ¤ÏÂÛ ÙËÓ ‚¿ÛË ÁÈ· ‰‡Ô Â-
fiÌÂÓ˜, ÔÏ˘ÎÂÓÙÚÈΤ˜, Ù˘¯·ÈÔÔÈË̤Ó˜, ‰ÈϤ˜Ù˘ÊϤ˜, ÂÏÂÁ¯fiÌÂÓ˜ Ì ÂÈÎÔÓÈÎfi Ê¿ÚÌ·ÎÔ (placebo-controlled) ÌÂϤÙ˜. ™ÙËÓ ÚÒÙË, ÂϤÁ¯Ô˘ ‰fiÛ˘ ÌÂϤÙË, 82 ·ÛıÂÓ›˜ Ù˘¯·ÈÔÔÈ‹ıËÎ·Ó Û 4 ÔÌ¿‰Â˜ Î·È ¤Ï·‚·Ó Ì›· ‰fiÛË ÙˆÓ 20, 40, 80Ìg/kg rFVIIa ‹ ÂÈÎÔÓÈÎfi Ê¿ÚÌ·ÎÔ (placebo) ·Ì¤Ûˆ˜ ÚÈÓ ÙËÓ ¤Ó·ÚÍË Ù˘ ÌÂÙ·ÌfiÛ¯Â˘Û˘44. ¢ÂÓ ‰È·ÈÛÙÒıËΠÛÙ·ÙÈÛÙÈο ÛËÌ·ÓÙÈ΋ ‰È·ÊÔÚ¿ ÛÙȘ ÌÂÙ·ÁÁ›ÛÂȘ ÂÚ˘ıÚÒÓ ·ÈÌÔÛÊ·ÈÚ›ˆÓ Î·È ·Ú·ÁÒÁˆÓ ·Ó¿ÌÂÛ· ÛÙËÓ ÔÌ¿‰· Ì ÙÔ ÂÈÎÔÓÈÎfi Ê¿ÚÌ·ÎÔ Î·È ÛÙȘ ÔÌ¿‰Â˜ Ô˘ ¤Ï·‚·Ó rFVIIa. ªÈ· ¿ÏÏË ÛËÌ·ÓÙÈ΋ ·Ú·Ù‹ÚËÛË ·˘Ù‹˜ Ù˘ ÌÂϤÙ˘ Â›Ó·È fiÙÈ ‰ÂÓ ‚Ú¤ıËΠÛÙ·ÙÈÛÙÈο ÛËÌ·ÓÙÈ΋ ‰È·ÊÔÚ¿ ÛÙËÓ Û˘¯ÓfiÙËÙ· ÙˆÓ ıÚÔÌ‚ÔÂÌ‚ÔÏÈÎÒÓ ÂÂÈÛÔ‰›ˆÓ ·Ó¿ÌÂÛ· ÛÙȘ Ù¤ÛÛÂÚÂȘ ÔÌ¿‰Â˜ ÙˆÓ ·ÛıÂÓÒÓ (ÛÙÔ˘˜ ·ÛıÂÓ›˜ Ô˘ ‹Ú·Ó rFVIIa Î·È ÛÙÔ˘˜ ·ÛıÂÓ›˜ Ô˘ ‹Ú·Ó ÙÔ ÂÈÎÔÓÈÎfi Ê¿ÚÌ·ÎÔ). ™ÙËÓ ÌÂϤÙË ·˘Ù‹ ·Ó·Ï‡ıËÎÂ Î·È Ë Ê·ÚÌ·ÎÔÎÈÓËÙÈ΋ ÙÔ˘ rFVIIa Î·È ·Ú·ÙËÚ‹ıËΠfiÙÈ Â·Ú΋˜ Û˘ÁΤÓÙÚˆÛË rFVIIa ˘‹Ú¯Â ÙȘ ÚÒÙ˜ 3 ÒÚ˜ ÌÂÙ¿ ÙËÓ ¯ÔÚ‹ÁËÛË ÙÔ˘ Ê·ÚÌ¿ÎÔ˘ Î·È ‹Ù·Ó ‰ÔÛÔÂÍ·ÚÙÒÌÂÓË. ∂›Û˘, Ë Î¿ı·ÚÛË ÙÔ˘ Ê·ÚÌ¿ÎÔ˘ ‹Ù·Ó Ù·¯‡ÙÂÚË Û ۯ¤ÛË Ì ÙÔ˘˜ ÎÈÚÚˆÙÈÎÔ‡˜ ·ÛıÂÓ›˜ Ô˘ ‰ÂÓ ˘Ô‚Ï‹ıËÎ·Ó Û ¯ÂÈÚÔ˘ÚÁÈ΋ ¤̂·ÛË Î·È Ô ¯ÚfiÓÔ˜ ÚÔıÚÔÌ‚›Ó˘ ·ÓÂÚ¯fiÙ·Ó ÛÙ· ÚÔ Ù˘ ¯ÔÚ‹ÁËÛ˘ ›‰· ̤۷ Û 4 ÒÚ˜. ŒÙÛÈ, ÂÓÒ Ô Ì¤ÛÔ˜ ¯ÂÈÚÔ˘ÚÁÈÎfi˜ ¯ÚfiÓÔ˜ Ù˘ O.ª.∏. ‹Ù·Ó 7.3 ÒÚ˜ (7.1-7.4), Ë Ì›· Î·È ÌfiÓÔ ‰fiÛË ÙÔ˘ rFVIIa ‰ÂÓ Â·ÚÎÔ‡ÛÂ Î·È ÔÈ ‰È·Ù·Ú·¯¤˜ ·ÈÌfiÛÙ·Û˘ ·ӤگÔÓÙ·Ó ÛÙËÓ ÚÔ ¯ÔÚ‹ÁËÛ˘ rFVIIa ÙÈ̤˜, ÚÈÓ ÙÂÏÂÈÒÛÂÈ Ë Â¤Ì‚·ÛË. ΔÔ ÁÂÁÔÓfi˜ ·˘Ùfi ›Ûˆ˜ ˘Ô‰ÂÈÎÓ‡ÂÈ ˘ÔÂÎÙ›ÌËÛË Ù˘ ηٿÏÏËÏ˘ ‰fiÛ˘ Ô˘ Ô‰‹ÁËÛ Û ·ӷÈÌÔÚÚ·Á›· Î·È Û ÌÂÙ·ÁÁ›ÛÂȘ ·›Ì·ÙÔ˜ Ì ÙËÓ ›‰È· Û˘¯ÓfiÙËÙ· fiˆ˜ Î·È ÛÙËÓ placebo ÔÌ¿‰· (›Ó·Î·˜ 2). ™Â ÌÈ· ¿ÏÏË ÔÏ˘ÎÂÓÙÚÈ΋ ÌÂϤÙË, 183 ·ÛıÂÓ›˜ Ù˘¯·ÈÔÔÈ‹ıËÎ·Ó Û 3 ÔÌ¿‰Â˜ Î·È ¤Ï·‚·Ó placebo, 80 ‹ 120 Ìg/kg rFVIIa ·ÓÙ›ÛÙÔȯ·. OÈ ‰fiÛÂȘ ·ӷϷ̂·ÓfiÙ·Ó Î¿ı 2 ÒÚ˜ ηٿ ÙËÓ ‰È¿ÚÎÂÈ· Ù˘ ÌÂÙ·ÌfiÛ¯Â˘Û˘ ̤¯ÚÈ Î·È 30 min Ú›Ó ÙËÓ Â·Ó·ÈÌ¿ÙˆÛË ÙÔ˘ ÌÔۯ‡̷ÙÔ˜ Î·È Ì›· ÙÂÏÈ΋ ‰fiÛË ¯ÔÚËÁÔ‡ÓÙ·Ó ÛÙÔ Ù¤ÏÔ˜ Ù˘ ¤̂·Û˘45. ¶·ÚfiÏÔ Ô˘ ·Ú·ÙËÚ‹ıËΠÌÈ· ÛËÌ·ÓÙÈ΋ ‚Ú¿¯˘ÓÛË ÙÔ˘ ¯ÚfiÓÔ˘ ÚÔıÚÔÌ‚›Ó˘ ÁÈ· ÌÂÁ·Ï‡ÙÂÚÔ ¯ÚÔÓÈÎfi ‰È¿ÛÙËÌ· (5 ÒÚ˜) Ë ÌÂϤÙË ·˘Ù‹ ‰ÂÓ Î·Ù¿ÊÂÚ ӷ ·Ô‰Â›ÍÂÈ ÛÙ·ÙÈÛÙÈο ÛËÌ·ÓÙÈ΋ Ì›ˆÛË ÙˆÓ ÌÂÙ·ÁÁ›ÛÂˆÓ ÛÙÔ˘˜ ·ÛıÂÓ›˜ Ô˘ ‹Ú·Ó rFVIIa Û ۯ¤ÛË Ì ÙÔ˘˜ ·ÛıÂÓ›˜ Ô˘ ¤Ï·‚·Ó placebo. ŸÌˆ˜ ·Ú·ÙËÚ‹ıËΠÌÈ· ÛËÌ·ÓÙÈ΋
METAMO™XEY™Eπ™ 2008
111
¶›Ó·Î·˜ 2. AÔÙÂϤÛÌ·Ù· ÎÏÈÓÈÎÒÓ ÌÂÏÂÙÒÓ ¯ÔÚ‹ÁËÛ˘ rFVIIa Û ·ÛıÂÓ›˜ Ô˘ ˘Ô‚¿ÏÏÔÓÙ·È Û O.ª.∏. ∫ÏÈÓÈ΋
∫ÏÈÓÈο
¢fiÛË
º¿ÚÌ·ÎÔ
∞ÚÈıÌfi˜
ªÂÙ¿ÁÁÈÛË
ªÂÙ¿ÁÁÈÛË
£ÚÔÌ‚ÔÂÌ‚ÔÏÈο
ÌÂϤÙË
¯·Ú·ÎÙË-
rFVIIa
Û‡ÁÎÚÈÛ˘
·ÛıÂÓÒÓ
∂Ú˘ıÚÒÓ (U)
FFP (U)
ÂÂÈÛfi‰È·
rFVIIa/placebo
rFVIIa/placebo
3/9
1/9
p=0.002
p>0.05
20 Ìg/kg:10
20 Ìg/kg:8.5
40 Ìg/kg: 13
40 Ìg/kg: 15.5
80 Ìg/kg:10
80 Ìg/kg:6
/placebo:11
/placebo:11
p>0.05
p>0.05
60 Ìg/kg:7
60 Ìg/kg:9.4
120 Ìg/kg: 6.3
120 Ìg/kg: 11.9
/placebo: 8.2
/placebo: 11
p>0.05
p>0.05
3.9±2.6
12.6± 5.9
ÚÈÛÙÈο Hendriks et al
H.A.
2001
O.ª.∏.
80Ìg/kg
Planinsic et al
H.A.
20 ‹ 40 ‹ Placebo
2005
O.ª.∏.
80 Ìg/kg
Lodge et al
H.A.
60 ‹ 120
2005
O.ª.∏.
Ìg/kg
Niemann et al 2006
H.A.
58±18
O.ª.∏.
Ìg/kg
Placebo
Placebo
Placebo
N=6
N=82
N=183
N=22
/ 6.9±2.3
Meld Score>20,
–
p>0.05
p>0.05
–
/ 19.8±7.1 p>0.05
p= 0.01
p=0.02
PT>2 ÊÔÚ¤˜ ÙÔ Ê˘ÛÈÔÏÔÁÈÎfi O.M.H.: oÚıÔÙÔÈ΋ ÌÂÙ·ÌfiÛ¯Â˘ÛË ‹·ÙÔ˜, ∏.∞.: Ë·ÙÈ΋ ·Ó¿ÚÎÂÈ·, rFVIIa: recombinant activated factor VII
·‡ÍËÛË ÙÔ˘ ÔÛÔÛÙÔ‡ ÙˆÓ ·ÛıÂÓÒÓ Ô˘ ‰ÂÓ ¯ÚÂÈ¿ÛÙËΠӷ ÌÂÙ·ÁÁÈÛıÔ‡Ó Î·ıfiÏÔ˘ ÛÙËÓ ÔÌ¿‰· Ô˘ ¤Ï·‚ rFVIIa. ∞˘Ùfi ÙÔ ·ÔÙ¤ÏÂÛÌ· ›Ûˆ˜ Ó· ÚԤ΢„ ·fi ÙÔ ÁÂÁÔÓfi˜ fiÙÈ ¯ÚËÛÈÌÔÔÈ‹ıËÎ·Ó ÌÂÁ·Ï‡ÙÂÚ˜ ‰fiÛÂȘ rFVIIa Î·È Û ·ӷϷ̂·ÓfiÌÂÓ˜ ‰fiÛÂȘ. ∫·È Û ·˘Ù‹Ó ÙËÓ ÌÂϤÙË fiˆ˜ Î·È ÛÙËÓ ÚÔËÁÔ‡ÌÂÓË, ‰ÂÓ ˘‹ÚÍ ÛÙ·ÙÈÛÙÈο ÛËÌ·ÓÙÈ΋ ‰È·ÊÔÚ¿ ÛÙËÓ Û˘¯ÓfiÙËÙ· ÙˆÓ ıÚÔÌ‚ÔÂÌ‚ÔÏÈÎÒÓ ÂÂÈÛÔ‰›ˆÓ ·Ó¿ÌÂÛ· ÛÙȘ ÔÌ¿‰Â˜ rFVIIa Î·È placebo (›Ó·Î·˜ 2). ™Â ÌÈ· ÚfiÛÊ·ÙË ·Ó·‰ÚÔÌÈ΋ ÌÂϤÙË, ÌÂÏÂÙ‹ıËÎ·Ó 22 ·ÛıÂÓ›˜ ·ÛıÂÓ›˜ Ô˘ ˘Ô‚Ï‹ıËÎ·Ó Û ª.∏. Î·È Â›¯·Ó ‰‡Ô Û˘ÁÎÂÎÚÈ̤ӷ ¯·Ú·ÎÙËÚÈÛÙÈο: ÛËÌ·ÓÙÈο ·˘ÍË̤ÓÔ ¯ÚfiÓÔ ÚÔıÚÔÌ‚›Ó˘ (ƒΔ ÌÂÁ·Ï‡ÙÂÚÔ 1.5-2 ÊÔÚ¤˜ ÙÔ˘ ¯ÚfiÓÔ˘ Ì¿ÚÙ˘Ú·) Î·È MELD score (Model of End-stage Liver Disease) ÌÂÁ·Ï‡ÙÂÚÔ ÙÔ˘ 20. OÈ ·ÛıÂÓ›˜ ·˘ÙÔ› Ù˘¯·ÈÔÔÈ‹ıËÎ·Ó Û 2 ÔÌ¿‰Â˜: Ë Ì›· ÔÌ¿‰· ¤Ï·‚ rFVIIa Û ‰fiÛË 58±18Á/kg ÛÙËÓ ¤Ó·ÚÍË ÙÔ˘ ¯ÂÈÚÔ˘ÚÁ›Ԣ ÂÓÒ Ë ‰Â‡ÙÂÚË ÔÌ¿‰· ¤Ï·‚ ÂÈÎÔÓÈÎfi Ê¿ÚÌ·ÎÔ46. ™ÙËÓ ÔÌ¿‰· ÙˆÓ ·ÛıÂÓÒÓ Ô˘ ¤Ï·‚·Ó rFVIIa ·Ú·ÙËÚ‹ıËΠÛÙ·ÙÈÛÙÈο ÛËÌ·ÓÙÈ΋ Ì›ˆÛË ÙˆÓ ÌÂÙ·ÁÁ›ÛÂˆÓ ÛÂ Û˘Ì˘Îӈ̤ӷ ÂÚ˘ıÚ¿ (p=0.01) Î·È Û ÊÚ¤Ûη ηÙ„˘Á̤ӷ Ï¿ÛÌ·Ù·
(p=0.02) Û ۯ¤ÛË Ì ÙËÓ ÔÌ¿‰· ÂϤÁ¯Ô˘ Ô˘ ‰ÂÓ ¤Ï·‚ rFVIIa (placebo ÔÌ¿‰·) (›Ó·Î·˜ 2).
¶ÔÈÔ˜ Â›Ó·È Ô ÚfiÏÔ˜ ÙÔ˘ ·Ú¿ÁÔÓÙ· VII ÛÙËÓ ÌÂÙ·ÌfiÛ¯Â˘ÛË ‹·ÙÔ˜; ΔÔ ÂÚÒÙËÌ· Ô˘ ÚÔ·ÙÂÈ Â›Ó·È ·Ó ÙÂÏÈο Ô rFVIIa ÌÔÚ› Ó· ¯ÚËÛÈÌÔÔÈËı› ÛÙËÓ ª.∏. Œ¯Ô˘Ì ÛÙË ‰È¿ıÂÛ‹ Ì·˜ ¤Ó· Ê¿ÚÌ·ÎÔ Ô˘ ¤¯ÂÈ ·Ô‰Â›ÍÂÈ Û ÔÏϤ˜ (in vitro Î·È ÎÏÈÓÈΤ˜) ÌÂϤÙ˜ fiÙÈ ¤¯ÂÈ ÛËÌ·ÓÙÈ΋ ÚÔËÎÙÈ΋ ‰Ú·ÛÙËÚÈfiÙËÙ·. ŸÌˆ˜ ̤¯ÚÈ ÙÒÚ· ‰ÂÓ ¤¯ÂÈ ·Ô‰Âȯı› Ó· ÚÔηÏ› ÛËÌ·ÓÙÈ΋ ÂÏ¿ÙÙˆÛË Ù˘ ·ÈÌÔÚÚ·ÁÈ΋˜ ‰È¿ıÂÛ˘ Î·È Î·Ù’ ¤ÎÙ·ÛË ÙˆÓ ·Ó·ÁÎÒÓ ÁÈ· ÌÂÙ·ÁÁ›ÛÂȘ ·›Ì·ÙÔ˜ Î·È ·Ú·ÁfiÓÙˆÓ Û ·ÛıÂÓ›˜ Ô˘ ˘Ô‚¿ÏÏÔÓÙ·È Û ª.∏. OÈ ‰‡Ô ÌÂÁ¿Ï˜ Ù˘¯·ÈÔÔÈË̤Ó˜ ÌÂϤÙ˜ Ô˘ ¤ÁÈÓ·Ó Û ·ÛıÂÓ›˜ Ô˘ ˘Ô‚¿ÏÏÔÓÙ·È Û ª.∏. ·¤Ù˘¯·Ó Ó· ·Ô‰Â›ÍÔ˘Ó ÛÙ·ÙÈÛÙÈο ÛËÌ·ÓÙÈ΋ ‰È·ÊÔÚ¿ ÛÙȘ ÌÂÙ·ÁÁ›ÛÂȘ ÙˆÓ ·ÛıÂÓÒÓ ·˘ÙÒÓ ‰ÈÂÁ¯ÂÈÚËÙÈο. OÈ ÂÚÌËÓ›· ÙÔ˘ ·ÔÙÂϤÛÌ·ÙÔ˜ ·˘ÙÔ‡ Â›Ó·È ÔÏÏ·Ï‹. ¶ÚÒÙ· ·fi fiÏ·, Ô Î›Ó‰˘ÓÔ˜ ·ÈÌÔÚÚ·Á›·˜ ÛÙËÓ Ë·ÙÈ΋ ·Ó¿ÚÎÂÈ· ÙÂÏÈÎÔ‡ ÛÙ·‰›Ô˘ Â›Ó·È Ì›· Û‡ÓıÂÙË ‰È·‰Èηۛ· Ô˘ ηıÔÚ›˙ÂÙ·È ·fi ÔÏÏÔ‡˜ ·Ú¿ÁÔÓÙ˜:
112
X. ¶∞¶∞°∂øƒ°π√À
ñ ‰È·Ù·Ú·¯‹ ÛÙËÓ Û‡ÓıÂÛË ÙˆÓ ·Ú·ÁfiÓÙˆÓ ‹Í˘ ñ ·˘ÍË̤ÓË ÈÓˆ‰fiÏ˘ÛË ñ ıÚÔÌ‚ÔÂÓ›· ñ ˘Ï·›· ˘¤ÚÙ·ÛË ñ Û˘Ó˘¿Ú¯Ô˘Û· ÓÂÊÚÈ΋ ·Ó¿ÚÎÂÈ· ñ ¯ÂÈÚÔ˘ÚÁÈ΋ Ù¯ÓÈ΋ ñ ·Ó·ÈÛıËÛÈÔÏÔÁÈ΋ ·ÓÙÈÌÂÙÒÈÛË. ŸÏÔÈ ·˘ÙÔ› ÔÈ ·Ú¿ÁÔÓÙ˜ Ô˘ÛÈ·ÛÙÈο ÌÂÙ·‚¿ÏÏÔ˘Ó ÙÔÓ ·ÈÌÔÚÚ·ÁÈÎfi ΛӉ˘ÓÔ Î·È ‰È·ÊÔÚÔÔÈÔ‡Ó ÙËÓ ·Ó¿ÁÎË ÁÈ· ıÂڷ›·47. ª›· ÚfiÛÊ·ÙË ÌÂϤÙË, ¯ÚËÛÈÌÔÔÈÒÓÙ·˜ ÙÔÓ ¯ÚfiÓÔ ÚÔıÚÔÌ‚›Ó˘ ˆ˜ ‰Â›ÎÙË ·ÈÌÔÚÚ·ÁÈÎÔ‡ ÎÈÓ‰‡ÓÔ˘, ηٿÊÂÚ ӷ ·Ó·‰Â›ÍÂÈ ÙËÓ ·Ó¿ÁÎË ÁÈ· ÔÈÔ Û·Ê‹ ÔÚÈÛÌfi ÙÔ˘ ·ÈÌÔÚÚ·ÁÈÎÔ‡ ÎÈÓ‰‡ÓÔ˘ Î·È Ù˘ ˘ÔΛÌÂÓ˘ Ë·ÙÈ΋˜ ·Ó¿ÚÎÂÈ·˜ Ì ÛÎÔfi Ó· ·Ó·ÚÔÛ‰ÈÔÚÈÛÙ› Ë ÔÌ¿‰· ·ÛıÂÓÒÓ Ô˘ ¯Ú‹˙Ô˘Ó ıÂڷ›·˜ Ì ÚÔËÎÙÈÎÔ‡˜ ·Ú¿ÁÔÓÙ˜48. H ¯Ú‹ÛË ÙÔ˘ rFVIIa ‰ÂÓ ÚÔÙ›ÓÂÙ·È ˆ˜ Ù˘ÊÏ‹ ıÂڷ›· ÁÈ· ÂÏ¿ÙÙˆÛË ÙÔ˘ ÎÈÓ‰‡ÓÔ˘ ·ÈÌÔÚÚ·Á›·˜ Û fiÏÔ˘˜ ÙÔ˘˜ ·ÛıÂÓ›˜ Ô˘ ˘Ô‚¿ÏÏÔÓÙ·È Û ª.∏49. ¢Â Û˘ÓÈÛÙ¿Ù·È Ë ¯Ú‹ÛË ÙÔ˘ ˆ˜ ÚÔÊ˘Ï·ÎÙÈÎÔ‡ Ê·ÚÌ¿ÎÔ˘ Ô˘ ı· ÂÚÈÔÚ›ÛÂÈ ÙËÓ Èı·Ó‹ ‰ÈÂÁ¯ÂÈÚËÙÈ΋ Î·È ÌÂÙÂÁ¯ÂÈÚËÙÈ΋ ·ÈÌÔÚÚ·Á›·. ∏ ÈÔ ÂÍÂȉÈÎÂ˘Ì¤ÓË ‰ÈÂÁ¯ÂÈÚËÙÈ΋ ·Ú·ÎÔÏÔ‡ıËÛË Ù˘ ‹Í˘ ̤ۈ Ù˘ ıÚÔÌ‚ÔÂÏ·ÛÙÔÁÚ·Ê›·˜40,50, ÔÈ ‚ÂÏÙȈ̤Ó˜ ¯ÂÈÚÔ˘ÚÁÈΤ˜ Ù¯ÓÈΤ˜ Î·È Ë Î·Ï‡ÙÂÚË ÂÈÏÔÁ‹ ÙˆÓ ˘Ô„ËÊ›ˆÓ ÚÔ˜ ÌÂÙ·ÌfiÛ¯Â˘ÛË ¤¯ÂÈ Ô‰ËÁ‹ÛÂÈ Û ÂÂÌ‚¿ÛÂȘ Ì ÌÈÎÚfiÙÂÚ˜ ·ÒÏÂȘ ·›Ì·ÙÔ˜ ·Ú¿ ÙÔÓ ·Ú¯ÈÎfi ˘„ËÏfi ·ÈÌÔÚÚ·ÁÈÎfi ΛӉ˘ÓÔ. ¶ÚÔÙ›ÓÂÙ·È Ë ¯Ú‹ÛË ÙÔ˘ rFVIIa ÂÎÙfi˜ ÂӉ›ÍÂˆÓ (off-label) Û ·ÛıÂÓ›˜ Ô˘ Ù· ˘fiÏÔÈ· ıÂڷ¢ÙÈο ̤۷ ¤¯Ô˘Ó ·ÔÙ‡¯ÂÈ Î·È Ë ¯Ú‹ÛË ÙÔ˘ rFVIIa ·ÔÙÂÏ› ÙËÓ ıÂڷ›· ‰È¿ÛˆÛ˘ (rescue therapy)51. OÈ ‰‡Ô ·˘Ù¤˜ ÌÂÁ¿Ï˜ Ù˘¯·ÈÔÔÈË̤Ó˜ ÌÂϤÙ˜ ÙÔ˘ rFVIIa ÛÙËÓ ª.∏. ·¤‰ÂÈÍ·Ó fiÙÈ Ë Î¿ı·ÚÛ‹ ÙÔ˘ Â›Ó·È Ù·¯‡ÙÂÚË ÛÙÔ˘˜ ·ÛıÂÓ›˜ ·˘ÙÔ‡˜ Û ۯ¤ÛË Ì ÙÔ˘˜ ÎÈÚÚˆÙÈÎÔ‡˜ ·ÛıÂÓ›˜ Ô˘ ·ÓÙÈÌÂÙˆ›˙ÔÓÙ·È ÌÂ Û˘ÓÙËÚËÙÈο ̤۷, ÂÓÒ Ô ¯ÚfiÓÔ˜ ËÌ›ÛÂÈ·˜ ˙ˆ‹˜ ÙÔ˘ Ê·ÚÌ¿ÎÔ˘ ‹Ù·Ó ÌÈÎÚfiÙÂÚÔ˜ ÙÔ˘ ¯ÂÈÚÔ˘ÚÁÈÎÔ‡ ¯ÚfiÓÔ˘ Ì ·ÔÙ¤ÏÂÛÌ· ·ӷÈÌÔÚÚ·Á›·41,42. ∞˘Ùfi ÛËÌ·›ÓÂÈ fiÙÈ ÙfiÛÔ Ë ‰fiÛË ÙÔ˘ rFVIIa Ô˘ ¯ÔÚËÁ‹ıËΠfiÛÔ Î·È Ô ÙÚfiÔ˜ ¯ÔÚ‹ÁËÛ˘ (ÂÊ¿·Í ‰fiÛË ÛÙËÓ ¤Ó·ÚÍË ÙÔ˘ ¯ÂÈÚÔ˘Á›Ԣ) ‰ÂÓ ‹Ù·Ó Ë È‰·ÓÈ΋ Î·È Èı·ÓfiÓ Ó· ‹Ù·Ó Û ˘ÔıÂڷ¢ÙÈ΋ Û˘ÁΤÓÙÚˆÛË ÛÙÔ Ï¿ÛÌ·. ∏ ıˆڛ· ·˘Ù‹ ÂÓÈÛ¯‡ÂÙ·È ·fi ÙÔ ÁÂÁÔÓfi˜ fiÙÈ ÛÙËÓ ‰Â‡ÙÂÚË ÌÂϤÙË fiÔ˘ ¯ÔÚËÁÔ‡ÓÙ·Ó rFVIIa Û ·ӷϷ̂·ÓfiÌÂÓ˜ ‰fiÛÂȘ, Ô ·ÚÈıÌfi˜ ÙˆÓ ·ÛıÂÓÒÓ Ô˘ ‰ÂÓ ÌÂÙ·Á-
Á›ÛıËÎ·Ó Î·ıfiÏÔ˘ Ì ÂÚ˘ıÚ¿ ‹Ù·Ó ÌÂÁ·Ï‡ÙÂÚÔ˜ ÛÙËÓ ÔÌ¿‰· ·˘Ù‹ Û ۯ¤ÛË Ì ÙËÓ ÔÌ¿‰· Ô˘ ¤Ï·‚ ÂÈÎÔÓÈÎfi Ê¿ÚÌ·ÎÔ41. ∂Ô̤ӈ˜, ¯ÚÂÈ¿˙ÂÙ·È Â·Ó·ÚÔÛ‰ÈÔÚÈÛÌfi˜ Ù˘ ‰fiÛ˘ Î·È ÙÔ˘ ¯ÚfiÓÔ˘ ¯ÔÚ‹ÁËÛ˘ ÙÔ˘ rFVIIa ÛÙÔ˘˜ ·ÛıÂÓ›˜ ˘fi ª.∏. Δ¤ÏÔ˜, Û ·ÛıÂÓ›˜ Ô˘ ·ÔÊ·Û›˙ÂÙ·È Ë ¯ÔÚ‹ÁËÛË rFVIIa Ú¤ÂÈ Ó· ÂÎÙÈÌ¿Ù·È Î·È Ô Î›Ó‰˘ÓÔ˜ ·ÚÙËÚȷ΋˜ ‹ ÊÏ‚È΋˜ ıÚfiÌ‚ˆÛ˘ ÙfiÛÔ ÙˆÓ ·ÁÁ›ˆÓ ÙÔ˘ ÌÔۯ‡̷ÙÔ˜ fiÛÔ Î·È ÙˆÓ ˘ÔÏÔ›ˆÓ ·ÁÁ›ˆÓ.
™Àª¶∂ƒ∞™ª∞ ∏ ÌÂÙ·ÌfiÛ¯Â˘ÛË ‹·ÙÔ˜ ·ÔÙÂÏ› ÌÈ· ‚·Ú‡Ù·ÙË Â¤Ì‚·ÛË. ∏ ·ÈÌÔÚÚ·Á›· ÙfiÛÔ ‰ÈÂÁ¯ÂÈÚËÙÈο fiÛÔ Î·È ¿ÌÂÛ· ÌÂÙÂÁ¯ÂÈÚËÙÈο, Â›Ó·È ÌÈ· ·fi ÙȘ ·ÚȘ ÂÈÏÔΤ˜ Ù˘ Î·È ·›ÙÈÔ ÛËÌ·ÓÙÈ΋˜ ÓÔÛËÚfiÙËÙ·˜ Î·È ıÓËÙfiÙËÙ·˜. O ÂÓÂÚÁÔÔÈË̤ÓÔ˜ ·Ú¿ÁÔÓÙ·˜ VIIa ·ÔÙÂÏ› ¤Ó· ıÂڷ¢ÙÈÎfi ̤ÛÔ ÁÈ· ıÂڷ›· ‰È¿ÛˆÛ˘ ÛÙȘ ÂÚÈÙÒÛÂȘ ÛÔ‚·Ú‹˜ ·ÈÌÔÚÚ·Á›·˜ Û ·ÛıÂÓ›˜ Ô˘ ˘Ô‚¿ÏÏÔÓÙ·È Û ÔÚıÔÙÔÈ΋ ÌÂÙ·ÌfiÛ¯Â˘ÛË ‹·ÙÔ˜. ªÂÏÏÔÓÙÈΤ˜ ÎÏÈÓÈΤ˜ ÌÂϤÙ˜ ›Ûˆ˜ ·Ó·‰Â›ÍÔ˘Ó Ì ۷ʋÓÂÈ· ÙȘ ‚¤ÏÙÈÛÙ˜ ÂӉ›ÍÂȘ ¯Ú‹Û˘ ÙÔ˘ rFVIIa ÛÙÔ˘˜ ·ÛıÂÓ›˜ Ô˘ ˘Ô‚¿ÏÏÔÓÙ·È Û ÌÂÙ·ÌfiÛ¯Â˘ÛË ‹·ÙÔ˜.
μπμ§πO°ƒ∞ºπ∞ 1. Starlz TE, Marchioro TL, von Kaulla KN, Herman G. Homotransplantation of the liver in humans. Surg Gynecol Obstet 1963: 659-676. 2. Liang TB, Bai XL, Li DL et al. Early postoperative hemorrhage requiring urgent surgical reintervention after orthotopic liver transplantation. Transpl Proceed 2007; 39:1549-1553. 3. Schroeder RA, Johnson LB, Plotkin JS et al. Total blood transfusion and mortality after orthotopic liver transplantation. Anesthesiology 1999; 91:329-30. 4. ªÔr E, Jennings L, Gonwa TA, Holman MJ, Gibbs J, Solomon H. The impact of operative bleeding on outcome in transplantation of the liver. Surg Gynecol Obstet 1993; 176:219-227. 5. Palomo Sanchez JC, Jimenez C, Gonzalez G. Effects of intraoperative blood transfusion on postoperative complications and survival after orthotopic liver transplantation. Hepatogastroenterology 1998; 45: 1026-33. 6. μennett-Guerrero E, Feierman DE, Barcklay GR et al. Preoperative and intraoperative predictors of postoperative morbidity, poor graft function and early rejection in 190 patients undergoing liver transplantation. Arch Surg 2001; 136:1177. 7. Porte RJ, Hendriks HG, Slooff MJ. Blood conservation in liver transplantation: The role of aprotinin. J Cardiothorac Vasc Anesth 2004; 18:S31-S37.
METAMO™XEY™Eπ™ 2008
8. ªiyamoto S, Polak WG, Geuken E et al. Liver transplantation with preservation of the inferior vena cava. A comparison of conventional and piggyback technique in adults. Clin Transplant 2004; 18:686-93. 9. Belzer FO, Southard JH. Principles of solid-organ preservation by cold storage. Transplantation 1988; 45:673-76. 10. ∫ang YG, Martin DJ, Marquez J et al. Intraoperative changes in blood coagulation and thromboelastographic monitoring in liver transplantation. Anest Analg 1985; 64:888-896.
113
25. Moriau M, Kestens PJ, Masure R. Heparin and antifibrinolytic agents during experimental hepatectomy and liver transplantation. Path Eur 1969; 4:172-82. 26. Faeh M, Hauser SP, Nydegger UE. Transient thrombopoietin peak after liver transplantation for end-stage liver disease. Br. J Hematol 2001; 112:493-98. 27. Reed RL, Bracey AW, Hudson JD et al. Hypothermia and blood coagulation:dissociation between enzyme activity and clotting factor levels. Circ Shock 1990; 32:141-152.
11. Copeland GR, Jones D, Walters M. POSSUM: a scoring system for surgical audit. Br J Surg 1991; 78:355.
28. Ferrara A, Mac Arthur JD, Wright HK et al. Hypothermia and acidosis worsen coagulopathy in the patient requiring massive transfusion. Am J Surg 1990; 160:515-518.
12. Boyd CR, Tolson MA, Copes WS. Evaluating trauma care:the TRISS method. Trauma score and the Injury Severity Score. J Trauma 1987; 27:370.
29. Jones RM, Moulton CE, Hardy KJ. Central venous pressure and its effect on blood loss during liver resection. Br J Surg 1998; 85:1058-60.
13. Lisman T, Leebeek FW, de Groot PG. Haemostatic abnormalities in patients with liver disease. J Hepatol. 2002 Aug; 37(2):280-7.
30. Veldman A, Hoffman M, Ehleforth S. New insights into the coagulation system and implication for new therapeutic options with recombinant factor VIIa. Curr Med Chem 2003; 10:797-811.
14. Rapaport SI. Coagulation problems in liver disease. Blood coagulation Fibrinolysis 2000; 11:S69-S74. 15. Stein SF, Harker LA. Kinetic and functional studies of platelets,fibrinogen and plasminogen in patients with hepatic cirrhosis. J Lab Clin Med 1982; 99:217-30. 16. Tripodi A, Salerno F, Chantarangkul V, Clerici M, Cazzaniga M, Primignani M, Mannuccio Mannucci P. Evidence of normal thrombin generation in cirrhosis despite abnormal conventional coagulation tests. Hepatology. 2005 Mar; 41(3):553-8. 17. ∫aul V, Munoz SJ. Coagulopathy of liver disease. Curr Treat Options Gastroenterol 2000; 3:433-438. 18. De Boer MT, Molennar Q, Hendriks H et al. Minimizing blood loss in liver transplantation: Progress through research and evolution of technique. Dig Surg 2006; 22:265-75. 19. Senzolo M, Burra E, Cholongitas E et al. New insights into the coagulopathy of liver disease and liver transplantation. World J Gastroenterology 2006; 12(48): 7725-7736. 20. Ben-Ari Z, Panagou M,Patch D et al. Hypercoagulability in patients with primary biliary cirrhosis and primary sclerosing cholangitis evaluated by thromboelastography. J Hepatol 1997; 26:554-559. 21. Kang Y. Coagulation and liver transplantation:current concepts. Liver Transpl Surg 1997; 3:465-67. 22. Emeis JJ,van den Hoogen CM, Jense D. Hepatic clearance of tissue-type plasminogen activator in rats. Thromb Hemost 1985; 54:661-64. 23. Hutchison DE, Genton E, Porter KA et al. Platelet changes following clinical and experimental hepatic homotransplantations. Arch Surg 1968; 97:27-33. 24. Sindram D, Porte RJ,Hoffman MR. Synergism between platelets and leucocytes in inducing endothelial cell apoptosis upon reperfusion of the cold ischemic rat liver: a Kuppfer cell-mediated injury. Faseb J 2001; 15:1230-32.
31. ªÔnroe DM, Hoffman M, Oliver JA. Platelet activity of high-dose factor VIIa is independent of tissue factor. Br J Haematol 1997; 99:542-47. 32. Kristensen J, Killander A, Hippe E et al. Clinical experience with recombinant factor VIIa in patients with thrombocytopenia. Hemostasis 1996; 26(1):159-64. 33. Gerotziafas GT, Zervas C, Gavrielidis G et al. Effective hemostasis with rFVIIa treatment in two patients with severe thrombocytopenia and life threatening hemorrhage. Am J Hematol 2002; 69:219-222. 34. Gerotziafas G, Chakroun T, Depasse F et al. The role of platelets and recombinant factor VIIa on thrombin generation, platelet activation and clot formation. Thromb Haemost 2004; 91:977-85. 35. Goodnough LT, Ludlin DM, Zhang L et al. Tranfusion medicine service policies for recombinant FVIIa administration. Tranfusion 2004; 44:1325-31. 36. Grounds RM, Bolan C. Clinical experiences and current evidence for therapeutic rFVIIa treatment in non trauma settings. Crit Care 2005; 9:S36-45. 37. μosch J, Thabut D, Bendsen F et al. Recombint factor VIIa for upper gastrointestinal bleeding in patients with cirrhosis:a randomized, double blind trial. Gastroenyerology 2004; 127:1123-30. 38. Boffard KD, Riou B, Warren B et al. Recombinant rFVIIa as adjuctive therapy for bleeding control in severely injured trauma patients. Two parallel randomized, placebo-controlled, double blind clinical trials. J Trauma 2005; 59:8-15. 39. Novo Nordisk, Denmark. Phase 3 stroke trial shows that NovoSeven reduces bleeding in the brain, but does not improve long-term clinical outcomes ( available at www.novinordisk.com, updated 26 February 2007). 40. Friederich PW, Henny CP, Messelik EJ et al. Effect of rFVIIa on perioperative blood loss in patients under-
114
X. ¶∞¶∞°∂øƒ°π√À
going retropubic prostatectomy: a double-blind placebo controlled randomized trial. Lancet 2003; 361:138-43. 41. Bernstein DE, Jeffers L, Erhardsten E et al. Recombinant rFVIIa corrects prothrombin time in cirrhotic patients: a preliminary study. Gastroenterology 1997; 113:1930-37. 42. Hendriks H, Meijer K, De Wolf TM et al. Reduced transfusion requirements by recombinant factor VIIa in orthotopic liver transplantation. Transplantation 2001; 71:402-405. 43. Hendriks H, Meijer K, De Wolf TM et al. Effects of recombinant activated factor VII on coagulation measured by thromboelastography in liver transplantation. Blood Coagulation Fibrinol 2002; 13(4):309-313. 44. Planincic R, Meer J, Testa J et al. Safety and efficacy of a single bolus administration of recombinant factor VIIa in liver transplantation due to chronic liver disease. Liver Transplant 2005; 11(8):895-900. 45. Lodge JP, Jonas S, Jones RM et al. Efficacy and safety of repeated perioperative doses of recombinant factor
VIIa in live transplantation. Liver transplantation 2005; 11(8): 973-979. 46. Niemann CU, Behrends M, Quan D et al. Recombinant factor VIIa reduces transfusion requirements in liver transplant patients with high MELD scores. Tranfusion Medicine 2006; 16:93-100. 47. Porte RJ, Caldwell SH. The role of recombinant factor VIIa in liver transplantation. Liver Transplantation 2005; 11(8):872-874. 48. Δripodi A, Saleno F, Chantarangkul V et al. Evidence of normal thrombin generation in cirrhosis despite abnormal conventional coagulation tests. Hepatology 2005; 41:553-558. 49. Gasperi A. Use of recombinant factor VIIa during orthotopic liver transplantation (Letter). Liver Transplantation 2006; 12:1176-77. 50. ∫oh MB, Hunt BJ. The management of perioperative bleeding. Blood Rev 2003; 17:179-85. 51. Weiskorf RB. Intraoperative use of recombinant activated coagulatiob factor VII (Editorial). Anesthesiology 2002; 96:1287-9.
KÂÚ·˘ÓÔ‚fiÏÔ˜ Ë·Ù›Ùȉ· ∂. ∫·Ùۛη
5-26 ‚‰ÔÌ¿‰Â˜, ÌÂÙ¿ ÙËÓ ÂÌÊ¿ÓÈÛË ›ÎÙÂÚÔ˘ (ÂÈ‚›ˆÛË 14 %).
∏ ÎÂÚ·˘ÓÔ‚fiÏÔ˜ Ë·Ù›Ùȉ· ‹ ÔÍ›· Ë·ÙÈ΋ ·Ó¿ÚÎÂÈ· (O.∏.∞.) Â›Ó·È ÌÈ· Û¿ÓÈ· ηٿÛÙ·ÛË Ì ηٷÛÙÚÔÊÈΤ˜ Û˘Ó¤ÂȘ. ÷ڷÎÙËÚ›˙ÂÙ·È ·fi ÔÍ›· ¤Ó·ÚÍË ÛÔ‚·Ú‹˜ Ë·ÙÈ΋˜ ‰˘ÛÏÂÈÙÔ˘ÚÁ›·˜ › ·Ô˘Û›·˜ ÚÔ¸¿Ú¯Ô˘Û·˜ Ë·ÙÈ΋˜ ÓfiÛÔ˘, ÌÂ Û˘ÓÔ‰fi ÂÌÊ¿ÓÈÛË ÈÎÙ¤ÚÔ˘, Ë·ÙÈ΋˜ ÂÁÎÂÊ·ÏÔ¿ıÂÈ·˜ Î·È ‰È·Ù·Ú·¯ÒÓ ÛÙËÓ ‹ÍË ÙÔ˘ ·›Ì·ÙÔ˜. ∏ ·ÒÏÂÈ· Ù˘ ÏÂÈÙÔ˘ÚÁ›·˜ ÙÔ˘ ‹·ÙÔ˜ Ô‰ËÁ› Û ÔÏ˘ÔÚÁ·ÓÈ΋ ·Ó¿ÚÎÂÈ· Ô˘ Û˘¯Ó¿ ÚÔηÏ› ÙÔ ı¿Ó·ÙÔ. ∏ ıÓËÛÈÌfiÙËÙ· ÚÈÓ ÙË ‰˘Ó·ÙfiÙËÙ· ‰ÈÂÓ¤ÚÁÂÈ·˜ ÌÂÙ·ÌfiÛ¯Â˘Û˘ ‹·ÙÔ˜ ÍÂÂÚÓÔ‡Û ÙÔ 80%. ™‹ÌÂÚ·, Ì ÙË ÌÂÙ·ÌfiÛ¯Â˘ÛË ‹·ÙÔ˜, Ë ÂÈ‚›ˆÛË Êı¿ÓÂÈ Ì¤¯ÚÈ Î·È ÙÔ 80%.
∞Èٛ˜ ∫‡ÚȘ ·Èٛ˜ Ù˘ ÔÍ›·˜ Ë·ÙÈ΋˜ ·Ó¿ÚÎÂÈ·˜ Â›Ó·È Ê¿Ú̷η (.¯. ·Ú·ÎÂÙ·ÌfiÏË) Ë·Ù›Ùȉ· μ Î·È Ë·Ù›Ùȉ· non ∞ non μ, ÏÈ҉˜ ‹·Ú Ù˘ ·ËÛ˘, ÌÂÙ·‚ÔÏÈο ÓÔÛ‹Ì·Ù·. ∏ ·Ó·ÁÓÒÚÈÛË Ù˘ ·ÈÙ›·˜ Ù˘ O.∏.∞. Â›Ó·È ÛËÌ·ÓÙÈ΋ ηıÒ˜ Ë ·ÈÙÈÔÏÔÁ›· ÂËÚ¿˙ÂÈ ÙËÓ ÚfiÁÓˆÛË ·ÏÏ¿ Î·È ÙËÓ ·ÓÙÈÌÂÙÒÈÛË.
∫ÏÈÓÈΤ˜ Û˘Ó¤ÂȘ ∫·Ú‰È·ÁÁÂÈ·Îfi Û‡ÛÙËÌ· – ∞ÓÙÈÌÂÙÒÈÛË
OÚÈÛÌfi˜
OÈ Î·Ú‰È·ÁÁÂȷΤ˜ ÌÂÙ·‚ÔϤ˜ Ô˘ ·Ú·ÙËÚÔ‡ÓÙ·È ÛÙËÓ O.∏.∞. ¯·Ú·ÎÙËÚ›˙ÔÓÙ·È ·fi ÂÚÈÊÂÚÈ΋ ·ÁÁÂÈԉȷÛÙÔÏ‹ Ô˘ ¤¯ÂÈ ˆ˜ ·ÔÙ¤ÏÂÛÌ· ÂÏ¿ÙÙˆÛË ÙÔ˘ ÌÂÙ·ÊÔÚÙ›Ô˘ Î·È ·‡ÍËÛË Ù˘ ηډȷ΋˜ ·ÚÔ¯‹˜. OÈ ÌÂÙ·‚ÔϤ˜ ·˘Ù¤˜ ¤¯Ô˘Ó ˆ˜ ·ÔÙ¤ÏÂÛÌ· ÙËÓ ÂÏ¿ÙÙˆÛË ÙÔ˘ «‰Ú·ÛÙÈÎÔ‡» ΢ÎÏÔÊÔÚÔ‡ÓÙ· fiÁÎÔ˘. ∏ ¯ÔÚ‹ÁËÛË ˘ÁÚÒÓ Â›Ó·È È‰È·›ÙÂÚ˘ ÛËÌ·Û›·˜ ÛÙËÓ ·ÓÙÈÌÂÙÒÈÛË Ù˘ ˘fiÙ·Û˘ Î·È ÙËÓ ‰ÈfiÚıˆÛË Ù˘ ÔͤˆÛ˘. ¢ÂÓ ˘¿Ú¯Ô˘Ó ÂȉÈΤ˜ ηÙ¢ı˘ÓÙ‹ÚȘ ÁÚ·Ì̤˜ Û¯ÂÙÈο Ì ÙÔÓ Ù‡Ô ÙˆÓ ¯ÔÚËÁÔ‡ÌÂÓˆÓ ˘ÁÚÒÓ. ™ÙËÓ O.∏.∞. ‰ÂÓ ·ÓÙÂӉ›ÎÓ˘ÓÙ·È ˘ÁÚ¿ Ô˘ ÂÚȤ¯Ô˘Ó ¡·+. ∏ ÎÂÓÙÚÈ΋ ÊÏ‚È΋ ›ÂÛË ‰ÂÓ Ú¤ÂÈ Ó· ÍÂÂÚÓ¿ Ù· 10 cm H2O. ŸÙ·Ó Ë ¯ÔÚ‹ÁËÛË ˘ÁÚÒÓ ‰ÂÓ Â›Ó·È ·ÔÙÂÏÂÛÌ·ÙÈ΋ ÛÙËÓ ·ÓÙÈÌÂÙÒÈÛË Ù˘ ˘fiÙ·Û˘, Ë ¯ÔÚ‹ÁËÛË ÈÓÔÙÚfiˆÓ ‚ÔËı¿ ÛÙËÓ ·ÔηٿÛÙ·ÛË Ù˘ ª.∞.¶. (60-70mHg). ¡ÔÚ·‰ÚÂÓ·Ï›ÓË ‹/Î·È ·‰ÚÂÓ·Ï›ÓË ÚÔηÏÔ‡Ó ·‡ÍËÛË Ù˘ ª.∞.¶. Î·È Ù˘ ·ÚÔ¯‹˜ Ô͢ÁfiÓÔ˘ (DO2) Û ·ÛıÂÓ›˜ Ì O.∏.∞. Î·È ¯ÔÚËÁÔ‡ÓÙ·È Û ·Ú¯È΋ ‰¤ÛË 0,1Á/kgr/min. ∫ÏÈÓÈΤ˜ ÌÂϤÙ˜ ·Ô‰ÂÈÎÓ‡Ô˘Ó Â˘ÂÚÁÂÙÈ΋ ÙË Û˘Á¯ÔÚ‹ÁËÛË ÓÙÔÂÍ·Ì›Ó˘, ÂÓfi˜ Ê·ÚÌ¿ÎÔ˘ Ì ÓÙÔ·ÌÈÓÂÚÁÈ΋ Î·È ‚-·‰ÚÂÓÂÚÁÈ΋ ‰Ú¿ÛË. ∏ ÓÙÔÂÍ·Ì›ÓË ·˘Í¿ÓÂÈ ÙË ÛÏ·Á¯ÓÈ΋ Î·È ÓÂÊÚÈ΋ ÚÔ‹
O fiÚÔ˜ ÎÂÚ·˘ÓÔ‚fiÏÔ˜ Ë·ÙÈ΋ ·Ó¿ÚÎÂÈ· ¯ÚËÛÈÌÔÔÈ‹ıËΠÚÒÙË ÊÔÚ¿ ÚÈÓ 20 ¯ÚfiÓÈ·, ·fi ÙÔ˘˜ Trey Î·È Û˘Ó. ÁÈ· ÙÔÓ ÔÚÈÛÌfi Ù˘ «ÔÍ›·˜ ÂÌÊ¿ÓÈÛ˘ Ì·˙È΋˜ Ó¤ÎÚˆÛ˘ ÙˆÓ Ë·ÙÈÎÒÓ Î˘ÙÙ¿ÚˆÓ». ∫ÏÈÓÈο, ÙÔ Û‡Ó‰ÚÔÌÔ ÂÚÈÁÚ¿ÊËΠˆ˜ «·ÈÊÓ›‰È·» ÛÔ‚·Ú‹ ‰˘ÛÏÂÈÙÔ˘ÚÁ›· Ô˘ ¤¯ÂÈ ˆ˜ ·ÔÙ¤ÏÂÛÌ· ÙËÓ ÂÌÊ¿ÓÈÛË ÈÎÙ¤ÚÔ˘ Ô˘ ·ÎÔÏÔ˘ıÂ›Ù·È ·fi Ë·ÙÈ΋ ÂÁÎÂÊ·ÏÔ¿ıÂÈ· ̤۷ Û 8 ‚‰ÔÌ¿‰Â˜ ·fi ÙËÓ ¤Ó·ÚÍ‹ Ù˘, › ·Ô˘Û›·˜ ÚÔ¸¿Ú¯Ô˘Û·˜ Ë·ÙÈ΋˜ ÓfiÛÔ˘. §fiÁˆ ÙˆÓ ‰È·ÊfiÚˆÓ ·ÈÙÈÒÓ ÙÔ˘ Û˘Ó‰ÚfiÌÔ˘ Ë ÂÁÎÂÊ·ÏÔ¿ıÂÈ· ‰ÂÓ ÂÌÊ·Ó›˙ÂÙ·È ¿ÓÙ· ̤۷ Û’·˘Ù‹ ÙË ¯ÚÔÓÈ΋ ÂÚ›Ô‰Ô. ∞ÚÁfiÙÂÚ·, ÔÈ O’Grady Î·È Û˘Ó. ÚfiÙÂÈÓ·Ó ÌÈ· Ó¤· ÛÙ·‰ÈÔÔ›ËÛË Ù˘ O.∏.∞. ‚·ÛÈṲ̂ÓË Û ̛· ·Ó·‰ÚÔÌÈ΋ ÌÂϤÙË 539 ·ÛıÂÓÒÓ. OÈ O’Grady Î·È Û˘Ó. ¯ÚËÛÈÌÔÔ›ËÛ·Ó ÙÔ˘˜ fiÚÔ˘˜: ˘ÂÚÔÍ›·, ÔÍ›· Î·È ˘ÔÍ›· Ë·ÙÈ΋ ·Ó¿ÚÎÂÈ·. O fiÚÔ˜ ˘ÂÚÔÍ›· ÂÚÈÁÚ¿ÊÂÈ ÙÔ˘˜ ·ÛıÂÓ›˜ Ô˘ ÂÌÊ·Ó›˙Ô˘Ó ÂÁÎÂÊ·ÏÔ¿ıÂÈ· ̤۷ Û 7 Ë̤Ú˜ ·fi ÙËÓ ÂÌÊ·Ó›ÛË ÙÔ˘ ÈÎÙ¤ÚÔ˘ (ÂÈ‚›ˆÛË 36%). ∏ ÔÍ›· Ë·ÙÈ΋ ·Ó¿ÚÎÂÈ· ÂÚÈÏ·Ì‚¿ÓÂÈ ·ÛıÂÓ›˜ Ô˘ ·Ó·Ù‡ÛÛÔ˘Ó ÂÁÎÂÊ·ÏÔ¿ıÂÈ· 8-28 Ë̤Ú˜ ÌÂÙ¿ ÙËÓ ÂÌÊ¿ÓÈÛË ÈÎÙ¤ÚÔ˘ (ÂÈ‚›ˆÛË 7%). ∏ ˘ÔÍ›· ÌÔÚÊ‹ ÂÚÈÁÚ¿ÊÂÈ ÙËÓ ÂÌÊ¿ÓÈÛË ÂÁÎÂÊ·ÏÔ¿ıÂÈ·˜
115
116
∂. ∫∞Δ™π∫∞
Î·È ‚ÂÏÙÈÒÓÂÈ ÙËÓ ·ÚÔ¯‹ Ô͢ÁfiÓÔ˘. ∂ÈϤÔÓ, Ë ·ÓÙÈÊÏÂÁÌÔÓ҉˘ ‰Ú¿ÛË Ù˘ ÌÂÙÚÈ¿˙ÂÈ ÙËÓ Û˘ÁÎfiÏÏËÛË ÙˆÓ Ï¢ÎÔ΢ÙÙ¿ÚˆÓ ÛÙË ÌÈÎÚÔ·ÁÁÂȷ΋ ÛÏ·Á¯ÓÈ΋ ΢ÎÏÔÊÔÚ›·.
∫.¡.™. OÈ ÈÔ Û˘¯Ó¤˜ ÂÈÏÔΤ˜ Ù˘ O.∏.∞. Â›Ó·È Ë ÂÁÎÂÊ·ÏÔ¿ıÂÈ·, ÙÔ ÂÁÎÂÊ·ÏÈÎfi Ô›‰ËÌ· Î·È Ë ÂÓ‰ÔÎÚ¿ÓÈÔ˜ ˘¤ÚÙ·ÛË. ΔÔ Î·Ù¿ÏÏËÏÔ monitoring ‚ÔËı¿ ÛÙË ‰È¿ÁÓˆÛË Î·È ıÂڷ›· ·˘ÙÒÓ ÙˆÓ ÂÈÏÔÎÒÓ.
·) ∂ÁÎÂÊ·ÏÔ¿ıÂÈ· ∏ Ë·ÙÈ΋ ÂÁÎÂÊ·ÏÔ¿ıÂÈ· Â›Ó·È ·ÔÙ¤ÏÂÛÌ· ·Ó¿ÚÎÂÈ·˜ ‚ÈÔÌÂÙ·ÊÔÚ¿˜ Î·È ·¤ÎÎÚÈÛ˘ ÙÔÍÈÓÒÓ Ô˘ Ê˘ÛÈÔÏÔÁÈο Ú·ÁÌ·ÙÔÔÈÂ›Ù·È ·fi ÙÔ ‹·Ú. ™ÙÔ Ï¿ÛÌ· ·ÓȯÓ‡ÔÓÙ·È ·˘ÍË̤ӷ ›‰· ·Ì̈ӛ·˜, ÌÂÚηٷÓÒÓ, ÏÈ·ÚÒÓ ÔͤˆÓ, ·ÌÈÓÔͤˆÓ ·ÚˆÌ·ÙÈÎÔ‡ ‰·ÎÙ‡ÏÈÔ˘, Ô˘ÛÈÒÓ ·ÚfiÌÔÈˆÓ Ì ÙȘ ‚ÂÓ˙ԉȷ˙›Ó˜, Á-·ÌÈÓÔ‚Ô˘Ù˘ÚÈÎÔ‡ ÔͤԘ, ÁÏÔ˘Ù·Ì›Ó˘ Î·È ÙÔÍÈÎÒÓ ÌÂÙ¿ÏÏˆÓ (.¯. „¢‰¿ÚÁ˘ÚÔ˘, ¯·ÏÎÔ‡, Ì·ÁÓËÛ›Ô˘). ∂ÈϤÔÓ, ·Ú·ÙËÚÔ‡ÓÙ·È ·ÏÏ·Á¤˜ ÛÙË ‰È·ÂÚ·ÙfiÙËÙ· ÙÔ˘ ·ÈÌ·ÙÂÁÎÂÊ·ÏÈÎÔ‡ ÊÚ·ÁÌÔ‡. ∏ Ë·ÙÈ΋ ÂÁÎÂÊ·ÏÔ¿ıÂÈ· ¯ˆÚ›˙ÂÙ·È Û 4 ÛÙ¿‰È· (I- IV). – ÛÙ¿‰ÈÔ π: ·ÏÏ·Á¤˜ ÛÙË Û˘ÌÂÚÈÊÔÚ¿, ÂÏ¿¯ÈÛÙ˜ ·ÏÏ·Á¤˜ ÛÙÔ Â›Â‰Ô Û˘Ó›‰ËÛ˘ – ÛÙ¿‰ÈÔ ππ: ‰È·Ù·Ú·¯¤˜ ÚÔÛ·Ó·ÙÔÏÈÛÌÔ‡, ÓˆıÚfiÙËÙ·, ‰È·Ù·Ú·Á̤ÓË Û˘ÌÂÚÈÊÔÚ¿ – ÛÙ¿‰ÈÔ πππ: Û‡Á¯˘ÛË, ˘ÓËÏ›·, ·ÏÏ¿ ¤ÁÂÚÛË Î·È ·¿ÓÙËÛË Û ˯ËÙÈο ÂÚÂı›ÛÌ·Ù· – ÛÙ¿‰ÈÔ IV: ÎÒÌ· Δ· ÛÙ¿‰È· π /ππ ÂÁÎÂÊ·ÏÔ¿ıÂÈ·˜ ¤¯Ô˘Ó ηχÙÂÚË ÚfiÁÓˆÛË ÂÓÒ ÛÙ· ÛÙ¿‰È· III/ IV Û˘¯Ó¿ Û˘Ó˘¿Ú¯ÂÈ ÂÁÎÂÊ·ÏÈÎfi Ô›‰ËÌ·. ™Â ·ÛıÂÓ›˜ Ì ÂÁÎÂÊ·ÏÔ¿ıÂÈ· ÛÙ·‰›Ô˘ ππ ÚÔ˜ πππ ÂӉ›ÎÓ˘Ù·È Ë ÂÈÏÂÎÙÈ΋ ‰È·ÛˆÏ‹ÓˆÛË Î·È Ô Ì˯·ÓÈÎfi˜ ·ÂÚÈÛÌfi˜.
‚) ∂ÊÎÂÊ·ÏÈÎfi Ô›‰ËÌ· ∞ÛıÂÓ›˜ Ì ÂÁÎÂÊ·ÏÔ¿ıÂÈ· ÛÙ·‰›Ô˘ IV ·Ó·Ù‡ÛÛÔ˘Ó ÂÁÎÂÊ·ÏÈÎfi Ô›‰ËÌ· (80%) Î·È ÂÌÊ·Ó›˙Ô˘Ó ·˘ÍË̤ÓË ÂÓ‰ÔÎÚ¿ÓÈ· ›ÂÛË (∂∫¶) Ô˘ Â›Ó·È Ë Î‡ÚÈ· ·ÈÙ›· ı·Ó¿ÙÔ˘. ∫ÏÈÓÈο ÛËÌ›· Ù˘ ·˘ÍË̤Ó˘ ∂∫¶ Â›Ó·È Ë Û˘ÛÙËÌ·ÙÈ΋ ˘¤ÚÙ·ÛË, Ë ‚Ú·‰˘Î·Ú‰›·, Ë ·ÓÈÛÔÎÔÚ›·, ÔÈ Û·ÛÌÔ›, ÔÈ ·Ó·Ó¢ÛÙÈΤ˜ ‰È·Ù·Ú·¯¤˜ Î·È Ë ¿ÓÔÈ· ·fi ÂÁÎÔÏ·ÛÌfi ÙÔ˘ ÂÁÎÂÊ·ÏÈÎÔ‡ ÛÙÂϤ¯Ô˘˜.
‚π ) ∞ÓÙÈÌÂÙÒÈÛË ∞ÛıÂÓ›˜ Ì ·˘ÍË̤ÓÔ Î›Ó‰˘ÓÔ ·Ó¿Ù˘Í˘ ÂÁÎÂÊ·ÏÈÎÔ‡ Ôȉ‹Ì·ÙÔ˜ (ÛÙ¿‰ÈÔ πππ/IV) ηٷÛÙ¤ÏÏÔÓÙ·È, ‰È·ÛˆÏËÓÒÓÔÓÙ·È Î·È Ù›ıÂÓÙ·È Û Ì˯·ÓÈÎfi ·ÂÚÈÛÌfi. OÈ Davenpont Î·È Û˘Ó. ÚÔÙ›ÓÔ˘Ó ÙËÓ ·Ó‡„ˆÛË Ù˘ ÎÂÊ·Ï‹˜ ηٿ 30Ô ÁÈ· ‚ÂÏÙ›ˆÛË Ù˘ ÂÁÎÂÊ·ÏÈ΋˜ ›ÂÛ˘ ‰È‹ıËÛ˘ [∂¶¢(mmHg) = MA¶ – ∂∫¶]
Á)∂Ó‰ÔÎÚ¿ÓÈÔ˜ ›ÂÛË – Monitoring ΔÔ monitoring Ù˘ ÂÓ‰ÔÎÚ·Ó›Ô˘ ›ÂÛ˘ Ú·ÁÌ·ÙÔÔÈÂ›Ù·È Ì ÙËÓ ÙÔÔı¤ÙËÛË Î·ıÂÙ‹Ú· ÛÙÔ ÂÁÎÂÊ·ÏÈÎfi ·Ú¤Á¯˘Ì·, ‹ ÛÙÔÓ ÂÈÛÎÏËÚ›‰ÈÔ ‹ ÛÙÔÓ ˘ÔÛÎÏËÚ›‰ÈÔ ¯ÒÚÔ. OÈ ÂÈÛÎÏËÚ›‰ÈÔÈ Î·ıÂÙ‹Ú˜ ¤¯Ô˘Ó ÏÈÁfiÙÂÚ˜ ÂÈÏÔΤ˜ (3,8%) ·fi ÙÔ˘˜ ˘ÔÛÎÏËÚ›‰ÈÔ˘˜ (20%) Î·È ÙÔ˘˜ ·ÚÂÁ¯˘Ì·ÙÈÎÔ‡˜ (22%). ∏ ΢ÚÈfiÙÂÚË ÂÈÏÔ΋ Â›Ó·È Ë ÂÁÎÂÊ·ÏÈ΋ ·ÈÌÔÚÚ·Á›·. ™ÙȘ ÂÚÈÙÒÛÂȘ Ô˘ ÙÔ INR> 1,5, ‹ Ù· ·ÈÌÔÂÙ¿ÏÈ·<50.000, ‹ ˘¿Ú¯ÂÈ ÎÏÈÓÈο ÛËÌ·ÓÙÈ΋ ÌÈÎÚÔ·ÁÁÂȷ΋ ·ÈÌÔÚÚ·Á›·, ÂӉ›ÎÓ˘Ù·È Ë ¯ÔÚ‹ÁËÛË FFP ‹ PLT ‹ ·ÎfiÌË Î·È ÙÔ˘ rFVII ÚÈÓ ÙËÓ ÙÔÔı¤ÙËÛË ÙÔ˘ ÂÓ‰ÔÎÚ¿ÓÈÔ˘ ηıÂÙ‹Ú·. ªË ÂÂÌ‚·ÙÈÎfi monitoring Ù˘ ÂÓ‰ÔÎÚ·Ó›Ô˘ ›ÂÛ˘ ·ÔÙÂÏÔ‡Ó ÙÔ ‰È·ÎÚ·ÓÈ·Îfi Doppler, Ë Ì·ÁÓËÙÈ΋ ÙÔÌÔÁÚ·Ê›· Î·È ÙÔ SjVO2. ∞˘ÍË̤ÓË ∂∫¶ Î·È ·Ú·ÙÂٷ̤ÓË ÂÁÎÂÊ·ÏÈ΋ ›ÂÛË ‰È‹ıËÛ˘ (∂.¶.¢.) οو ·fi 50mmHg, ‹ ∂∫¶ ¿Óˆ ·fi 40mmHg Û¯ÂÙ›˙ÔÓÙ·È Ì ÊÙˆ¯‹ Ó¢ÚÔÏÔÁÈ΋ ·Ó¿ÓË„Ë. ™Ùfi¯Ô˜ Ù˘ ıÂڷ›·˜ Â›Ó·È ∂∫¶ οو ·fi 20mmHg Î·È ∂.¶.¢.> 60mmHg. ∫¿ÔÈÔÈ Û˘ÁÁÚ·Ê›˜ ıˆÚÔ‡Ó ∂¶¢<40mmHg ÁÈ· ‰È¿ÛÙËÌ· ÌÂÁ·Ï‡ÙÂÚÔ Ù˘ Ì›·˜ ÒÚ·˜ ˆ˜ ·ÓÙ¤Ó‰ÂÈÍË ÁÈ· ÌÂÙ·ÌfiÛ¯Â˘ÛË ‹·ÙÔ˜. ¶·ÚfiÏ· ·˘Ù¿ ˘¿Ú¯Ô˘Ó ·Ó·ÊÔÚ¤˜ ·ÛıÂÓÒÓ Ì ϋÚË Ó¢ÚÔÏÔÁÈ΋ ·Ó¿ÓË„Ë ÌÂÙ¿ ·fi ·Ú·ÙÂٷ̤ÓË ∂∫¶ (>35mmHg ÁÈ· 24-38h) Î·È ÂËÚ·Ṳ̂ÓË ∂.¶.¢. ·ÓıÂÎÙÈ΋ ÛÙË Î·ıÈÂڈ̤ÓË ıÂڷ›·.
ÁI) ∞ÓÙÈÌÂÙÒÈÛË ª·ÓÓÈÙfiÏË: ÃÔÚËÁÂ›Ù·È Û ·ӷϷ̂·ÓfiÌÂÓ˜ ÂÊ¿·Í ‰fiÛÂȘ (0,5-1gr/kgr) ‰È·ÙËÚÒÓÙ·˜ ÙËÓ ÔÛ̈ÙÈÎfiÙËÙ· ÙÔ˘ Ï¿ÛÌ·ÙÔ˜ οو ·fi 320mOsm/lt. £ÂÈÔÂÓÙ¿ÏË: ÃÚËÛÈÌÔÔÈÂ›Ù·È Û ÂÚÈÙÒÛÂȘ fiÔ˘ Â›Ó·È ·ÓıÂÎÙÈΤ˜ ÛÙË ¯ÔÚ‹ÁËÛË Ì·ÓÓÈÙfiÏ˘. ¶ÚÔηÏ› ·ÁÁÂÈÔÛ‡Û·ÛË ÛÙ· ÂÁÎÂÊ·ÏÈο ·ÁÁ›· ÂÏ·ÙÙÒÓÔÓÙ·˜ ÙËÓ ˘ÂÚ·ÈÌ›· ÙÔ˘ ÂÁÎÂÊ¿ÏÔ˘ Î·È ÙËÓ Î·Ù·Ó¿ÏˆÛË O2 (CªRO2). ∂ÈϤÔÓ, ‰Ú· Î·È ˆ˜ Û·ÛÌÔÏ˘ÙÈÎfi. ∞ÓÂÈı‡ÌËÙË ÂÓ¤ÚÁÂÈ·
METAMO™XEY™Eπ™ 2008
Ù˘ ¯ÔÚ‹ÁËÛ‹˜ Ù˘ ·ÔÙÂÏ› Ë ˘fiÙ·ÛË Î·È ·ÓÙÈÌÂÙˆ›˙ÂÙ·È Ì ˘ÁÚ¿ Î·È ÈÓfiÙÚÔ·. ÀÂÚ·ÂÚÈÛÌfi˜: O ˘ÂÚ·ÂÚÈÛÌfi˜ ÂÏ·ÙÙÒÓÂÈ ÙËÓ PaCO2 Î·È Î·Ù¿ Û˘Ó¤ÂÈ· ÙËÓ ·ÈÌ¿ÙˆÛË ÙÔ˘ ÂÁÎÂÊ¿ÏÔ˘. ◊È· ˘ÔıÂÚÌ›·: ∏ ‹È· ˘ÔıÂÚÌ›· ‚Ô‹ıËÛ ·ÛıÂÓ›˜ Ì O.∏.∞. Î·È ÂÓ‰ÔÎÚ¿ÓÈÔ ˘¤ÚÙ·ÛË ·ÓıÂÎÙÈ΋ ÛÙË ıÂڷ›· Ì ̷ÓÓÈÙfiÏË. ªÂ ıÂÚÌÔÎÚ·Û›· ˘Ú‹Ó· ÛÒÌ·ÙÔ˜ 32-33Ô C ÁÈ· ÙÔ˘Ï¿¯ÈÙÔÓ 13 ÒÚ˜, Ë ÂÓ‰ÔÎÚ¿ÓÈ· ›ÂÛË ÂÏ·ÙÙÒıËΠ·fi 45mmHg Û 16mmHg Î·È Ë ÂÁÎÂÊ·ÏÈ΋ ÚÔ‹ ·›Ì·ÙÔ˜ (CBF) ·fi 103ml/100gr/min Û 44ml/100gr/min. ∞ÓÙ›ÛÙÔȯ˜ ÌÂÙ·‚ÔϤ˜ ·Ú·ÙËÚ‹ıËÎ·Ó ÛÙËÓ ÂÁÎÂÊ·ÏÈ΋ ›ÂÛË ‰È‹ıËÛ˘ Ô˘ ·˘Í‹ıËΠ·fi 45mmHg Û 70mmHg. ∂ÈϤÔÓ, Ì ÙËÓ ˘ÔıÂÚÌ›· ÂÏ·ÙÙÒıËÎ·Ó Ù· ›‰· ·Ì̈ӛ·˜ ÛÙÔ ·›Ì· ηıÒ˜ Î·È Ë ÂÁÎÂÊ·ÏÈ΋ ÚfiÛÏË„Ë ·Ì̈ӛ·˜. ∏ Ù¯ÓÈ΋ ·˘Ù‹ Ì ÂÈÙ˘¯›· Ì›ˆÛ ÙÔ ÂÁÎÂÊ·ÏÈÎfi Ô›‰ËÌ· Î·È ÏÂÈÙÔ‡ÚÁËÛ ˆ˜ Á¤Ê˘Ú· ÁÈ· ÙË ÌÂÙ·ÌfiÛ¯Â˘ÛË ‹·ÙÔ˜. ¶·Ú·ÙÂٷ̤ÓË, ·ÓıÂÎÙÈ΋ Û οı ıÂڷ›· ÂÓ‰ÔÎÚ¿ÓÈÔ˜ ˘¤ÚÙ·ÛË Ô‰‹ÁËÛ ÛÙËÓ ·ÎÚ·›· χÛË Ù˘ ÔÏÈ΋˜ Ë·ÙÂÎÙÔÌ‹˜ Î·È Ù˘ ‰ÈÂÓ¤ÚÁÂÈ·˜ ˘Ï·ÈÔ-ÎÔÈÏÈÎÔ‡ shunt. ∏ Ù¯ÓÈ΋ ·˘Ù‹ ÂÏ·ÙÙÒÓÂÈ ÙËÓ ∂∫¶ Î·È ‚ÂÏÙÈÒÓÂÈ ÙËÓ ·ÈÌÔ‰˘Ó·ÌÈ΋ ηٿÛÙ·ÛË ÙÔ˘ ·ÚÚÒÛÙÔ˘, ·ÏÏ¿ ÂÚÈÔÚ›˙ÂÈ ÙËÓ ÂÈ‚›ˆÛ‹ ÙÔ˘˜, ÂÎÙfi˜ ·Ó Ú·ÁÌ·ÙÔÔÈËı› ÌÂÙ·ÌfiÛ¯Â˘ÛË ‹·ÙÔ˜ ̤۷ Û 12-24 ÒÚ˜.
¢È·Ù·Ú·¯¤˜ ÛÙËÓ ‹ÍË ÙÔ˘ ·›Ì·ÙÔ˜ ΔÔ ‹·Ú Â›Ó·È ˘Â‡ı˘ÓÔ ÁÈ· ÙË Û‡ÓıÂÛË ÙˆÓ ·Ú·ÁfiÓÙˆÓ Ù˘ ‹Í˘ Î·È ÂÔ̤ӈ˜ ‰È·Ù·Ú·¯¤˜ ÛÙËÓ ‹ÍË ÂÌÊ·Ó›˙ÔÓÙ·È ¿ÌÂÛ· ÛÙËÓ O.∏.∞. ∞ÈÌÔÚÚ·Á›Â˜ ÂΉËÏÒÓÔÓÙ·È Î˘Ú›ˆ˜ ·fi ÙÔ ·ÓÒÙÂÚÔ ÂÙÈÎfi, ·fi ÙÔ ÚÈÓÔÊ¿Ú˘ÁÁ·, ÙÔ˘˜ Ó‡ÌÔÓ˜ Î·È ÙÔ˘˜ ˘Ô‰fiÚÈÔ˘˜ ÈÛÙÔ‡˜. ∏ ¯ÔÚ‹ÁËÛË ∏ 2-·Ó·ÛÙÔϤˆÓ ‹ ·Ó·ÛÙÔϤˆÓ Ù˘ ·ÓÙÏ›·˜ ÚˆÙÔÓ›ˆÓ ÂÏ·ÙÙÒÓÔ˘Ó ÙË ıÓËÙfiÙËÙ· Î·È ıÓËÛÈÌfiÙËÙ· ÙˆÓ ·ÛıÂÓÒÓ. Δ· Ê¿Ú̷η ·˘Ù¿ ¯ÔÚËÁÔ‡ÓÙ·È ·ÓÂÍ¿ÚÙËÙ· ·fi ÙÔ ·Ó ˘¿Ú¯ÂÈ ‹ fi¯È ÂÓÂÚÁfi˜ ·ÈÌÔÚÚ·Á›· ÙÔ˘ °.∂.™. ™ÙËÓ O.∏.∞. ·Ú·ÙËÚÂ›Ù·È ‰˘ÛÏÂÈÙÔ˘ÚÁ›· ÙˆÓ ·ÈÌÔÂÙ·Ï›ˆÓ, ÂÏ·Ùو̤ӷ ›‰· ÙˆÓ ·Ú·ÁfiÓÙˆÓ Î·È ÙˆÓ ·Ó·ÛÙÔϤˆÓ Ù˘ ‹Í˘, ÈÓˆ‰fiÏ˘ÛË Î·È ‰È¿¯˘ÙË ÂÓ‰·ÁÁÂȷ΋ ‹ÍË. O ·ÚÈıÌfi˜ ÙˆÓ ·ÈÌÔÂÙ·Ï›ˆÓ ÂÏ·ÙÙÒÓÂÙ·È Ú·Á‰·›· ›Ù ÏfiÁˆ ηٷÛÙÚÔÊ‹˜ ÙÔ˘˜ ›Ù ÏfiÁˆ ÂÏ·Ùو̤Ó˘ Ë·ÙÈ΋˜ Û‡ÓıÂÛ˘ Ù˘ ıÚÔÌ‚ÔÔÈËÙ›Ó˘. ∏ Û‡ÓıÂÛË ÙˆÓ ·Ú·ÁfiÓÙˆÓ ππ, V, VII, IX Î·È Ã Â›Ó·È ÂÏ·Ùو̤ÓË ÁÂÁÔÓfi˜ Ô˘ ÚÔηÏ› ·Ú¿-
117
Ù·ÛË ÙÔ˘ ¯ÚfiÓÔ˘ ÚÔıÚÔÌ‚›Ó˘. ™Â ·ÓÙ›ıÂÛË, Ù· ›‰· ÙÔ˘ ·Ú¿ÁÔÓÙ· VIII Â›Ó·È Û˘Ó‹ıˆ˜ ·˘ÍË̤ӷ. Δ· ›‰· ÙˆÓ ·Ó·ÛÙÔϤˆÓ Ù˘ ‹Í˘, Ù˘ ·ÓÙÈıÚÔÌ‚›Ó˘ πππ, Ù˘ ÚˆÙ½Ó˘ C, Î·È Ù˘ ÚˆÙ½Ó˘ S Â›Ó·È ÂÏ·Ùو̤ӷ ηıÒ˜ Î·È Ù· ›‰· ÛÙÔ Ï¿ÛÌ· ÙÔ˘ ÈÓˆ‰ÔÁfiÓÔ˘, Ï·ÛÌÈÓÔÁfiÓÔ˘ Î·È ÙÔ˘ ·Ó·ÛÙÔϤ· Ù˘ Ï·ÛÌ›Ó˘. °ÂÓÈο, ·Ú·ÙËÚÂ›Ù·È ·˘ÍË̤ÓË ÈÓˆ‰fiÏ˘ÛË Ô˘ ÈÛÙÔÔÈÂ›Ù·È Ì ÙËÓ ·‡ÍËÛË ÙˆÓ ÚÔ˚fiÓÙˆÓ ‰È¿Û·Û˘ ÙÔ˘ ÈÓÒ‰Ô˘˜ Î·È ÙÔ ÌË Û¯ËÌ·ÙÈÛÌfi ıÚfiÌ‚Ô˘.
¢È·Ù·Ú·¯¤˜ Ù˘ ÓÂÊÚÈ΋˜ ÏÂÈÙÔ˘ÚÁ›·˜ ∏ ÓÂÊÚÈ΋ ‰˘ÛÏÂÈÙÔ˘ÚÁ›· ÂΉËÏÒÓÂÙ·È Ì ÔÏÈÁÔ˘Ú›· Î·È Î·Ù·ÎÚ¿ÙËÛË Ó·ÙÚ›Ô˘ Î·È ‡‰·ÙÔ˜. ∂ÌÊ·Ó›˙ÂÙ·È ÛÙÔ 55% Ì 84% ÙˆÓ ÂÚÈÙÒÛˆÓ, Û¯ÂÙ›˙ÂÙ·È Ì ÊÙˆ¯‹ ÚfiÁÓˆÛË Î·È ÔÊ›ÏÂÙ·È Â›Ù Û ÏÂÈÙÔ˘ÚÁÈ΋ ‰È·Ù·Ú·¯‹ (Ë·ÙÔÓÂÊÚÈÎfi Û‡Ó‰ÚÔÌÔ) ›Ù Û ÔÍ›· ÛˆÏËÓ·Úȷ΋ Ó¤ÎÚˆÛË ‹ Û ÚÔÓÂÊÚÈο ·›ÙÈ· ÏfiÁˆ ÂÏ¿ÙÙˆÛ˘ ÙÔ˘ ÂÓ‰·ÁÁÂÈ·ÎÔ‡ fiÁÎÔ˘. ∏ ¯ÔÚ‹ÁËÛË ˘ÁÚÒÓ ÁÈ· ·‡ÍËÛË ÙÔ˘ ÂÓ‰·ÁÁÂÈ·ÎÔ‡ fiÁÎÔ˘ ·ÔÙÂÏ› ηıÔÚÈÛÙÈÎfi ‚‹Ì· ÛÙËÓ ·ÓÙÈÌÂÙÒÈÛË Ù˘ ÔÏÈÁÔ˘Ú›·˜. ∏ ¯Ú‹ÛË ÙˆÓ ‰ÈÔ˘ÚËÙÈÎÒÓ Ù˘ ·Á·Ï˘ ·Ú·Ì¤ÓÂÈ ·ÌÊÈÏÂÁfiÌÂÓË, ÂÓÒ Ë ·ÓÔ˘Ú›·, Ë ÔͤˆÛË, Ë ˘ÂÚηÏÈ·ÈÌ›·, Ë ˘ÔÓ·ÙÚÈ·ÈÌ›·, Ë ˘ÂÚÊfiÚÙˆÛË Ì ˘ÁÚ¿ Î·È Ë ·‡ÍËÛË Ù˘ ÎÚ·ÙÈÓ›Ó˘ ··ÈÙÔ‡Ó ÓÂÊÚÈ΋ ˘ÔÛÙ‹ÚÈÍË. ∏ Û˘Ó¯‹˜ ÊÏ‚Ô-ÊÏ‚È΋ ·ÈÌԉȇÏÈÛË Â›Ó·È Ë ÂӉ‰ÂÈÁ̤ÓË ·ÓÙÈÌÂÙÒÈÛË Î·ıÒ˜ ÚÔÛʤÚÂÈ ·ÈÌÔ‰˘Ó·ÌÈ΋ ÛÙ·ıÂÚfiÙËÙ· Î·È ÂÏÂÁ¯fiÌÂÓÔ, ÛÙ·‰È·Îfi ¤ÏÂÁ¯Ô ÙˆÓ ÌÂÙ·‚ÔÏÈÎÒÓ ‰È·Ù·Ú·¯ÒÓ.
ªÂÙ·‚ÔÏÈΤ˜ ‰È·Ù·Ú·¯¤˜ ÀÔÁÏ˘Î·ÈÌ›· Û˘¯Ó¿ ÂÌÊ·Ó›˙ÂÙ·È ÏfiÁˆ ÂÍ¿ÓÙÏËÛ˘ ÙˆÓ Ë·ÙÈÎÒÓ ·ÔıËÎÒÓ ÁÏ˘ÎÔÁfiÓÔ˘ Î·È ·‰˘Ó·Ì›· ÓÂÔÁÏ˘ÎÔÁ¤ÓÂÛ˘.
ªÂÙ·ÌfiÛ¯Â˘ÛË ‹·ÙÔ˜ (ª.∏.) ∏ ÌÂÙ·ÌfiÛ¯Â˘ÛË ‹·ÙÔ˜ ·ÔηıÈÛÙ¿ ÙË ÏÂÈÙÔ˘ÚÁ›· ÙÔ˘ ‹·ÙÔ˜ Î·È ‚ÂÏÙÈÒÓÂÈ ÙËÓ ¤Î‚·ÛË ÙˆÓ ·ÛıÂÓÒÓ Ì O.∏.∞. À¿Ú¯Ô˘Ó ·˘ÛÙËÚ¿ ÎÚÈÙ‹ÚÈ· ÁÈ· ÙËÓ ÂÈÏÔÁ‹ ÙˆÓ ·ÛıÂÓÒÓ Ô˘ ı· ˘Ô‚ÏËıÔ‡Ó Û ª.∏. (ÈÓ. π). OÈ ·ÛıÂÓ›˜ ·˘ÙÔ›, ·ÔÙÂÏÔ‡Ó ÚfiÎÏËÛË ÁÈ· ÙÔÓ ·Ó·ÈÛıËÛÈÔÏfiÁÔ ÏfiÁˆ Ù˘ ‚·Ú‡ÙËÙ·˜ Ù˘ ηٿÛÙ·Û‹˜ ÙÔ˘˜. π‰È·›ÙÂÚË ÚÔÛÔ¯‹ Ú¤ÂÈ Ó· ‰Ôı› ÛÙËÓ ‰È·Ù‹ÚËÛË Ù˘ ÂÁÎÂÊ·ÏÈ΋˜ ›ÂÛ˘ ‰È‹ıËÛ˘ Î·È ÙË ÌË ·‡ÍËÛË Ù˘ ÂÓ‰ÔÎÚ·Ó›Ô˘ ›ÂÛ˘ ÛÙË ‰È¿ÚÎÂÈ· Ù˘ ª.∏. Œ¯ÂÈ ·Ô‰Âȯı› fiÙÈ «ÂÈΛӉ˘Ó· ÛÙ¿‰È·» Ù˘ ¤̂·Û˘ ÁÈ· ·‡ÍËÛË Ù˘ ÂÓ‰ÔÎÚ·Ó›Ô˘
118
∂. ∫∞Δ™π∫∞
›ÂÛ˘ Â›Ó·È Ë ‰È·ÛˆÏ‹ÓˆÛË, Ë Ë·ÙÂÎÙÔÌ‹ Î·È ÙÔ ÛÙ¿‰ÈÔ Â·Ó·ÈÌ¿ÙˆÛ˘ ÙÔ˘ ÌÔۯ‡̷ÙÔ˜. ¶ÚÔÙ›ÓÂÙ·È Ë ¯Ú‹ÛË ÚÔÔÊfiÏ˘ ‹ ıÂÈÔÂÓÙ¿Ï˘ Î·È Ë ¯ÔÚ‹ÁËÛË Í˘ÏÔη˝Ó˘ ÁÈ· ÙË ‰È·ÛˆÏ‹ÓˆÛË. ∏ ÚÔÔÊfiÏË ÚÔÙ›ÓÂÙ·È Î·È ÁÈ· ÙË ‰È·Ù‹ÚËÛË Ù˘ ·Ó·ÈÛıËÛ›·˜. ∏ ›ÂÛË ‰È‹ıËÛ˘ ÙÔ˘ ÂÁÎÂÊ¿ÏÔ˘ Ú¤ÂÈ Ó· ‰È·ÙËÚÂ›Ù·È ¿Óˆ ·fi 50mmHg Î·È Ë ÂÓ‰ÔÎÚ¿ÓÈÔ˜ ›ÂÛË Î¿Ùˆ ·fi 20mmHg. ª¤ÙÚ· ÁÈ· ÙË ‰È·Ù‹ÚËÛË ·˘ÙÒÓ ÙˆÓ ·Ú·Ì¤ÙÚˆÓ ¤¯Ô˘Ó Û˘˙ËÙËı› ÚÔËÁÔ˘Ì¤Óˆ˜. ™˘¯Ó¿, Ú¤ÂÈ Ó· Ú·ÁÌ·ÙÔÔÈÂ›Ù·È ¤ÏÂÁ¯Ô˜ Ù˘ ÁÏ˘Îfi˙˘, ÙˆÓ ËÏÂÎÙÚÔÏ˘ÙÒÓ Î·È Ù˘ ÔÍÂÔ‚·ÛÈ΋˜ ÈÛÔÚÚÔ›·˜. OÈ ·ÈÌÔ‰˘Ó·ÌÈΤ˜ ÌÂÙ·‚ÔϤ˜ ÛÙ· ‰È¿ÊÔÚ· ÛÙ¿‰È· Ù˘ ¤̂·Û˘ Â›Ó·È ·ÚfiÌÔȘ Ì’·˘Ù¤˜ ÙˆÓ ·ÛıÂÓÒÓ Ì ¯ÚfiÓÈ· Ë·ÙÈ΋ ·Ó¿ÚÎÂÈ· Ô˘ ˘Ô‚¿ÏÏÔÓÙ·È Û ª.∏. π‰È·ÈÙÂÚfiÙËÙ· ÂÌÊ·Ó›˙Ô˘Ó ÛÙË Ê¿ÛË ·ÔÎÏÂÈÛÌÔ‡ Ù˘ ˘Ï·›·˜ ÊϤ‚·˜, ÔÈ ·ÛıÂÓ›˜ Ô˘ ‰ÂÓ ¤¯Ô˘Ó ÚÔÏ¿‚ÂÈ Ó· ·Ó·Ù‡ÍÔ˘Ó ·Ú¿Ï¢ÚÔ Î˘ÎÏÔÊÔÚ›·. ™’·˘Ù¤˜ ÙȘ ÂÚÈÙÒÛÂȘ ·Ú·ÙËÚÂ›Ù·È ÛËÌ·ÓÙÈ΋ ÂÏ¿ÙÙˆÛË Ù˘ ηډȷ΋˜ ·ÚÔ¯‹˜, Ù˘ ·ÚÙËÚȷ΋˜ ›ÂÛ˘ Î·È ÙÔ˘ ÚÔÊÔÚÙ›Ô˘. ¶›Ó·Î·˜ π. ∫ÚÈÙ‹ÚÈ· ÁÈ· ÌÂÙ·ÌfiÛ¯Â˘ÛË ‹·ÙÔ˜ ·ÛıÂÓÒÓ Ì ÔÍ›· Ë·ÙÈ΋ ·Ó¿ÚÎÂÈ·. ∫ÚÈÙ‹ÚÈ· King’s College ñ OHA ·fi ·Ú·ÎÂÙ·ÌfiÏË – pH <7,3 ‹ – INR >4 +ÎÚ·ÙÈÓ›ÓË ÔÚÔ‡ > 3,4mg/dl Û ·ÛıÂÓ›˜ ÛÙ·‰›Ô˘ πππ/ IV Ë·ÙÈ΋˜ ÂÁÎÂÊ·ÏÔ¿ıÂÈ·˜ (∏.∂.) ñ O∏∞ ¿ÏÏ˘ ·ÈÙÈÔÏÔÁ›·˜ ñ – π¡R >4 ‹ – ÙÚ›· ·fi Ù· ·ÎfiÏÔ˘ı· ÎÚÈÙ‹ÚÈ· ·ÓÂÍ·Úًو˜ ÛÙ·‰›Ô˘ (∏.∂.) – ∏ÏÈΛ· < 10 ‹ > 40 ¤ÙË – ∞ÈÙ›·: º·Ú̷΢ÙÈ΋ Ë·ÙÔÍÈÎfiÙËÙ·, non-A – non- B Ë·Ù›Ùȉ·, Ë·Ù›Ùȉ· ·fi ·ÏÔı¿ÓÈÔ – ªÂÛԉȿÛÙËÌ· ÈÎÙ¤ÚÔ˘ ̤¯ÚÈ ÙÔ ÎÒÌ· > 7 Ë̤Ú˜ – πNR > 3,5 – ÃÔÏÂÚ˘ıÚ›ÓË ÔÚÔ‡ > 17,5 mgr/dl. ∫ÚÈÙ‹ÚÈ· Clichy – Paul Brousse ∂ÁÎÂÊ·ÏÔ¿ıÂÈ· ÛÙ·‰›Ô˘ ππ-IV ¶·Ú¿ÁÔÓÙ· V < 20% ÁÈ· ËÏÈΛ· < 30 ÂÙÒÓ ¶·Ú¿ÁÔÓÙ· V < 30% ÁÈ· ËÏÈΛ· > 30 ÂÙÒÓ ∫ÚÈÙ‹ÚÈ· MELD MELD score > 30.
¶ƒOΔ∂π¡Oª∂¡∏ μπμ§πO°ƒ∞ºπ∞ 1. Shakil O, Mazariegos G, Kramer D. Fulminant hepatic failure. Surg clin north am, 1999; 79:77-108. 2. Rahman T, Hodgson H. Clinical management of acute hepatic failure. Intensive care med, 2001; 27:467-76. 3. Harry R, Wendon J. The management of acute liver failure. CME gastroenterology, 2001; 4:58-61. 4. Tofteng F, Larsen F. Management of patients with fulminant hepatic failure and brain edema. Metabolic brain disease, 2004; 19:207-14. 5. Jalan R. Pathophysiological basis of therapy of raised intracranial pressure in acute liver failure. Neurochemistry international, 2005; 47:78-83. 6. Detry O, Roover A, Honore P. Brain edema and intracranial hypertension in fulminant hepatic failure: pathophysiology and management. World j gastroenterology, 2006; 12:7405-12. 7. Filho J, Marchado M, Nani R et al. Hypertonic saline solutions increases cerebral perfusion pressure during clinical orthotopic liver transplantation for fulminant hepatic failure : preliminary results. Clinics, 2006; 61:1-9. 8. Belanger M, Desjardins P, Chatauret N et al. Mild hypothermia prevents brain edema and attenuates up-regulation of the astrocytic benzodiazepine receptor in experimental acute liver failure. J hepatol, 2005; 42:694-9. 9. £. μ·ÛÈÏÂÈ¿‰Ë˜. ∫ÂÚ·˘ÓÔ‚fiÏÔ˜ Ë·ÙÈ΋ ·Ó¿ÚÎÂÈ·. ™ÙÔ ‚È‚Ï›Ô «ÃÂÈÚÔ˘ÚÁÈ΋ ÙÔ˘ ‹·ÙÔ˜» ∞. ∞ÓÙˆÓÈ¿‰Ë˜, 1Ë ¤Î‰ÔÛË, 2007, ÛÂÏ. 524-38. 10. Lidofsky S, Bass N, Prager M et al. Intracranial pressure monitoring and liver transplantation for fulminant hepatic failure. Hepatology, 1992; 16:1-7. 11. Vaquero J, Fontana R, Larson A et al. Complications and use of intracranial pressure monitoring in patients with acute liver failure and severe encephalopathy. Liver transplantation, 2005; 11:1581-9. 12. Sidi A, Mahla M. Noninvasive monitoring of cerebral perfusion by transcranial Doppler during fulminant hepatic failure and liver transplantation. Anesth analg, 1995; 80:194-200. 13. Pavese P, Bonadona A, Beaubien J et al. FVIIa corrects the coagulopathy of fulminant hepatic failure but may be associated with thrombosis : a report of four cases. General anesthesia, 2005; 52:26-9. 14. Bismuth H, Samuel D, Castaing D et al. Orthotopic liver transplantation in fulminant and subfulminant hepatitis. Annals of surgery, 1995; 222:109-19.
¶ÚÒÈÌË ‰˘ÛÏÂÈÙÔ˘ÚÁ›· ÙÔ˘ Ë·ÙÈÎÔ‡ ÌÔۯ‡̷ÙÔ˜ ÛÙË MÔÓ¿‰· EÓÙ·ÙÈ΋˜ £Âڷ›·˜ ª.∞. ¶·Û·ÎÈÒÙÔ˘
∂π™∞°ø°∏
Û˜ (SGOT/SGPT) Â›Ó·È ·˘ÍË̤Ó˜ ÙȘ ÚÒÙ˜ 2-3 ̤Ú˜, ·ӤگÔÓÙ·È ‰Â ÛÙ·‰È·Î¿ ÛÙ· Ê˘ÛÈÔÏÔÁÈο ›‰·, ÂÊ’ fiÛÔÓ ‰ÂÓ ÚÔ·ÙÔ˘Ó ÚÔ‚Ï‹Ì·Ù·.
OÈ ·ÛıÂÓ›˜ Ô˘ ¤¯Ô˘Ó ˘Ô‚ÏËı› Û ÔÚıÔÙÔÈ΋ ÌÂÙ·ÌfiÛ¯Â˘ÛË ‹·ÙÔ˜ ¯ÚÂÈ¿˙ÔÓÙ·È ÓÔÛËÏ›· ÙÔ˘Ï¿¯ÈÛÙÔÓ 24-48 ÒÚ˜ ÛÙË ªÔÓ¿‰· ∂ÓÙ·ÙÈ΋˜ £Âڷ›·˜ (ª∂£). ∏ ·Ê·›ÚÂÛË ÙÔ˘ ÙÚ·¯ÂÈÔۈϋӷ ÚÔ¸Ôı¤ÙÂÈ ÙËÓ ÔÌ·Ï‹ ÏÂÈÙÔ˘ÚÁ›· ÙÔ˘ ÌÔۯ‡̷ÙÔ˜ Î·È ÙÔ ÈηÓÔÔÈËÙÈÎfi Â›Â‰Ô Â·Ê‹˜ ÙÔ˘ ·ÛıÂÓÔ‡˜, Ô‡Ùˆ˜ ÒÛÙ ӷ ÚÔÛٷهÂÙ·È Ô ·ÂÚ·ÁˆÁfi˜. ¶Ú¤ÂÈ Ó· Ï·Ì‚¿ÓÂÙ·È ˘’ fi„Ë fiÙÈ Ô ÌÂÙ·‚ÔÏÈÛÌfi˜ Î·È Ë ·Ô‚ÔÏ‹ ·fi ÙÔÓ ÔÚÁ·ÓÈÛÌfi ÙˆÓ ·Ó·ÈÛıËÙÈÎÒÓ Ê·ÚÌ¿ÎˆÓ Â›Ó·È ÂÈ‚Ú·‰˘Ì¤ÓÔ˜ ·fi ÙÔ ÚfiÛÊ·Ù· ÌÂÙ·ÌÔÛ¯Â˘Ì¤ÓÔ ‹·Ú. ∏ ·Ó¿ÁÎË Â·Ó·‰È·ÛˆÏ‹ÓˆÛ˘ ¤¯ÂÈ Û˘Ó‰Âı› Ì و¯‹ ¤Î‚·ÛË Î·È ·˘ÍË̤ÓË ıÓËÛÈÌfiÙËÙ·1. ¶¿ÓÙˆ˜, ˘¿Ú¯Ô˘Ó ÂӉ›ÍÂȘ fiÙÈ Ë ÚÒÈÌË-Û¯ÂÙÈο- ·Ô‰È·ÛˆÏ‹ÓˆÛË ÂÏ·ÙÙÒÓÂÈ ÙË ÓÔÛËÏ›· ÛÙË ª∂£2.
∞πªO¢À¡∞ªπ∫O™ ∂§∂°ÃO™ ∏ ·ÒÏÂÈ· ˘ÁÚÒÓ Î·È ·›Ì·ÙÔ˜ ηٿ ÙË ‰È¿ÚÎÂÈ· ÙÔ˘ ¯ÂÈÚÔ˘ÚÁ›Ԣ Â›Ó·È ÛËÌ·ÓÙÈ΋, Ì ·ÔÙ¤ÏÂÛÌ· Ó· ·Ú·ÙËÚÔ‡ÓÙ·È ‰È·Ù·Ú·¯¤˜ Ù˘ ÔÌÔÈfiÛÙ·Û˘. ∏ ¯Ú‹ÛË ·ÚÔÙÈÓ›Ó˘ ηٿ ÙË ‰È¿ÚÎÂÈ· Ù˘ ÌÂÙ·ÌfiÛ¯Â˘Û˘ Û˘ÓÈÛÙ¿Ù·È ·fi ÔÚÈṲ̂ӷ ΤÓÙÚ·, ÂÂȉ‹ ÂÏ·ÙÙÒÓÂÈ ÙȘ ·Ó¿ÁΘ ÁÈ· ÌÂÙ¿ÁÁÈÛË, ÂϤÁ¯ÔÓÙ·˜ ÙËÓ ·ÈÌÔÚÚ·Á›· Î·È ÌÂÈÒÓÔÓÙ·˜ ÙȘ ·Ó¿ÁΘ ÁÈ· ÈÓfiÙÚÔË Î·È ·ÁÁÂÈÔÛ˘Û·ÛÙÈ΋ ˘ÔÛÙ‹ÚÈÍË3. ∂›Û˘, ·Ú·ÙËÚ‹ıËΠfiÙÈ ‚ÂÏÙÈÒÓÂÙ·È Ë ÓÂÊÚÈ΋ ÏÂÈÙÔ˘ÚÁ›·4. øÛÙfiÛÔ, ˘¿Ú¯Ô˘Ó ÌÂϤÙ˜ Ô˘ ıˆÚÔ‡Ó fiÙÈ Ô ÂÓıÔ˘ÛÈ·ÛÌfi˜ Ô˘ ˘‹ÚÍ ÁÈ· ÙË ¯ÔÚ‹ÁËÛË Ù˘ ·ÚÔÙÈÓ›Ó˘ ·ÓÙÈηı›ÛÙ·Ù·È ·fi ÙÔÓ ÚÔ‚ÏËÌ·ÙÈÛÌfi ÁÈ· ÙËÓ ·˘ÍË̤ÓË Û˘¯ÓfiÙËÙ· ÂÌÊ¿ÓÈÛ˘ ıÚÔÌ‚ÔÂÌ‚ÔÏ‹˜5. ∫·Ù¿ ÙË ‰È¿ÚÎÂÈ· Ù˘ ¤̂·Û˘, ÔÈ ·ÛıÂÓ›˜ ¤¯Ô˘Ó ÌÂÁ¿Ï˜ ·ÒÏÂȘ ˘ÁÚÒÓ Î·È ÚˆÙÂïÓÒÓ, ȉ›ˆ˜ fiÙ·Ó Û˘Ó˘¿Ú¯ÂÈ ÂÎÛÂÛËÌ·Ṳ̂ÓÔ˜ ·ÛΛÙ˘. O ·ÈÌ·ÙÔÎÚ›Ù˘ Ú¤ÂÈ Ó· ÂϤÁ¯ÂÙ·È, ·Ú¯Èο, οı 46 ÒÚ˜, ÂÓÒ Ë ˘ÂÚ‰˘Ó·ÌÈ΋ ΢ÎÏÔÊÔÚ›· Ô˘ ¯·Ú·ÎÙËÚ›˙ÂÈ ÙËÓ Ë·ÙÈ΋ ·Ó¿ÚÎÂÈ· , Û˘Ó‹ıˆ˜ ÂÌ̤ÓÂÈ Î·È ÛÙËÓ ÌÂÙÂÁ¯ÂÈÚËÙÈ΋ ÂÚ›Ô‰Ô. ¶·Ú·ÙËÚÂ›Ù·È ·˘ÍË̤ÓË Î·Ú‰È·Î‹ ·ÚÔ¯‹ Ì ÂÏ·Ùو̤Ó˜ Û˘ÛÙËÌ·ÙÈΤ˜ ·ÓÙÈÛÙ¿ÛÂȘ, ηٿÛÙ·ÛË Ô˘ ¯Ú‹˙ÂÈ ·Ó·Ï‹ÚˆÛ˘ Ì ˘ÁÚ¿, ÂÓÒ Ë ÂÌÊ¿ÓÈÛË ÛÔ‚·ÚÒÓ ÂÈÏÔÎÒÓ ·fi ÙÔ Î·Ú‰È·ÁÁÂÈ·Îfi ‰ÂÓ Â›Ó·È ·Û˘Ó‹ı˘6. ∂›Û˘, Â›Ó·È Û˘Ó‹ı˘ Ë ˘ÔÓ·ÙÚÈ·ÈÌ›·, Ë ·fiÙÔÌË ‰ÈfiÚıˆÛË Ù˘ ÔÔ›·˜ ÌÔÚ› Ó· Ô‰ËÁ‹ÛÂÈ ÛÙÔ Û‡Ó‰ÚÔÌÔ ÔÛ̈ÙÈ΋˜ ·ÔÌ˘ÂϛӈÛ˘6. π‰È·›ÙÂÚË ÚÔÛÔ¯‹ ¯ÚÂÈ¿˙ÂÙ·È ÛÙÔ˘˜ ·ÛıÂÓ›˜ Ì ÛËÌ·ÓÙÈÎÔ‡ ‚·ıÌÔ‡ ÚÔÂÁ¯ÂÈÚËÙÈ΋ ˘Ï·ÈÔÓ¢ÌÔÓÈ΋ ˘¤ÚÙ·ÛË, ‰ÈfiÙÈ ·ÚÔ˘ÛÈ¿˙Ô˘Ó ·ÈÌÔ‰˘Ó·ÌÈ΋ ·ÛÙ¿ıÂÈ·, Ì ÔÛÔÛÙ¿ ıÓËÛÈÌfiÙËÙ·˜ ȉȷÈÙ¤Úˆ˜ ·˘ÍË̤ӷ fiÙ·Ó Ë ÚÔÂÁ¯ÂÈÚËÙÈ΋ ̤ÛË Ó¢ÌÔÓÈ΋ ›ÂÛË ˘ÂÚ‚·›ÓÂÈ Ù· 35mmHg7, ÁÂÁÔ-
∂§∂°ÃO™ Δ∏™ ∏¶∞Δπ∫∏™ §∂πΔOÀƒ°π∞™ ∏ ÏÂÈÙÔ˘ÚÁÈÎfiÙËÙ· ÙÔ˘ Ó¤Ô˘ Ë·ÙÈÎÔ‡ ÌÔۯ‡̷ÙÔ˜ ÂϤÁ¯ÂÙ·È fiˆ˜ ·ÎÚÈ‚Ò˜ Î·È Û ÔÔÈÔÓ‰‹ÔÙ ·ÛıÂÓ‹. ™ÙËÓ ¿ÌÂÛË ÌÂÙÂÁ¯ÂÈÚËÙÈ΋ ÂÚ›Ô‰Ô, ˘¿Ú¯ÂÈ ‰È·Ù·Ú·¯‹ ÙÔ˘ ËÎÙÈÎÔ‡ Ì˯·ÓÈÛÌÔ‡, Ô˘ ‰ÈÔÚıÒÓÂÙ·È Û‡ÓÙÔÌ· ÌÂÙ¿ ÙË ÌÂÙ·ÌfiÛ¯Â˘ÛË. O ¯ÚfiÓÔ˜ ÚÔıÚÔÌ‚›Ó˘ (PT) Î·È ÙÔ INR (International Normalized Ratio) Ú¤ÂÈ Ó· ÂϤÁ¯ÔÓÙ·È Û˘¯Ó¿. ∏ ¯ÔÚ‹ÁËÛË FFP ÂËÚ¿˙ÂÈ ÙËÓ ÈηÓfiÙËÙ· ÂϤÁ¯Ô˘ ÙÔ˘ ËÎÙÈÎÔ‡ Ì˯·ÓÈÛÌÔ‡, ÁÈ’ ·˘Ùfi Î·È Ë ¯ÔÚ‹ÁËÛË ·˘ÙÒÓ ÙˆÓ ·Ú·ÁfiÓÙˆÓ Ú¤ÂÈ Ó· Á›ÓÂÙ·È Ì ÊÂȉÒ. ∞·Ú·›ÙËÙÔ˜ Â›Ó·È Ô ¤ÏÂÁ¯Ô˜ Ù˘ ÁÏ˘Îfi˙˘ ÙÔ˘ ·›Ì·ÙÔ˜ ‰ÈfiÙÈ Ë ˘ÔÁÏ˘Î·ÈÌ›· ·ÔÙÂÏ› ‰Â›ÎÙË Ë·ÙÈ΋˜ ·Ó¿ÚÎÂÈ·˜, ÂÓÒ Ë ¯ÔÚ‹ÁËÛË ÎÔÚÙÈÎÔÛÙÂÚÔÂȉÒÓ Ô‰ËÁ› Û ˘ÂÚÁÏ˘Î·ÈÌ›· Î·È ·ÓÙ›ÛÙ·ÛË ÛÙËÓ ÈÓÛÔ˘Ï›ÓË. ∏ ¯ÔÏÂÚ˘ıÚ›ÓË ·Ú·Ì¤ÓÂÈ ·˘ÍË̤ÓË ÁÈ’ ·ÚÎÂÙ¤˜ ̤Ú˜ ÌÂÙ¿ ÙËÓ Â¤Ì‚·ÛË, Ù· ›‰¿ Ù˘, fï˜, Ú¤ÂÈ Ó· ÂϤÁ¯ÔÓÙ·È Î·ıËÌÂÚÈÓ¿ ‰ÈfiÙÈ Ë ÛÙ·ıÂÚ‹ ·‡ÍËÛË ı¤ÙÂÈ ÙËÓ ˘fiÓÔÈ· ‰˘ÛÏÂÈÙÔ˘ÚÁ›·˜ ÙÔ˘ ÌÔۯ‡̷ÙÔ˜. OÈ ÙÚ·ÓÛ·ÌÈÓ¿-
119
ª. ¶∞™∞∫πøΔ√À
120 ¶π¡∞∫∞™ 1 Δ¿ÍË
ÀÂÚ‰˘Ó·ÌÈ΋ ΢ÎÏÔÊÔÚ›·
ÀÔÓ·ÙÚÈ·ÈÌ›·
∫·ÎÔıÚ„›·
¶˘Ï·ÈÔ-Ó¢ÌÔÓÈ΋ ˘¤ÚÙ·ÛË
∫·Ú‰È·Î‹ ‰˘ÛÏÂÈÙÔ˘ÚÁ›·
π
_
_
_
_
_
ππ
+
+/-
_
_
_
πππ
++
++
_
_
_
πV
++
++
+
+
+
Ófi˜ Ô˘ ·ÔÙÂÏ› ·fiÏ˘ÙË ·ÓÙ¤Ó‰ÂÈÍË ÁÈ· ÌÂÙ·ÌfiÛ¯Â˘ÛË. ŸÙ·Ó ‰È·ÁÈÁÓÒÛÎÂÙ·È Ó¢ÌÔÓÈ΋ ˘¤ÚÙ·ÛË ÚÔÂÁ¯ÂÈÚËÙÈο, ·ÎÔÏÔ˘ıÂ›Ù·È Û˘ÁÎÂÎÚÈ̤ÓË ·ÁˆÁ‹ Ì ·ÁÁÂÈԉȷÛÙ·ÏÙÈο Ù˘ Ó¢ÌÔÓÈ΋˜ Î·È ¤ÏÂÁ¯Ô˜ Ì ‰ÈÔÈÛÔÊ¿ÁÂÈÔ ˘ÂÚ˯ÔηډÈÔÁÚ¿ÊËÌ· ÁÈ· ¤Ó· ÂÍ¿ÌËÓÔ ÙÔ˘Ï¿¯ÈÛÙÔÓ. ∞Ó, ÙÂÏÈο, ÔÈ ÙÈ̤˜ Ù˘ Ó¢ÌÔÓÈ΋˜ ÂÈÙÚ¤Ô˘Ó ÙËÓ ÌÂÙ·ÌfiÛ¯Â˘ÛË, ÙfiÙ ıˆÚÂ›Ù·È ··Ú·›ÙËÙË Ë ÙÔÔı¤ÙËÛË Î·ıÂÙ‹Ú· ÛÙËÓ Ó¢ÌÔÓÈ΋ (Swan-Ganz),ÂÓÒ Û˘¯Ó¿ ··ÈÙÂ›Ù·È Ë ¯ÔÚ‹ÁËÛË ·ÁÁÂÈԉȷÛÙ·ÏÙÈÎÒÓ Ù˘ Ó¢ÌÔÓÈ΋˜ ΢ÎÏÔÊÔÚ›·˜ ‰ÈÂÁ¯ÂÈÚËÙÈο Î·È ¿ÌÂÛ· ÌÂÙÂÁ¯ÂÈÚËÙÈο (ÂÈÛÓÂfiÌÂÓÔ˘ ÓÈÙÚÈÎÔ‡ ÔÍÂȉ›Ô˘ Ë ÚÔÛÙ·ÁÏ·Ó‰ÈÓÒÓ). Δ¤ÏÔ˜, ·Ó ‰È·ÈÛÙˆı› Ó¢ÌÔÓÈ΋ ˘¤ÚÙ·ÛË ÛÙËÓ ·›ıÔ˘Û· ¯ÂÈÚÔ˘ÚÁ›Ԣ ÁÈ· ÚÒÙË ÊÔÚ¿, ÙfiÙ ·ÓÙÈÌÂÙˆ›˙ÂÙ·È ¿ÌÂÛ· Ì ¯ÔÚ‹ÁËÛË ·Ó·ÈÛıËÛ›·˜, ˘ÂÚ·ÂÚÈÛÌfi, ÊÔ˘ÚÔÛÂÌ›‰Ë, epoprostanol, milrinone ηÈ, ÌÂÙ¿ ÙËÓ ·Ó¿Ù·ÍË, ·Ú¯›˙ÂÈ Ë ÌÂÙ·ÌfiÛ¯Â˘ÛË. À¿Ú¯ÂÈ ¤Ó· Û‡ÛÙËÌ· Ù·ÍÈÓfiÌËÛ˘ ÙˆÓ ·ÛıÂÓÒÓ ·Ó¿ÏÔÁ· Ì ÙȘ ÚÔÛ‰ÔÎfiÌÂÓ˜ ·Ó¿ÁΘ ÙÔ˘˜ Û ˘ÁÚ¿ Î·È ËÏÂÎÙÚÔχÙ˜, ÙÔ ÔÔ›Ô ÚÔÙ›ÓÂÙ·È ·fi ‰È¿ÊÔÚÔ˘˜ ÂÚ¢ÓËÙ¤˜ Î·È ÙÔ˘ ÔÔ›Ô˘ Ë ¯ÚËÛÈÌfiÙËÙ· ·ÊÔÚ¿ ÛÙËÓ Úfi‚ÏÂ„Ë Ù˘ ÂͤÏÈ͢ ÙÔ˘ ÌÂÙ·ÌÔÛ¯Â˘Ì¤ÓÔ˘ ·ÛıÂÓ‹8 (›Ó·Î·˜ 1). ™‡Ìʈӷ Ì ÙËÓ ·Ú·¿Óˆ ηٿٷÍË, ·ÛıÂÓ›˜ Ù˘ Ù¿Í˘ π ·Ó·Ì¤ÓÂÙ·È Ó· ¤¯Ô˘Ó Ê˘ÛÈÔÏÔÁÈ΋ ·¿ÓÙËÛË ÛÙË ¯ÔÚ‹ÁËÛË ˘ÁÚÒÓ ÌÂÙÂÁ¯ÂÈÚËÙÈο. ∞ÛıÂÓ›˜ Ù˘ Ù¿Í˘ ππ ‹ πππ ¤¯Ô˘Ó ÛËÌ·ÓÙÈÎÔ‡ ‚·ıÌÔ‡ ·ÛΛÙË, ¿Ú· ÔÈ ·ÒÏÂȘ Û ˘ÁÚ¿ Î·È ÚˆÙ½Ó˜ ı· Â›Ó·È ÌÂÁ·Ï‡ÙÂÚ˜ Î·È Ë ¯ÔÚ‹ÁËÛË ˘ÁÚÒÓ ¯ÚÂÈ¿˙ÂÙ·È È‰È·›ÙÂÚË ÚÔÛÔ¯‹. ∞ÛıÂÓ›˜ Ù˘ Ù¿Í˘ πV ¤¯Ô˘Ó ·Ó¿ÁÎË ·fi ηıÂÙ‹Ú· ÛÙËÓ Ó¢ÌÔÓÈ΋ ‰ÈfiÙÈ Û˘Ó˘¿Ú¯ÂÈ Î·Ú‰È·Î‹ ‰˘ÛÏÂÈÙÔ˘ÚÁ›·.
ÙÔ˘ÚÁ›·˜ ÛÙÔ 1/3 ÂÚ›Ô˘ ÙˆÓ ·ÛıÂÓÒÓ. øÛÙfiÛÔ, ·Ôηı›ÛÙ·Ù·È Û‡ÓÙÔÌ· Î·È ÌfiÓÔÓ ÙÔ 5% ÙˆÓ ·ÛıÂÓÒÓ ¯ÚÂÈ¿˙ÂÙ·È ¯ÚfiÓÈ· ·ÈÌÔ‰È¿Ï˘ÛË ÌÂÙ¿ ÙË ÌÂÙ·ÌfiÛ¯Â˘ÛË ‹·ÙÔ˜9.
∞πΔπ∂™ ¶ƒøπª∏™ ¢À™§∂πΔOÀƒ°π∞™ ΔOÀ ∏¶∞Δπ∫OÀ ªO™Ã∂Àª∞ΔO™ 1) §ÂÈÙÔ˘ÚÁÈΤ˜ ñ ¶ÚˆÙÔ·ı‹˜ ‰˘ÛÏÂÈÙÔ˘ÚÁ›· ÌÔۯ‡̷ÙÔ˜ (Primary ¡on Function- PNF) 2) AÁÁÂȷΤ˜ ñ £ÚfiÌ‚ˆÛË Ë·ÙÈ΋˜ ·ÚÙËÚ›·˜ (Hepatic Artery Thrombosis – HAT) ñ £ÚfiÌ‚ˆÛË ˘Ï·›·˜ ÊϤ‚·˜ (Portal Vein Thrombosis – PVT) 3) ÃÔÏËÊfiÚ· ñ ¢È·Ê˘Á‹ ·fi ÙȘ ·Ó·ÛÙÔÌÒÛÂȘ, ·Ó·ÙÔÌÈΤ˜ ·ÓˆÌ·Ï›Â˜ 4)∞ÈÌfiÛÙ·ÛË 5)∞fiÚÚÈ„Ë
¶ƒøπª∏ ¢À™§∂πΔOÀƒ°π∞ ªO™Ã∂Àª∞ΔO™ ∏ ÚÒÈÌË ÌË ÏÂÈÙÔ˘ÚÁ›· (‰˘ÛÏÂÈÙÔ˘ÚÁ›·) ÙÔ˘ ÌÔۯ‡̷ÙÔ˜ (primary non function-PNF) ‹ Ë ‚·ÚÈ¿ Ë·ÙÈ΋ ·Ó¿ÚÎÂÈ· ¤¯Ô˘Ó ‰˘ÛÌÂÓ‹ ¤Î‚·ÛË, fiˆ˜ ı¿Ó·ÙÔ˜ ‹ ·Ó¿ÁÎË ÁÈ· ·ӷÌÂÙ·ÌfiÛ¯Â˘ÛË. ∏ Û˘¯ÓfiÙËÙ· Î˘Ì·›ÓÂÙ·È ·fi 6-22%, ÂÓÒ Ù· ·›ÙÈ· ·Ú·Ì¤ÓÔ˘Ó, ÂÓ ÔÏÏÔ›˜, ¿ÁÓˆÛÙ·. ø˜ ·ÈÙÈÔÏÔÁÈÎÔ› ·Ú¿ÁÔÓÙ˜ ÂÓÔ¯ÔÔÈÔ‡ÓÙ·È ÔÈ ·Ú¿ÁÔÓÙ˜ ÎÈÓ‰‡ÓÔ˘ Ô˘ Û¯ÂÙ›˙ÔÓÙ·È: Ì ÙÔÓ ‰fiÙË: ñ ¶ÚÔ¯ˆÚË̤ÓË ËÏÈΛ· >50¯ÚÔ-
ÓÒÓ
ª∂Δ∂°Ã∂πƒ∏Δπ∫∏ ¡∂ºƒπ∫∏ ¢À™§∂πΔOÀƒ°π∞ ªÂÙ¿ ÙË ÌÂÙ·ÌfiÛ¯Â˘ÛË ‹·ÙÔ˜ ·Ú·ÙËÚÂ›Ù·È Û˘¯Ó¿ ‰˘ÛÏÂÈÙÔ˘ÚÁ›· ÙˆÓ ÓÂÊÚÒÓ, Ë ÔÔ›· ηٷϋÁÂÈ Û Â͈ۈ̷ÙÈ΋ ˘ÔÛÙ‹ÚÈÍË Ù˘ ÓÂÊÚÈ΋˜ ÏÂÈ-
ñ ª·ÎÚÔÛÙ¿وÛË >30% ñ º‡ÏÔ (F>M)
ÌÂ ÙÔÓ Ï‹ÙË: ñ ™Ô‚·Ú‹ ÂÁÎÂÊ·ÏÔ¿ıÂÈ· ñ PTT >50sec
METAMO™XEY™Eπ™ 2008
121
¢π∞ºÀ°∏ ∞¶O Δ∞ ÃO§∏ºOƒ∞
ÌÂÙ·‚ÔÏÈÎÔ›: ñ ∞ÂÏ¢ı¤ÚˆÛË ÂÏ¢ı¤ÚˆÓ ÚÈ-
˙ÒÓ? ñ ¢È·Ù·Ú·¯¤˜ Ù˘ ΢ÙÙ·ÚÈ΋˜ ÌÂÌ‚Ú¿Ó˘? ñ ∞ÓÔÛÔÏÔÁÈÎÔ› ·Ú¿ÁÔÓÙ˜ ? ∏ ‰È¿ÁÓˆÛË Ù˘ PNF ÛÙËÚ›˙ÂÙ·È ÛÙ· ÎÚÈÙ‹ÚÈ· UNOS Î·È Â›Ó·È Ù· ·Ú·Î¿Ùˆ: ¯ÚfiÓÔ˜ ÂÌÊ¿ÓÈÛ˘ ≤ 10 ËÌÂÚÒÓ, SGOT ≥5000 IU/L, INR≥3.0 sec (·Û¯¤Ùˆ˜ Ù˘ ¯ÔÚ‹ÁËÛ˘ FFP) ‹ ÔͤˆÛË (pH ≤ 7.3) Î·È Û˘ÁΤÓÙÚˆÛË Á·Ï·ÎÙÈÎÒÓ ‰ÈÏ¿ÛÈ· ÙˆÓ Ê˘ÛÈÔÏÔÁÈÎÒÓ ÙÈÌÒÓ. ∂›Û˘, ¿ÏÏ· ÎÚÈÙ‹ÚÈ· Ô˘ ı¤ÙÔ˘Ó ÙËÓ ˘fiÓÔÈ· PNF Â›Ó·È Ë ˘ÔÁÏ˘Î·ÈÌ›·, Ë ˘ÂÚηÏÈ·ÈÌ›·, Ë ˘ÂÚ¯ÔÏÂÚ˘ıÚÈÓ·ÈÌ›·, Ë ÂÌÊ¿ÓÈÛË ÏÔÈÌÒ͈Ó, ÙÔ ÌÈÎÚÔ‡ ÌÂÁ¤ıÔ˘˜ ÌfiÛ¯Â˘Ì· (hyperperfusion), Ë ·Ú·ÙÂٷ̤ÓË ÓÔÛËÏ›· ÙÔ˘ ‰fiÙË ÛÙË ª∂£ Î·È Ë ·ÈÌÔ‰˘Ó·ÌÈ΋ ·ÛÙ¿ıÂÈ·. ∏ ıÂڷ›· ÛÙË ª∂£ ÂÚÈÏ·Ì‚¿ÓÂÈ ·ÈÌÔ‰˘Ó·ÌÈ΋ Î·È ·Ó·Ó¢ÛÙÈ΋ ˘ÔÛÙ‹ÚÈÍË, ‰ÈfiÚıˆÛË Ù˘ ÔͤˆÛ˘ Î·È ÙˆÓ ÏÔÈÒÓ ÌÂÙ·‚ÔÏÈÎÒÓ Î·È ËÏÂÎÙÚÔÏ˘ÙÈÎÒÓ ‰È·Ù·Ú·¯ÒÓ, Â͈ۈ̷ÙÈ΋ ˘ÔÛÙ‹ÚÈÍË Ù˘ ÓÂÊÚÈ΋˜ ÏÂÈÙÔ˘ÚÁ›·˜, ¯ÔÚ‹ÁËÛË Nacetylocysteine ˆ˜ ‰ÂÛÌÂ˘Ù‹ ÙˆÓ ÂÏ¢ı¤ÚˆÓ ÚÈ˙ÒÓ, ÚÔÛÙ·ÁÏ·Ó‰›Ó˘ (Ì ·ÌÊÈÛ‚ËÙÔ‡ÌÂÓÔ ÎÏÈÓÈÎfi ·ÔÙ¤ÏÂÛÌ·) ηÈ, Ù¤ÏÔ˜, Â͈ۈ̷ÙÈ΋ ˘ÔÛÙ‹ÚÈÍË Ù˘ Ë·ÙÈ΋˜ ÏÂÈÙÔ˘ÚÁ›·˜.
∞°°∂π∞∫∂™ ∂¶π¶§O∫∂™ ∏ Û˘¯ÓfiÙËÙ· ÂÌÊ¿ÓÈÛ˘ ·ÁÁÂÈ·ÎÒÓ ÂÈÏÔÎÒÓ Î˘Ì·›ÓÂÙ·È ·fi 8-14%10. ∂ÌÊ·Ó›˙ÔÓÙ·È Û˘Ó‹ıˆ˜ ÙËÓ ÚÒÙË ÌÂÙÂÁ¯ÂÈÚËÙÈ΋ ̤ڷ, ·Ó Î·È ÌÔÚ› Ó· ÂÌÊ·ÓÈÛıÔ‡Ó ÌÂÚÈΤ˜ ‚‰ÔÌ¿‰Â˜ ÌÂÙ¿ ÙËÓ Â¤Ì‚·ÛË. ∏ ıÚfiÌ‚ˆÛË Â›Ó·È Ë Ï¤ÔÓ ÚÒÈÌË ÂÈÏÔ΋, ÂÓÒ Ë ÛÙ¤ÓˆÛË Î·È ÙÔ „¢‰Ô·Ó‡ڢÛÌ· Û¯ËÌ·Ù›˙ÔÓÙ·È ·ÚÁfiÙÂÚ·. ∏ ÎÏÈÓÈ΋ ÂÈÎfiÓ· ÔÈΛÏÏÂÈ ·fi ·Û˘Ìو̷ÙÈ΋ ·‡ÍËÛË ÙˆÓ Ë·ÙÈÎÒÓ ÂÓ˙‡ÌˆÓ ̤¯ÚÈ ÔÍ›· ÎÂÚ·˘ÓÔ‚fiÏÔ Ë·ÙÈ΋ ·Ó¿ÚÎÂÈ·. ∞·ÈÙÂ›Ù·È Â›ÁÔ˘Û· Ï··ÚÔÙÔÌ›· Î·È ·Ó·ıÂÒÚËÛË Ù˘ ·Ó·ÛÙfïÛ˘ Ù˘ Ë·ÙÈ΋˜ ·ÚÙËÚ›·˜, ÂÓÒ, Û˘¯Ó¿ ··ÈÙÂ›Ù·È Â·Ó·ÌÂÙ·ÌfiÛ¯Â˘ÛË ÏfiÁˆ Ë·ÙÈ΋˜ Ó¤ÎÚˆÛ˘. ∏ ıÚfiÌ‚ˆÛË Ù˘ ˘Ï·›·˜ ÊϤ‚·˜ ·Ó·Ù‡ÛÛÂÙ·È Û·ÓÈfiÙÂÚ· Ì ·Ì‚Ï˯ڋ Û˘Ìو̷ÙÔÏÔÁ›·, Ì ÂÈÎfiÓ· ·ÛΛÙË Î·È ÎÈÚÛÔÚÚ·Á›·˜. ∏ ·ÓÙÈÌÂÙÒÈÛË Û˘Ó›ÛÙ·Ù·È Û ıÚÔÌ‚ÂÎÙÔÌ‹ Î·È ·Ó·ıÂÒÚËÛË Ù˘ ·Ó·ÛÙfïÛ˘, ÂÊ’ fiÛÔÓ ‰È·ÁÓˆÛı› ÂÁη›Úˆ˜ ·˘Ù‹ Ë ÂÈÏÔ΋.
OÈ ÂÈÏÔΤ˜ ·fi Ù· ¯ÔÏËÊfiÚ· ÚÔ·ÙÔ˘Ó ÛÙÔ 15% ÂÚ›Ô˘ ÙˆÓ ·ÛıÂÓÒÓ Ì ÔÚıÔÙÔÈ΋ ÌÂÙ·ÌfiÛ¯Â˘ÛË ‹·ÙÔ˜11. ∞fi ·˘Ù¤˜, Ë ÈÔ Û˘ÓËıÈṲ̂ÓË Â›Ó·È Ë ‰È·Ê˘Á‹ ¯ÔÏ‹˜ , fiÔ˘ Ù· Û˘ÌÙÒÌ·Ù· ‰ÂÓ Â›Ó·È ÂȉÈο Î·È ÂÚÈÏ·Ì‚¿ÓÔ˘Ó ˘ÚÂÙfi, ¿Ù˘· ÎÔÈÏȷο ¿ÏÁË Î·È ÛËÌ›· ÊÏÂÁÌÔÓ‹˜ ÙÔ˘ ÂÚÈÙÔÓ·›Ô˘. ∏ ‰È¿ÁÓˆÛË Ù›ıÂÙ·È Ì ¯ÔÏ·ÁÁÂÈÔÁÚ·Ê›· Î·È Ë ıÂڷ›· Û˘Ó›ÛÙ·Ù·È Â›Ù ÛÙËÓ ÂÓ‰ÔÛÎÔÈ΋ ÙÔÔı¤ÙËÛË stents ›Ù ÛÙËÓ ¯ÂÈÚÔ˘ÚÁÈ΋ ·ÔηٿÛÙ·ÛË. OÈ ÛÙÂÓÒÛÂȘ Î·È Ë ·ÚÔ˘Û›· Ï›ıˆÓ ÛÙÔ ¯ÔÏËÊfiÚÔ ‰¤Ó‰ÚÔ ÂÌÊ·Ó›˙ÔÓÙ·È ÛÙËÓ ·ÒÙÂÚË ÌÂÙÂÁ¯ÂÈÚËÙÈ΋ ÂÚ›Ô‰Ô. ∏ ·fiÊÚ·ÍË ·ÓÙÈÌÂÙˆ›˙ÂÙ·È ÂÓ‰ÔÛÎÔÈο ‹ ̤ۈ Ù˘ ÂÂÌ‚·ÙÈ΋˜ ·ÎÙÈÓÔÏÔÁ›·˜, ÂÓÒ Ë ¯ÂÈÚÔ˘ÚÁÈ΋ ·ÔηٿÛÙ·ÛË Â›Ó·È, οÔȘ ÊÔÚ¤˜, ·Ó·fiÊ¢ÎÙË12.
∞¶Oƒƒπæ∏ ∏ ·fiÚÚÈ„Ë ÙÔ˘ Ë·ÙÈÎÔ‡ ÌÔۯ‡̷ÙÔ˜ ·Ú·Ì¤ÓÂÈ ÌÈ· ÛËÌ·ÓÙÈ΋ ·ÈÙ›· ıÓËÙfiÙËÙ·˜ Û ·ÛıÂÓ›˜ Ô˘ ˘Ô‚Ï‹ıËÎ·Ó Û ÌÂÙ·ÌfiÛ¯Â˘ÛË ‹·ÙÔ˜13. ¢È·ÎÚ›ÓÔÓÙ·È 3 ηÙËÁÔڛ˜: ˘ÂÚÔÍ›·, ÔÍ›· Î·È ¯ÚfiÓÈ·. ∏ ˘ÂÚÔÍ›· ·fiÚÚÈ„Ë ˘ÚÔ‰ÔÙÂ›Ù·È ·fi ÚÔÛ¯ËÌ·ÙÈṲ̂ӷ ·ÓÙÈÛÒÌ·Ù· ÂÓ¿ÓÙÈ· ÛÙ· ·ÓÙÈÁfiÓ· ÙÔ˘ ‰fiÙË Î·È ÂÌÊ·Ó›˙ÂÙ·È ¿ÌÂÛ·, ÌÂÙ¿ ÙËÓ Â¤Ì‚·ÛË. ∏ ·ÓÔÛÔηٷÛÙ·ÏÙÈ΋ ıÂڷ›· Â›Ó·È ·Ó·ÔÙÂÏÂÛÌ·ÙÈ΋ Û’ ·˘Ù‹ ÙË ÂÚ›ÙˆÛË Î·È Ë ÌfiÓË Ï‡ÛË Â›Ó·È Ë Â·Ó·ÌÂÙ·ÌfiÛ¯Â˘ÛË. ∏ ÔÍ›· ·fiÚÚÈ„Ë Â›Ó·È ÈÔ Û˘¯Ó‹ Î·È ·ÚÔ˘ÛÈ¿˙ÂÙ·È ÛÙÔ 20% ÙˆÓ ÌÂÙ·ÌÔۯ‡ÛÂˆÓ ÓÂÊÚÒÓ·ÁÎÚ¤·ÙÔ˜, 30% ‹·ÙÔ˜ Î·È 40% Ó¢ÌfiÓˆÓηډȿ˜ ÙÔÓ ÚÒÙÔ ¯ÚfiÓÔ. ™˘Ó‹ıˆ˜ Ë ·fiÚÚÈ„Ë ‰ÂÓ Â›Ó·È ÂÌÊ·Ó‹˜ ÙȘ ÚÒÙ˜ ̤Ú˜ ÌÂÙ¿ ÙË ÌÂÙ·ÌfiÛ¯Â˘ÛË. ¶ÚÔ·ÙÂÈ Û·Ó ·ÔÙ¤ÏÂÛÌ· Ù˘ ΢ÙÙ·ÚÈ΋˜ ·ÓÔÛ›·˜ ηÈ, ÁÂÓÈο, ··ÓÙ¿ ηϿ ÛÙ· ÈÛ¯˘Ú¿ ·ÓÔÛÔηٷÛÙ·ÏÙÈο Û¯‹Ì·Ù·. ∏ ¯ÚfiÓÈ· ·fiÚÚÈ„Ë, Û˘Ó‹ıˆ˜, ‰ÂÓ ·Ó·Ù‡ÛÛÂÙ·È Î·Ù¿ ÙË ‰È¿ÚÎÂÈ· Ù˘ ÓÔÛËÏ›·˜ ÙÔ˘ ·ÛıÂÓÔ‡˜ ÛÙË ª∂£, ˆÛÙfiÛÔ ÔÈ ·ÛıÂÓ›˜ ¯Ú‹˙Ô˘Ó ÓÔÛËÏ›·˜ ÛÙË ª∂£, ÏfiÁˆ ÙˆÓ ÂÈÏÔÎÒÓ Ù˘ ¯ÚfiÓÈ·˜ ÊÏÂÁÌÔÓ‹˜ Î·È ›ÓˆÛ˘ Ô˘ ¯·Ú·ÎÙËÚ›˙Ô˘Ó ·˘ÙÔ‡ ÙÔ˘ ›‰Ô˘˜ ÙËÓ ·fiÚÚÈ„Ë. OÈ ÂΉËÏÒÛÂȘ Ù˘ ¯ÚfiÓÈ·˜ ·fiÚÚȄ˘ ¤¯Ô˘Ó ȉȷ›ÙÂÚ· ¯·Ú·ÎÙËÚÈÛÙÈο ÁÈ· ÙÔ Â›‰Ô˜ ÙÔ˘ ÔÚÁ¿ÓÔ˘, ¤ÙÛÈ ÛÙË ÌÂÙ·ÌfiÛ¯Â˘ÛË ‹·ÙÔ˜ ϤÁÂÙ·È “Û‡Ó‰ÚÔÌÔ ·Ô˘Û›·˜ ¯ÔÏˉfi¯Ô˘ fiÚÔ˘ – vanishing-bile-duct syndrome”. ∏ ÏÂÈÙÔ˘ÚÁ›· ÙÔ˘ ÌÔۯ‡̷ÙÔ˜ ÌÔÚ› Ó· ·-
122
ª. ¶∞™∞∫πøΔ√À
ڷ̤ÓÂÈ ÛÙ·ıÂÚ‹ Û ÔÏÏÔ‡˜ ·ÛıÂÓ›˜, ÛÙÔ˘˜ ÔÔ›Ô˘˜ ¤¯Ô˘Ó ‚ÚÂı› ÂÛÙȷΤ˜ ‹ ‹È˜ ÈÛÙÔÏÔÁÈΤ˜ ·ÏÏÔÈÒÛÂȘ ·fiÚÚȄ˘, ·ÎfiÌ· Î·È fiÙ·Ó ‰ÂÓ ¯ÔÚËÁÂ›Ù·È ·ÁˆÁ‹14. ∞˘Ù‹ Ë Û˘ÛÛÒÚ¢ÛË ÙˆÓ ÏÂÌÊÔ΢ÙÙ¿ÚˆÓ ÛÙÔ ÌfiÛ¯Â˘Ì· ˘ÔÙ›ıÂÙ·È fiÙÈ Û˘Ì‚¿ÏÏÂÈ ÛÙËÓ ·Ó¿Ù˘ÍË ÂÓfi˜ ‚·ıÌÔ‡ ·ÓÔÛÔÏÔÁÈ΋˜ ·ÓÔ¯‹˜ Î·È ·ÓÙÔ¯‹˜. ∞fi ÙËÓ ¿ÏÏË ÏÂ˘Ú¿, ÂÚ›Ô˘ ÙÔ 5-10% ÙˆÓ Ë·ÙÈο ÌÂÙ·ÌÔÛ¯Â˘Ì¤ÓˆÓ Ô˘ ÂÌÊ·Ó›˙Ô˘Ó ÔÍ›· ΢ÙÙ·ÚÈ΋ ·fiÚÚÈ„Ë, ηٷϋÁÔ˘Ó Û ÛÔ‚·Ú‹ ·fiÚÚÈ„Ë ·Ú¿ ÙËÓ ·ÓÙÈ·ÔÚÚÈÙÈ΋ ·ÁˆÁ‹15. ∞˘ÙÔ› ÔÈ ·ÛıÂÓ›˜ ¯ÚÂÈ¿˙ÔÓÙ·È Â·Ó·ÌÂÙ·ÌfiÛ¯Â˘ÛË.
O ¯ÚfiÓÔ˜ Î·È ÔÈ ·Ú¿ÁÔÓÙ˜ ÎÈÓ‰‡ÓÔ˘ ÁÈ· ·fiÚÚÈ„Ë ∏ ÚÒÈÌË ÔÍ›· ΢ÙÙ·ÚÈ΋ ·fiÚÚÈ„Ë ÂÌÊ·Ó›˙ÂÙ·È Ì¤Û· Û 5-30 ̤Ú˜ ·fi ÙË ÌÂÙ·ÌfiÛ¯Â˘ÛË ‹·ÙÔ˜. Δ· ÂÂÈÛfi‰È· Ù˘ ÚÒÈÌ˘ ÔÍ›·˜ ·fiÚÚȄ˘ ‰ÂÓ ÂËÚ¿˙Ô˘Ó ·ÚÓËÙÈο ÙÔ ÌfiÛ¯Â˘Ì· ‹ ÙËÓ ¤Î‚·ÛË ÙÔ˘ ·ÛıÂÓÔ‡˜16. Δ· ÂÂÈÛfi‰È· Ù˘ ·ÒÙÂÚ˘ ΢ÙÙ·ÚÈ΋˜ ·fiÚÚȄ˘ Û˘¯Ó¿ Û˘Ó‰¤ÔÓÙ·È Ì ¯·ÌËÏ¿ ›‰· ΢ÎÏÔÛÔÚ›Ó˘ ‹ tacrolimus ÛÙÔ ·›Ì·, fiˆ˜ ›Û˘ Î·È Ì ¯·ÌËÏ‹ ÂÈ‚›ˆÛË ÙÔ˘ ÌÔۯ‡̷ÙÔ˜. ™Â ÌÈ· ÌÂϤÙË ÙˆÓ Wiesner et al 17, Û 762 ÂÓ‹ÏÈΘ Ô˘ ˘Ô‚Ï‹ıËÎ·Ó Û ÌÂÙ·ÌfiÛ¯Â˘ÛË ‹·ÙÔ˜, ÔÈ 490 (64%) ÂÌÊ¿ÓÈÛ·Ó ÙÔ˘Ï¿¯ÈÛÙÔÓ ¤Ó· ÂÂÈÛfi‰ÈÔ ·fiÚÚȄ˘, Û˘Ó‹ıˆ˜ ÙȘ ÚÒÙ˜ 6 ‚‰ÔÌ¿‰Â˜ ·fi ÙË ÌÂÙ·ÌfiÛ¯Â˘ÛË. ¶ÂÚ›Ô˘ ÙÔ 20% ·˘ÙÒÓ ÙˆÓ ·ÛıÂÓÒÓ ·Ó¤Ù˘Í·Ó Î·È ‰Â‡ÙÂÚÔ ÂÂÈÛfi‰ÈÔ ·fiÚÚȄ˘ ̤۷ ÛÙÔÓ ÚÒÙÔ ¯ÚfiÓÔ ·fi ÙË ÌÂÙ·ÌfiÛ¯Â˘ÛË. OÈ Ramji et al 18 ·Ó·Ê¤ÚÔ˘Ó ·ÒÙÂÚË ÔÍ›· ·fiÚÚÈ„Ë ( ÌÂÙ¿ ·fi 180 ̤Ú˜) Û 97 ·fi 415 ·ÛıÂÓ›˜ (23%). OÈ ÂÚÈÛÛfiÙÂÚÔÈ (73%) ·¿ÓÙËÛ·Ó ÛÙËÓ ÂÓ‰ÔÊϤ‚È· ¯ÔÚ‹ÁËÛË ÛÙÂÚÔÂȉÒÓ, ÂÓÒ ÙÔ 5% ·ÚÔ˘Û›·Û·Ó ·ÓÙ›ÛÙ·ÛË ÛÙ· ÛÙÂÚÔÂȉ‹. ∏ ·ÒÙÂÚË ·fiÚÚÈ„Ë ‹Ù·Ó Û·ÓÈfiÙÂÚË Û ÂΛÓÔ˘˜ Ô˘ ˘Ô‚Ï‹ıËÎ·Ó Û ÌÂÙ·ÌfiÛ¯Â˘ÛË ÏfiÁˆ Ë·ÙÈ΋˜ ‚Ï¿‚˘ ·fi ÈÔÁÂÓ‹ ·ÈÙÈÔÏÔÁ›·. OÈ Soin et al15 ‚Ú‹Î·Ó fiÙÈ ·fi 717 Ë·ÙÈο ÌÂÙ·ÌÔÛ¯Â˘Ì¤ÓÔ˘˜, ÙÔ 7,5% ›¯·Ó ÙÔ˘Ï¿¯ÈÛÙÔÓ ¤Ó· ÂÂÈÛfi‰ÈÔ ·ÒÙÂÚ˘ ÔÍ›·˜ ·fiÚÚȄ˘, Ô˘ ÂÌÊ·Ó›ÛıËÎ·Ó ÙÔÓ ÚÒÙÔ ¯ÚfiÓÔ, ÂÓÒ ˘‹ÚÍ·Ó Î·È ÂÚÈÙÒÛÂȘ ·fiÚÚȄ˘ 6 ¯ÚfiÓÈ· ÌÂÙ¿ ÙË ÌÂÙ·ÌfiÛ¯Â˘ÛË. ŒÙÛÈ, Ô fiÚÔ˜ «ÔÍ›·» Ì¿ÏÏÔÓ ‰ÂÓ Â›Ó·È ‰fiÎÈÌÔ˜ ÁÈ· ÙËÓ ÂÚÈÁÚ·Ê‹ ·˘ÙÔ‡ ÙÔ˘ Ù‡Ô˘ Ù˘ ·fiÚÚȄ˘. ∂ÎÙfi˜ ·fi Ù· ¯·ÌËÏ¿ ›‰· ·ÓÔÛÔηٷÛÙ·ÏÙÈÎÒÓ Ô˘ ·ÓȯÓ‡ıËÎ·Ó ÛÙÔ ·›Ì·, ˘¿Ú¯Ô˘Ó Î·È ¿ÏÏÔÈ ·Ú¿ÁÔÓÙ˜ Ô˘ ÂÓÔ¯ÔÔÈÔ‡ÓÙ·È ÁÈ· ÙËÓ
ÔÍ›· ΢ÙÙ·ÚÈ΋ ·fiÚÚÈ„Ë. ∞ÓÂÍ¿ÚÙËÙ˜ ÌÂÙ·‚ÏËÙ¤˜ Ô˘ Û˘Ó‰¤ÔÓÙ·È Ì ÙËÓ ÔÍ›· ΢ÙÙ·ÚÈ΋ ·fiÚÚÈ„Ë Ì¤Û· Û 42 ̤Ú˜ ·fi ÙË ÌÂÙ·ÌfiÛ¯Â˘ÛË ÂÚÈÏ·Ì‚¿ÓÔ˘Ó ÙË ÌÈÎÚfiÙÂÚË ËÏÈΛ· ÙÔ˘ Ï‹ÙË (·fi ·˘Ù‹ ÙÔ˘ ‰fiÙË), ¯·ÌËÏ‹ ÈÛÙÔÛ˘Ì‚·ÙfiÙËÙ· HLA-DR, ‹ ¯ÚfiÓÔ „˘¯Ú‹˜ ÈÛ¯·ÈÌ›·˜ ÌÂÁ·Ï‡ÙÂÚÔ ·fi 15 ÒÚ˜17. ™ÙÔ˘˜ ·ÛıÂÓ›˜ Ô˘ ÌÂÙ·ÌÔۯ‡ıËÎ·Ó ÏfiÁˆ ·ÏÎÔÔÏÈ΋˜ ΛÚÚˆÛ˘ ·Ú·ÙËÚ‹ıËΠ¯·ÌËÏfi˜ Ú˘ıÌfi˜ ΢ÙÙ·ÚÈ΋˜ ·fiÚÚȄ˘, ·ÓÙ›ıÂÙ· ·fi ÙÔ˘˜ ·ÛıÂÓ›˜ Ô˘ ÙÔ ·›ÙÈÔ Ù˘ Ë·ÙÈ΋˜ ÌÂÙ·ÌfiÛ¯Â˘Û˘ ‹Ù·Ó ·˘ÙÔ¿ÓÔÛÔ ÓfiÛËÌ·16. ∏ ηٿÛÙ·ÛË Ù˘ ıÚ¤„˘ ·›˙ÂÈ ÚfiÏÔ ÛÙËÓ ·Ó¿Ù˘ÍË Ù˘ ÔÍ›·˜ ΢ÙÙ·ÚÈ΋˜ ·fiÚÚȄ˘, Û‡Ìʈӷ Ì ÙËÓ ÂÚÁ·Û›· ÙˆÓ Bathgate et al 19, ÛÙËÓ ÔÔ›· ·Ú·Ù‹ÚËÛ·Ó fiÙÈ Ë ÂÚ›ÌÂÙÚÔ˜ ÙÔ˘ ‚Ú·¯›ÔÓ· Û˘Ó‰¤ÂÙ·È Ì ÙË Û˘¯ÓfiÙËÙ· ÂÌÊ¿ÓÈÛ˘ ·fiÚÚȄ˘. ∂›Û˘, ÔÈ Rosen et al20 ‚Ú‹Î·Ó fiÙÈ Ô ÁÔÓfiÙ˘Ô˜ gB1 ÙÔ˘ ΢ÙÙ·ÚÔÌÂÁ·ÏÔ˚Ô‡ (CMV) Û˘Ó‰¤ÂÙ·È Ì ÌÈ· ·˘ÍË̤ÓË Û˘¯ÓfiÙËÙ· ÔÍ›·˜ ·fiÚÚȄ˘.
∫ÏÈÓÈ΋ – ÂÚÁ·ÛÙËÚȷ΋ ÂÈÎfiÓ· ¶ÔÏÏ¿ Î·È ÔÈΛÏÏ· Â›Ó·È Ù· Û˘ÌÙÒÌ·Ù· Ô˘ ÂÌÊ·Ó›˙ÔÓÙ·È ÛÙÔ˘˜ ·ÛıÂÓ›˜ Ì ·fiÚÚÈ„Ë, fiˆ˜ ˘ÚÂÙfi˜, ηÎÔ˘¯›·, ÎÔÈÏȷο ¿ÏÁË, Ë·ÙÔÌÂÁ·Ï›·, ÛÏËÓÔÌÂÁ·Ï›·, ÂȉÂÈÓÔ‡ÌÂÓÔ˜ ·ÛΛÙ˘, ηӤӷ fï˜ ·fi Ù· ·Ú·¿Óˆ ‰ÂÓ Â›Ó·È ·ıÔÁÓˆÌÔÓÈο ÁÈ· ÙËÓ ·fiÚÚÈ„Ë. ∏ ˘fiÓÔÈ· Ù›ıÂÙ·È fiÙ·Ó ˘¿Ú¯Ô˘Ó ‰È·Ù·Ú·¯¤˜ ÛÙȘ ÙÈ̤˜ ÙˆÓ ÂÚÁ·ÛÙËÚÈ·ÎÒÓ: ·Ú·ÙËÚÂ›Ù·È ·‡ÍËÛË ÙˆÓ ÙÚ·ÓÛ·ÌÈÓ·ÛÒÓ, Ù˘ ·ÏηÏÈ΋˜ ʈÛÊ·Ù¿Û˘, Ù˘ Á-ÁÏÔ˘Ù·Ì˘Ï-ÙÚ·ÓÛÂÙȉ¿Û˘ Î·È Ù˘ ¯ÔÏÂÚ˘ıÚ›Ó˘. ¶¿ÓÙˆ˜, ·˘Ù¤˜ ÔÈ ‚ÈÔ¯ËÌÈΤ˜ ·Ú¿ÌÂÙÚÔÈ ‰ÂÓ Â›Ó·È Ô‡Ù ¢·›ÛıËÙ˜ Ô‡Ù ÂȉÈΤ˜ ÁÈ· Ó· ‰È·ÊÔÚԉȷÁÓˆÛı› Ë ÔÍ›· ΢ÙÙ·ÚÈ΋ ·fiÚÚÈ„Ë ·fi ÔÔÈ·‰‹ÔÙ ¿ÏÏË ‰˘ÛÏÂÈÙÔ˘ÚÁ›· ÙÔ˘ Ë·ÙÈÎÔ‡ ÌÔۯ‡̷ÙÔ˜ Î·È ‰ÂÓ Û˘Ó‰¤ÂÙ·È Ì ÙË ‚·Ú‡ÙËÙ· ÙˆÓ ·ÔÚÚÈÙÈÎÒÓ ÂÂÈÛÔ‰›ˆÓ. ∂Í ·ÈÙ›·˜ ·˘ÙÒÓ ÙˆÓ ÂÚÈÔÚÈÛÌÒÓ, ·ÍÈÔÏÔÁ‹ıËÎ·Ó ¿ÏϘ ‚ÈÔ¯ËÌÈΤ˜ ·Ú¿ÌÂÙÚÔÈ ÁÈ· ÙË ‰È¿ÁÓˆÛË Ù˘ ·fiÚÚȄ˘ ÙÔ˘ Ë·ÙÈÎÔ‡ ÌÔۯ‡̷ÙÔ˜, ÏËÓ Ù˘ ‚ÈÔ„›·˜ ÙÔ˘ ‹·ÙÔ˜. ¶ÚÔÙ¿ıËÎ·Ó Û·Ó ‰Â›ÎÙ˜ ·fiÚÚȄ˘ ÙÔ˘ Ë·ÙÈÎÔ‡ ÌÔۯ‡̷ÙÔ˜ Ë Ì¤ÙÚËÛË ÙˆÓ Û˘ÁÎÂÓÙÚÒÛÂˆÓ ÛÙÔÓ ÔÚfi ÙˆÓ ÂȤ‰ˆÓ ÙÔ˘ ˘Ô‰Ô¯¤· Ù˘ ÈÓÙÂÚÏ¢ΛÓ˘-2 (interleukin-2 receptor), CD8 Î·È ÙˆÓ ‰È·Î˘ÙÙ¿ÚÈˆÓ ÌÔÚÈ·ÎÒÓ Û˘ÌʇÛˆÓ21. øÛÙfiÛÔ, ÔÈ ÌÂÙÚ‹ÛÂȘ ·˘Ù¤˜ ‰ÂÓ Â›Ó·È ·ÎÚȂ›˜ Û ÌÂÙ·ÌÔÛ¯Â˘Ì¤ÓÔ˘˜ ·ÛıÂÓ›˜ Ì CMV Ë·Ù›Ùȉ·. ÕÏÏÔÈ ‰Â›ÎÙ˜ ÂÚÈÏ·Ì‚¿ÓÔ˘Ó ÙË Ì¤ÙÚËÛË Ù˘ ‚‹Ù·-2-ÌÈÎÚÔÛÊ·ÈÚ›Ó˘ (beta-2-
METAMO™XEY™Eπ™ 2008
microglobulin) ÛÙÔÓ ÔÚfi Î·È ÛÙË ¯ÔÏ‹, ÙÔ˘ tumor necrosis factor-alpha (TNF-·) ÛÙÔÓ ÔÚfi, ÙÔ˘ ·ÚÈıÌÔ‡ ÙˆÓ ËˆÛÈÓfiÊÈÏˆÓ ÛÙÔ ·›Ì· Î·È ÙÔ˘˜ ÈÛÙÔ‡˜ Î·È Ù˘ ÈÓÙÂÚÏ¢ΛÓ˘-6 ÛÙË ¯ÔÏ‹21. ¶¿ÓÙˆ˜, ·˘ÙÔ› ÔÈ ‰Â›ÎÙ˜ ‰ÂÓ ¯ÚËÛÈÌÔÔÈÔ‡ÓÙ·È ·ÎfiÌË ÛÙËÓ Î·ıËÌÂÚÈÓ‹ Ú·ÎÙÈ΋, ˘Ô¯ÚÂÒÓÔÓÙ·˜ ÙÔ˘˜ È·ÙÚÔ‡˜ Ó· ηٷʇÁÔ˘Ó ÛÙËÓ ÎÏ·ÛÛÈ΋ ‚ÈÔ„›· ÙÔ˘ ‹·ÙÔ˜ Î·È ÙËÓ ÈÛÙÔÏÔÁÈ΋ ÌÂϤÙË ÙÔ˘ ·Ú·Û΢¿ÛÌ·ÙÔ˜.
μÈÔ„›· ‹·ÙÔ˜ ∏ ÈÛÙÔÏÔÁÈ΋ ÂͤٷÛË ÙÔ˘ ‹·ÙÔ˜ ·Ú·Ì¤ÓÂÈ Ë ÂͤٷÛË ÂÎÏÔÁ‹˜ Ù˘ ÔÍ›·˜ ·fiÚÚȄ˘ ÙÔ˘ ÌÔۯ‡̷ÙÔ˜. ∏ ‚ÈÔ„›· ÙÔ˘ ‹·ÙÔ˜, ·Ú¿ ÙËÓ ·‰È·ÌÊÈÛ‚‹ÙËÙË ¯ÚËÛÈÌfiÙËÙ¿ Ù˘, ÂÓ¤¯ÂÈ ÎÈÓ‰‡ÓÔ˘˜ ÂÈÏÔÎÒÓ ÛÙÔ˘˜ ÌÂÙ·ÌÔÛ¯Â˘Ì¤ÓÔ˘˜ ·ÛıÂÓ›˜. ™Â ÌÈ· ÌÂϤÙË ÙˆÓ Bubak et al22, ÙÔ 1,8% ÙˆÓ ‚ÈÔ„ÈÒÓ ‹·ÙÔ˜ Û˘Óԉ¢fiÙ·Ó ·fi ÂÈÏÔΤ˜, Ì ÛÔ‚·ÚfiÙÂÚË ÙË Û‹„Ë. À¿Ú¯Ô˘Ó ÙÚÂȘ ÈÛÙÔÏÔÁÈΤ˜ ÔÓÙfiÙËÙ˜ Ô˘ Û˘Ó‰¤ÔÓÙ·È Ì ÙËÓ Î˘ÙÙ·ÚÈ΋ ·fiÚÚÈ„Ë: ªÈ· ÌÂÈÎÙ‹ ÊÏÂÁÌÔÓ҉˘ ‰È‹ıËÛË ÛÙËÓ ˘Ï·›· ÙÚÈ¿‰· ªË ˘Ò‰Ë˜ ¯ÔÏ·ÁÁÂÈ›ÙȘ Ô˘ ·ÊÔÚ¿ ÛÙÔ ÂÓ‰ÔÏÔ‚È·Îfi ÂÈı‹ÏÈÔ ÙÔ˘ ¯ÔÏˉfi¯Ô˘ fiÚÔ˘ ∂Ó‰ÔıËÏ›ÙȘ ∂Âȉ‹ Ë ÔÛfiÙËÙ· ÙÔ˘ ‰Â›ÁÌ·ÙÔ˜ ·›˙ÂÈ ÛËÌ·ÓÙÈÎfi ÚfiÏÔ, ÌÂÙ¿ ·fi ÌÈ· ‰ÈÂıÓ‹ Û˘Ó¿ÓÙËÛË, Û˘ÌʈӋıËΠfiÙÈ ÌÈ· ÂͤٷÛË Â›Ó·È ·ÍÈfiÈÛÙË fiÙ·Ó ¤¯Ô˘Ó ÏËÊı› ÙÔ˘Ï¿¯ÈÛÙÔÓ ‰‡Ô ÈÛÙÔÙÂÌ¿¯È· ·fi ‰‡Ô ‰È·ÊÔÚÂÙÈο ›‰·, Ô˘ ÂÚȤ¯Ô˘Ó ÙÔ˘Ï¿¯ÈÛÙÔÓ ¤ÓÙ ˘Ï·›Â˜ ÙÚÈ¿‰Â˜23. ™ÙÔ Û˘Ó¤‰ÚÈÔ ÙÔ˘ Banff, Canada ÙÔ 1995 ·ÔÊ·Û›ÛÙËΠӷ ÂÚÈÁÚ¿ÊÂÙ·È Ë ÔÍ›· ΢ÙÙ·ÚÈ΋ ·fiÚÚÈ„Ë ‚¿ÛÂÈ ÌÈ·˜ Îϛ̷η˜ ·fi 0-3. Δ· ÎÚÈÙ‹ÚÈ· ÂÚÈÏ·Ì‚¿ÓÔ˘Ó: ÂÚÈ˘Ï·›· ÊÏÂÁÌÔÓ‹ (portal inflammation), ÊÏÂÁÌÔÓ‹ ¯ÔÏ·ÁÁ›ˆÓ (bile duct inflammation) Î·È ÊÏÂÁÌÔÓ‹ ÊÏ‚ȉ›ˆÓ (venular inflammation). TÔ ¿ıÚÔÈÛÌ· ÙˆÓ ÙÚÈÒÓ scores ‰›‰ÂÈ ÙÔÓ ÙÂÏÈÎfi ‰Â›ÎÙË RAI (rejection activity index), Ô ÔÔ›Ô˜ Â›Ó·È ·ÚfiÌÔÈÔ˜ Ì ÙÔ Û‡ÛÙËÌ· ‚·ıÌÔÓfiÌËÛ˘ Ù˘ ¯ÚfiÓÈ·˜ Ë·Ù›Ùȉ·˜ (.¯ RAI ≤ 4 ‰Â›¯ÓÂÈ ‹È· ÔÍ›· ·fiÚÚÈ„Ë). O ‰Â›ÎÙ˘ ·˘Ùfi˜ ¤¯ÂÈ ·ÌÊÈÛ‚ËÙËı› ·fi ÌÈ· ÛËÌ·ÓÙÈ΋ ·Ó·‰ÚÔÌÈ΋ ÌÂϤÙË, fiÔ˘ ·Ô‰Â›¯ıËΠfiÙÈ ‰ÂÓ Û˘Ì‚·‰›˙ÂÈ Ì ÙËÓ ·¿ÓÙËÛË ÙÔ˘ ·ÛıÂÓÔ‡˜ ÛÙ· ÎÔÚÙÈÎÔÛÙÂÚÔÂȉ‹ ‹/Î·È Ì ÙËÓ ÂÈ‚›ˆÛË ÙÔ˘ ÌÔۯ‡̷ÙÔ˜24.
123
¢È·ÊÔÚÈ΋ ‰È¿ÁÓˆÛË ∏ ‰È·ÊÔÚÈ΋ ‰È¿ÁÓˆÛË Ù˘ ‰˘ÛÏÂÈÙÔ˘ÚÁ›·˜ ÙÔ˘ Ë·ÙÈÎÔ‡ ÌÔۯ‡̷ÙÔ˜ ÂÍ·ÚٿٷÈ, ηٿ ¤Ó· ÌÂÁ¿ÏÔ Ì¤ÚÔ˜, ·fi ÙË ¯ÚÔÓÈ΋ ÛÙÈÁÌ‹ Ô˘ ÂÌÊ·Ó›˙ÂÙ·È. ∫·Ù¿ ÙË ‰È¿ÚÎÂÈ· ÙˆÓ ÚÒÙˆÓ ËÌÂÚÒÓ ÌÂÙ¿ ÙË ÌÂÙ·ÌfiÛ¯Â˘ÛË, ÌË Ê˘ÛÈÔÏÔÁÈο Ë·ÙÈο ÂÚÁ·ÛÙËÚȷο Â˘Ú‹Ì·Ù· ÌÔÚ› Ó· ·ÓÙ·Ó·ÎÏÔ‡Ó Ù¯ÓÈο ‹ ÏÂÈÙÔ˘ÚÁÈο ÚÔ‚Ï‹Ì·Ù·, fiˆ˜ ıÚfiÌ‚ˆÛË Ù˘ Ë·ÙÈ΋˜ ·ÚÙËÚ›·˜, ‰È·Ê˘Á‹ ·fi ÙȘ ·Ó·ÛÙÔÌÒÛÂȘ ÙÔ˘ ¯ÔÏËÊfiÚÔ˘ ‰¤Ó‰ÚÔ˘, ÛÙÂÓÒÛÂȘ ÛÙȘ ·Ó·ÛÙÔÌÒÛÂȘ, ÚˆÙÔ·ı‹ ‰˘ÛÏÂÈÙÔ˘ÚÁ›· ÙÔ˘ ÌÔۯ‡̷ÙÔ˜, shock Î·È ÛË„·ÈÌ›·. ∞Ó Î·È ·˘Ù¿ Ù· ÚÔ‚Ï‹Ì·Ù· ÌÔÚ› Ó· Â›Ó·È ÂÌÊ·Ó‹ ÎÏÈÓÈο ‹ Ì ÙËÓ ˘ÂÚ˯ÔÙÔÌÔÁÚ·Ê›· Doppler, ˆÛÙfiÛÔ Ù· Â˘Ú‹Ì·Ù· Ù˘ ‚ÈÔ„›·˜ Â›Ó·È ÂΛӷ Ù· ÔÔ›· ı· ı¤ÛÔ˘Ó ÙËÓ ÚÒÈÌË ‰È¿ÁÓˆÛË. Δ· ·›ÙÈ· Ù˘ ‰˘ÛÏÂÈÙÔ˘ÚÁ›·˜ ÙÔ˘ ÌÔۯ‡̷ÙÔ˜ ÂÚÈÏ·Ì‚¿ÓÔ˘Ó ÏÔÈÌÒÍÂȘ ·fi ΢ÙÙ·ÚÔÌÂÁ·ÏÔ˚fi (CMV)Î·È Èfi Epstein-Barr, ˘ÔÙÚÔ‹ Ë·Ù›Ùȉ·˜ μ Î·È C, ÏÂÈÙÔ˘ÚÁÈ΋ ¯ÔÏfiÛÙ·ÛË, ÙÔÍÈÎfiÙËÙ· Ù˘ ΢ÎÏÔÛÔÚ›Ó˘, Ì·˙È΋ ·ÈÌÔÚÚ·ÁÈ΋ Ó¤ÎÚˆÛË Î·È ·Û˘Ì‚·ÙfiÙËÙ· ÔÌ¿‰·˜ ·›Ì·ÙÔ˜-·ÈÌfiÏ˘ÛË.
£Âڷ›· OÈ ˘„ËϤ˜ ‰fiÛÂȘ ÎÔÚÙÈÎÔÛÙÂÚÔÂȉÒÓ Â›Ó·È, Û˘Ó‹ıˆ˜, Ë ÚÒÙË ıÂڷ¢ÙÈ΋ ·ÓÙÈÌÂÙÒÈÛË Ù˘ ÔÍ›·˜ ΢ÙÙ·ÚÈ΋˜ ·fiÚÚȄ˘. OÈ ‰fiÛÂȘ Ù˘ ÌÂı˘ÏÚ‰ÓÈ˙ÔÏfiÓ˘ ÔÈΛÏÏÔ˘Ó ·fi 500-1000mg bolus ËÌÂÚËÛ›ˆ˜ ÁÈ· 1-3 ̤Ú˜. ™Â ÔÚÈṲ̂ӷ ΤÓÙÚ·, ÙÔ Û¯‹Ì· ·˘Ùfi ·ÎÔÏÔ˘ıÂ›Ù·È ·fi ÛÙ·‰È·Î¿ ÌÂÈÔ‡ÌÂÓË ‰fiÛË ÎÔÚÙÈÎÔÛÙÂÚÔÂȉÒÓ ‰È¿ÚÎÂÈ·˜ 6 ËÌÂÚÒÓ (Ì›ˆÛË Î·Ù¿ 200mg/∏-ÙÂÏÈ΋ ‰fiÛË 20mg ÙËÓ Ë̤ڷ), ıˆÚÒÓÙ·˜ fiÙÈ ·˘Ù‹ Ë ÌÔÚÊ‹ Ù˘ ıÂڷ›·˜ Â›Ó·È ÈÔ ·ÔÙÂÏÂÛÌ·ÙÈ΋ ÛÙËÓ ·fiÚÚÈ„Ë Î·È Û˘Ó‰¤ÂÙ·È Ì ÏÈÁfiÙÂÚ˜ ÏÔÈÌÒÍÂȘ ·fi fiÙÈ Ë ¯ÔÚ‹ÁËÛË ÌÂı˘ÏÚ‰ÓÈ˙ÔÏfiÓ˘ 1000mg ÁÈ· 3 ̤Ú˜25. ¶ÂÚ›Ô˘, ÙÔ 70-80% ÙˆÓ ÂÚÈÙÒÛÂˆÓ ÔÍ›·˜ ΢ÙÙ·ÚÈ΋˜ ·fiÚÚȄ˘ ·ÓÙÈÌÂÙˆ›˙ÔÓÙ·È ÂÈÙ˘¯Ò˜ Ì ÙȘ ˘„ËϤ˜ ‰fiÛÂȘ ÎÔÚÙÈÎÔÛÙÂÚÔÂȉÒÓ, ÂÓÒ ÌÈ· ‰Â‡ÙÂÚË Û˘Ó‰ڛ· Â›Ó·È ··Ú·›ÙËÙË ÛÙȘ ÂÌ̤ÓÔ˘Û˜ ÂÚÈÙÒÛÂȘ. ∏ ‚ÈÔ¯ËÌÈ΋ Î·È ÈÛÙÔÏÔÁÈ΋ ‚ÂÏÙ›ˆÛË ‰È·ÈÛÙÒÓÔÓÙ·È ÙËÓ 3Ë-5Ë Ì¤Ú· Î·È ÙÂÎÌËÚÈÒÓÂÙ·È Ì ÙË ‚ÈÔ„›· ‹·ÙÔ˜. ∏ ·ıÚÔÈÛÙÈ΋ ·ÓÔÛÔηٷÛÙ·ÏÙÈ΋ ‰Ú¿ÛË ÙˆÓ ÌÂÁ¿ÏˆÓ ‰fiÛÂˆÓ ÎÔÚÙÈÎÔÛÙÂÚÔÂȉÒÓ ·˘Í¿ÓÂÈ ÙËÓ Û˘¯ÓfiÙËÙ· ÂÌÊ¿ÓÈÛ˘ ÏÔÈÌÒ͈Ó, fiˆ˜ ÛÙÔÌ·ÙÈ΋˜ Ì˘ÎËÙ›·Û˘, Ïԛ̈͢ ·fi ΢ÙÙ·ÚÔÌÂÁ·ÏÔ˚fi, ·Û¤ÚÁÈÏÏÔ, Ó¢ÌÔÓÔ·ÛÙË carinii Î·È ·ıÔÁfiÓ· ‚·ÎÙËÚ›‰È·. ÕÏϘ ‰˘ÓËÙÈΤ˜ ÂÈÏÔΤ˜ Â›Ó·È Ë ˘-
124
ª. ¶∞™∞∫πøΔ√À
ÂÚÁÏ˘Î·ÈÌ›·, Ë ·ÈÌÔÚÚ·Á›· ·fi ÙÔ Á·ÛÙÚÂÓÙÂÚÈÎfi Î·È ÔÈ ‰È·Ù·Ú·¯¤˜ ÙÔ˘ Û˘Ó·ÈÛı‹Ì·ÙÔ˜. ∏ ·ÓÙÈÌÂÙÒÈÛË ÙˆÓ ·Ú·¿Óˆ ÂÚÈÏ·Ì‚¿ÓÂÈ ÙË ¯ÔÚ‹ÁËÛË ·Ó·ÛÙÔϤˆÓ Ù˘ ·ÓÙÏ›·˜ ÚˆÙÔÓ›ˆÓ, ÙÚÈÌÂıÔÚ›Ì˘-ÛÔ˘ÏÊÔÌÂıÔÍ·˙fiÏ˘ Î·È Û˘¯Ófi ¤ÏÂÁ¯Ô Ù˘ ÁÏ˘Îfi˙˘ ÙÔ˘ ·›Ì·ÙÔ˜.
∏·Ù›Ùȉ· C ∏ ·ÓÙÈÌÂÙÒÈÛË Ù˘ ÔÍ›·˜ ΢ÙÙ·ÚÈ΋˜ ·fiÚÚȄ˘ Û ·ÛıÂÓ›˜ Ì ˷ٛÙȉ· C (HCV) ··ÈÙ› ȉȷ›ÙÂÚË ÚÔÛÔ¯‹. ∏ ıÂڷ›· Ì ÎÔÚÙÈÎÔÛÙÂÚÔÂȉ‹ ÂÈÙ·¯‡ÓÂÈ ÙËÓ ÂͤÏÈÍË Ù˘ HCV, ÌÂ Û˘Ó¤ÂÈ· ÙËÓ ·˘ÍË̤ÓË ıÓËÛÈÌfiÙËÙ·26. ∂ÈϤÔÓ, Ù· ‚ÈÔ¯ËÌÈο Î·È ÈÛÙÔÏÔÁÈο Â˘Ú‹Ì·Ù· Â›Ó·È ·ÚfiÌÔÈ· ÛÙËÓ ÔÍ›· ·fiÚÚÈ„Ë Î·È ÛÙËÓ HCV, ηıÈÛÙÒÓÙ·˜ ¤ÙÛÈ ‰‡ÛÎÔÏË ÙË ‰È¿ÁÓˆÛË. ŒÙÛÈ, ÔÏÏ¿ ΤÓÙÚ· «·Ó·‚¿ÏÏÔ˘Ó» ÙËÓ ·ÓÙÈ·ÔÚÚÈÙÈ΋ ıÂڷ›· Ì ÎÔÚÙÈÎÔÂȉ‹ (fiÙ·Ó ÔÈ ÈÛÙÔÏÔÁÈΤ˜ ‚Ï¿‚˜ ‰Â›¯ÓÔ˘Ó ‹È· ·fiÚÚÈ„Ë) ÁÈ· Ó· ÌËÓ ‰È·ÎÈÓ‰˘Ó‡ÛÔ˘Ó ÙË Û˘ÓÔÏÈ΋ ¤Î‚·ÛË ÙˆÓ ÌÂÙ·ÌÔÛ¯Â˘Ì¤ÓˆÓ ·ÛıÂÓÒÓ Ì HCV26. ªÈ· ÂÓ·ÏÏ·ÎÙÈ΋ χÛË Â›Ó·È Ë ·‡ÍËÛË Ù˘ ‰fiÛ˘ ÙÔ˘ ·Ó·ÛÙÔϤ· Ù˘ calcineurin ‹/Î·È Ë ¯ÔÚ‹ÁËÛË Ù˘ mycophenolate mofetil (MMF), ÂÓÒ ··ÈÙÔ‡ÓÙ·È ÂÚ·ÈÙ¤Úˆ ÌÂϤÙ˜ Ô˘ Ó· ‰›ÓÔ˘Ó ÙË ‰˘Ó·ÙfiÙËÙ· ÙÔ˘ Û·ÊÔ‡˜ ‰È·¯ˆÚÈÛÌÔ‡ Ù˘ ÔÍ›·˜ ΢ÙÙ·ÚÈ΋˜ ·fiÚÚȄ˘ Î·È Ù˘ ˘ÔÙÚÔ‹˜ Ù˘ HCV, Èı·Ófiٷٷ ̤ۈ Ù˘ ¯Ú‹Û˘ ÙˆÓ Ë·ÙÈÎÒÓ ÁÔÓȉ›ˆÓ27.
∞fiÚÚÈ„Ë Ì ·ÓÙ›ÛÙ·ÛË ÛÙ· ÛÙÂÚÔÂȉ‹ ŒÓ· 10% ÂÚ›Ô˘ ÙˆÓ ·ÛıÂÓÒÓ Ì ÔÍ›· ΢ÙÙ·ÚÈ΋ ·fiÚÚÈ„Ë ·ÚÔ˘ÛÈ¿˙Ô˘Ó ·ÓÙ›ÛÙ·ÛË ÛÙ· ÛÙÂÚÔÂȉ‹26. ™Â ·˘ÙÔ‡˜ ÙÔ˘˜ ·ÛıÂÓ›˜ ¯ÔÚËÁÔ‡ÓÙ·È ¿ÏÏ· ıÂڷ¢ÙÈο Û¯‹Ì·Ù· Ô˘ ·ÓÙÈÌÂÙˆ›˙Ô˘Ó ÙËÓ ÂÈÏÔ΋ ·˘Ù‹, fiˆ˜ ÌÔÓÔÎψÓÈο ·ÓÙÈÛÒÌ·Ù· (O∫Δ3 – muromonab), mycophenolate mofetil, ·ÓÙÈÛÒÌ·Ù· ÙˆÓ ˘Ô‰Ô¯¤ˆÓ Ù˘ IL-2, sirolimus Î·È tacrolimus (·Ó·ÛÙÔÏ›˜ Ù˘ calcineurin).
∂•ø™øª∞Δπ∫∏ À¶O™Δ∏ƒπ•∏ Δ∏™ ∏¶∞Δπ∫∏™ §∂πΔOÀƒ°π∞™ ∏ ÔÚıÔÙÔÈ΋ ÌÂÙ·ÌfiÛ¯Â˘ÛË ‹·ÙÔ˜ ·Ú·Ì¤ÓÂÈ Ë Ì¤ıÔ‰Ô˜ ÂÎÏÔÁ‹˜ ÁÈ· ÙËÓ ‚·ÚÈ¿ Ë·ÙÈ΋ ·Ó¿ÚÎÂÈ·. øÛÙfiÛÔ, Ë ¤Ó‰ÂÈ· ÌÔÛ¯Â˘Ì¿ÙˆÓ Â›Ó·È ÌÈ· Ú·ÁÌ·ÙÈÎfiÙËÙ· Î·È ÔÏÏÔ› ·ÛıÂÓ›˜ ‰ÂÓ Î·Ù·Ê¤ÚÓÔ˘Ó Ó· ˘Ô‚ÏËıÔ‡Ó Û ÌÂÙ·ÌfiÛ¯Â˘ÛË ‹·ÙÔ˜. ŒÙÛÈ, ÔÈ Ì¤ıÔ‰ÔÈ Â͈ۈ̷ÙÈ΋˜ ˘ÔÛÙ‹ÚÈ͢ Ù˘ Ë·ÙÈ΋˜ ÏÂÈÙÔ˘ÚÁ›·˜ ·ÔÙÂÏÔ‡Ó ÌÈ· χÛË-Á¤Ê˘Ú· ˙ˆ‹˜!
ΔÔ 1993 ¤ÁÈÓ ÙÔ ÚÒÙÔ ‚‹Ì· « οı·ÚÛ˘-·ÔÙÔ͛ӈÛ˘» ÙÔ˘ ‹·ÙÔ˜ Ì ÙË ‚Ô‹ıÂÈ· Ù˘ ·Ï‚Ô˘Ì›Ó˘, Ù˘ ÔÔ›·˜ ‚·ÛÈ΋ ȉÈfiÙËÙ· Â›Ó·È Ë Û‡Ó‰ÂÛ‹ Ù˘ Ì ÙȘ ÙÔ͛Ә ÙÔ˘ ·›Ì·ÙÔ˜28. ∏ ·ÓıÚÒÂÈÔ˜ ·Ï‚Ô˘Ì›ÓË ÙÔ˘ ÔÚÔ‡ Â›Ó·È ¤Ó·˜ ÈÛ¯˘Úfi˜ ·ÓÙÈÔÍÂȉˆÙÈÎfi˜ ÌÂÙ·ÊÔÚ¤·˜ Ê·ÚÌ¿ÎˆÓ Î·È ÂÓ‰ÔÁÂÓÒÓ ·ÓÈfiÓÙˆÓ, fiˆ˜ ¯ÔÏÂÚ˘ıÚ›Ó˘, ¯ÔÏÈÎÒÓ ·Ï¿ÙˆÓ, Ì·ÎÚ¿˜ ·Ï‡ÛÔ˘ ÏÈ·ÚÒÓ ÔͤˆÓ, ÓÈÙÚÈÎÔ‡ ÔÍÂȉ›Ô˘. ¶ÔÏϤ˜ ·fi ÙȘ Ô˘Û›Â˜ Ô˘ Û˘Ó‰¤ÔÓÙ·È Ì ÙËÓ ·Ï‚Ô˘Ì›ÓË ¤¯Ô˘Ó ‰˘ÓËÙÈο ÙÔÍÈ΋ ‰Ú¿ÛË ÛÙÔ ‹·Ú, fiÙ·Ó Ë Û˘ÁΤÓÙÚˆÛ‹ ÙÔ˘˜ Â›Ó·È ·˘ÍË̤ÓË. ŒÙÛÈ, ÏÔÈfiÓ, ‰ËÌÈÔ˘ÚÁ‹ıËΠÌÈ· ̤ıÔ‰Ô˜ Ô˘ ÛÙËÚ›˙ÂÙ·È ÛÙËÓ ÂÚÈÁÚ·Ê›۷ ȉÈfiÙËÙ· Ù˘ ·Ï‚Ô˘Ì›Ó˘, ÙÔ MARS (Molecular Absorbent Recycling System), ÂÓÒ ÂÚÈÁÚ¿ÊÔÓÙ·È Î·È ¿ÏϘ ‰‡Ô ̤ıÔ‰ÔÈ, Ë SPAD (Single-Pass Albumine Dialysis) Î·È Ë Prometheus (Fractionated Plasma Separation)29. ΔÔ MARS Â›Ó·È ¤Ó· Û‡ÛÙËÌ· ˘ÔÛÙ‹ÚÈ͢ ÙÔ˘ ‹·ÙÔ˜, ÙÔ ÔÔ›Ô ¯ÚËÛÈÌÔÔÈ› ¤Ó· ‰È¿Ï˘Ì· ÂÌÏÔ˘ÙÈṲ̂ÓÔ Ì ·Ï‚Ô˘Ì›ÓË Ô˘ ‰È¢ÎÔχÓÂÈ ÙËÓ ·ÔÌ¿ÎÚ˘ÓÛË ÙˆÓ ÙÔÍÈÓÒÓ. ΔÔ Û‡ÛÙËÌ· ·ÔÙÂÏÂ›Ù·È ·fi 3 ‰È·ÊÔÚÂÙÈο ‰È·ÌÂÚ›ÛÌ·Ù·: ¤Ó· ·Îψ̷ ·›Ì·ÙÔ˜, ¤Ó· ‰È¿Ï˘Ì· 600ml ·Ï‚Ô˘Ì›Ó˘ 20% Ì ʛÏÙÚÔ ÂÓÂÚÁÔ‡ ¿Óıڷη Î·È Ê›ÏÙÚÔ˘ ·ÓÙ·ÏÏ·Á‹˜ ·ÓÈfiÓÙˆÓ Î·È ¤Ó·Ó ‰È·Ï‡ÙË, ÂÓÒ Â›Ó·È ··Ú·›ÙËÙË Ë ·ÚÔ˘Û›· Û˘Û΢‹˜ Û˘Ó¯ԇ˜ ÊÏ‚Ô-ÊÏ‚È΋˜ ·ÈÌԉȋıËÛ˘. ΔÔ Prometheus ·ÔÌ·ÎÚ‡ÓÂÈ ÙȘ Ô˘Û›Â˜ Ô˘ Û˘Ó‰¤ÔÓÙ·È Ì ÙËÓ ·Ï‚Ô˘Ì›ÓË Î·ıÒ˜ Î·È ÙȘ ÂÓ‰ÔÁÂÓ›˜ ˘‰·ÙÔ‰È·Ï˘Ù¤˜ ÙÔ͛Ә, ÂÓÒ ÙÔ SPAD Â›Ó·È ¤Ó· Û‡ÛÙËÌ· Û˘Ó¯ԇ˜ ÊÏ‚Ô-ÊÏ‚È΋˜ ·ÈÌԉȋıËÛ˘ (CVVHD), fiÔ˘ Ù· ˘ÁÚ¿ Ù˘ ‰È‹ıËÛ˘ ÂÌÏÔ˘Ù›˙ÔÓÙ·È Ì ·Ï‚Ô˘Ì›ÓË 4.4%. ™˘ÌÂÚ·ÛÌ·ÙÈο, fiÛÔÓ ·ÊÔÚ¿ ÙȘ ÌÂıfi‰Ô˘˜ Â͈ۈ̷ÙÈ΋˜ ˘ÔÛÙ‹ÚÈ͢ ÙÔ˘ ‹·ÙÔ˜, ˘¿Ú¯Ô˘Ó Û·Ê›˜ ÂӉ›ÍÂȘ fiÙÈ ˘ÔÛÙËÚ›˙Ô˘Ó ÙÔÓ ·ÛıÂÓ‹ Ì ÔÍ›· Ë·ÙÈ΋ ·Ó¿ÚÎÂÈ·, ·ÔÙÂÏÔ‡Ó ÌÈ· Á¤Ê˘Ú· ̤¯ÚÈ ÙËÓ ·Ó‡ÚÂÛË Î·Ù¿ÏÏËÏÔ˘ ÌÔۯ‡̷ÙÔ˜ – fiÙ·Ó Ô ·ÛıÂÓ‹˜ ÏËÚ› Ù· ÎÚÈÙ‹ÚÈ· ÁÈ· ÌÂÙ·ÌfiÛ¯Â˘ÛË– ˆÛÙfiÛÔ, ¯ÚÂÈ¿˙ÂÙ·È ÂÚ·ÈÙ¤Úˆ ¤Ú¢ӷ Î·È Û˘ÁÎÚÈÙÈΤ˜ ÌÂϤÙ˜ ÁÈ· ÙËÓ ÙÂÏÈ΋ ÂÈÏÔÁ‹ Ù˘ ÌÂıfi‰Ô˘ Ô˘ ı· ÂÊ·ÚÌÔÛı›.
μπμ§πO°ƒ∞ºπ∞ 1. Glanemann M, et al. Incidence and indications for reintubation during postoperative care following orthotopic liver transplantation. J Clin Anesth 13:77, 2001. 2. Mandell MS, et al. Reduced use of intensive care after liver transplantation: influence of early extubation. Liver Transpl 8:676, 2002.
METAMO™XEY™Eπ™ 2008
3. Findlay JY, Kufner RP. Aprotinin reduces vasoactive use during adult liver transplantation. J Clin Anesth 15:19, 2003. 4. Molenaar IQ, et al. The effect of aprotinin on renal function in orthotopic liver transplantation. Transplantation 71:247, 2001. 5. Molenaar IQ, Porte RJ. Aprotinin and thromboembolism in liver transplantation: Is there really a causal effect? Anesth Analg 94:1367, 2002 6. Levy MF, et al. Readmission to the intensive care unit after liver transplantation. Crit Care Med 29:18, 2001. 7. Krowka MJ,et al. Pulmonary hemodynamics and perioperative cardiopulmonary-related mortality in patients with portopulmonary hypertemsion undergoing liver transplantation. Liver Transpl 6:443, 2000. 8. McGilvray ID, Greig PD. Critical care of the liver transplant patient: un update. Curr Opin Crit Care 8:178, 2002. 9. Cardenas A, et al. Hepatorenal syndrome. Liver Transpl 6(4 Suppl 1):S63, 2000. 10. Pungpapong S, et al. Cigarette smoking is associated with an increased incidence of vascular complications after liver transplantation. Liver Transpl 8:582, 2002. 11. Fleck A, et al. Biliary tract complications after orthotopic liver transplantation in adult patients. Transplant Proc 34:519, 2002. 12. Park JS, et al. Efficacy of endoscopic and percutaneous treatment for biliary complications after cadaveric and living donor liver transplantation. Gastrointest Endosc 57:78, 2003. 13. Klintmalm GBG, et al. Rejection in liver transplantation. Hepatology 10:98, 1989. 14. McVicar JP, et al. The natural history of untreated focal allograft rejection in liver transplant recipients. Liver Transpl Surg 2:154, 1996. 15. Soin AS, et al. CsA levels in the early posttransplant period. Transplantation 8:1119, 1995. 16. Neuberger J, et al. What is the significance of acute liver allograft rejection? J Hepatol 29:143, 1998.
125
17. Wiesner RH, et al. Acute hepatic allograft rejection: incidence, risk factors, impact and outcome. Hepatology 28:638, 1995. 18. Ramji A, et al. Late acute rejection after liver transplantation: the Western Canada experience. Liver Transpl 8:945, 2002 19. Bathgate AJ, et al. The prediction of acute cellular rejection in orthotopic liver transplantation. Liver Transpl Surg 5:475, 1999. 20. Rosen HR, et al. Association of cytomegalovirus genotype with graft rejection after liver transplantation. Transplantation 66:1627, 1998. 21. Adams DH, et al. Soluble IL-2 receptors in serum and bile of liver transplant recipients. Lancet 1:469, 1989. 22. Bubak ME, et al. Complications of liver biopsy in liver transplant patients: increased sepsis associated with choledochojejunostomy. Hepatology 14:1063, 1991. 23. Banff schema for grading liver allograft rejection: An international consensus document. Hepatology 25:658, 1997. 24. Horoldt BS, et al. Does the Banff rejection activity index predict outcome in patients with early acute cellular rejection following liver transplantation? Liver Transpl 12:1144, 2006. 25. Volpin R, et al. Comparison between two high-dose methylprednisolone schedules in the treatment of acute hepatic cellular rejection in liver transplant recipients: a controlled clinical trial. Liver Transpl 8:527, 2002. 26. Burton JR Jr, et al. Acute rejection in HCV-infected liver transplant recipients: the great conundrum. Liver Transpl 12:S38, 2006. 27. Sreekumar R, et al. Differential allograft gene expression in acute cellular rejection and recurrence of hepatitis C after liver transplantation. Liver Transpl 8:814, 2002. 28. Stange J, Mitzner S, Ranlow W. A new procedure for the removal of protein bound drugs and toxins. ASAIO J 39:M621-25, 1993. 29. Mitzner S, Klammt S, Stange J, Schmidt R. Albumine regeneration in liver support: comparison of different methods. Ther Apher Dial 10(2):108-17, 2006.
¢È¿ÁÓˆÛË Î·È ·ÓÙÈÌÂÙÒÈÛË ÛÔ‚·Ú‹˜ Û‹„˘ Î·È ÛËÙÈÎÔ‡ ÛÔÎ ÛÙË ME£ Û ·ÛıÂÓ›˜ Ì ÌÂÙ·ÌfiÛ¯Â˘ÛË ‹·ÙÔ˜ ∂. ªÔ˘ÏÔ‡‰Ë
(grade A), ̤ÙÚÈ· (grade B), ¯·ÌËÏ‹ (grade C) Î·È Ôχ ¯·ÌËÏ‹ (grade D). ΔÔ Û‡ÛÙËÌ· GRADE ηÙËÁÔÚÈÔÔÈ› ›Û˘ ÙȘ Û˘ÛÙ¿ÛÂȘ Û ÈÛ¯˘Ú¤˜ (grade 1) ‹ ·ÛıÂÓ›˜ (grade 2). ∏ ÈÛ¯˘Ú‹ Û‡ÛÙ·ÛË ·Ô‰›‰ÂÙ·È Ì ÙÔÓ fiÚÔ «Û‡ÛÙ·ÛË», «Û˘ÓÈÛٿٷȻ, ÂÓÒ Ë ·ÛıÂÓ‹˜ Ì ÙÔÓ fiÚÔ «ÚfiÙ·ÛË», «ÚÔÙ›ÓÂÙ·È». °È· ÙË ‰È¿ÁÓˆÛË ÙÔ˘ Û˘Ó‰ÚfiÌÔ˘ Û˘ÛÙËÌ·ÙÈ΋˜ ÊÏÂÁÌÔÓÒ‰Ô˘˜ ·ÓÙ›‰Ú·Û˘, Ù˘ Û‹„˘, Ù˘ ÛÔ‚·Ú‹˜ Û‹„˘ Î·È ÙÔ˘ ÛËÙÈÎÔ‡ ÛÔÎ ¯ÚËÛÈÌÔÔÈÔ‡ÓÙ·È ÔÈ ÔÚÈÛÌÔ› fiˆ˜ ‰È·Ù˘ÒıËÎ·Ó ·fi ÙÔ Surviving Sepsis Campaign (›Ó·Î·˜ 1)8. ΔÔ Û‡Ó‰ÚÔÌÔ Û˘ÛÙËÌ·ÙÈ΋˜ ÊÏÂÁÌÔÓÒ‰Ô˘˜ ·ÓÙ›‰Ú·Û˘ ‰ÂÓ ·Ó·Ê¤ÚÂÙ·È ·ÔÎÏÂÈÛÙÈο Û ÛËÙÈÎÔ‡˜ ·ÛıÂÓ›˜. Œ¯ÂÈ ‚ÚÂı› fiÙÈ ÙÔ 39,8%ÙˆÓ ·ÛıÂÓÒÓ Ì ÔÍ›· Ë·ÙÈ΋ ·Ó¿ÚÎÂÈ· ÂÌÊ·Ó›˙ÂÈ ÙÔ Û‡Ó‰ÚÔÌÔ Î·È Ì¿ÏÈÛÙ· ·˘Ùfi Û˘Û¯ÂÙ›ÛÙËΠ̠ÙË ÛÔ‚·ÚfiÙËÙ· Ù˘ ÓfiÛÔ˘ Î·È ÙËÓ ÂÌÊ¿ÓÈÛË ÂÁÎÂÊ·ÏÔ¿ıÂÈ·˜5. ∏ ·ÓÙÈÌÂÙÒÈÛË Ù˘ ÛÔ‚·Ú‹˜ Û‹„˘ Î·È ÙÔ˘ ÛËÙÈÎÔ‡ ÛÔÎ ·Ó·Ê¤ÚÂÙ·È ÛÙËÓ: 1. ·Ú¯È΋ ·Ó·˙ˆÔÁfiÓËÛË 2. ·ÈÌÔ‰˘Ó·ÌÈ΋ ˘ÔÛÙ‹ÚÈÍË Î·È ÛÙËÓ 3. ˘ÔÛÙËÚÈÎÙÈ΋ ıÂڷ›·
OÈ ‰Â›ÎÙ˜ ÂÈ‚›ˆÛ˘ ÌÂÙ¿ ÌÂÙ·ÌfiÛ¯Â˘ÛË ‹·ÙÔ˜ Û˘Ó¯Ҙ ‚ÂÏÙÈÒÓÔÓÙ·È ·˘Í¿ÓÔÓÙ·˜ ÙÔ ÔÛÔÛÙfi ÂÙ‹ÛÈ·˜ ÂÈ‚›ˆÛ˘ ÛÙÔ 85%. ∏ ‚ÂÏÙ›ˆÛË ·˘Ù‹ ·Ô‰›‰ÂÙ·È Î˘Ú›ˆ˜ ÛÙË ¯Ú‹ÛË Î·Ï˘Ù¤ÚˆÓ ·ÓÔÛÔηٷÛÙ·ÏÙÈÎÒÓ ·Ú·ÁfiÓÙˆÓ, ÛÙËÓ ÚfiÏË„Ë Î·È ·ÓÙÈÌÂÙÒÈÛË ÙˆÓ ÏÔÈÌÒÍÂˆÓ Î·È ÛÙË ‚ÂÏÙ›ˆÛË ÙˆÓ ¯ÂÈÚÔ˘ÚÁÈÎÒÓ Ù¯ÓÈÎÒÓ1. ∏ ÓÔÛËÚfiÙËÙ· fï˜ Î·È Ë ıÓËÙfiÙËÙ· Ô˘ ÔÊ›ÏÂÙ·È ÛÙË ÛËÙÈΤ˜ ÂÈÏÔΤ˜ ·Ú·Ì¤ÓÂÈ Ì›˙ÔÓ Úfi‚ÏËÌ·. ™Â ÔÏÏ¿ ΤÓÙÚ·, ÔÈ ÏÔÈÌÒÍÂȘ ·ÔÙÂÏÔ‡Ó ÙËÓ Û˘¯ÓfiÙÂÚË ·ÈÙ›· ı·Ó¿ÙÔ˘ ÌÂÙ¿ ÌÂÙ·ÌfiÛ¯Â˘ÛË ‹·ÙÔ˜, ·ÁÁ›˙ÔÓÙ·˜ ÔÛÔÛÙfi ¤ˆ˜ Î·È 64% ÙˆÓ ı·Ó¿ÙˆÓ2. OÈ Û˘ÓËı¤ÛÙÂÚ˜ ÏÔÈÌÒÍÂȘ Â›Ó·È ÔÈ ‚·ÎÙËÚȷΤ˜ (48%), ÔÈ Ì˘ÎËÙÈ·ÛÈΤ˜ (22%) Î·È ÔÈ ÈÔÁÂÓ›˜ (12%). ΔÔ 1/3 ÙˆÓ ·ÛıÂÓÒÓ Ô˘ ı· ˘Ô‚ÏËıÔ‡Ó Û ÌÂÙ·ÌfiÛ¯Â˘ÛË ‹·ÙÔ˜ ı· ÂÌÊ·Ó›ÛÂÈ ÙÔ˘Ï¿¯ÈÛÙÔÓ ¤Ó· ÛËÙÈÎfi ÂÂÈÛfi‰ÈÔ3. ∏ ÛÔ‚·Ú‹ Û‹„Ë Î·È ÙÔ ÛËÙÈÎfi ÛÔÎ ·ÔÙÂÏÔ‡Ó ÙÂÚ¿ÛÙÈÔ Úfi‚ÏËÌ· ÛÙÔ ¯ÒÚÔ Ù˘ ˘Á›·˜, ·ÊÔÚÒÓÙ·˜ ÂηÙÔÌ̇ÚÈ· ·ÓıÚÒÔ˘˜ ·ÁÎÔÛÌ›ˆ˜ Î·È Ì ıÓËÙfiÙËÙ· ÙÔ˘Ï¿¯ÈÛÙÔÓ 25%4. ∏ ıÓËÙfiÙËÙ· Ù˘ ÛÔ‚·Ú‹˜ Û‹„˘ Û ¢·›ÛıËÙ˜ ÔÌ¿‰Â˜ ·ÛıÂÓÒÓ, fiˆ˜ ·ÛıÂÓÒÓ Ì ÔÍ›· Ë·ÙÈ΋ ·Ó¿ÚÎÂÈ· ·Ó¤Ú¯ÂÙ·È Û 59%, ÂÓÒ ÙÔ˘ ÛËÙÈÎÔ‡ ÛÔÎ Û 98%5. ΔÔ 2004, ‰ÈÂıÓ‹˜ ÔÌ¿‰· ÂȉËÌfiÓˆÓ ÛÙË ‰È¿ÁÓˆÛË Î·È ·ÓÙÈÌÂÙÒÈÛË ÙˆÓ ÏÔÈÌÒÍÂˆÓ Î·È Ù˘ Û‹„˘, ·ÓÙÈÚÔۈ‡ÔÓÙ·˜ 11 ‰ÈÂıÓ›˜ ÔÚÁ·ÓÈÛÌÔ‡˜ (Surving Sepsis Campaign), ‰ËÌÔÛ›Â˘Û ÙȘ ÚÒÙ˜ ‰ÈÂıÓÒ˜ ·Ô‰ÂÎÙ¤˜ ηÙ¢ı˘ÓÙ‹ÚȘ Ô‰ËÁ›Â˜ ÁÈ· ÙË ‰È·¯Â›ÚÈÛË Ù˘ ÛÔ‚·Ú‹˜ Û‹„˘ Î·È ÙÔ˘ ÛËÙÈÎÔ‡ ÛÔÎ6. ΔÔ 2008 ‰ËÌÔÛȇıËÎ·Ó ÔÈ Ó¤Â˜ ‰ÈÂıÓÒ˜ ·Ô‰ÂÎÙ¤˜ ηÙ¢ı˘ÓÙ‹ÚȘ Ô‰ËÁ›Â˜ ÁÈ· ÙË ‰È·¯Â›ÚÈÛË Ù˘ ÛÔ‚·Ú‹˜ Û‹„˘ Î·È ÙÔ˘ ÛËÙÈÎÔ‡ ÛÔÎ7. ¶Ú¤ÂÈ fï˜ Ó· ÂÈÛËÌ·Óı›, fiÙÈ ÔÈ Î·Ù¢ı˘ÓÙ‹ÚȘ Ô‰ËÁ›Â˜ ‰ÂÓ ·ÓÙÈηıÈÛÙÔ‡Ó ÙÔ ÎÏÈÓÈÎfi ÎÚÈÙ‹ÚÈÔ Î·È Ë ·ÓÙÈÌÂÙÒÈÛË Î¿ı ·ÛıÂÓ‹ Ú¤ÂÈ Ó· ÂÍ·ÙÔÌÈ·ÂÙ·È. ∏ ÔÈfiÙËÙ· ÙÂÎÌËÚ›ˆÛ˘ ÙˆÓ Ô‰ËÁÈÒÓ ·˘ÙÒÓ ‚·Û›ÛÙËΠÛÙÔ Û‡ÛÙËÌ· GRADE Ô˘ ηÙËÁÔÚÈÔÔÈ› ÙËÓ ÙÂÎÌËÚ›ˆÛË ˆ˜ ˘„ËÏ‹
1. ∞ƒÃπ∫∏ ∞¡∞∑øO°O¡∏™∏ ÃÚËÛÈÌÔÔÈÔ‡ÓÙ·È Ù· ۇ̂ÔÏ· fiÙ·Ó Û˘ÓÈÛٿٷÈ, fiÙ·Ó ÚÔÙ›ÓÂÙ·È Î·È ÛÙËÓ ·Ú¤ÓıÂÛË Ô ‚·ıÌfi˜ ÙÂÎÌËÚ›ˆÛ˘ ‚¿ÛÂÈ ÙÔ˘ Û˘ÛÙ‹Ì·ÙÔ˜ GRADE.
1·. ∞Ú¯È΋ ·Ó·˙ˆÔÁfiÓËÛË (ÙȘ 6 ÚÒÙ˜ ÒÚ˜)9 ÕÌÂÛË ¤Ó·ÚÍË ·Ó·˙ˆÔÁfiÓËÛ˘ Û οı ·ÛıÂÓ‹ Ì ˘fiÙ·ÛË ‹ Ì Á·Ï·ÎÙÈÎfi ÔÚÔ‡ >4 mmol/L, ¿ÌÂÛË ÌÂÙ·ÊÔÚ¿ Û ª∂£ (1C) ™Ùfi¯ÔÈ ·Ó·˙ˆÔÁfiÓËÛ˘ (1C) ∫ÂÓÙÚÈ΋ ºÏ‚È΋ ¶›ÂÛË (∫º¶) 8-12 mmHg ª¤ÛË ∞ÚÙËÚȷ΋ ¶›ÂÛË (ª∞¶) ≥65 mmHg ¢ÈÔ‡ÚËÛË ≥0,5 mL/kg/hour ∫ÔÚÂÛÌfi˜ ÊÏ‚ÈÎÔ‡ ·›Ì·ÙÔ˜ ¿Óˆ ÎÔ›Ï˘ ≥70%, Î·È ÌÈÎÙÔ‡ ÊÏ‚ÈÎÔ‡ ≥65%
126
METAMO™XEY™Eπ™ 2008
127
¶›Ó·Î·˜ 1. OÚÈÛÌÔ› Û‹„˘, ÛÔ‚·Ú‹˜ Û‹„˘ Î·È ÛËÙÈÎÔ‡ ÛÔÎ ø˜ Û‹„Ë ÔÚ›˙ÂÙ·È Ì›· ÂȂ‚·ÈˆÌ¤ÓË ‹ Èı·Ó‹ Ïԛ̈ÍË Ì ¤Ó· ‹ ÂÚÈÛÛfiÙÂÚ· ·fi Ù· ·Ú·Î¿Ùˆ: °ÂÓÈÎÔ› ‰Â›ÎÙ˜ ¶˘ÚÂÙfi˜ (ÂÛˆÙÂÚÈ΋ ıÂÚÌÔÎÚ·Û›· >38,3Ô C) ÀÔıÂÚÌ›· (ÂÛˆÙÂÚÈ΋ ıÂÚÌÔÎÚ·Û›· <36Ô C) ∫·Ú‰È·Î‹ Û˘¯ÓfiÙËÙ· >90/ÏÂÙfi ‹ >2 SD ¿Óˆ ·fi ÙË Ê˘ÛÈÔÏÔÁÈ΋ Û˘¯ÓfiÙËÙ· Δ·¯‡ÓÔÈ· ¢È·Ù·Ú·¯¤˜ ÂȤ‰Ô˘ Û˘Ó›‰ËÛ˘ ™ËÌ·ÓÙÈÎfi Ô›‰ËÌ· ‹ ıÂÙÈÎfi ÈÛÔ˙‡ÁÈÔ ˘ÁÚÒÓ (>20 mL/kg Û 24 ÒÚ˜) ÀÂÚÁÏ˘Î·ÈÌ›· (ÁÏ˘Îfi˙Ë ÔÚÔ‡ >120 mg/dL) Û ·Ô˘Û›· ‰È·‚‹ÙË ¢Â›ÎÙ˜ ÊÏÂÁÌÔÓ‹˜ §Â˘ÎÔ΢ÙÙ¿ÚˆÛË (WBC >12000/ÌL) §Â˘ÎÔÂÓ›· (WBC <4000/ÌL) º˘ÛÈÔÏÔÁÈÎfi˜ ·ÚÈıÌfi˜ WBC Ì >10% ¿ˆÚ˜ ÌÔÚʤ˜ C-·ÓÙȉÚÒÛ· ÚˆÙ½ÓË ÔÚÔ‡ (CRP) >2 SD ¿Óˆ ·fi ÙË Ê˘ÛÈÔÏÔÁÈ΋ ÙÈÌ‹ ¶ÚÔηÏÛÈÙÔÓ›ÓË ÔÚÔ‡ >2 SD ¿Óˆ ·fi ÙË Ê˘ÛÈÔÏÔÁÈ΋ ÙÈÌ‹ ø˜ ÛÔ‚·Ú‹ Û‹„Ë ÔÚ›˙ÂÙ·È Ë Û‹„Ë Ì ÛËÌ›· ‰˘ÛÏÂÈÙÔ˘ÚÁ›·˜ ÔÚÁ¿ÓˆÓ, ˘Ô¿Ú‰Â˘Û˘ ‹ ˘fiÙ·Û˘ ¢Â›ÎÙ˜ ‰˘ÛÏÂÈÙÔ˘ÚÁ›·˜ ÔÚÁ¿ÓˆÓ ∞ÚÙËÚȷ΋ ˘Ô͢ÁÔÓ·ÈÌ›· (PaO2/FiO2 <300) Oͤˆ˜ ÂÌÊ·ÓÈ˙fiÌÂÓË ÔÏÈÁÔ˘Ú›· (‰ÈÔ‡ÚËÛË <0,5 mL/kg/ÒÚ· ÁÈ· 2 ÙÔ˘Ï¿¯ÈÛÙÔÓ ÒÚ˜) ∫Ú·ÙÈÓ›ÓË ÔÚÔ‡ >2 mg/dL ¢È·Ù·Ú·¯¤˜ ËÎÙÈÎfiÙËÙ·˜ (INR >1,5 ‹ aPTT >60 secs) £ÚÔÌ‚ÔÂÓ›· (PLT <100.000/ÌL) ÀÂÚ¯ÔÏÂÚ˘ıÚÈÓ·ÈÌ›· (ÔÏÈ΋ ¯ÔÏÂÚ˘ıÚ›ÓË ÔÚÔ‡ >2 mg/dL) ¢Â›ÎÙ˜ ˘Ô¿Ú‰Â˘Û˘ °·Ï·ÎÙÈÎfi ÔÚÔ‡ >2mmol/L ∞ÈÌÔ‰˘Ó·ÌÈÎÔ› ‰Â›ÎÙ˜ ∞ÚÙËÚȷ΋ ˘fiÙ·ÛË (™∞¶ <90 mmHg, ª∞¶ <65 mmHg, ‹ ÙÒÛË ™∞¶ >40 mmHg) ø˜ ÛËÙÈÎfi ÛÔÎ ÔÚ›˙ÂÙ·È Ë ÔÍ›· ΢ÎÏÔÊÔÚÈ΋ ·Ó¿ÚÎÂÈ· Ô˘ ‰ÂÓ ÌÔÚ› Ó· ·Ô‰Ôı› Û ¿ÏÏË ·ÈÙ›· (™∞¶ <90 mmHg, ª∞¶ <65 mmHg, ‹ ÙÒÛË ™∞¶ >40 mmHg ·fi ÙÈÌ‹ ·Ó·ÊÔÚ¿˜ ·Ú¿ ÙËÓ Â·Ú΋ ·Ó¿Ù·ÍË Ì fiÁÎÔ).
∞Ó Ô ÎÔÚÂÛÌfi˜ ÙÔ˘ ÊÏ‚ÈÎÔ‡ ·›Ì·ÙÔ˜ ‰ÂÓ ÂÈÙ˘Á¯¿ÓÂÙ·È (2C) ™Î¤„Ë ÁÈ· ¯ÔÚ‹ÁËÛË ÂÚÈÛÛÔÙ¤ÚˆÓ ˘ÁÚÒÓ ªÂÙ¿ÁÁÈÛË Û˘Ì˘ÎÓˆÌ¤ÓˆÓ ÂÚ˘ıÚÒÓ (RBC) ÒÛÙ ·ÈÌ·ÙÔÎÚ›Ù˘ ≥30% ‹/Î·È ŒÓ·ÚÍË ‰Ô‚Ô˘Ù·Ì›Ó˘ (‰fiÛË ¤ˆ˜ 20Á/kg/min) ∏ ∫º¶ Ú¤ÂÈ Ó· ‰È·ÙËÚÂ›Ù·È Û ›‰· ˘„ËÏfiÙÂÚ· (12-15 mmHg) Û ÂÚÈÙÒÛÂȘ Ì˯·ÓÈÎÔ‡ ·ÂÚÈÛÌÔ‡, ˘„ËÏ‹˜ ÂÓ‰ÔÎÔÈÏȷ΋˜ ›ÂÛ˘ ‹ ‰È·ÛÙÔÏÈ΋˜ ‰˘ÛÏÂÈÙÔ˘ÚÁ›·˜ Ù˘ ηډȿ˜10.
1‚. ¢È¿ÁÓˆÛË11,12 §‹„Ë ··Ú·›ÙËÙˆÓ Î·ÏÏÈÂÚÁÂÈÒÓ ÚÈÓ ÙËÓ ¤Ó·ÚÍË ·ÓÙÈÌÈÎÚԂȷ΋˜ ·ÁˆÁ‹˜, ¯ˆÚ›˜ fï˜ ÛËÌ·ÓÙÈ΋ ηı˘ÛÙ¤ÚËÛË (1C) §‹„Ë 2 ÙÔ˘Ï¿¯ÈÛÙÔÓ ·ÈÌÔηÏÏÈÂÚÁÂÈÒÓ ˆ˜ ÂÍ‹˜: ª›· ÙÔ˘Ï¿¯ÈÛÙÔÓ ·ÈÌÔηÏÏȤÚÁÂÈ· ·fi ÂÚÈÊÂÚÈ΋ ·Ú·Î¤ÓÙËÛË Î·È ª›· ·ÈÌÔηÏÏȤÚÁÂÈ· ·fi οı ÂÓ‰·ÁÁÂÈ·Îfi
ηıÂÙ‹Ú·, Ô˘ Â›Ó·È ÙÔÔıÂÙË̤ÓÔ˜ >48 ÒÚ˜ ∫·ÏÏȤÚÁÂȘ ·fi ¿ÏϘ ı¤ÛÂȘ, ·Ó·ÏfiÁˆ˜ ÙˆÓ ÎÏÈÓÈÎÒÓ ÂӉ›ÍÂˆÓ ∂¿Ó Â›Ó·È ·ÛʷϤ˜, ·ÂÈÎÔÓÈÛÙÈÎfi˜ ¤ÏÂÁ¯Ô˜ ÁÈ· Èı·Ó‹ ÂÛÙ›· Ïԛ̈͢. ¶·Ú·ÎÏ›ÓÈÔ˜ ¤ÏÂÁ¯Ô˜, fiˆ˜ Ì ˘ÂÚ‹¯Ô˘˜, Â›Ó·È ¯Ú‹ÛÈÌÔ˜ Û ·˘Ù¤˜ ÙȘ Û˘Óı‹Î˜ (1C) ∂›Ó·È ÛËÌ·ÓÙÈÎfi ÔÈ Î·ÏÏȤÚÁÂȘ Ó· Â›Ó·È ÔÛÔÙÈΤ˜ ‹ ËÌÈÔÛÔÙÈΤ˜ ȉ›ˆ˜ ÛÙË ‰È¿ÁÓˆÛË Ù˘ Ó¢ÌÔÓ›·˜ Ù˘ Û¯ÂÙÈ˙fiÌÂÓ˘ Ì ÙÔÓ ·Ó·Ó¢ÛÙ‹Ú· (Ventilator-Associated Pneumonia-VAP). ¢Â›ÎÙ˜ ÊÏÂÁÌÔÓ‹˜ fiˆ˜ Ë ÚÔηÏÛÈÙÔÓ›ÓË, ·Ó Î·È ¯Ú‹ÛÈÌÔÈ ‰ÂÓ Â›Ó·È ÂȉÈÎÔ›.
1Á. ∞ÓÙÈ‚ÈÔÙÈ΋ ıÂڷ›·13-16 ŒÓ·ÚÍË ÂÓ‰ÔÊϤ‚È·˜ ·ÓÙÈ‚›ˆÛ˘ fiÛÔÓ ÙÔ ‰˘Ó·ÙfiÓ ÁÚËÁÔÚfiÙÂÚ· Î·È ¿ÓÙ· ̤۷ ÛÙËÓ ÚÒÙË ÒÚ· Ù˘ ‰È¿ÁÓˆÛ˘ Ù˘ ÛÔ‚·Ú‹˜ Û‹„˘ (1D) ‹ ÙÔ˘ ÛËÙÈÎÔ‡ ÛÔÎ (1B)
∂. ª√À§√À¢∏
128
∂˘Ú¤ˆ˜ Ê¿ÛÌ·ÙÔ˜ ·ÓÙÈ‚ÈÔÙÈο ¤Ó·ÓÙÈ Èı·ÓÒÓ ÌÈÎÚÔ‚›ˆÓ/Ì˘Î‹ÙˆÓ Î·È Ì ηϋ ‰ÈÂÈÛ‰˘ÙÈÎfiÙËÙ· ÛÙËÓ Èı·Ó‹ ÂÛÙ›· Ïԛ̈͢ (1B) ∫·ıËÌÂÚÈÓ‹ ·ÓÂÎÙ›ÌËÛË ·ÓÙÈ‚ÈÔÙÈ΋˜ ·ÁˆÁ‹˜ ÁÈ· ‚ÂÏÙ›ˆÛË ·ÔÙÂÏÂÛÌ·ÙÈÎfiÙËÙ·˜, ÚfiÏË„Ë ·ÓÙÔ¯‹˜, ·ÔÊ˘Á‹ ÙÔÍÈÎfiÙËÙ·˜ Î·È ÂÏ¿ÙÙˆÛ˘ ÙÔ˘ ÎfiÛÙÔ˘˜ (1C) ™˘Ó‰È·ÛÌfi˜ ·ÓÙÈ‚ÈÔÙÈÎÒÓ ÁÈ· „¢‰ÔÌÔÓ·‰ÈΤ˜ ÏÔÈÌÒÍÂȘ (2D) ™˘Ó‰È·ÛÌfi˜ ·ÓÙÈ‚ÈÔÙÈÎÒÓ Û Ԣ‰ÂÙÂÚÔÂÓÈÎÔ‡˜ ·ÛıÂÓ›˜ (2D) ÃÔÚ‹ÁËÛË Û˘Ó‰È·ÛÌÔ‡ ·ÓÙÈ‚ÈÔÙÈÎÒÓ ≤3-5 ̤Ú˜ Î·È ·ÔÎÏÈ̿ΈÛË ·Ó·ÏfiÁˆ˜ ÂӉ›ÍÂˆÓ (2D) ¢È¿ÚÎÂÈ· ıÂڷ›·˜ ¤ˆ˜ 7-10 ̤Ú˜, ÂÚÈÛÛfiÙÂÚ˜ Û ·ÚÁ‹ ·ÓÙ·fiÎÚÈÛË ‹ ÛÂ Ì˘ÎËÙÈ·ÛÈΤ˜ ÏÔÈÌÒÍÂȘ ‹ Û ·ÓÔÛÔ·Ó¿ÚÎÂȘ, fiˆ˜ Ô˘‰ÂÙÂÚÔÂÓ›· (1D) ¢È·ÎÔ‹ ·ÓÙÈ‚ÈÔÙÈÎÒÓ ·Ó Ë ·ÈÙ›· ‰ÂÓ Â›Ó·È ÏÔÈÌ҉˘ (1D) ∫·ı˘ÛÙ¤ÚËÛË ¤Ó·Ú͢ ·ÓÙÈ‚ÈÔÙÈ΋˜ ·ÁˆÁ‹˜ ¤ÛÙˆ Î·È ÁÈ· Ì›· ÒÚ· ‹ ¯ÔÚ‹ÁËÛË ·Î·Ù¿ÏÏËÏ˘ ·ÁˆÁ‹˜ Û˘Óԉ‡ÂÙ·È ·fi ÌÂÁ¿ÏË ·‡ÍËÛË Ù˘ ıÓËÙfiÙËÙ·˜13,17. ¶Ú¤ÂÈ Â›Û˘ Ó· ÙÔÓÈÛÙ› fiÙÈ ÔÈ ·ÚÓËÙÈΤ˜ ·ÈÌÔηÏÏȤÚÁÂȘ ·Ó¤Ú¯ÔÓÙ·È Û ÔÛÔÛÙfi ¤ˆ˜ Î·È 50% Û ÂÚÈÙÒÛÂȘ ÛÔ‚·Ú‹˜ Û‹„˘ Î·È ÛËÙÈÎÔ‡ ÛÔÎ Î·È ÙÔ ÎÏÈÓÈÎfi ÎÚÈÙ‹ÚÈÔ Û ·˘Ù¤˜ ÙȘ ÂÚÈÙÒÛÂȘ ·ÔÎÙ¿ ηıÔÚÈÛÙÈ΋ ÛËÌ·Û›·. ∏ ÎÚ›ÛÈÌË ÚÒÙË ÂÈÏÔÁ‹ ·ÓÙÈ‚ÈÔÙÈ΋˜ ·ÁˆÁ‹˜ ÂÍ·ÚÙ¿Ù·È ·fi ÙËÓ ÂÛÙ›· Ïԛ̈͢, Ù· Èı·Ó¿ ·ıÔÁfiÓ· Ù˘ ÂÛÙ›·˜ Î·È ·fi ·Ú¿ÁÔÓÙ˜ ÎÈÓ‰‡ÓÔ˘ ÔÏ˘·ÓıÂÎÙÈÎÒÓ ·ıÔÁfiÓˆÓ fiˆ˜: – Ï‹„Ë ·ÓÙÈ‚ÈÔÙÈÎÒÓ Î·Ù¿ ÙȘ ÙÂÏÂ˘Ù·›Â˜ 90 Ë̤Ú˜, – ÓÔÛÔÎÔÌÂȷ΋ ÓÔÛËÏ›· Ô˘ ‰È·ÚΛ ÂÚÈÛÛfiÙÂÚÔ ·fi 5 Ë̤Ú˜
– ·ÓÔÛÔηٷÛÙÔÏ‹ – ‰È¿ÚÎÂÈ· Ì˯·ÓÈÎÔ‡ ·ÂÚÈÛÌÔ‡ Î·È – ÂȉËÌÈÔÏÔÁ›· ·ÓÙÔ¯‹˜ ÛÙË Û˘ÁÎÂÎÚÈ̤ÓË ª∂£ ∂ȉÈÎfiÙÂÚ·, ÔÈ ÏÔÈÌÒ‰ÂȘ ÂÈÏÔΤ˜ ÌÂÙ¿ ÌÂÙ·ÌfiÛ¯Â˘ÛË ‹·ÙÔ˜ Â›Ó·È ÛËÌ·ÓÙÈÎfiٷ٘ ÁÈ·Ù› ÂËÚ¿˙Ô˘Ó ¿ÌÂÛ· ÙËÓ ÂÈ‚›ˆÛË. ¶ÚԉȷıÂÛÈÎÔ› ·Ú¿ÁÔÓÙ˜ ÁÈ· ÂÌÊ¿ÓÈÛË Ïԛ̈͢ ÌÂÙ¿ ·fi ÌÂÙ·ÌfiÛ¯Â˘ÛË ‹·ÙÔ˜ ıˆÚÔ‡ÓÙ·È: Ë ÚÔËÁÔ‡ÌÂÓË Ïԛ̈ÍË Ô˘ ·Ó·˙ˆÔ˘ÚÒÓÂÙ·È ÌÂÙ¿ ÙËÓ ¤Ó·ÚÍË Ù˘ ·ÓÔÛÔηٷÛÙÔÏ‹˜, Ë ÌÂÁ¿ÏË ‰È¿ÚÎÂÈ· ¯ÂÈÚÔ˘ÚÁ›Ô˘ (>12 ÒÚ˜), Ë ÚÔÂÁ¯ÂÈÚËÙÈ΋ ÙÈÌ‹ SGOT ¿Óˆ ·fi 60 IU/L, Ë ÂÈÏÔÁ‹ ¯ÔÏÈ΋˜ ·Ó·ÛÙfïÛ˘ Ù‡Ô˘ Roux-en-Y, ÔÈ ÔÏϷϤ˜ ¯ÂÈÚÔ˘ÚÁÈΤ˜ ÂÂÌ‚¿ÛÂȘ ÎÔÈÏ›·˜, Ë ÚÔÂÁ¯ÂÈÚËÙÈ΋ Ïԛ̈ÍË ·fi ÌÂÁ·ÏÔ΢ÙÙ·ÚÔ˚fi Î·È Ë ·fiÚÚÈ„Ë ‹ ‰˘ÛÏÂÈÙÔ˘ÚÁ›· ÙÔ˘ ÌÔۯ‡̷ÙÔ˜3,18. O ΛӉ˘ÓÔ˜ ÂÌÊ¿ÓÈÛ˘ Ïԛ̈͢ Î·È ÙÔ Â›‰Ô˜ Ù˘ Ïԛ̈͢ ‰È·Ê¤ÚÔ˘Ó ·Ó·ÏfiÁˆ˜ ÙÔ˘ ¯ÚfiÓÔ˘ ÂÌÊ¿ÓÈÛ‹˜ ÙÔ˘˜ ÌÂÙ¿ ÙË ÌÂÙ·ÌfiÛ¯Â˘ÛË. OÈ ÂÚÈÛÛfiÙÂÚ˜ ÌÂÙÂÁ¯ÂÈÚËÙÈΤ˜ ÏÔÈÌÒÍÂȘ ÌÔÚÔ‡Ó Ó· ηÙËÁÔÚÈÔÔÈËıÔ‡Ó Û 3 ¯ÚÔÓÈΤ˜ ÂÚÈfi‰Ô˘˜: ·fi ÙË ÌÂÙ·ÌfiÛ¯Â˘ÛË ¤ˆ˜ 1 Ì‹Ó·, 1-6 Ì‹Ó˜ Î·È ÌÂÙ¿ ÙÔ ÂÍ¿ÌËÓÔ (›Ó·Î·˜ 2). ÃÚÔÓÈ΋ ÂÚ›Ô‰Ô˜ ·fi ÙË ÌÂÙ·ÌfiÛ¯Â˘ÛË ¤ˆ˜ 1 Ì‹Ó·: ÔÈ ¿ÌÂÛ˜ ÌÂÙÂÁ¯ÂÈÚËÙÈΤ˜ ÏÔÈÌÒÍÂȘ Â›Ó·È ·ÚfiÌÔȘ ÌÂ ÙˆÓ ÌË ·ÓÔÛÔηÙÂÛÙ·ÏÌ¤ÓˆÓ ·ÛıÂÓÒÓ. ∂ÈÎÚ·ÙÔ‡Ó ÔÈ ‚·ÎÙËÚȷΤ˜ ÏÔÈÌÒÍÂȘ Ô˘ Û˘Ó‹ıˆ˜ ¤¯Ô˘Ó ÓÔÛÔÎÔÌÂȷ΋ ÚԤϢÛË fiˆ˜ ‡·ÚÍË ÎÂÓÙÚÈÎÔ‡ ÊÏ‚ÈÎÔ‡ ηıÂÙ‹Ú·, ·ÚÔ¯ÂÙ‡ÛÂˆÓ Î·È ÂÓ‰ÔÙÚ·¯ÂÈ·ÎÔ‡ ۈϋӷ19. ™˘ÓËı¤ÛÙÂÚ˜ Â›Ó·È ÔÈ ÂÓ‰ÔÎÔÈÏȷΤ˜ ÏÔÈÌÒÍÂȘ Î·È Ë Ó¢ÌÔÓ›·. ∂Ó‰ÔÎÔÈÏȷο ·ÔÛÙ‹Ì·Ù· ÌÔÚ› Ó· ÔÊ›ÏÔÓÙ·È Û ‰È·Ê˘Á‹ ¯ÔÏ‹˜ ÂÓÒ ÂÓ‰ÔË·ÙÈο ÌÔÚ› Ó· Û¯ÂÙ›˙ÔÓÙ·È Ì ıÚfiÌ‚ˆÛË Ë·ÙÈ΋˜ ·ÚÙËÚ›·˜3. ∞ÓÙÈ‚ÈÔÙÈο Ô˘ ¯ÚËÛÈÌÔÔÈÔ‡ÓÙ·È ÁÈ· Â-
¶›Ó·Î·˜ 2. §ÔÈÌÒÍÂȘ ÌÂÙ¿ ÌÂÙ·ÌfiÛ¯Â˘ÛË ‹·ÙÔ˜.
∂˘Î·ÈÚȷΤ˜
∫ÔÈÓfiÙËÙ·˜
<4 ‚‰ÔÌ¿‰Â˜
1-6 Ì‹Ó˜
>6-12 Ì‹Ó˜
MRSA, candida, VRE, aspergillus, ÂÈÛÚfiÊËÛË, Ïԛ̈ÍË ·fi ηıÂÙ‹Ú·, ÓÔÛÔÎÔÌÂȷ΋ Ó¢ÌÔÓ›·, C. difficile
HSV, CMV, HBV, HCV, EBV, listeria, TB, PCP, aspergillus, nocardia, toxoplasma, strongvloides, leismania
¶Ó¢ÌÔÓ›· ÎÔÈÓfiÙËÙ·˜, aspergillus, ÌËÓÈÁÁ›Ùȉ· ·fi Cryptococcus, CMV ÎÔÏ›Ùȉ·, ÌËÓÈÁÁ›Ùȉ· ‹ Ë·Ù›Ùȉ· ·fi listeria
¡ÔÛÔÎÔÌȷΤ˜ ªÂÙ·ÌfiÛ¯Â˘ÛË
METAMO™XEY™Eπ™ 2008
ÌÂÈÚÈ΋ ıÂڷ›· ÛÙËÓ ·Ú¯È΋ ÌÂÙÂÁ¯ÂÈÚËÙÈ΋ ÂÚ›Ô‰Ô Ú¤ÂÈ Ó· ηχÙÔ˘Ó Gram ıÂÙÈÎÔ‡˜ ÎfiÎÎÔ˘˜, Gram ·ÚÓËÙÈο ‚·ÎÙ‹ÚÈ· Î·È ·Ó·ÂÚfi‚È·. ¶ÚÔÙ›ÓÂÙ·È ÌÈ· ÎÂÊ·ÏÔÛÔÚ›ÓË 3˘ ÁÂÓÈ¿˜ ‹ ÊıÔÚÈÔÎÈÓÔÏfiÓË Ì ÈÂÚ·ÎÈÏÏ›ÓË/Ù·˙ÔÌ·ÎÙ¿ÌË ‹ ·ÌÈÎÈÏÏ›ÓË/ÛÔ˘ÏÌ·ÎÙ¿ÌË3. Δ· ÙÂÏÂ˘Ù·›· ¯ÚfiÓÈ· ÂÈÎÚ·ÙÔ‡Ó ÔÈ Gram ·ÚÓËÙÈΤ˜ ÏÔÈÌÒÍÂȘ Û ÔÛÔÛÙfi ¤ˆ˜ Î·È ÙÔ 52% ÙˆÓ ÛË„·ÈÌÈÒÓ. Δ· ÙÚ›· Û˘ÓËı¤ÛÙÂÚ· ÌÈÎÚfi‚È· Â›Ó·È Ô Ô ·ÓıÂÎÙÈÎfi˜ ÛÙËÓ ÌÂıÈÎÈÏÏ›ÓË ¯Ú˘Û›˙ˆÓ ÛÙ·Ê˘ÏfiÎÔÎÎÔ˜ (MRSA), Ë ÎÏÂÌÛȤÏÏ· Ù˘ Ó¢ÌÔÓ›·˜ Î·È Ë „¢‰ÔÌÔÓ¿‰·20. ∫·Ù¿ ÙÔÓ ÚÒÙÔ Ì‹Ó· ÌÂÙ¿ ÙË ÌÂÙ·ÌfiÛ¯Â˘ÛË ˘¿Ú¯ÂÈ Â›Û˘ ˘„ËÏfi˜ ΛӉ˘ÓÔ˜ ÁÈ· Ì˘ÎËÙÈ·ÛÈΤ˜ ÏÔÈÌÒÍÂȘ ·fi οÓÙÈÓÙ· ÂÓÒ ÔÈ ÈÔÁÂÓ›˜ ÏÔÈÌÒÍÂȘ Â›Ó·È Û¿ÓȘ ηٿ ÙË ¯ÚÔÓÈ΋ ·˘Ù‹ ÂÚ›Ô‰Ô. ÃÚÔÓÈ΋ ÂÚ›Ô‰Ô˜ ·fi 1-6 Ì‹Ó˜: ÂÌÊ·Ó›˙ÔÓÙ·È Â˘Î·ÈÚȷΤ˜ ÏÔÈÌÒÍÂȘ Ô˘ Û¯ÂÙ›˙ÔÓÙ·È Ì ÙË ÌÂÁ¿ÏË ‰fiÛË ·ÓÔÛÔηٷÛÙ·ÏÙÈÎÒÓ. ™˘Ó‹ıˆ˜ ÔÊ›ÏÔÓÙ·È Û ÌÂÁ·ÏÔ΢ÙÙ·ÚÔ˚fi Î·È Û ·Ô˘Û›· ÚÔʇϷ͢, ÌÔÚ› Ó· ÂÌÊ·ÓÈÛÙÔ‡Ó ÛÙÔ 50-60% ÙˆÓ ÌÂÙ·ÌÔÛ¯Â˘Ì¤ÓˆÓ3. ¶Úԉȷı¤ÙÔ˘Ó Â›Û˘ Û ‚·ÎÙËÚȷΤ˜ ÏÔÈÌÒÍÂȘ ÏfiÁˆ Ù˘ ÌÂÁ·Ï‡ÙÂÚ˘ ·ÓÔÛÔ·Ó¿ÚÎÂÈ·˜ Ô˘ ÚÔηÏ› Ô ÌÂÁ·ÏÔ΢ÙÙ·ÚÔ˚fi˜. ∞·ÈÙÔ‡Ó ıÂڷ›· ÁÈ· 2-4 ‚‰ÔÌ¿‰Â˜ ̤¯ÚÈ ÙËÓ ·ÚÓËÙÈÎÔÔ›ËÛË ÙˆÓ ·ÔÙÂÏÂÛÌ¿ÙˆÓ. §ÔÈÌÒÍÂȘ ·fi ·Û¤ÚÁÈÏÏÔ ÌÔÚÔ‡Ó Â›Û˘ Ó· ÂÌÊ·ÓÈÛÙÔ‡Ó ·˘Ù‹ ÙË ¯ÚÔÓÈ΋ ÂÚ›Ô‰Ô. ∞ÓÙÈÚÔÛˆÂ‡Ô˘Ó ÙÔ 1520% ÙˆÓ Ì˘ÎËÙÈ·ÛÈÎÒÓ ÏÔÈÌÒÍÂˆÓ Î·È ‰˘ÛÙ˘¯Ò˜ Ë ıÓËÙfiÙËÙ¿ ÙÔ˘˜ ·Ó¤Ú¯ÂÙ·È ÛÙÔ 100%21. ÕÏϘ ÈÔÁÂÓ›˜ ÏÔÈÌÒÍÂȘ ·˘Ù‹˜ Ù˘ ÂÚÈfi‰Ô˘ ÔÊ›ÏÔÓÙ·È ÛÙÔÓ Èfi Epstein-Barr, ÛÙÔÓ ·ÓıÚÒÈÓÔ ÂÚËÙÔ˚fi-6, Û ÈÔ‡˜ Ù˘ ÈÓÊÏÔ˘¤ÓÙ˙·˜ Î·È Û ·‰ÂÓÔ˚Ô‡˜19. ÃÚÔÓÈ΋ ÂÚ›Ô‰Ô˜ ¤Ú·Ó ÙˆÓ 6 ÌËÓÒÓ: ∂˘Î·ÈÚȷΤ˜ ÏÔÈÌÒÍÂȘ Â›Ó·È Û¿ÓȘ ·˘Ù‹ ÙË ¯ÚÔÓÈ΋ ÂÚ›Ô‰Ô Û ÌÂÙ·ÌÔÛ¯Â˘ı¤ÓÙ˜ Ô˘ Ï·Ì‚¿ÓÔ˘Ó ÛÙ·ıÂÚ‹ ‰fiÛË ·ÓÔÛÔηٷÛÙ·ÏÙÈÎÒÓ Î·È ÂÌÊ·Ó›˙Ô˘Ó ÈηÓÔÔÈËÙÈ΋ ÏÂÈÙÔ˘ÚÁ›· ÙÔ˘ ÌÔۯ‡̷ÙÔ˜. ∞˘ÙÔ› ÔÈ ·ÛıÂÓ›˜ Û˘Ó‹ıˆ˜ ·Ó·Ù‡ÛÔ˘Ó ÏÔÈÌÒÍÂȘ Ù˘ ÎÔÈÓfiÙËÙ·˜ fiˆ˜ Î·È Ô ÁÂÓÈÎfi˜ ÏËı˘ÛÌfi˜, Â›Ó·È fï˜ ÈÔ ÂÈÚÚ›˜ ÛÙËÓ ·Ó¿Ù˘ÍË ÏÔÈÌÒÍÂˆÓ ·fi ÏÂÁÈÔÓ¤ÏÏ·22. ÃÚfiÓȘ ÈÔÁÂÓ›˜ ÏÔÈÌÒÍÂȘ ÌÔÚ› Ó· Ô‰ËÁ‹ÛÔ˘Ó Û ÂÈÏÔΤ˜ ÛÙËÓ ·ÒÙÂÚË ·˘Ù‹ ÌÂÙ·ÌÔÛ¯Â˘ÙÈ΋ ÂÚ›Ô‰Ô. π‰È·›ÙÂÚË ÚÔÛÔ¯‹ ¯ÚÂÈ¿˙ÂÙ·È Û ·ÛıÂÓ›˜ Ì ÌËÓÈÁÁ›Ùȉ· Ô˘ ÌÔÚ› Ó· ÔÊ›ÏÂÙ·È Û ÎÚ˘ÙfiÎÔÎÎÔ ‹ ÏÈÛÙ¤ÚÈ·.
1‰. ∞Ó·ÁÓÒÚÈÛË Î·È ¤ÏÂÁ¯Ô˜ ÂÛÙ›·˜ Ïԛ̈͢23-26 ∏ ÂȉÈ΋ ·Ó·ÙÔÌÈ΋ ÂÛÙ›· Ù˘ Ïԛ̈͢ Ú¤ÂÈ Ó· ÂÓÙÔÈÛÙ› fiÛÔ ÙÔ ‰˘Ó·ÙfiÓ ÁÚËÁÔÚfiÙÂÚ· (fiˆ˜
129
‰È¿¯˘ÙË ÂÚÈÙÔÓ›Ùȉ·, ¯ÔÏ·ÁÁÂï›Ùȉ·) (1C) Î·È ÂÓÙfi˜ 6 ˆÚÒÓ ·fi ÙËÓ ¤Ó·ÚÍË Ù˘ ÛÔ‚·Ú‹˜ Û‹„˘ Î·È ÙÔ˘ ÛËÙÈÎÔ‡ ÛÔÎ (1B) ∂ÎÙ›ÌËÛË ·Ó ··ÈÙÔ‡ÓÙ·È ¿ÏÏÔÈ ¯ÂÈÚÈÛÌÔ›, fiˆ˜ ·ÚÔ¯¤Ù¢ÛË ·ÔÛÙ‹Ì·ÙÔ˜ (1C) ÕÌÂÛË ·ÓÙÈÌÂÙÒÈÛË, ÌÂÙ¿ ÙËÓ ÂÈÙ˘¯‹ ·Ú¯È΋ ·Ó·˙ˆÔÁfiÓËÛË(1C) (ÂÍ·›ÚÂÛË: Ë ÂÈÌÔÏ˘Ṳ̂ÓË ·ÁÎÚ·ÙÈ΋ Ó¤ÎÚˆÛË, fiÔ˘ Ë ¯ÂÈÚÔ˘ÚÁÈ΋ ·ÓÙÈÌÂÙÒÈÛË Â›Ó·È Î·Ï‡ÙÂÚ· Ó· ηı˘ÛÙÂÚ‹ÛÂÈ) (2B) °È· ¤ÏÂÁ¯Ô ÂÛÙ›·˜ ÂÈÏÔÁ‹ ¯ÂÈÚÈÛÌÔ‡ Ì ÙËÓ ÌÂÁ·Ï‡ÙÂÚË ·ÔÙÂÏÂÛÌ·ÙÈÎfiÙËÙ· Î·È ÙȘ ÏÈÁfiÙÂÚ˜ ÂÈÏÔΤ˜ (fiˆ˜ ‰È·‰ÂÚÌÈ΋ ·Ú¿ ¯ÂÈÚÔ˘ÚÁÈ΋ ·ÚÔ¯¤Ù¢ÛË ·ÔÛÙ‹Ì·ÙÔ˜) (1D) ∞ÔÌ¿ÎÚ˘ÓÛË ÂÓ‰·ÁÁÂÈ·ÎÒÓ Î·ıÂÙ‹ÚˆÓ ·Ó ıˆÚÔ‡ÓÙ·È ‰˘ÓËÙÈο ÌÔÏ˘Ṳ̂ÓÔÈ (1C)
2. ∞πªO¢À¡∞ªπ∫∏ À¶O™Δ∏ƒπ•∏™Àª¶§∏ƒøª∞Δπ∫∏ £∂ƒ∞¶∂π∞ 2·. ÃÔÚ‹ÁËÛË ˘ÁÚÒÓ27,28,29 ÃÔÚ‹ÁËÛË ÎÚ˘ÛÙ·ÏÏÔÂȉÒÓ ‹ ÎÔÏÏÔÂȉÒÓ (1B) ™Ùfi¯Ô˜ ∫ÂÓÙÚÈ΋ ºÏ‚È΋ ¶›ÂÛË (∫º¶) ≥8 mmHg (≥12 mmHg Û Ì˯·ÓÈο ·ÂÚÈ˙fiÌÂÓÔ˘˜ ·ÛıÂÓ›˜) (1C) ÃÚ‹ÛË ÂÈıÂÙÈ΋˜ ÛÙÚ·ÙËÁÈ΋˜ ¯ÔÚ‹ÁËÛ˘ ˘ÁÚÒÓ ·Ó ˘¿Ú¯ÂÈ ·ÈÌÔ‰˘Ó·ÌÈ΋ ‚ÂÏÙ›ˆÛË (1D) ÃÔÚ‹ÁËÛË 1000 mL ÎÚ˘ÛÙ·ÏÏÔÂȉԇ˜ ‹ 300-500 mL ÎÔÏÏÔÂȉԇ˜ Û 30 ÏÂÙ¿. ªÂÁ·Ï‡ÙÂÚË Î·È ÁÚËÁÔÚfiÙÂÚË ¯ÔÚ‹ÁËÛËÌÔÚ› Ó· ··ÈÙËı› ·Ó ˘¿Ú¯Ô˘Ó ÂӉ›ÍÂȘ ÈÛÙÈ΋˜ ˘Ô¿Ú‰Â˘Û˘ (1D) O Ú˘ıÌfi˜ ¯ÔÚ‹ÁËÛ˘ Ú¤ÂÈ Ó· ÂÏ·ÙÙˆı› ·Ó ÔÈ È¤ÛÂȘ Ï‹ÚˆÛ˘ Ù˘ ηډȿ˜ ·˘Í¿ÓÔÓÙ·È Î·È ‰ÂÓ ˘¿Ú¯ÂÈ ÂÚ·ÈÙ¤Úˆ ·ÈÌÔ‰˘Ó·ÌÈ΋ ‚ÂÏÙ›ˆÛË (1D) ∏ ÌÂϤÙË SAFE ¤‰ÂÈÍ fiÙÈ Ë ¯ÔÚ‹ÁËÛË ÏÂ˘ÎˆÌ·Ù›Ó˘ Â›Ó·È ·ÛÊ·Ï‹˜ Î·È ÈÛ¿ÍÈ·˜ ·ÔÙÂÏÂÛÌ·ÙÈÎfiÙËÙ·˜ Ì ٷ ÎÚ˘ÛÙ·ÏÏÔÂȉ‹27. ¶ÚÔËÁÔ‡ÌÂÓ˜ ÌÂÙ·-·Ó·Ï‡ÛÂȘ ‰ÂÓ ·Ó¤‰ÂÈÍ·Ó ‰È·ÊÔÚ¤˜ ÌÂٷ͇ ¯ÔÚ‹ÁËÛ˘ ÎÔÏÏÔÂȉÒÓ ‹ ÎÚ˘ÛÙ·ÏÏÔÂȉÒÓ28. ∞Ó Î·È Ë ¯ÔÚ‹ÁËÛË ·Ú·ÁfiÓÙˆÓ ˘‰ÚÔ͢·Ì‡ÏÈÔ˘ Èı·ÓfiÓ Ó· ·˘Í¿ÓÔ˘Ó ÙÔÓ Î›Ó‰˘ÓÔ ÔÍ›·˜ ÓÂÊÚÈ΋˜ ·Ó¿ÚÎÂÈ·˜ Û ·ÛıÂÓ›˜ Ì ۋ„Ë, Ë ÔÈÎÈÏÔÌÔÚÊ›· ÙˆÓ ·ÔÙÂÏÂÛÌ¿ÙˆÓ ·¤ÎÏÂÈÛ ÙÂÎÌËÚȈ̤ÓË Û‡ÛÙ·ÛË29. Δ· ÎÚ˘ÛÙ·ÏÏÔÂȉ‹ Â›Ó·È ÊÙËÓfiÙÂÚ·, ÂÓ¤¯Ô˘Ó fï˜ ·˘ÍË̤ÓÔ Î›Ó‰˘ÓÔ ÂÌÊ¿ÓÈÛ˘ Ó¢ÌÔÓÈÎÔ‡ Ôȉ‹Ì·ÙÔ˜ ÁÈ·Ù› ··ÈÙÔ‡Ó Ôχ ÂÚÈÛÛfiÙÂÚÔ fiÁÎÔ ÁÈ· ÙËÓ Â›Ù¢ÍË ÙÔ˘ ›‰ÈÔ˘ ·ÔÙÂϤÛÌ·ÙÔ˜ Ì ٷ ÎÔÏÏÔÂȉ‹. ™Â ·ÛıÂÓ›˜ ÌÂÙ¿ ÌÂÙ·Ìfi-
130
∂. ª√À§√À¢∏
Û¯Â˘ÛË ‹·ÙÔ˜, Ë ¯ÔÚ‹ÁËÛË ·Ï‚Ô˘Ì›Ó˘ ÎÚ›ÓÂÙ·È ÔÏϤ˜ ÊÔÚ¤˜ ·Ó·Áη›· ÏfiÁˆ ÙÔ˘ Û˘Ó˘¿Ú¯ÔÓÙÔ˜ ·ÛΛÙË30. ™Ùfi¯Ô˜ Â›Ó·È Ë ‰È·Ù‹ÚËÛË ÏÂ˘ÎˆÌ·Ù›Ó˘ ÔÚÔ‡ >2g/L. ∏ ¯ÔÚ‹ÁËÛ‹ Ù˘ ÂÚÈÔÚ›˙ÂÙ·È, fiÙ·Ó Û˘Á¯ÔÚËÁÔ‡ÓÙ·È Û˘Ì˘Îӈ̤ӷ ¤Ú˘ıÚ¿ Î·È ·Ú¿ÁˆÁ· ·›Ì·ÙÔ˜.
2‚. ∞ÁÁÂÈÛ˘Û·ÛÙÈο31-34 ¢È·Ù‹ÚËÛË ª¤Û˘ ∞ÚÙËÚȷ΋˜ ¶›ÂÛ˘ (ª∞¶) ≥65 mmHg (1C) ∞ÁÁÂÈÔÛ˘Û·ÛÙÈÎfi ÚÒÙ˘ ÂÈÏÔÁ‹˜ Ë ÓÔÚ·‰ÚÂÓ·Ï›ÓË Î·È Ë ÓÙÔ·Ì›ÓË (1C) ∏ ·‰ÚÂÓ·Ï›ÓË, Ë Ê·ÈÓ˘ÏÂÊÚ›ÓË, ‹ Ë ‚·ÛÔÚÂÛÛ›ÓË ‰ÂÓ Ú¤ÂÈ Ó· ¯ÔÚËÁÔ‡ÓÙ·È Û·Ó ·ÁÁÂÔÛ˘Û·ÛÙÈο ÚÒÙ˘ ÂÈÏÔÁ‹˜ ÛÙÔ ÛËÙÈÎfi ÛÔÎ (2C) ÃÚ‹ÛË ·‰ÚÂÓ·Ï›Ó˘ Û·Ó ÂfiÌÂÓË ÂÈÏÔÁ‹ Û ÛËÙÈÎfi ÛÔÎ fiÔ˘ Ë ·ÚÙËÚȷ΋ ›ÂÛË ‰ÂÓ ·ÓÙ·ÔÎÚ›ÓÂÙ·È ÛÙË ¯ÔÚ‹ÁËÛË ÓÔÚ·‰ÚÂÓ·Ï›Ó˘ ‹ ÓÙÔ·Ì›Ó˘ (2μ) ¢ÂÓ Ú¤ÂÈ Ó· ¯ÚËÛÈÌÔÔÈÂ›Ù·È Ë ÓÙÔ·Ì›ÓË ÁÈ· ÚÔÛÙ·Û›· Ù˘ ÓÂÊÚÈ΋˜ ÏÂÈÙÔ˘ÚÁ›·˜ (1A) ™Â ·ÛıÂÓ›˜ Ô˘ Ï·Ì‚¿ÓÔ˘Ó ·ÁÁÂÈÔÛ˘Û·ÛÙÈο, Ú¤ÂÈ Ó· ÙÔÔıÂÙÂ›Ù·È ÂÓ‰Ô·ÚÙËÚÈ·Îfi˜ ηıÂÙ‹Ú·˜ ̤ÙÚËÛ˘ ∞¶ fiÙ·Ó ·˘Ùfi Â›Ó·È ÂÊÈÎÙfi (1D) ™ÙÔ ÛËÙÈÎfi ÛÔÎ Ë ·˘ÙÔÚÚ‡ıÌÈÛË ÙÔ˘ ÙfiÓÔ˘ ÙˆÓ ·ÁÁ›ˆÓ ÌÔÚ› Ó· ¤¯ÂÈ ¯·ı› Î·È Ë ÈÛÙÈ΋ ¿Ú‰Â˘ÛË Ó· ÂÍ·ÚÙ¿Ù·È Â˘ı¤ˆ˜ ·Ó¿ÏÔÁ· ·fi ÙËÓ ›ÂÛË. ŒÙÛÈ, Ë ¯ÔÚ‹ÁËÛË ·ÁÁÂÈÔÛ˘Û·ÛÙÈÎÒÓ ÌÔÚ› Ó· ··ÈÙËı› ÁÈ· ‰È·Ù‹ÚËÛË Â·ÚÎÔ‡˜ ¿Ú‰Â˘Û˘ ÙˆÓ ÈÛÙÒÓ31. ∏ ÓÙÔ·Ì›ÓË ÚÔηÏ› ÂÚÈÛÛfiÙÂÚË Ù·¯˘Î·Ú‰›· Î·È ·ÚÚ˘ı̛˜ Û ۯ¤ÛË Ì ÙË ÓÔÚ·‰ÚÂÓ·Ï›ÓË Î·È Èı·ÓfiÓ ÂÈÙ›ÓÂÈ ÙËÓ ·ÓÔÛÔηٷÛÙÔÏ‹35. ™Â ÚfiÛÊ·ÙË ÔÏ˘ÎÂÓÙÚÈ΋, Ù˘¯·ÈÔÔÈË̤ÓË, ‰ÈÏ‹-Ù˘ÊÏ‹ ÌÂϤÙË Ê¿ÓËΠfiÙÈ Ë ¯ÔÚ‹ÁËÛË ÌÈÎÚ‹˜ ‰fiÛ˘ ‚·ÛÔÚÂÛÛ›Ó˘ ¤Ó·ÓÙÈ Ù˘ ÓÔÚ·‰ÚÂÓ·Ï›Ó˘, ‰ÂÓ ‚ÂÏÙÈÒÓÂÈ ÙË ÂÈ‚›ˆÛË34.
2Á. πÓfiÙÚÔ·36 ÃÚ‹ÛË ‰Ô‚Ô˘Ù·Ì›Ó˘ Û ·ÛıÂÓ›˜ Ì ηډȷ΋ ‰˘ÛÏÂÈÙÔ˘ÚÁ›· (·‡ÍËÛË È¤ÛÂˆÓ Ï‹ÚˆÛ˘ Ù˘ ηډȿ˜ Î·È ¯·ÌËÏ‹ ηډȷ΋ ·ÚÔ¯‹) (1C) ¢ÂÓ Ú¤ÂÈ Ó· ·˘Í¿ÓÂÙ·È Ô Î·Ú‰È·Îfi˜ ‰Â›ÎÙ˘ Û ˘ÂÚÊ˘ÛÈÔÏÔÁÈο ›‰· (1μ) O ÛËÙÈÎfi˜ ·ÛıÂÓ‹˜ Ô˘ ·Ú·Ì¤ÓÂÈ ˘ÔÙ·ÛÈÎfi˜ ÌÂÙ¿ ÙËÓ ·Ó¿Ù·ÍË Ì ˘ÁÚ¿ ÌÔÚ› Ó· ¤¯ÂÈ ¯·ÌËÏ‹, Ê˘ÛÈÔÏÔÁÈ΋ ‹ ˘„ËÏ‹ ηډȷ΋ ·ÚÔ¯‹. ŒÙÛÈ Ë ¯Ú‹ÛË ÈÓÔÙÚÔÔ˘/·ÁÁÂÈÔÛ˘Û·ÛÙÈÎÔ‡ ·Ú¿ÁÔÓÙ·, fiˆ˜ Ë ÓÔÚ·‰ÚÂÓ·Ï›ÓË ‹ Ë ÓÙÔ·Ì›ÓË,
Û˘ÓÈÛÙÒÓÙ·È fiÙ·Ó ‰ÂÓ ÌÂÙÚ¿Ù·È Ë Î·Ú‰È·Î‹ ·ÚÔ¯‹. ™Â ·ÛıÂÓ›˜ Û ÛËÙÈÎfi ÛÔÎ ÌÂÙ¿ ÌÂÙ·ÌfiÛ¯Â˘ÛË ‹·ÙÔ˜, ÂÂȉ‹ ÌÔÚ› Ó· ÚÔ˘‹Ú¯Â ˘ÂÚ‰˘Ó·ÌÈ΋ ΢ÎÏÔÊÔÚ›· ÚÈÓ ÙËÓ ÂÌÊ¿ÓÈÛË ÙÔ˘ ÛËÙÈÎÔ‡ ÛÔÎ, Ë ÂÎÙ›ÌËÛË Ù˘ ηډȷ΋˜ ·ÚÔ¯‹˜ Û·Ó ·fiÏ˘ÙË ÙÈÌ‹ ‰ÂÓ Â›Ó·È ·ÛÊ·Ï‹˜. ™’ ·˘Ù¤˜ ÙȘ ÂÚÈÙÒÛÂȘ Â›Ó·È ÚÔÙÈÌÒÙÂÚÔ Ó· ·ÍÈÔÏÔÁÔ‡ÓÙ·È ÔÈ ‰È·Î˘Ì¿ÓÛÂȘ Ù˘ ηډȷ΋˜ ·ÚÔ¯‹˜.
2‰. ™ÙÂÚÔÂȉ‹37-39 ÃÚ‹ÛË ÂÓ‰ÔÊϤ‚È·˜ ˘‰ÚÔÎÔÚÙÈ˙fiÓ˘ Û ÂÓ‹ÏÈΘ ·ÛıÂÓ›˜ Û ÛËÙÈÎfi ÛÔÎ fiÙ·Ó Ë ˘fiÙ·ÛË ÂÈ̤ÓÂÈ ·Ú¿ ÙËÓ ·Ó¿Ù·ÍË Ì ·Ú΋ ˘ÁÚ¿ Î·È ÙËÓ ¯Ú‹ÛË ·ÁÁÂÈÔÛ˘Û·ÛÙÈÎÒÓ (2C) ¢ÔÎÈÌ·Û›· ‰È¤ÁÂÚÛ˘ Ì ACTH ‰ÂÓ ÎÚ›ÓÂÙ·È ··Ú·›ÙËÙË ÁÈ· ÙËÓ ÂÓÙfiÈÛË ÙˆÓ ·ÛıÂÓÒÓ Ì ÛËÙÈÎfi ÛÔÎ Ô˘ ı· Ï¿‚Ô˘Ó ˘‰ÚÔÎÔÚÙÈ˙fiÓË (2B) ∏ ˘‰ÚÔÎÔÚÙÈ˙fiÓË Â›Ó·È ÚÔÙÈÌÒÙÂÚË ·fi ÙË ‰ÂÍ·ÌÂı·˙fiÓË (2B) ∏ ÊıÔÚÈÔ¸‰ÚÔÎÔÚÙÈ˙fiÓË ÌÔÚ› Ó· Û˘ÌÂÚÈÏËÊı› ÚÔ·ÈÚÂÙÈο (2C) ∏ ıÂڷ›· Ì ÛÙÂÚÔÂȉ‹ ÌÔÚ› Ó· ·ÔÛ˘Úı›, ·Ó ‰ÂÓ ··ÈÙÔ‡ÓÙ·È Ï¤ÔÓ ·ÁÁÂÈÔÛ˘Û·ÛÙÈο (2D) ∏ ‰fiÛË ˘‰ÚÔÎÔÚÙÈ˙fiÓ˘ Ú¤ÂÈ Ó· Â›Ó·È ≤300 mg/24ˆÚÔ (1A) ¢ÂÓ Ú¤ÂÈ Ó· ¯ÚËÛÈÌÔÔÈÔ‡ÓÙ·È ÎÔÚÙÈÎÔÛÙÂÚÔÂȉ‹ ÁÈ· ıÂڷ›· Û‹„˘ ·Ó ‰ÂÓ ˘¿Ú¯ÂÈ ÛÔÎ, ÂÎÙfi˜ ·Ó ˘¿Ú¯Ô˘Ó ÂӉ›ÍÂȘ ÈÛÙÔÚÈÎÔ‡ ·‰ÚÂÓÂÚÁÈ΋˜ ·Ó¿ÚÎÂÈ·˜ (1D) ∏ ¯Ú‹ÛË ÂÙÔÌȉ¿Ù˘ Â›Ó·È ÚÔÙÈÌÒÙÂÚÔ Ó· ·ÔʇÁÂÙ·È Î·Ù¿ ÙË ‰È·‰Èηۛ· Ù˘ ‰È·ÛˆÏ‹ÓˆÛ˘, ÁÈ·Ù› ÌÔÚ› Ó· ηٷÛÙ›ÏÂÈ ÙÔÓ ˘Ôı·Ï·ÌÔ-˘ÔÊ˘ÛÈÔ-ÂÈÓÂÊÚȉÈÎfi ¿ÍÔÓ·40. ∏ Û¯ÂÙÈ΋ ÂÈÓÂÊÚȉÈ΋ ·Ó¿ÚÎÂÈ· Â›Ó·È Û˘ÓËıÈṲ̂ÓË Û ·ÛıÂÓ›˜ Ì ˷ÙÈ΋ ÓfiÛÔ, ÊÙ¿ÓÔÓÙ·˜ ÛÙÔ 33% ÙˆÓ ·ÛıÂÓÒÓ Ì ÔÍ›· Ë·ÙÈ΋ ·Ó¿ÚÎÂÈ· Î·È ÙÔ 65% ÙˆÓ ¯ÚfiÓÈˆÓ Ë·ÙÔ·ıÒÓ Ì ۋ„Ë. ™Â ·ÛıÂÓ›˜ ÌÂÙ¿ ÌÂÙ·ÌfiÛ¯Â˘ÛË ‹·ÙÔ˜ ÛÙÔ˘˜ ÔÔ›Ô˘˜ ¯ÚËÛÈÌÔÔÈÂ›Ù·È ÚˆÙfiÎÔÏÏÔ ÂχıÂÚÔ ÎÔÚÙÈÎÔÂȉÒÓ, Û¯ÂÙÈ΋ ÂÈÓÂÊÚȉÈ΋ ·Ó¿ÚÎÂÈ· ˘¿Ú¯ÂÈ Û ÔÛÔÛÙfi ¤ˆ˜ Î·È 92%, ·ÎfiÌ· Î·È Û ·Ô˘Û›· Û‹„˘41.
2Â. ∂ÓÂÚÁÔÔÈË̤ÓË ·ÓıÚÒÈÓË ÚˆÙ›ÓË C (rhAPC)42-45 ÃÚ‹ÛË rhAPC Û ÂÓ‹ÏÈΘ ·ÛıÂÓ›˜ Ì ۋ„Ë Ô˘ Ô‰ËÁ› Û ‰˘ÛÏÂÈÙÔ˘ÚÁ›· ÔÚÁ¿ÓˆÓ Ì ÌÂÁ¿ÏÔ ÎÏÈÓÈÎfi ΛӉ˘ÓÔ ı·Ó¿ÙÔ˘ (APACHE II ≥25 ‹ Û‡Ó‰ÚÔÌÔ ‰˘ÛÏÂÈÙÔ˘ÚÁ›·˜ ÔÏÏ·ÏÒÓ ÔÚÁ¿-
METAMO™XEY™Eπ™ 2008
ÓˆÓ) ·Ó ‰ÂÓ ˘¿Ú¯Ô˘Ó ·ÓÙÂӉ›ÍÂȘ (2B, 2C ÁÈ· ÌÂÙÂÁ¯ÂÈÚËÙÈÎÔ‡˜ ·ÛıÂÓ›˜) ∂Ó‹ÏÈΘ ·ÛıÂÓ›˜ Ì ÛÔ‚·Ú‹ Û‹„Ë Î·È ¯·ÌËÏfi ΛӉ˘ÓÔ ı·Ó¿ÙÔ˘ (APACHE II <20 ‹ ‰˘ÛÏÂÈÙÔ˘ÚÁ›· ÂÓfi˜ ÔÚÁ¿ÓÔ˘) ‰ÂÓ Ú¤ÂÈ Ó· Ï·Ì‚¿ÓÔ˘Ó rhAPC (1A) ∏ ¯Ú‹ÛË ÙÔ˘ rhAPC Û ·ÛıÂÓ›˜ ÌÂÙ¿ ÌÂÙ·ÌfiÛ¯Â˘ÛË ‹·ÙÔ˜ Ô˘ ÂÌÊ·Ó›˙Ô˘Ó ‰È·Ù·Ú·¯¤˜ ËÎÙÈÎfiÙËÙ·˜ Î·È ıÚÔÌ‚ÔÂÓ›· Â›Ó·È ÂÚÈÛÛfiÙÂÚÔ ÚÔ‚ÏËÌ·ÙÈ΋, ÁÈ·Ù› ·˘Í¿ÓÂÈ ÙÔÓ Î›Ó‰˘ÓÔ ·ÈÌÔÚÚ·ÁÈÎÒÓ ÂÈÏÔÎÒÓ. ∏ ¯Ú‹ÛË ÙÔ˘ Û ÌÂÙ·ÌÔÛ¯Â˘ı¤ÓÙ˜ ÂÚÈÔÚ›˙ÂÙ·È Û ÂÏ¿¯ÈÛÙ· case reports46.
3. À¶O™Δ∏ƒπ∫Δπ∫∏ £∂ƒ∞¶∂π∞ 3·. ÃÔÚ‹ÁËÛË ·Ú·ÁÒÁˆÓ ·›Ì·ÙÔ˜47-50 ÃÔÚ‹ÁËÛË Û˘Ì˘ÎÓˆÌ¤ÓˆÓ ÂÚ˘ıÚÒÓ ·ÈÌÔÛÊ·ÈÚ›ˆÓ fiÙ·Ó Ë ·ÈÌÔÛÊ·ÈÚ›ÓË ÂÏ·ÙÙˆı› <7 g/dL, Ì ÛÙfi¯Ô Ë ·ÈÌÔÛÊ·ÈÚ›ÓË Ó· ‰È·ÙËÚÂ›Ù·È ÌÂٷ͇ 7-9 g/dL ÛÙÔ˘˜ ÂÓ‹ÏÈΘ (1B). ¶Èı·ÓfiÓ ··ÈÙÔ‡ÓÙ·È ˘„ËÏfiÙÂÚ· ›‰· Û ÂȉÈΤ˜ ηٷÛÙ¿ÛÂȘ (Ì˘Ôηډȷ΋ ÈÛ¯·ÈÌ›·, ÛÔ‚·Ú‹ ˘ÔÍ›·, ÔÍ›· ·ÈÌÔÚÚ·Á›·, ΢·ÓˆÙÈ΋ ηډȷ΋ ÓfiÛÔ˜ ‹ Á·Ï·ÎÙÈ΋ ÔͤˆÛË) ∏ ÂÚ˘ıÚÔÔÈËÙ›ÓË ‰ÂÓ Ú¤ÂÈ Ó· ¯ÚËÛÈÌÔÔÈÂ›Ù·È Û ·Ó·ÈÌ›· Û¯ÂÙÈ˙fiÌÂÓË Ì ۋ„Ë. ªÔÚ› Ó· ¯ÚËÛÈÌÔÔÈËı› Û ¿ÏϘ ÂȉÈΤ˜ ηٷÛÙ¿ÛÂȘ fiˆ˜ ÓÂÊÚÈ΋ ·Ó¿ÚÎÂÈ· (2B) ¢ÂÓ Ú¤ÂÈ Ó· ¯ÚËÛÈÌÔÔÈÂ›Ù·È ÊÚ¤ÛÎÔ Î·Ù„˘Á̤ÓÔ Ï¿ÛÌ· ÁÈ· ‰ÈfiÚıˆÛË ÂÚÁ·ÛÙËÚÈ·ÎÒÓ ‰Â‰ÔÌ¤ÓˆÓ ÂÎÙfi˜ ·Ó Û˘Ó˘¿Ú¯ÂÈ ·ÈÌÔÚÚ·Á›· ‹ ÚfiÎÂÈÙ·È Ó· Á›ÓÂÈ ÚÔÁÚ·ÌÌ·ÙÈṲ̂ÓË ÂÂÌ‚·ÙÈ΋ ·Ú¤Ì‚·ÛË (2D) ¢ÂÓ ··ÈÙÂ›Ù·È ıÂڷ›· Ì ·ÓÙÈıÚÔÌ‚›ÓË (1B) ÃÔÚ‹ÁËÛË ·ÈÌÔÂÙ·ÏÏ›ˆÓ fiÙ·Ó (2D) Â›Ó·È <5000/mm3 ·ÓÂÍ·Úًو˜ ·ÈÌÔÚÚ·Á›·˜ Â›Ó·È 5000-30000/mm3 Î·È ˘¿Ú¯ÂÈ ·˘ÍË̤ÓÔ˜ ΛӉ˘ÓÔ˜ ·ÈÌÔÚÚ·Á›·˜ ÙÈ̤˜ > 50000/mm3 ··ÈÙÔ‡ÓÙ·È ÁÈ· ¯ÂÈÚÔ˘ÚÁÂ›Ô ‹ ÂÂÌ‚·ÙÈ΋ ·Ú¤Ì‚·ÛË
3‚. ªË¯·ÓÈÎfi˜ ·ÂÚÈÛÌfi˜ Û ·ÛıÂÓ›˜ Ì ÔÍ›· ‚Ï¿‚Ë Ó‡ÌÔÓ·/Û‡Ó‰ÚÔÌÔ ÔÍ›·˜ ·Ó·Ó¢ÛÙÈ΋˜ ‰˘Û¯¤ÚÂÈ·˜ (ALI/ARDS) ÔÊÂÈÏfiÌÂÓÔ Û ۋ„Ë51-60 ™Ùfi¯Ô˜ ·Ó·ÓÂfiÌÂÓÔ˜ fiÁÎÔ˜ 6mL/kg ȉ·ÓÈÎÔ‡ ‚¿ÚÔ˘˜ ÛÒÌ·ÙÔ˜ Û ·ÛıÂÓ›˜ Ì ALI/ARDS (1B) ™Ùfi¯Ô˜ ·Ú¯È΋ ÛÙ·ÙÈ΋ ›ÂÛË (PPlateau)) ≤30 cm H2O (1C)
131
∂ÈÙÚ¤ÂÙ·È Ë ˘ÂÚηӛ· Ì ÛÙfi¯Ô ÙËÓ ÂÏ¿ÙÙˆÛË ÙÔ˘ ·Ó·ÓÂfiÌÂÓÔ˘ fiÁÎÔ˘ Î·È Ù˘ ÛÙ·ÙÈ΋˜ ›ÂÛ˘ (fi¯È Û ·ÛıÂÓ›˜ Ì ÚÔ˘¿Ú¯Ô˘Û· ÂÍÂÛËÌ·Ṳ̂ÓË ÌÂÙ·‚ÔÏÈ΋ ÔͤˆÛË Î·È Ï‹Ú˘ ·ÓÙ¤Ó‰ÂÈÍË Û ·ÛıÂÓ›˜ Ì ÂÓ‰ÔÎÚ·Óȷ΋ ˘¤ÚÙ·ÛË) (1C) ∞·ÈÙÂ›Ù·È ıÂÙÈ΋ ÙÂÏÈÎÔÂÎÓ¢ÛÙÈ΋ ›ÂÛË (PEEP) ÁÈ· ·ÔÊ˘Á‹ Û‡ÌÙ˘Í˘ ÙˆÓ Î˘„ÂÏ›‰ˆÓ ÛÙÔ Ù¤ÏÔ˜ Ù˘ ÂÎÓÔ‹˜ (1C) ÃÚ‹ÛË ÚËÓÔ‡˜ ı¤Û˘ Û ·ÛıÂÓ›˜ Ô˘ ·ÂÚ›˙ÔÓÙ·È Ì ÌÂÁ¿ÏË Û˘ÁΤÓÙÚˆÛË ÂÈÛÓÂÔ̤ÓÔ˘ Ô͢ÁfiÓÔ˘ (FiO2) ‹ Ôχ ˘„ËÏ‹ ÛÙ·ÙÈ΋ ›ÂÛË, ÚÔÓÔÒÓÙ·˜ ÁÈ· ÙÔ˘˜ Èı·ÓÔ‡˜ ÎÈÓ‰‡ÓÔ˘˜ ·fi ÙËÓ ·ÏÏ·Á‹ ı¤Û˘ (2C) ¢È·Ù‹ÚËÛË ÙˆÓ Ì˯·ÓÈο ·ÂÚÈ˙fiÌÂÓˆÓ ·ÛıÂÓÒÓ Û ËÌÈηıÂÛÙË΢›· ı¤ÛË (450), ÂÎÙfi˜ ·Ó ·ÓÙÂӉ›ÎÓ˘Ù·È, ÔfiÙ ٛıÂÓÙ·È ÌÂٷ͇ 30-450 (1C) ªË ÂÂÌ‚·ÙÈÎfi˜ Ì˯·ÓÈÎfi˜ ·ÂÚÈÛÌfi˜ ¯ÚËÛÈÌÔÔÈÂ›Ù·È Û ÂÚÈÔÚÈṲ̂ÓÔ ·ÚÈıÌfi ·ÛıÂÓÒÓ Ì ̤ÙÚÈ· ¤ˆ˜ ÛÔ‚·Ú‹ ˘ÔÍ·ÈÌÈ΋ ·Ó·Ó¢ÛÙÈ΋ ·Ó¿ÚÎÂÈ·. OÈ ·ÛıÂÓ›˜ Ú¤ÂÈ Ó· Â›Ó·È ·ÈÌÔ‰˘Ó·ÌÈο ÛÙ·ıÂÚÔ›, Ó· ÓÈÒıÔ˘Ó ¿ÓÂÙ·, Ó· Â›Ó·È Â‡ÎÔÏ· ·Ê˘Ó›ÛÈÌÔÈ, ÈηÓÔ› Ó· ÚÔÛٷهԢÓ/ηı·Ú›˙Ô˘Ó ÙÔÓ ·ÂÚ·ÁˆÁfi ÙÔ˘˜ Î·È Ó· ·Ó·Ì¤ÓÂÙ·È Û‡ÓÙÔÌË ‚ÂÏÙ›ˆÛ‹ ÙÔ˘˜ (2B) ÃÚ‹ÛË ÚˆÙÔÎfiÏÏÔ˘ ·ÔÁ·Ï·ÎÙÈÛÌÔ‡ Î·È ‰ÔÎÈÌ·Û›·˜ ·˘ÙfiÌ·ÙÔ˘ ·ÂÚÈÛÌÔ‡ ÁÈ· ÂÎÙ›ÌËÛË Ù˘ ‰˘Ó·ÙfiÙËÙ·˜ ‰È·ÎÔ‹˜ ÙÔ˘ Ì˯·ÓÈÎÔ‡ ·ÂÚÈÛÌÔ‡ (1A) ∏ ‰ÔÎÈÌ·Û›· ·˘ÙfiÌ·ÙÔ˘ ·ÂÚÈÛÌÔ‡ Á›ÓÂÙ·È ‹ Ì ¯·ÌËÏfi Â›Â‰Ô ›ÂÛ˘ ˘ÔÛÙ‹ÚÈ͢ (pressure support) Î·È Û˘Ó¯ԇ˜ ıÂÙÈ΋˜ ›ÂÛ˘ ·ÂÚ·ÁˆÁÒÓ 5 cm H2O ‹ Ì ‰ÔÎÈÌ·Û›· T-piece ¶ÚÈÓ ·fi ÙË ‰ÔÎÈÌ·Û›· ·˘ÙfiÌ·ÙÔ˘ ·ÂÚÈÛÌÔ‡ Ô ·ÛıÂÓ‹˜ Ú¤ÂÈ Ó· ›ӷÈ: ∂‡ÎÔÏ· ·Ê˘Ó›ÛÈÌÔ˜ ∞ÈÌÔ‰˘Ó·ÌÈο ÛÙ·ıÂÚfi˜ ¡· ÌËÓ ¤¯ÂÈ ÂÌÊ·Ó›ÛÂÈ Ó¤· ‰˘ÓËÙÈο ÂÈΛӉ˘ÓË ÂÈÏÔ΋ ¡· ··ÈÙ› ¯·ÌËÏ‹ ·Ó·Ó¢ÛÙÈ΋ ˘ÔÛÙ‹ÚÈÍË ¡· ··ÈÙ› ˘ÎÓfiÙËÙ˜ ÂÈÛÓÂÔ̤ÓÔ˘ Ô͢ÁfiÓÔ˘ ¯·ÌËϤ˜ Ô˘ Ó· ÌÔÚÔ‡Ó Ó· ¯ÔÚËÁËıÔ‡Ó Ì ·ÛÊ¿ÏÂÈ· ̤ۈ Ì¿Ûη˜ ¢ÂÓ ··ÈÙÂ›Ù·È Ë ¯Ú‹ÛË Î·ıÂÙ‹Ú· ̤ÙÚËÛ˘ Ù˘ ›ÂÛ˘ Ù˘ Ó¢ÌÔÓÈ΋˜ ·ÚÙËÚ›·˜ ÁÈ· ¤ÏÂÁ¯Ô ÚÔ˘Ù›Ó·˜ Û ·ÛıÂÓ›˜ Ì ALI/ARDS (1A) ™ÙÚ·ÙËÁÈ΋ Û˘ÓÙËÚËÙÈ΋˜ ¯ÔÚ‹ÁËÛ˘ ˘ÁÚÒÓ Û ·ÛıÂÓ›˜ Ì ALI Ô˘ ‰ÂÓ ÂÌÊ·Ó›˙Ô˘Ó ÛÙÔȯ›· ÈÛÙÈ΋˜ ˘Ô¿Ú‰Â˘Û˘ (1C)
132
∂. ª√À§√À¢∏
™Â ·ÛıÂÓ›˜ ÌÂÙ¿ ÌÂÙ·ÌfiÛ¯Â˘ÛË ‹·ÙÔ˜ Ë ÂÏÂÁ¯fiÌÂÓË ˘ÂÚηӛ· Ú¤ÂÈ Ó· ÂÊ·ÚÌfi˙ÂÙ·È Ì ȉȷ›ÙÂÚË ÚÔÛÔ¯‹ ÏfiÁˆ Ù˘ Èı·Ó‹˜ Û˘Ó‡·Ú͢ Ë·ÙÈ΋˜ ÂÁÎÂÊ·ÏÔ¿ıÂÈ·˜.
3Á. ∫·Ù·ÛÙÔÏ‹, ·Ó·ÏÁËÛ›· Î·È Ì˘Ô¯¿Ï·ÛË61-63 ÃÚ‹ÛË ÚˆÙÔÎfiÏÏˆÓ Î·Ù·ÛÙÔÏ‹˜ Û ‚·Ú¤ˆ˜ ¿Û¯ÔÓÙ˜ Ì˯·ÓÈο ·ÂÚÈ˙fiÌÂÓÔ˘˜ ·ÛıÂÓ›˜ (1B) ÃÚ‹ÛË Î·Ù·ÛÙ·ÏÙÈÎÒÓ ·Ú·ÁfiÓÙˆÓ Â›ÙÂ Û·Ó ÂÊ¿·Í ¯ÔÚ‹ÁËÛË Â›Ù ÛÂ Û˘Ó¯‹ ÂÓ‰ÔÊϤ‚È· ¯ÔÚ‹ÁËÛË, Ì ÛÙfi¯Ô ›Ù¢ÍË ÚÔηıÔÚÈṲ̂ÓÔ˘ ÂȤ‰Ô˘ ηٷÛÙÔÏ‹˜ (‚¿ÛÂÈ Îϛ̷η˜), Ì ‰˘Ó·ÙfiÙËÙ· ηıËÌÂÚÈÓ‹˜ ÂÏ¿ÙÙˆÛ˘ ‹ ‰È·ÎÔ‹˜ ÙÔ˘˜ ÁÈ· ›Ù¢ÍË ·Ê‡ÓÈÛ˘. ∂·Ó·ÚÔÛ‰ÈÔÚÈÛÌfi˜ ÙˆÓ ‰fiÛˆÓ, ·Ó ÎÚÈı› ·Ó·Áη›Ô (1B) ∞ÔÊ˘Á‹ ¯ÔÚ‹ÁËÛ˘ Ì˘Ô¯¿Ï·Û˘ ·Ó ·˘Ùfi Â›Ó·È ‰˘Ó·ÙfiÓ. ŒÏÂÁ¯Ô˜ ÙÔ˘ ‚·ıÌÔ‡ Ì˘Ô¯¿Ï·Û˘ Ì ‰ÔÎÈÌ·Û›· train-of-four, fiÙ·Ó ¯ÚËÛÈÌÔÔÈÂ›Ù·È Û˘Ó¯‹˜ ¯ÔÚ‹ÁËÛË Ì˘Ô¯·Ï·ÚˆÙÈÎÒÓ (1B)
3‰. ŒÏÂÁ¯Ô˜ ÁÏ˘Îfi˙˘64-66 ÃÚ‹ÛË ÂÓ‰ÔÊϤ‚È·˜ ÈÓÛÔ˘Ï›Ó˘ ÁÈ· ¤ÏÂÁ¯Ô Ù˘ ˘ÂÚÁÏ˘Î·ÈÌ›·˜ Û ·ÛıÂÓ›˜ Ì ÛÔ‚·Ú‹ Û‹„Ë (·ÎÔÏÔ˘ı› ÙËÓ ÛÙ·ıÂÚÔÔ›ËÛË ÛÙË ª∂£) (1B) ¶ÚÔÛ¿ıÂÈ· ‰È·Ù‹ÚËÛ˘ ÂȤ‰ˆÓ ÁÏ˘Îfi˙˘ <150 mg/dL ¯ÚËÛÈÌÔÔÈÒÓÙ·˜ ÂÁÁÂÎÚÈ̤ӷ ÚˆÙfiÎÔÏÏ· ¯ÔÚ‹ÁËÛ˘ ÈÓÛÔ˘Ï›Ó˘ (1C) ¶ÚfiÓÔÈ· ÁÈ· ¯ÔÚ‹ÁËÛË ÁÏ˘Îfi˙˘ Î·È ¤ÏÂÁ¯Ô˜ ÙÈÌÒÓ ÁÏ˘Îfi˙˘ ·Ó¿ 1-2 ÒÚ˜ (·Ó¿ 4 ÒÚ˜ fiÙ·Ó Ô ·ÛıÂÓ‹˜ ÛÙ·ıÂÚÔÔÈËı›) Û ·ÛıÂÓ›˜ Ô˘ Ï·Ì‚¿ÓÔ˘Ó ÂÓ‰ÔÊϤ‚È· ÈÓÛÔ˘Ï›ÓË (1C) ¶ÚÔÛÔ¯‹ ÛÙȘ ÙÈ̤˜ ÁÏ˘Îfi˙˘, ȉȷ›ÙÂÚ· ÙȘ ¯·ÌËϤ˜ ÁÈ·Ù› Ë Ì¤ÙÚËÛË ÁÏ˘Îfi˙˘ ÂËÚ¿˙ÂÙ·È ·fi ‰È¿ÊÔÚÔ˘˜ ·Ú¿ÁÔÓÙ˜, fiˆ˜ Ô Ù‡Ô˜ Î·È ÙÔ ÌÔÓÙ¤ÏÔ Ù˘ Û˘Û΢‹˜ Ô˘ ¯ÚËÛÈÌÔÔÈÂ›Ù·È Î·È Ô ·ÈÌ·ÙÔÎÚ›Ù˘ ÙÔ˘ ·ÛıÂÓ‹ (1B) ¶ÚfiÛÊ·Ù·, ÔÏ˘ÎÂÓÙÚÈ΋, Ù˘¯·ÈÔÔÈË̤ÓË ÌÂϤÙË ¤‰ÂÈÍ fiÙÈ Ë ÂÓÙ·ÙÈ΋ ÈÓÛÔ˘ÏÈÓÔıÂڷ›· Ì ÛÙfi¯Ô ÙËÓ Â˘ÁÏ˘Î·ÈÌ›· Û ·ÛıÂÓ›˜ Ì ÛÔ‚·Ú‹ Û‹„Ë Ô‰ËÁ› Û 4Ï·ÛÈ·ÛÌfi ÙˆÓ ÂÂÈÛÔ‰›ˆÓ ˘ÔÁÏ˘Î·ÈÌ›·˜, ¯ˆÚ›˜ Ó· ‚ÂÏÙÈÒÓÂÈ ÙËÓ ÂÈ‚›ˆÛË66. ™Â ·ÛıÂÓ›˜ Ì ΛÚÚˆÛË, ÌfiÓÔ ÙÔ 27% ¤¯ÂÈ Ê˘ÛÈÔÏÔÁÈ΋ ·ÓÔ¯‹ ÛÙË ÁÏ˘Îfi˙Ë, 38% ÂÌÊ·Ó›˙ÂÈ ‰˘Û·ÓÂÍ›· ÛÙË ÁÏ˘Îfi˙Ë Î·È 35% Â›Ó·È ‰È·‚ËÙÈÎÔ›. ∏ ÚÔÂÁ¯ÂÈÚËÙÈ΋ ‰˘Û·ÓÂÍ›· ÛÙË ÁÏ˘Îfi˙Ë Î·È Ô ÚÔ˘¿Ú¯ˆÓ ‰È·‚‹Ù˘ ·ÔÙÂÏÔ‡Ó ÙÔ˘˜ ·ÓÂÍ¿ÚÙËÙÔ˘˜ ·Ú¿ÁÔÓÙ˜ ÎÈÓ‰‡ÓÔ˘ ÁÈ· ÙËÓ ÂÌÊ¿ÓÈÛË ÙˆÓ ‰È·Ù·Ú·¯ÒÓ ·˘ÙÒÓ Î·È ÛÙËÓ ÌÂÙ¿ ÙËÓ ÌÂÙ·ÌfiÛ¯Â˘-
ÛË ‹·ÙÔ˜ ÂÚ›Ô‰Ô. OÈ ‰È·Ù·Ú·¯¤˜ ·˘Ù¤˜ ÛÙÔ˘˜ ÌÂÙ·ÌÔÛ¯Â˘Ì¤ÓÔ˘˜ Â›Ó·È ·ÓÂÍ¿ÚÙËÙ˜ ·fi ÙËÓ ·ÓÔÛÔηٷÛÙÔÏ‹ Ô˘ Ï·Ì‚¿ÓÔ˘Ó67 Î·È ÛÂ Û˘Ó‰˘·ÛÌfi Ì ÙÔ ÛÙÚ˜ Ù˘ ¤̂·Û˘ ηٿ ÙËÓ ¿ÌÂÛË Î˘Ú›ˆ˜ ÌÂÙ·ÌÔÛ¯Â˘ÙÈ΋ ÂÚ›Ô‰Ô, ηıÈÛÙÔ‡Ó Ôχ ÈÔ ‰‡ÛÎÔÏË ÙË Ú‡ıÌÈÛË ÙˆÓ ÂȤ‰ˆÓ ÁÏ˘Îfi˙˘, ȉ›ˆ˜ ·Ó ÔÈ ·ÛıÂÓ›˜ ·˘ÙÔ› ÂÈÏ·ÎÔ‡Ó Ì ۋ„Ë.
3Â. £Âڷ›˜ ˘ÔηٿÛÙ·Û˘ ÓÂÊÚÈ΋˜ ÏÂÈÙÔ˘ÚÁ›·˜68 ∏ ‰È·ÎÂÎÔÌ̤ÓË ·ÈÌÔ‰È¿Ï˘ÛË Î·È Ë Û˘Ó¯‹˜ ÊÏ‚Ô-ÊÏ‚È΋ ·ÈÌԉȷ‰È‹ıËÛË Û˘ÓÈÛÙÒÓÙ·È ÂÍ ›ÛÔ˘ (2B) ∏ Û˘Ó¯‹˜ ÊÏ‚Ô-ÊÏ‚È΋ ·ÈÌԉȷ‰È‹ıËÛË Î·ıÈÛÙ¿ ¢ÎÔÏfiÙÂÚË ÙËÓ ·ÓÙÈÌÂÙÒÈÛË ÙˆÓ ·ÈÌÔ‰˘Ó·ÌÈο ·ÛÙ·ıÒÓ ·ÛıÂÓÒÓ (2D)
3ÛÙ. £Âڷ›· Ì ‰ÈÙÙ·ÓıÚ·ÎÈο69 ¢ÂÓ ··ÈÙÂ›Ù·È Ë ¯ÔÚ‹ÁËÛË ‰ÈÙÙ·ÓıÚ·ÎÈÎÒÓ Ì ÛÎÔfi ÙË ·ÈÌÔ‰˘Ó·ÌÈ΋ ‚ÂÏÙ›ˆÛË ‹ ÙËÓ ÂÏ¿ÙÙˆÛË ÙˆÓ ·ÁÁÂÈÔÛ˘Û·ÛÙÈÎÒÓ Ô˘ ··ÈÙÔ‡ÓÙ·È fiÙ·Ó ıÂڷ‡ÂÙ·È Ô͢·ÈÌ›· ÔÊÂÈÏfiÌÂÓË Û ·Ú·ÁˆÁ‹ Á·Ï·ÎÙÈÎÒÓ Ì pH ≥7,15 (1μ)
3˙. ¶ÚÔʇϷÍË Ù˘ ÂÓ Ùˆ ‚¿ıÂÈ ÊÏ‚ÔıÚfiÌ‚ˆÛ˘70,71 ÃÚ‹ÛË ¯·ÌËÏÒÓ ‰fiÛÂˆÓ ÎÏ·ÛÈ΋˜ Ë·Ú›Ó˘ ‹ Ë·Ú›ÓË ¯·ÌËÏÔ‡ ÌÔÚÈ·ÎÔ‡ ‚¿ÚÔ˘˜, ÂÎÙfi˜ ·Ó ·ÓÙÂӉ›ÎÓ˘Ù·È (fiˆ˜ Û ÌÂÁ¿ÏË ıÚÔÌ‚ÔÂÓ›·, Û ÂÓÂÚÁfi ·ÈÌÔÚÚ·Á›· Î·È Û ÚfiÛÊ·ÙË ÂÓ‰ÔÎÚ·Óȷ΋ ·ÈÌÔÚÚ·Á›·) (1∞) ÃÚ‹ÛË Ì˯·ÓÈÎÒÓ Ì¤ÛˆÓ ÚÔʇϷ͢, ·Ó ˘¿Ú¯Ô˘Ó ·ÓÙÂӉ›ÍÂȘ ÁÈ· Ë·Ú›ÓË (1∞) ÃÚ‹ÛË Û˘Ó‰È·ÛÌÔ‡ Ê·Ú̷΢ÙÈ΋˜ Î·È Ì˯·ÓÈ΋˜ ÚÔʇϷ͢ Û ·ÛıÂÓ›˜ ˘„ËÏÔ‡ ÎÈÓ‰‡ÓÔ˘ ÁÈ· ·Ó¿Ù˘ÍË ÊÏ‚È΋˜ ıÚfiÌ‚ˆÛ˘ (2C) ™Â ·ÛıÂÓ›˜ ˘„ËÏÔ‡ ÎÈÓ‰‡ÓÔ˘ Â›Ó·È ÚÔÙÈÌÒÙÂÚË Ë ¯Ú‹ÛË Ë·Ú›Ó˘ ¯·ÌËÏÔ‡ ÌÔÚÈ·ÎÔ‡ ‚¿ÚÔ˘˜ ·Ú¿ ÎÏ·ÛÈ΋˜ Ë·Ú›Ó˘ (2C)
3Ë. ¶ÚÔʇϷÍË ·fi ¤ÏÎÔ˜ ÔÊÂÈÏfiÌÂÓÔ Û ÛÙÚ˜72 ÃÚ‹ÛË H2-·ÔÎÏÂÈÛÙÒÓ (1A) ‹ ÛÔ˘ÏÎÚ·Ê¿Ù˘ (1B): Ú¤ÂÈ Ó· ÛÙ·ıÌ›˙ÂÙ·È Ë ÚÔʇϷÍË ·fi ·ÈÌÔÚÚ·Á›· ·fi ÙÔ ·ÓÒÙÂÚÔ Á·ÛÙÚÂÓÙÂÚÈÎfi Ì ÙÔÓ Î›Ó‰˘ÓÔ ·Ó¿Ù˘Í˘ Ó¢ÌÔÓ›·˜, ÏfiÁˆ ·ÒÏÂÈ·˜ Ù˘ Á·ÛÙÚÈ΋˜ Ô͇ÙËÙ·˜ Î·È ÙÔ˘ ÏÂÈÙÔ˘ÚÁÈÎÔ‡ ÊÚ·ÁÌÔ‡ ÁÈ· ÙÔÓ ·ÔÈÎÈÛÌfi ÙÔ˘ ÛÙÔÌ¿¯Ô˘
METAMO™XEY™Eπ™ 2008
3ı. ∞ÔÎÏÈ̿ΈÛË ÊÚÔÓÙ›‰·˜73 ¶Ú¤ÂÈ Ó· Û˘˙ËÙÂ›Ù·È ÙÔ Ï¿ÓÔ ·ÓÙÈÌÂÙÒÈÛ˘ Ì ÙÔÓ ·ÛıÂÓ‹ Î·È ÙÔ˘˜ Û˘ÁÁÂÓ›˜ ÙÔ˘, Ó· ÂÚÈÁÚ¿ÊÔÓÙ·È ÔÈ Èı·Ó¤˜ Â΂¿ÛÂȘ Î·È Ó· ˘¿Ú¯Ô˘Ó Ú·ÏÈÛÙÈΤ˜ ÚÔÛ‰Ô˘ (1D).
μπμ§πO°ƒ∞ºπ∞ 1. Kanj, SS, Sharara, AI, Clavien, PA, Hamilton, JA. Cytomegalovirus infection following liver transplantation: Review of the literature. Clin Infect Dis 1996; 22:537. 2. Torbenson, M, Jinzhou, W, Nichols, L, et al. Causes of death in autopsied liver transplantation patients. Mod Pathol 1998; 11:37. 3. Winston, DJ, Emmanouilides, C, Busuttil, RW. Infections in liver transplant recipients. Clin Infect Dis 1995; 21:1077.
133
14. Hughes WT, Armstrong D, Bodey GP, et al. 2002 Guidelines for the use of antimicrobial agents in neutropenic patients with cancer. http://www.idsociety.org. Accessed July 10, 2007 16. Garnacho-Montero J, Sa-Borges M, Sole- Violan J, et al. Optimal management therapy for Pseudomonas aeruginosa ventilator associated pneumonia: An observational, multicenter study comparing monotherapy with combination antibiotic therapy. Crit Care Med 2007; 25:1888–1895. 17. Ibrahim EH, Sherman G, Ward S, et al. The influence of inadequate antimicrobial treatment of bloodstream infections on patient outcomes in the ICU setting. Chest 2000; 118:146–155 18. Kusne, S, Dummer, JS, Singh, N, et al. Infections after liver transplantation. An analysis of 101 consecutive cases. Medicine (Baltimore) 1988; 67:132. 19. Fishman, JA, Rubin, RH. Infection in organ-transplant recipients. N Engl J Med 1998; 338:1741.
4. Dombrovskiy VY, Martin AA, Sunderram J, et al. Rapid increase in hospitalization and mortality rates for severe sepsis in the United States: A trend analysis from 1993 to 2003. Crit Care Med 2007; 35:1414–1415.
20. Singh, N, Wagener, MM, Obman, A, et al. Bacteremias in liver transplant recipients: shift toward gramnegative bacteria as predominant pathogens. Liver Transpl 2004; 10:844.
5. Rolando N, Wade J, Davalos M et al. The systemic inflammatory response syndrome in acute liver failure. Hepatology 2000; 32:734-739.
21. Paya, CV. Fungal infections in solid-organ transplantation. Clin Infect Dis 1993; 16:677.
6. Dellinger RP, Carlet JM, Masur H, et al. Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock. Crit Care Med 2004; 32:858–873. 7. Dellinger RP, Levy MM, Carlet JM, et al. Surviving Sepsis Campaign: International guidelines for management of severe sepsis and septic shock: Crit Care Med 2008; 36:296-327. 8. Levy MM,Fink MP, Marshall JC et al. SCCM/ESISM/ ACCP/ATS/SIS Inernational Sepsis Definitions Conference. Crit Care Med 2003; 31:1250-1256. 9. Rivers E, Nguyen B, Havstad S, et al. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med 2001; 345:1368–1377. 10. Malbrain ML, Deeren D, De Potter TJ. Intraabdominal hypertension in the critically ill: It is time to pay attention. Curr Opin Crit Care 2005; 11:156–171. 11. Mermel LA, Maki DG. Detection of bacteremia in adults: Consequences of culturing an inadequate volume of blood. Ann Intern Med 1993; 119:270–272. 12. Guidelines for the management of adults with hospitalacquired, ventilator-associated, and healthcare-associated pneumonia. Am J Respir Crit Care Med 2005; 171:388–416. 13. Kumar A, Roberts D, Wood KE, et al. Duration of hypotension prior to initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock. Crit Care Med 2006; 34:1589–1596. 14. Pappas PG, Rex JH, Sobel JD, et al. Guidelines for treatment of candidiasis. Clin Infect Dis 2004; 38:161–189.
22. Singh, N, Muder, RR, Yu, VL, et al. Legionella infections in liver transplant recipients: Implications for management. Transplantation 1993; 56:1549. 23. Jimenez MF, Marshall JC. Source control in the management of sepsis. Intensive Care Med 2001; 27:S49–S62. 24. Bufalari A, Giustozzi G, Moggi L. Postoperative intraabdominal abscesses: Percutaneous versus surgical treatment. Acta Chir Belg 1996; 96:197–200. 25. O’Grady NP, Alexander M, Dellinger EP, et al. Guidelines for the prevention of intravascular catheterrelated infections. Clin Infect Dis 2002; 35:1281–1307. 26. Mier J, Leon EL, Castillo A, et al. Early versus late necrosectomy in severe necrotizing pancreatitis. Am J Surg 1997; 173: 71–75. 27. Finfer S, Bellomo R, Boyce N, et al. A comparison of albumin and saline for fluid resuscitation in the intensive care unit. N Engl J Med 2004;350:2247–2256. 28. Cook D, Guyatt G. Colloid use for fluid resuscitation: Evidence and spin. Ann Intern Med 2001; 135:205–208. 29. Sakr Y, Payen D, Reinhart K, et al. Effects of hydroxyethyl starch administration on renal function in critically ill patients. Br J Anaesth 2007; 98:216–224. 30. Romanelli RG, La Villa G, Barletta G et al. Long-term albumin infusion improves survival in patients with cirrhosis and ascites: an unblinded randomized trial. World J Gastroenterol 2006; 12:1403-1407. 31. Hollenberg SM, Ahrens TS, Annane D, et al. Practice parameters for hemodynamic support of sepsis in adult patients: 2004 update. Crit Care Med 2004; 32:1928–1948.
134
∂. ª√À§√À¢∏
32. Djillali A, Vigno P, Renault A, et al, for the CATS STUDY Group: Norepinephrine plus dobutamine versus epinephrine alone for management of septic shock: A randomized trial. Lancet 2007; 370:676–684. 33. Bellomo R, Chapman M, Finfer S, et al. Low-dose dopamine in patients with early renal dysfunction: A placebo-controlled randomised trial. Australian and New Zealand Intensive Care Society (ANZICS) Clinical Trials Group. Lancet 2000; 356: 2139–2143. 34. Russell JA, Walley KR, Singer J et al. Vasopressin versus Norepinephrine infusion in patients with septic shock. N Engl J Med 2008; 358:877-887. 35. Regnier B, Rapin M, Gory G, et al. Haemodynamic effects of dopamine in septic shock. Intensive Care Med 1977; 3:47–53. 36. Gattinoni L, Brazzi L, Pelosi P, et al. A trial of goaloriented hemodynamic therapy in critically ill patients. N Engl J Med 1995; 333:1025–1032. 37. Annane D, Sebille V, Charpentier C, et al. Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock. JAMA 2002; 288:862–871. 38. Sprung CL, Annane D, Briegel J, et al. Corticosteroid therapy of septic shock (CORTICUS). Abstr. Am Rev Respir Crit Care Med 2007; 175:A507. 39. Sprung CL, Annane D, Keh D et al. Hydrocortisone therapy for patients with septic shock. N Engl J Med 2008; 358: 111-124. 40. Allolio B, Dorr H, Stuttmann R, et al. Effect of a single bolus of etomidate upon eight major corticosteroid hormone and plasma ACTH. Clin Endocrinol (Oxf) 1985; 22: 281–286. 41. O’Beirne J, Holmes M, Agarwal B et al. Adrenal insufficiency in liver disease-what is the evidence? J Hepatol 2007; 47:418-423. 42. Bernard GR, Vincent JL, Laterre PF, et al. Efficacy and safety of recombinant human activated protein c for severe sepsis. N Engl J Med 2001; 344:699–709. 43. Abraham E, Laterre PF, Garg R, et al. Drotrecogin alfa (activated) for adults with severe sepsis and a low risk of death. N Engl J Med 2005; 353:1332–1341. 44. Vincent JL, Bernard GR, Beale R, et al. Drotrecogin alfa (activated) treatment in severe sepsis from the global open-label trial ENHANCE: Further evidence for survival and safety and implications for early treatment. Crit Care Med 2005; 33:2266–2277. 45. Ely EW, Laterre PF, Angus DC, et al. Drotrecogin alfa (activated) administration across clinically important subgroups of patients with severe sepsis. Crit Care Med 2003; 31:12–19. 46. Kulmarni S, Naureckas E, Cronin DC. Solid-organ transplant recipients with drotrecogin alfa (activated) for severe sepsis. Transplantation 2003; 75:899-901. 47. Hébert PC, Wells G, Blajchman MA, et al. A multicenter, randomized, controlled clinical trial of transfusion in critical care. N Engl J Med 1999; 340:409–417.
48. Corwin HL, Gettinger A, Pearl RG, et al. Efficacy of recombinant human erythropoietin in critically ill patients. JAMA 2002; 28:2827–2835. 49. College of American Pathologists: Practice parameter for the use of fresh-frozen plasma, cryoprecipitate, and platelets. JAMA 1994; 271:777–781. 50. Wiedermann CJ, Hoffmann JN, Juers M, et al. Highdose antithrombin III in the treatment of severe sepsis in patients with a high risk of death: Efficacy and safety. Crit Care Med 2006; 34:285–292. 51. The Acute Respiratory Distress Syndrome Network: Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Engl J Med 2000; 342:1301–1308. 52. Villar J, Kacmarek RM, Pérez-Méndez L, et al, for the ARIES Network: A high PEEP-low tidal volume ventilatory strategy improves outcome in persistent ARDS: A randomized controlled trial. Crit Care Med 2006; 34:1311–1318. 53. Gattinoni L, Caironi P, Cressoni M, et al. Lung recruitment in patients with acute respiratory distress syndrome. N Engl J Med 2006; 354:1775–1786. 54. Gattinoni L, Tognoni G, Pesenti A, et al. Effect of prone positioning on the survival of patients with acute respiratory failure. N Engl J Med 2001; 345:568–573. 55. Mancebo J, Fernandez R, Blanch L, et al. A multicenter trial of prolonged prone ventilation in severe acute respiratory distress syndrome. Am J Respir Crit Care Med 2006; 173:1233–1239. 56. Antonelli M, Conti G, Rocco M, et al. A comparison of noninvasive positive-pressure ventilation and conventional mechanical ventilation in patients with acute respiratory failure. N Engl J Med 1998; 339: 429–435. 57. Esteban A, Alia I, Gordo F, et al. Extubation outcome after spontaneous breathing trials with T-tube or pressure support ventilation. Am J Respir Crit Care Med 1997; 156: 459–465. 58. Richard C, Warszawski J, Anguel N, et al. Early use of the pulmonary artery catheter and outcomes in patients with shock and acute respiratory distress syndrome: A randomized controlled trial. JAMA 2003; 290: 2713–2720. 59. Wheeler AP, Bernard GR. National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome (ARDS) Clinical Trials Network: Pulmonary-artery versus central venous catheter to guide treatment of acute lung injury. N Engl J Med 2006; 354:2213–2224. 60. Wiedemann HP, Wheeler AP. National Heart, Lung, and Blood Institute Acute RespiratoryDistress Syndrome (ARDS) Clinical Trials Network: Comparison of two fluid-management strategies in acute lung injury. N Engl J Med 2006; 354:2564–2575. 61. Brook AD, Ahrens TS, Schaiff R, et al. Effect of a nursing-implemented sedation protocol on the duration
METAMO™XEY™Eπ™ 2008
of mechanical ventilation. Crit Care Med 1999; 27:2609– 2615. 62. Kress JP, Vinayak AG, Levitt J, et al. Daily sedative interruption in mechanically ventilated patients at risk for coronory disease. Crit Care Med 2007; 35:365–371. 63. Murray MJ, Cowen J, Deblock H, et al. Clinical practice guidelines for sustained neuromuscular blockade in the critically ill adult. Crit Care Med 2002; 30:142–156. 64. Van den Berghe G, Wouters P, Weekers F, et al. Intensive insulin therapy in critically ill patients. N Engl J Med 2001; 345: 1359–1367. 65. Van den Berghe G, Wilmer A, Hermans G, et al. Intensive insulin therapy in the medical ICU. N Engl J Med 2006; 354:449–461. 66. Brunkhorst FM, Engel C, Bloos F et al. Intensive Insulin Therapy and Pentastarch resuscitation in severe sepsis. N Engl J Med 2008; 358:125-139. 67. Tietge UJ, Selberg O, Kreter A et al. Alterations in glucose metabolism associated with liver cirrhosis persist in the clinically stable long-term course after liver tranplantation. Liver Transpl 2004; 10 :1030-40. 68. Vinsonneau C, Camus C, Combes A, et al. Continuous venovenous haemodiafiltration versus intermittent
135
haemodialysis for acute renal failure in patients with multipleorgan dysfunction syndrome: A multicentre randomised trial. Lancet 2006; 368:379–85. 69. Mathieu D, Neviere R, Billard V, et al. Effects of bicarbonate therapy on hemodynamics and tissue oxygenation in patients with lactic acidosis: A prospective, controlled clinical study. Crit Care Med 1991; 19:1352–1356. 70. Geerts W, Cook D, Shelby R, et al. Venous thromboembolism and its prevention in critical care. J Crit Care 2002; 17:95–104. 71. Geerts WH, Jay RM, Code KI, et al. A comparison of low-dose heparin with lowmolecular- weight heparin as prophylaxis against venous thromboembolism after major trauma. N Engl J Med 1996; 335: 701–707. 72. Kahn JM, Doctor JN, Rubenfeld GD. Stress ulcer prophylaxis in mechanically ventilated patients: Integrating evidence and judgment using a decision analysis. Intensive Care Med 2006; 32:1151–1158. 73. Thompson BT, Cox PN, Antonelli M, et al. Challenges in end-of-life care in the ICU: Statement of the 5th International Consensus Conference in Critical Care: Brussels, Belgium, April 2003: Executive summary. Crit Care Med 2004; 32:1781–1784.
NÂÊÚÈ΋ ‰˘ÛÏÂÈÙÔ˘ÚÁ›· ÛÙÔ˘˜ ·ÛıÂÓ›˜ Ì ÌÂÙ·ÌfiÛ¯Â˘ÛË ‹·ÙÔ˜. AÓÙÈÌÂÙÒÈÛË ÛÙË ME£ Ã. ∫˘‰ÒÓ·
∂π™∞°ø°π∫∞
ªÂ Ù· Ó¤· - Û˘ÌʈÓË̤ӷ ‰ÈÂıÓÒ˜ - ÎÚÈÙ‹ÚÈ· ÔÈ ÂfiÌÂÓ˜ ÌÂϤÙ˜ ı· ηٷϋÍÔ˘Ó Û ÈÔ ·ÍÈfiÈÛÙ· ÔÛÔÛÙ¿. ¶¿ÓÙˆ˜, ˆ˜ ÙÒÚ· Ë Û˘¯ÓfiÙËÙ· Ù˘ ÛÔ‚·Ú‹˜ O¡∞ Ô˘ ¯ÚÂÈ¿˙ÂÙ·È ıÂڷ›· ÓÂÊÚÈ΋˜ ˘ÔηٿÛÙ·Û˘ (renal replacement therapy RRT), ÌÂÙ¿ ·fi ÌÂÙ·ÌfiÛ¯Â˘ÛË ‹·ÙÔ˜ Â›Ó·È 817%. Δ· Û˘¯ÓfiÙÂÚ· ·›ÙÈ· O¡∞ ÂÚÈÏ·Ì‚¿ÓÔ˘Ó ÙËÓ ÔÍ›· ÛˆÏËÓ·Úȷ΋ Ó¤ÎÚˆÛË (O™¡)-·fiÙÔÎÔ ÈÛ¯·ÈÌÈ΋˜ ‹ ÙÔÍÈ΋˜ ÚÔÛ‚ÔÏ‹˜ ÙˆÓ ÓÂÊÚÒÓ-, ÙÔ ÚÔ¸¿Ú¯ÔÓ Ë·ÙÔÓÂÊÚÈÎfi Û‡Ó‰ÚÔÌÔ Î·È ÙË ‰È¿ÌÂÛË ÓÂÊÚ›Ùȉ· Ê·Ú̷΢ÙÈ΋˜ ·ÈÙÈÔÏÔÁ›·˜. ∞Ó·Ï˘ÙÈÎfiÙÂÚ· O™¡ ÚÔηÏÔ‡Ó Ë ·Ú·ÙÂٷ̤ÓË ‰ÈÂÁ¯ÂÈÚËÙÈ΋ ˘fiÙ·ÛË, Ë ÛËÙÈ΋ ηٷÏËÍ›·, Ë ÂÁηÙÂÛÙË̤ÓË ÚÔÓÂÊÚÈ΋ ·˙ˆı·ÈÌ›·, Ë ÚˆÙÔ·ı‹˜ ‰˘ÛÏÂÈÙÔ˘ÚÁ›· ÌÔۯ‡̷ÙÔ˜ Î·È Ë ¯Ú‹ÛË ÓÂÊÚÔÙÔÍÈÎÒÓ ·Ú·ÁfiÓÙˆÓ8,9. ŸÛÔÓ ·ÊÔÚ¿ ÙË ‰È·ÊÔÚÂÙÈ΋ ·ÈÙÈÔ·ıÔÁ¤ÓÂÈ· Ù˘ ÚÒÈÌ˘ ‹ fi„ÈÌ˘ O¡∞, Û ̛· ÚfiÛÊ·ÙË ÌÂϤÙË ÙÔ˘ Cabezuelo1 ÌÂÏÂÙ‹ıËÎ·Ó 184 ÌÂÙ·ÌÔÛ¯Â˘Ì¤ÓÔÈ ·ÛıÂÓ›˜. πÛ¯·ÈÌÈ΋ O™¡ Î·È ÚÔÓÂÊÚÈ΋ ·˙ˆı·ÈÌ›· ‹Ù·Ó Ù· ‚·ÛÈο ·›ÙÈ· Ù˘ ÚÒÈÌ˘ O¡∞(1Ë Â‚‰ÔÌ¿‰· ÌÂÙ¿ ÙË ÌÂÙ·ÌfiÛ¯Â˘ÛË), ÂÓÒ Ë Û‹„Ë Î·È Ë ¯Ú‹ÛË Î˘ÎÏÔÛÔÚ›Ó˘ ‹Ù·Ó Ù· ·›ÙÈ· Ù˘ fi„ÈÌ˘ (2Ë – 4Ë Â‚‰ÔÌ¿‰· ÌÂÙ¿ ÙË ÌÂÙ·ÌfiÛ¯Â˘ÛË).
∏ ÓÂÊÚÈ΋ ·Ó¿ÚÎÂÈ· ·Ú·Ì¤ÓÂÈ Ì›· Û˘¯Ó‹ ÂÈÏÔ΋ ÌÂÙ¿ ·fi ÌÂÙ·ÌfiÛ¯Â˘ÛË ‹·ÙÔ˜, ·Ú¿ ÙËÓ ÚfiÔ‰Ô ÙˆÓ ÙÂÏÂ˘Ù·›ˆÓ ÂÙÒÓ Û ·˘ÙfiÓ ÙÔÓ ÙÔ̤·. ∞ÚÎÂÙ¤˜ ÌÂϤÙ˜ ·¤‰ÂÈÍ·Ó ÙË ‰˘ÛÌÂÓ‹ ›وÛË ÙfiÛÔ Ù˘ ÔÍ›·˜ ÓÂÊÚÈ΋˜ ·Ó¿ÚÎÂÈ·˜ fiÛÔ Î·È Ù˘ ¯ÚfiÓÈ·˜ ÓÂÊÚÈ΋˜ ÓfiÛÔ˘ ÛÙËÓ ÂÈ‚›ˆÛË ÙˆÓ ÌÂÙ·ÌÔÛ¯Â˘Ì¤ÓˆÓ ·ÛıÂÓÒÓ. £· ·Ó·Ï‡ÛÔ˘Ì ٷ ·›ÙÈ·, ÙË Û˘¯ÓfiÙËÙ·, ÙË ıÂڷ›·, ÙËÓ ¤Î‚·ÛË ·ÏÏ¿ Î·È ÙËÓ ÚfiÏË„Ë ·˘Ù‹˜ Ù˘ ‰È·Ù·Ú·¯‹˜.
™ÀáOΔ∏Δ∞ – ¶ƒO¢π∞£∂™π∫Oπ ¶∞ƒ∞°O¡Δ∂™ – ∂•∂§π•∏ ∏ ÔÍ›· ÓÂÊÚÈ΋ ·Ó¿ÚÎÂÈ· (O¡∞) Ô˘ ÂÌÊ·Ó›˙ÂÙ·È Û ·ÛıÂÓ›˜ ÌÂÙ¿ ·fi ÔÚıÔÙÔÈ΋ ÌÂÙ·ÌfiÛ¯Â˘ÛË ‹·ÙÔ˜ (Oª∏) Î˘Ì·›ÓÂÙ·È ÌÂٷ͇ 17% ¤ˆ˜ 64%1,2,3,4,5,6. ∏ ·ÍÈÔÛËÌ›ˆÙË ·˘Ù‹ ‰È·Î‡Ì·ÓÛË ÙˆÓ ÔÛÔÛÙÒÓ ÛÙË ‰ÈÂıÓ‹ ‚È‚ÏÈÔÁÚ·Ê›·, ÔÊ›ÏÂÙ·È Ì¿ÏÏÔÓ ÛÙË ‰È·ÊÔÚÔÔ›ËÛË ÙˆÓ ÎÚÈÙËÚ›ˆÓ Ô˘ ¯ÚËÛÈÌÔÔÈÔ‡ÓÙ·È ÁÈ· Ó· ÔÚ›ÛÔ˘Ó ÙËÓ O¡∞. ¶ÚfiÛÊ·Ù·, ÌÈ· ‰ÈÂıÓ‹˜ ÂÈÙÚÔ‹ ÂȉÈÎÒÓ Î·Ù¤ÏËÍ ÛÙËÓ Ù·ÍÈÓfiÌËÛË ÙˆÓ ÛÙ·‰›ˆÓ Ù˘ ÓÂÊÚÈ΋˜ ÚÔÛ‚ÔÏ‹˜ Î·È ÛÙËÓ ÂÈÛ·ÁˆÁ‹ ÎÚÈÙËÚ›ˆÓ, ÙˆÓ ÁÓˆÛÙÒÓ Ï¤ÔÓ RIFLE criteria7, Ô˘ Ê·›ÓÔÓÙ·È ÛÙÔÓ ·Ú·Î¿Ùˆ ›Ó·Î·:
RIFLE criteria for acute kidney injury (AKI) GFR criteria Urine Risk
Creat increase 1.5* baseline
Injury
Creat increase 2* baseline
Output criteria UO<0.5ml/kg/h * 6hr
high sensitivity
UO<0.5ml/kg/h * 12hr
high sensitivity
UO<0.3ml/kg/h * 24hr
high specificity
GFR decrease >25% GFR decrease >50% Failure
Creat increase 3* baseline GFR decrease >75% Creat >4mg/dl
anuria * 12hr
Loss
Persistent AKI
loss of function >4weeks
ESKD
End stage kidney disease
>3 months
136
high specificity
METAMO™XEY™Eπ™ 2008
OÈ Nuno et al 2 ÂÍ¤Ù·Û·Ó 60 ÌÂÙ·‚ÏËÙ¤˜ Ô˘ ÌÔÚ› Ó· Û¯ÂÙ›˙ÔÓÙ·È Ì ÙËÓ ÂÌÊ¿ÓÈÛË Ù˘ O¡∞. ∂Ó‰ÂÈÎÙÈο, ÌÂϤÙËÛ·Ó 1] ÚÔÂÁ¯ÂÈÚËÙÈο: ÙÔ ÈÛÙÔÚÈÎfi ·˘ÙfiÌ·Ù˘ ‚·ÎÙËÚȉȷ΋˜ ÂÚÈÙÔÓ›Ùȉ·˜ / ·ÛΛÙË / ÂÁÎÂÊ·ÏÔ¿ıÂÈ·˜, ÙÔ ÛÙ¿‰ÈÔ Child-Pugh C, ÙË Ì·ÎÚfi¯ÚÔÓË ÓÔÛÔÎÔÌÂȷ΋ ÓÔÛËÏ›· ÚÔ Ù˘ ÌÂÙ·ÌfiÛ¯Â˘Û˘, ÙËÓ ÙÈÌ‹ ·Ï‚Ô˘Ì›Ó˘<3mg/dl, ÙË ¯Ú‹ÛË ÙÔ˘ ‰È·Ï‡Ì·ÙÔ˜ University of Wisconsin Ì ¯ÚfiÓÔ „˘¯Ú‹˜ ÈÛ¯·ÈÌ›·˜ > 12ÒÚ˜ 2] ‰ÈÂÁ¯ÂÈÚËÙÈο: ÙË ‰È¿ÚÎÂÈ· ¯ÂÈÚÔ˘ÚÁ›Ԣ > 9 ÒÚ˜ Î·È ÙȘ ÌÂÁ¿Ï˜ ·Ó¿ÁΘ Û ÚÔ˚fiÓÙ· ·›Ì·ÙÔ˜ Î·È 3] ÌÂÙÂÁ¯ÂÈÚËÙÈο: ÙË ‚·ÚÈ¿ Ì˘ÎËÙÈ·ÛÈ΋ Ïԛ̈ÍË, ÙÔÓ ›ÎÙÂÚÔ Î·È ÙËÓ Â·Ó¤̂·ÛË. øÛÙfiÛÔ Û ÔÏ˘·Ú·ÁÔÓÙÈ΋ ·Ó¿Ï˘ÛË ·Â‰Â›¯ıËÛ·Ó ˆ˜ ÛËÌ·ÓÙÈÎÔ› ·ÓÂÍ¿ÚÙËÙÔÈ ÚÔÁÓˆÛÙÈÎÔ› ·Ú¿ÁÔÓÙ˜ ÔÈ ·Ú·Î¿Ùˆ: ÔÏϷϤ˜ ÌÂÙ·ÁÁ›ÛÂȘ ÂÚ˘ıÚÒÓ, ¯ÚfiÓÔ˜ ÈÛ¯·ÈÌ›·˜ >8ÒÚ˜, ÈÛÙÔÚÈÎfi ÂÁÎÂÊ·ÏÔ¿ıÂÈ·˜ Î·È ·ÛΛÙË. ∂ȉÈÎfiÙÂÚ· fiÛÔÓ ·ÊÔÚ¿ ÙȘ ‰ÈÂÁ¯ÂÈÚËÙÈΤ˜ Û˘Óı‹Î˜ Â›Ó·È Û·Ê¤˜ È· fiÙÈ Ë Û‡Á¯ÚÔÓË ¯ÂÈÚÔ˘ÚÁÈ΋ Ù¯ÓÈ΋ (piggypack technique), Ô˘ ·ÓÙÈη٤ÛÙËÛ ÙÔÓ ÎÏ·ÛÛÈÎfi ·ÔÎÏÂÈÛÌfi (clamping) Ù˘ οو ÎÔ›Ï˘ ÊϤ‚·˜, Û˘ÓÂÈÛ¤ÊÂÚ ÛÙË Ì›ˆÛË Ù˘ ÚÒÈÌ˘ O¡∞ ÌÂÙ¿ ÙË ÌÂÙ·ÌfiÛ¯Â˘ÛË, ÁÈ·Ù› ‰È·ÙËÚ› ÙË ÓÂÊÚÈ΋ ·ÈÌ·ÙÈ΋ ÚÔ‹ Î·È ÙËÓ ›ÂÛË ‰È‹ıËÛ˘ ÙÔ˘ ÓÂÊÚÔ‡.10 £· ‹Ù·Ó ÂÍ·ÈÚÂÙÈο ÔχÙÈÌÔ Î·È ÂӉȷʤÚÔÓ ·Ó ÌÔÚÔ‡Û·Ì ӷ ·Ó·ÁÓˆÚ›ÛÔ˘Ì ¤ÁηÈÚ· ÔÈÔ› ·ÛıÂÓ›˜ Â›Ó·È Èı·Ófi Ó· ÂÌÊ·Ó›ÛÔ˘Ó O¡∞. ∏ ÚÒÈÌË ‰È¿ÁÓˆÛË ı· Ì·˜ ‚ÔËıÔ‡Û ӷ ¿ÚÔ˘Ì ·ÔÊ¿ÛÂȘ ÁÈ· ÙËÓ ¤Ó·ÚÍË Ù˘ ÓÂÊÚÈ΋˜ ˘Ôηٿ-
137
ÛÙ·Û˘, Ó· ÙÚÔÔÔÈ‹ÛÔ˘Ì ηٿÏÏËÏ· ÙËÓ ·ÓÔÛÔηٷÛÙÔÏ‹ Î·È Ó· ¯ÚËÛÈÌÔÔÈ‹ÛÔ˘Ì ٷ ‰È·ı¤ÛÈÌ· Ù¯ÓÈο ̤۷ Ì ÙÔÓ Ï¤ÔÓ ÔÚıÔÏÔÁÈÎfi ÙÚfiÔ. Ÿˆ˜ Ê·›ÓÂÙ·È ÛÙÔ Û¯‹Ì· 1 ·fi ÙËÓ ÌÂϤÙË ÙˆÓ Parikh et al11, Ù· ›‰· 2 ‚ÈÔ‰ÂÈÎÙÒÓ (biomarkers) ÛÙ· Ô‡Ú· ¤¯Ô˘Ó ÚÔÁÓˆÛÙÈ΋ ÛËÌ·Û›·. ™˘ÁÎÂÎÚÈ̤ӷ, interleukin-18 (IN-18) Î·È neutrophil gelatinase-associated lipocalin (NGAL) ·˘Í¿ÓÔÓÙ·È 2-4 ÒÚ˜ ÌÂÙ¿ ·fi ηډÈÔÓ¢ÌÔÓÈÎfi bypass Û ·˘ÙÔ‡˜ ÙÔ˘˜ ·ÛıÂÓ›˜ Ô˘ ÚfiÎÂÈÙ·È Ó· ·ÚÔ˘ÛÈ¿ÛÔ˘Ó AKI (acute kidney injury) 48-72 ÒÚ˜ ÌÂÙÂÁ¯ÂÈÚËÙÈο. ∏ ÔÌ¿‰· ÙÔ˘ Yalavarthy12 ‰ÈÂÚÂ˘Ó¿ ·˘Ù‹Ó ÙËÓ ÂÚ›Ô‰Ô, Â¿Ó ÙÔ ›‰ÈÔ ÈÛ¯‡ÂÈ Î·È ÌÔÚ› Ó· ÂÊ·ÚÌÔÛÙ› ÛÙÔ˘˜ ·ÛıÂÓ›˜ Ì ÌÂÙ·ÌfiÛ¯Â˘ÛË ‹·ÙÔ˜. ∏ ·ÔηٿÛÙ·ÛË Ù˘ ÓÂÊÚÈ΋˜ ‰˘ÛÏÂÈÙÔ˘ÚÁ›·˜ ÌÂÙ¿ ·fi Oª∏ ‰ÂÓ ¤¯ÂÈ ÌÂÏÂÙËı› ȉȷ›ÙÂÚ·. Δ· ÌfiÓ· ‰ËÌÔÛÈÂ˘Ì¤Ó· ÛÙÔȯ›· ·ÊÔÚÔ‡Ó ÙË ‚ÂÏÙ›ˆÛË ÌÂÙ¿ ·fi Ë·ÙÔÓÂÊÚÈÎfi Û‡Ó‰ÚÔÌÔ (∏¡™). OÈ Marik et al13 ·Ú·ÎÔÏÔ‡ıËÛ·Ó 28 ·ÛıÂÓ›˜ Ô˘ ÏËÚÔ‡Û·Ó Ù· ÎÚÈÙ‹ÚÈ· ÙÔ˘ ∏¡™ ÁÈ· 4 Ì‹Ó˜ ÌÂÙ¿ ÙËÓ Oª∏. ΔÔ 58% ÙˆÓ ·ÛıÂÓÒÓ ·Ôη٤ÛÙËÛ ÙË ÓÂÊÚÈ΋ ÏÂÈÙÔ˘ÚÁ›· Î·È ·Ú¤ÌÂÈÓ ÂÎÙfi˜ ‰È¿Ï˘Û˘. ∞fi ÙËÓ ¿ÏÏË, Ë ÌË ·ÔηٿÛÙ·ÛË Ù˘ ÓÂÊÚÈ΋˜ ÏÂÈÙÔ˘ÚÁ›·˜ ·Ú·Ù›ÓÂÈ ÙË ‰È¿ÚÎÂÈ· ÓÔÛËÏ›·˜ Î·È ·˘Í¿ÓÂÈ ÙÔ ÎfiÛÙÔ˜ Î·È ÙË ıÓËÙfiÙËÙ· (Ù· ÔÛÔÛÙ¿ ÔÈΛÏÏÔ˘Ó ·fi 28 ¤ˆ˜ 75%). ΔÔ ÌfiÓÔ ÍÂοı·ÚÔ Â›Ó·È fiÙÈ Ë ÌÂÙÂÁ¯ÂÈÚËÙÈ΋ O¡∞ Û ۯ¤ÛË Ì ÙËÓ ÚÔÂÁ¯ÂÈÚËÙÈ΋ ÂËÚ¿˙ÂÈ ‰˘ÛÌÂÓ¤ÛÙÂÚ· ÙËÓ ÂÈ‚›ˆÛË. ™ÙË ‰ËÌÔÛ›Â˘ÛË ÙˆÓ Fraley et al14
250 IL-18 (pg/ml) AKI
Mean biomarker level
200
150
100
NGAL (ng/ml) AKI
50 IL-18 (pg/ml) no AKI
0
NGAL (ng/ml) no AKI
0
2
4 6 12 24 Time after cardio-pulmonary bypass (h)
™¯‹Ì· 1. ∂›Â‰· biomarkers.
48
138
Ã. ∫À¢ø¡∞
ÛËÌÂÈÒÓÂÙ·È Ë ‰ÈÏ¿ÛÈ· ıÓËÙfiÙËÙ· fiÛˆÓ ÌÂÙ·ÌÔÛ¯Â˘Ì¤ÓˆÓ Â›¯·Ó ÚÔÂÁ¯ÂÈÚËÙÈ΋ O¡∞ - Û ۇÁÎÚÈÛË Ì ·˘ÙÔ‡˜ Ô˘ ›¯·Ó Ê˘ÛÈÔÏÔÁÈ΋ ÓÂÊÚÈ΋ ÏÂÈÙÔ˘ÚÁ›· (29% ¤Ó·ÓÙÈ 16%), ·ÏÏ¿ ·ÎfiÌË ¯ÂÈÚfiÙÂÚ·, ÔÎÙ·Ï¿ÛÈ· ıÓËÙfiÙËÙ· ÙˆÓ ÌÂÙ·ÌÔÛ¯Â˘Ì¤ÓˆÓ Ì ÌÂÙÂÁ¯ÂÈÚËÙÈ΋ O¡∞ - Û ۇÁÎÚÈÛË Ì ·˘ÙÔ‡˜ Ô˘ ›¯·Ó Ê˘ÛÈÔÏÔÁÈ΋ ÓÂÊÚÈ΋ ÏÂÈÙÔ˘ÚÁ›· (41% ¤Ó·ÓÙÈ 5%). ¶ÚÔÏËÙÈο, Ë ÂÈÏÔÁ‹ ‰ÔÙÒÓ ·ÏÏ¿ Î·È ÏËÙÒÓ ¯ˆÚ›˜ ÓÂÊÚÈ΋ ¿ıËÛË, Ë ·ÔÊ˘Á‹ ‰ÈÂÁ¯ÂÈÚËÙÈ΋˜ ·ÈÌÔ‰˘Ó·ÌÈ΋˜ ·ÛÙ¿ıÂÈ·˜ Î·È Ë Ì›ˆÛË Ù˘ ‰fiÛ˘ ÓÂÊÚÔÙÔÍÈÎÒÓ Ê·Ú̿ΈÓ, Â›Ó·È Ù· ÛËÌ·ÓÙÈÎfiÙÂÚ· ̤ÙÚ· Ô˘ ı· ÌÔÚÔ‡Û·Ó Ó· ÏËÊıÔ‡Ó ÁÈ· ÙËÓ ·ÔÊ˘Á‹ ÂÁηٿÛÙ·Û˘ O¡∞. ŸÛÔÓ ·ÊÔÚ¿ ÙËÓ ÂÌÊ¿ÓÈÛË Ã¡∞ Û ϋÙ˜ Ë·ÙÈÎÔ‡ ÌÔۯ‡̷ÙÔ˜ ·Ó·Ê¤ÚÔÓÙ·È ÔÛÔÛÙ¿ 480%3-15,16. ∂·Ó·Ï·Ì‚¿ÓÂÙ·È Â‰Ò Ë ·Ó˘·ÚÍ›· ÎÔÈÓÒÓ ÎÚÈÙËÚ›ˆÓ ¤ˆ˜ ÚfiÛÊ·Ù· ÁÈ· ÙÔÓ ÔÚÈÛÌfi Ù˘ á∞, ·ÏÏ¿ Î·È Ë ‰È·ÊÔÚÂÙÈ΋ ‰È¿ÚÎÂÈ· ·Ú·ÎÔÏÔ‡ıËÛ˘ (follow up). OÈ ÈÔ ÂÈ‚·Ú˘ÓÙÈÎÔ› ·Ú¿ÁÔÓÙ˜ ıˆÚÔ‡ÓÙ·È Ë ÓÂÊÚÔÙÔÍÈÎfiÙËÙ· ÙˆÓ ·Ó·ÛÙÔϤˆÓ Ù˘ ηÏÛÈÓ¢ڛÓ˘ (calcineurin inhibitors CNI), ÙÔ ÚÔ¸¿Ú¯ÔÓ Ë·ÙÔÓÂÊÚÈÎfi Û‡Ó‰ÚÔÌÔ, Ô Û·Î¯·Ú҉˘ ‰È·‚‹Ù˘ Î·È Ë ÚÔÂÁ¯ÂÈÚËÙÈ΋ ÓÂÊÚÈ΋ ·Ó¿ÚÎÂÈ·9-15,17,18. ∂›Û˘, Ë ·Ó¿ÁÎË ÁÈ· ·ÈÌÔοı·ÚÛË ÛÙË ÌÂÙ·ÌÔÛ¯Â˘ÙÈ΋ ÂÚ›Ô‰Ô, Ë HCV Ïԛ̈ÍË Î·È Ë ËÏÈΛ· ÂËÚ¿˙Ô˘Ó Û ¤Ó· ‚·ıÌfi ÙËÓ ÂͤÏÈÍË Û ¯ÚfiÓÈ· ÓÂÊÚÈ΋ ÓfiÛÔ. ™Â Ì›· ·Ó·‰ÚÔÌÈ΋ ÌÂϤÙË 15 ÂÙÒÓ, Ô˘ ·ÊÔÚÔ‡Û 834 Ï‹Ù˜ Ë·ÙÈÎÔ‡ ÌÔۯ‡̷ÙÔ˜, ÂÌÊ¿ÓÈÛ·Ó Ã¡∞ 14.4% ÙˆÓ ·ÛıÂÓÒÓ, Ì ÂÚÈÛÛfiÙÂÚÔ˘˜ ·fi ÙÔ˘˜ ÌÈÛÔ‡˜ Ó· Â›Ó·È ÙÂÏÈÎÔ‡ ÛÙ·‰›Ô˘19. Δ· ·Ó·ÁÓˆÚÈṲ̂ӷ ·›ÙÈ· ‹Ù·Ó: ÓÂÊÚÔÙÔÍÈÎfiÙËÙ· ÙˆÓ ·Ó·ÛÙÔϤˆÓ Ù˘ ηÏÛÈÓ¢ڛÓ˘ (CNI) 73.3%, Ë·ÙÔÓÂÊÚÈÎfi Û‡Ó‰ÚÔÌÔ 6.66%, ÂÛÙȷ΋ ÙÌËÌ·ÙÈ΋ ÛÂÈÚ·Ì·ÙÔÛÎÏ‹Ú˘ÓÛË 6.66%, ÂͤÏÈÍË Ù˘ ˘ÔΛÌÂÓ˘ ÓÂÊÚÈ΋˜ ÓfiÛÔ˘ 11.1% Î·È O™¡-ÓÂÊÚÔÙÔÍÈÎfiÙËÙ· Ù˘ ·ÌÊÔÙÂÚÈΛÓ˘ 2.22%. ¡· ÛËÌÂȈı› fiÙÈ Ë ÂͤÏÈÍË Ù˘ ÓÂÊÚÈ΋˜ ÓfiÛÔ˘ Ì ÙÔ ¯ÚfiÓÔ Û˘Ì‚·›ÓÂÈ Î·È ÛÙÔ ÓÂÊÚÈÎfi ÌfiÛ¯Â˘Ì·, Â¿Ó Ù˘¯fiÓ ¤¯ÂÈ ÚÔËÁËı› Û˘Ó‰˘·Ṳ̂ÓË ÌÂÙ·ÌfiÛ¯Â˘ÛË ‹·ÙÔ˜-ÓÂÊÚÔ‡. OÈ Cohen et al20 Û ¤Ó· 5ÂÙ¤˜ follow up η٤ÁÚ·„·Ó ÔÛÔÛÙfi ÂÌÊ¿ÓÈÛ˘ á∞ 27.5%, ÂÓÒ ÔÈ Gonwa et al21 ·¤‰ÂÈÍ·Ó ÙË ÛÙ·‰È·Î‹ Ì ÙÔ ¯ÚfiÓÔ Ì›ˆÛË ÙÔ˘ Ú˘ıÌÔ‡ ÛÂÈÚ·Ì·ÙÈ΋˜ ‰È‹ıËÛ˘ (GFR) ·fi 90.7ml/min ÚÔ ÌÂÙ·ÌfiÛ¯Â˘Û˘ Û 59.5ml/min 3 Ì‹Ó˜ ÌÂÙ¿ Î·È 55.3ml/min 5 ¯ÚfiÓÈ· ÌÂÙ¿. ÿÛˆ˜ Ë ÈÔ ·ÍÈfiÏÔÁË ÌÂϤÙË Â›Ó·È ÙˆÓ Ojo et al15 Ô˘ Û˘ÁΤÓÙÚˆÛ·Ó ÛÙÔȯ›· ·fi 37000 Ï‹Ù˜
‹·ÙÔ˜ (database from the Center for Medicare and Medicaid Services, the Social Security Administration and the Scientific Registry of Transplant Recipients). ¶¤ÓÙ ¯ÚfiÓÈ· ÌÂÙ¿ ÙË ÌÂÙ·ÌfiÛ¯Â˘ÛË Ô ·ıÚÔÈÛÙÈÎfi˜ ΛӉ˘ÓÔ˜ ÁÈ· ÙË ÓÂÊÚÈ΋ ·Ó¿ÚÎÂÈ· (ÔÚÈ˙fiÌÂÓÔ˜ ˆ˜ GFR<29ml/min/1.73m2) ‹Ù·Ó 18.1%, Ô ÔÔ›Ô˜ ·˘Í‹ıËΠηٿ 25% ÌÂÙ¿ ·fi 10 ¯ÚfiÓÈ·. ™Â Ì›· Ôχ ÚfiÛÊ·ÙË Á·ÏÏÈ΋ ÌÂϤÙË, Ô˘ ÂͤٷÛ ‚ÈÔ„›Â˜ ÓÂÊÚÒÓ ÛÙ· 5 ¯ÚfiÓÈ· ÌÂÙ¿ ÙË ÌÂÙ·ÌfiÛ¯Â˘ÛË ‹·ÙÔ˜, Ù· ÈÛÙÔ·ıÔÏÔÁÈο Â˘Ú‹Ì·Ù· Û˘Ó‰ÂfiÙ·Ó Ì CNI ÓÂÊÚÔÙÔÍÈÎfiÙËÙ· , ‰È·‚ËÙÈ΋ ÓÂÊÚÔ¿ıÂÈ·, ıÚÔÌ‚ˆÙÈ΋ ÌÈÎÚÔ·ÁÁÂÈÔ¿ıÂÈ· Î·È ÛˆÏËÓ·ÚȷΤ˜ ·ÏÏÔÈÒÛÂȘ Ô˘ ÔÊÂÈÏfiÙ·Ó ÛÙË ‰ÈÂÁ¯ÂÈÚËÙÈ΋ ¯Ú‹ÛË hydroxyethylstarch, ˆ˜ ÔÁΈÙÈÎÔ‡ ‰È·Ï‡Ì·ÙÔ˜22. ¢˘ÛÙ˘¯Ò˜ Ë Ã¡∞ ÌÂÈÒÓÂÈ ÙËÓ ÂÈ‚›ˆÛË. OÈ Gonwa et al23 η٤ÁÚ·„·Ó 13ÂÙ‹ ÂÈ‚›ˆÛË ÛÙËÓ ÔÌ¿‰· ÙˆÓ ÌÂÙ·ÌÔÛ¯Â˘Ì¤ÓˆÓ 28.2% ¤Ó·ÓÙÈ 54.6% ÛÙËÓ ÔÌ¿‰· ÂϤÁ¯Ô˘. ŸÛÔÈ ·Ú¤ÌÂÓ·Ó Û ·ÈÌÔοı·ÚÛË, ·ÚÔ˘Û›·˙·Ó 27% 6ÂÙ‹ ÂÈ‚›ˆÛË ·fi ÙËÓ ¤Ó·ÚÍË Ù˘ οı·ÚÛ˘, ÂÓÒ ÔÈ ·ÛıÂÓ›˜ Ô˘ ˘Ô‚·ÏÏfiÙ·Ó Û ÌÂÙ·ÌfiÛ¯Â˘ÛË ÓÂÊÚÔ‡ 71.4%. Δ¤ÏÔ˜, ÔÈ Ojo et al15 ·Ó·ÎÔ›ÓˆÛ·Ó fiÙÈ Ë Ã¡∞ Û ÌÂÙ·ÌfiÛ¯Â˘ÛË ÌË ÓÂÊÚÈÎÔ‡ ÔÚÁ¿ÓÔ˘, ÔÏÏ·Ï·ÛÈ¿˙ÂÈ ÙÔÓ Î›Ó‰˘ÓÔ ı·Ó¿ÙÔ˘ ηٿ 4.55 ÊÔÚ¤˜. ∏ ÚfiÏË„Ë ÏÔÈfiÓ, Â›Ó·È ·Ó·Áη›· ÎÈ ·˘Ùfi ÂÚÈÏ·Ì‚¿ÓÂÈ ·fi ÙË Ì›· ÙËÓ ÂÈıÂÙÈ΋ ·ÓÙÈÌÂÙÒÈÛË Ù˘ ˘¤ÚÙ·Û˘, Ù˘ ˘ÂÚÏÈȉ·ÈÌ›·˜ Î·È Ù˘ ˘ÂÚÁÏ˘Î·ÈÌ›·˜ ÎÈ ·fi ÙËÓ ¿ÏÏË ÙËÓ ·ÛÊ·Ï‹ Ì›ˆÛË Ù˘ ‰fiÛ˘ ÙˆÓ CNI.
¡∂ºƒOΔO•π∫OΔ∏Δ∞ ∞¡O™O∫∞Δ∞™Δ∞§Δπ∫ø¡ º∞ƒª∞∫ø¡ ∞Ó Î·È ‚ÈÔ¯ËÌÈο ‰È·ÊÔÚÂÙÈΤ˜ Ô˘Û›Â˜, ÔÈ ·Ó·ÛÙÔÏ›˜ Ù˘ ηÏÛÈÓ¢ڛÓ˘ (CNI), ‰ËÏ·‰‹ Ë Î˘ÎÏÔÛÔÚ›ÓË Î·È ÙÔ tacrolimus, ·ÔÙÂÏÔ‡Ó ÈηÓÔ‡˜ ·ÓÔÛÔηٷÛÙ·ÏÙÈÎÔ‡˜ ·Ú¿ÁÔÓÙ˜ Ô˘ ¯ÚËÛÈÌÔÔÈÔ‡ÓÙ·È ÛÙË ÌÂÙ·ÌfiÛ¯Â˘ÛË ‹·ÙÔ˜ Î·È ·ÚÔ˘ÛÈ¿˙Ô˘Ó ·ÚfiÌÔÈÔ Ì˯·ÓÈÛÌfi ‰Ú¿Û˘, ·ÏÏ¿ Î·È ÙÔÓ ›‰ÈÔ ÙÚfiÔ ÚÔÛ‚ÔÏ‹˜ ÙÔ˘ ÓÂÊÚÔ‡. £ÂˆÚÔ‡ÓÙ·È Ï¤ÔÓ ˆ˜ Ë Î˘ÚÈfiÙÂÚË ·ÈÙ›· Ù˘ á∞ ÛÙÔ˘˜ ·ÛıÂÓ›˜ Ì ÌÂÙ·ÌfiÛ¯Â˘ÛË24. ªÂÈÒÓÔ˘Ó ÙË ÓÂÊÚÈ΋ ·ÈÌ·ÙÈ΋ ÚÔ‹ Î·È ÙÔ Ú˘ıÌfi ÛÂÈÚ·Ì·ÙÈ΋˜ ‰È‹ıËÛ˘ (GFR) Î·È Û·ÓÈfiÙÂÚ· ÚÔηÏÔ‡Ó ıÚÔÌ‚ˆÙÈ΋ ÌÈÎÚÔ·ÁÁÂÈÔ¿ıÂÈ·25. ™˘ÁÎÂÎÚÈ̤ӷ Ë ÓÂÊÚÈ΋ ‰˘ÛÏÂÈÙÔ˘ÚÁ›· Â›Ó·È «ÚÔÛÂÈÚ·Ì·ÙÈ΋» ÏfiÁˆ ÔÍ›·˜, ‰ÔÛÔÂÍ·ÚÙÒÌÂÓ˘ - ·ÏÏ¿ ·ÓÙÈÛÙÚÂÙ‹˜ ·ÁÁÂÈÔÛ‡Û·Û˘ ÙˆÓ ÚÔÛ·ÁˆÁÒÓ ·ÚÙËÚÈÔÏ›ˆÓ. ™Â ΢ÙÙ·ÚÈÎfi Â›Â‰Ô ÚÔ¿ÁÂÙ·È Ë ·Ú·Áˆ-
METAMO™XEY™Eπ™ 2008
Á‹ ÂÓ‰ÔıËÏ›Ó˘-I Î·È ·ÁÁÂÈÔÙÂÓÛ›Ó˘ II, Ë ·ÂÏ¢ı¤ÚˆÛË ÓÔÚÂÈÓÂÊÚ›Ó˘ Î·È Á›ÓÔÓÙ·È ·ÏÏ·Á¤˜ ÛÙÔÓ Î·Ù·ÚÚ¿ÎÙË ÚÔÛÙ·ÁÏ·Ó‰ÈÓÒÓ-ıÚÔÌ‚ÔÍ¿Ó˘, Ì ·ÔÙ¤ÏÂÛÌ· ÙÔÓ Û¯ËÌ·ÙÈÛÌfi matrix Û˘ÛÛˆÚ‡ÛˆÓ, Ô˘ ÚÔηÏÔ‡Ó ˘·Ï›ÓˆÛË ÙˆÓ ·ÚÙËÚÈÔÏ›ˆÓ Î·È ÛˆÏËÓ·Úȷ΋ ·ÙÚÔÊ›·. ∏ ÙÒÛË ÙÔ˘ (GFR) ·ÚÔ˘ÛÈ¿˙ÂÙ·È ¿ÌÂÛ· ÌÂÙ¿ ÙË ¯ÔÚ‹ÁËÛË Ù˘ ΢ÎÏÔÛÔÚ›Ó˘ Î·È ‰Ë ÙËÓ ÂÓ‰ÔÊϤ‚È·, ÂÓÒ Â‡ÎÔÏ· ·ӤگÂÙ·È Ì¤Û· Û 24-48 ÒÚ˜ ÌÂÈÒÓÔÓÙ·˜ ÙË ‰fiÛË. ∞ÓÙÈı¤Ùˆ˜ ·Ú·Ù›ÓÂÙ·È ÂÚÈÛÛfiÙÂÚÔ Ë ÙÔÍÈÎfiÙËÙ· ÙÔ˘ tacrolimus. ∞fi ÙËÓ ¿ÏÏË ÌÂÚÈ¿ Ë ¯ÚfiÓÈ· ¯Ú‹ÛË ·˘ÙÒÓ ÙˆÓ ·Ú·ÁfiÓÙˆÓ ÌÔÚ› Ó· ÚÔηϤÛÂÈ ‰È¿ÌÂÛË ›ÓˆÛË Ì ÂÁηÙÂÛÙË̤ÓË ¯ÚfiÓÈ· ÓÂÊÚÈ΋ ÓfiÛÔ. ™Â Â›Â‰Ô ÌÈÎÚÔ΢ÎÏÔÊÔÚ›·˜ Ë ›ÓˆÛË ÚÔ¿ÁÂÙ·È ·fi ÌfiÚÈ·, fiˆ˜ ‚-ÙÚÔÔÔÈËÙÈÎÔ‡ ·˘ÍËÙÈÎÔ‡ ·Ú¿ÁÔÓÙ·, ÂÓ‰ÔıËÏ›Ó˘ -1 Î·È ÔÛÙÂÔÔÓÙ›Ó˘ 26. ¶·ÏÈfiÙÂÚ˜ ÌÂϤÙ˜ ÙˆÓ Fisher Î·È Platz 10-17 ‰ÂÓ ¤‰ÂÈ¯Ó·Ó ·ÍÈÔÛËÌ›ˆÙË ‰È·ÊÔÚ¿ ÛÙË ÓÂÊÚÔÙÔÍÈÎfiÙËÙ· ÌÂٷ͇ ΢ÎÏÔÛÔÚ›Ó˘ Î·È tacrolimus Û ·ÛıÂÓ›˜ Ì Oª∏. ŸÌˆ˜ ÛÙË ‰ËÌÔÛ›Â˘ÛË ÙÔ˘ Pham26 ÙÔ˘ 2003 ·Ô‰Â›¯ıËΠ̠5ÂÙ‹ ·Ú·ÎÔÏÔ‡ıËÛË fiÙÈ ÌË ‰È·‚ËÙÈÎÔ› ·ÛıÂÓ›˜ Ì Oª∏ ›¯·Ó ηχÙÂÚË ÓÂÊÚÈ΋ ÏÂÈÙÔ˘ÚÁ›· Ì tacrolimus ·ãfiÙÈ Ì ΢ÎÏÔÛÔÚ›ÓË. ŸÛÔÓ ·ÊÔÚ¿ ÙÔ˘˜ ‰È·‚ËÙÈÎÔ‡˜ ‰ÂÓ ‰È·Ê¿ÓËΠÛÙ·ÙÈÛÙÈ΋ ‰È·ÊÔÚ¿. ™Â Ì›· ‰Â ÚfiÛÊ·ÙË ÌÂϤÙË Ô˘ ·Ú·ÎÔÏÔ‡ıËÛ 32000 ·ÛıÂÓ›˜ ηٷÁÚ¿ÊËΠÌÂÁ·Ï‡ÙÂÚÔ˜ ΛӉ˘ÓÔ˜ ÁÈ· ÂÌÊ¿ÓÈÛË ¯ÚfiÓÈ·˜ ÓÂÊÚÈ΋˜ ÓfiÛÔ˘ Ì ÙËÓ Î˘ÎÏÔÛÔÚ›ÓË (relative risk 1.25; P<0.001). ΔÔ ÂӉȷʤÚÔÓ Â›Ó·È fiÙÈ ·˘Ù‹ Ë ‰È·ÊÔÚ¿ ‰ÂÓ ·Ú·ÙËÚ‹ıËΠ۠·ÛıÂÓ›˜ Ì ÌÂÙ·ÌfiÛ¯Â˘ÛË ¿ÏÏÔ˘ Û˘Ì·ÁÔ‡˜ ÔÚÁ¿ÓÔ˘22. ¢ÂÓ ¤¯ÂÈ Û¯Â‰È·ÛÙ› ·ÎfiÌË ¤Ó· ηıÔÏÈÎfi ÚˆÙfiÎÔÏÏÔ ÁÈ· Ó· ·ÔÊ¢¯ı› Ë ÓÂÊÚÔÙÔÍÈÎfiÙËÙ· ·˘ÙÒÓ ÙˆÓ ·Ú·ÁfiÓÙˆÓ. ¢È¿ÊÔÚ· ΤÓÙÚ· ÂÈÛËÁÔ‡ÓÙ·È Ù· ‰Èο ÙÔ˘˜ ÚˆÙfiÎÔÏÏ·, fiˆ˜ ÁÈ· ·Ú¿‰ÂÈÁÌ· Ô Gonwa Ô˘ ·ÓÙÈηıÈÛÙ¿ ÙËÓ Î˘ÎÏÔÛÔÚ›ÓË Û ·ÛıÂÓ›˜ Ì ˷ÙÔÓÂÊÚÈÎfi Û‡Ó‰ÚÔÌÔ ‹ ̤ÙÚÈ· ÓÂÊÚÈ΋ ·Ó¿ÚÎÂÈ· Ì ÙÔ Û˘Ó‰˘·ÛÌfi ·˙·ıÂÈÔÚ›Ó˘ Ì ÛÙÂÚÔÂȉ‹27. ¶Ï¤ÔÓ ˘¿Ú¯ÂÈ Ë Ù¿ÛË Ó· ·ÓÙÈηı›ÛÙ·Ù·È Ë ¯Ú‹ÛË ÙˆÓ CNI Ì ¿ÏÏ· ·ÓÔÛÔηٷÛÙ·ÏÙÈο, fiˆ˜ Ù· ÌÔÓÔÎψÓÈο ·ÓÙÈÛÒÌ·Ù· ¤Ó·ÓÙÈ ÙˆÓ ˘Ô‰Ô¯¤ˆÓ Ù˘ interleukin 2 (antiCD25: basiliximab/daclizumab), ÙÔ mycophenolate mofetil (MMF) Î·È ÙÔ sirolimus. ŸÛÔÓ ·ÊÔÚ¿ ÙË daclizumab, Â›Ó·È ÌÈ· ·ÓıÚÒÈÓË ·ÓÔÛÔÛÊ·ÈÚ›ÓË G1 Ô˘ ÌÏÔοÚÂÈ ÙËÓ ·Ï˘Û›‰· · ÙˆÓ ˘Ô‰Ô¯¤ˆÓ Ù˘ interleukin 2 ÛÙ· ÂÓÂÚ-
139
ÁÔÔÈË̤ӷ Δ ÏÂÌÊÔ·ÙÙ·Ú·. ¢ÂÓ ·Ú·ÙËÚ‹ıËÎ·Ó ÂÈÏÔΤ˜ ÙÔ˘ Ù‡Ô˘ ÙÔ˘ Û˘Ó‰ÚfiÌÔ˘ ·ÂÏ¢ı¤ÚˆÛ˘ ΢ÙÔÎÈÓÒÓ, Ó¢ÚÔÙÔÍÈÎfiÙËÙ· ‹ ÓÂÊÚÔÙÔÍÈÎfiÙËÙ·28. 줂·È· Ë ¯Ú‹ÛË Ù˘ Á›ÓÂÙ·È ÛÂ Û˘Ó‰˘·ÛÌfi Ì CNI, ·ÏÏ¿ Û ÌÂȈ̤ÓË ‰fiÛË, ÔfiÙÂ Î·È ‚ÂÏÙÈÒÓÂÙ·È Ë ÓÂÊÚÈ΋ ÏÂÈÙÔ˘ÚÁ›· Î·È ‰ÂÓ ·˘Í¿ÓÂÙ·È Ô Î›Ó‰˘ÓÔ˜ Ù˘ ·fiÚÚȄ˘29,30. ΔÔ MMF Â›Ó·È ¤Ó·˜ ËÌÈÛ˘ÓıÂÙÈÎfi˜ ÂÛÙ¤Ú·˜ ÙÔ˘ Ì˘ÎÔÊÂÓÔÏÈÎÔ‡ ÔͤԘ Ô˘ ·Ó·ÛÙ¤ÏÏÂÈ ÂÎÏÂÎÙÈο ÙÔÓ ÔÏÏ·Ï·ÛÈ·ÛÌfi ÙˆÓ μ Î·È Δ ÏÂÌÊÔ΢ÙÙ¿ÚˆÓ. ÃÚËÛÈÌÔÔÈ‹ıËΠÛÂ Û˘Ó‰˘·ÛÌfi Ì ÌÈÎÚfiÙÂÚ˜ ‰fiÛÂȘ CNI ‹ ÛÙË Ê¿ÛË Ù˘ Ï‹ÚÔ˘˜ ·fiÛ˘ÚÛ˘ ÙÔ˘˜, ÏfiÁˆ ÛÔ‚·Ú‹˜ ÙÔÍÈÎfiÙËÙ·˜. °È· ·Ú¿‰ÂÈÁÌ· ÔÈ Cantarovich et al31 Û ·ÛıÂÓ›˜ Ì ̤ÙÚÈ· ÓÂÊÚÈ΋ ·Ó¿ÚÎÂÈ· ¯ÔÚ‹ÁËÛ·Ó MMF Ì ÛÙ·‰È·Î‹ Ì›ˆÛË Ù˘ ΢ÎÏÔÛÔÚ›Ó˘ Û 25mg ‰‡Ô ÊÔÚ¤˜ ÙËÓ Ë̤ڷ Î·È Î·Ù¿ÊÂÚ·Ó Ó· ‚ÂÏÙÈÒÛÔ˘Ó Î·Ù¿ Ôχ ÙË ÓÂÊÚÈ΋ ÏÂÈÙÔ˘ÚÁ›·, Ì ÌÂÈÔÓ¤ÎÙËÌ· ÙËÓ ÂÌÊ¿ÓÈÛË ÔÍ›·˜ ·fiÚÚȄ˘ Û ÔÛÔÛÙfi 29%. ∞ÓÙÈı¤Ùˆ˜, Û ¿ÏÏË ÌÂϤÙË32 Ì ·Ô‰Â‰ÂÈÁ̤ÓË Ì ‚ÈÔ„›· CNI-related ¯ÚfiÓÈ· ÓÂÊÚÈ΋ ÓfiÛÔ, Ë ¤Ó·ÚÍË MMF ÛÙË ı¤ÛË Î˘ÎÏÔÛÔÚ›Ó˘ ‹ tacrolimus ‰ÂÓ Â·Ó¤ÊÂÚ ÙË ÓÂÊÚÈ΋ ÏÂÈÙÔ˘ÚÁ›·, Ô‡Ù ·fi ÙËÓ ¿ÏÏË ·‡ÍËÛ ٷ ÂÂÈÛfi‰È· ·fiÚÚȄ˘. ∞Ó Î·È Î¿ÔÈ· ΤÓÙÚ· ÂÈ̤ÓÔ˘Ó Ó· ÙÔ ‰ÔÎÈÌ¿˙Ô˘Ó ˆ˜ ÌÔÓÔıÂڷ›· Ì ÂÓı·ÚÚ˘ÓÙÈο ÚfiÛÊ·Ù· ·ÔÙÂϤÛÌ·Ù·33,34,35, ›Ûˆ˜ Ë ÈÔ ·ÛÊ·Ï‹˜ ̤ıÔ‰Ô˜ Â›Ó·È ·˘Ù‹ Ô˘ ÚÔÙ›ÓÂÙ·È ·fi ÌÈ· ÈÙ·ÏÈ΋ ÔÌ¿‰· ÙÔ 2007 Ì 1.5gr MMF (·ÓÙ› 2gr) Ì 25% Ù˘ ·Ú¯È΋˜ ‰fiÛ˘ CNI36. ΔÔ sirolimus ˆ˜ Ó¤Ô Î·È ÈηÓfi ·ÓÔÛÔηٷÛÙ·ÏÙÈÎfi Ì ‰È·ÊÔÚÂÙÈÎfi Ì˯·ÓÈÛÌfi ‰Ú¿Û˘ ·fi Ù· CNI ··ÏÏ¿ÛÛÂÙ·È Ù˘ ηÙËÁÔÚ›·˜ Ù˘ ÓÂÊÚÔÙÔÍÈÎfiÙËÙ·˜. Δ·˘ÙÔÔÈ‹ıËΠÚÒÙ· ˆ˜ ·ÓÙÈÌÈÎÚÔ‚È·Îfi Ê¿ÚÌ·ÎÔ Ù˘ ηÙËÁÔÚ›·˜ ÙˆÓ Ì·ÎÚÔÏȉÒÓ, ·ÏÏ¿ ·ÚÁfiÙÂÚ· ·Ó·ÁÓˆÚ›ÛÙËÎ·Ó ÔÈ ·ÓÔÛÔÙÚÔÔÔÈËÙÈΤ˜ ÙÔ˘ ȉÈfiÙËÙ˜ Î·È Ë ÈηÓfiÙËÙ· ÙÔ˘ Ó· ·Ú·Ù›ÓÂÈ ÙË ˙ˆ‹ ÙÔ˘ ÌÔۯ‡̷ÙÔ˜. ∏ ¯Ú‹ÛË ÙÔ˘ Û ·ÛıÂÓ›˜ Ì ‰È·ÊÔÚÂÙÈÎfi ‚·ıÌfi ÓÂÊÚÈ΋˜ ·Ó¿ÚÎÂÈ·˜ Ì ٷ˘Ùfi¯ÚÔÓË ‰È·ÎÔ‹ ÙˆÓ CNI, ‚ÂÏÙ›ˆÛ ÙË ÓÂÊÚÈ΋ ÏÂÈÙÔ˘ÚÁ›· ¯ˆÚ›˜ ÂÌÊ¿ÓÈÛË ·fiÚÚȄ˘37. ŸÌˆ˜ ÙÔ FDA ÚÔÂȉÔÔ›ËÛ fiÙÈ Ë ¯ÔÚ‹ÁËÛ‹ ÙÔ˘ ‰ÂÓ Â›Ó·È ·ÛÊ·Ï‹˜ ÛÙËÓ ÚÒÈÌË ÂÚ›Ô‰Ô ÌÂÙ¿ ÙË ÌÂÙ·ÌfiÛ¯Â˘ÛË –ÏfiÁˆ ÚfiÎÏËÛ˘ ·ÚÙËÚȷ΋˜ ıÚfiÌ‚ˆÛ˘– ·ÏÏ¿ ÌÔÚ› Ó· ¯ÔÚËÁËı› 6 Ì‹Ó˜ ÌÂÙ¿38,39. ∞ÓÙÈÎÚÔ˘fiÌÂÓ˜ ÌÂϤÙ˜ ˘ÔÛÙËÚ›˙Ô˘Ó ÙË ¯Ú‹ÛË ÙÔ˘, ÁÈ·Ù› ‰ÂÓ ÂȂ‚·›ˆÛ·Ó ·˘ÍË̤ÓË Â›ÙˆÛË ÛÙË ıÚfiÌ‚ˆÛË Ù˘ Ë·ÙÈ΋˜ ·ÚÙËÚ›·˜40,41.
140
Ã. ∫À¢ø¡∞
∂›Ó·È ÏÔÈfiÓ ÏÔÁÈÎfi, ÏfiÁˆ Ù˘ ¤ÏÏÂȄ˘ ÌÂÁ¿ÏˆÓ ÚÔÔÙÈÎÒÓ Ù˘¯·ÈÔÔÈËÌ¤ÓˆÓ ÌÂÏÂÙÒÓ Î·È ÙˆÓ ·ÌÊÈÏÂÁfiÌÂÓˆÓ ·ÔÙÂÏÂÛÌ¿ÙˆÓ ÌÂÏÂÙÒÓ Ì ÌÈÎÚ¤˜ ÛÂÈÚ¤˜ ·ÛıÂÓÒÓ, Ë ·ÓÔÛÔηٷÛÙ·ÏÙÈ΋ ıÂڷ›· Ó· ÚÔÛ‰ÈÔÚ›˙ÂÙ·È Ì ‚¿ÛË ÙȘ ·Ó¿ÁΘ ÙÔ˘ Û˘ÁÎÂÎÚÈ̤ÓÔ˘ ·ÚÚÒÛÙÔ˘. ŒÙÛÈ, ÌÔÚ› ·fi ÙË Ì›· Ù· ÌÔÓÔÎψÓÈο ·ÓÙÈÛÒÌ·Ù· ¤Ó·ÓÙÈ ÙˆÓ ˘Ô‰Ô¯¤ˆÓ Ù˘ interleukin 2 Ì ‰È·ÎÔ‹ Ù˘ ΢ÎÏÔÛÔÚ›Ó˘ Ó· ‚ÂÏÙ›ˆÛ·Ó ÙË ÓÂÊÚÈ΋ ÏÂÈÙÔ˘ÚÁ›·, ·fi ÙËÓ ¿ÏÏË fï˜ Ë ¯ÔÚ‹ÁËÛ‹ ÙÔ˘˜ Ì·˙› Ì MMF ·‡ÍËÛ ÙÔÓ Î›Ó‰˘ÓÔ Â·ÓÂÓÂÚÁÔÔ›ËÛ˘ ÙÔ˘ ÈÔ‡ Î·È ÙËÓ ÂÌÊ¿ÓÈÛË Ë·Ù›Ùȉ·˜ C ÛÙÔ ÌfiÛ¯Â˘Ì· 4243. ∞Ó Î·È ÙÔ MMF ‰È·ı¤ÙÂÈ ·ÓÙÈ-È˚΋ ‰Ú¿ÛË ·ÚfiÌÔÈ· Ù˘ ÚÈÌ·‚·Ú›Ó˘ Î·È ¤¯ÂÈ Û˘Ó¤ÚÁÂÈ· Ì ÙËÓ ÈÓÙÂÚÊÂÚfiÓË-·, Ë ¯Ú‹ÛË ÙÔ˘ ÛÙË ÌÂÙ·ÌÔÛ¯Â˘ÙÈ΋ ÂÚ›Ô‰Ô ‰ÂÓ ÙÂÎÌËÚÈÒıËΠ·ÎfiÌË Â·ÚÎÒ˜. ∫·Ù·Ï‹ÁÔÓÙ·˜, ‰ÂÓ ˘¿Ú¯ÂÈ Û·Ê‹˜ Ô‰ËÁ›· ÁÈ· ÙËÓ ·ÓÙÈηٿÛÙ·ÛË ÙˆÓ CNI Ì ¿ÏÏÔ˘˜ ·ÓÔÛÔηٷÛÙ·ÏÙÈÎÔ‡˜ ·Ú¿ÁÔÓÙ˜, fiÙ·Ó ‰È·ÈÛÙÒÓÂÙ·È Ë ÓÂÊÚÈ΋ ‚Ï¿‚Ë, ·ÏÏ¿ ·fi ·ÚÎÂÙÔ‡˜ ¯ÚËÛÈÌÔÔÈÔ‡ÓÙ·È ÔÈ ·Ó·ÛÙÔÏ›˜ ÙÔ˘ ÌÂÙ·ÙÚÂÙÈÎÔ‡ ÂÓ˙‡ÌÔ˘ Ù˘ ·ÁÁÂÈÔÙÂÓÛ›Ó˘ (·-ª∂∞) ÁÈ· Ó· ηı˘ÛÙÂÚ‹ÛÔ˘Ó ÙËÓ ÚfiÔ‰Ô Ù˘ ‰È¿ÌÂÛ˘ ›ÓˆÛ˘44. ∞ÔÁÔËÙ¢ÙÈο ‹Ù·Ó Ù· ·ÔÙÂϤÛÌ·Ù· ÙˆÓ ÂÚ¢ÓÒÓ ÁÈ· ÙÔ˘˜ ·Ó·ÛÙÔÏ›˜ ·Û‚ÂÛÙ›Ô˘, ÙË ‚ÈÙ·Ì›ÓË ∂, ÙÔ È¯ı˘¤Ï·ÈÔ, ÙË ÛÈÏ·ÛÙ·Ù›ÓË Î·È ÙÔ˘˜ ·ÔÎÏÂÈÛÙ¤˜ ‚·‰ÚÂÓÂÚÁÈÎÒÓ ˘Ô‰Ô¯¤ˆÓ.
∞¡Δπª∂Δø¶π™∏ ™Δ∏ ª∂£ ™ÙËÓ ÎÚ›ÛÈÌË ¿ÌÂÛ· ÌÂÙÂÁ¯ÂÈÚËÙÈ΋ ÂÚ›Ô‰Ô ·Ú·ÎÔÏÔ˘ıÂ›Ù·È Ô ¿ÚÚˆÛÙÔ˜ ÛÙË ªÔÓ¿‰· ∂ÓÙ·ÙÈ΋˜ £Âڷ›·˜, fiÔ˘ Ï·Ì‚¿ÓÔÓÙ·È Ù· ··Ú·›ÙËÙ· ıÂڷ¢ÙÈο ̤ÙÚ· ÁÈ· ÙËÓ ÚfiÏË„Ë Î·È ·ÓÙÈÌÂÙÒÈÛË Ù˘ ÓÂÊÚÈ΋˜ ·Ó¿ÚÎÂÈ·˜. ∏ ·Ú΋˜ ·ÔηٿÛÙ·ÛË ÙÔ˘ ÂÓ‰·ÁÁÂÈ·ÎÔ‡ fiÁÎÔ˘, Ë ·ÈÌÔ‰˘Ó·ÌÈ΋ ˘ÔÛÙ‹ÚÈÍË, Ë ÂÈıÂÙÈ΋ ıÂڷ›· Û ÂÌÊ·ÓÈ˙fiÌÂÓË Û‹„Ë, Ë ¯Ú‹ÛË ÓÂÊÚÔÚÔÛٷ٢ÙÈÎÒÓ Ì¤ÙÚˆÓ Î·Ù¿ ÙË ‰ÈÂÓ¤ÚÁÂÈ· ‰È·ÁÓˆÛÙÈÎÒÓ ÂÍÂÙ¿ÛÂˆÓ Ì ÛÎÈ·ÁÚ·ÊÈο ̤۷ (¡-·ÎÂÙ˘ÏÔ΢ÛÙ½ÓË – ‰ÈÙÙ·ÓıÚ·ÎÈο – ÎÚ˘ÛÙ·ÏÏÔÂȉ‹) Î·È Ë Ú‡ıÌÈÛË Ù˘ ˘ÂÚÁÏ˘Î·ÈÌ›·˜ ·ÔÙÂÏÔ‡Ó ıÂÌÂÏÈÒ‰Ë Ú·ÎÙÈ΋ ÛÙË ª∂£. ∏ ̤ÙÚËÛË Ù˘ ÎÚ·ÙÈÓ›Ó˘ ÔÚÔ‡ Â›Ó·È ÚÔ˘Ù›Ó·, fï˜ ‰Â ıˆÚÂ›Ù·È ·fiÏ˘Ù· ·ÍÈfiÈÛÙÔ˜ ‰Â›ÎÙ˘ Ù˘ ÓÂÊÚÈ΋˜ ÏÂÈÙÔ˘ÚÁ›·˜. ∏ ÂÏ·Ùو̤ÓË Ì˘È΋ Ì¿˙·, Ë ˘ÂÚ¯ÔÏ˘ÚÂıÚÈÓ·ÈÌ›· Î·È Ë ÂÏÏÈ‹˜ Ë·ÙÈ΋ ‚ÈÔÛ‡ÓıÂÛË Ù˘ ÎÚ·ٛÓ˘ ÌÔÚ› Ó· Û˘Ì‚¿ÏÏÔ˘Ó Û „¢‰Ò˜ ¯·ÌËÏ¿ ›‰· Ù˘ ÎÚ·ÙÈÓ›Ó˘ ÔÚÔ‡. £ÂˆÚËÙÈο, Ë Î·Ï‡ÙÂÚË Ì¤ıÔ‰Ô˜ ı· ‹-
Ù·Ó Ë Ì¤ÙÚËÛË ÙÔ˘ GFR Ì ÈÓÔ˘Ï›ÓË ‹ Ú·‰ÈÔ˚ÛfiÙÔ·, ·ÏÏ¿ ÎÔÛÙ›˙ÂÈ, Â›Ó·È ¯ÚÔÓÔ‚fiÚÔ˜ Î·È ·ÓÂÊ¿ÚÌÔÛÙË Û·Ó Î·ıËÌÂÚÈÓ‹ Ú·ÎÙÈ΋. Δ· ÙÂÏÂ˘Ù·›· ¯ÚfiÓÈ· ÂÚÂ˘Ó¿Ù·È Ë Û˘ÛÙ·Ù›ÓË ÔÚÔ‡ (serum cystatin C) ˆ˜ ¢·›ÛıËÙÔ˜ ‰Â›ÎÙ˘ Ù˘ Ì›ˆÛ˘ ÙÔ˘ GFR45-46. ∏ cystatin C Â›Ó·È ¤Ó· ÔÏ˘ÂÙ›‰ÈÔ Ô˘ ·Ú¿ÁÂÙ·È Û fiÏÔ˘˜ ÙÔ˘˜ ˘Ú‹Ó˜ ÙˆÓ Î˘ÙÙ¿ÚˆÓ Û˘Ó¯Ҙ ̤۷ ÛÙÔ ¯ÚfiÓÔ, ÂÚÓ¿ ÙË ÛÂÈÚ·Ì·ÙÈ΋ ÌÂÌ‚Ú¿ÓË, ·ӷÔÚÚÔÊ¿Ù·È Î·È ÌÂÙ·‚ÔÏ›˙ÂÙ·È ÛÙ· ÛˆÏËÓ¿ÚÈ·. ¢È¿ÊÔÚÔÈ ÌÂÏÂÙËÙ¤˜ η٤ÏËÍ·Ó ÛÙÔ Û˘Ì¤Ú·ÛÌ· fiÙÈ Â›Ó·È Ô Î·Ï‡ÙÂÚÔ˜ ‰Â›ÎÙ˘ ÂÎÙ›ÌËÛ˘ ÙÔ˘ GFR ÛÙÔ˘˜ Ï‹Ù˜ Ë·ÙÈÎÔ‡ ÌÔۯ‡̷ÙÔ˜ Î·È ÌÔÚ› Ó· ·ÔÙÂϤÛÂÈ ÙËÓ Ú·ÎÙÈ΋ ÙÔ˘ ̤ÏÏÔÓÙÔ˜ ÛÙË ª∂£47,48,49. ™ËÌ·ÓÙÈ΋ Â›Ó·È ÂÈϤÔÓ Ë Î·Ù·Ì¤ÙÚËÛË Ù˘ ÂÓ‰ÔÎÔÈÏȷ΋˜ ›ÂÛ˘ (intraabdominal pressure IAP), ÌÈ· Î·È ıˆÚÂ›Ù·È ÎÚ›ÛÈÌÔ˜ ÚÔÁÓˆÛÙÈÎfi˜ ‰Â›ÎÙ˘ Ù˘ ÁÂÓÈ΋˜ ηٿÛÙ·Û˘ ÙÔ˘ ‚·Ú¤ˆ˜ ¿Û¯ÔÓÙÔ˜50,51. ∞ÛıÂÓ›˜ Ì ÌÂÙ·ÌfiÛ¯Â˘ÛË ‹·ÙÔ˜ ÂÌÊ·Ó›˙Ô˘Ó Û˘¯Ó¿ ·‡ÍËÛË Ù˘ IAP ÙfiÛÔ ÚÔÂÁ¯ÂÈÚËÙÈο (·ÛΛÙ˘ ˘fi Ù¿ÛË) fiÛÔ Î·È ÌÂÙÂÁ¯ÂÈÚËÙÈο (Û˘ÛÛÒÚ¢ÛË ·›Ì·ÙÔ˜ Î·È ıÚfiÌ‚ˆÓ ÛÙËÓ ÂÚÈÙÔÓ·˚΋ ÎÔÈÏfiÙËÙ·, ÙÔÔı¤ÙËÛË ·ÈÌÔÛÙ·ÙÈÎÒÓ Á·˙ÒÓ Á‡Úˆ ·fi ÙÔ ÌfiÛ¯Â˘Ì· ÁÈ· ÙËÓ ·ÓÙÈÌÂÙÒÈÛË ‰È¿¯˘Ù˘ ·ÈÌÔÚÚ·Á›·˜, Û˘ÌÊfiÚËÛË Î·È Ô›‰ËÌ· ÙÔ˘ ÂÓÙ¤ÚÔ˘ ÏfiÁˆ ˘Ï·›·˜ ˘¤ÚÙ·Û˘ ‹ Ì·˙È΋ ÌÂÙ¿ÁÁÈÛË ÚÔ˚fiÓÙˆÓ ·›Ì·ÙÔ˜ Î·È ÎÔÏÏÔÂȉÒÓ)52. Œ¯ÂÈ ·Ô‰Âȯı› fiÙÈ Ë ÔÍ›· ·‡ÍËÛË Ù˘ IAP ÚÔηÏ› ‰˘ÛÏÂÈÙÔ˘ÚÁ›· ‰È·ÊfiÚˆÓ ÔÚÁ¿ÓˆÓ, Û ·ÓÙ›ıÂÛË Ì ÙËÓ ¯ÚfiÓÈ· ·‡ÍËÛ‹ Ù˘ - fiˆ˜ Û˘Ì‚·›ÓÂÈ ÛÙËÓ ·¯˘Û·ÚΛ· - fiÔ˘ ˘¿Ú¯ÂÈ ¯ÚfiÓÔ˜ ÁÈ· ·ÓÙÈÚÚfiËÛË53. ∏ ‰È·Ú΋˜ ·‡ÍËÛË Ù˘ IAP Ô‰ËÁ› Û Ì›ˆÛË Ù˘ ηډȷ΋˜ ·ÚÔ¯‹˜, Ù˘ ÛÏ·¯ÓÈ΋˜ Î·È Ë·ÙÈ΋˜ ·ÈÌ·ÙÈ΋˜ ÚÔ‹˜ Î·È ÙÔ˘ ‰Ú·ÛÙÈÎÔ‡ ·Ó·ÓÂfiÌÂÓÔ˘ fiÁÎÔ˘. O Ì˯·ÓÈÛÌfi˜ Ì ÙÔÓ ÔÔ›Ô Ë ˘„ËÏ‹ IAP ÚÔηÏ› ÓÂÊÚÈ΋ ·Ó¿ÚÎÂÈ· ‰ÂÓ ¤¯ÂÈ Ï‹Úˆ˜ ‰È¢ÎÚÈÓÈÛÙ›, ·ÏÏ¿ ÁÓˆÚ›˙Ô˘Ì οÔÈÔ˘˜ ·ÈÙÈÔ·ıÔÏÔÁÈÎÔ‡˜ ·Ú¿ÁÔÓÙ˜ fiˆ˜ : Ì›ˆÛË Ù˘ ÓÂÊÚÈ΋˜ ·ÚÙËÚȷ΋˜ ÚÔ‹˜, ·ÈÌ·ÙÈÎfi shunt ·fi ÙË ÊÏÔÈÒ‰Ë ÛÙË Ì˘ÂÏÒ‰Ë ÌÔ›Ú· ÙÔ˘ ÓÂÊÚÔ‡, ˘ÂÚ¤ÎÎÚÈÛË ÚÂÓ›Ó˘-·Ï‰ÔÛÙÂÚfiÓ˘-·ÓÙȉÈÔ˘ÚËÙÈ΋˜ ÔÚÌfiÓ˘54. ∞Ó Î·È ˘¿Ú¯ÂÈ ‰È¯ÔÁӈ̛· ÁÈ· ÙÔ ÔÈ· Â›Ó·È Ë ·fiÏ˘ÙË ÙÈÌ‹ Ù˘ IAP Ô˘ ıˆÚÂ›Ù·È ·ıÔÏÔÁÈ΋ Î·È ÙÔ Î·ÙÒÊÏÈ ¿Óˆ ·fi ÙÔ ÔÔ›Ô Â›Ó·È ÎÚ›ÛÈÌË ÁÈ· ÙÔ˘˜ ÓÂÊÚÔ‡˜, ‚Ú¤ıËΠ۠ÂÈÚ·Ì·ÙÈο ÌÔÓ٤Ϸ fiÙÈ ÙÈ̤˜ ÌÂٷ͇ 20 Î·È 40mmHg ÌÂÈÒÓÔ˘Ó ÙË ÌÂÛÂÓÙ¤ÚÈÔ ·ÈÌ·ÙÈ΋ ÚÔ‹ ηٿ 40-70%. IAP>20mmHg ÂÏ·ÙÙÒÓÂÈ ÙË ÛÂÈÚ·Ì·ÙÈ΋ ‰È‹ıËÛË Î·Ù¿ 25% Î·È ÂÈʤÚÂÈ ÔÏÈÁÔ˘-
METAMO™XEY™Eπ™ 2008
Ú›·55. ™Â ÌÈ· ÌÂϤÙË Ô˘ ·ÊÔÚ¿ ÂȉÈο ÙËÓ ÂÓ‰ÔÎÔÈÏȷ΋ ˘¤ÚÙ·ÛË Û ϋÙ˜ ‹·ÙÔ˜ Î·È ÙË Û˘Û¯¤ÙÈÛ‹ Ù˘ Ì ÌÂÙÂÁ¯ÂÈÚËÙÈ΋ O¡∞, ‚Ú¤ıËΠfiÙÈ ÔÈ ·ÛıÂÓ›˜ Ì IAP>25mmHg ›¯·Ó ˘„ËÏfiÙÂÚ˜ ÙÈ̤˜ ÎÚ·ÙÈÓ›Ó˘, ÌÂÁ·Ï‡ÙÂÚË ·Ó¿ÁÎË ‰ÈÔ˘ÚËÙÈÎÒÓ Î·È ·˘ÍË̤ÓÔ ÔÛÔÛÙfi Ù¯ÓËÙ‹˜ ·ÈÌÔοı·ÚÛ˘56. ∂›Ó·È ·ÎfiÌË ·ÍÈÔÛËÌ›ˆÙÔ fiÙÈ Ë ˘„ËÏ‹ IAP ÂËÚ¿˙ÂÈ Î¿ÔȘ ·ÈÌÔ‰˘Ó·ÌÈΤ˜ ·Ú·Ì¤ÙÚÔ˘˜, fiˆ˜ ÙË Ì¤ÛË ·ÚÙËÚȷ΋ ›ÂÛË (MAP), ÙËÓ ÎÂÓÙÚÈ΋ ÊÏ‚È΋ ›ÂÛË (CVP ) Î·È ÙËÓ ›ÂÛË ÂÓÛÊ‹ÓˆÛ˘ Ó¢ÌÔÓÈÎÒÓ ÙÚȯÔÂȉÒÓ (PCWP ). ŒÙÛÈ Ë ÂÓ‰ÔÎÔÈÏȷ΋ ˘¤ÚÙ·ÛË ÌÔÚ› Ó· ·ÓÙ·Ó·ÎÏ¿ Û „¢‰Ò˜ ˘„ËϤ˜ ÙÈ̤˜ CVP Î·È PCWP57 Î·È Ó· ·Ú·Ï·Ó¿ ÙÔÓ ÎÏÈÓÈÎfi ÁÈ·ÙÚfi, Ô ÔÔ›Ô˜ ‰ÂÓ ·ÓÙÈÏ·Ì‚¿ÓÂÙ·È ÙËÓ ˘ÔÁηÈÌ›· Î·È ¿Ú· ‰ÂÓ ÙËÓ ·ÓÙÈÌÂÙˆ›˙ÂÈ Ì ·ÔÙ¤ÏÂÛÌ· ÙËÓ ÚÔÓÂÊÚÈ΋ ·˙ˆı·ÈÌ›·. ¶·Ú·ÙËÚ‹ıËΠÏÔÈfiÓ, ¿ÌÂÛË Û˘Û¯¤ÙÈÛË Ù˘ ·˘ÍË̤Ó˘ IAP Ì ÌÂÁ·Ï‡ÙÂÚË Û˘¯ÓfiÙËÙ· O¡∞, ·ÏÏ¿ Î·È Ì ·˘ÍË̤ÓË ÂÓ‰ÔÓÔÛÔÎÔÌÂȷ΋ ıÓËÙfiÙËÙ· ÏfiÁˆ Ù˘ ÔÏ˘ÔÚÁ·ÓÈ΋˜ ·Ó¿ÚÎÂÈ·˜ (MODS) Ô˘ ÚÔηÏ›56,57,58. ∞˘Ùfi˜ Â›Ó·È Ô ÏfiÁÔ˜ Ô˘ ÛÙË ª∂£ Ë Ì¤ÙÚËÛË Ù˘ IAP ·ÔÙÂÏ› ··Ú·›ÙËÙÔ ÂÚÁ·ÏÂ›Ô ÛÙËÓ ·Ú·ÎÔÏÔ‡ıËÛË ÙÔ˘ ·ÚÚÒÛÙÔ˘. ∫ÔÌ‚ÈÎfi ÛËÌÂ›Ô ÁÈ· ÙËÓ ·ÓÙÈÌÂÙÒÈÛË Ù˘ ÂÁηÙÂÛÙË̤Ó˘ ϤÔÓ O¡∞ ÛÙË ªÔÓ¿‰· Â›Ó·È Ô ¯ÚfiÓÔ˜ ¤Ó·Ú͢ Î·È Ô Ù‡Ô˜ Ù˘ ıÂڷ›·˜ ÓÂÊÚÈ΋˜ ˘ÔηٿÛÙ·Û˘. ∏ ÂÈÏÔÁ‹ ·Ó¿ÌÂÛ· ÛÙË Û˘Ó¯‹ 24ˆÚË Î¿ı·ÚÛË (continuous renal replacement therapy: CRRT) Î·È ÛÙËÓ ÎÏ·ÛÛÈ΋ 4ˆÚË (intermittent hemodialysis: IHD) ‚·Û›˙ÂÙ·È Î˘Ú›ˆ˜ ÛÙËÓ ‡·ÚÍË ‹ ÌË ·ÈÌÔ‰˘Ó·ÌÈ΋˜ ÛÙ·ıÂÚfiÙËÙ·˜. ¢ÂÓ ˘¿Ú¯ÂÈ Û˘Ìʈӛ· ÁÈ· ÙÔ fiÙ ·ÎÚÈ‚Ò˜ Â›Ó·È Î·Ï‡ÙÂÚ· Ó· ·Ú¯›˙ÂÈ Ë Î¿ı·ÚÛË, ·Ó Î·È Î¿ÔÈÔÈ ÂÚ¢ÓËÙ¤˜ ¤¯Ô˘Ó ·Ô‰Â›ÍÂÈ ÙËÓ ˆÊ¤ÏÂÈ· Ù˘ ÚÒÈÌ˘ CRRT ÛÙËÓ ÚfiÁÓˆÛË ·ÛıÂÓÒÓ Ì ÔÏ˘ÔÚÁ·ÓÈ΋ ·Ó¿ÚÎÂÈ· ÂÍ·ÈÙ›·˜ Û‹„˘59 ‹ ÌÂÙ¿ ·fi ÌÂÁ¿Ï˜ ¯ÂÈÚÔ˘ÚÁÈΤ˜ ÂÂÌ‚¿ÛÂȘ60. ∞˘Ùfi ÂÍËÁÂ›Ù·È ·fi ÙÔ fiÙÈ Ë ·ÚÁ‹ Î·È Û˘Ó¯‹˜ ̤ıÔ‰Ô˜ ÂÈÙÚ¤ÂÈ ÙËÓ ÛÙ·ıÂÚ‹ ·ÔÌ¿ÎÚ˘ÓÛË ÙˆÓ Ô˘Ú·ÈÌÈÎÒÓ ÙÔÍÈÓÒÓ Î·È ÙÔ˘ ÏÂÔÓ¿˙ÔÓÙÔ˜ ‡‰·ÙÔ˜ Î·È ÙËÓ ÙÈÙÏÔÔÈË̤ÓË ˆÚÈ·›· ·Ê˘‰¿ÙˆÛË ·Ó¿ÏÔÁ· Ì ÙËÓ ÂÌÊ¿ÓÈÛË ·ÈÌÔ‰˘Ó·ÌÈ΋˜ ·ÛÙ¿ıÂÈ·˜. ∂›Ó·È ÛËÌ·ÓÙÈÎfi fiÙÈ ‰ÂÓ ÂÈ‚·Ú‡ÓÂÙ·È Ë Î·Ú‰È·Î‹ ÏÂÈÙÔ˘ÚÁ›· Î·È ˘¿Ú¯ÂÈ ÌÂÁ·Ï‡ÙÂÚÔ ÂÚÈıÒÚÈÔ ·ÚÂÓÙÂÚÈ΋˜ Û›ÙÈÛ˘ ÎÈ ¤ÙÛÈ ·ÔʇÁÔÓÙ·È ÔÈ ‰Ú·Ì·ÙÈΤ˜ ·ÏÏ·Á¤˜ fiÁÎÔ˘ Î·È ÔÈ ÁÚ‹ÁÔÚ˜ ÌÂÙ·ÎÈÓ‹ÛÂȘ ÔÛ̈ϛˆÓ ÌÂٷ͇ ÂÓ‰Ô΢ÙÙ¿ÚÈÔ˘ ÎÈ ÂÍˆÎ˘ÙÙ¿ÚÈÔ˘ ¯ÒÚÔ˘. ∂›Û˘ Ë CRRT ¤¯ÂÈ ‰˘ÓËÙÈο ·ÓÙÈÊÏÂÁÌÔÓÒ‰ÂȘ ȉÈfiÙËÙ˜ (ÂÍ·ÈÙ›·˜ Ù˘ ·ÔÌ¿ÎÚ˘ÓÛ˘ ΢Ù-
141
ÙÔÎÈÓÒÓ)61 Î·È ÚÔÊ˘Ï¿ÛÛÂÈ ÙÔÓ ¿ÚÚˆÛÙÔ ·fi ÙËÓ ·‡ÍËÛË Ù˘ ÂÓ‰ÔÎÚ¿ÓÈ·˜ ›ÂÛ˘ Î·È ÙÔ˘ ÂÁÎÂÊ·ÏÈÎÔ‡ Ôȉ‹Ì·ÙÔ˜, Ô˘ Û˘Ì‚·›ÓÂÈ Î·Ù¿ ÙËÓ IHD62. ∂ÓÙ˘ˆÛȷ΋ Â›Ó·È Ë ÌÂϤÙË Ô˘ ¤‰ÂÈÍ ÙË ÌÂÁ·Ï‡ÙÂÚË ıÓËÙfiÙËÙ· ÙˆÓ ·ÚÚÒÛÙˆÓ Ì O¡∞, Ô˘ ›¯·Ó ηχÙÂÚË ˆÚÈ·›· ‰ÈÔ‡ÚËÛË Î·È ÌÈÎÚfiÙÂÚ˜ ÙÈ̤˜ ÎÚ·ÙÈÓ›Ó˘, ·ÎÚÈ‚Ò˜ ÁÈ·Ù› Û ·˘ÙÔ‡˜ ηı˘ÛÙ¤ÚËÛÂ Ë ÓÂÊÚÔÏÔÁÈ΋ ÂÎÙ›ÌËÛË Î·È Ë ¤Ó·ÚÍË Î¿ı·ÚÛ˘63. ∂ȉÈο Û ·ÛıÂÓ›˜ Ì O¡∞ Î·È ÔÍ›· Ë·ÙÈ΋ ·Ó¿ÚÎÂÈ· Ê¿ÓËΠfiÙÈ Ë ¤ÁηÈÚË ¤Ó·ÚÍË CRRT (Û ÙÈÌ‹ BUN>80mg/dl) ‚ÂÏÙÈÒÓÂÈ ÙËÓ ÚfiÁÓˆÛË64, ¤Ó· ‡ÚËÌ· Ô˘ ¤¯ÂÈ ÛËÌ·Û›· ÁÈ· ÙÔ˘˜ ·ÛıÂÓ›˜ Ì·˜ Ì ÚÒÈÌË ‰˘ÛÏÂÈÙÔ˘ÚÁ›· ÌÔۯ‡̷ÙÔ˜ Ô˘ ·Ú¿ÏÏËÏ· ÂÌÊ·Ó›˙Ô˘Ó Î·È ÓÂÊÚÈ΋ ‰˘ÛÚ·Á›·. ∂Âȉ‹ fï˜ Û˘Ó¯›˙ÂÙ·È Ë ‰È¯ÔÁӈ̛· ‰ÈÂıÓÒ˜ ÁÈ· ÙÔ ÔÈ· ̤ıÔ‰Ô˜ Â›Ó·È ÈÔ ˆÊ¤ÏÈÌË65, Ë ·fiÊ·ÛË ÙÔ˘ ÂÓÙ·ÙÈÎÔÏfiÁÔ˘ Â›Ó·È ÂÍ·ÙÔÌÈÎÂ˘Ì¤ÓË ÎÈ ÂÍ·ÚÙ¿Ù·È ·fi ÙȘ ·ÓÙÈÎÂÈÌÂÓÈΤ˜ Û˘Óı‹Î˜ Ô˘ ÂÈÎÚ·ÙÔ‡Ó Û οı ÓÔÛÔÎÔÌÂ›Ô (·ÚÈıÌfi˜ ÓÔÛËÏ¢ÙÒÓ, ÂÍÔÈΛˆÛË ÙÔ˘ ÚÔÛˆÈÎÔ‡ Ì ÙË Ì¤ıÔ‰Ô, ˙ËÙ‹Ì·Ù· ÎfiÛÙÔ˘˜).
™Àª¶∂ƒ∞™ª∞ ªÂ ÙË ‰È·Ú΋ ÚfiÔ‰Ô Ù˘ ÁÓÒÛ˘ ·ÏÏ¿ Î·È Ù˘ ¯ÂÈÚÔ˘ÚÁÈ΋˜ Ù¯ÓÈ΋˜ ¿Óˆ ÛÙË ÌÂÙ·ÌfiÛ¯Â˘ÛË ‹·ÙÔ˜, Ë ıÓËÙfiÙËÙ· ÙˆÓ ·ÛıÂÓÒÓ Ï¤ÔÓ ÂËÚ¿˙ÂÙ·È ·fi ¿ÏÏÔ˘˜ ·Ú¿ÁÔÓÙ˜, fiˆ˜ ηډȷÁÁÂȷο ÓÔÛ‹Ì·Ù·, ÌÂÙ·‚ÔÏÈΤ˜ ‹ ·ÓÔÛÔÏÔÁÈΤ˜ ‰È·Ù·Ú·¯¤˜ Î·È ¯ÚfiÓÈ· ÓÂÊÚÈ΋ ·Ó¿ÚÎÂÈ·. ∞ÊÔ‡ ‰È·Ó‡Ô˘Ì ÙËÓ 3Ë ‰ÂηÂÙ›· ÂÈÙ˘¯Ô‡˜ Oª∏, ÌÈ· ‰È·‰Èηۛ· Ô˘ ¤ÊÂÚ ÙËÓ Â·Ó¿ÛÙ·ÛË ÛÙËÓ ·ÓÙÈÌÂÙÒÈÛË ÙÔ˘ ÙÂÏÈÎÔ‡ ÛÙ·‰›Ô˘ Ë·ÙÈ΋˜ ·Ó¿ÚÎÂÈ·˜, Ë ÚÔÛÔ¯‹ Ì·˜ Ú¤ÂÈ Ó· ÛÙÚ·Ê› ÛÙË ‚ÂÏÙ›ˆÛË Ù˘ ÔÈfiÙËÙ·˜ ˙ˆ‹˜ Î·È ÙË Ì·ÎÚfi¯ÚÔÓË ÂÈ‚›ˆÛË ÙˆÓ ·ÛıÂÓÒÓ ÎÈ ·˘Ùfi ÂȉÈο ÂÌÂÚȤ¯ÂÈ ÙËÓ ÚÔÛÙ·Û›· ÙÔ˘ ÓÂÊÚÔ‡.
μπμ§πO°ƒ∞ºπ∫∂™ ∞¡∞ºOƒ∂™ 1. Cabezuelo JB, Ramirez P, Rios A, at al. Risk factors of acute renal failure after liver transplantation. Kidney Int. 2006; 69:1073-1080. 2. Nuno J, Cuervas-Mons V, Vicente E, et al. Renal failure after liver transplantation: Analysis of risk factors in 139 liver transplant recipients. Transplant Proc. 1995; 27:2319-2320. 3. Chuang FR, Lin CC, Wang PH, et al. Acute renal failure after cadaveric related liver transplantation. Transplant Proc. 2004; 36:2328-2330. 4. Bilbao I, Charco R, Balsells J, et al. Risk factors for acute renal failure requiring dialysis after liver transplantation. Clin Ttansplant. 1998; 12:123-129.
142
Ã. ∫À¢ø¡∞
5. Ishitani M, Wilkowski M, Stevenson W, Pruett T. Outcome of patients requiring hemodialysis after liver transplantation. Transplant Proc. 1993;.25:1762-1763. 6. Lebron GM, Herrera Gutierez ME, Seller PG, Curiel BE, Fernantez Ortega JF, Quesada GG. Risk factors for renal dysfunction in the postoperative course of liver transplant. Liver Transpl 2004; 10:1379-1385. 7. Bellomo R, Ronco C, Kellum JA, Mehta RL, Palevsky P. Acute dialysis quality initiative workgroup. Acute renal failure-definition, outcome measures, animal models, fluid therapy and information technology needs: The second international consensus conference of the acute dialysis quality initiative (ADQI) group. Crit Care. 2004; 8:R204-R212. 8. Lima EQ, Zanetta DM, Castro I, et al. Risk factors for development of acute renal failure after liver transplantation. Ren Fail 2003; 25:553-560. 9. Pawarode A, Fine DM, Thuluvath PJ. Independent risk factors and natural history of renal dysfunction in liver transplant recipients. Liver Transpl 2003; 9:741-747. 10. Cabezuelo JB, Ramirez P, Acosta F, Torres D, Sansano T, Pons JA, Bru M, Montoya M, Rios A, Bueno FS, Robles R, Parilla P. Does the standard vs piggypack surgical technique affect the development of early acute renal failure after orthotopic liver transplantation? Transplant Proc. 2003; 35:1913-1914. 11. Parikh CR, Mishra J, Thiessen-Philbrook H, et al. Urinary IL-18 is an early predictive biomarker of acute kidney injury after cardiac surgery. Kidney Int 2006; 70:199-203. 12. Yalavarthy R, Edelstein CL, Teitelbaum I. Acute renal failure and chronic kidney disease following liver transplantation. Hemodialysis International 2007; 11:S7-S12. 13. Marik PE, Wood K, Starzl TE. The course of type 1 hepato-renal syndrome post liver transplantation. Nephron Dial Transplant. 2006; 21:478-482. 14. Fraley DS, Burr R, Bernardini J, Angus D, Kramer DJ, Johnson JP. Impact of acute renal failure on mortality in end-stage liver disease with or without transplantation. Kidney Int 1998; 54:518-524. 15. Fisher NC, Nightingale PG, Gunson BK et al. Chronic renal failure following liver transplantation. Transplantation 1998; 66:59-66. 16. Ojo AO, Held PJ, Port FK, et al. Chronic renal failure after transplantation of a non renal organ. N Engl J Med 2003; 349:931-940. 17. Davis CL, Gonwa TA, Wilkinson AH. Identification of patients best suited for combined liver-kidney transplantation. Part II. Liver Transpl 2002; 8:193-211. 18. Platz KP, Mueller AR, Blumhardt G, et al. Nephrotoxicity following orthotopic liver transplantation. A comparison between cyclosporine and FK506. Transplantation 1994; 58:170-178. 19. Velidedeoglu E, Desai CNM, Campos L, et al. Predictors of late kidney dysfunction post-liver transplantation. Transplant Proc. 2002; 34:3315-3316. 20. Cohen AJ, Stegall MD, Rosen CB, et al. Chronic renal dysfunction late after liver transplantation. Liver Transpl 2002; 8:916-921.
21. Gonwa TA, Jennings L, Mai ML, Stark PC, Levey AS, Klintmalm GB. Estimation of glomerular filtration rates before and after orthotopic liver transplantation: evaluation of current equations. Liver Transpl 2004; 10:301-309. 22. Pillebout E, Nochy D, Hill G, et al. Renal histopathological lesions after orthotopic liver transplantation. Am J Transplantation 2005; 5:1120-1129. 23. Gonwa TA, Mai ML, Melton LB, et al. End-stage renal disease after orthotopic liver transplantation using calcineurin-based immunotherapy: risk of development and treatment. Transplantation 2001; 72:1934-1939. 24 Morard I, Mentha G, Spahr L, Majno P, Hadengue A, Huber O, et al. Long-term renal function after liver transplantation is related to calcineurin inhibitors blood levels. Clin Transplant 2006; 20:96-101. 25. Phan PT, Nast C, Pham PC, et al. Diagnosis and therapy of graft dysfunction. In: Sayegh MH, Pereira BJG, Blake P, eds. Chronic kidney disease: dialysis and treatment, 2nd edit, Philadelphia, PA: W.B. Saunders, 2005. 26. Davis CL, Gonwa TA, Wilkinson AH. Pathophysiology of renal disease associated with liver disorders: implications for liver transplantation. Part I. Liver Transpl 2002; 8:91-109. 27. Gonwa TA, Klintmalm GB, Levy M, et al. Impact of pre-transplant renal function on survival after liver transplantation. Transplantation 1995; 59:361. 28. Hirose R, Roberts J, Quan D, Osorio R, Freise C, Ascher N, Stock P. Experience with daclizumab in liver transplantation. Renal transplant dosing without calcineurin inhibitors is insufficient to prevent acute rejection in liver transplantation. Transplantation 2000; 69:307-311. 29. Eckhoff DE, McGuire B, Sellers M, Contreras J, Frenette L, Young C, et al. The safety and efficacy of a two-dose daclizumab induction therapy in liver transplant patients. Transplantation 2000; 69:1867-1872. 30. Emre S, Gondolesi G, Polat K, Ben-Haim M, Artis T, Fishbein TM, Sheiner PA, Kim-Schluger L, Schwartz ME, Miller CM. Use of daclizumab as initial immunosuppression in liver transplant recipients with impaired renal function. Liver Transpl 2001; 7:220-225. 31. Cantarovich M, Tzimas GN, Barkun J, et al. Efficacy of mycophenolate mofetil combined with very low-dose cyclosporine micro emulsion in long-term liver transplant patients with renal dysfunction. Transplantation 2003; 15:98-102. 32. Neau-Cransac M, Morel D, Bernard PH, et al. Renal failure after liver transplantation. Clin Transplant 2002; 16:368-373. 33. Raimondo ML, Dagher L, Papatheodoridis GV, Rolando N, Patch DW, Davidson BR, et al. Long-term mycophenolate mofetil monotherapy in combination with calcineurin inhibitors for chronic renal dysfunction after liver transplantation. Transplantation 2003; 75:186-190. 34. Moreno Planas JM, Cuervas-Mons Martinez V, Rubio Gonzalez E, Gomez Cruz A, Lopez-Monclus J, SanchezTurrion V, et al. Mycophenolate mofetil can be used as monotherapy late after liver transplantation. Am J Transpl 2004; 4:1650-1655.
METAMO™XEY™Eπ™ 2008
35. Pierini A, Mirabella S, Brunati A, Ricchiuti A, Franchello A, Salizzoni M. Mycophenolate mofetil monotherapy in liver transplantation. Transpl Proc 2005; 37:2614-2615. 36. Orlando G, Baiocchi L, Cardillo A, Iaria G, De Liguori N, De Luca L, Ielpo B, Tariciotti L, Angelico M, Tisone G. Switch to 1.5 grams MMF monotherapy for CNIrelated toxicity in liver transplantation is safe and improves renal function, dyslipidemia and hypertension. Liver Transplantation 2007; 13:46-54. 37. Nair S, Eason J, Loss G. Sirolimus monotherapy in nephrotoxicity due to calcineurin inhibitors in liver transplant recipients. Liver Transpl 2003; 9:126-129. 38. Marks AR. Rapamycin:signaling in vascular smooth muscle. Transplant Proc 2003; 35(3suppl): 231S-233S. 39. Saikali JA, Truong LD, Suki WN. Sirolimus may promote thrombotic microangiopathy. Am J Transplant 2003; 3:229-230. 40. Dunkelberg JC, Trotter JF, Wachs M, Bak T, Kugelmas M, Steinberg T, et al. Sirolimus as primary immunosuppression in liver transplantation is not associated with hepatic artery or wound complications. Liver Transpl 2003; 9:463-468. 41. Yang YJ, Li LX, He Q, Fan H, Jin ZK, Lang R, Kou JT, Li P, Xie DH, Chen DZ. Sirolimus as primary immunosuppressant for calcineurin inhibitor-related renal insufficiency after liver transplantation. Hepatobiliary Pancreat Dis Int 2007; 6:376-378. 42. Nelson DR, Soldevila-Pico C, Reed A, et al. Antiinterleukin-2 receptor therapy in combination with mycophenolate mofetil is associated with more severe hepatitis C recurrence after liver transplantation. Liver Transpl 2001; 7:1064-1070. 43. Everson TE. Impact of immunosuppressive therapy on hepatitis C recurrence. Liver Transpl 2002; 8(suppl): S19-S27. 44. Wilkinson A, Pham PT. Kidney dysfunction in the recipients of liver transplants. Liver Transpl 2005; 11(suppl): S47-S51. 45. Randers E, Kristensen JH, Erlandsen EJ, Danielsen H. Serum cystatin C as a marker of the renal function. Scand J Clin Lab Invest 1998; 58:585-592. 46. Chantrel F, Agin A, Offner M, Koehl C, Moulin B, Hannedouche T. Comparison of cystatin C versus creatinine for detection of mild renal failure. Clin Nephrol 2000; 54:374-381. 47. Hermida J, Romero R, Tutor JC. Relationship between serum cystatin C and creatinine in kidney and liver transplant patients. Clin Chim Acta 2002; 316:165-170. 48. Gerbes AL, Gulberg V, Bilzer M, Vogeser M. Evaluation of serum cystatin C concentration as a marker of renal function in patients with cirrhosis of the liver. Gut 2002; 50:106-110. 49. Schuck O, Gottfriedova H, Maly J, Jabor A, Stollova M, Bruzkova I, et al. Glomerular filtration rate assessment in individuals after orthotopic liver transplantation based on serum cystatin C levels. Liver Transpl 2002; 8:594-599.
143
50. Malbrain M. Abdominal pressure in the critically ill: measurement and clinical relevance. Intensive Care Med 1999; 25:1453-1458. 51. Pusajo JF, Bumaschny E, Agurrola A. Postoperative intra-abdominal pressure: its relation to splachnic perfusion, sepsis, multiple organ failure and surgical reintervention. Int Crit Care Dig 1994; 13:2-8. 52. Ivatury RR, Diebel L, Porter JM, Simon RJ. Intraabdominal hypertension and the abdominal compartment syndrome. Surg Clin North Am 1997; 77:783. 53. Meldrum DR, Moore FA, Moore EE, Franciose RJ, Sauaia A, Burch JM. Prospective characterization and selective management of the abdominal compartment syndrome. Am J Surg 1997; 174:667-673. 54. Saggi BH, Sugerman HJ, Ivatury RR, Bloomfield GL. Abdominal compartment syndrome. J Trauma 1998; 45:597-609. 55. Cheatham ML, White MW, Sagraves SG, Johnson JL, Block EFJ. Abdominal perfusion pressure: a superior parameter in the assessment of intra-abdominal hypertension. J Trauma 2000; 49:621-627. 56. Biancofiore G, Bindi L, Romanelli AM, Bisa M, Boldrini A, Consani G, et al. Renal failure and abdominal hypertension after liver transplantation: determination of critical intra-abdominal pressure. Liver Transpl 2002; 8:1175-1181. 57. Sugrue M. Intra-abdominal pressure. Clin Intensive Care 1995; 6:76-79. 58. Eddy V, Nunn C, Morris JA. Abdominal compartment syndrome. Surg Clin North Am 1997; 74:801-811. 59. Page B, Vieillard-Baron A, Chergui K, et al. Early venovenous haemodiafiltration for sepsis-related multiple organ failure. Critical Care 2005; 9:R755-763. 60. Elahi MM, Lim MY, Joseph RN, et al. Early hemofiltration improves survival in post-cardiotomy patients with acute renal failure. Eur L Cardiothorac Surg 2004; 26:1027-1031. 61. Ronco C, Tetta C, Mariano F, et al. Interpreting the mechanisms of continuous renal replacement therapy in sepsis: the peak concentration hypothesis. Artif Organs 2003; 27:792-801. 62. Palevsky PM, Baldwin I, Davenport A, et al. Renal replacement therapy and the kidney: minimising the impact of renal replacement therapy on recovery of acute renal failure. Curr Opin Crit Care 2005; 11:548-554. 63. Mehta RL, McDonald B, Gabbai F, et al. Nephrology consultation in acute renal failure: does timing matter? Am J Med 2002; 113:456-461. 64. Wu VC, Ko WJ, Chang HW, Chen YS, et al. Early renal replacement therapy in patients with postoperative acute liver failure associated with acute renal failure: effect on postoperative outcomes. J Am Coll Surg 2007; 205:266-276. 65. Uehlinger DE, Jakob SM, Ferrari P, et al. Comparison of continuous and intermittent renal replacement therapy for acute renal failure. Nephrol Dial Transplant 2005; 20:1630-1637.
A›ÙÈ· ¯ÂÈÚÔ˘ÚÁÈ΋˜ ‰ÈÂÚ‡ÓËÛ˘ ÛÙË ÚÒ˚ÌË ÌÂÙ·ÌÔÛ¯Â˘ÙÈ΋ ÂÚ›Ô‰Ô °. ÿÌ‚ÚÈÔ˜
∏ ÂÁ¯ÂÈÚËÙÈ΋ ‚·Ú‡ÙËÙ· Î·È Ë Î·Ù¿ÛÙ·ÛË Î·ÎÔ˘¯›·˜ Ô˘ ¢ڛÛÎÔÓÙ·È ÔÈ ·ÛıÂÓ›˜ Ô˘ ·Ó·Ì¤ÓÔ˘Ó ÌÂÙ·ÌfiÛ¯Â˘ÛË ‹·ÙÔ˜(ª∏), Úԉȷı¤ÙÔ˘Ó Û ¤Ó· ÛËÌ·ÓÙÈÎfi ·ÚÈıÌfi ÂÈÏÔÎÒÓ, ÔÏϤ˜ ·Ô ÙȘ Ôԛ˜ Ô‰ËÁÔ‡Ó ÙÔ ÌÂÙ·ÌÔÛ¯Â˘Ì¤ÓÔ ÛÙÔ ı¿Ó·ÙÔ. OÈ ÂÈÏÔΤ˜ ÛÙË ª∏ Ô˘ ··ÈÙÔ‡Ó ¯ÂÈÚÔ˘ÚÁÈ΋ ‰ÈÂÚ‡ÓËÛË, ı· ÌÔÚÔ‡Û·Ó Ó· ‰È·ÈÚÂıÔ‡Ó Û ‰‡Ô ηÙËÁÔڛ˜: ÛÙȘ ÚÒ˚̘ Ô˘ ·ÚÔ˘ÛÈ¿˙ÔÓÙ·È ÛÙËÓ ¿ÌÂÛË ÌÂÙÂÁ¯ÂÈÚËÙÈ΋ ÂÚ›Ô‰Ô Î·È ·ÊÔÚÔ‡Ó ÙȘ 3 ÚÒÙ˜ ÌÂÙÂÁ¯ÂÈÚËÙÈΤ˜ ‚‰ÔÌ¿‰Â˜ Î·È ÛÙȘ ·ÒÙÂÚ˜ Ô˘ ÌÔÚÔ‡Ó Ó· ·ÚÔ˘ÛÈ·ÛıÔ‡Ó ÌÂÙ¿ ÙÔ ¤Ú·˜ Ù˘ ÓÔÛËÏ›·˜ ÙÔ˘ ·ÛıÂÓÔ‡˜ Î·È ÙËÓ ÂÈÛÙÚÔÊ‹ ÛÙÔ Û›ÙÈ ÙÔ˘. ¶ÚÔÎÂÈ̤ÓÔ˘ Ó· ‰Ôı› Ì›· ÛÊ·ÈÚÈ΋ ÂÈÎfiÓ·, ı· ·ÚÔ˘ÛÈ·ÛÙÔ‡Ó ÔÈ ÂÚÈÛÛfiÙÂÚÔ ÎÔÈÓ¤˜ ÂÈÏÔΤ˜ Ô˘ ÌÔÚÔ‡Ó Ó· ÂÈÛ˘Ì‚Ô‡Ó ÛÙËÓ ¿ÌÂÛË ÌÂÙÂÁ¯ÂÈÚËÙÈ΋ ÂÚ›Ô‰Ô, Û ·ÛıÂÓ‹ Ô˘ ˘Ô‚Ï‹ıËΠ۠ÌÂÙ·ÌfiÛ¯Â˘ÛË ‹·ÙÔ˜.
ÂÚÈÙÔÓ·˚΋ ÎÔÈÏfiÙËÙ·, Ë ÚfiÎÏËÛË ÌË ÂÏÂÁ¯fiÌÂÓ˘ ‰ÈÂÁ¯ÂÈÚËÙÈ΋˜ ‹ Î·È ÌÂÙÂÁ¯ÂÈÚËÙÈ΋˜ ·ÈÌÔÚÚ·Á›·˜ ‰ÂÓ Â›Ó·È ·Û˘Ó‹ı˘ ηÈ, ÔÊ›ÏÂÙ·È ÛÙÔ ÂÎÙÂٷ̤ÓÔ ÂÁ¯ÂÈÚËÙÈÎfi ÙÚ·‡Ì· ‹ Û η΋ Ù¯ÓÈ΋ ·Ó·ÛÙÔÌÒÛˆ˜ ÙˆÓ ·ÁÁ›ˆÓ. ∏ ÂÈÌÂÏ‹˜ ·ÈÌfiÛÙ·ÛË Û˘¯Ó¿ ‰ÂÓ Â·ÚΛ ÁÈ· ÙËÓ ÚfiÏË„Ë ·˘Ù‹˜ Ù˘ ÂÈÏÔ΋˜ Î·È Ë ¯Ú‹ÛË ·ÈÌÔÛÙ·ÙÈÎÔ‡ ÂȈ̷ÙÈÛÌÔ‡ ÂÓ›ÔÙ ·Ú¤¯ÂÈ ÔχÙÈÌÔ ¯ÚfiÓÔ ¤ˆ˜ fiÙÔ˘ ·Ó·Ï¿‚ÂÈ ÙÔ ÌfiÛ¯Â˘Ì· ÙË Û˘ÓıÂÙÈ΋ ÙÔ˘ ÏÂÈÙÔ˘ÚÁ›·. ™ÙËÓ ¿ÌÂÛË ÌÂÙÂÁ¯ÂÈÚËÙÈ΋ ÂÚ›Ô‰Ô Ë ·ÈÌÔÚÚ·Á›· Ô˘ ··ÈÙ› ¯ÂÈÚÔ˘ÚÁÈ΋ ‰ÈÂÚ‡ÓËÛË, ‰È·ÁÓÒÛÎÂÙ·È ·Ô ÙËÓ ÌÂÁ¿ÏË ÔÛfiÙËÙ· ·ÈÌÔÚÚ·ÁÈÎÔ‡ ˘ÁÚÔ‡ Ì ˘„ËÏ‹ ·ÈÌÔÛÊ·ÈÚ›ÓË (Hb) Ô˘ ·Ô‰›‰ÂÙ·È ·Ô ÙȘ ·ÚÔ¯ÂÙ‡ÛÂȘ, ·Ô ÙËÓ ·ÈÌÔ‰˘Ó·ÌÈ΋ ·ÛÙ¿ıÂÈ· Ô˘ ·ÚÔ˘ÛÈ¿˙ÂÈ Ô ·ÛıÂÓ‹˜ Î·È ·Ô ÙËÓ ÙÒÛË Ù˘ Hb Ô˘ ·ÚÔ˘ÛÈ¿˙ÂÈ ÛÙË °ÂÓÈ΋ ∞›Ì·ÙÔ˜, ·Ú¿ ÙËÓ ¯ÔÚ‹ÁËÛË ÂÚ˘ıÚÒÓ Î·È ·Ú·ÁÒÁˆÓ ·›Ì·ÙÔ˜. ™ÙȘ ÂÚÈÙÒÛÂȘ Ô˘ ÔÈ ·ÚÔ¯ÂÙ‡ÛÂȘ ‰ÂÓ ÏÂÈÙÔ˘ÚÁÔ‡Ó, Ë ÌË ·ÓÙ·fiÎÚÈÛË Ù˘ Hb ÛÙËÓ ¯ÔÚ‹ÁËÛË ÂÚ˘ıÚÒÓ, Ë ·ÈÌÔ‰˘Ó·ÌÈ΋ ·ÛÙ¿ıÂÈ·, Ë ‰È¿Ù·ÛË Ù˘ ÎÔÈÏ›·˜ Î·È Ë ·‡ÍËÛË Ù˘ ÂÓ‰ÔÏÔÈÏȷ΋˜ ›ÂÛ˘ fiˆ˜ ·˘Ù‹ ÌÂÙÚÈ¤Ù·È ·Ô ÙÔÓ Î·ıÂÙ‹Ú· ÛÙËÓ Ô˘ÚÔ‰fi¯Ô ·ÛÙË, Ô‰ËÁÔ‡Ó ÛÙËÓ ¤Ó‰ÂÈÍË Ù˘ ÂÁ¯ÂÈÚËÙÈ΋˜ ‰ÈÂÚ‡ÓËÛ˘. OÈ ·ÛıÂÓ›˜ Ì ÌË ÂÏÂÁ¯fiÌÂÓË ·ÈÌÔÚÚ·Á›· Û˘ÓËı¤Ûٷٷ ¤¯Ô˘Ó η΋ ÚfiÁÓˆÛË ·Ú¿ ÙȘ ÚÔÛ¿ıÂȘ ÂÁ¯ÂÈÚËÙÈÎÔ‡ ÂϤÁ¯Ô˘ Ù˘ ·ÈÌÔÚÚ·Á›·˜, ÂÓÒ ÙÔ Ì¤ÁÈÛÙÔ ÔÛÔÛÙfi ÙˆÓ ·ÈÌÔÚÚ·ÁÈÛ¿ÓÙˆÓ ··ÈÙ› ÂÈÛ·ÁˆÁ‹ ÛÙÔ ¯ÂÈÚÔ˘ÚÁÂ›Ô ÙȘ ÂfiÌÂÓ˜ 4872 ÒÚ˜ ÌÂÙ¿ ÙË ÌÂÙ·ÌfiÛ¯Â˘ÛË, ÁÈ· ·ÔÌ¿ÎÚ˘ÓÛË ÙˆÓ Ï·ÎÔ‡ÓÙˆÓ ·›Ì·ÙÔ˜.
¶ÚÒ˚̘ ÃÂÈÚÔ˘ÚÁÈΤ˜ ªÂÙÂÁ¯ÂÈÚËÙÈΤ˜ ∂ÈÏÔΤ˜ OÈ ÂÈÏÔΤ˜ Ô˘ ÂÌÊ·Ó›˙ÔÓÙ·È ÛÙËÓ ¿ÌÂÛË ÌÂÙÂÁ¯ÂÈÚËÙÈ΋ ÂÚ›Ô‰Ô Î·È Î·ıfiÓ ¯ÚfiÓÔ Ô ·ÛıÂÓ‹˜ ¢ڛÛÎÂÙ·È ÛÙË ª∂£, ÂÚÈÏ·Ì‚¿ÓÔ˘Ó ÙËÓ ·ÈÌÔÚÚ·Á›·, ÙȘ ·ÁÁÂȷΤ˜ ÂÈÏÔΤ˜, ÙËÓ ·ÈÌÔÚÚ·Á›· ·Ô ÙÔ ÂÙÈÎfi, ÙË ‰È¿ÙÚËÛË ÎÔ›ÏÔ˘ ÛÏ¿¯ÓÔ˘ ÙË ‰È·Ê˘Á‹ ·Ô ÙËÓ ·Ó·ÛÙfïÛË ÙˆÓ ¯ÔÏËÊfiÚˆÓ ‹ ÙÔ ¯ÔÏÔÂÚÈÙfiÓ·ÈÔ. Δ¤ÏÔ˜ Ò˜ ¯ÂÈÚÔ˘ÚÁÈ΋ ÂÈÏÔ΋ Ô˘ ··ÈÙ› ¿ÌÂÛË ¯ÂÈÚÔ˘ÚÁÈ΋ ·ÓÙÈÌÂÙÒÈÛË Ì ÙËÓ ¤ÓÓÔÈ· Ù˘ ·ӷÌÂÙ·ÌfiÛ¯Â˘Û˘, Â›Ó·È Î·È Ë ÌË ÏÂÈÙÔ˘ÚÁ›· ÙÔ˘ ÌÔۯ‡̷ÙÔ˜. ∏ Û˘¯ÓfiÙËÙ· ·˘ÙÒÓ ÙˆÓ ÂÈÏÔÎÒÓ ÂÍ·ÚÙ¿Ù·È ·Ô ÙËÓ ÔÈfiÙËÙ· ÙÔ˘ ÌÔۯ‡̷ÙÔ˜, ·Ô ÙË ‚·Ú‡ÙËÙ· ·˘Ù‹˜ ηı·˘Ù‹˜ Ù˘ ÂÁ¯Â›ÚËÛ˘ ·ÏÏ¿ Î·È ·Ô ÙË ‚·Ú‡ÙËÙ· Ù˘ ÁÂÓÈ΋˜ ηٷÛÙ¿Ûˆ˜ ÙÔ˘ ·ÛıÂÓÔ‡˜ Ô˘ ÌÂÙ·ÌÔۯ‡ıËÎÂ.
πÛ¯·ÈÌ›· ÌÔۯ‡̷ÙÔ˜ ∏ ıÚfiÌ‚ˆÛË Ù˘ Ë·ÙÈ΋˜ ·ÚÙËÚ›·˜ (5%-10% ÛÙÔ˘˜ ÂÓ‹ÏÈΘ, 10%-20% ÛÙ· ·È‰È¿), ·ÔÙÂÏ› Ì›· ‚·Ú‡Ù·ÙË ÂÈÏÔ‹ Ô˘ Û˘Ó‹ıˆ˜ ÂÈÛ˘Ì‚·›ÓÂÈ ÙÔÓ ÚÒÙÔ Ì‹Ó· ÌÂÙ¿ ÙË ÌÂÙ·ÌfiÛ¯Â˘ÛË Î·È Ô‰ËÁ› Û ӤÎÚˆÛË ÙÔ˘ ÌÔۯ‡̷ÙÔ˜, ÂÓ‰ÔË·ÙÈΤ˜ Û˘ÏÏÔÁ¤˜ ‹ Ó¤ÎÚˆÛË ¯ÔÏËÊfiÚˆÓ Î·È ‰È·Ê˘Á‹ ¯ÔÏ‹˜.
∞ÈÌÔÚÚ·Á›· ™ÙÔ˘˜ ·ÛıÂÓ›˜ Ì ÌÂÁ¿ÏÔ˘ ‚·ıÌÔ‡ ˘Ï·›· ˘¤ÚÙ·ÛË ‹ ÚÔËÁËı›۷ Ì›˙ÔÓ· ÂÁ¯Â›ÚËÛË ÛÙËÓ
144
METAMO™XEY™Eπ™ 2008
∏ ÂÈÏÔ΋ ·˘Ù‹, ÂÊfiÛÔÓ Û˘Ì‚Â› ÙȘ ÚÒÙ˜ ÌÂÙÂÁ¯ÂÈÚËÙÈΤ˜ Ë̤Ú˜, Â›Ó·È ıÔÚ˘‚҉˘, Ì ÁÂÓÈ΋ ηÎÔ˘¯›· ÙÔ˘ ·ÛıÂÓÔ‡˜, Ì·˙È΋ Î·È ·ÈÊÓ›‰È· ·‡ÍËÛË ÙˆÓ ÙÚ·ÓÛ·ÌÈÓ·ÛÒÓ ÂÓÒ, Â¿Ó Û˘Ì‚Â› ·ÚÁfiÙÂÚ· Â›Ó·È ÏÈÁfiÙÂÚÔ ÔÍ›·, ÂΉËÏÔ‡ÌÂÓË Ì ‰È·Ê˘Á‹ ¯ÔÏ‹˜ ‹ ÂÈÎfiÓ· Û‹„ˆ˜ ·Ô Gram (-) ‚·ÎÙËÚ›‰È·. ™Â οı ÂÚ›ÙˆÛË Ú¤ÂÈ Ó· Á›ÓÂÙ·È ¤ÏÂÁ¯Ô˜ ‚·ÙfiÙËÙÔ˜ Ù˘ Ë·ÙÈ΋˜ ·ÚÙËÚ›·˜ Ì Triplex ‹ Ì Spiral CT- ·ÁÁÂÈÔÁÚ·Ê›·. ∏ ·ÓÙÈÌÂÙÒÈÛË Ù˘ ÂÈÏÔ΋˜ ·˘Ù‹˜ Â›Ó·È Ë Â·Ó·ÌÂÙ·ÌfiÛ¯Â˘ÛË, ȉȷ›ÙÂÚ· fiÙ·Ó Ë ıÚfiÌ‚ˆÛË Û˘Ì‚Â› ÙÔÓ ÚÒÙÔ ÌÂÙÂÁ¯ÂÈÚËÙÈÎfi Ì‹Ó·. ∏ ¯ÂÈÚÔ˘ÚÁÈ΋ ‰ÈÂÚ‡ÓËÛË ÂÓfi˜ ·ÛıÂÓÔ‡˜ ÛÙÔÓ ÔÔ›Ô ‰È·ÁÓÒÛıËΠıÚfiÌ‚ˆÛË Ù˘ Ë·ÙÈ΋˜ ·ÚÙËÚ›·˜, ÂÊ fiÛÔÓ Á›ÓÂÈ Û¯Â‰fiÓ ¿ÌÂÛ· ÌÂÙ¿ ÙÔ Û˘Ì‚¿Ó, ÌÔÚ› Ó· Ô‰ËÁ‹ÛÂÈ Û ‰È¿ÛˆÛË ÙÔ˘ ÌÔۯ‡̷ÙÔ˜, ÂÊfiÛÔÓ Á›ÓÂÈ ·ÔÌ¿ÎÚ˘ÓÛË ÙÔ˘ ıÚfiÌ‚Ô˘ Ì ηıÂÙ‹Ú· Fogarty Î·È Û˘ÌÏËڈ̷ÙÈ΋ ¤Á¯˘ÛË ıÚÔÌ‚ÔÏ˘ÙÈÎÒÓ Ô˘ÛÈÒÓ (¯, ÛÙÂÙÔÎÈÓ¿ÛË, Ô˘ÚÔÎÈÓ¿ÛË ÎÏ). ∏ ·ÔÙÂÏÂÛÌ·ÙÈÎfiÙËÙ· Ù˘ ÌÂıfi‰Ô˘ ·ÌÊÈÛ‚ËÙ›ٷÈ, ·Ó Î·È ÛÙË ‚È‚ÏÈÔÁÚ·Ê›· ·Ó·Ê¤ÚÔÓÙ·È ÂÈÙ˘¯Â›˜ ÚÔÛ¿ıÂȘ. ∏ ·ÓÙÈÌÂÙÒÈÛË Ù˘ ÂÈÏÔ΋˜ ·˘Ù‹˜ Â›Ó·È Ë Â·Ó·ÌÂÙ·ÌfiÛ¯Â˘ÛË, ȉȷ›ÙÂÚ· fiÙ·Ó Ë ıÚfiÌ‚ˆÛË Û˘Ì‚Â› ÙÔÓ ÚÒÙÔ ÌÂÙÂÁ¯ÂÈÚËÙÈÎfi Ì‹Ó·. ™ÙȘ ·ÁÁÂȷΤ˜ ÂÈÏÔΤ˜ Ú¤ÂÈ Ó· Û˘ÌÂÚÈÏËÊı› Ë ıÚfiÌ‚ˆÛË Ù˘ ˘Ï·›·˜ (1.5%-2%), Ë ÔÔ›· Û˘Ó‹ıˆ˜ ‰È·ÁÓÒÛÎÂÙ·È Ì ÌÂÁ·Ï‡ÙÂÚË Î·ı˘ÛÙ¤ÚËÛË ·fiÙÈ Ë ıÚfiÌ‚ˆÛË Ù˘ Ë·ÙÈ΋˜ ·ÚÙËÚ›·˜, ÂÂȉ‹ Ë ‚ÈÔ¯ËÌÈ΋ Ù˘ ÂÈÎfiÓ· ‰ÂÓ Â›Ó·È ÙfiÛÔ ¿ÌÂÛ· ıÔÚ˘‚҉˘. ∫·È Û ·˘Ù‹ ÙËÓ ÂÚ›ÙˆÛË ÌÔÚ› Ó· ÂȯÂÈÚËı› ¯ÂÈÚÔ˘ÚÁÈ΋ ‰ÈÂÚ‡ÓËÛË Î·È ÂÌ‚ÔÏÂÎÙÔÌ‹, Ë ·ÓÙ·fiÎÚÈÛË fï˜ ÂÍ·ÚÙ¿Ù·È ·Ô ÙÔ ‚·ıÌfi ηٷÛÙÚÔÊ‹˜ Ô˘ ˘¤ÛÙË ÙÔ Ïfi‚ÈÔ ·Ô ÙËÓ ˘Ï·›· ÈÛ¯·ÈÌ›·, ηıÒ˜ Î·È ·Ô ÙÔ fiÛÔ ·Ú¤ÌÂÈÓ·Ó ‚·ÙÔ› ÔÈ ÌÈÎÚÔ› ÂÓ‰ÔË·ÙÈÎÔ› ˘Ï·›ÔÈ ÎÏ·‰ÔÈ.
∂ÈÏÔΤ˜ ·Ô Ù· ¯ÔÏËÊfiÚ· OÈ ÂÈÏÔΤ˜ ·Ô Ù· ¯ÔÏËÊfiÚ· (10% ÛÙÔ˘˜ ÂÓ‹ÏÈΘ) ·ÔÙÂÏÔ‡Ó ÛËÌ·ÓÙÈÎfi Úfi‚ÏËÌ· ÛÙȘ ÂÚÈÛÛfiÙÂÚ˜ ÌÂÙ·ÌÔÛ¯Â˘ÙÈΤ˜ ÌÔÓ¿‰Â˜. ™ÙȘ ÂÈÏÔΤ˜ ·˘Ù¤˜ ÛÙË ÚÒ˚ÌË ÌÂÙÂÁ¯ÂÈÚËÙÈ΋ ÂÚ›Ô‰Ô, ÂÚÈÏ·Ì‚¿ÓÂÙ·È Ë ‰È·Ê˘Á‹ ·Ô ÙË ÙÂÏÈÎÔÙÂÏÈ΋ ¯ÔÏˉԯÔ-¯ÔÏˉfi¯Ô (Ã-Ã) ·Ó·ÛÙfïÛË ‹ ·Ô ÙË ¯ÔÏÔÂÙÈ΋ ·Ó·ÛÙfïÛË Î·È ÙÔ ¯ÔÏÔÂÚÈÙfiÓ·ÈÔ, ÙÔ ÔÔ›Ô ·ÚÔ˘ÛÈ¿˙ÂÙ·È, ›Ù ÏfiÁˆ ÌË ÏÂÈÙÔ˘ÚÁ›·˜ ÙˆÓ ·ÚÔ¯ÂÙ‡ÛÂˆÓ Â›Ù ÌÂÙ¿ ÙËÓ ·Ê·›ÚÂÛ‹ ÙÔ˘˜. ∏ ·ÚÔ˘Û›· ¯ÔÏ‹˜, ΢ڛˆ˜ ·Ô ÙËÓ ˘ÊË·ÙÈ΋
145
·Ó·ÛÙfïÛË, ·ÔÙÂÏ› ¯·Ú·ÎÙËÚÈÛÙÈÎfi ‰È·Ê˘Á‹˜ ·Ô ÙËÓ ·Ó·ÛÙfïÛË ÙˆÓ ¯ÔÏËÊfiÚˆÓ. ∂ÊfiÛÔÓ ¤¯ÂÈ ÙÔÔıÂÙËı› ۈϋӷ˜ Kehr ÛÙË Ã-à ·Ó·ÛÙfïÛË Î·È ÌÂÙ¿ ·Ô ÂȂ‚·›ˆÛË ÌÂ Û˘ÚÈÁÁÔÁÚ·Ê›·,- Ô˘ ÌÔÚ› Ó· Á›ÓÂÈ Î·È ÂÈ Ù˘ ÎÏ›Ó˘-, Ë ¿ÌÂÛË ¯ÂÈÚÔ˘ÚÁÈ΋ ‰ÈÂÚ‡ÓËÛË ‰ÂÓ Â›Ó·È ··Ú·›ÙËÙË Î·È ÌÔÚ› Ó· ÚÔÁÚ·ÌÌ·ÙÈÛı› Ó· ‰ÈÂÓÂÚÁËı› Ì ÙȘ ηÏÏ›ÙÂÚ˜ ‰˘Ó·Ùfi Û˘Óı‹Î˜ ÁÈ· ÙÔÓ ·ÛıÂÓ‹. ™ÙȘ ÂÚÈÙÒÛÂȘ fï˜ Ù˘ ¯ÔÏÔÂÙÈ΋˜ ·Ó·ÛÙfïÛ˘ ‹ Ù˘ ¯ˆÚ›˜ ۈϋӷ Kehr Ã-à ·Ó·ÛÙfïÛ˘, ÂÊfiÛÔÓ Ë ‰È·Ê˘Á‹ Â›Ó·È ÛËÌ·ÓÙÈ΋ Î·È ‰ÂÓ ·ÓÙÈÌÂÙˆ›˙ÂÙ·È Ë ÂÈÏÔ΋ ·Ô ÙË ÏÂÈÙÔ˘ÚÁ›· ˆ˜ <ηÙ¢ı˘ÓfiÌÂÓÔ Û˘Ú›ÁÁÈÔ> Ù˘ ˘ÊË·ÙÈ΋˜ ·ÚÔ¯¤Ù¢Û˘, ÙfiÙÂ Â›Ó·È ··Ú·›ÙËÙË Ë ·ÓÙÈÌÂÙÒÈÛ‹ Ù˘ ÂÁ¯ÂÈÚËÙÈο. ∏ ¯Ú‹ÛË ÛˆÏ‹ÓÔ˜ Kehr ÁÈ· ÙËÓ «ÂÍ·ÛÊ¿ÏÈÛË» Ù˘ ·Ó·ÛÙfïÛ˘, ‰ÂÓ ¤Ï˘Û ÙÔ Úfi‚ÏËÌ·, ·ÏÏ¿ ·ÓÙ›ıÂÙ· ÚÔÛÂÙ¤ıË Ë ÓÔÛËÚfiÙËÙ· Î·È Ë ıÓËÙfiÙËÙ· Ô˘ ·ÎÔÏÔ˘ı› ÙËÓ ·Ê·›ÚÂÛ‹ ÙÔ˘. ∏ ‰ÈÂÚ‡ÓËÛË Ù˘ ‰È·Ê˘Á‹˜ ¯ÔÏ‹˜ ÂÚÈÏ·Ì‚¿ÓÂÈ Triplex Ù˘ Ë·ÙÈ΋˜ ·ÚÙËÚ›·˜ ÚÔÎÂÈ̤ÓÔ˘ Ó· ÂÏÂÁ¯Â› Ë Î·Ï‹ ‚·ÙfiÙËÙ· Ù˘ Ë·ÙÈ΋˜ ·ÚÙËÚ›·˜, ECHO ÌÔۯ‡̷ÙÔ˜, MRI ¯ÔÏ·ÁÁÂÈÔÁÚ·Ê›· Î·È ERCP. ∏ ıÂڷ›· ÂÍ·ÚÙ¿Ù·È ·Ô ÙË Ê‡ÛË Ù˘ ÂÈÏÔ΋˜ Î·È Û˘Ó›ÛÙ·Ù·È ·fi ·Ï‹ Û˘ÚÚ·Ê‹ Ù˘ ÂÚÈÔ¯‹˜ Ì›·˜ ÌÈÎÚ‹˜ ‰È·Ê˘¯‹˜ ¯ÔÏ‹˜ ÛÙË ¯ÔÏˉԯÔ-¯ÔÏË‰Ô¯Ô Δ-Δ ·Ó·ÛÙfïÛË, ÙËÓ Â·Ó·‰ËÌÈÔ˘ÚÁ›· Ù˘ ·Ó·ÛÙfïÛ˘, ÙËÓ ÙÔÔı¤ÙËÛË stent ÂÓÙfi˜ ÙÔ˘ ¯ÔÏˉfi¯Ô˘ fiÚÔ˘ ¤ˆ˜ ÙË ÌÂÙ·ÙÚÔ‹ Ù˘ ¯ÔÏˉԯÔ-¯ÔÏˉfi¯Ô (Ã-Ã) ·Ó·ÛÙfïÛ˘, Û ¯ÔÏÔÂÙÈ΋ ·Ó·ÛÙfïÛË (Roux-en-À). ™ÙȘ ÂÚÈÙÒÛÂȘ ‰È·Ê˘Á‹˜ ·Ô ÙËÓ ¯ÔÏÔÂÙÈ΋ ·Ó·ÛÙfïÛË, Û˘Ó‹ıˆ˜ ·ÚΛ Ë Û˘ÚÚ·Ê‹ ÙÔ˘ ÛËÌ›Ԣ ·Ô fiÔ˘ ·Ú·ÙËÚÂ›Ù·È Ë ‰È·Ê˘Á‹ ηÈ, Û ·ÎÚ·›Â˜ ÂÚÈÙÒÛÂȘ, Ë ÙÔÔı¤ÙËÛË ÂȉÈÎÔ‡ ۈϋÓÔ˜-ÎˉÂÌfiÓÔ˜ ÛÙËÓ ·Ó·ÛÙfïÛË, Ô ÔÔ›Ô˜ ÂÍÂÚ¯ÂÙ·È Ì¤Ûˆ Ù˘ ÚÔÛÈÔ‡Û˘ ¤ÏÈÎÔ˜ Ù˘ Rouxen-À ·Ô ÙÔ ÎÔÈÏÈ·Îfi ÙÔ›¯ˆÌ·.
∞ÈÌÔÚÚ·Á›· ·Ô ÙÔ ÂÙÈÎfi ™˘Ó‹ı˘ ÂÓÙfiÈÛË ·˘Ù‹˜ Ù˘ ·ÈÌÔÚÚ·Á›·˜ Â›Ó·È Ô ÛÙfiÌ·¯Ô˜ (Á·ÛÙÚÔÚÚ·Á›· ·Ô ÎÈÚÛÔ‡˜ ÙÔ˘ ıfiÏÔ˘/stress ulcer), Ë ¯ÔÏÔÂÙÈ΋ ·Ó·ÛÙfïÛË, ¤ÎÙÔÔÈ ÎÈÚÛÔ› ÛÙÔ ÏÂÙfi ¤ÓÙÂÚÔ ‹ Ë ¤ÓÙÂÚÔ-ÂÓÙÂÚÔ ·Ó·ÛÙfïÛË Ù˘ Roux-en-À. ∏ Á·ÛÙÚÔÚÚ·Á›· Û˘Ó‹ıˆ˜ ·ÓÙÈÌÂÙˆ›˙ÂÙ·È Û˘ÓÙËÚËÙÈο. ∏ ¿ÏÏ˘ ·ÈÙÈÔÏÔÁ›·˜ fï˜ ·ÈÌÔÚÚ·Á›· ··ÈÙ› ÂÁÂÈÚËÙÈ΋ ‰ÈÂÚ‡ÓËÛË, ÚÔÎÂÈ̤ÓÔ˘ Ó· ÂÓÙÔÈÛı› Î·È Ó· ÂÏÂÁ¯ı›.
146
°. πªμƒπ√™
¢È¿ÙÚËÛË ÎÔ›ÏÔ˘ ÛÏ¿¯ÓÔ˘ ™˘Ó‹ıˆ˜ ·ÊÔÚ¿ ÙÔÓ ÛÙfiÌ·¯Ô ›ÙÂ Û·Ó ·ÔÙ¤ÏÂÛÌ· ÙÔ˘ stress Ù˘ ÌÂÙ·ÌfiÛ¯Â˘Û˘, Ù˘ ¯ÔÚ‹ÁËÛ˘ ÌÂÁ¿ÏˆÓ ‰fiÛÂˆÓ ÎÔÚÙÈ˙fiÓ˘ (ˆ˜ ·ÓÔÛÔηٷÛÙ·ÏÙÈÎÔ‡) ÙȘ ÚÒÙ˜ ÌÂÙ·ÌÔÛ¯Â˘ÙÈΤ˜ Ë̤Ú˜ ·ÏÏ¿ Î·È È·ÙÚÔÁÂÓ‹˜, Û˘Ó‹ıˆ˜ ÌÂÙ¿ ÂÚÁÒ‰Ë ·Ú·Û΢‹ ÙˆÓ Û˘ÌʇÛÂˆÓ ÛÙË Ê¿ÛË ÂÎÙÔÌ‹˜ ÙÔ˘ Èı·ÁÂÓÔ‡˜ ‹·ÙÔ˜. ∏ ·ÓÙÈÌÂÙÒÈÛË Â›Ó·È Ë Û˘Ó‹ı˘ ÂÁ¯ÂÈÚËÙÈ΋, fiˆ˜ Î·È ÛÙË ‰È·Ê˘Á‹ ·Ô ÙËÓ ¤ÓÙÂÚÔ-ÂÓÙÂÚÔ ·Ó·ÛÙfïÛË Ù˘ Roux-en-À.
∂·Ó·ÌÂÙ·ÌfiÛ¯Â˘ÛË OÈ ÂӉ›ÍÂȘ ÁÈ· ·ӷÌÂÙ·ÌfiÛ¯Â˘ÛË ÛÙȘ 3 ÚÒÙ˜ ‚‰ÔÌ¿‰Â˜ ÌÂÙ¿ ÙË ÌÂÙ·ÌfiÛ¯Â˘ÛË ÂÚÈÏ·Ì‚¿ÓÂÈ ÙËÓ ÌË ÏÂÈÙÔ˘ÚÁ›· ÙÔ˘ ÌÔۯ‡̷ÙÔ˜ Î·È ÙȘ ·ÁÁÂȷΤ˜ ÈÛ¯·ÈÌÈΤ˜ ‚Ï¿‚˜. ¶ÂÚ›Ô˘ 10% ¤ˆ˜ 15% ÙˆÓ ·ÛıÂÓÒÓ Ì ¤ÎÙˆÛË Ù˘ ÏÂÈÙÔ˘ÚÁ›·˜ ÙÔ˘ Ë·ÙÈÎÔ‡ ÌÔۯ‡̷ÙÔ˜ ı· ··ÈÙ‹ÛÔ˘Ó Â·Ó·ÌÂÙ·ÌfiÛ¯Â˘ÛË.
™˘ÌÂÚ¿ÛÌ·Ù· ™ÙËÓ ¿ÌÂÛË ÌÂÙ·ÌÔÛ¯Â˘ÙÈ΋ ÂÚ›Ô‰Ô, Ô ·ÛıÂÓ‹˜ Ì ÌÂÙ·ÌfiÛ¯Â˘ÛË ‹·ÙÔ˜ ÌÔÚ› Ó· ÂÌÊ·Ó›ÛÂÈ ¤Ó·Ó ÛËÌ·ÓÙÈÎfi ·ÚÈıÌfi ÂÈÏÔÎÒÓ, Ô˘ fiϘ Â›Ó·È ·ÂÈÏËÙÈΤ˜ ÁÈ· ÙËÓ ÂÈ‚›ˆÛ‹ ÙÔ˘. ∏ Û˘¯ÓfiÙËÙ· Î·È Ë ‚·Ú‡ÙËÙ¿ ÙÔ˘˜ Â›Ó·È Û ¿ÌÂÛË Û˘Ó¿Ú-
ÙËÛË Ì ÙËÓ ‚·Ú‡ÙËÙ· Ù˘ ÁÂÓÈ΋˜ ÙÔ˘ ηٿÛÙ·Û˘ ÚÔÂÁ¯ÂÈÚËÙÈο (ÛÙ¿‰ÈÔ Child-Pough/MELD), ÙˆÓ ÂÓ‰ÔÎÔÈÏÈ·ÎÒÓ ÂÂÌ‚¿ÛÂˆÓ Ô˘ ÚÔËÁ‹ıËÛ·Ó ÛÙË ‰È¿ÚÎÂÈ· Ù˘ ˙ˆ‹˜ ÙÔ˘, ·ÏÏ¿ Î·È Ù˘ ÂÍÔÈΛˆÛ˘ ÙˆÓ ¯ÂÈÚÔ˘ÚÁÒÓ Ì ÙËÓ ÂÁ¯ÂÈÚËÙÈ΋ Ù¯ÓÈ΋ Ù˘ ÌÂÙ·ÌfiÛ¯Â˘Û˘ ‹·ÙÔ˜.
μπμ§πO°ƒ∞ºπ∞ 1. Jagganath S, ∫aloo AN. Biliary complications after liver transplantation. Curr Treat Opin Gastoenterol 5:101112. 2002. 2. Cavallari A, Vivarelli M, Bellusci R,et al. Treatment of vascular complications following liver transplantation: Multidisciplinary approach. Heepatogastroenterology 48: 179-183, 2001. 3. Holt CD, Winston DJ. Infections after liver transplantation. In: Transplantation of the liver. Busuttil RW, Klintmaim GK (eds), Philadelphia, Elsevier Saunders, 2005, pp 963-994. 4. Klintmalm GB, Nery JR, HusbergbBS, et al. Rejection in liver transplantation. Hepatologyn 10: 978-985, 1989. 5. Lipshutz GS, Ascher NL. Roberts JP. Rejection after transplantation. In: Transplantation of the liver. Busuttil RW, Klintmaim GK, (eds), Philadelphia, Elsevier Saunders, 2005, pp 1167-1182. 6. Adam R, McMaster P, O’Grady JG, et al. Evolution of liver Transplantation in Europe: Reporet of the European Liver Transplantation Registry. Liver Transpl 9: 1231-1243, 2003.
Infections in liver transplant patients: A short Overview and two case reports F.H. Saner, I. Fouzas, G. Sotiropoulos, A. Radtke, S. Nadalin, A. Paul
Abstract
the incidence of such infections are the nature of the operation and the technical skill with which the surgery and postoperative care are accomplished. As with any patient, the risk of postoperative infection increases with the duration of vascular access and use of drainage catheters, the duration of intubation, the presence of indwelling stents and other foreign bodies, and the presence of devitalized tissue or fluid collections. Antimicrobial prophylaxis can only delay the occurrence of infection in such circumstances and should not be extend over the perioperative period2,3. The aim of this short review is to delineate the principal infectious disease practice in liver transplant patient, emphasizing the early recognition of infection and prompt treatment in two selected cases.
Infection is one of the leading causes of morbidity and mortalitiy in liver transplant recipients. Up to 60% of liver transplant patients have infection in the first year after transplantation, and infection remains the leading cause of death in these patients. Particular pulmonary complications in liver transplant patients are a major cause of morbidity and mortality. The majority of pneumonias after liver transplantation (LT) are caused by bacteria (58-63%). Beside gram-negative bacteria, Aspergillus species are the most common organisms causing pneumonia in the first month after transplantation. Blood stream infections or bacteraemia frequently follows LT. Gram-positive bacteria such as Staphylococcus aureus and Enterococcus species are responsible for a high proportion of these infections. Invasive fungal blood stream infections have been reported in 5% to 42% of the liver transplant recipients with mortality rate ranging from 50% to 78%. Candida species encounted for the majority of fungal infections and showed a significantly better survival as compared with Aspergillus infections, which were always fatal.
Bacterial Infection When Thomas Starzl reported about the first 93 successful liver transplant patients 4 , one year survival was documented with only 30%4. When cyclosporine (CSA) was approved to prevent acute and chronic rejection in liver transplant patients in 1983, the one year survival rate increased above 80% 5. Bacteraemia remains a significant complication and by far the most frequent major infection in liver transplant recipients. Bacteraemia in patients following liver transplantation was reported in 24% to 64% of the patients and accounts 20% to 30% of all infections5-9. More than 90% of infections occurring in the first month are the same bacterial or candidal infections like in nonimmunosuppressed ICU patients2,3. Bacteraemia has been a significant predictor of mortality in some, but not all, studies of liver transplant recipients8,9. A frequent dilemma in a patient suspected of having infection is discerning the likelihood of bacteraemia. The primary objectives of new studies in this field
Introduction The incidence of sepsis and the number of sepsis-related deaths are increasing in the recent two decades. Gram-positive bacteria and fungal organisms are increasingly common causes of sepsis1. Primary goal in organ transplantation is the prevention or effective treatment of infection. More than 90 percent of the infections occurring in the first month are the same nosocomial bacterial or candidal infections of the surgical wound, lungs, or vascular-access devices that occur in surgical patients who are not in a state of immunosuppression. The key factors in determining
147
148
F.H. SANER, I. FOUZAS, G. SOTIROPOULOS, A. RADTKE, S. NADALIN, A. PAUL
should be addressed to determine readily assessable clinical variables to identify liver transplant recipients who are likely to have bacteraemia. Such data might permit more judicious antibiotic use in these patients, when pending culture results. The mortality of bacterial sepsis remains high and is consistently not the same at different centers. Lumbreras 6 reported an incidence of bacterial sepsis of 64% with a mortality rate of 13%, whereas Wade et al.9 recorded in his patient cohort an incidence for bacterial sepsis with 56% and a mortality rate related to sepsis with 30%, and Singh et al.8,9 obtained a bacterial sepsis rate of 49% with a mortality rate of 28%. In our own patient cohort we recorded the rate for blood stream infections (BSI) at 24% for all liver transplant patients. While the rate of BSI in patients transplanted with a cadaveric graft was 21% this rate was higher in patients transplanted with a living donor graft (33%). However this difference did not reach statistical significance10. While the main diagnoses before 1983 leading to death was acute and chronic rejection5, nowadays the leading cause of death in the first year have changed to infection5,11.
Case 1: We report about a 62 year old male patient.. He had a body-mass-index (BMI) of 43 (height 166 cm, weight: 122 kg), suffering from arterial hypertension and portopulmonary hypertension (PPH) with a mean pulmonary arterial pressure (mPAP) of 58 mmHg. After careful preoperative evaluation and extensively discussion in our transplant board this patient was accepted as a suitable candidate for transplantation despite his high risk for mortality according to his severe obesity and the PPH. However our group recently could show that in some selected cases patients, even with a severe PPH, could benefit from transplantation12. After an uneventful transplantation the patient was admitted to the ICU. The data obtained from the right-heart catheter confirmed the PPH. The mPAP was 56 mmHg, the pulmonary vascular resistance (PVR) was 332 dyn*sec*m -5 , the measurement of the cardiac index showed 2.1 L*min-1*m2. The intraoperative started inhalation with iloprost (Ventavisì, Bayer Health Care, Leverkusen, Germany) was con-
tinued with 20 Ìg, six times a day. However, this treatment decreased the mPAP to only 48 mmHg; therefore we completed his therapy with sildenafil (Revatioì, Pfizer, New York, USA) and Bosentan (Tracleerì, Actelion, Allschwill, Switzerland). Bosentan is an inducer of the cytochrome P450 (CYP) isoenzymes CYP2C9 and CYP3A4. In vitro data also suggest an induction of CYP2C19. Consequently, plasma concentrations of substances metabolised by these isoenzymes (like calicneurin inhibitors, e.g. cyclosporine or tacrolimus) could be decreased when bosentan is coadministered. However, we monitored tacrolimus level daily and adjusted the dose if necessary. Under this treatment the hemodynamics improved dramatically. CI increased to 3.5 L*min-1*m2 and the mPAP decreased to 27 mmHg. The patient could be extubated on the second postoperative day (POD). The liver function tests were within normal limits within one week. He was immediately scheduled for an extensive respiratory training with a fixed protocol. He received extensively physiotherapy, mobilisation, and non-invasive ventilation over night. However, due to respiratory failure, caused by impaired ability to cough and the patient was re-intubated on POD 10. In order of long-term ventilation the patient underwent a perctanuous dilatational tracheotomy. In the further clinical course the patient developed an acute renal failure with the requirement for continuous veno-venous hemodialyses (CVVHD). The initial infection surveillance consists of change of all invasive catheters, computed tomography-scan of both, thorax and abdomen, blood culture, bronchoscopy and broncho-alveolar lavage (BAL), and virology. However, all results were negative. Ten days later the patient developed an esophageal bleeding and underwent an endoscopy. The reason for the bleeding were not varices, but herpes simplex ulcer bleeding. We started immediately acyclovir treatment. The patient’s condition improved, kidney function recovered, the dialyses treatment could be stopped. Five weeks following transplantation the patient recovered and was decanulated again. However, he developed again a respiratory failure and had to be recanulated for further long-term ventilation. A couple of days later he developed fever again. Initially all invasive catheters was changed an anti-
METAMO™XEY™Eπ™ 2008
149
Temparture course 41
Temparture in °C
40 39
21.11.2006 Caspofungin without proved yeast inf.
18.11.2006 BAL: Pseudomonas Blood culture: E. faecium Ceftazidim/Colisitin inh/Linezolid
09.11.2006 Line Change BAL: Pseudomas/Yeast Ciprofloxacin/Imipenem
38 37
23.11.2006 CMV Infect, Gancyclovir
36
06
06
20 1. .1
25
24
23
.1
.1
1.
1.
20
20
06
06 20
06 1. 22
.1 21
.1
1.
20
20
06
06 20
.1
1.
1. .1 19
18
.1
1.
20
20
06
06 20
06 1.
20 17
.1
1.
20 .1 16
15
.1
1.
1. .1 14
.1 13
06
06 20
06
06
20 1.
20
06 1.
20 .1 12
11
.1
1.
1. .1 10
09
.1
1.
20
20
06
06
35
Date
Figure 1. Temperature Course and Results of infection surveillance.
biotic treatment with imipenem and ciprofloxacin in order to expect a pseudomonas was initiated. Indeed the BAL revealed pseudomonas and yeast (Figure 1). Yeast in the BAL is mostly a contamination and was not treated. Under this regime temperature and infection parameters in the lab returned within normal limits. Antibiotic treatment was stopped after 10 days. Two days later the patient experienced again fever and increase of infection parameters, like procalcitonin and C-reactive protein. We initiated again an antibiotic treatment with ceftazidime and inhalational colistin, when pending the culture results. The initial microscopic results of the blood culture showed gram-positive coccus, why we extended the antibiotic treatment with linezolid. The results of the BAL and blood culture, which were obtained three days after initiation the adequate therapy showed in the BAL an imipenem resistant, but ceftazidime susceptible pseudomonas and in the blood culture a linezolid susceptible enterococcus faecium. Despite this obviously correct antibiotic treatment the fever raised up to 41ÆC. Now we decided to add caspofungin in the treatment, despite not proved yeast infection. Under this regime the patient recovered. The fever and infection parameters went down to normal limits. Five days after launching caspofungin treatment one of the blood cultures showed a Candida krusei, which is azole resistant, but susceptible to caspofungin. The patient could first be mobilized on the 66’Th POD and again decanulated on the 80’Th
POD. The patient remained for 2 more weeks on the ICU for extensive physiotherapy and intensive respiratory training. He was discharged from our hospital to a rehabilitation center after 4 months following transplantation.
Case 2: The second case has been already published13. A 57-year old male, suffering from hepatitis C (HCV) cirrhosis with a MELD-score of 9, not MRSA carrier, underwent living donor liver transplantation. The patient could be extubated on the first postoperative day (POD). Due to respiratory failure, caused by impaired power for coughing and additional development of encephalopathy the patient was reintubated on 5’Th POD. After 3 days the patient recovered and could be extubated. He was alert, the liver function was excellent. He was discharged from ICU on POD 10. Six weeks after transplantation the patient was readmitted to the ICU, requiring artificial ventilation due to severe sepsis and septic shock. The sepsis was caused by intraabdominal abscess following bile leakage. The abscess was percutaneously drained. Endoscopically a stent was placed in the main bile duct to repair the bile leakage. Bacterial culture from the abscess detected MRSA. The patient was initially treated with vancomycin and rifampicin. However, under this treatment he developed fever and pneumonia. The BAL confirmed our suspicion on MRSA pneumonia and we
150
F.H. SANER, I. FOUZAS, G. SOTIROPOULOS, A. RADTKE, S. NADALIN, A. PAUL
switched our antibiotic therapy to linezolid. Nevertheless, the pneumonia spread out to both lung lobes. The BAL revealed MRSA from both lungs, in spite of sensitivity to linezolid. Then we continued with tigecycline. After a 3 weeks treatment with tigecycline the MRSA could be eradicated. However the extended use of antibiotics induced a superinfection with Stenotrophomonas maltophilia and Klebsiella pneumonia. Unfortunately, these isolates were not available for later susceptibility testing to tigecycline. However, these bacterias had a good response to trimethoprim/sulfamethoxazol and ciprofloxacin. The patient could be decanulated 14 weeks following artificial ventilation and discharged from the ICU after a 16 week stay. Five months after hospital admission the patient was discharged out of the hospital in a good clinical condition. Singh et al. assessed predictors for bacteraemia and mortality in liver transplant recipients. The basic conclusion of their study was that kidney dysfunction, diabetes mellitus, and APACHE Score higher than 25 was significantly associated with BSI8. From the order of appearance we have to recognize that in the first four weeks the same bacterial like in non-immuncompromised patients will occur. In contrast to fewer studies fungal infection can also occur during the first 4 weeks2. Inappropriate use of antibiotics for the treatment of suspected pneumonia is widely prevalent in the intensive care unit (ICU), particular in liver transplant patients, with implications for the emergence of drug-resistant organisms. Singh et al14 developed an approach that would reduce unnecessary antibiotic use, based on the clinical pneumonia infection score (CPIS), which was developed by Pugin15. CPIS criteria (see table 1), regardless of whether they could truly define a patient population with pneumonia, were used for decision-making regarding antibiotic therapy. Patients with CPIS < 6 were randomized to either the control or experimental group. Patients in the control group received the current standard therapy, i.e., the choice, number, and duration of antibiotics was at the discretion of the care providers. Patients randomized to the experimental group received a second generation chinolone. Patients assigned to the experimental group were revaluated 3 days after start of chinolone treatment. Chinolone was discontinued if the CPIS remained < 6 at 3 d (implying low likelihood
of pneumonias). Patients with CPIS â&#x2030;Ľ 6 at 3 d were treated as pneumonia, either by continuation of current treatment or the therapy was modified based on the culture and sensitivity results. In patients in whom CPIS remained < 6 at the 3 d evaluation point, antibiotics were still continued in 96% (24 of 25) in the standard therapy group but in 0% (0 of 25) of the patients in the experimental therapy group (p = 0.0001). Mortality and length of ICU stay did not differ despite a shorter duration (p = 0.0001) and lower cost (p = 0.003) of antimicrobial therapy in the experimental as compared with the standard therapy arm. Antimicrobial resistance, or superinfections, or both, developed in 15% (5 of 37) of the patients in the experimental versus 35% (14 of 37) of the patients in the standard therapy group (p = 0.017). This is a really cornerstone paper which provides a very useful decision tool for appropriate use of antibiotics. In conclusion infection is a major cause of morbidity and mortality in liver recipients in the first year after transplantation. To increase the safety of organ transplantation further, we need improved diagnostic tests to detect infection early and to monitor immune function. By limiting the number and duration of antibiotics in those with low likelihood of pneumonia, the emergence of antimicrobial resistance could be reduced.
References 1. Martin GS, Mannino DM, Eaton S, et al. The epidemiology of sepsis in the United States from 1979 through 2000. N Engl J Med 348: 1546, 2003. 2. Fishman JARubin RH. Infection in organ-transplant recipients. N Engl J Med 338: 1741, 1998. 3. Rubin RH. The direct and indirect effects of infection in liver transplantation: pathogenesis, impact, and clinical management. Curr Clin Top Infect Dis 22: 125, 2002. 4. Starzl TE, Porter KA, Putnam CW, et al. Orthotopic liver transplantation in ninety-three patients. Surg Gynecol Obstet 142: 487, 1976. 5. Adam R, McMaster P, Oâ&#x20AC;&#x2122;Grady JG, et al. Evolution of liver transplantation in Europe: report of the European Liver Transplant Registry. Liver Transpl 9: 1231, 2003. 6. Lumbreras C, Lizasoain M, Moreno E, et al. Major bacterial infections following liver transplantation: a prospective study. Hepatogastroenterology 39: 362, 1992. 7. Mora NP, Husberg BS, Gonwa TA, et al. The impact of the different severe infections on the outcome of liver transplantation. A study of 150 patients. Transpl Int 5 Suppl 1: S209, 1992.
METAMO™XEY™Eπ™ 2008
151
Table 1. Clinical Pulmonary Infection Score calculation (Modified from Pugin15).
Clinical Pulmonary Infection Score (CPIS) Temperature (ÆC) 36,5 – 38,4 38,5 – 38,9 ≥ 39 – < 36
Points 0 1 2
WBC > 4 – < 11/nl < 4 – > 11/nl
0 1
Tracheal Secretion No secretion Nonpurulent tracheal secretions Purulentent secretion
0 1 2
Oxygenation: paO2/FiO2 (mmHg) > 240 ARDS (defined as paO2 ≤ 200, PCWP ≤ 18 mmHg, bilateral infilatrate) < 240 and no ARDS
Band forms ≥ 50%: 2
0
2
Chest X ray No infiltrate Diffuse (or patchy) infiltrate Localized infiltrate
0 1 2
Progression of pulmonary infiltrate no progression Progression ( ARDS and lung edema excluded)
0 2
Culture of tracheal aspirate Pathogenic bacteria light quantity or no growth Pathogenic bacteria cultured in moderate or heavy quantity Same pathogenic bacteria seen on Gram stain
0 1 2
Definition of abbreviations: ARDS = acute respiratory distress syndrome; PaO2/FIO2 = ratio of arterial oxygen pressure to fraction of inspired oxygen. CPIS at baseline has to be assessed on the basis of the first five variables, i.e., temperature, blood leukocyte count, tracheal secretions, oxygenation, and character of pulmonary infiltrate. CPIS at 72 h has to be calculated based on all seven variables and took into consideration the progression of the infiltrate and culture results of the tracheal aspirate. A score of 6 at baseline or at 72 h is considered suggestive of pneumonia.
8. Singh N, Paterson DL, Gayowski T, et al. Predicting bacteremia and bacteremic mortality in liver transplant recipients. Liver Transpl 6: 54, 2000. 9. Wade JJ, Rolando N, Hayllar K, et al. Bacterial and fungal infections after liver transplantation: an analysis of 284 patients. Hepatology 21: 1328, 1995. 10. Saner F, Oldedamink S, Pavalkovic G, et al. Pulmonary and blood stream infections in living related liver transplant patients. Transplantation in press. 11. Jain A, Reyes J, Kashyap R, et al. Long-term survival after liver transplantation in 4,000 consecutive patients at a single center. Ann Surg 232: 490, 2000. 12. Saner FH, Nadalin S, Pavlakovic G, et al. Portopulmonary hypertension in the early phase following liver transplantation. Transplantation 82: 887, 2006.
13. Saner FH, Heuer M, Rath PM, et al. Successful salvage therapy with tigecycline after linezolid failure in a liver transplant recipient with MRSA pneumonia. Liver Transpl 12: 1689, 2006. 14. Singh N, Rogers P, Atwood CW, et al. Short-course empiric antibiotic therapy for patients with pulmonary infiltrates in the intensive care unit. A proposed solution for indiscriminate antibiotic prescription. Am J Respir Crit Care Med 162: 505, 2000. 15. Pugin J, Auckenthaler R, Mili N, et al. Diagnosis of ventilator-associated pneumonia by bacteriologic analysis of bronchoscopic and nonbronchoscopic “blind” bronchoalveolar lavage fluid. Am Rev Respir Dis 143: 1121, 1991.