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Kidney Transplantation in Highly sensitized recipients .................................................................................................................. 45 G. Tsoulfas, T. Kawai

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™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 ∞¶£, °¡£ πÔÎÚ¿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 ∞¶£, °¡£ πÔÎÚ¿ÙÂÈÔ 3. °È·ÎÔ˘ÛÙ›‰Ë˜ ¢ËÌ‹ÙÚÈÔ˜, ÃÂÈÚÔ˘ÚÁfi˜ §¤ÎÙÔÚ·˜ ∞¶£, ÃÂÈÚÔ˘ÚÁÈ΋ ∫ÏÈÓÈ΋ ªÂÙ·ÌÔۯ‡ÛÂˆÓ ∞¶£, °¡£ πÔÎÚ¿ÙÂÈÔ 4. °Ô˘Ï‹˜ πˆ¿ÓÓ˘, °·ÛÙÚÂÓÙÂÚÔÏfiÁÔ˜ ∂›ÎÔ˘ÚÔ˜ ∫·ıËÁËÙ‹˜ ∞¶£, ¢’ ¶·ıÔÏÔÁÈ΋ ∫ÏÈÓÈ΋, °¡£ πÔÎÚ¿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 ∞¶£, °¡£ πÔÎÚ¿ÙÂÈÔ 8. ∫·Ùۛη ∂ϤÓË, ∞Ó·ÈÛıËÛÈÔÏfiÁÔ˜ ∂ÈÌÂÏ‹ÙÚÈ· ∞’, ∞Ó·ÈÛıËÛÈÔÏÔÁÈÎfi ΔÌ‹Ì·, °¡£ πÔÎÚ¿ÙÂÈÔ 9. ∫˘‰ÒÓ· ÃÚÈÛÙ›Ó·, ¶·ıÔÏfiÁÔ˜-∂ÓÙ·ÙÈÎÔÏfiÁÔ˜, ∂ÈÌÂÏ‹ÙÚÈ· μ’ ª∂£, °¡£ πÔÎÚ¿ÙÂÈÔ 10. ªÔ˘ÏÔ‡‰Ë ∂ϤÓË, ∞Ó·ÈÛıËÛÈÔÏfiÁÔ˜-∂ÓÙ·ÙÈÎÔÏfiÁÔ˜, ∂ÈÌÂÏ‹ÙÚÈ· ∞’, ª∂£, °¡£ πÔÎÚ¿ÙÂÈÔ 11. ªÔ‡ÙÛÈ·ÓÔ˜ °ÂÒÚÁÈÔ˜, ∞Ó·ÈÛıËÛÈÔÏfiÁÔ˜ ∂ÈÌÂÏËÙ‹˜ ∞’, ∞’ ∞Ó·ÈÛıËÛÈÔÏÔÁÈÎfi ΔÌ‹Ì·, °¡£ πÔÎÚ¿ÙÂÈÔ 12. ªÔϤÙ˘ πˆ¿ÓÓ˘, ¡ÂÊÚÔÏfiÁÔ˜ ¢È¢ı˘ÓÙ‹˜ ¡ÂÊÚÔÏÔÁÈ΋˜ ∫ÏÈÓÈ΋˜, °¡∞ §·˚Îfi 13. ªÔ‡ÎÏ· ÕÓÓ·, μÈÔÏfiÁÔ˜, ∂ıÓÈÎfi ¶ÂÚÈÊÂÚÂÈ·Îfi ∫¤ÓÙÚÔ πÛÙÔÛ˘Ì‚·ÙfiÙËÙ·˜-ΔÌ‹Ì· ∞ÓÔÛÔÏÔÁ›·˜, °¡£ πÔÎÚ¿ÙÂÈÔ 14. ¶··ÁˆÚÁ›Ô˘ ÃÚ˘ÛԇϷ, ∞Ó·ÈÛıËÛÈÔÏfiÁÔ˜, ∂ÍÂȉÈ΢fiÌÂÓË ª∂£, °¡£ πÔÎÚ¿ÙÂÈÔ 15. ¶·Û·ÎÈÒÙÔ˘ ª·Ú›ÏË, ÃÂÈÚÔ˘ÚÁfi˜-∂ÓÙ·ÙÈÎÔÏfiÁÔ˜, ∞Ó·ÏËÚÒÙÚÈ· ¢È¢ı‡ÓÙÚÈ· ª∂£, °¡£ πÔÎÚ¿ÙÂÈÔ 16. ¶··‰ÔÔ‡ÏÔ˘ ¢ÒÚ·, ∂ÈÌÂÏ‹ÙÚÈ· ∞’ ¡ÂÊÚÔÏÔÁ›·˜, °¡£ ¶··ÁˆÚÁ›Ô˘ 17. Δ·ÎÔ‡‰·˜ ¢ËÌ‹ÙÚÈÔ˜, ÃÂÈÚÔ˘ÚÁfi˜, ∫·ıËÁËÙ‹˜ ∞¶£, ¢È¢ı˘ÓÙ‹˜ ÃÂÈÚÔ˘ÚÁÈ΋˜ ∫ÏÈÓÈ΋˜ ªÂÙ·ÌÔۯ‡ÛÂˆÓ ∞¶£, °¡£ πÔÎÚ¿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 ∞¶£, °¡£ πÔÎÚ¿ÙÂÈÔ 19. ºÔ‡˙·˜ πˆ¿ÓÓ˘, ÃÂÈÚÔ˘ÚÁfi˜ §¤ÎÙÔÚ·˜ ∞¶£, ÃÂÈÚÔ˘ÚÁÈ΋ ∫ÏÈÓÈ΋ ªÂÙ·ÌÔۯ‡ÛÂˆÓ ∞¶£, °¡£ πÔÎÚ¿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›·˜, °¡£ πÔÎÚ¿ÙÂÈÔ

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AÓÔÛÔÏÔÁÈÎÔ› ·Ú¿ÁÔÓÙ˜ ÛÙË ÌÂÙ·ÌfiÛ¯Â˘ÛË ÓÂÊÚÔ‡: H ÂÌÂÈÚ›· 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 ·ÔηχÊıËΠÂ›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 ÂÈ‚›ˆÛË ÙÔ˘ ÓÂÊÚÈÎÔ‡ ÌÔۯ‡̷ÙÔ˜, ο. ™¯ÂÙÈο Ì ÙÔÓ ÚfiÏÔ ÙÔ˘ ÚˆÙÔ·ıÔ‡˜ ÓÔÛ‹Ì·ÙÔ˜, Ì ‚¿ÛË ÌÂϤÙ˜ ÙÔ˘ CTS ‰È·ÈÛÙÒıËΠfiÙÈ ·˘ÍË̤ÓË ÂÈ‚›ˆÛË ÂÌÊ·Ó›˙Ô˘Ó ·ÛıÂÓ›˜ Ì ÓÂÊÚÈ΋ ·ÓÂ¿ÚÎÂÈ· ÔÊÂÈÏfiÌÂÓË Û ·Ó·ÙÔÌÈο ·›ÙÈ· Î·È ‰˘ÛϷۛ˜, 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˘ ÛÂÈÚ·Ì·ÙÔÓÂÊÚ›Ùȉ·˜ ÙÔ˘ Ï‹ÙË Û˘ÁηٷϤÁÂÙ·È Â›Û˘ ÌÂٷ͇ ÙˆÓ ·ÓÔÛÔÏÔÁÈÎÒÓ ·Ú·ÁfiÓÙˆÓ ÔÈ ÔÔ›ÔÈ ÂËÚ¿˙Ô˘Ó ÙËÓ ÂÈ‚›ˆÛË ÙˆÓ Ó. ÌÔÛ¯Â˘Ì¿ÙˆÓ: ηχÙÂÚË ÂÈ‚›ˆÛË ·ÚÔ˘ÛÈ¿˙Ô˘Ó ÔÈ Ï‹Ù˜ Ì ٷ¯¤ˆ˜ ÂÍÂÏÈÛÛfiÌÂÓË Â›Ù ÌÂÛ·ÁÁÂȷ΋ ÛÂÈÚ·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˘ ÂȉÚÔ‡Ó ÛÙË Ì·ÎÚfi¯ÚÔÓË ÂÈ‚›ˆÛË ÙˆÓ ÌÔÛ¯Â˘Ì¿ÙˆÓ, ÂÓÒ ·Ú¿ÏÏËÏ· Ë ÂÈ‚›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 ÂÂÈÛfi‰ÈÔ. ∞›ÙÈ· ı·Ó¿ÙÔ˘ ÙÔ˘ ‰fiÙË Ù· ÔÔ›· ¢ÓÔÔ‡Ó ÙË Ì·ÎÚfi¯ÚÔÓË ÂÈ‚›ˆÛË و̷ÙÈÎÒÓ 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 ÂÂÎÙ·ı› Î·È ÛÙË ÛËÌ·Û›· ÌË ·ÓÔÛÔÏÔÁÈÎÒÓ ·Ú·Ì¤ÙÚˆÓ, fiˆ˜ 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˘ ¶·ÓÂÈÛÙËÌ›Ô˘ ÷˚‰ÂÏ‚¤ÚÁ˘, ÛÙÔ Î·ÈÓÔ‡ÚÁÈÔ ¶·ÓÂÈÛÙ‹ÌÈÔ NeuenHeimerfeld, ÛÂ Û˘ÓÂÚÁ·Û›· ·Ú¯Èο Ì 162 ∫¤ÓÙÚ· ªÂÙ·ÌÔۯ‡ÛÂˆÓ ·fi 28 ¯ÒÚ˜. ™ÎÔfi˜ Ù˘ ¢Ú›·˜ ·˘Ù‹˜ ÂÈÛÙËÌÔÓÈ΋˜ Û˘ÓÂÚÁ·Û›·˜ Â›Ó·È Ë ÌÂϤÙË, ÂÂÍÂÚÁ·Û›· Î·È ‰ËÌÔÛ›Â˘ÛË ·ÓÔÛÔÏÔÁÈÎÒÓ, ·ÓÔÛÔÁÂÓÂÙÈÎÒÓ ·ÏÏ¿ Î·È ¿ÏÏˆÓ ‰Â‰ÔÌ¤ÓˆÓ ·fi ÙÔÓ ¯ÒÚÔ ÙˆÓ ÌÂÙ·ÌÔۯ‡ÛÂˆÓ ÔÚÁ¿ÓˆÓ. ÃÚËÛÈÌÔÔÈÒÓÙ·˜ ‰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˘ ÂËÚ¿˙Ô˘Ó ÙË Ì·ÎÚfi¯ÚÔÓË ÂÈ‚›ˆÛË ÙˆÓ ÓÂÊÚÈÎÒÓ ÌÔÛ¯Â˘Ì¿ÙˆÓ, ·ÏÏ¿ Î·È ÁÈ· ÙÔÓ ÙÚfiÔ ·ÓÙÈÌÂÙÒÈÛ‹˜ 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· ÂÈ‚›ˆÛË ÙÔ˘ ÓÂÊÚÈÎÔ‡ ÌÔۯ‡̷ÙÔ˜, Ô ÚfiÏÔ˜ Ù˘ ¢·ÈÛıËÙÔÔ›ËÛ˘ ÛÙ· ·ÓıÚÒÈÓ· 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. Ÿˆ˜ ‰È·ÈÛÙÒıËÎÂ, ÛÙÔ˘˜ ·ÛıÂÓ›˜ ˘„ËÏÔ‡ ÎÈÓ‰‡ÓÔ˘ Ú¤ÂÈ Ó· Û˘ÌÂÚÈÏËÊıÔ‡Ó Î·Ù¿ ·ÚÈÔ ÏfiÁÔ ÔÈ ˘Ô„‹ÊÈÔÈ Ì ΢ÙÙ·ÚÔÙÔÍÈο ·ÓÙÈÛÒÌ·Ù· (Panel Reactive Antibodies, PAR) ÂÚÈÛÛfiÙÂÚ· ·fi 50%, ÔÈ ·ÛıÂÓ›˜ Ì Â·Ó·ÌÂÙ·ÌfiÛ¯Â˘ÛË Î·È ÔÈ ·ÛıÂÓ›˜ Ì ‰È·‚‹ÙË. O ÚfiÏÔ˜ Ù˘ Û˘Ì‚·ÙfiÙËÙ·˜ ÛÙ· HLA Ù¿Í˘ ππ Â›Ó·È ϤÔÓ ÁÓˆÛÙfi fiÙÈ Â›-

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ª. ¢∞¡π∏§π¢∏™

∏ ÚÔÛÊÔÚ¿ ÙÔ˘ CTS ‰ÂÓ ÂÚÈÔÚ›ÛÙËΠÛÙËÓ Ú·ÁÌ·ÙÔÔ›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˘ÔÔ›ËÛ˘, ÛÙË ÌÂÙÂÎ·›‰Â˘ÛË ÚÔÛˆÈÎÔ‡, Î.¿. ¶Ôχ ·ÍÈfiÏÔÁ˜ Â›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 ÂÂÍÂÚÁ¿˙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 ÂÂÍÂÚÁ¿˙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 ÏÔÈÔ‡˜ ·Ú¿ÁÔÓÙ˜ Ô˘ ÂËÚ¿˙Ô˘Ó ÙËÓ ÂÈ‚›ˆÛË ÓÂÊÚÈÎÒÓ ÌÔÛ¯Â˘Ì¿ÙˆÓ Î·È ·ÛıÂÓÒÓ ÔÊ›ÏÂÙ·È ÛÙË ‰ÈÂıÓ‹ ÌÂϤÙË CTS.

°ÂÓˆÌÈ΋ – ¶ÚˆÙˆÌÈ΋ ÛÙË ÌÂÙ·ÌfiÛ¯Â˘ÛË ∞. ªÔ‡ÎÏ·

∂ÈÛ·ÁˆÁ‹

·Ó¿Ï˘Û˘ ÓÔ˘ÎÏÂ˚ÓÈÎÒÓ ÔͤˆÓ, Ì ÛÎÔfi ·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‰ÈÎÔÔÈ› RNA ÙÔ ÔÔ›Ô ÌÂÙ·ÊÚ¿˙ÂÙ·È Û ÚˆÙ½Ó˜. ∏ ÚÔËÁÔ‡ÌÂÓË ‰ÂηÂÙ›· Ì ÙËÓ Â›Ù¢ÍË Ù˘ ÔÏÔÎÏ‹ÚˆÛ˘ Ù˘ ·Ó¿ÁÓˆÛ˘ ÙÔ˘ ·ÓıÚÒÈÓÔ˘ ÁÔÓȉÈÒÌ·ÙÔ˜ (genomics) ¯·Ú·ÎÙËÚ›ÛÙËÎÂ Û·Ó ‰ÂηÂÙ›· ÙˆÓ –omics. OÈ ÂÈÛÙ‹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 ÚˆÙ½Ó˜), 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 ÙÚÔÔÔÈ‹ÛÂˆÓ ÌÈ·˜ ÚˆÙ½Ó˘ fiˆ˜ 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·ÚfiÏ·ÛÌ· ÛÙÔÓ ˘Ú‹Ó·, Î·È Ù¤ÏÔ˜ Ô ÌÂÙ·‚ÔÏÈÛÌfi˜ Ù˘. ŸÏ˜ ÔÈ ·Ú·¿Óˆ ÌÂÙ·ÙÚÔ¤˜ ·ÔÙÂÏÔ‡Ó ‚ÈÔÏÔÁÈο ÌÔÓÔ¿ÙÈ· ÙˆÓ ÔÔ›ˆÓ Ë ÔÚ›· ÈÛÔÚÚÔ› ·Ó¿ÌÂÛ· ÛÙȘ ¤ÓÓÔȘ ˘Á›·-·Ûı¤ÓÂÈ·.

∏ Û‡Á¯ÚÔÓË ¤Ú¢ӷ Û ı¤Ì·Ù· ÌÂÙ·ÌfiÛ¯Â˘Û˘, ÂÈÎÂÓÙÚÒÓÂÙ·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˘ ÂÌϤÎÔÓÙ·È ÛÙȘ ·Ú·¿Óˆ ‰È·ÊÔÚÔÔÈ‹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˘ ‚ÈÔÏËÚÔÊÔÚÈ΋˜ ˘fiÛ¯ÔÓÙ·È ÚfiÔ‰Ô ÛÙË ‰È·Ï‡ηÓÛË Ù˘ ‚ÈÔÏÔÁ›·˜ ΢ÙÙ¿ÚÔ˘, Ô˘ Ô‰ËÁ› Û ÂÈ‚›ˆÛË ÙÔ˘ ÌÔۯ‡̷ÙÔ˜: ➤ ➤ ➤ ➤ ➤ ➤ ➤ ➤ ➤ ➤ ➤ ➤

ÀÂÚÊ˘ÁÔΤÓÙÚËÛË ∏ÏÂÎÙÚÔÊfiÚËÛË À‚ÚȉÈÛÌfi˜ ÓÔ˘ÎÏÂ˚ÓÈÎÒÓ ÔͤˆÓ DNA sequencing ªÂÙ·ÌfiÚʈÛË Â˘Î·Ú˘ˆÙÈÎÒÓ Î˘ÙÙ¿ÚˆÓ Δ¯ÓÈΤ˜ ÎψÓÔÔ›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 ™ÎÔfi˜ Ù˘ ÁÂÓˆÌÈ΋˜ (genomics) ‰ÂÓ Â›Ó·È ·Ï¿ Ó· ‰ÒÛÂÈ ¤Ó· ηٿÏÔÁÔ Ì fiÏ· Ù· ÁÔÓ›‰È· Ô˘ ·ÔÙÂÏÔ‡Ó ÙÔ ·ÓıÚÒÈÓÔ ÁÔÓȉ›ˆÌ· Î·È ÏËÚÔÊÔڛ˜ ÁÈ· ÙË ÏÂÈÙÔ˘ÚÁ›· ÙÔ˘˜, ·ÏÏ¿ ΢ڛˆ˜ Ó· Á›ÓÔ˘Ó Î·Ù·ÓÔËÙÔ› ÔÈ ÂÈ̤ÚÔ˘˜ Ì˯·ÓÈÛÌÔ› ̤ۈ ÙˆÓ ÔÔ›ˆÓ ·ÏÏËÏÂȉڿ 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· ÔÔ›· fï˜ ı· Ô‰ËÁ‹ÛÔ˘Ó Î·È ÛÙË ıÂÚ·›·. OÈ ÚÒÙ˜ ÂÊ·ÚÌÔÁ¤˜ Ù˘ ÁÂÓˆÌÈ΋˜ Û Â›Â‰Ô ‰È¿ÁÓˆÛ˘/ÚfiÁÓˆÛ˘ ¤ÁÈÓ·Ó ÛÙËÓ ¤-

¶·Ú¿ÏÏËÏ·, ·Ó·Ù‡ÛÛÂÙ·È Ô ÎÏ¿‰Ô˜ Ù˘ ÌÔÚȷ΋˜ ‰È·ÁÓˆÛÙÈ΋˜, Ë ÔÔ›· ·ÍÈÔÔÈ› 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 ÂÂÎÙ·ı› Î·È ÂÊ·ÚÌfi˙ÂÙ·È ÛÙË ‚ÈÔÏÔÁ›· Ù˘ ÌÂÙ·ÌfiÛ¯Â˘Û˘. ΔÔ ÂӉȷʤÚÔÓ ÂÓÙÔ›˙ÂÙ·È ÛÙËÓ Ù·˘ÙÔÔ›ËÛË ÙˆÓ ÌÔÚÈ·ÎÒÓ Ì˯·ÓÈÛÌÒÓ Û ÔÍ›· Î·È ¯ÚfiÓÈ· ·fiÚÚÈ„Ë ÌÔۯ‡̷ÙÔ˜, ηıÒ˜ Î·È ÛÙÔÓ ÂÓÙÔÈÛÌfi ‚ÈÔÏÔÁÈÎÒÓ ‰ÂÈÎÙÒÓ, Ô˘ Û¯ÂÙ›˙ÔÓÙ·È Ì ÙË Ú‡ıÌÈÛË Ù˘ ·ÓÔÛÔηٷÛÙÔÏ‹˜ Ì ÛÙfi¯Ô ÙËÓ ÂÈ‚›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˜ ¯ÚËÛÈÌÔÔÈÒÓÙ·˜ ÔÛÔÙÈ΋ ¤ÎÊÚ·ÛË ÁÔÓȉ›ˆÓ Ì ˘ÏÈÎfi ·fi ‚ÈÔ„›Â˜ ÂÌϤÎÔÓÙ·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˜. ™˘ÌÂÚ·›ÓÔ˘Ì ‰ËÏ·‰‹ ‰È·ÊÔÚÂÙÈ΋ ÁÔÓȉȷ΋ ¤ÎÊÚ·ÛË Û ‰È·ÊÔÚÂÙÈÎÔ‡˜ Ù‡Ô˘˜ ·fiÚÚȄ˘. ÃÚËÛÈÌÔÔÈÒÓÙ·˜ real time PCR ‰È·ÈÛÙÒıËΠÂ›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 ÂÈÎÂÓÙÚˆı› ΢ڛˆ˜ ÛÙȘ ÚˆÙ½Ó˜ perforin, granzyne Î·È granulysin6,7,8 Î·È ¯ÚËÛÈÌÔÔÈ› ‰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 ÂÓÂÚÁÔÔÈË̤ӷ ·ÙÙ·Ú· fiˆ˜ Ë Ù¯ÓÔÏÔÁ›· Lunimex (beads). ¶·Ú¿ÏÏËÏ· ·Ó·Ù‡¯ıËÎ·Ó ÚÔ-

ÌÔÙÈΤ˜ ̤ıÔ‰ÔÈ PCR ÈηӤ˜ Ó· ·Ó·Ï‡ÛÔ˘Ó ÂηÙÔÓÙ¿‰Â˜ ÁÔÓȉȷΤ˜ ı¤ÛÂȘ. °È· Ù· DNA micro-arrays Ô˘ ¯ÚËÛÈÌÔÔÈ‹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 ÂÈÛÙËÌfiÓˆÓ ‹Ù·Ó Ë Ù·˘ÙÔÔ›ËÛË ‚ÈÔÌÔÚ›ˆÓ Ù· ÔÔ›· ·ÚÔ˘ÛÈ¿˙Ô˘Ó ·˘ÍË̤ÓË ¤ÎÊÚ·ÛË ·ÚÎÂÙfi ¯ÚfiÓÔ ÚÈÓ ÙËÓ ÂӉ¯fiÌÂÓË ·fiÚÚÈ„Ë ÙÔ˘ ÌÔۯ‡̷ÙÔ˜ Î·È Ù· ÔÔ›· ı· ¯ÚËÛÈÌÔÔÈËıÔ‡Ó Ì ÛÎÔfi ·ÊÂÓfi˜ ÌÂÓ ÙËÓ Úfi‚ÏÂ„Ë Ù˘ ÔÚ›·˜ ÙÔ˘ ÌÔۯ‡̷ÙÔ˜ Î·È ·ÊÂÙ¤ÚÔ˘ ÙË ıÂÚ·›·. ÃÚËÛÈÌÔÔÈÒÓÙ·˜ 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 fiÔ˘ ‹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, ¯ÚËÛÈÌÔÔÈ‹ıËÎ·Ó Affymetix Gene Chips FL6800 Ù· ÔÔ›· ÂÚÈ›¯·Ó 6,800 probe sets ÁÈ· ·ÓıÚÒÈÓ· 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¤ıËΠÂ›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· ÂÙ¿ ‰Â›ÁÌ·Ù· ·ÛıÂÓÒÓ Ì ÔÍ›· ·fiÚÚÈ„Ë. ∞ÓÙ›ıÂÙ·, ‰ÂÓ ·Ú·ÙËÚ‹ıËΠ·˘ÍË̤ÓË ‰Ú·ÛÙÈÎfiÙËÙ· Û ÌfiÚÈ· cytoxine T-cell effectror fiˆ˜ Ë perforin Î·È ÙÔ

METAMO™XEY™Eπ™ 2008

granzyme Ù· ÔÔ›· ›¯·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 ÂfiÌÂÓ˘ 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· ÂÈÙÚ¤„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΋ ÂȂ‚·›ˆÛË Ù˘ ¯ÚfiÓÈ·˜ ÓÂÊÚÔ¿ıÂÈ·˜ ·ÏÏÔÌÔۯ‡̷ÙÔ˜.

O Stegall Î·È ÔÈ Û˘ÓÂÚÁ¿Ù˜ ÙÔ˘11 ¯ÚËÛÈÌÔÔ›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 ÂȂ‚·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 ÂÈϤÔÓ ÌfiÚÈ· fiˆ˜ ÁÈ· ·Ú¿‰ÂÈÁÌ· Ô ÌÂÙ·ÁÚ·ÊÈÎfi˜ ·Ú¿ÁÔÓÙ·˜ 19 Î·È Ë ÚˆÙ½ÓË decotin (ÚˆÙÂÔÁÏ˘Î¿ÓË Ô˘ ‰Ú· Ì ÙÔÓ ÂȉÂÚÌÈÎfi ·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 ÂÈÏÂÁ̤ӷ ÁÔÓ›‰È· ·fi ÙËÓ ÔÌ¿‰· ÙÔ˘ Stanford12. ΔÔ ÂÈÚ·Ì·ÙÈÎfi ˘ÏÈÎfi Ô˘ ¯ÚËÛÈÌÔÔÈ‹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, ·ԉ›ÎӢ ÙÚ›· ›‰Ë ÔÍ›·˜ ·fiÚÚȄ˘ Ô˘ Û¯ÂÙ›˙ÔÓÙ·Ó Ì ‰‡Ô ¯ÚfiÓÈ· ÂÈ‚›ˆÛ˘ ÌÔۯ‡̷ÙÔ˜. ∏ ·˘ÍË̤ÓË ¤ÎÊÚ·ÛË ÁÔÓȉ›ˆÓ ÂÚÈÏ¿Ì‚·Ó ÂÎÙfi˜ ·fi Ù· ÁÔÓ›‰È· Ô˘ Έ‰ÈÎÔÔÈÔ‡Ó ÙȘ ÚˆÙ½Ó˜ granzyme Î·È PRF Î·È ¿ÏÏ· ¿ÁÓˆÛÙ· ̤¯ÚÈ ÙfiÙ ÁÔÓ›‰È· Ù· ÔÔ›· Û¯ÂÙ›˙ÔÓÙ·Ó Ì ÙËÓ ¤Î‚·ÛË ÂÈ‚›ˆÛ˘ ÌÔۯ‡̷ÙÔ˜ Î·È ÙËÓ Èı·ÓfiÙËÙ· ÔÍ›·˜ ·fiÚÚȄ˘. Δ· ›‰È· ·ÔÙÂϤÛÌ·Ù· ÂȂ‚·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 ÂÈÛÙËÌÔÓÈÎfi ÂÚÁ·ÏÂ›Ô ÁÈ· ÙËÓ ·Ó›¯Ó¢ÛË ‚ÈÔÏÔÁÈÎÒÓ Ì˯·ÓÈÛÌÒÓ. ¶ÚfiÛÊ·Ù·, Ú·ÁÌ·ÙÔÔÈ‹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¤˜ ¯ÚËÛÈÌÔÔÈ‹ıËÎ·Ó arrays Ì ˘„ËÏ‹ Û˘ÁΤÓÙÚˆÛË ÔÏÈÁÔÓÔ˘ÎÏÂÔÙȉ›ˆÓ. ™ÙËÓ ÚÒÙË13 ¯ÚËÛÈÌÔÔÈ‹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˘˜ ÔÔ›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 ÔÔ›Ô Î·Ù¤ÏËÍ·Ó ÔÈ ÂÈÛÙ‹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 ·ÍÈÔÈÛÙ›·˜ Ù˘ ÌÂıfi‰Ô˘ ¤ÁÈÓ ÂȂ‚·›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˘ ÂÌϤÎÔÓÙ·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 ÂÈÙ˘¯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¤ıËΠÂ›Û˘ fiÙÈ ÙÔ 98% ÙˆÓ ·ÓÙÈÁÚ¿ÊˆÓ Ì ÙËÓ ¿ÓÈÛË ¤ÎÊÚ·ÛË Â·ÓÂÚ¯fiÙ·Ó ÛÙ· Ê˘ÛÈÔÏÔÁÈο Â›‰· ÌÂÙ¿ ÙËÓ ·fiÚÚÈ„Ë. ¶ÔÛÔÙÈ΋ PCR Ô˘ Û˘ÌÏ‹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 ÚˆÙfiÎÔÏÏÔ ·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 ıÂÚ·›· calcineurin inhibitor ‚·ÛÈṲ̂ÓË Û ΢ÎÏÔÛÔÚ›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˜ Â›Û˘ Ì ›ÓˆÛË ÙÔ˘ ÈÛÙÔ‡. OÈ ÂÈÛÙ‹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 ¯ÚËÛÈÌÔÔÈ‹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 ¯ÚËÛÈÌÔÔÈ‹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 ÔÔ›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˘ ÛÂÈÚ¿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 ÂȂ‚·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˘ÌÏËڈ̷ÙÈο Ì ¿ÏϘ ·Ó·Ù˘ÛÛfiÌÂÓ˜ Ù¯ÓÔÏÔÁ›Â˜ Ù˘ ÏÂÈÙÔ˘ÚÁÈ΋˜ ÁÔÓȉȈ̷ÙÈ΋˜, fiˆ˜ ÔÈ Û˘ÛÙÔȯ›Â˜ ÁÔÓȉ›ˆÓ (chips, arrays) Î·È ·ԂϤÂÈ 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 ÙÚÔÔÔÈ‹ÛÂˆÓ Ì ÙȘ Ôԛ˜ 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 Û Â›Â‰Ô Î˘ÙÙ¿ÚÔ˘, ÈÛÙÔ‡ ‹ ÔÚÁ¿ÓÔ˘. ∫·Ù·Ú¯‹Ó οı ·ÙÙ·ÚÔ ÛÙÔÓ ›‰ÈÔ ÈÛÙfi ÌÔÚ› 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˜ ÌÔÚԇ̠ӷ ‰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 ÔÌÔÈÔÔÏÈΤ˜ ‰È·ÊÔÚÔÔÈ‹ÛÂȘ ÛÙË ‰ÔÌ‹ ÌÈ·˜ ÚˆÙ½Ó˘ (.¯. ʈÛÊÔÚ˘Ï›ˆÛË), ÂÓ·ÏÏ·ÎÙÈÎfi splicing, ·ÔÌfiÓˆÛË ‹ ÂÓÙfiÈÛË ÚˆÙÂ˚ÓÒÓ Û ˘Ô΢ÙÙ·ÚÈο ÙÌ‹Ì·Ù· ̤ۈ ·ÏÏËÏÂ›‰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 ÂÓÙÔÈÛÌfi ÚˆÙÂ˚ÓÒÓ, ÙȘ ÌÂÙ·ÙÚÔ¤˜- ÙÚÔÔÔÈ‹ÛÂȘ Ô˘ ˘Ê›ÛÙ·ÓÙ·È ·˘Ù¤˜, ÙËÓ Ì¤ÙÚËÛË ·ÏÏ·ÁÒÓ ÛÙËÓ ÔÛfiÙËÙ· ÙÔ˘˜, ÙȘ ·ÏÏËÏÂȉڿÛÂȘ 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˜ fiˆ˜ 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˜ ¯ÚËÛÈÌÔÔÈ‹ıËÎÂ Ë ËÏÂÎÙÚÔÊfiÚËÛË ÔÏ˘·ÎÚ˘Ï·Ìȉ›Ô˘ ‰‡Ô ‰È·ÛÙ¿ÛÂˆÓ (2D PAGE), Ù· ·ÔÙÂϤÛÌ·Ù· Ù˘ ÔÔ›·˜, 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˜ ÂÙȉ›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‰Ô̤ӈÓ

Δ·˘ÙÔÔ›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 Ôԛ˜ ı· ·ÓȯÓ‡ÔÓÙ·È ÚÈÓ ÙËÓ ÂÌÊ¿ÓÈÛË ÙˆÓ ÎÏÈÓÈÎÒÓ Û˘Ìو̿وÓ. 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 ¯ÚËÛÈÌÔÔÈ‹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¤˜ ÂÓÙfiÈÛ·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, fiˆ˜ 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 ÚˆÙ½Ó˜ ÓÂÊÚÒÓ Ì ΢ÙÙ·ÚÈÎfi ηÚΛӈ̷. OÈ ÂÚ¢ÓËÙ¤˜, ¯ÚËÛÈÌÔÔÈÒÓÙ·˜ 2D PAGE, ÚÔÛ‰ÈfiÚÈÛ·Ó Ù¤ÛÛÂÚÂȘ ÚˆÙ½Ó˜ ÔÈ Ôԛ˜ ÂÎÊÚ¿˙ÔÓÙ·Ó ÌfiÓÔ ÛÂ Ê˘ÛÈÔÏÔÁÈÎÔ‡˜ ÓÂÊÚÔ‡˜. ∏ ·ÒÏÂÈ· ÙˆÓ ‰‡Ô, ·fi ÙȘ Ù¤ÛÛÂÚÂȘ ÚˆÙ½Ó˜, ÔÈ Ôԛ˜ 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 ÌÔÚ› Ó· ˘¿Ú¯Ô˘Ó ·ÏÏ·Á¤˜ ÛÙË ÌÈÙÔ¯ÔÓ‰Úȷ΋ ÏÂÈÙÔ˘ÚÁ›· Ô˘ Ì οÔÈÔ ÙÚfiÔ ·˘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¿˙·˜ ¯ÚËÛÈÌÔÔÈ‹ıËΠÁÈ· ÙÔ ÚÔÊ›Ï Ê¿ÛÌ·ÙÔ˜ ÚˆÙÂ˚ÓÒÓ ·fi Ô‡Ú· ·ÛıÂÓÒÓ ÔÈ ÔÔ›ÔÈ ¯ˆÚ›ÛıËÎ·Ó Û ٤ÛÛÂÚÂȘ ηÙËÁÔڛ˜: (1) ·ÛıÂÓ›˜ Ì ÔÍ›· ·fiÚÚÈ„Ë, (2) ·ÛıÂÓ›˜ Ì ÔÍ›· ÛˆÏËÓ·Úȷ΋ Ó¤ÎÚˆÛË, (3) ·ÛıÂÓ›˜ Ì Â·Ó·Ï·Ì‚·ÓfiÌÂÓË ‹ de-novo ÛÂÈÚ·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‚ÈÔÏËÚÔÊÔÚÈ΋ ·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 ÔÔ›ÔÈ ı· ÌÔÚÔ‡Ó Ó· Ù·˘Ù›˙ÔÓÙ·È Ì ÔÍ›· ·fiÚÚÈ„Ë ÙÔ˘ ÌÔۯ‡̷ÙÔ˜. £· Ú¤ÂÈ ÂÔ̤ӈ˜ Ó· ·Ó·Ù˘¯ıÔ‡Ó Î·È Î·ÈÓÔ‡ÚÁÈ· ÚˆÙfiÎÔÏÏ· ‰È¿ÁÓˆÛ˘ – ıÂÚ·›·˜ 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˘ÙÔÔ›ËÛË ÚˆÙÂ˚ÓÒÓ ‹ ÛÙËÓ ·Ó·ÁÓÒÚÈÛË ÙÔ˘ ‚ÈÔÏÔÁÈÎÔ‡ Ì˯·ÓÈÛÌÔ‡ ÛÙÔÓ ÔÔ›Ô ÂÌϤÎÔÓÙ·È ÔÈ Û˘ÁÎÂÎÚÈ̤Ó˜ ÚˆÙ½Ó˜. ∏ ¯Ú‹ÛË Ù˘ 2D PAGE ÌÔÚ› Ó· ‰ÒÛÂÈ ÙË ‰˘Ó·ÙfiÙËÙ· ÚÔÛ‰ÈÔÚÈÛÌÔ‡ ÌÂÚÈÎÒÓ ÂȉÈÎÒÓ ÚˆÙÂ˚ÓÒÓ. ƒÔÌÔÙÈο Û˘ÛÙ‹Ì·Ù· ÌÂÙ·ÙÚ¤Ô˘Ó Ù· spots Ù˘ Á¤Ï˘ Ù˘ ËÏÂÎÙÚÔÊfiÚËÛ˘ Û ÎÔÚ˘Ê¤˜ ÔÈ Ôԛ˜ Û˘Ó‰˘¿˙ÔÓÙ·È Ì ÙÔ ·ÔÙ¤ÏÂÛÌ· Ù˘ Ê·ÛÌ·ÙÔÌÂÙÚ›·˜ Ì¿˙·˜. Δ· ·ÔÙÂϤÛÌ·Ù· ·˘Ù¿ ÌÔÚÔ‡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 ¯ÚËÛÈÌÔÔ›ËÛ·Ó Ì›· ·Ó¿Ï˘ÛË Ë ÔÔ›· 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 ÚˆÙ¿Û˜. °È· ÙÔ ‰È·¯ˆÚÈÛÌfi ÙÔ˘ Ì›ÁÌ·ÙÔ˜ ÙˆÓ ÚˆÙÂ˚ÓÒÓ Ô˘ ÚԤ΢„ ¯ÚËÛÈÌÔÔÈ‹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 fiˆ˜ ÙÔ Swiss-Prot Î·È Ù· “translations” ÂÚÁ·ÛÙ‹ÚÈ· Ù˘ ∂˘Úˆ·˚΋˜ ªÔÚȷ΋˜ μÈÔÏÔÁ›·˜, ÒÛÙ ӷ Ù·˘ÙÔÔÈËıÔ‡Ó ÔÈ ˘fi ÌÂϤÙË ÚˆÙ½Ó˜. ∏ ·Ú·¿Óˆ Ù¯ÓÔÏÔÁ›· (MuDPIT) ¤¯ÂÈ ÙË ‰˘Ó·ÙfiÙËÙ· Ó· Ù·˘ÙÔÔÈ‹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 Ôԛ˜ 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˘ ·ÏÏËÏÔÂ›‰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· ÌÔÚÔ‡Û·Ó Ó· ıˆÚËıÔ‡Ó Û·Ó ÂȉÈÎÔ› ‰Â›ÎÙ˜ ÁÈ· ÙËÓ ÂÓÂÚÁÔÔ›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 ÂÙȉ›ˆÓ ÂÈÛËÌ·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· ÂÈÛËÌ·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· ÂfiÌÂÓË ÁÂÓÈ¿ Ù¯ÓÔÏÔÁ›·˜ Ë ÔÔ›· ÂÚÈÏ·Ì‚¿ÓÂÈ

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Fourier-transformed tandem Ê·ÛÌÔʈÙfiÌÂÙÚ· Ì¿˙·˜ Ù· ÔÔ›· ı· Û˘Ó‰˘·ÛÙÔ‡Ó ÌÂ Û˘ÛÙ‹Ì·Ù· fiˆ˜ ÙÔ ªuDPIT ÛÙÔ ÔÔ›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.

™˘ÌÂÚ¿ÛÌ·Ù· ∞Ó·Ù‡ÛÛÔÓÙ·È Î·ÈÓÔ‡ÚÁȘ Ù¯ÓÔÏÔÁ›Â˜ Ì ÛÎÔfi 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 ·ÏÏËÏÂȉڿÛÂȘ ¤ÎÊÚ·Û˘ ÁÔÓȉ›ˆÓ – ÚˆÙÂ˚ÓÒÓ Î·È ÔÈ ÏÂÈÙÔ˘ÚÁÈΤ˜ Û¯¤ÛÂȘ ÙˆÓ ‚ÈÔÏÔÁÈÎÒÓ ÌÔÚ›ˆÓ ‰Â›¯ÓÔ˘Ó ÙË ÏÂÙ‹ 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 ÛÎÔfi Ó· ·ÚÂÌ‚·›ÓÔ˘Ó ÛÙËÓ ÌÂÙ·ÁÚ·Ê‹ ÂȉÈÎÒÓ ÁÔÓȉ›ˆÓ. Δ· siRNA ı· ÌÔÚÔ‡Ó Ó· ÂȂ‚·ÈÒÓÔ˘Ó ÙËÓ ÔÚ›· ‚ÈÔÏÔÁÈÎÒÓ ÌÔÓÔ·ÙÈÒÓ ‹ Ó· ¯ÚËÛÈÌÔÔÈÔ‡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˘ ÂÈϤÁÔ˘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 ıÂÚ·›· Î·È Ê˘ÛÈο Ë Î·Ï‡ÙÂÚË ÔÈfiÙËÙ· ˙ˆ‹˜ fiÏˆÓ ÙˆÓ ·ÛıÂÓÒÓ Ô˘ ¤¯Ô˘Ó ˘ÔÛÙ› ÌÂÙ·ÌfiÛ¯Â˘ÛË.

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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 ‰›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˘ÌÂÚÈÏ·Ì‚·ÓÔÌ¤ÓˆÓ ÙˆÓ ‰ÂÓ‰ÚÈÙÈÎÒÓ Î˘ÙÙ¿ÚˆÓ [DCs], Ì·ÎÚÔÊ¿ÁˆÓ, ÏÂÌÊÔ΢ÙÙ¿ÚˆÓ, ÂÈıËÏÈ·ÎÒÓ Î·È ÂÓ‰ÔıËÏÈ·ÎÒÓ Î˘ÙÙ¿ÚˆÓ). ∞˘ÙÔ› ÔÈ ˘ԉԯ›˜ ·Ó·ÁÓˆÚ›˙Ô˘Ó Û˘ÁÎÂÎÚÈ̤Ó˜ ‰Ô̤˜ ÙˆÓ ÌÈÎÚÔÔÚÁ·ÓÈÛÌÒÓ, (pathogen-associated molecular patterns-PAMPs) Û·Ó Â͈ÁÂÓ›˜ Û˘Ó‰¤Ù˜, ηıÒ˜ Â›Û˘ Î·È ÚÔηÏÔ‡ÌÂÓ˜ ·fi ÙÚ·‡Ì·-‚Ï¿‚Ë Î·Ù¿ ÙËÓ IRI ‰È·ÊÔÚÔÔÈË̤Ó˜ ‰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˘ ÂÓÂÚÁÔÔ›ËÛ˘ ÌÂÙ·ÁÚ·ÊÈÎÒÓ ·Ú·ÁfiÓÙˆÓ fiˆ˜ ÔÈ NFÎB, AP-1, Î·È IRF3, ÛÙËÓ ¤ÎÊÚ·ÛË ÁÔÓȉ›ˆÓ Ô˘ ÂÌϤÎÔÓÙ·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 ·ÏÏËÏÂȉÚÔ‡Ó Ì ٷ ·Úı¤Ó· Δ ÏÂÌÊÔ·ÙÙ·Ú·, Â¿ÁÔÓÙ·˜ ÙËÓ ·¿ÓÙËÛË ÙˆÓ ÂȉÈÎÒÓ Δ-΢ÙÙ¿ÚˆÓ, ·ÔÙÂÏÒÓÙ·˜ ¤ÙÛÈ ÙÔÓ Û˘Ó‰¤ÙË Ì ÙËÓ ÂȉÈ΋ ·ÓÔÛ›·. Ÿˆ˜ ·ÚÔ˘ÛÈ¿˙ÂÙ·È ÛÙÔ Û¯‹Ì· 1, ·Ú¯Èο Ë ·ÓÔÛȷ΋ ·¿ÓÙËÛË ÂÌÊ·Ó›˙ÂÙ·È Ó· ¤¯ÂÈ ÌÔÚÊ‹ «ÎÏ„‡‰Ú·˜». ∂ÓÙÔ‡ÙÔȘ, fiˆ˜ ÚÔÙ¿ıËΠÙÔ 2002, Î·È ÂȂ‚·ÈÒıËΠÚÔÛÊ¿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˜ ÌÔÚ› Ó· ηıÔÚ›˙ÔÓÙ·È Ì¤Ûˆ ÂÍ·ÚÙˆÌ¤ÓˆÓ ·fi ÙÔ ÔÍÂȉˆÙÈÎfi stress ÌÂÙ¿-ÌÂÙ·ÁÚ·ÊÈÎÒÓ ÙÚÔÔÔÈ‹ÛˆÓ, Ô˘ ηٷϋÁÔ˘Ó Û ¤Ó· ÂÈÚfiÛıÂÙÔ (˘„ËÏfiÙÂÚÔ) Â›Â‰Ô TLR ÌËӇ̷ÙÔ˜. ∂›Ó·È ÛËÌ·ÓÙÈÎfi Â›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 ÔχÏÔÎÔ Û‡ÛÙËÌ· ÙÔ ÔÔ›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 ÂÈΛӉ˘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˜, fiˆ˜ ·Ú¿‰ÂÈÁÌ· ·˘Ùfi Ô˘ Û˘Ì‚·›ÓÂÈ Î·Ù¿ ÙË ‰È¿ÚÎÂÈ· Ù˘ Â·Ó·ÈÌ¿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›· / Â·Ó·ÈÌ¿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 ÔÔ›· Âȉڿ ÛËÌ·ÓÙÈο ÛÙËÓ ¿ÌÂÛË Î·È ·ÒÙÂÚË ÂÈ‚›ˆÛË ÙˆÓ ÌÔÛ¯Â˘Ì¿ÙˆÓ, fiˆ˜ ¤¯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 ÙÚfiÔ Û˘ÓÙ‹ÚËÛ˘ ÙˆÓ ÌÔÛ¯Â˘Ì¿ÙˆÓ Î·È ÛÙËÓ ¯ÂÈÚÔ˘ÚÁÈ΋ Â¤Ì‚·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. ¶ÔÏÏ·Ϥ˜ 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‡ÌÏÂÁÌ· ÈÛÙÔÛ˘Ì·‚ÙfiÙËÙ·˜ (MHC) ·fi Ù· DCs fiˆ˜ 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 ·ÏÏËÏÂȉÚÒÓÙ·˜ Ì ٷ DAMPs fiˆ˜ 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 fiˆ˜ ·˘Ù¿ ηٿ ÙËÓ ·Ó·ÁÓÒÚÈÛË ÙˆÓ PAMPs ·fi ÙÔ˘˜ TLRs. ∂›Û˘, ÔÈ ·˘ÍË̤Ó˜ Û˘ÁÎÂÓÙÚÒÛÂȘ ÙˆÓ ROS, ÏÂÈÙÔ˘ÚÁÔ‡Ó Û·Ó ÂÈÚfiÛıÂÙ· 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 ÂÓÂÚÁÔÔ›ËÛ‹ ÙÔ˘˜ Î·È ¯ÚfiÓÈ· ·fiÚÚÈ„Ë, ÏfiÁˆ ·ıËÚÔÛÎÏ‹ÚˆÛ˘ ÙÔ˘ ÌÔۯ‡̷ÙÔ˜1,8-11. ∂ÎÙfi˜ ·fi Ù· ·ÙÙ·Ú·, ¯˘ÌÈÎÔ› ·Ú¿ÁÔÓÙ˜ fiˆ˜ ÙÔ Û˘Ìϋڈ̷ 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 ÂÌϷΛ Û ·˘Ù‹Ó ÙËÓ «Ê˘ÛÈ΋˜ ·ÓÔÛ›·˜» ·ÓÙ›‰Ú·ÛË «·ÓÙÈÁfiÓÔ˘-·ÓÙÈÛÒÌ·ÙÔ˜», ÂÓÂÚÁÔÔÈ› ÙÔÓ Î·Ù·ÚÚ¿ÎÙË ÙÔ˘ Û˘ÌÏËÚÒÌ·ÙÔ˜ ̤ۈ Ù˘ Ô‰Ô‡ Ù˘ ÏÂÎÙ›Ó˘. Δ· ÁÂÁÔÓfiÙ· ·˘Ù¿ Èı·Ó¿ Û˘Ì‚¿ÏÔ˘Ó Û ÂÈÚfiÛıÂÙË ÈÛÙÈ΋ ‚Ï¿‚Ë ÙÔ˘ ÌÔۯ‡̷ÙÔ˜12,13.

O ÚfiÏÔ˜ ÙÔ˘ Û˘ÛÙ‹Ì·ÙÔ˜ ÙÔ˘ Û˘ÌÏËÚÒÌ·ÙÔ˜ ÛÙËÓ IRI Â›Ó·È ·fi ηÈÚfi ·ԉ‰ÂÈÁ̤ÓÔ˜. ∏ ·‡ÍËÛË Ù˘ ·Ú·ÁˆÁ‹˜ ÙˆÓ ÌÔÚ›ˆÓ ÙÔ˘ Û˘ÌÏËÚÒÌ·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‡ ÂÓÂÚÁÔÔ›ËÛ˘ ¤¯ÂÈ Î·Ù·‰Âȯı›, ÚfiÛÊ·Ù· ‰Â‰Ô̤ӷ ·fi ÔÓÙ›ÎÈ· ÚÔÙ›ÓÔ˘Ó ¤Ó· ÂÈÚfiÛıÂÙÔ ÚfiÏÔ ÁÈ· ÙËÓ Ô‰fi Û‡Ó‰ÂÛ˘ Ì ÏÂÎÙ›ÓË. ∏ ÈÛ¯·ÈÌ›· Î·È Ë Û˘ÓÂ·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 ÂÌϤÎÂÙ·È ÛÙËÓ ÂÓÂÚÁÔÔ›ËÛË ÙÔ˘ Û˘ÌÏËÚÒÌ·ÙÔ˜. ∏ ÂÓ·fiıÂÛË MBL ÛÙ· ÂÚÈÛˆÏËÓ·Úȷο ÙÚȯÔÂȉ‹ Î·È ÛÙ· ÂÈıËÏȷο ·ÙÙ·Ú· ÙˆÓ ÛˆÏËÓ·Ú›ˆÓ ÌÔÚ› Â›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. ∂ÈÚÔÛı¤Ùˆ˜, ÚˆÙ½Ó˜ Ú˘ıÌÈÛÙÈΤ˜ ÙÔ˘ Û˘ÌÏËÚÒÌ·ÙÔ˜ (΢ڛˆ˜ ·Ó·ÛÙ·ÏÙÈΤ˜) fiˆ˜ Ë CD55 ÂÎÊÚ¿˙ÔÓÙ·È ÂÏ¿¯ÈÛÙ¿ Û ·˘Ù¿ Ù· ·ÙÙ·Ú·. ∏ ÛËÌ·Û›· Ù˘ ÙÔÈ΋˜ ·Ú·ÁˆÁ‹˜ ÙÔ˘ Û˘ÌÏËÚÒÌ·ÙÔ˜ ÛÙÔ ÓÂÊÚfi ·Ô‰ÂÈÎÓ‡ÂÙ·È ·fi knockout ÌÂϤÙ˜ ηٿ ÙȘ Ôԛ˜ ÓÂÊÚÈο ·ÏÏÔÌÔۯ‡̷ٷ Ô˘ ÛÙÂÚÔ‡ÓÙ·Ó C3 ›¯·Ó Ôχ ηχÙÂÚË ÂÈ‚›ˆÛË Û ıÂÙÈÎÔ‡˜ Û C3 Ï‹Ù˜ ·fi fiÙÈ Ù· ıÂÙÈο Û C3 ÌÔۯ‡̷ٷ. Δ· ·ÏÏÔÌÔۯ‡̷ٷ Â›Û˘ ·fi ÓˆÚ›˜ ·ÚÔ˘ÛÈ¿˙Ô˘Ó ·‡ÍËÛË Ù˘ ÙÔÈ΋˜ ·Ú·ÁˆÁ‹˜ Û˘ÌÏËÚÒÌ·ÙÔ˜ Ì ÌÈ· ÂÈÚfiÛıÂÙË ‰Â‡ÙÂÚË Ê¿ÛË Á‡Úˆ ÛÙËÓ Ù¤Ù·ÚÙË Ë̤ڷ. ¶·Ú·ÙËÚÂ›Ù·È ·fiÙÔÌË ·‡ÍËÛË ÙˆÓ ÂÈ¤‰ˆÓ ηٿ ÙËÓ ·fiÚÚÈ„Ë Î·È ¿Óˆ ·fi ÙÔ 10% ÙÔ˘ ÔÏÈÎÔ‡ ΢ÎÏÔÊÔÚÔ‡ÓÙÔ˜ C ÌÔÚ› Ó· ÂÎÎÚÈı› ·fi ÙÔ ÌfiÛ¯Â˘Ì·16. ™ÙÔ ÛËÌÂ›Ô ·˘Ùfi ı· Ú¤ÂÈ Ó· ÙÔÓÈÛÙ› fiÙÈ ÙÔ Û‡ÛÙËÌ· ÙÔ˘ Û˘ÌÏËÚÒÌ·ÙÔ˜ ‰Â Û¯ÂÙ›˙ÂÙ·È ÌfiÓÔ Ì ÙËÓ IRI ·ÏÏ¿ ·ÔÙÂÏ› Â›Û˘ Á¤Ê˘Ú· (fiˆ˜ Î·È ÔÈ TLRs) ÌÂٷ͇ Ê˘ÛÈ΋˜ Î·È Â›ÎÙËÙ˘ ·ÓÔÛÔ·¿ÓÙËÛ˘17.

27

ΔÔ Û‡ÛÙËÌ· Ù˘ ‹Í˘ ÙÔ ÔÔ›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. ∏ ÂÓÂÚÁÔÔ›ËÛË ÙÔ˘ ηٷÚÚ¿ÎÙË Ù˘ ‹Í˘ ¤¯ÂÈ ÛËÌ·ÓÙÈ΋ ÂÌÏÔ΋ ÛÙËÓ IRI, fiˆ˜ ¤¯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. ∂ÈϤÔÓ ÙÔ Û‡ÛÙËÌ· ÙˆÓ ¯ËÌÂÈÔÎÈÓÒÓ (˘ԉԯ›˜ Î·È Û˘Ó‰¤Ù˜ ÙÔ˘˜) ÂÌϤÎÔÓÙ·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˜ Â›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›·/Â·Ó·ÈÌ¿ÙˆÛË, Ë ÂÓÂÚÁÔÔ›ËÛË ÙˆÓ TLR, ÙˆÓ Î˘ÙÙ·ÚÔÎÈÓÒÓ Î·È ÙÔ˘ Û˘ÌÏËÚÒÌ·ÙÔ˜ Â¿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˘ Â¿ÁÔÓÙ·È Û˘ÌÂÚÈÏ·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 ıÂÚ·¢ÙÈÎÒÓ ÛÙÚ·ÙËÁÈÎÒÓ Ô˘ ·ÔÛÎÔÔ‡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

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∞. 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 ÙÚfiÔ ÔÈ ÛÙÚ·ÙËÁÈΤ˜ ·˘Ù¤˜ ı· Ú¤ÂÈ Ó· ·ÓÙ·Ó·ÎÏÔ‡Ó ¤Ó· a priori «ıÂÚ·¢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·¯ÈÛÙÔÔ›ËÛË Ù˘ ‚Ï¿‚˘ ·fi ÙÔ ÔÍÂȉˆÙÈÎfi stress, (2) Ë ·Ó·ÛÙÔÏ‹ Ù˘ ÂÓÂÚÁÔÔ›ËÛ˘ ÙÔ˘ Û˘ÌÏËÚÒÌ·ÙÔ˜ ΢ڛˆ˜ ̤ۈ Ù˘ Ô‰Ô‡ Ù˘ MBL, (3) Ë ·Ó·ÛÙÔÏ‹ Ù˘ ˆÚ›Ì·ÓÛ˘ ÙˆÓ ‰ÂÓ‰ÚÈÙÈÎÒÓ Î˘ÙÙ¿ÚˆÓ ÌÏÔοÚÔÓÙ·˜ ÙËÓ ¤ÎÊÚ·ÛË ÙÔ˘ TLR4 ‹ ÙÔ˘ NFÎμ-gene Î·È (4) Ô ·ÔÎÏÂÈÛÌfi˜ ÙˆÓ ‰Ú·ÛÙÈÎÒÓ ÏÂÈÙÔ˘ÚÁÈÒÓ Ù˘ Ê˘ÛÈ΋˜ ·ÓÔÛ›·˜ fiˆ˜ 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

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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¢·ÈÛıËÙÔÔ›ËÛË ·ÛıÂÓÒÓ ˘Ô„‹ÊÈˆÓ ÁÈ· ÌÂÙ·ÌfiÛ¯Â˘ÛË ·fi ˙ˆÓÙ·Ófi ‰fiÙË ÓÂÊÚÔ‡ ¢. ¶··‰ÔÔ‡ÏÔ˘

ø˜ ıÂÚ·›· Â·ÁˆÁ‹˜ ¯ÚËÛÈÌÔÔÈ‹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 ıÂÚ·›· 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· ÂÂÈÛfi‰È· ·fiÚÚȄ˘, ÁÈ· ¯ÚÔÓÈÎfi ‰È¿ÛÙËÌ· Ô˘ ÍÂÂÚÓÔ‡Û ÙÔ 1 ¤ÙÔ˜. ™ÙË ‰Â‡ÙÂÚË ÌÂϤÙË4, 45 ˘ÂÚ¢·ÈÛıËÙÔÔÈË̤ÓÔÈ ·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 ·¢·ÈÛıËÙÔÔ›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 ıÂÚ·¢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· Â·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 Â·Ó·Ï·Ì‚·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 ·ÚÓËÙÈÎÔÔÈ‹ıËΠ̛̠· Î·È ÌfiÓÔ ‰fiÛË ·ÓÔÛÔÛÊ·ÈÚ›Ó˘, ÂÓÒ ÛÙÔ˘˜ ˘fiÏÔÈÔ˘˜ 2 ·ÛıÂÓ›˜, ··ÈÙ‹ıËÎÂ Ë ÌËÓÈ·›· ¯ÔÚ‹ÁËÛË ÂÈϤÔÓ ‰fiÛÂˆÓ ÙÔ˘ Ê·ÚÌ¿ÎÔ˘ ÚÈÓ Ô‰ËÁËıÔ‡Ó ÛÙÔ ÂÈı˘ÌËÙfi ·ÔÙ¤ÏÂÛÌ·. ŸÏÔÈ ÔÈ ·ÛıÂÓ›˜ ¤Ï·‚·Ó ıÂÚ·›· Â·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· ÂÂÈÛfi‰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 ·¢·ÈÛıËÙÔÔ›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 οÔÈ· ÌÂÙ·ÌÔÛ¯Â˘ÙÈο ΤÓÙÚ·, Û˘ÌÂÚÈÏ·Ì‚¿ÓÂÙ·È ÛÙ· ıÂÚ·¢ÙÈο Û¯‹Ì·Ù· ·¢·ÈÛıËÙÔÔ›ËÛ˘ Î·È Ë ¯ÔÚ‹ÁËÛË ÙÔ˘ ÌÔÓÔÎψÓÈÎÔ‡ ·ÓÙÈ-CD20 ·ÓÙÈÛÒÌ·ÙÔ˜ rituximab, Ì ÛÎÔfi ÙËÓ ·ÔÊ˘Á‹ Â·Ó·‰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 ·¢·ÈÛıËÙÔÔ›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 ·¢·ÈÛıËÙÔÔ›ËÛ˘ (ÂÏ¿ÙÙˆÛË ÙÔ˘ Ù›ÙÏÔ˘ ÙˆÓ ·ÓÙÈ-HLA ·ÓÙÈÛˆÌ¿ÙˆÓ ÙÔ˘Ï¿¯ÈÛÙÔÓ Î·Ù¿ 50% ‹ Â·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 Â·Ó·¯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

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Ù›·˜ ·fiÚÚȄ˘. ™Ù· 2 ¤ÙË, Ë Ì¤ÛË ÙÈÌ‹ Ù˘ ÎÚ·ÙÈÓ›Ó˘ ÔÚÔ‡ ‹Ù·Ó 1,4mg/dl Î·È Ë ÂÈ‚›ˆÛË ÙˆÓ ·ÛıÂÓÒÓ ¤Êı·Ó ÙÔ 98%. ∏ ÂÈ‚›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¢ÛıËÙÔÔÈËÌ¤ÓˆÓ ÏËÙÒÓ.

OÈ ·ÓÂÈı‡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 ÈηÓÔÔÈËÙÈο ·ÔÙÂϤÛÌ·Ù· ÛÙËÓ ·¢·ÈÛıËÙÔÔ›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 ÂÚÈÙÒÛÂȘ ÚÔÂÙÔÈÌ·Û›·˜ ÁÈ· ÌÂÙ·ÌfiÛ¯Â˘ÛË ÓÂÊÚÔ‡ ·fi ˙ˆÓÙ·Ófi ‰fiÙË, Ô ·Ú·¿Óˆ Û˘Ó‰˘·ÛÌfi˜ ÂÈÙÚ¤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 ¯ÚËÛÈÌÔÔÈËı› 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˜ ÂÈÏÔÁ‹ 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 ·ÚÓËÙÈÎÔÔ›ËÛË ÙÔ˘ crossmatch, ÔÈ ·ÛıÂÓ›˜ ıˆÚÔ‡ÓÙ·È ϤÔÓ ¤ÙÔÈÌÔÈ ÁÈ· ÌÂÙ·ÌfiÛ¯Â˘ÛË. ΔÔ ·Ú·¿Óˆ ıÂÚ·¢ÙÈÎfi Û¯‹Ì· ÚÔÙ¿ıËΠ·fi ÙÔ˘˜ Montgomery Î·È Û˘Ó.6, ÔÈ ÔÔ›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˜ ıÂÚ·›· Â·ÁˆÁ‹˜ ¯ÚËÛÈÌÔÔÈ‹ıËÎÂ Ë daclizumab Î·È ˆ˜ ıÂÚ·›· Û˘ÓÙ‹ÚËÛ˘ Ô Û˘Ó‰˘·ÛÌfi˜ MMF, ÎÔÚÙÈÎÔÛÙÂÚÔÂȉÒÓ Î·È tacrolimus. ΔÔ ÚˆÙfiÎÔÏÏÔ ·¢·ÈÛıËÙÔÔ›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 ÔÔ›· 11 ·fi ÙÔ˘˜ 15 ·ÛıÂÓ›˜ Ì ıÂÙÈÎfi crossmatch ˘Ô‚Ï‹ıËÎ·Ó Ì ÂÈÙ˘¯›· Û ÌÂÙ·ÌfiÛ¯Â˘ÛË ÓÂÊÚÔ‡ ·fi ˙ˆÓÙ·Ófi ‰fiÙË, ÌÂÙ¿ ·fi ÂÊ·ÚÌÔÁ‹ ÚˆÙÔÎfiÏÏÔ˘ ·¢·ÈÛıËÙÔÔ›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 ·¢·ÈÛıËÙÔÔ›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, ¯ÚËÛÈÌÔÔÈ‹ıËÎ·Ó Ù· ·Ú·Î¿Ùˆ ıÂÚ·¢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 ıÂÚ·¢ÙÈÎÒÓ Û¯ËÌ¿ÙˆÓ ·¢·ÈÛıËÙÔÔ›ËÛ˘ Ô˘ ÂÚÈÏ·Ì‚¿ÓÔ˘Ó ÙË ‰ÈÂÓ¤ÚÁÂÈ· Û˘Ó‰ÚÈÒÓ ƒƒ, ÙfiÛÔ ˆ˜ ÚÔ˜ ÙËÓ Èı·ÓfiÙËÙ· ·ÚÓËÙÈÎÔÔ›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˘ ÂÂÈÛÔ‰›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˘ ÂÈÊ¿ÓÂÈ·˜ CD20 ÙˆÓ Ê˘ÛÈÔÏÔÁÈÎÒÓ Î·È ÓÂÔÏ·ÛÌ·ÙÈÎÒÓ μ-ÏÂÌÊÔ΢ÙÙ¿ÚˆÓ. ∞ӷʤÚıËΠ‹‰Ë Ë ¯ÔÚ‹ÁËÛË rituximab Û 2 ·fi Ù· ÚˆÙfiÎÔÏÏ· ·¢·ÈÛıËÙÔÔ›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 ·¢·ÈÛıËÙÔÔ›ËÛ˘ Û˘ÌÏËÚˆÓfiÙ·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˘ Â¤Ì‚·Û˘, ÁÈÓfiÙ·Ó Ù·˘Ùfi¯ÚÔÓ· Î·È ÛÏËÓÂÎÙÔÌ‹. ø˜ ıÂÚ·›· Â·ÁˆÁ‹˜ ¯ÚËÛÈÌÔÔÈ‹ıËÎÂ Ë ÔÏ˘ÎψÓÈ΋ ·ÓÙÈı˘ÌÔ΢ÙÙ·ÚÈ΋ ÛÊ·ÈÚ›ÓË, ÂÓÒ Ë ıÂÚ·›· 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 ÂÈ‚›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 ÂÂÈÛfi‰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 ·¢·ÈÛıËÙÔÔ›ËÛ˘, ¯ˆÚ›˜ fï˜ ÙË ‰ÈÂÓ¤ÚÁÂÈ· ÛÏËÓÂÎÙÔÌ‹˜ ηٿ ÙË ‰È¿ÚÎÂÈ· Ù˘ ÌÂÙ·ÌfiÛ¯Â˘Û˘11.

∞ÓÔÛÔÚÔÛÚfiÊËÛË (π∞) ΔÔ 1995, ÔÈ Reisaeter Î·È Û˘Ó.12 ‰ËÌÔÛ›Â˘Û·Ó Ù· ·ÔÙÂϤÛÌ·Ù· ÂÊ·ÚÌÔÁ‹˜ ÚˆÙÔÎfiÏÏÔ˘ ·¢·ÈÛıËÙÔÔ›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˘ÌÂÚÈÂÏ‹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 ÂÂÈÛfi‰ÈÔ ˘ÂÚÔÍ›·˜ ·fiÚÚȄ˘, ·ÏÏ¿ Ë ÂÈ‚›ˆÛË ÙˆÓ ÌÔÛ¯Â˘Ì¿ÙˆÓ ÌÂÙ¿ ·fi 1 Î·È 4 ¤ÙË ‹Ù·Ó 77% Î·È 64% ·ÓÙ›ÛÙÔȯ·, ÔÛÔÛÙ¿ Û·ÊÒ˜ ˘ԉ¤ÛÙÂÚ· ·fi ÂΛӷ ÙˆÓ ÌË ˘ÂÚ¢·ÈÛıËÙÔÔÈËÌ¤ÓˆÓ ·ÛıÂÓÒÓ. ™ÙËÓ ÈÔ ÚfiÛÊ·ÙË ‚È‚ÏÈÔÁÚ·Ê›·, Ë ÂÊ·ÚÌÔÁ‹ Ù˘ ·ÓÔÛÔÚÔÛÚfiÊËÛ˘ 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 ·¢·ÈÛıËÙÔÔ›ËÛ˘15. ™‡Ìʈӷ Ì ٷ ·Ú·¿Óˆ ÛÙÔȯ›·, ˘¿Ú¯ÂÈ ‰˘Ó·ÙfiÙËÙ· ÂÈÙ˘¯Ô‡˜ ÌÂÙ·ÌfiÛ¯Â˘Û˘ ÓÂÊÚÔ‡ Û ÌÂÁ¿ÏÔ ·ÚÈıÌfi ˘ÂÚ¢·ÈÛıËÙÔÔÈËÌ¤ÓˆÓ ·ÛıÂÓÒÓ ·ÏÏ¿ ··ÈÙÂ›Ù·È Ì·ÎÚfi¯ÚÔÓË ·Ú·ÎÔÏÔ‡ıËÛ‹ ÙÔ˘˜, ÚÔÎÂÈ̤ÓÔ˘ Ó· ÂȂ‚·ÈˆıÔ‡Ó Ë ·ÔÙÂÏÂÛÌ·ÙÈÎfiÙËÙ· Î·È Ë ·ÛÊ¿ÏÂÈ· ÙˆÓ ıÂÚ·¢ÙÈÎÒÓ Û¯ËÌ¿ÙˆÓ. ¶·Ú¿ ÙȘ Û‡Á¯ÚÔÓ˜ ÚÔfi‰Ô˘˜, Ë ·¢·ÈÛıËÙÔÔ›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 ÏÂÙÔÌÂÚ‹˜ ÂÓË̤ڈÛË ÙˆÓ ·ÛıÂÓÒÓ ÁÈ· ÙËÓ Èı·ÓfiÙËÙ· ÂÌÊ¿ÓÈÛ˘ ÂÂÈÛÔ‰›ˆÓ ÔÍ›·˜ ·fiÚÚȄ˘ ηıÒ˜ Î·È ÁÈ· ÙȘ ‰˘ÓËÙÈΤ˜ ÂÈÏÔΤ˜ ·fi ÙË ¯ÔÚËÁÔ‡ÌÂÓË ·ÓÔÛÔηٷÛÙÔÏ‹, ȉȷ›ÙÂÚ· fiÙ·Ó ÚfiÎÂÈÙ·È Ó· Ï¿‚Ô˘Ó ÌfiÛ¯Â˘Ì· ·fi ˙ˆÓÙ·Ófi ‰fiÙË.

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¢. ¶∞¶∞¢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¢·ÈÛıËÙÔÔ›ËÛË ÓÂÊÚÔ·ıÔ‡˜ Û ηٿÏÔÁÔ ·Ó·ÌÔÓ‹˜ ÁÈ· و̷ÙÈ΋ ÌÂÙ·ÌfiÛ¯Â˘ÛË ∫. ºÔ˘ÚÙÔ‡Ó·˜

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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· ¢·ÈÛıËÙÔÔ›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˘·ÈÛıËÙÔÔ›ËÛË Î·ı›ÛÙ·Ù·È ÂÓÙÔÓfiÙÂÚË Î·È ·ÚÔ˘ÛÈ¿˙ÂÈ ÈÔ Ì·ÎÚfi¯ÚÔÓË ‰È¿ÚÎÂÈ· Û ÂÚÈÙÒÛÂȘ fiÔ˘ 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 ¢·ÈÛıËÙÔÔ›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‹˜ ¢·ÈÛıËÙÔÔ›ËÛ˘ Ì ÙËÓ ¿ÚÔ‰Ô ÙˆÓ ÂÙÒÓ ÌÔÚ› 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¢·ÈÛıËÙÔÔ›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). ∏ ÔÛÔÙÈÎÔÔ›ËÛË ÙÔ˘ Á›ÓÂÙ·È Ì ÙËÓ ·Ó›¯Ó¢ÛË ÙÔ˘ ÔÛÔÛÙÔ‡ ÙˆÓ Èı·ÓÒÓ ‰ÔÙÒÓ ¤Ó·ÓÙÈ ÙˆÓ ÔÔ›ˆÓ Ô ÔÚfi˜ ÂÓfi˜ ·ÛıÂÓÔ‡˜ ·ÓÙȉڿ (ıÂÙÈÎfi Δ-cell crossmatch), ÏfiÁˆ ÚÔÛ¯ËÌ·ÙÈÛÌ¤ÓˆÓ IgG ·ÓÙÈۈ̿وÓ. ¶¿ÓÙˆ˜, οÔÈÔ˜ ˘„ËÏfi˜ Ù›ÙÏÔ˜ PRA ‰ÂÓ ·ÓÙÈηÙÔÙÚ›˙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 ÏËÙÒÓ ÔÈ ÔÔ›ÔÈ ·ÚÔ˘ÛÈ¿˙Ô˘Ó ıÂÙÈ΋ ‰ÔÎÈÌ·Û›· cross-match ¤¯Ô˘Ó ÌÂÈÒÛÂÈ ‰Ú·Ì·ÙÈο Ù· ÂÂÈÛfi‰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˘ÓÙÚÈÙÈ΋ ÏÂÈÔ„ËÊ›· ÙˆÓ ÂÚÈÙÒÛÂˆÓ ¿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˘. ∏ ¢·ÈÛıËÙÔÔ›ËÛË, ‰ËÏ·‰‹ Ë ‰ËÌÈÔ˘ÚÁ›· ·ÓÙÈHLA IgG ·ÓÙÈۈ̿وÓ, ÌÔÚ› Ó· Á›ÓÂÈ Ì ÙÚÂȘ ÙÚfiÔ˘˜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˜ ÌÔÚ› Ó· Ô‰ËÁ‹ÛÂÈ Û ¢·ÈÛıËÙÔÔ›ËÛË ÂÚ›Ô˘ ÛÙÔ 10% ÙˆÓ ·ÛıÂÓÒÓ. ∏ ¢Ú›· ÂÊ·ÚÌÔÁ‹ Ù˘ ·ÓÙÈÌÂÙÒÈÛ˘ Ù˘ ·Ó·ÈÌ›·˜ Ù˘ ¯ÚfiÓÈ·˜ ÓÂÊÚÈ΋˜ ÓfiÛÔ˘ Ì ·Ó·Û˘Ó‰È·Ṳ̂ÓË ·ÓıÚÒÈÓË ÂÚ˘ıÚÔÔÈËÙ›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˘ ¢·ÈÛıËÙÔÔ›ËÛ˘ Ì ·˘ÙfiÓ ÙÔÓ Ì˯·ÓÈÛÌfi. ª›· Èı·Ó‹ ·ËÛË ¤¯ÂÈ ÙÔÓ Î›Ó‰˘ÓÔ Â˘·ÈÛıËÙÔÔ›ËÛ˘ Ù˘ ÌËÙ¤Ú·˜ ηٿ 5-10%8. ∏ ΢ÚÈfiÙÂÚË Î·È Ë Û˘¯ÓfiÙÂÚË ¿ÓÙˆ˜ ·ÈÙ›· ¢·ÈÛıËÙÔÔ›ËÛ˘ Û‹ÌÂÚ· Â›Ó·È Î¿ÔÈ· ÚÔËÁËı›-

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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˘ ¢·ÈÛıËÙÔÔ›ËÛ˘. ™‹ÌÂÚ· Ì ÙË ‚ÂÏÙ›ˆÛË ÙˆÓ Ù¯ÓÈÎÒÓ Ù·˘ÙÔÔ›ËÛ˘ ·ÓÙÈÛˆÌ¿ÙˆÓ ıˆÚÂ›Ù·È Ôχ ÈÔ ÛËÌ·ÓÙÈ΋ Ë ·Ó›¯Ó¢ÛË Î·È ÛˆÛÙ‹ Ù·˘ÙÔÔ›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¢·ÈÛıËÙÔÔÈË̤ÓÔ ¤Ó·Ó ·ÛıÂÓ‹ fiÙ·Ó ÂÌÊ·Ó›˙ÂÈ Ù›ÙÏÔ PRA> 50%, ÂÓÒ ¿ÏÏ· ¯ÚËÛÈÌÔÔÈÔ‡Ó ˘„ËÏfiÙÂÚÔ˘˜ ·ÚÈıÌÔ‡˜ (∂urotranspant Registry> 85%)7. ™ÙË ¯ÒÚ· Ì·˜ ˆ˜ ˘ÂÚ¢·ÈÛıËÙÔÔÈË̤ÓÔ˜ ¯·Ú·ÎÙËÚ›˙ÂÙ·È Î¿ı ·ÛıÂÓ‹˜ Ô ÔÔ›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˘·ÈÛıËÙÔÔÈËÌ¤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 οÔÈÔ˘ ‚·ıÌÔ‡ HLA ¢·ÈÛıËÙÔÔ›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¢·ÈÛıËÙÔÔÈË̤ÓÔ˘˜ ·ÛıÂÓ›˜, ·ÚfiÏÔ Ô˘ ·ÔÙÂÏÔ‡Û·Ó ÂÚ›Ô˘ ÙÔ 14% ÙˆÓ ˘Ô„ËÊ›ˆÓ ÏËÙÒÓ. 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 ıÂÚ·›˜ ˘ÔηٿÛÙ·Û˘ Ù˘ ÓÂÊÚÈ΋˜ ÏÂÈÙÔ˘ÚÁ›·˜ Ì ·ÈÌÔοı·ÚÛË ‹ ÂÚÈÙÔÓ·˚΋ οı·ÚÛË. O ¯ÚfiÓÔ˜ ·Ú·ÌÔÓ‹˜ ÛÙȘ ıÂÚ·›˜ ·˘Ù¤˜ ¤¯ÂÈ ·Ô‰Âȯı› fiÙÈ ·ÔÙÂÏ› ·ÓÂÍ¿ÚÙËÙÔ ·Ú¿ÁÔÓÙ· ÁÈ· ÌÂȈ̤ÓË ÂÈ‚›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 ÂÓÂÚÁÔÔÈË̤ÓÔÈ 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¢·ÈÛıËÙÔÔÈË̤ÓÔÈ. ΔÔ ÔÛÔÛÙfi ·˘Ùfi Â›Ó·È ÌÈÎÚfiÙÂÚÔ ·fi ¿ÏϘ ¯ÒÚ˜, ·Ï-

Ï¿ ÌÔÚ› 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¢·ÈÛıËÙÔÔÈËÌ¤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 ÂÈ‚›ˆÛË ÙˆÓ ÌÔÛ¯Â˘Ì¿ÙˆÓ.

OÈ ‰‡Ô ÙÚfiÔÈ ÚÔÛ¤ÁÁÈÛ˘ ̤¯ÚÈ Û‹ÌÂÚ· ›ӷÈ: ·) Ë «‚ÈÔÏÔÁÈ΋» ÚÔÛ¤ÁÁÈÛË, fiÔ˘ Á›ÓÂÙ·È ÚÔÛ¿ıÂÈ· ·Ó‡ÚÂÛ˘ ηٿÏÏËÏˆÓ ‰ÔÙÒÓ Ì ÙÔ˘˜ ÔÔ›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, fiÔ˘ Á›ÓÂÙ·È ÚÔÛ¿ıÂÈ· ·ÔÌ¿ÎÚ˘ÓÛ˘ / ·‰Ú·ÓÔÔ›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 ÛÎÔfi ÙˆÓ Î·ıÔÚÈÛÌfi ·ÓÙÈÁfiÓˆÓ HLA ÛÙ· ÔÔ›· Ô ˘ÂÚ¢·ÈÛıËÙÔÔÈË̤ÓÔ˜ ·ÛıÂÓ‹˜ ‰ÂÓ ¤¯ÂÈ ÚÔÛ¯ËÌ·ÙÈṲ̂ӷ ·ÓÙÈÛÒÌ·Ù· Î·È Û˘ÓÂÒ˜ 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˘ ÌÔÚ› Ó· ˘ÔÏÔÁ›˙ÂÈ Èı·Ó‹ Û˘Ì‚·ÙfiÙËÙ· Ì ˘ÂÚ¢·ÈÛıËÙÔÔÈË̤ÓÔ˘˜ ·ÛıÂÓ›˜. ™Â Ù¤ÙÔÈ· ÂÚ›ÙˆÛË ÙÔ ÓÂÊÚÈÎfi ÌfiÛ¯Â˘Ì· ÌÂٷʤÚÂÙ·È ÛÙÔ Î¤ÓÙÚÔ ÙÔ˘ ·ÛıÂÓÔ‡˜, fiÔ˘ 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¢·ÈÛıËÙÔÔÈË̤ÓÔÈ ·ÛıÂÓ›˜ Â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‹˜ ÂÈ‚›ˆÛË ÙˆÓ ÌÔÛ¯Â˘Ì¿ÙˆÓ Ì¤Ûˆ ÙÔ˘ AMP Â›Ó·È 87%, ·ÎÚÈ‚Ò˜ ·Ú·Ï‹ÛÈ· Ì ÙÔ˘˜ ÌË Â˘·ÈÛıËÙÔÔÈË̤ÓÔ˘˜ ·ÛıÂÓ›˜7.

¶ÚˆÙfiÎÔÏÏÔ ªÂÁ¿Ï˘ μÚÂÙ·Ó›·˜ (UK) ∏ ÂÈÏÔÁ‹ 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¢·ÈÛıËÙÔÔÈË̤ÓÔÈ ·ÛıÂÓ›˜ ¤¯Ô˘Ó ÚÔÙÂÚ·ÈfiÙËÙ· ¤Ó·ÓÙÈ ÙˆÓ ˘ÔÏÔ›ˆÓ. ∞Ó·ÊÔÚÈο Ì ÙÔ˘˜ ˘ÂÚ¢·ÈÛıËÙÔÔÈË̤ÓÔ˘˜ ·ÛıÂÓ›˜ ÙÔ Û‡ÛÙËÌ· ‚·Û›˙ÂÙ·È ÛÙËÓ ·Ó›¯Ó¢ÛË Ù˘ ÂȉÈÎfiÙËÙ·˜ ÙˆÓ anti-HLA ·ÓÙÈÛˆÌ¿ÙˆÓ Ù· ÔÔ›· ·ÚÔ˘ÛÈ¿˙ÂÈ Ô ˘ÂÚ¢·ÈÛıËÙÔÔÈË̤ÓÔ˜ ·ÛıÂÓ‹˜ ηıÒ˜ Î·È ÂȉÈÎfiÙËÙ˜ Ô˘ ıˆÚÔ‡ÓÙ·È ÌË ·Ô‰ÂÎÙ¤˜ (HLA mismatches ·fi ÚÔËÁÔ‡ÌÂÓË ÌÂÙ·ÌfiÛ¯Â˘ÛË, ÔÏÏ·Ϥ˜ ΢‹ÛÂȘ). ªÂ ÙÔ ÚˆÙfiÎÔÏÏÔ ·˘Ùfi ηٿ ÙËÓ ÙÂÏÂ˘Ù·›· ‰ÂηÂÙ›· ¤¯ÂÈ ÙÚÈÏ·ÛÈ·ÛÙ› Ô ·ÚÈıÌfi˜ ÙˆÓ ÌÂÙ·ÌÔۯ‡ÛÂˆÓ Û ˘ÂÚ¢·ÈÛıËÙÔÔÈË̤ÓÔ˘˜ ·ÛıÂÓ›˜ ÛÙË ªÂÁ¿Ï˘ μÚÂÙ·Ó›· 9. ¶·ÚfiÌÔÈÔ ÚˆÙfiÎÔÏÏÔ ·ÎÔÏÔ˘ıÂ›Ù·È Ì ÂÈÙ˘¯›· Î·È ÛÙË ¯ÒÚ· Ì·˜.

¶ÚˆÙfiÎÔÏÏÔ ¶·ÓÂÈÛÙËÌ›Ô˘ Emory (∏¶∞)«∂ÈÎÔÓÈÎfi» crossmatch ΔÔ ∞ÌÂÚÈηÓÈÎfi ¶·ÓÂÈÛÙ‹ÌÈÔ ÙÔ˘ Emory ÛÙËÓ ∞ÙÏ¿ÓÙ· ¤¯ÂÈ ·ÚÔ˘ÛÈ¿ÛÂÈ ÚfiÛÊ·Ù· ÙËÓ ÂÌÂÈÚ›· ÙÔ˘ Û¯ÂÙÈο Ì ÙËÓ ÚÔÛÊÔÚ¿ ÓÂÊÚÈÎÒÓ ÌÔÛ¯Â˘Ì¿ÙˆÓ Û ¢·ÈÛıËÙÔÔÈË̤ÓÔ˘˜ 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·˘ÙÔÔ›ËÛ˘ ÌË ·Ô‰ÂÎÙÒÓ ‰ÔÙÒÓ. ∏ ‚·ÛÈ΋ ÙÔ˘ ·Ú¯‹ Â›Ó·È Ë Ù·˘ÙÔÔ›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 و̷ÙÈÎfi˜ ‰fiÙ˘ ʤÚÂÈ Ù· HLA ·ÓÙÈÁfiÓ· Ù· ÔÔ›· ·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

ÙÔÔÈË̤ÓÔ˘˜ ·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 ÔÔ›· ·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 ·¢·ÈÛıËÙÔÔ›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 ÔÔ›ˆÓ Ë ·ÓÔÛÔÛÊ·ÈÚ›ÓË ·ÚÔ˘ÛÈ¿˙ÂÈ ·ÓÔÛÔÙÚÔÔÔÈËÙÈΤ˜ ȉÈfiÙËÙ˜2: ·) ÌÂÙ·‚ÔÏ‹ ÙˆÓ ÂÈ¤‰ˆÓ ·˘Ùfi- Î·È ¿ÏÏÔ-·ÓÙÈÛˆÌ¿ÙˆÓ Ì¤Ûˆ ·ÓÙÈ-ȉÈÔÙ˘ÈÎÒÓ ·ÓÙÈۈ̿وÓ, ‚) ·Ó·ÛÙÔÏ‹ ÂÓÂÚÁÔÔ›ËÛ˘ ÁÔÓȉ›ˆÓ ΢ÙÙ·ÚÔÎÈÓÒÓ, Á) ‰Ú·ÛÙËÚÈfiÙËÙ· ¤Ó·ÓÙÈ ÙÔ˘ ˘Ô‰Ô¯¤· ÙÔ˘ Δ-ÏÂÌÊÔ΢ÙÙ¿ÚÔ˘, ‰) ·ÏÏËÏÂ›‰Ú·ÛË ·ÓÙÈÁÔÓÔ-·ÚÔ˘ÛÈ·ÛÙÈÎÒÓ Î˘ÙÙ¿ÚˆÓ Î·È Fc ˘Ô‰Ô¯¤·, Â) anti-CD4 ‰Ú·ÛÙÈÎfiÙËÙ·, ÛÙ) ÂÓÂÚÁÔÔ›ËÛË ·ÓÙ·ÁˆÓÈÛÙÒÓ ˘Ô‰Ô¯¤ˆÓ ΢ÙÙ·ÚÔÎÈÓÒÓ, ˙) ·Ó·ÛÙÔÏ‹ ÙÔ˘ Û˘ÌÏËÚÒÌ·ÙÔ˜. ∏ ÙÂÏÂ˘Ù·›· ‰Ú¿ÛË ·Ó·Ê¤ÚıËΠÚfiÛÊ·Ù· Î·È ·ÊÔÚ¿ ÙË Û‡Ó‰ÂÛË ÙÔ˘ Fc ÙÌ‹Ì·ÙÔ˜ Ù˘ ·ÓÔÛÔÛÊ·ÈÚ›Ó˘ Ì ÂÓÂÚÁÔÔÈË̤ӷ ÛÙÔȯ›· ÙÔ˘ Û˘ÌÏËÚÒÌ·ÙÔ˜ (C3b, C4b), ·ÏÏ¿ Î·È ·Ó·ÛÙÔÏ‹ Ù˘ ‰ËÌÈÔ˘ÚÁ›·˜ ÙÔ˘ Û˘ÌϤÁÌ·ÙÔ˜ C5bC9 MAC12.

OÈ Glotz Î·È Û˘Ó ·ÚÔ˘Û›·Û·Ó ÙËÓ ÂÌÂÈÚ›· 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 Â·ÁˆÁ‹ Ì thymoglobulin Î·È ÙÚÈÏfi 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¢·ÈÛıËÙÔÔÈË̤ÓÔ˘˜ ·ÛıÂÓ›˜ ÔÈ ÔÔ›ÔÈ ¤Ï·‚·Ó 1-4 ‰fiÛÂȘ IVIG14. §fiÁˆ ÔÈÎÔÓÔÌÈÎÒÓ ÂÚÈÔÚÈÛÌÒÓ ÔÈ ·ÛıÂÓ›˜ ˘‚ϋıËÛ·Ó ÚÈÓ ÙËÓ ¯ÔÚ‹ÁËÛË πVIG Û ÂÚÁ·ÛÙËÚÈ·Îfi ¤ÏÂÁ¯Ô ÁÈ· ÂÈÏÔÁ‹ ·˘ÙÒÓ Ô˘ Èı·ÓÒ˜ Ó· ˆÊÂÏÔ‡ÓÙ·Ó ÂÚÈÛÛfiÙÂÚÔ ·fi ÙË ıÂÚ·›·. ∏ 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 ıÂÚ·›·. ™·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΋ ÂÈ‚›ˆÛË ÙˆÓ ÌÔÛ¯Â˘Ì¿ÙˆÓ. ∏ ÌÂϤÙË πG02 Â›Ó·È Ë ÌfiÓË ‰ÈÏ‹ Ù˘ÊÏ‹ Ù˘¯·ÈÔÔÈË̤ÓË ÌÂϤÙË Ì ÔÌ¿‰· ¤ÏÂÁ¯Ô˘ (placebo) ·Ó·ÊÔÚÈο Ì ÙË ‰Ú·ÛË Ù˘ IVIG Û ˘ÂÚ¢·ÈÛıËÙÔÔÈË̤ÓÔ˘˜ ·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‹˜ ÂÈ‚›ˆÛË ÙˆÓ ÌÔÛ¯Â˘Ì¿ÙˆÓ ‹Ù·Ó 80% Î·È 75% ·ÓÙ›ÛÙÔȯ·. ∏ ÙÒÛË ÙˆÓ ÂÈ¤‰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˘ ¯ÚËÛÈÌÔÔÈ‹ıËÎÂ15.

∏ ıÂÚ·›· ·¢·ÈÛıËÙÔÔ›ËÛ˘ Ì IVIG ıˆÚÂ›Ù·È ÂÍ·ÈÚÂÙÈο ‰··ÓËÚ‹. ™‡Ìʈӷ Ì ÌÈ· ÔÈÎÔÓÔÌÔÙ¯ÓÈ΋ ÌÂϤÙË ÛÙȘ ∏¶∞, ÙÔ ÎfiÛÙÔ˜ Ù˘ ıÂÚ·›·˜ 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 ·ÓÂÈı‡ÌËÙ˜ ÂÓ¤ÚÁÂȘ ÛÙËÓ ÔÌ¿‰· Ù˘ IVIG Î·È 23 ÛÙËÓ ÔÌ¿‰· ÙÔ˘ ÂÈÎÔÓÈÎÔ‡ Ê·ÚÌ¿ÎÔ˘. ∏ ÈÔ Û˘¯Ó‹ ·ÓÂÈı‡ÌËÙË ÂÓ¤ÚÁÂÈ· ÛÙËÓ ÔÌ¿‰· Ù˘ IVIG ‹Ù·Ó Ë ÎÂÊ·Ï·ÏÁ›·, Ë ÔÔ›· ˘Ô¯ˆÚÔ‡Û Ì ÂÏ¿ÙÙˆÛË ÙÔ˘ Ú˘ıÌÔ‡ ¤Á¯˘Û˘ ÙÔ˘ Ê·ÚÌ¿ÎÔ˘ Î·È ¯ÔÚ‹ÁËÛË ·Ú·ÎÂÙ·ÌfiÏ˘. ÕÏϘ ·ÓÂÈı‡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‹ ·ÓÂ¿ÚÎÂÈ· IgA, ıÚÔÌ‚ˆÙÈο ÂÂÈÛfi‰È· (Ù· ÂÚÈÛÛfiÙÂÚ· ΤÓÙÚ· Û‹ÌÂÚ· ¯ÚËÛÈÌÔÔÈÔ‡Ó ÚÔÊ˘Ï·ÎÙÈ΋ ·ÓÙÈıÚÔÌ‚ˆÙÈ΋ ·ÁˆÁ‹) Î·È ÔÍ›· ÓÂÊÚÈ΋ ·ÓÂ¿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 ÚˆÙfiÎÔÏÏ· ·¢·ÈÛıËÙÔÔÏ›ËÛ˘ ‚·ÛÈṲ̂ӷ ÛÙËÓ ‰ÈÂÓ¤ÚÁÂÈ· Ï·ÛÌ·Ê·›ÚÂÛ˘17-20. Δ· ÚˆÙfiÎÔÏÏ· ·˘Ù¿ ·ÊÔÚÔ‡Ó Î˘Ú›ˆ˜ ˘ÂÚ¢·ÈÛıËÙÔÔÈË̤ÓÔ˘˜ ·ÛıÂÓ›˜ Ì ˘Ô„‹ÊÈÔ˘˜ ˙ÒÓÙ˜ ‰fiÙ˜ Ì ÙÔ˘˜ ÔÔ›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 Ï·ÛÌ·Ê·›ÚÂÛË Î·È ÙË ¯ÔÚ‹ÁËÛË ÌÈÎÚÒÓ ‰fiÛÂˆÓ IVIG Ë ÔÔ›· ¤¯ÂÈ ·ÓÔÛÔÙÚÔÔÔÈËÙÈΤ˜ 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 ·ÓÙÈÌÂÙÒÈÛË Ù˘ ÔÍ›·˜ ·fiÚÚȄ˘ ·fi ·ÓÙÈÛÒÌ·Ù· Ô˘ ·Ú·ÙËÚÂ›Ù·È Û˘¯Ó¿ ÛÙÔ˘˜ ·ÛıÂÓ›˜ Ô˘ ˘Ô‚¿ÏÏÔÓÙ·È Û ÚˆÙfiÎÔÏÏ· ·¢·ÈÛıËÙÔÔ›ËÛ˘2,8.

∞ÓÔÛÔÚÔÛÚfiÊËÛË ∏ ̤ıÔ‰Ô˜ Ù˘ ·ÓÔÛÔÚÔÛÚfiÊËÛ˘ ¤¯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 fiˆ˜ ÔÈ ·Ú¿ÁÔÓÙ˜ ‹Í˘ ‹ ÙËÓ ·Ó¿ÁÎË ¯ÔÚ‹ÁËÛ˘ ˘ÁÚÒÓ ·Ó·Ï‹ÚˆÛ˘.

OÈ Lorenz Î·È Û˘Ó ¯ÚËÛÈÌÔÔ›ËÛ·Ó ÙËÓ ·ÓÔÛÔÚÔÛÚfiÊËÛË ˆ˜ ıÂÚ·›· ·¢·ÈÛıËÙÔÔ›ËÛ˘ Û ·ÛıÂÓ›˜ Ì ıÂÙÈÎfi crossmatch ¤Ó·ÓÙÈ و̷ÙÈÎÔ‡ ‰fiÙË21. ∂¿Ó ÌÂÙ¿ ·fi Ì›· Û˘Ó‰ڛ· ·ÓÔÛÔÚÔÛÚfiÊËÛ˘ 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 ·ÓÔÛÔÚÔÛÚfiÊËÛ˘ ÎÚ›ıËΠ·Ó·Áη›· ÁÈ· ÙËÓ ·ÔÊ˘Á‹ ÌÂÁ¿Ï˘ ·Ú¿Ù·Û˘ ÙÔ˘ ¯ÚfiÓÔ˘ „˘¯Ú‹˜ ÈÛ¯·ÈÌ›·˜. OÈ Û˘Ó‰ڛ˜ ·ÓÔÛÔÚÔÛÚfiÊËÛ˘ 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‹ ÂÈ‚›ˆÛË ÌÔÛ¯Â˘Ì¿ÙˆÓ. ΔÔ ÌÂÈÔÓ¤ÎÙËÌ· ·˘ÙÔ‡ ÙÔ˘ ÚˆÙÔÎfiÏÏÔ˘ Â›Ó·È fiÙÈ ·Ó ‰ÂÓ ·ÚÓËÙÈÎÔÔÈËı› ÙÔ crossmatch, Ô ÂfiÌÂÓÔ˜ 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˘ ¯ÚËÛÈÌÔÔÈÂ›Ù·È ÛÙËÓ ·ÓÔÛÔÚÔÛÚfiÊËÛË ·ÂÏ¢ıÂÚÒÓÂÙ·È Î·Ù¿ ÙË Û˘Ó‰ڛ· Ù˘ ıÂÚ·›·˜ 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 ·¢·ÈÛıËÙÔÔ›ËÛ˘!

Rituximab To rituximab Â›Ó·È ¯ÈÌÂÚÈÎfi ÌÔÓÔÎψÓÈÎfi ·Óٛۈ̷ ¤Ó·ÓÙÈ ÙÔ˘ ·ÓÙÈÁfiÓÔ˘ ÂÈÊ·Ó›·˜ CD20, ÙÔ ÔÔ›Ô Â˘Ú›ÛÎÂÙ·È ÛÙËÓ ÂÈÊ¿ÓÂÈ· Ê˘ÛÈÔÏÔÁÈÎÒÓ Î·È ÓÂÔÏ·ÛÌ·ÙÈÎÒÓ μ-ÏÂÌÊÔ΢ÙÙ¿ÚˆÓ. ΔÔ Ê¿ÚÌ·ÎÔ ¤¯ÂÈ Ï¿‚ÂÈ Â›ÛËÌ· ¿‰ÂÈ· ¯Ú‹Û˘ ÁÈ· ÙË ıÂÚ·›· non-Hodgkin ÏÂÌÊˆÌ¿ÙˆÓ (Û˘ÌÂÚÈÏ·Ì‚·ÓÔÌ¤ÓˆÓ Î·È ÙˆÓ ÏÂÌÊÔ-˘ÂÚÏ·ÛÙÈÎˆÓ ÓÔÛËÌ¿ÙˆÓ ÌÂÙ¿ ·fi ÙË ÌÂÙ·ÌfiÛ¯Â˘ÛË, PTLD), Î·È ÛÂ

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ÂÚ¢ÓËÙÈο ÚˆÙfiÎÔÏÏ· ·˘ÙÔ¿ÓÔÛˆÓ ÓÔÛËÌ¿ÙˆÓ Ì ÂÌÏÔ΋ Ù˘ ¯˘ÌÈ΋˜ ·ÓÔÛ›·˜2. ∫¿ÔÈ· ÌÂÙ·ÌÔÛ¯Â˘ÙÈο ΤÓÙÚ· Û˘ÌÂÚÈÏ·Ì‚¿ÓÔ˘Ó ÙÔ rituximab ÛÙ· ÚˆÙfiÎÔÏÏ· ·¢·ÈÛıËÙÔÔ›ËÛ˘ ÁÈ· ÙËÓ ·ÔÊ˘Á‹ Â·Ó·‰ËÌÈÔ˘ÚÁ›·˜ ÙˆÓ anti-HLA ·ÓÙÈۈ̿وÓ. £ÂˆÚËÙÈο ÙÔ ·ÓÙÈÁfiÓÔ CD20 ‰ÂÓ ÂÎÊÚ¿˙ÂÙ·È ÛÙ· Ï·ÛÌ·ÙÔ·ÙÙ·Ú· Ù· ÔÔ›· Â›Ó·È Ù· ·ÙÙ·Ú· ·Ú·ÁˆÁ‹˜ ÙˆÓ ·ÓˆÙ¤Úˆ ·ÓÙÈۈ̿وÓ, ·ÏÏ¿ ¤¯Ô˘Ó ÚÔÙ·ı› ‰‡Ô Ì˯·ÓÈÛÌÔ› Èı·Ó‹˜ ÂÌÏÔ΋˜ 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-¢·ÈÛıËÙÔÔÈË̤ÓÔ˘˜ ·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›˜. ÃÚËÛÈÌÔÔÈÂ›Ù·È Ì ۯÂÙÈ΋ ÂÈÙ˘¯›· (off-label) ÛÙÔ ÚˆÙfiÎÔÏÏÔ ·¢·ÈÛıËÙÔÔ›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 ÂÚÈÙÒÛÂȘ ·ÓıÂÎÙÈ΋˜ ÛÙË ıÂÚ·›· ÔÍ›·˜ ·fiÚÚȄ˘ ÔÊÂÈÏfiÌÂÓ˘ Û ·Óٛۈ̷. ∏ ıÂÚ·›· Ì rituximab Â›Ó·È ÂÍ·ÈÚÂÙÈο ‰··ÓËÚ‹ Î·È ¯ÚÂÈ¿˙ÔÓÙ·È Ù˘¯·ÈÔÔÈË̤Ó˜ 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 ÂÈÙ˘¯‹ ‰ÈÏ‹ ÌÂÙ·ÌfiÛ¯Â˘ÛË ‹·ÙÔ˜ Î·È ÓÂÊÚÔ‡ Û ˘ÂÚ¢·ÈÛıËÙÔÔÈË̤ÓÔ˘˜ ·ÛıÂÓ›˜ Ì ıÂÙÈÎfi crossmatch, ·ÏÏ¿ ÔÈ ·ÛıÂÓ›˜ ·˘ÙÔ› ·ÚÔ˘Û›·˙·Ó ¿ÌÂÛË ¤Ó‰ÂÈÍË ÁÈ· ‰ÈÏ‹ Ù·˘Ùfi¯ÚÔÓË ÌÂÙ·ÌfiÛ¯Â˘ÛË (·ÈÌÔηı·ÈÚfiÌÂÓÔÈ ·ÛıÂÓ›˜ Ì Ë·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˘

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∫. ºOÀƒΔOÀ¡∞™

‹·ÙÔ˜ ›¯Â ¯ÚËÛÈÌÔÔÈËı› 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›˜ ÂÂÈÛfi‰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· ÂÈϤÁÔ˘Ó ÈÛ¯˘Ú¿ ·ÓÔÛÔηٷÛÙ·ÏÙÈο Û¯‹Ì·Ù· Ì ıÂÚ·›· Â·ÁˆÁ‹˜ Ì ÔÏ˘ÎψÓÈ΋ ·ÓÙÈı˘ÌÔ΢ÙÙ·ÚÈ΋ ÛÊ·ÈÚ›ÓË (thymoglobulin) Î·È ÙÚÈÏ‹ ıÂÚ·›· Ì tacrolimus, MMF Î·È ÛÙÂÚÔÂȉ‹. ªÂÚÈο ΤÓÙÚ· Û˘ÌÂÚÈÏ·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 ıÂÚ·›˜ Â·ÁˆÁ‹˜ Ì basiliximab ‹ daclizumab. ∞Í›˙ÂÈ Ó· ÛËÌÂȈı› fiÙÈ ÙÔ ÌÔÓÔÎψÓÈÎfi ·Óٛۈ̷ ¤Ó·ÓÙÈ ÙÔ˘ ·ÓÙÈÁfiÓÔ˘ CD52 alemtuzumab (Campath 1H) ÙÔ ÔÔ›Ô ¯ÚËÛÈÌÔÔÈÂ›Ù·È Û‹ÌÂÚ· ¢ڤˆ˜ Û ÚˆÙfiÎÔÏÏ· ·ÔÊ˘Á‹˜ ·Ó·ÛÙÔϤˆÓ ηÏÛÈÓ¢ڛÓ˘ ‹ ÛÙÂÚÔÂȉÒÓ Û˘Óԉ‡ÙËΠ·fi ·˘ÍË̤ÓÔ Î›Ó‰˘ÓÔ ·fiÚÚȄ˘ ÔÊÂÈÏfiÌÂÓ˘ Û ·ÓÙÈÛÒÌ·Ù·3 Û ÌË Â˘·ÈÛıËÙÔÔÈË̤ÓÔ˘˜ ·ÛıÂÓ›˜. OÈ Vo Î·È Û˘Ó ÚfiÛÊ·Ù· ·Ó¤ÊÂÚ·Ó ÂÈÙ˘¯‹ ˘Ô‰fiÚÈ· ¯ÔÚ‹ÁËÛË alemtuzumab Û ˘ÂÚ¢·ÈÛıËÙÔÈË̤ÓÔ˘˜ ·ÛıÂÓ›˜, ÌË ÂȂ‚·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 ÔÔ›ÔÈ Î·È ı· Ú¤ÂÈ Ó· ÂÈÛËÌ·ÓıÔ‡Ó: – ∫·Ù·Ú¯‹Ó Ì ÌÔÓ·‰È΋ ÂÍ·›ÚÂÛË ÙË ÌÂϤÙË IG02, Ù· ÚˆÙfiÎÔÏÏ· ·˘Ù¿ ‰ÂÓ ¤¯Ô˘Ó ÌÂÏÂÙËı› ÛÂ Ù˘¯·ÈÔÔÈË̤Ó˜ ÌÂϤÙ˜ Ì ÔÌ¿‰· ÂϤÁ¯Ô˘.

OÈ ˘ÔÛÙËÚÈÎÙ¤˜ ÙÔ˘˜ ÂÎÊÚ¿˙Ô˘Ó ÙËÓ ÂÔ›ıËÛË fiÙÈ Ù· ·ÔÙÂϤÛÌ·Ù· Â›Ó·È ·ÓÒÙÂÚ· ·fi ÙËÓ ÂÌÂÈÚ›· ·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 ÂÈ‚›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 ÂÈÙ˘¯›·, ·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 ÓÂÔÏ·ÛÈÒÓ. ∂Ô̤ӈ˜, ÔÈ ˘Ô„‹ÊÈÔÈ ·ÛıÂÓ›˜ ÁÈ· ·ÚfiÌÔÈ· ÚˆÙfiÎÔÏÏ· ı· Ú¤ÂÈ Ó· Â›Ó·È Î·Ï¿ ÏËÚÔÊÔÚË̤ÓÔÈ ÁÈ· ÙȘ Èı·Ó¤˜ ÌÂÏÏÔÓÙÈΤ˜ ÂÈÏÔΤ˜.

– ¢ÂÓ ˘¿Ú¯Ô˘Ó ·ÎfiÌË ·ÔÙÂϤÛÌ·Ù· Ì·ÎÚfi¯ÚÔÓ˘ ·Ú·ÎÔÏÔ‡ıËÛ˘. OÈ ÔϤÌÈÔÈ ÙˆÓ ÚˆÙÔÎfiÏÏˆÓ ·˘ÙÒÓ ÂÎÊÚ¿˙Ô˘Ó ¤ÓÙÔÓ˜ ÂÈÊ˘Ï¿ÍÂȘ ÁÈ· ÙËÓ Ì·ÎÚfi¯ÚÔÓË Û˘ÌÂÚÈÊÔÚ¿ ÙÔ˘ ·ÓÔÛÔÔÈËÙÈÎÔ‡ Û˘ÛÙ‹Ì·ÙÔ˜ ·Ó·ÊÔÚÈο Ì ÙË ÛÙ·‰È·Î‹ Â·Ó·‰ËÌÈÔ˘ÚÁ›· anti-HLA ·ÓÙÈۈ̿وÓ

METAMO™XEY™Eπ™ 2008

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Î·È ÙȘ Èı·Ó¤˜ ˘Ô-ÎÏÈÓÈΤ˜ ÌÔÚʤ˜ ÔÍ›·˜ ·fiÚÚȄ˘ ·fi ·ÓÙÈÛÒÌ·Ù·. ∏ ÚfiÏË„Ë Ù˘ Èı·Ó‹˜ ¢·ÈÛıËÙÔÔ›ËÛ˘ ÙˆÓ ·ÛıÂÓÒÓ ıˆÚÂ›Ù·È ıÂÌÂÏÈ҉˘. ∏ ¿ÛÎÔË ¯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˘ıÚÔÔÈËÙ›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 ÂÈ‚›ˆÛ˘, Ë Î·Ù¿ÏÏËÏË ÂÈÏÔÁ‹ ÂÓfi˜ ÚÒÙÔ˘ ÌÔۯ‡̷ÙÔ˜, Ì ÙËÓ Î·Ï‡ÙÂÚË ‰˘Ó·Ù‹ ÈÛÙÔÛ˘Ì‚·ÙfiÙËÙ·, ıˆÚÂ›Ù·È ÛËÌ·ÓÙÈ΋ ÁÈ· ÙËÓ ·ÔÊ˘Á‹ ¢·ÈÛıËÙÔÔ›ËÛ˘ ÛÙÔ Ì¤ÏÏÔÓ.

O ÚfiÏÔ˜ Ù˘ ·Ê·›ÚÂÛ˘ ÙÔ˘ ÓÂÊÚÈÎÔ‡ ÌÔۯ‡̷ÙÔ˜ ÌÂÙ¿ ÙËÓ Â·Ó¤ÓÙ·ÍË Û ıÂÚ·›· ˘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·˘ÙÔÔ›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· ÌÔÚÔ‡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 (fiˆ˜ ÔÈ solid phase assays) ›Ûˆ˜ ·ÔÎÏÂ›Ô˘Ó Î·ÎÒ˜ ·fi Èı·Ó‹ ÌÂÙ·ÌfiÛ¯Â˘ÛË Î¿ÔÈÔ˘˜ ¢·ÈÛıËÙÔÔÈË̤ÓÔ˘˜ ·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˘¯·ÈÔÔÈË̤Ó˘ ÌÂϤÙ˘ fiˆ˜ 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· ÂÂÈÛfi‰È· ÔÍ›·˜ ·fiÚÚȄ˘ ‹Ù·Ó Û˘ÓÙÚÈÙÈο ˘„ËÏfiÙÂÚ· ÛÙË ‰Â‡ÙÂÚË ÔÌ¿‰·. ∞ÎfiÌË Ù· ‰ÈÂÙ‹ ·ÔÙÂϤÛÌ·Ù· Ù˘ Eurotransplant, Ù· ÔÔ›· Â›Ó·È ·ÚfiÌÔÈ· Ì ·˘Ù¿ Û ÌË Â˘·ÈÛıËÙÔÔÈË̤ÓÔ˘˜ ·ÛıÂÓ›˜ ÂÈ΢ÚÒÓÔ˘Ó ·˘Ù‹Ó ÙËÓ ˘ÂÚÔ¯‹.

41

– ∂Ô̤ӈ˜ ÙÔ ÂӉȷʤÚÔÓ ı· Ú¤ÂÈ Ó· ÂÈÎÂÓÙÚˆı› ÛÙËÓ ·‡ÍËÛË Ù˘ ‰ÂÍ·ÌÂÓ‹˜ ÙˆÓ ‰ÔÙÒÓ Î·È ÌfiÓÔÓ Û ÂȉÈΤ˜ ÂÚÈÙÒÛÂȘ (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 ÂÌÂÈÚ›· 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· ÂÍÔÏÈṲ̂ӷ ·ÓÔÛÔÏÔÁÈο ÂÚÁ·ÛÙ‹ÚÈ·, ·ÊÔ‡ ÔÈ ‰ÔÎÈ̷ۛ˜ crossmatch ÌÂÙ¿ ÙË ÌÂÙ·ÌfiÛ¯Â˘ÛË ÂËÚ¿˙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˘ÌÏËÚÒÌ·ÙÔ˜ Ì ÙÔ ÌÔÓÔÎψÓÈÎfi ·Óٛۈ̷ eculizumab (ÂÁÎÂÎÚÈ̤ÓÔ Û··ÛÌ· ÁÈ· ÙË ıÂÚ·›· Ù˘ Ó˘ÎÙÂÚÈÓ‹˜ ·ÚÔ͢ÓÙÈ΋˜ ·ÈÌÔÛÊ·ÈÚÈÓÔ˘Ú›·˜) Û ¢·ÈÛıËÙÔÔÈË̤ÓÔ˘˜ Â›Ì˘Â˜, ÌÔÚ› Ó· Ô‰ËÁ‹ÛÂÈ Û ̷ÎÚfi¯ÚÔÓË ÂÈ‚›ˆÛË ÙÔ˘ ÓÂÊÚÈÎÔ‡ ÌÔۯ‡̷ÙÔ˜ Ì ÙË ¯Ú‹ÛË ÂÏ¿¯ÈÛÙ˘ ·ÓÔÛÔηٷÛÙÔÏ‹˜30. ∏ ÎÏÈÓÈ΋ ÙÔ˘ ÂÊ·ÚÌÔÁ‹ Û ˘ÂÚ-¢·ÈÛıËÙÔÔÈË̤ÓÔ˘˜ ·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.

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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¢·ÈÛıËÙÔÔÈË̤ÓÔ˜ Ï‹Ù˘ ÓÂÊÚÈÎÔ‡ ÌÔۯ‡̷ÙÔ˜ ª. ¢·ÚÂÌ¿, π.¡. ªÔϤÙ˘

Ô›ÔÈ ‰ÂÓ ¤¯Ô˘Ó ˘Ô‚ÏËı› Û ÌÂÙ·ÁÁ›ÛÂȘ ‹ Û ÚÔËÁÔ‡ÌÂÓË ÌÂÙ·ÌfiÛ¯Â˘ÛË, ·ÏÏ¿ ÂÌÊ·Ó›˙Ô˘Ó HLA ¢·ÈÛıËÙÔÔ›ËÛË. ∏ Èı·ÓfiÙËÙ· ¢·ÈÛıËÙÔÔ›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 ‹ οÔÈÔ ÙÚ·‡Ì·, ÌÔÚ› Ó· Ô‰ËÁ‹ÛÂÈ Û Â·ÓÂÓÂÚÁÔÔ›ËÛË Ì›·˜ ηı˘ÛÙÂÚË̤Ó˘ ·ÏÏÔ·¿ÓÙËÛ˘ ‹ ‰È·Ù‹ÚËÛË ÌÈ·˜ Û˘Ó¯È˙fiÌÂÓ˘ ·Ú·ÁˆÁ‹˜ ·ÓÙۈ̿وÓ8. ∞ÚÎÂÙ¤˜ ‰È·ÊÔÚÂÙÈΤ˜ ̤ıÔ‰ÔÈ ¯ÚËÛÈÌÔÔÈÔ‡ÓÙ·È, ÔÈ Ôԛ˜ ηıÔÚ›˙Ô˘Ó fiÛÔ Â˘·ÈÛıËÙÔÔÈË̤ÓÔ˜ Â›Ó·È ¤Ó·˜ ˘Ô„‹ÊÈÔ˜ Ï‹Ù˘ ÓÂÊÚÈÎÔ‡ ÌÔۯ‡̷ÙÔ˜ ÛÙ· HLA . OÈ Ì¤ıÔ‰ÔÈ ÔÈ Ôԛ˜ ηıÔÚ›˙Ô˘Ó ÙËÓ Â˘·ÈÛıËÙÔÔ›ËÛË ·ÓȯÓÂ‡Ô˘Ó ·ÓÙÈÛÒÌ·Ù· ¤Ó·ÓÙÈ ÂÓfi˜ ¢ڤˆ˜ Ê¿ÛÌ·ÙÔ˜ ΢ÙÙ¿ÚˆÓ (panel) ·fi Ì›· ‰ÂÍ·ÌÂÓ‹ ‰˘ÓËÙÈÎÒÓ ‰ÔÙÒÓ. ∏ ¢·ÈÛıËÙÔÔ›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˘ ¯ÚËÛÈÌÔÔÈÔ‡ÓÙ·È ÁÈ· ÙÔÓ ÚÔÛ‰ÈÔÚÈÛÌfi ÙˆÓ Î˘ÙÙ·ÚÔÙÔÍÈÎÒÓ ·ÓÙÈÛˆÌ¿ÙˆÓ Â›Ó·È Ë CDC (complement dependent cytotoxicity), Ë ÔÔ›· ·ÓȯÓ‡ÂÈ Ù· PRA fiÙ·Ó ÚÔÛı¤ÙÔÌ ÔÚfi ÙÔ˘ Ï‹ÙË Û ̛· ‰ÂÍ·ÌÂÓ‹ ÏÂÌÊÔ΢ÙÙ¿ÚˆÓ Ì ÁÓˆÛÙ¿ Ù·˘ÙÔÔÈË̤ӷ HLA Î·È ·ÎÔÏÔ˘ı› Ë ÚÔÛı‹ÎË Û˘ÌÏËÚÒÌ·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 ÔÔ›· ÁÓˆÛÙ¿ HLA ·ÓÙȉÚÔ‡Ó Ì ÔÚfi ÙÔ˘ Ï‹ÙË Î·È Ë ÔÔ›· ¤¯ÂÈ ·ÓÙÈηٷÛÙ·ı› ·fi ÙË Ì¤ıÔ‰Ô Luminex, Ë ÔÔ›· ÛÙËÚ›˙ÂÙ·È ÛÙËÓ Î˘ÙÙ·ÚÔÌÂÙÚ›· ÚÔ‹˜ (flow cytometry). ∞Ó¿ÏÔÁ· Ì ÙË Ì¤ıÔ‰Ô Ô˘ ¯ÚËÛÈÌÔÔÈ›ٷÈ

∂˘·ÈÛıËÙÔÔÈË̤ÓÔÈ ˘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 ÔÔ›ÔÈ ¤¯Ô˘Ó ¢·ÈÛıËÙÔÔÈËı› Û HLA ÌÂÙ¿ ·fi οÔÈÔ ÁÂÁÔÓfi˜ ¢·ÈÛıËÙÔÔ›ËÛ˘,fiˆ˜ Â›Ó·È Ë Î‡ËÛË,ÔÈ ÌÂÙ·ÁÁ›ÛÂȘ ·›Ì·ÙÔ˜ ‹ ÚÔËÁÔ‡ÌÂÓË ÌÂÙ·ÌfiÛ¯Â˘ÛË1,2. ÀÂÚ¢·ÈÛıËÙÔÔÈË̤ÓÔÈ ıˆÚÔ‡ÓÙ·È ÔÈ ·ÛıÂÓ›˜ Ô˘ ¤¯Ô˘Ó PRA>80%. O ‚·ıÌfi˜ ·ÏÏ¿ Î·È Ë ‰È¿ÚÎÂÈ· Ù˘ ¢·ÈÛıËÙÔÔ›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˘·ÈÛıËÙÔÔ›ËÛË ÌÂÙ¿ ·fi ÌÂÙ·ÌfiÛ¯Â˘ÛË ÂÌÊ·Ó›˙ÂÈ ÌÂÁ·Ï‡ÙÂÚË ‰È¿ÚÎÂÈ·3. ∏ ¯Ú‹ÛË Ù˘ ·ÓıÚÒÈÓ˘ ·Ó·Û˘Ó‰˘·Ṳ̂Ó˘ ÂÚ˘ıÚÔÔÈËÙ›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˘·ÈÛıËÙÔÔÈËÌ¤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· ¢·ÈÛıËÙÔÔ›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· ¢·ÈÛıËÙÔÔ›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-

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ÛÙÔÓ ¤ÏÂÁ¯Ô ¢·ÈÛıËÙÔÔ›ËÛ˘ Î·È crossmatch, ·ÓȯÓ‡ÔÓÙ·È ‰È·ÊÔÚÂÙÈÎÔ› Ù‡ÔÈ ·ÓÙÈۈ̿وÓ, ÙˆÓ ÔÔ›ˆÓ Ë ÎÏÈÓÈ΋ ÛËÌ·Û›· ÌÔÚ› Û ÔÚÈṲ̂Ó˜ ÂÚÈÙÒÛÂȘ Ó· ÌËÓ Â›Ó·È ·fiÏ˘Ù· Û·Ê‹˜. Δ· IgG ·ÓÙÈÛÒÌ·Ù· ÁÂÓÈο, ıˆÚÂ›Ù·È fiÙÈ ‰Â›¯ÓÔ˘Ó ·ÏËıÈÓ‹ ¢·ÈÛıËÙÔÔ›ËÛË ¤Ó·ÓÙÈ HLA, ÂÓÒ Ù· IgM ·ÓÙÈÛÒÌ·Ù· ‰ÂÓ ıˆÚÂ›Ù·È fiÙÈ ·ÓÙÈÚÔÛˆÂ‡Ô˘Ó Ì›· ·ÏËıÈÓ‹ ·ÓÙÈ-HLA ·¿ÓÙËÛË. ∞ÓÙÈÛÒÌ·Ù· Ô˘ ·ÓȯÓ‡ÔÓÙ·È ¤Ó·ÓÙÈ ÙˆÓ T΢ÙÙ¿ÚˆÓ ıˆÚÂ›Ù·È fiÙÈ ·ÓÙÚÔÛˆÂ‡Ô˘Ó Ú·ÁÌ·ÙÈ΋ ·ÓÙÈ-HLA ¢·ÈÛıËÙÔÔ›ËÛË ¤Ó·ÓÙÈ ÙˆÓ Ù¿Í˘ I ·ÓÙÈÁfiÓˆÓ. ™˘ÁÎÚÈÙÈο, ¤Ó· B (+) crossmatch ·ÓÙÈÚÔÛˆ‡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˜ ¢·ÈÛıËÙÔÔÈË̤ÓÔ 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˘Ìϋڈ̷,Ù· ÔÔ›· ·ÓȯÓ‡ıËÎ·Ó ÔÔÈ·‰‹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˘·ÈÛıËÙÔÔÈË̤ÓÔÈ ·ÛıÂÓ›˜ ÂÚÈ̤ÓÔ˘Ó ÌÂÁ·Ï‡ÙÂÚÔ ¯ÚÔÓÈÎfi ‰È¿ÛÙËÌ· ÁÈ· ÙËÓ Â͇ÚÂÛË ÌÔۯ‡̷ÙÔ˜ ÂÌÊ·Ó›˙Ô˘Ó ÂÚÈÛÛfiÙÂÚ· ÂÂÈÛfi‰È· ·fiÚÚȄ˘ Û˘ÁÎÚÈÙÈο Ì ÙÔ˘˜ ÌË Â˘·ÈÛıËÙÔÔÈË̤ÓÔ˘˜ ·ÛıÂÓ›˜. ∞fi Ùo 1985 Ë Eurotransplant ‰›ÓÂÈ ÚÔÙÂÚ·ÈfiÙËÙ· Û ·ÛıÂÓ›˜ Ì «acceptable missmatch» Î·È PRA >85%. ¶ÚfiÎÂÈÙ·È ÁÈ· ·ÛıÂÓ›˜ ÔÈ ÔÔ›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˘·ÈÛıËÙÔÔÈË̤ÓÔÈ9. 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¢·ÈÛıËÙÔÔÈË̤ÓÔ˘ 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:

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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.

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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 ÔÔ›· 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 ÔÔ›· ÂÈÙÚ¤ÂÈ ÙÔÓ ‰È·¯ˆÚÈÛÌfi ÙÔ˘ Û ÂÈ̤ÚÔ˘˜ 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 ÂÈÓÔ‹ÛÂˆÓ ÔÈ Ôԛ˜ ›¯·Ó ˆ˜ ÛÙfi¯Ô ÙËÓ ·ÓÙÈÌÂÙÒÈÛË Ù˘ ‰Ú·Ì·ÙÈ΋˜ ·‡ÍËÛ˘ ÙˆÓ ÏËÙÒÓ 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 ÙÚÔÔÔ›ËÛË Ù˘ ÎÏ·ÛÈ΋˜ Ù¯ÓÈ΋˜ Ù˘ ÔÚıÔÙÔÈ΋˜ ÌÂÙ·ÌfiÛ¯Â˘Û˘ ‹·ÙÔ˜ ‹Ù·Ó ¤ÏÏÂÈ„Ë ·È‰È·ÙÚÈÎÒÓ و̷ÙÈÎÒÓ ÌÔÛ¯Â˘Ì¿ÙˆÓ, Ì ·ÔÙ¤ÏÂÛÌ· Ë ıÓËÙfiÙËÙ· ÛÙȘ Ï›ÛÙ˜ ·Ó·ÌÔÓ‹˜ ·È‰È·ÙÚÈÎÒÓ ·ÛıÂÓÒÓ Ó· ÍÂÂÚÓ¿ ÙÔ 25%, Û ÔÚÈṲ̂ӷ ÌÂÙ·ÌÔÛ¯Â˘ÙÈο ΤÓÙÚ·6. ∏ ÚÔÛ¿ıÂÈ· ÁÈ· ÙËÓ ·ÓÙÈÌÂÙÒÈÛË ·˘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 ÌÔÚ› Ó· ÚÔÁÚ·ÌÌ·ÙÈÛı› ÚÈÓ Ë Î·Ù¿ÛÙ·ÛË ÙÔ˘ Ï‹ÙË ÂȉÂÈÓˆı› Û ÌË ·Ó·ÛÙÚ¤„ÈÌÔ ÛËÌ›Ô, Ó· ÂÈÏÂÁ› 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· Â¤ÎÙ·Û˘ ÙˆÓ ÎÚÈÙËÚ›ˆÓ ÂÈÏÔÁ‹˜ ÙˆÓ ÏËÙÒÓ 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 ÂÈÙÚ¤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˘˜). ∂ÈϤÔÓ, ÙÔ ¿ÙÔÌÔ Ô˘ ÂÈϤÁÂÙ·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˘ ÂÂÌ‚¿Ûˆ˜ Ô˘ ı· ˘ÔÛÙ› Î·È ÁÈ· ÙȘ ÂÓ·ÏÏ·ÎÙÈΤ˜ χÛÂȘ ÁÈ· ÙËÓ ıÂÚ·›· 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˜.

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π. ºOÀ∑∞™, ¢. Δ∞∫OÀ¢∞™

Δ· ÎÚÈÙ‹ÚÈ· ÂÈÏÔÁ‹˜ ‰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›·˜. ∂ÈϤÔÓ, ÈÛÙ‡ÂÙ·È fiÙÈ Ë ËÏÈΛ· ÂËÚ¿˙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˜ ÂÚÈÙÒÛÂȘ ÌÔÚ› Ó· ‰ÈÂÓÂÚÁËı› ÌË Û˘Ì‚·Ù‹ ÌÂÙ·ÌfiÛ¯Â˘ÛË, fiˆ˜ Û ‚Ú¤ÊË ÌÈÎÚfiÙÂÚ· ÙÔ˘ ÂÓfi˜ ¤ÙÔ˘˜ Ô˘ ‰ÂÓ ¤¯Ô˘Ó ·Ó·Ù‡ÍÂÈ ·ÎfiÌË ·ÓÙÈÛÒÌ·Ù· ¤Ó·ÓÙÈ ÙˆÓ ÔÌ¿‰ˆÓ ·›Ì·ÙÔ˜ ‹ Û Â›ÁÔ˘Û˜ ÂÚÈÙÒÛÂȘ ÛÙȘ Ôԛ˜ ‰ÂÓ ˘¿Ú¯ÂÈ Û˘Ì‚·Ùfi و̷ÙÈÎfi ÌfiÛ¯Â˘Ì·18,19. ¶ÚfiÛÊ·Ù·, ¤¯Ô˘Ó ‰ËÌÔÛÈ¢ı› ÌÈÎÚ¤˜ ÛÂÈÚ¤˜ Ì ÂÈÙ˘¯Â›˜ ÌË Û˘Ì‚·Ù¤˜ ÌÂÙ·ÌÔۯ‡ÛÂȘ ÌÂÙ¿ ·fi ¤ÓÙÔÓË ÂȉÈ΋ ÚÔÂÙÔÈÌ·Û›· ·¢·ÈÛıËÙÔÔ›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‹ ÂÈÏÔÎÒÓ ·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 ÂÂÌ‚·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 ÔÔÈ·‰‹ÔÙ ÓfiÛÔ Ë ÔÔ›· ·˘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· ÏÈÒ‰Ô˘˜ ‰ÈËı‹Ûˆ˜ ÙÔ˘ ‹·ÙÔ˜ ÌÂ Û˘Ó¤ÂÈ· ÙËÓ ·‡ÍËÛË ÙÔ˘ ÎÈÓ‰‡ÓÔ˘ ÌÂÙÂÁ¯ÂÈÚËÙÈ΋˜ Ë·ÙÈ΋˜ ·ÓÂ¿ÚÎÂÈ·˜ ÙfiÛÔ ÛÙÔÓ ‰fiÙË fiÛÔ Î·È ÛÙÔÓ Ï‹ÙË15.

OÚÈṲ̂ӷ ΤÓÙÚ· ··ÈÙÔ‡Ó ‚ÈÔ„›· ‹·ÙÔ˜ ÁÈ· ÙÔÓ ·ÔÎÏÂÈÛÌfi Ù˘ ÏÈÒ‰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˘ ÂÂÌ‚¿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. ÀÔÁÚ·Ê‹ Ù˘ 1˘ ·Ô‰Ô¯‹˜ Ù˘ ÂÂÌ‚¿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 ÎÔÒÛˆ˜), Ó¢ÌÔÓÔÏÔÁÈÎfi˜ ¤ÏÂÁ¯Ô˜, ÂȉÈΤ˜ ‚ÈÔ¯ËÌÈΤ˜ ÂÍÂÙ¿ÛÂȘ (TSH, FT3, FT4, IgA, IgG, IgM, Fe, ÙÚ·ÓÛÊÂÚÚ›ÓË, ·1-·ÓÙÈıÚ˘„›ÓË, ÛÂÚÔ˘ÏÔÏ·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˜ ÂÈÙÚÔ‹˜ μÈÔËıÈ΋˜ ÀÔÁÚ·Ê‹ Ù˘ ÙÂÏÈ΋˜ ·Ô‰Ô¯‹˜ Ù˘ ÂÂÌ‚¿Ûˆ˜

METAMO™XEY™Eπ™ 2008

53

¶›Ó·Î·˜ 2. ∞ÓÙÂӉ›ÍÂȘ ÂÈÏÔÁ‹˜ 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΋ ·ÓÂ¿ÚÎÂÈ·

∞Ó·Ó¢ÛÙÈÎfi

ÃÚÔÓ›· ·ÔÊÚ·ÎÙÈ΋ Ó¢ÌÔÓÔ¿ıÂÈ· ¶Ó¢ÌÔÓÈ΋ ˘¤ÚÙ·ÛË

¶‹ÍË ·›Ì·ÙÔ˜

∞ÓÂ¿ÚÎÂÈ· ÚˆÙÂ˚ÓÒÓ C ‹ S ∞ÓÙ›ÛÙ·ÛË ÛÙËÓ ÚˆÙ½ÓË C ∞ÈÌÔÚÚÔÊÈÏ›·

¡ÂÔÏ¿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΋ ·ÓÂ¿ÚÎÂÈ· ™. ¢È·‚‹Ù˘ Ù‡Ô˘ 1 ÀÂÚ- / ˘Ôı˘ÚÂÔÂȉÈÛÌfi˜

·ÓıÂÎÙÈÎfi˜ Û ıÂÚ·›·

∂ÈÓÂÊÚȉÈ΋ ·ÓÂ¿ÚÎÂÈ· ∞ÓÔÛÔÔÈËÙÈÎfi

∞˘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·. ∂ÈϤÔÓ, Ù· ÈÛÙÔÏÔÁÈο ÎÚÈÙ‹ÚÈ· ·ÔÎÏÂÈÛÌÔ‡ ˙ÒÓÙÔ˜ ‰fiÙË ‹·ÙÔ˜ ›ӷÈ: ·) ˘Ï·›· ‹ ÂÚÈÎÔÏÔÂȉÈ΋ ›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˘ Â¿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˘ ÂÂÌ‚¿Ûˆ˜.

ª¤ÙÚËÛË ÙÔ˘ fiÁÎÔ˘ ÙÔ˘ Ë·ÙÈÎÔ‡ ÌÔۯ‡̷ÙÔ˜ ∏ ÚÔÂÁ¯ÂÈÚËÙÈ΋ ÂÎÙ›ÌËÛË Ù˘ Â¿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 ÀÔÏÔÁÈÛÌfi˜ 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 Â·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˘ ¯ÚËÛÈÌÔÔÈÔ‡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· ÌÔÚ› Ó· ‰È·¯ˆÚÈÛı› ÂÚ·ÈÙ¤Úˆ Î·È Ó· ¯ÚËÛÈÌÔÔÈËı› 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˜ ∏ ÔχÏÔÎË ·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 ÂÂÌ‚·ÙÈΤ˜ ÌÂıfi‰Ô˘˜, fiˆ˜ Ë ·ÁÁÂÈÔÁÚ·Ê›· Ù˘ ·ÔÚÙ‹˜ Î·È Ù˘ Ë·ÙÈ΋˜ ·ÚÙËÚ›·˜, Ì fiÏÔ˘˜ ÙÔ˘˜ Û¯ÂÙÈÎÔ‡˜ ÎÈÓ‰‡ÓÔ˘˜ Î·È ÂÈÏÔΤ˜38. ™‹ÌÂÚ·, ÚÔÙÈÌÒÓÙ·È ÏÈÁfiÙÂÚÔ ÂÂÌ‚·ÙÈΤ˜, ·ÏÏ¿ ÙÔ ›‰ÈÔ ·ÍÈfiÈÛÙ˜ ̤ıÔ‰ÔÈ fiˆ˜ 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 ÂÈÏÔΤ˜ ·fi Ù· ¯ÔÏËÊfiÚ·, fiˆ˜ 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˜ Â› ÙÔȘ ÂηÙfi ÔÛÔÛÙÔ‡ ÙÔ˘ ۈ̷ÙÈÎÔ‡ ‚¿ÚÔ˘˜ ÙÔ˘ ÏËÙË (Graft Weight/Recipient Body Weight Ratio, GW/RBW), Î·È ÙÔ˘ Â› 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. AÂÈÎfiÓÈÛË 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˜ (ÂÈ‚¿Ú˘ÓÛË T1, Ì ηٷÛÙÔÏ‹ Ï›Ô˘˜ Î·È ¤Á¯˘ÛË ·Ú·Ì·ÁÓËÙÈ΋˜ Ô˘Û›·˜), ÛÙËÓ ÔÔ›· ·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· ÔÔ›· ˘ÔÏÔÁ›˙ÂÙ·È ÙÔ ÂÌ‚·‰fiÓ ÙÔ˘˜30. °. M·ÁÓËÙÈ΋ ÙÔÌÔÁÚ·Ê›· ÛÙÔ ‡„Ô˜ ÙÔ˘ ÛÙÂϤ¯Ô˘˜ Ù˘ ˘Ï·›·˜ ÊϤ‚·˜ (MPV) (ÂÈ‚¿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˜, ÂÈÙÚ¤Ô˘Ó ÙÔÓ ÚÔÛ‰ÈÔÚÈÛÌfi ÙˆÓ ÂÌ‚·‰ÒÓ ÙÔ˘˜30. ΔÔ ¿ıÚÔÈÛÌ· ÙˆÓ ÂÌ‚·‰ÒÓ ÙˆÓ ÙÔÌÒÓ Â› ÙÔ ¿¯Ô˜ Ù˘ οı ÙÔÌ‹˜ ÂÈÙÚ¤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, Â›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 ÂÂÌ‚·ÙÈ΋ Î·È ÌÔÚ› Ó· ·ÚÔ˘ÛÈ¿ÛÂÈ ÛÔ‚·Ú¤˜ ÂÈÏÔΤ˜, fiˆ˜ 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 ¯ÚËÛÈÌÔÔ›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 ¯ÚËÛÈÌÔÔ›ËÛ·Ó ÙȘ ‰È·ÎÏ·‰ÒÛÂȘ Ù˘ ˘Ï·›·˜ ÊϤ‚·˜.

‰fiÙ˜31. ∫·Ù¿ Û˘Ó¤ÂÈ·, Ë ÏÂÙÔÌÂÚ‹˜ ·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· ¯ÚËÛÈÌÔÔÈÔ‡ÌÂÓË Ì¤ıÔ‰Ô˜ ·ÂÈÎfiÓÈÛ˘ ÙˆÓ ¯ÔÏËÊfiÚˆÓ, ¤¯ÂÈ ¿ÚÈÛÙË ‰È·ÎÚÈÙÈ΋ ÈηÓfiÙËÙ· ·ÏÏ¿ ÚÔηÏ› ηı˘ÛÙ¤ÚËÛË ÛÙÔ ¯ÂÈÚÔ˘ÚÁÂ›Ô Î·È ‰ÂÓ ÂÈÙÚ¤ÂÈ ÙÔÓ ÚÔÂÁ¯ÂÈÚËÙÈÎfi ۯ‰ȷÛÌfi Ù˘ ÂÂÌ‚¿Ûˆ˜. ¶ÚÔÂÁ¯ÂÈÚËÙÈο, ÌÔÚ› Ó· ¯ÚËÛÈÌÔÔÈËı› Ë ÂÓ‰ÔÛÎÔÈ΋ ·Ï›Ó‰ÚÔÌË ¯ÔÏ·ÁÁÂÈÔ-·ÁÎÚ·ÙÔÁÚ·Ê›· (ERCP), Ë ÔÔ›· ¤¯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 ÌÔÚÔ‡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). ∂ÈϤÔÓ, Ë Î·ÙÂÚÁ·Û›· ÙˆÓ ·ÓˆÙ¤Úˆ ‰Â‰ÔÌ¤ÓˆÓ Ì ÙÔ ÏÔÁÈÛÌÈÎfi HepaVision (MeVis, Bremen, Germany) ÂÈÙÚ¤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 ÔÔ›· ·ÂÈÎÔÓ›˙ÂÙ·È ·ÓÙÈηٷÛÙ·ı›۷ ‰ÂÍÈ¿ Ë·ÙÈ΋ ·ÚÙËÚ›· ·fi ÙËÓ ¿Óˆ ÌÂÛÂÓÙ¤ÚÈÔ (Ï¢Îfi ‚¤ÏÔ˜). μ. ¶˘Ï·ÈÔÁÚ·Ê›· Ì ¤ÎÙÔË ¤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˜ (*ÂÈÚÔ‚ÔÏ‹ ÙˆÓ ¯ÔÏËÊfiÚˆÓ). ‰. ÃÔÏ·ÁÁÂÈÔÁÚ·Ê›· Ì Â΂ÔÏ‹ ÙÔ˘ ‰ÂÍÈÔ‡ ÔÈÛı›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˘ ÂÈ¤‰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‹ ÂÈÏÔÎÒÓ 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· ÂÈÙ¢¯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 ÚÔÛ¤Ï·ÛË Á›ÓÂÙ·È Ì ·ÌÊÔÙÂÚfiÏ¢ÚË ˘ÔχÚÈ· ÙÔÌ‹ Î·È Î¿ıÂÙË Â¤ÎÙ·ÛË Ù˘ ÚÔ˜ ÙÔ ÛÙ¤ÚÓÔ. AÎÔÏÔ˘ı› Ë ‰È·ÙÔÌ‹ ÙÔ˘ ÛÙÚÔÁÁ‡ÏÔ˘ Î·È ÙÔ˘ ‰ÚÂ·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 ÔÔ›· ÌÔÚ› Ó· ÚÔηϤÛÂÈ Î¿Ì„Ë ÙˆÓ Ë·ÙÈÎÒÓ ÊÏ‚ÒÓ Î·È Û˘ÌÊfiÚËÛË ÙÔ˘ ‹·ÙÔ˜. ∏ ÙÂÏÈ΋ ÂÈÏÔÁ‹ 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 ¯ÔÏÔÂÙÈÎÒÓ ·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 ÂÈÙ˘Á¯¿ÓÂÙ·È Î·Ï‡ÙÂÚÔ˜ ηıÔÚÈÛÌfi˜ ÙÔ˘ ÂÈ¤‰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 ϤÁÌ· 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 ÚÔÛ¤Ï·ÛË 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˜, Â› ¤Ó· ÏÂÙfi, ÚÔηÏ› ÈÛ¯·ÈÌ›· ÙÔ˘ ‰ÂÍÈÔ‡ ‹·ÙÔ˜ Î·È ÙËÓ ÂÌÊ¿ÓÈÛË ‰È·¯ˆÚÈÛÙÈ΋˜ ÁÚ·ÌÌ‹˜, Ë ÔÔ›· ˘Ô‚ÔËı¿ ÛÙÔÓ Î·ıÔÚÈÛÌfi ÙÔ˘ ÂÈ¤‰Ô˘ Ù˘ Ë·ÙÂÎÙÔÌ‹˜.

I‰È·›ÙÂÚË ÚÔÛÔ¯‹ ‰›ÓÂÙ·È ÛÙËÓ ·ÁÁ›ˆÛË ÙÔ˘ ÙÌ‹Ì·ÙÔ˜ IV ÙÔ ÔÔ›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 ÂÈ‚›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˜

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EÈÎfiÓ· 6.·. ¢ÈÂÁ¯ÂÈÚËÙÈ΋ ˘ÂÚ˯ÔÁÚ·ÊÈ΋ ÌÂϤÙË ÙÔ˘ ‹·ÙÔ˜ Ì ÙËÓ ÔÔ›· 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. AÂÈÎfiÓÈÛË Ù˘ ·ÎÔ˘ÛÙÈ΋˜ ÛÎÈ¿˜ ÙÔ˘ ÂÈ¤‰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 ÙÚfiÔ Á›ÓÂÙ·È Î·È Ë ·Ú·Û΢‹ ÙÔ˘ ‰ÂÍÈÔ‡ ÎÏ¿‰Ô˘ Ù˘ ˘Ï·›·˜ ÊϤ‚·˜ (EÈÎfiÓ· 8)52,53. ∏ ÎÈÓËÙÔÔ›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˘ ÔÈÛıÔË·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 ÔÔ›Ô˜ ÂÎÙ›ÓÂÙ·È ÌÂٷ͇ ÙÔ˘ ÔÈÛı›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˘ÌȤ˙ÂÈ ÙËÓ ‰ÂÍÈ¿ Ë·ÙÈ΋ ÊϤ‚· Î·È ÌÔÚ› Ó· ÚÔηϤÛÂÈ ÊÏ‚È΋ Û˘ÌÊfiÚËÛË ÙÔ˘ ÌÔۯ‡̷ÙÔ˜.

(EÈÎfiÓ· 9 ·-Á). ™ÙÔ 10% ÙˆÓ ‰ÔÙÒÓ ·Ó¢ڛÛÎÂÙ·È Ì›· ÂÈÎÔ˘ÚÈ΋ ‰ÂÍÈ¿ Ë·ÙÈ΋ ÊϤ‚·, Ì ‰È¿ÌÂÙÚÔ ÌÂÁ·Ï‡ÙÂ-

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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‚ÏÂfiÌÂÓÔ 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 ÔÔ›· ·ÚÔ¯ÂÙ‡ÂÈ ÙÔ Ô›ÛıÈÔ Î¿Ùˆ ÙÌ‹Ì· ÙÔ˘ ‰ÂÍÈÔ‡ ÏÔ‚Ô‡ ÚÔ˜ ÙËÓ ÔÈÛıÔË·ÙÈ΋ KKº. (EÈÎfiÓ· 9‰). TÔ ·ÁÁÂ›Ô ·˘Ùfi ÌÔÚ› Ó· Û˘ÓÂÈÛʤÚÂÈ ÛËÌ·ÓÙÈο ÛÙËÓ ÊÏ‚È΋ ·Ô¯¤Ù¢ÛË ÙÔ˘ ‰ÂÍÈÔ‡ ÏÔ‚Ô‡ Î·È Ë ·Ôϛӈۋ ÙÔ˘ ÌÔÚ› Ó· ÚÔηϤÛÂÈ ÊÏ‚È΋ Û˘ÌÊfiÚËÛË ÌÂÙ¿ ÙËÓ Â·ÓÂÌʇÙ¢ÛË. OÈ ÂÚÈÛÛfiÙÂÚÔÈ Û˘ÁÁÚ·Ê›˜ ·Ó·Ê¤ÚÔ˘Ó fiÙÈ fiÙ·Ó Ë ÂÈÎÔ˘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 ÔÔ›Ô ÌÔÚ› 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˘ ‰ÚÂ·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 ÌÔÚ› 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, fiˆ˜ 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˘ÌÂÚÈÏËÊı› 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, ÌÔÚ› 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 ÂÈ‚›ˆÛË ÙÔ˘ Ï‹ÙË56,57. Δ· Â˘Ú‹Ì·Ù· ·˘Ù¿ ÂȂ‚·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 ÌÔÚ› Ó· ·ÔÊ·ÛÈÛı› Ë ¤ÎÙ·ÛË Ù˘ ‰ÂÍÈ¿˜ Ë·ÙÂÎÙÔÌ‹˜, Ì ‹ ¯ˆÚ›˜ ÙË Ì¤ÛË Ë·ÙÈ΋ ÊϤ‚·, Ì ÈηÓÔÔÈËÙÈο ·ÔÙÂϤÛÌ·Ù· Î·È ÁÈ· ÙÔÓ ‰fiÙË Î·È ÁÈ· ÙÔÓ Ï‹ÙË. ∏ ÔÌ¿‰· ÙÔ˘ Essen ÂȂ‚·›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. ∂ÈϤÔÓ, ¤‰ÂÈÍ fiÙÈ Ì ÙËÓ «ÂÎ˘Ú‹ÓËÛË» (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¿ ÓÂÔÏ¿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 ÌÔÚ› 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·. Afi 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 ÔÔ›· ¿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 ÂÎϤÓÂÙ·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. ·. OÈÛı›· ÂÈÊ¿ÓÂÈ· ÙÔ˘ ‹·ÙÔ˜. O Û‡Ó‰ÂÛÌÔ˜ Ù˘ KKº ÂÎÙ›ÓÂÙ·È ÌÂٷ͇ ÙÔ˘ ÔÈÛı›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˘ ÔÈÛıÔË·ÙÈÎÔ‡ ÙÌ‹Ì·ÙÔ˜ Ù˘ KKº Î·È ÙËÓ ÛÙÚÔÊ‹ ÙÔ˘ ‹·ÙÔ˜ ÚÔ˜ Ù· ·ÚÈÛÙÂÚ¿, Ô Û‡Ó‰ÂÛÌÔ˜ Ù˘ KKº Û˘ÌȤ˙ÂÈ ÙËÓ ‰ÂÍÈ¿ Ë·ÙÈ΋ ÊϤ‚·. ‰. AÂÈÎÔÓ›˙ÂÙ·È Î·È Ë ‰ÂÍÈ¿ Ë·ÙÈ΋ ÊϤ‚·, fiˆ˜ Î·È ÔÈ ‚Ú·¯Â›Â˜ Ë·ÙÈΤ˜ ÊϤ‚˜ Î·È ÂÈÎÔ˘ÚÈ΋ ‰ÂÍÈ¿ Ë·ÙÈ΋ ÊϤ‚·.

Ì ‰ÈÔÏÈ΋ ‰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 ÂÈÊ·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 ÂÈÎÔ˘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˜ ÂÈÎÔ˘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 ÂÎϤÓÂÙ·È Ì ‰È¿Ï˘Ì· ÙÔ˘ ¶·ÓÂÈÛÙËÌ›Ô˘ ÙÔ˘ Wisconsin. AÎÔÏÔ˘ı› ÂÈÌÂÏ‹˜ ·ÈÌfiÛÙ·ÛË Ù˘ ÂÈÊ·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). AÔÁ˘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˜ ÂÈÎÔ˘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‡. TÔÔıÂÙÔ‡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˘ ÂÈÙ˘¯›·˜ ÛÙÔÓ Ï‹ÙË Î·È Ù˘ ·ÛÊ¿ÏÂÈ·˜ ÙÔ˘ ‰fiÙË ‹Ïı ÛÙÔ ÚÔÛ΋ÓÈÔ. ΔÔ ÔÛÔÛÙfi ÂÈÏÔÎÒÓ ÙÔ˘ ‰fiÙË Â›Ó·È ÂÚ›Ô˘ 20%, ·ÏÏ¿ Êı¿ÓÂÈ Ì¤¯ÚÈ ÙÔ 67% Û ̛· ·Ó·ÛÎfiËÛË63. ΔÔ Â‡ÚÔ˜ ·˘Ùfi ÈÛÙ‡ÂÙ·È fiÙÈ ı· ÌÂȈı› Ì ÙËÓ ÂÊ·ÚÌÔÁ‹ ÂÓfi˜ ÂÓÔÔÈË̤ÓÔ˘ Û˘ÛÙ‹Ì·ÙÔ˜ ·Ó·ÊÔÚ¿˜ ÙˆÓ ÌÂÙÂÁ¯ÂÈÚËÙÈÎÒÓ ÂÈÏÔÎÒÓ64. ∂ÈϤÔÓ,

64

π. ºOÀ∑∞™, ¢. Δ∞∫OÀ¢∞™

ÔÈΛÏÏÂÈ Î·È Ë ‚·Ú‡ÙËÙ· ÙˆÓ ·Ó·ÊÂÚÔÌ¤ÓˆÓ ÂÈÏÔÎÒÓ. ∏ ÏÂÈÔÓfiÙËÙ· ÙˆÓ ÂÈÏÔÎÒÓ ·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 ÔÔ›· ÌÂÈÒÓÂÙ·È Î·ıÒ˜ ·˘Í¿ÓÂÙ·È Ë ÂÌÂÈÚ›· ÙÔ˘ ÌÂÙ·ÌÔÛ¯Â˘ÙÈÎÔ‡ ΤÓÙÚÔ˘65.

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METAMO™XEY™Eπ™ 2008

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OÚÈ·ÎÔ› ‰fiÙ˜ ‹·ÙÔ˜ (¢fiÙ˜ Ì ‰È¢ڢṲ̂ӷ ÎÚÈÙ‹ÚÈ· ÂÈÏÔÁ‹˜) ¡. ∞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 Â͈Ë·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˘ ÌÔÚÔ‡Ó Ó· ÂËÚ¿ÛÔ˘Ó ÂÚÈÛÛfiÙÂÚÔ ÙËÓ ÂÌÊ¿ÓÈÛË ÚÒÈÌ˘ ‰˘ÛÏÂÈÙÔ˘ÚÁ›·˜ ‹ ·ÓÂ¿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 ÏÈ҉˘ ‰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·ÎÚÔÚfiıÂÛÌË ÂÈ‚›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›· ‹ ·ÓÂ¿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 ÌÔÚÔ‡Ó Ó· ¯ÚËÛÈÌÔÔÈËıÔ‡Ó Ì ηϿ ·ÔÙÂϤÛÌ·Ù·.3 ∏ Ù¿ÛË Ù˘ ¯ÚËÛÈÌÔÔ›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 ÌÔÚ› Ó· ¯ÚËÛÈÌÔÔÈËı› ˆ˜ ÔÚÈ·Îfi ÌfiÛ¯Â˘Ì· ·fi οÔÈÔ ¿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 ¯ÚËÛÈÌÔÔ›ËÛË ÂÓfi˜ Ë·ÙÈÎÔ‡ ÌÔۯ‡̷ÙÔ˜ ÏfiÁˆ ÙÔ˘ ·ÓÂ›ÙÚÂÙ· ·˘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 ϋÙË. Œ¯Ô˘Ó ·Ó·ÁÓˆÚÈÛÙ› οÔÈÔÈ ·Ú¿ÁÔÓÙ˜ Ô˘ ÌÔÚ› Ó· ¯·Ú·ÎÙËÚ›˙Ô˘Ó Î¿ÔÈÔÓ ‰fiÙË ˆ˜ ÔÚÈ·Îfi Î·È ·ÔÙÂÏÔ‡Ó ‰È¢ڢṲ̂ӷ ÎÚÈÙ‹ÚÈ· ÂÈÏÔÁ‹˜ ‰fiÙË: ËÏÈΛ· > 65 ¯ÚÔÓÒÓ, ·Ú·ÌÔÓ‹ ÛÙË ª.∂.£. ˘fi Ì˯·ÓÈÎfi ·ÂÚÈÛÌfi > 7 Ë̤Ú˜ (‹ > 4 Ë̤Ú˜ Û οÔȘ ÌÂϤÙ˜), ‰Â›ÎÙ˘ Ì¿˙·˜ ÛÒÌ·ÙÔ˜ > 30, ‚ÈÔ„›· Ì ÏÈÒ‰Ë ‰È‹ıËÛË ‹·ÙÔ˜ > 40%, ¡¿ÙÚÈÔ ·›Ì·ÙÔ˜ > 165 mmol/l, ÙÈ̤˜ Ë·ÙÈÎÒÓ ÂÓ˙‡ÌˆÓ SGOT (AST) Î·È SGPT (ALT) > ÙÚÈÏ¿ÛȘ ÙˆÓ Ê˘ÛÈÔÏÔÁÈÎÒÓ, ÔÏÈ΋ ¯ÔÏÂÚ˘ıÚ›ÓË > 3 mg/dl,

∏ÏÈΛ· ÙÔ˘ ‰fiÙË ¶·Ï·ÈfiÙÂÚ·, Ë ¯ÚËÛÈÌÔÔ›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΋˜ ·ÓÂ¿ÚÎÂÈ·˜ ÙÔ˘ ÌÔۯ‡̷ÙÔ˜.14 ™ÙËÓ Ú·ÁÌ·ÙÈÎfiÙËÙ· fï˜, Ù· ·ÔÙÂϤÛÌ·Ù· ÙˆÓ ÌÂÙ·ÌÔۯ‡ÛÂˆÓ ¯ÚËÛÈÌÔÔÈÒÓÙ·˜ ‰fiÙ˜ ÚÔ¯ˆÚË̤Ó˘ ËÏÈΛ·˜, Ô˘ ‰ÂÓ ¤¯Ô˘Ó ¿ÏÏÔ˘˜ ÂÈ‚·Ú˘ÓÙÈÎÔ‡˜ ·Ú¿ÁÔÓÙ˜, Ê¿ÓËÎ·Ó Ó· Â›Ó·È ›‰È· Ì ٷ ·ÔÙÂϤÛÌ·Ù· fiÙ·Ó ¯ÚËÛÈÌÔÔÈÔ‡ÓÙ·È Û¯ÂÙÈο Ó·ÚfiÙÂÚ˘ ËÏÈΛ·˜ ‰fiÙ˜. 15,16 ™‡Ìʈӷ Ì ٷ ‰Â‰Ô̤ӷ ÙÔ˘ UNOS, ÙÔ ·ÓÒÙÂÚÔ fiÚÈÔ ÙˆÓ و̷ÙÈÎÒÓ ‰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 و̷ÙÈÎÒÓ

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‰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 و̷ÙÈÎÒÓ Ë·ÙÈÎÒÓ ÌÂÙ·ÌÔۯ‡ÛÂˆÓ Î·È fiÙ·Ó ·Ô˘ÛÈ¿˙Ô˘Ó ¿ÏÏÔÈ ÂÈ‚·Ú˘ÓÙÈÎÔ› ·Ú¿ÁÔÓÙ˜ Ô Î›Ó‰˘ÓÔ˜ ·˘ÍË̤Ó˘ ıÓËÙfiÙËÙ·˜ ÂÏ·ÙÙÒÓÂÙ·È Û ÚÔÛÂÎÙÈο ÂÈÏÂÁ̤ÓÔ˘˜ Ï‹Ù˜.20 Δ· Û¯ÂÙÈο ηϿ ·ÔÙÂϤÛÌ·Ù· ·fi ÙË ¯ÚËÛÈÌÔÔ›ËÛË ÌÂÁ¿Ï˘ ËÏÈΛ·˜ Ë·ÙÈÎÒÓ ÌÔÛ¯Â˘Ì¿ÙˆÓ Èı·ÓÒ˜ Ó· ÔÊ›ÏÔÓÙ·È ÛÙȘ Â·ÚΛ˜ ÏÂÈÙÔ˘ÚÁÈΤ˜ Âʉڛ˜, ÛÙËÓ ·Ó·ÁÂÓÓËÙÈ΋ ÈηÓfiÙËÙ· Î·È ÛÙË ‰ÈÏ‹ ·ÈÌ¿ÙˆÛË ÙÔ˘ ‹·ÙÔ˜ Ù· ÔÔ›· ˘ÂÚηχÙÔ˘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 ÏÈÒ‰Ô˘˜ ‰È‹ıËÛ˘ ‹·ÙÔ˜. ¶Ú¤ÂÈ Ó· ‰›ÓÂÙ·È ÚÔÛÔ¯‹ ÛÙËÓ Èı·Ó‹ ‡·ÚÍË ·ıËÚÔÛÎÏËÚˆÙÈÎÒÓ ‚Ï·‚ÒÓ ÛÙ· ·ÁÁ›· ÙÔ˘ ÌÔۯ‡̷ÙÔ˜ ‰ÈfiÙÈ ÌÔÚ› Ó· Á›ÓÔ˘Ó ·ÈÙ›· ÛËÌ·ÓÙÈÎÒÓ ÌÂÙÂÁ¯ÂÈÚËÙÈÎÒÓ ÂÈÏÔÎÒÓ.16 ∂›Û˘, Ô Û˘Ó‰˘·ÛÌfi˜ ÌÂÁ¿Ï˘ ËÏÈΛ·˜ ‰fiÙË Î·È Ì¤ÙÚÈ·˜ ÚÔ˜ ‚·Ú›·˜ ÛÙ¿وÛ˘ ÂËÚ¿˙ÂÈ ‰˘ÛÌÂÓÒ˜ ÙËÓ ÂÈ‚›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 οÔÈ· ·‰È¿ÁÓˆÛÙË Î·ÎÔ‹ıÂÈ· Ô˘ ÌÔÚ› Ó· ÙË ÌÂÙ·‰ÒÛÔ˘Ó ÛÙÔÓ ·ÓÙ›ÛÙÔÈ¯Ô Ï‹ÙË. ™ÙÔ˘˜ Ï‹Ù˜ Ì Ë·Ù›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 ·ÓÂ¿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 ÂÈÏÔÁ‹ 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 ‰ÈÏ¿ÛÈ· ·‡ÍËÛË Ù˘ ‚·Ú‡ÙËÙ·˜ Ù˘ ‚Ï¿‚˘ Û˘ÓÙ‹ÚËÛ˘, ¤¯ÔÓÙ·˜ ˆ˜ ·ÔÙ¤ÏÂÛÌ· ÙËÓ ÂÈÏÂÁ̤ÓË 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 ÂÈ‚›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 ÂÈÚfiÛıÂÙÔ˘˜ ÂÈ‚·Ú˘ÓÙÈÎÔ‡˜ ·Ú¿ÁÔÓÙ˜ fiˆ˜ ÏÈ҉˘ ‰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 ÂÈ‚·Ú˘ÓÙÈÎfi ·Ú¿ÁÔÓÙ· ÌÔÚÔ‡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˘ÌÂÚ·›ÓÂÙ·È fiÙÈ ÌÔۯ‡̷ٷ ·fi Ù¤ÙÔÈÔ˘˜ ‰fiÙ˜ ÏÂÈÙÔ˘ÚÁÔ‡Ó ÈηÓÔÔÈËÙÈο, ¯ˆÚ›˜ Ó· ÚÔÛÙ›ıÂÙ·È ÛËÌ·ÓÙÈÎfi˜ ÂÈ‚·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˘ ·ÓÂ¿ÚÎÂÈ·˜ ÌÂÙ¿ ÙË ÌÂÙ·ÌfiÛ¯Â˘ÛË. ∏ Èı·ÓfiÙËÙ· ·ÓÂ¿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΋ Â›ÙˆÛË ÛÙËÓ ·Ú¯È΋ ÏÂÈÙÔ˘ÚÁ›· ÙÔ˘ ÌÔۯ‡̷ÙÔ˜. ŸÌˆ˜, Ë ‡·ÚÍË Ë fi¯È ÚfiÛıÂÙˆÓ ÂÈ‚·Ú˘ÓÙÈÎÒÓ ·Ú·ÁfiÓÙˆÓ (¯. ËÏÈΛ·, ÏÈ҉˘ ‰È‹ıËÛË) ηıÔÚ›˙ÂÈ ÙÂÏÈο ÙÔÓ ‚·ıÌfi Ù˘ Â›ÙˆÛ˘ Ù˘ ·Ú·ÙÂٷ̤Ó˘ ˘fiÙ·Û˘ ÛÙË ÌÂÙÂÁ¯ÂÈÚËÙÈ΋ ÏÂÈÙÔ˘ÚÁ›· ÙÔ˘ ÌÔۯ‡̷ÙÔ˜.36

§È҉˘ ‰È‹ıËÛË (ÛÙ¿وÛË) ΔÔ 13%-26% ÙˆÓ ‰ÔÙÒÓ ¤¯Ô˘Ó ÏÈÒ‰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 ÂÈÙÒÛÂȘ ÙÔ˘ ÂÁÎÂÊ·ÏÈÎÔ‡ ı·Ó¿ÙÔ˘. ¢‡Ô ÈÛÙÔÏÔÁÈÎÔ› Ù‡ÔÈ ÏÈÒ‰Ô˘˜ ‰È‹ıËÛ˘ ÂÚÈÁÚ¿ÊÔÓÙ·È: Ë ÌÈÎÚÔÊ˘ÛÛ·Ïȉ҉˘, Î·È Ë ÌÂÁ·ÏÔÊ˘ÛÛ·Ïȉ҉˘. ∏ ÔÛÔÙÈ΋ ·ÍÈÔÏfiÁËÛË ÙÔ˘ ‚·ıÌÔ‡ Ù˘ ÏÈÒ‰Ô˘˜ ‰È‹ıËÛ˘ ‚·Û›˙ÂÙ·È ÛÙÔ ÔÛÔÛÙfi ÙˆÓ Ë·ÙÔ΢ÙÙ¿ÚˆÓ Ô˘ ·ÚÔ˘ÛÈ¿˙Ô˘Ó ÂÓ‰Ô΢ÙÙ·ÚÔÏ·ÛÌ·ÙÈΤ˜ Ê˘ÛÛ·Ï›‰Â˜ Ï›Ô˘˜. ∏ ‡·ÚÍË ÌÈÎÚÔÊ˘ÛÛ·ÏÈ‰Ò‰Ô˘˜ ÏÈÒ‰Ô˘˜ ‰È‹ıËÛ˘ Ê·›ÓÂÙ·È Ó· ÌËÓ ÂËÚ¿˙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 ÏÈÒ‰Ë ‰È‹ıËÛË (< 30% ÙˆÓ Ë·ÙÔ΢ÙÙ¿ÚˆÓ) ÌÔÚÔ‡Ó Ó· ¯ÚËÛÈÌÔÔÈËıÔ‡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›˜ ÏÈÒ‰Ë ‰È‹ıËÛË.40 Δ· Ë·ÙÈο ÌÔۯ‡̷ٷ Ì ¤ÓÙÔÓË ÏÈÒ‰Ë ‰È‹ıËÛË (> 60% ÙˆÓ Ë·ÙÔ΢ÙÙ¿ÚˆÓ) ¤¯Ô˘Ó ÛËÌ·ÓÙÈο ·˘ÍË̤ÓÔ Î›Ó‰˘ÓÔ Ó· ·ÚÔ˘ÛÈ¿ÛÔ˘Ó ·ÓÂ¿ÚÎÂÈ· ÏÂÈÙÔ˘ÚÁÈÎfiÙËÙ·˜ ÌÂÙ¿ ÙË ÌÂÙ·ÌfiÛ¯Â˘ÛË Î·È ‰ÂÓ Ú¤ÂÈ Ó· ¯ÚËÛÈÌÔÔÈÔ‡ÓÙ·È.41 ∏ ¯ÚËÛÈÌÔÔ›ËÛË Ë·ÙÈÎÒÓ ÌÔÛ¯Â˘Ì¿ÙˆÓ Ì ̤ÙÚÈÔ˘ ‚·ıÌÔ‡ ÏÈÒ‰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˘ ·ÓÂ¿ÚÎÂÈ·˜ (13% ¤Ó·ÓÙÈ ÙÔ˘ 3% ÁÈ· Ù· Ê˘ÛÈÔÏÔÁÈο ÌÔۯ‡̷ٷ).40 ∂›Ó·È ·Ô‰ÂÎÙfi fiÙÈ Ù· ÌÔۯ‡̷ٷ Ì ̤ÙÚÈÔ˘ ‚·ıÌÔ‡ ÏÈÒ‰Ë ‰È‹ıËÛË Â›Ó·È ÚÔÙÈÌfiÙÂÚÔ Ó· ¯ÚËÛÈÌÔÔÈÔ‡ÓÙ·È fiÙ·Ó ‰ÂÓ ˘¿Ú¯Ô˘Ó ¿ÏÏÔÈ ÂÈÚfiÛıÂÙÔÈ ÂÈ‚·Ú˘ÓÙÈÎÔ› ·Ú¿ÁÔÓÙ˜ ÎÈÓ‰‡ÓÔ˘ ÛÙÔÓ ‰fiÙË ·ÏÏ¿ Î·È ÛÙÔÓ Ï‹ÙË.

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∏·Ù›Ùȉ· μ Î·È C ™ÙÔ ·ÚÂÏıfiÓ ‰ÂÓ ‹Ù·Ó ·Ô‰ÂÎÙ‹ Ë ÂÈÏÔÁ‹ ‰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 ÂÈÊ·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 ϋÙ˜ 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˘ ÂÈÊ·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 ÂËÚ¿˙ÂÈ ÙËÓ ÂÈ‚›ˆÛË ÙÔ˘ ÌÔۯ‡̷ÙÔ˜ ‹ ÙÔ˘ Ï‹ÙË, ·ÏÏ¿ ·˘Í¿ÓÂÙ·È Ë Èı·ÓfiÙËÙ· ηٿ 2,5 ÊÔÚ¤˜ Ó· ˘ÔÙÚÔÈ¿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΋ ıÂÚ·›· Ì ·ÓÔÛÔÛÊ·ÈÚ›ÓË Ë·Ù›Ùȉ·˜ μ (HBIG) Î·È lamivudine.45 ªÔۯ‡̷ٷ ·fi ‰fiÙ˜ HBc(+) Ú¤ÂÈ ÂÈÏÂÎÙÈο Ó· ‰›ÓÔÓÙ·È Û HbsAg(+) Ï‹Ù˜, ·ÊÔ‡ Ô‡Ùˆ˜ ‹ ¿Ïψ˜ ÙÔ˘˜ ¯ÔÚËÁÂ›Ù·È ‰È· ‚›Ô˘ HBIG. ø˜ ‰Â‡ÙÂÚË ÂÈÏÔÁ‹, ·˘Ù¿ Ù· ÌÔۯ‡̷ٷ Ú¤ÂÈ Ó· ‰›ÓÔÓÙ·È Û anti-HBs(+) Ï‹Ù˜, ÛÙÔ˘˜ ÔÔ›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 ϋÙË 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· ÂËÚ¿˙ÂÈ ÙËÓ ÂÈ‚›ˆÛË ÙÔ˘ ÌÔۯ‡̷ÙÔ˜ ‹ ÙÔ˘ Ï‹ÙË. ∞ÚÎÂÙ¤˜ ÌÂϤÙ˜ ¤‰ÂÈÍ·Ó fiÙÈ Ë ÂÈ‚›ˆÛË ÙˆÓ ·ÛıÂÓÒÓ Ì ÌÔۯ‡̷ٷ ·fi HCV(+) ‰fiÙ˜ Â›Ó·È ›‰È·, Î·È Î¿ÔȘ ÊÔÚ¤˜ ηχÙÂÚË, ·fi ÙËÓ ÂÈ‚›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¿ ·ÓÂ¿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 ¯ÚËÛÈÌÔÔ›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 ÂÈÏÔÁ‹˜ ‰fiÙË. ŸÌˆ˜, Ô ¯·ÌËÏ‹˜ ηÎÔ‹ıÂÈ·˜ ηÚΛÓÔ˜ ÙÔ˘ ‰¤ÚÌ·ÙÔ˜, fiˆ˜ 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 ÂÈÏÔÁ‹ οÔÈÔ˘ ‰fiÙË.53,54 ŸÛÔ ·Ó·ÊÔÚ¿ ÙÔ˘˜ ÂÁÎÂÊ·ÏÈÎÔ‡˜ fiÁÎÔ˘˜, οÔÈÔÈ ÈÛÙÔÏÔÁÈÎÔ› Ù‡ÔÈ, fiˆ˜ 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 ıÂÚ·¢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 ÓÂÔÏ·Û›·˜ Û˘Ì·ÁÔ‡˜ ÔÚÁ¿ÓÔ˘, Ú¤ÂÈ Ó· Ï·Ì‚¿ÓÂÙ·È ˘fi„Ë Ë ‚ÈÔÏÔÁÈ΋ Û˘ÌÂÚÈÊÔÚ¿ ÙÔ˘ Û˘ÁÎÂÎÚÈ̤ÓÔ˘ Ù‡Ô˘ Ù˘ ÓÂÔÏ·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 ÂÈÏÔÁ‹˜ ‰fiÙË ÂÂȉ‹ ·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

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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. Ÿˆ˜ ‹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 ϋÙ˜ anti-HBc (+) ÌÔÛ¯Â˘Ì¿ÙˆÓ ÌÔÚ› 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˘˜ ÙÚfiÔ˘˜ ·‡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˘ ÌÔÚ› Ó· Ô‰ËÁ‹ÛÂÈ Û ÔÚÈṲ̂Ó˜ ÂÚÈÙÒÛÂȘ Û ÛÔ‚·Ú‹ ÂÓÂÚÁÔÔ›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 ÔÔ›· 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 ÌÔÚÔ‡Ó Ó· ÌÂÙ·‰ÒÛÔ˘Ó ÙË Ïԛ̈ÍË4. O ΛӉ˘ÓÔ˜ ·˘Í¿ÓÂÈ ·Ó¿ÏÔÁ· Ì ÙÔÓ ÂÈÔÏ·ÛÌfi Ù˘ Ë·Ù›Ùȉ·˜ μ ÛÙÔÓ ·ÓÙ›ÛÙÔÈ¯Ô ÁÂÓÈÎfi ÏËı˘ÛÌfi. Oˆ˜ Â›Ó·È ·Ó·ÌÂÓfiÌÂÓÔ ·˘Ùfi Û˘Ì‚·›ÓÂÈ Û ˘ËÏfiÙÂÚ· ÔÛÔÛÙ¿ ÛÙȘ ¯ÒÚ˜ Ù˘ ∞Û›·˜ Û ۇÁÎÚÈÛË Ì ∂˘ÚÒË – 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 ÔÔ›· ·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 Â·Ê‹ Ì ÙÔÓ Èfi Ù˘ Ë·Ù›Ùȉ·˜ μ ÌÔÚ› Ó· ¤¯Ô˘Ó ÂÈÙ‡¯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 ÂÈÙÒÛÂȘ 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˜ fiÔ˘ 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

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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· ÂÈı˘ÌËÙ¿ Â›‰· 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 ÂÚÈÙÒÛÂˆÓ 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˜ ÂÓÂÚÁÔÔ›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 ·ÓÙÈÚÚÔÔ‡ÌÂÓË ∏μV ΛÚÚˆÛË ‹ ÎÂÚ·˘ÓÔ‚fiÏÔ HBV Ïԛ̈ÍË ·ÔÙÂÏ› ÌÈ· ÏÔÁÈ΋ ÚÒÙË ÂÈÏÔÁ‹, ηıÒ˜ ¤¯ÂÈ ‰Âȯı› fiÙÈ Ì ÙÔÓ ÙÚfiÔ ·˘Ùfi ‰ÂÓ ÂËÚ¿˙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 ÔÔ›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· ÌÔÚÔ‡Û ӷ ÚÔÛÊÂÚı› Û ϋÙË ¯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˜ ÌÔÓÔıÂÚ·›· ‹ Û ıÂÚ·›· Û˘Ó‰˘·ÛÌÔ‡ Ì ·ÓÔÛÔÛÊ·ÈÚ›ÓË ¤Ó·ÓÙÈ Ë·Ù›Ùȉ·˜ μ (HBIg), fiˆ˜ ı· ·Ó·Ï˘ı› ÛÙË Û˘Ó¤¯ÂÈ·.

¶ÚÔʇϷÍË ¤Ó·ÓÙÈ ·Ó·˙ˆ‡ÚˆÛ˘ HBV Ïԛ̈͢ OÈ ÛÙÚ·ÙËÁÈΤ˜ Ô˘ ¯ÚËÛÈÌÔÔÈÔ‡ÓÙ·È ÛÙËÓ ÚÔʇϷÍË ·fi ÙËÓ ˘ÔÙÚÔ‹ Ù˘ HBV Ïԛ̈͢ ÛÙÔ ÌfiÛ¯Â˘Ì· ¤¯Ô˘Ó ¯ÚËÛÈÌÔÔÈËı› Î·È ÛÙËÓ ÚÔʇϷÍË ·Ó·˙ˆ‡ÚˆÛ˘ HBV Ïԛ̈͢ Û ϋÙ˜ 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 ÙÚfiÔ ·˘Ùfi οÔÈÔÈ ·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 ¯ÚËÛÈÌÔÔÈËı› Â›Ó·È ÔÈ ·ÎfiÏÔ˘ı˜: ¯ÔÚ‹ÁËÛË ÌÔÓÔÚÔʇϷ͢ Ì HBIg, Û˘Ó‰˘·ÛÌfi˜ HBIg Î·È Ï·ÌÈ‚Ô˘‰›Ó˘, ¯ÔÚ‹ÁËÛË ÌÔÓÔÚÔʇϷ͢ 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. ∏ ÌÔÓÔÚÔʇϷÍË 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 ÌÔÓÔÚÔʇϷ͢ 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˘˜ ÔÔ›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˘ fiˆ˜ 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˘ fiˆ˜ 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΋ ·ÓÔÛÔÔ›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· ıÂÚ·›·˜ Ì ϷÌÈ‚Ô˘‰›ÓË13. H ÛÙÚ·ÙËÁÈ΋ ·˘Ù‹ ¤¯ÂÈ ÂÊ·ÚÌÔÛı› ÂÈÙ˘¯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· ÂÈϤÔÓ Ì¤ÙÚÔ Ô˘ ÌÔÚ› 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 ÂÈ‚›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›˜ ÂÈϤ¯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 ÂÈ‚›ˆÛË ·ÛıÂÓÔ‡˜, ÌÔۯ‡̷ÙÔ˜ ηıÒ˜ Î·È ÛÙËÓ ÂÈ‚›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¿ıËΠ۠ÚfiÛÊ·ÙË ÌÂϤÙË ÙˆÓ Khapra Î·È Û˘Ó16. OÈ Û˘ÁÁÚ·Ê›˜ ‰ÂÓ ‰È·›ÛÙˆÛ·Ó ‰È·ÊÔÚ¿ ÛÙËÓ Û˘ÓÔÏÈ΋ ÂÈ‚›ˆÛË ÌÂٷ͇ ·ÛıÂÓÒÓ Ô˘ ¤Ï·‚·Ó anti-HCV (+) ÌfiÛ¯Â˘Ì· Î·È ·ÛıÂÓÒÓ Ô˘ ¤Ï·‚·Ó anti-HCV (–) ÌfiÛ¯Â˘Ì·, fiˆ˜ ¤¯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 Â›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 ÂËÚ¿˙ÂÈ ÙÔ Ú˘ıÌfi ÚfiÔ‰Ô˘ Ù˘ ›ÓˆÛ˘ ÌÂÙ¿ ÙË ÌÂÙ·ÌfiÛ¯Â˘ÛË.

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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 ÂÈ‚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 ÂÂÈÛÔ‰›Ô˘ ·ÈÌÔÚÚ·Á›·˜ ÎÈÚÛÒÓ ¤¯ÂÈ Û‹ÌÂÚ· ÌÈÎÚfiÙÂÚÔ ·ÓÙ›ÎÙ˘Ô ÏfiÁˆ Ù˘ ·Ó¿Ù˘Í˘ Ôχ ·ÔÙÂÏÂÛÌ·ÙÈÎÒÓ ÙÚfiˆÓ ·ÓÙÈÌÂÙÒÈÛ˘ ·˘ÙÒÓ.

∏ ÌÂÙ·ÌfiÛ¯Â˘ÛË ‹·ÙÔ˜ ·ÔÙÂÏ› ÙËÓ ÌÔÓ·‰È΋ ÂÈÏÔÁ‹ ÁÈ· ÙËÓ ·Ó·ÛÙÚÔÊ‹ Ù˘ Ë·ÙÈ΋˜ ·ÓÂ¿ÚÎÂÈ·˜ Î·È ÙËÓ ·ÓÙÈÌÂÙÒÈÛË ÙˆÓ ÂÈÏÔÎÒÓ ÛÙÔ˘˜ ·ÛıÂÓ›˜ Ì ΛÚÚˆÛË ÙÂÏÈÎÔ‡ ÛÙ·‰›Ô˘. ∞Ó Î·È Ë ÌÂÙ·ÌfiÛ¯Â˘ÛË ‹·ÙÔ˜ ·ÔÙÂÏ› Ì›· ÂÈ‚·Ú˘ÓÙÈ΋ Î·È ··ÈÙËÙÈ΋ Â¤Ì‚·ÛË, ÔÈ ·ÛıÂÓ›˜ ÌÔÚÔ‡Ó Û˘Ó‹ıˆ˜ Ó· ÂÈÛÙÚ¤„Ô˘Ó ÛÙË Ê˘ÛÈÔÏÔÁÈ΋ ‹ ۯ‰fiÓ Ê˘ÛÈÔÏÔÁÈ΋ ˙ˆ‹ ̤۷ Û 3-6 Ì‹Ó˜. ¢˘ÛÙ˘¯Ò˜ ÏfiÁˆ Ù˘ ÌÂÁ¿Ï˘ ·ÓÂ¿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 ÂÈÏÔÁ‹ ÙˆÓ ÏËÙÒÓ Î·È ÙËÓ Î·Ù·ÓÔÌ‹ ÙˆÓ ÌÔÛ¯Â˘Ì¿ÙˆÓ. ™‹ÌÂÚ· Ë Î·Ù·ÓÔÌ‹ ÙˆÓ و̷ÙÈÎÒÓ 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 ÔÔ›ˆÓ Ë ·Ó·ÌÂÓfiÌÂÓË ÂÈ‚›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 fiˆ˜ Â›Û˘ Î·È ·ÛıÂÓ›˜ ÙˆÓ ÔÔ›ˆÓ Ë ÓfiÛÔ˜ ·Ó·Ì¤ÓÂÙ·È Ó· ˘ÔÙÚÔÈ¿ÛÂÈ ¿ÌÂÛ· Î·È ÂÈÙ·¯˘ÓfiÌÂÓ·, ›Ûˆ˜ ‰ÂÓ ı· ¤ÚÂ ӷ Û˘ÌÂÚÈÏ·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΋ ∂˘ÚÒË 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 ÂÈÏÂÁ̤ÓÔÈ ·ÛıÂÓ›˜ Ì ·ÏÎÔÔÏÈ΋ ÓfiÛÔ ‹·ÙÔ˜ (alcoholic liver disease, ALD) ¤¯Ô˘Ó ·ÚfiÌÔÈ· ÂÈ‚›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 ÂÈ‚›ˆÛË 1 ¯ÚfiÓÔ˘ Ó· ÍÂÂÚÓ¿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˜. ÀÔÏÔÁ›˙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΋ ıÂÚ·›· ¯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-·ÓÙÈÚÚfiËÛË 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˘ ÂÈ‚›ˆÛ˘. OÈ ·ÛıÂÓ›˜ Ô˘ ˘fiÎÂÈÓÙ·È ÛÙȘ ·Ú·¿Óˆ ÂÈÏÔΤ˜ ¤¯Ô˘Ó 20-50% ÌÂȈ̤ÓÔ ÚÔÛ‰fiÎÈÌÔ ÂÈ‚›ˆÛ˘ Û ۯ¤ÛË Ì ·˘ÙÔ‡˜ Ì ·ÓÙÈÚÚÔÔ‡ÌÂÓË Î›ÚÚˆÛË ·ÓÂÍ¿ÚÙËÙ· Ù˘ ‡·Ú͢

77

78

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ÌÂÙ·ÌfiÛ¯Â˘ÛË. ∂ÈϤÔÓ ·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-·ÓÙÈÚÚÔÔ‡ÌÂÓË Î›ÚÚˆÛË ÏfiÁˆ XHC ˘ÂÚ¤¯ÂÈ Ù˘ Û˘ÓÙËÚËÙÈ΋˜ ıÂÚ·›·˜.

∫›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 ·ÓÂ¿ÚÎÂÈ· ÙÔ˘ ÌÔۯ‡̷ÙÔ˜ ̤۷ Û ̋Ó˜ ¯ˆÚ›˜ ÚÒÈÌË ·ÓÙÈÈ΋ ıÂÚ·›·. ∏ ¯Ú‹ÛË ·ÓÙÈÈÎÒÓ Ê·ÚÌ¿ÎˆÓ fiˆ˜ Â›Ó·È Ë lamivudine, ÙÔ adefovir dipivoxil ¤¯ÂÈ Ô‰ËÁ‹ÛÂÈ Û Ì›ˆÛË ÙˆÓ ˘ÔÙÚÔÒÓ 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-·ÓÙÈÚÚÔÔ‡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 ÂÈ‚›ˆÛË Î·È ·Ó Ë ¯ÔÚ‹ÁËÛË ÙÔ˘ ·Ú¯›ÛÂÈ ÚÒÈÌ· ÌÔÚ› 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-·ÓÙÈÚÚÔÔ‡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-·ÓÙÈÚÚÔÔ‡ÌÂÓË Î›ÚÚˆÛË.

∏¶∞ΔO∫ÀΔΔ∞ƒπ∫O™ ∫∞ƒ∫π¡O™ (HCC) O Û˘ÛÙËÌ·ÙÈÎfi˜ ¤ÏÂÁ¯Ô˜ ÁÈ· HCC ¯ÚËÛÈÌÔÔÈÒÓÙ·˜ ÙÔ˘˜ ˘ÂÚ‹¯Ô˘˜ Î·È ÙËÓ aFP ÂÊ·ÚÌfi˙ÂÙ·È Â˘Ú¤ˆ˜ Ì ·ÔÙ¤ÏÂÛÌ· ÙËÓ ÚÒÈÌË ÂÓÙfiÈÛË HCC. ∏ ·ÓÙÈÌÂÙÒÈÛË ÙˆÓ HCC fiÁÎˆÓ ÛÙÔ˘˜ ·ÛıÂÓ›˜ Ì ·ÓÙÈÚÚÔÔ‡ÌÂÓË Î›ÚÚˆÛË ÂÚÈÏ·Ì‚¿ÓÂÈ ÔÏϤ˜ ÂÈÏÔÁ¤˜ fiˆ˜ 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‹ ÂÈ‚›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‹ ÂÈ‚›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·‰ÈÔÔ›ËÛË (downstaging) ÙˆÓ ·ÛıÂÓÒÓ Î·È ÙˆÓ fiÁÎˆÓ ÙÔ˘˜ (downsizing) ¯ÚËÛÈÌÔÔÈÂ›Ù·È ÁÈ· Â·Ó·ÊÔÚ¿ 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΋ ∞ÓÂ¿ÚÎÂÈ· ∏ ÔÍ›· ÓÂÊÚÈ΋ ·ÓÂ¿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΋ ∞ÓÂ¿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΋˜ Â¤Ì‚·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΋˜ ·ÓÂ¿ÚÎÂÈ·˜ Ô˘ ÂÈϤÎÂÈ ÚÔ¯ˆÚË̤ÓË ÓfiÛÔ ÙÔ˘ ‹·ÙÔ˜, Ë·ÙÈ΋ ·ÓÂ¿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˘ ÛÏ·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 ÔÔ›Ô ¯·Ú·ÎÙËÚ›˙ÂÙ·È ·fi Ì›· Ù·¯¤ˆ˜ ÂÍÂÏÈÛÛfiÌÂÓË Ì›ˆÛË Ù˘ ÓÂÊÚÈ΋˜ ÏÂÈÙÔ˘ÚÁ›·˜, Ë ÔÔ›· ÔÚ›˙ÂÙ·È Â›Ù Ì ÙÔÓ ‰ÈÏ·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΋ Â¤Ì‚·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¡∂™ ∏·ÙÔÓ¢ÌÔÓÈÎfi ™‡Ó‰ÚÔÌÔ ΔÔ Ë·ÙÔÓ¢ÌÔÓÈÎfi Û‡Ó‰ÚÔÌÔ Â›Ó·È Ì›· Û¿ÓÈ· ηٿÛÙ·ÛË Ë ÔÔ›· ¯·Ú·ÎÙËÚ›˙ÂÙ·È ·fi ÙËÓ ÂÌÊ¿ÓÈÛË ‚·ÚÈ¿˜ ˘ÔÍ·ÈÌ›·˜ Û·Ó ·ÔÙ¤ÏÂÛÌ· ÙˆÓ ‰È¿¯˘ÙˆÓ ÂÓ‰ÔÓ¢ÌÔÓÈÎÒÓ ·ÁÁÂÈ·ÎÒÓ shunt. ΔÔ Ë·ÙÔÓ¢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‰ÔÓ¢ÌÔÓÈ΋˜ ·ÁÁÂÈԉȷÛÙÔÏ‹˜. ∏ ·ÓÙÈÌÂÙÒÈÛË Á›ÓÂÙ·È Ì ÙËÓ ¯ÔÚ‹ÁËÛË Ô͢ÁfiÓÔ˘ Î·È ‰ÂÓ ˘¿Ú¯ÂÈ Î¿ÔÈ· ÂȉÈ΋ ·ÓÙÈÌÂÙÒÈÛË. ∏ ÌÂÙ·ÌfiÛ¯Â˘ÛË ‹·ÙÔ˜ ·Ó·ÛÙÚ¤ÊÂÈ ÙËÓ ÂÓ‰ÔÓ¢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·ÙÔÓ¢ÌÔÓÈÎÔ‡ Û˘Ó‰ÚfiÌÔ˘ ‰ÂÓ ·ÔÙÂÏ› ·ÓÙ¤Ó‰ÂÈÍË ÁÈ· ÌÂÙ·ÌfiÛ¯Â˘ÛË ‹·ÙÔ˜ Û ·ÛıÂÓ›˜ Ì ÌË-·ÓÙÈÚÔÔ‡ÌÂÓÔ ·ÛΛÙË.

79

¶˘Ï·ÈÔÓ¢ÌÔÓÈ΋ À¤ÚÙ·ÛË ∏ ˘Ï·ÈÔÓ¢ÌÔÓÈ΋ ˘¤ÚÙ·ÛË ·ÔÙÂÏ› ¤Ó· ·ÚÎÂÙ¿ ·Û˘Ó‹ıÈÛÙÔ Û‡Ó‰ÚÔÌÔ ÙÔ ÔÔ›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·ÈÔÓ¢ÌÔÓÈ΋ ˘¤ÚÙ·ÛË ·ÔÙÂÏ› ·Ú¿ÁÔÓÙ· Ôχ ˘„ËÏÔ‡ ÎÈÓ‰‡ÓÔ˘ Î·È ÔÈ ÂÚÈÛÛfiÙÂÚÔÈ ·ÛıÂÓ›˜ Âı·›ÓÔ˘Ó ·fi οډÈÔ-΢ÎÏÔÊÔÚÈΤ˜ ÂÈÏÔΤ˜ ·ÓÙ› ·fi ÂÈÏÔΤ˜ Ù˘ ΛÚÚˆÛ˘. ∏ ¯Ú‹ÛË Û˘Ó¯ԇ˜ ÂÓ‰ÔÊϤ‚È·˜ ¯ÔÚ‹ÁËÛ˘ ÂÓfi˜ ·Ó¿ÏÔÁÔ˘ Ù˘ ÚÔÛÙ·Î˘ÎÏ›Ó˘, Ù˘ ÂÔÚÔÛÙÂÓfiÏ˘, ÌÂÈÒÓÂÈ ÙËÓ Ó¢ÌÔÓÈ΋ ˘¤ÚÙ·ÛË ÛÙȘ ÂÚÈÛÛfiÙÂÚ˜ ÂÚÈÙÒÛÂȘ. OÈ ÂӉ›ÍÂȘ ÁÈ· ÌÂÙ·ÌfiÛ¯Â˘ÛË ‹·ÙÔ˜ ‰ÂÓ Â›Ó·È ÍÂοı·Ú˜ ÛÙËÓ ‡·ÚÍË ˘Ï·ÈÔÓ¢ÌÔÓÈ΋˜ ˘¤ÚÙ·Û˘ ÁÈ·Ù› ·ÔÙÂÏ› ÈÛ¯˘Úfi ·Ú¿ÁÔÓÙ· ÎÈÓ‰‡ÓÔ˘ ȉ›ˆ˜ fiÙ·Ó Ë Ì¤ÛË ·ÚÙËÚȷ΋ ›ÂÛË ÍÂÂÚÓ¿ 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‡ ÎfiÏÔ˘ Î·È ˘ÂÚÙÚÔÊ›· Ù˘ ·ÚÈÛÙÂÚ¿˜ ÎÔÈÏ›·˜. O ‰ÂÍÈfi˜ ÎfiÏÔ˜ Î·È Ë ‰ÂÍÈ¿ ÎÔÈÏ›· ¤¯Ô˘Ó Û˘Ó‹ıˆ˜ Ê˘ÛÈÔÏÔÁÈΤ˜ ‰È·ÛÙ¿ÛÂȘ Î·È ¿¯Ô˜ ÙÔȯÒÌ·ÙÔ˜ Û ·Ô˘Û›· ˘Ï·ÈÔÓ¢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 ÌÔÚÔ‡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‡ ÎfiÏÔ˘.

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 ·ÓÂ·Ú΋˜ Û˘ÌÌfiÚʈÛË, ·ÓÂ·Ú΋ ΛÓËÙÚ· Î·È ‚·Ú›˜ Â͈Ë·ÙÈΤ˜ Û˘Ó˘¿Ú¯Ô˘Û˜ ·ı‹ÛÂȘ. ∞fi ÙȘ ÈÔ ÛËÌ·ÓÙÈΤ˜ Â›Ó·È Ë ¯ÚfiÓÈ· ·ÔÊÚ·ÎÙÈ΋ ÓfiÛÔ˜, ÈÛÙÔÚÈÎfi Â͈Ë·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). ∂ÈϤÔÓ, 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 ÏÔÈfiÓ 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·ÙÔÔÈ‹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˘ ÂÈ‚›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 ıÂÚ·›· 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 ÛÔÚ·‰ÈΤ˜ Ì·ÎÚfi¯ÚÔÓ˜ ÂÈ‚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˜ ÂÚÈÙÒÛÂȘ ·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 ÂÌÂÈÚ›· 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 ıÂÚ·›· ÙÔ˘ ∏∫∫3. ΔÂÏÈο, ÙÔ 1989, ÙÔ ÀÔ˘ÚÁÂ›Ô ÀÁ›·˜ ÙˆÓ ∏¶∞ (Department of Health and Human Services) ·ÔÊ¿ÓıËΠˆ˜ Ë ‡·ÚÍË ∏∫∫ ·ÔÙÂÏÔ‡Û ·fiÏ˘ÙË ·ÓÙ¤Ó‰ÂÈÍË ÁÈ· ÙËÓ Ú·ÁÌ·ÙÔÔ›ËÛË Ë·ÙÈ΋˜ ÌÂÙ·ÌfiÛ¯Â˘Û˘. ™ÙÔ Ù¤ÏÔ˜ Ù˘ ‰ÂηÂÙ›·˜ ÙÔ˘ 1990 Â·Ó‹ÏıÂ Ô ÂÓıÔ˘ÛÈ·ÛÌfi˜ ÁÈ· ÙË ¯Ú‹ÛË Ù˘ Ë·ÙÈ΋˜ ÌÂÙ·ÌfiÛ¯Â˘Û˘ ˆ˜ ̤ÛÔ ıÂÚ·›·˜ ÙÔ˘ ∏∫∫, ηıÒ˜ ·ԉ›¯ıËΠfiÙÈ ‹Ù·Ó ‰˘Ó·Ù‹ Ë Â›Ù¢ÍË ÂÍ·ÈÚÂÙÈÎÒÓ ÂÈ‚ÈÒÛˆÓ, ·ÚΛ Ó· ÂÈϤÁÔÓÙ·Ó Î·Ù¿ÏÏËÏ· ÔÈ Ï‹Ù˜4. ™ÙÔ ÌÂٷ͇ ›¯Â ·Ó·Ù˘¯ı› Ï‹ıÔ˜ ıÂÚ·¢ÙÈÎÒÓ ·ÚÂÌ‚¿ÛÂˆÓ Ì ÙË ‚Ô‹ıÂÈ· ÙˆÓ ÔÔ›ˆÓ ·˘Í¿ÓÔÓÙ·Ó ÙÔ ÚÔÛ‰fiÎÈÌÔ ÂÈ‚›ˆÛ˘ (Î·È ÂÔ̤ӈ˜ Ë ‰˘Ó·ÙfiÙËÙ· ·Ó·ÌÔÓ‹˜ Û ϛÛÙ· ÌÂÙ·ÌfiÛ¯Â˘Û˘) ÙˆÓ ·ÛıÂÓÒÓ Ì ∏∫∫. ™ÙȘ ·ÚÂÌ‚¿ÛÂȘ ·˘Ù¤˜5,6 Û˘ÌÂÚÈÏ·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 ÂÈ‚›ˆÛË ‡ÛÙÂÚ· ·fi ÙË ÌÂÙ·ÌfiÛ¯Â˘ÛË Ú¤ÂÈ Ó· ˘ÂÚ‚·›ÓÂÈ ÙËÓ ÂÈ‚›ˆÛË Ô˘ ÌÔÚ› Ó· ÂÈÙ¢¯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΋ ¯ËÌÂÈÔıÂÚ·›·, Î.Ù.Ï.). Δ· ÎÚÈÙ‹ÚÈ·, fï˜, ÁÈ· ÌÂÙ·ÌfiÛ¯Â˘ÛË ‹·ÙÔ˜ ÛÙÔÓ ·ÛıÂÓ‹ Ì Ë·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 ÂÈ‚›ˆÛË ‡ÛÙÂÚ· ·fi ÌÂÙ·ÌfiÛ¯Â˘ÛË ÁÈ· ∏∫∫ Ú¤ÂÈ Ó· ˘ÂÚ‚·›ÓÂÈ ÙËÓ ÂÈ‚›ˆÛË Ô˘ ÂÈÙ˘Á¯¿ÓÂÙ·È ‡ÛÙÂÚ· ·fi ÌÂÙ·ÌfiÛ¯Â˘ÛË ÁÈ· ¿ÏÏÔ˘˜, ÂÎÙfi˜ ·fi ∏∫∫, ÏfiÁÔ˘˜. ¢ËÏ·‰‹, Ë ·Ó¿ÁÎË ı¤ÛÈÛ˘ ÎÚÈÙËÚ›ˆÓ ÚÔ·ÙÂÈ ·fi ÙËÓ ¤ÏÏÂÈ„Ë ÌÔÛ¯Â˘Ì¿ÙˆÓ Î·È Â͢ËÚÂÙ› ÛÙË ÌÂÁÈÛÙÔÔ›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΋ ÂȂ‚·›ˆÛË Ì ‚ÈÔ„›·8.

81

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82

3. ∏ Úfi‚ÏÂ„Ë Ù˘ Ê˘ÛÈ΋˜ ÈÛÙÔÚ›·˜ ÙÔ˘ ∏∫∫ °›ÓÂÙ·È ÏÔÈfiÓ Î·Ù·ÓÔËÙfi fiÙÈ ÁÈ· ÙËÓ ·fiÊ·ÛË Ú·ÁÌ·ÙÔÔ›ËÛ˘ ÌÂÙ·ÌfiÛ¯Â˘Û˘ ÛÙÔÓ ·ÛıÂÓ‹ Ì ∏∫∫ ··ÈÙÂ›Ù·È Ë ÁÓÒÛË Ù˘ Ê˘ÛÈ΋˜ ÈÛÙÔÚ›·˜ Ù˘ ÓfiÛÔ˘ (ÚÔ‚ÏÂfiÌÂÓË ÂÈ‚›ˆÛË), ηıÒ˜ Î·È ÙÔ ˆ˜ ·˘Ù‹ ÂËÚ¿˙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˘ ÔÔÈ·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‡˜ ÌÔÚ› Ó· Â¤ÏıÂÈ Â›Ù ÂÍ·ÈÙ›·˜ ÙÔ˘ ∏∫∫ (·‡ÍËÛË ÙÔ˘ ηÚÎÈÓÈÎÔ‡ ÊÔÚÙ›Ô˘, ηÚÎÈÓÈ΋ η¯ÂÍ›·, Î.Ù.Ï.), ›Ù ÂÍ·ÈÙ›·˜ Ù˘ Ë·ÙÈ΋˜ ·ÓÂ¿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·ÙÔÔ›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΋ ¯ËÌÂÈÔıÂÚ·›·, Î.Ù.Ï.), ÂȯÂÈÚÂ›Ù·È ˘ÔÛÙ·‰ÈÔÔ›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 ÂÈıÂÙÈÎfiÙËÙ· 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 ÔÔ›ÔÈ ÚÔÛʤÚÔ˘Ó ÚÔÁÓˆÛÙÈΤ˜ ÏËÚÔÊÔڛ˜ ·ÎfiÌ· Î·È ÌÂÌÔӈ̤ÓÔÈ (DCP, VEGF-P Î·È FAL), ¯ˆÚ›˜ ‰ËÏ·‰‹ Ó· ÂÓÙ¿ÛÛÔÓÙ·È ÛÙ· Ï·›ÛÈ· οÔÈÔ˘ ˘ÔÏÔÁÈÛÙÈÎÔ‡ ÂÚÁ·Ï›Ԣ10.

i. μ·ıÌÔÏÔÁ›Â˜ (scores) Ÿˆ˜ ¤¯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 ÚԂϤÂÈ ÙË ıÓËÙfiÙËÙ· ÙÔ˘ Ë·ÙÔ·ıÔ‡˜ ‡ÛÙÂÚ· ·fi ¯ÔÚ‹ÁËÛË ·Ó·ÈÛıËÛ›·˜ ÁÈ· ̤ÙÚÈ·˜ ‚·Ú‡ÙËÙ·˜ ¯ÂÈÚÔ˘ÚÁÈ΋ Â¤Ì‚·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· ÔÔ›· Û¯ÂÙ›˙ÔÓÙ·È Ì ÙÔÓ ∏∫∫ (‚·ıÌÔÏÔÁ›Â˜, Û˘ÛÙ‹Ì·Ù· Ù·ÍÈÓfiÌËÛ˘, ÚÔ¸Ôı¤ÛÂȘ ‰ÈÂÓ¤ÚÁÂÈ·˜ ÌÂÙ·ÌfiÛ¯Â˘Û˘). ÀÔÏÔÁÈÛÙÈÎfi ∂ÚÁ·Ï›Ô

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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). ÃÚËÛÈÌÔÔÈÂ›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‚ÏÂfiÌÂÓË ıÓËÙfiÙËÙ· ÙÔ˘ Ë·ÙÔ·ıÔ‡˜ ̤۷ ÛÙÔ˘˜ ÂfiÌÂÓÔ˘˜ 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˘˜ ÂfiÌÂÓÔ˘˜ 3 Ì‹Ó˜ Â›Ó·È 15%. ΔÔ MELD Ú¤ÂÈ Ó· Â·Ó˘ÔÏÔÁ›˙ÂÙ·È Î¿ı ÙÚÂȘ Ì‹Ó˜. ΔÔ MELD ‰ÂÓ ÌÔÚ› Ó· ¯ÚËÛÈÌÔÔÈËı› ÁÈ· ÙËÓ ÚfiÁÓˆÛË Ù˘ ·Ó·ÏÔÁÈÛÙÈ΋˜ ÂÈ‚›ˆÛ˘ ÙÔ˘ Ë·ÙÔ·ıÔ‡˜ Ì ∏∫∫. ∞˘Ùfi Û˘Ì‚·›ÓÂÈ ÁÈ·Ù› Ë Ë·ÙÈ΋ ·ÓÂ¿ÚÎÂÈ· ÔÏÏÒÓ ·ÛıÂÓÒÓ Ì ∏∫∫ ‰ÂÓ Â›Ó·È ÛÔ‚·Ú‹, ÔfiÙÂ 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 (fiˆ˜ ÏfiÁÔ˘ ¯¿ÚÈÓ ÛÙȘ ∏ӈ̤Ó˜ ¶ÔÏÈÙ›˜ Ù˘ ∞ÌÂÚÈ΋˜) Ô ·ÛıÂÓ‹˜ Ì ∏∫∫ ÚÈÌÔ‰ÔÙÂ›Ù·È Ì ÂÈϤÔÓ ‚·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‡˜. ∂ÈϤÔÓ, 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‚ÏÂfiÌÂÓË ıÓËÙfiÙËÙ· ÙÔ˘ Ë·ÙÔ·ıÔ‡˜ ̤۷ ÛÙÔÓ ÂfiÌÂÓÔ ¯ÚfiÓÔ. ™˘ÁÎÂÎÚÈ̤ӷ, ÔÈ ·ÛıÂÓ›˜ Ì ‚·ıÌÔÏÔÁ›Â˜ 0, 1, 2, 3, Î·È 4-6 ¤¯Ô˘Ó ÂÙ‹ÛȘ ÚÔ‚ÏÂfiÌÂÓ˜ ÂÈ‚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‚ÏÂfiÌÂÓË ıÓË-

83

¶›Ó·Î·˜ 2. ∏ ÙÂÏÈ΋ ‚·ıÌÔÏÔÁ›· CLIP ÚÔ·ÙÂÈ ·fi ÙËÓ ÚfiÛıÂÛË ÙˆÓ ‚·ıÌÒÓ Ô˘ ·ÓÙÈÛÙÔÈ¯Ô‡Ó ÛÙÔ˘˜ ÂÈ̤ÚÔ˘˜ 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˘˜ ÂfiÌÂÓÔ˘˜ ÙÚÂȘ Ì‹Ó˜. ™˘ÁÎÂÎÚÈ̤ӷ, ÔÈ ·ÛıÂÓ›˜ Ì ‚·ıÌÔÏÔÁ›Â˜ < 2, 2-7 Î·È >7, ¤¯Ô˘Ó ÚÔ‚ÏÂfiÌÂÓ˜ ÂÈ‚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) Ÿˆ˜ ¤¯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· ÂÈ‚›ˆÛ˘ ÙÔ˘ ·ÛıÂÓÔ‡˜ ÁÈ· ÂÚÈÛÛfiÙÂÚÔ ·fi ¤ÓÙ ¯ÚfiÓÈ·, ‡ÛÙÂÚ· ·fi R0 Ë·ÙÂÎÙÔÌ‹. ™˘ÁÎÂÎÚÈ̤ӷ, ÔÈ ·ÛıÂÓ›˜ ÛÙ·‰›Ô˘ π ¤¯Ô˘Ó ÂÓÙ·ÂÙ‹ ÂÈ‚›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‹ ÂÈ‚›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‹ ÂÈ‚›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 ÂȂ‚·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‹ ÂÈ‚›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˘˜ ÂÈ̤ÚÔ˘˜ ¤ÍÈ ‰Â›ÎÙ˜. ¢Â›ÎÙ˜ -3

-1

μ·ıÌÔ› 0

I / II

IIIa / IIIb

IVa / IVb

-4 ™Ù¿‰ÈÔ AJCC Ÿ¯È

™˘ÌÙÒÌ·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. ∞ÏÔÔÈË̤ÓÔ Û‡ÛÙËÌ· Ù·ÍÈÓfiÌËÛ˘ AJCC. ΔÔ ÛÙ¿‰ÈÔ ÙÔ˘ ∏∫∫ ÚÔ·ÙÂÈ ·Ó¿ÏÔÁ· Ì ÙÔ ‚·ıÌfi ‚·Ú‡ÙËÙ·˜ ÙˆÓ ÂÈ̤ÚÔ˘˜ ÛÙÔȯ›ˆÓ ÙÔ˘ Û˘ÛÙ‹Ì·ÙÔ˜. ŸÔ˘ i, ÙÔÔıÂÙÂ›Ù·È ÔÔÈ·‰‹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·ÊÔÚÔÔ›ËÛË

ª¤ÙÚÈ· ‰È·ÊÔÚÔÔ›ËÛË ∫·Î‹ ‰È·ÊÔÚÔÔ›ËÛË

∞‰È·ÊÔÚÔÔ›ËÙÔ˜ fiÁÎÔ˜

ÿÓˆÛË (F)

™Ô‚·ÚÔ‡ ‚·ıÌÔ‡ ›ÓˆÛË –

–

‹ ∫ ›ÚÚˆÛË

¢È‹ıËÛË ¿ÏψÓ

– ™Ù·‰ÈÔÔ›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·‰ÈÔÔ›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 ÂÈ‚›ˆÛË ÙˆÓ ·ÛıÂÓÒÓ ÛÙ·‰›Ô˘ π Â›Ó·È 8,3 Ì‹Ó˜ ¯ˆÚ›˜ η̛· ıÂÚ·›· Î·È 25,6 Ì‹Ó˜ ‡ÛÙÂÚ· ·fi R0 Ë·ÙÂÎÙÔÌ‹. ∏ ‰È¿ÌÂÛË ÂÈ‚›ˆÛË ÙˆÓ ·ÛıÂÓÒÓ ÛÙ·‰›Ô˘ ππ Â›Ó·È 2 Ì‹Ó˜ ¯ˆÚ›˜ η̛· ıÂÚ·›· Î·È 12,2 Ì‹Ó˜ ‡ÛÙÂÚ· ·fi R0 Ë·ÙÂÎÙÔÌ‹. ∏ ‰È¿ÌÂÛË ÂÈ‚›ˆÛË ÙˆÓ ·ÛıÂÓÒÓ ÛÙ·‰›Ô˘ πππ Â›Ó·È 0,7 Ì‹Ó˜ ¯ˆÚ›˜ η̛· ıÂÚ·›·, ÂÓÒ ÔÈ ¿ÚÚˆÛÙÔÈ ·˘ÙÔ› Û˘Ó‹ıˆ˜ ‰ÂÓ ˘Ô‚¿ÏÔÓÙ·È Û Ë·ÙÂÎÙÔÌ‹. Δ· Û˘ÛÙ‹Ì·Ù· Ù·ÍÈÓfiÌËÛ˘ JISS19 Î·È BCLC20 ΢ڛˆ˜ ·ÔÙÂÏÔ‡Ó ·ÏÁfiÚÈıÌÔ˘˜ ıÂÚ·›·˜ ÁÈ· ÙÔÓ ∞ÛÈ¿ÙË Î·È ÙÔÓ ∂˘Úˆ·›Ô ·ÓÙ›ÛÙÔȯ· ·ÛıÂÓ‹ Ì ∏∫∫. OÈ ·ÏÁfiÚÈıÌÔÈ ·˘ÙÔ› ¤¯Ô˘Ó ηٷÛÙÚˆı› ‡ÛÙÂÚ· ·fi ÂÎÙÂÙ·Ì̤ÓË ·Ó·ÛÎfiËÛË Ù˘ ‚È‚ÏÈÔÁÚ·Ê›·˜ ÛÂ Û˘Ó‰˘·ÛÌfi Ì ÂÓۈ̿وÛË Ù˘ ÂÌÂÈÚ›·˜ ÙˆÓ ÌÂÁ¿ÏˆÓ ΤÓÙÚˆÓ ·fi Ù· ÔÔ›· 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·ÎÚÔÛÎÔÈ΋ ·ÁÁÂȷ΋ Â¤ÎÙ·ÛË, Ë Â¿ÚÎÂÈ· ÙÔ˘ ‹·ÙÔ˜, Ë ‡·ÚÍË ÌÂÙ·ÛÙ¿ÛÂˆÓ Î·È Ë ·ÚÔ˘Û›· Û˘ÌÙˆÌ¿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 Ë·ÙÂÎÙÔÌ‹ (ÛÙ¿‰ÈÔ 0), ÌÂÙ·ÌfiÛ¯Â˘ÛË (ÛÙ¿‰ÈÔ A), ˘ÔÛÙ·‰ÈÔÔ›ËÛË (ÛÙ¿‰ÈÔ B), ·ÁˆÁ¤˜ ÚˆÙÔÎfiÏÏÔ˘ (ÛÙ¿‰ÈÔ C) Î·È ·ÚËÁÔÚÈ΋ ıÂÚ·›· (ÛÙ¿‰ÈÔ D).

iii. ¶ÚÔ¸Ôı¤ÛÂȘ ‰ÈÂÓ¤ÚÁÂÈ·˜ ÌÂÙ·ÌfiÛ¯Â˘Û˘ (criteria - provisions) Ÿˆ˜ ¤¯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· ÂÈ‚›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 ÔÔ›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‚ÏÂfiÌÂÓË ÂÙ‹ÛÈ· ÂÈ‚›ˆÛË ·Ó¤Ú¯ÂÙ·È ÛÙÔ 90%, ÂÓÒ Ë ÚÔ‚ÏÂfiÌÂÓË ÂÓÙ·ÂÙ‹˜ ÂÈ‚›ˆÛË ˘ÂÚ‚·›ÓÂÈ ÙÔ 70% (75% ÙÂÙÚ·ÂÙ‹˜ ÂÈ‚›ˆÛË).

OÈ ÚÔ¸Ôı¤ÛÂȘ ‰ÈÂÓ¤ÚÁÂÈ·˜ ÌÂÙ·ÌfiÛ¯Â˘Û˘ ηٿ UCSF ‰ÂÈÎÓ‡Ô˘Ó ÙËÓ Èı·ÓfiÙËÙ· ÂÈ‚›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 ÔÔ›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‚ÏÂfiÌÂÓË ÂÙ‹ÛÈ· ÂÈ‚›ˆÛË ·Ó¤Ú¯ÂÙ·È ÛÙÔ 91%, ÂÓÒ Ë ÚÔ‚ÏÂfiÌÂÓË ÂÓÙ·ÂÙ‹˜ ÊÙ¿ÓÂÈ ÛÙÔ 72%. ΔÔ ÔÛÔÛÙfi ÙˆÓ ·ÛıÂÓÒÓ Ô˘ ·Ú·¤ÌÂÙ·È Û ÌÂÙ·ÌfiÛ¯Â˘ÛË Ì ÙȘ ‰ÈÂ˘Ú˘Ì¤Ó˜ ·˘Ù¤˜ ÚÔ¸Ôı¤ÛÂȘ ‰ÂÓ ˘ÂÚ‚·›ÓÂÈ ÙÔ 5% ÂÎÂ›ÓˆÓ Ô˘ ÂÈϤÁÔÓÙ·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· ÂÈ‚›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 ÔÔ›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 ÔÔ›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‚ÏÂfiÌÂÓË ÂÓÙ·ÂÙ‹˜ ÂÈ‚›ˆÛË ÊÙ¿ÓÂÈ ÛÙÔ 50%.

iv. ªÂÌÔӈ̤ÓÔÈ ‰Â›ÎÙ˜ Ÿˆ˜ ¤¯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 Ë·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 ÂÈ‚›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 ıÂÚ·›· ¤¯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˜ ÂÈ‚›ˆÛ˘ Â›Ó·È 15,2 ¯ÚfiÓÈ· ÁÈ· ÙËÓ ÚÒÙË ÔÌ¿‰·, 8,5 ¯ÚfiÓÈ· ÁÈ· ÙË ‰Â‡ÙÂÚË ÔÌ¿‰· (ÂÓÙ·ÂÙ‹˜ ÂÈ‚›ˆÛË: 60%) Î·È 3,7 ¯ÚfiÓÈ· ÁÈ· ÙËÓ ÙÚ›ÙË ÔÌ¿‰·. ΔÔ ÔÛÔÛÙfi ÙˆÓ ·ÛıÂÓÒÓ Ô˘ ·Ú·¤ÌÂÙ·È Û ÌÂÙ·ÌfiÛ¯Â˘ÛË, ·Ó ÛÙÔ˘˜ Ï‹Ù˜ Û˘ÌÂÚÈÏËÊıÔ‡Ó ¿ÚÚˆÛÙÔÈ Ù˘ ÚÒÙ˘ Î·È ‰Â‡ÙÂÚ˘ ÔÌ¿‰·˜, ˘ÂÚ‚·›ÓÂÈ ÙÔ 20% (21.6%) ÂÎÂ›ÓˆÓ Ô˘ ÂÈϤÁÔÓÙ·È Ì ‚¿ÛË ÙȘ ÚÔ¸Ôı¤ÛÂȘ ηٿ Milan.

5. ∏ Ê˘ÛÈ΋ ÈÛÙÔÚ›· ÙÔ˘ ∏∫∫ i. ∏ Ê˘ÛÈ΋ ÈÛÙÔÚ›· ÙÔ˘ ∏∫∫ ¯ˆÚ›˜ ıÂÚ·›· ∏ ÂÈ‚›ˆÛË ÂÓfi˜ ·ÛıÂÓÔ‡˜ Ì ∏∫∫ ¯ˆÚ›˜ ΛÚÚˆÛË ÂÍ·ÚÙ¿Ù·È ‚¤‚·È· ·fi ÙÔ Î·ÚÎÈÓÈÎfi ÊÔÚÙ›Ô, fiˆ˜ ·˘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›˜ ıÂÚ·›·, ÂÙ‹ÛÈ· ÂÈ‚›ˆÛË 90%, ÂÊfiÛÔÓ ‰ÂÓ Â›Ó·È ÎÈÚÚˆÙÈÎfi˜. º˘ÛÈο, Ë ‡·ÚÍË Î›ÚÚˆÛ˘ ÂÏ·ÙÙÒÓÂÈ ÙËÓ ÂÈ‚›ˆÛË ÙÔ˘ ·ÚÚÒÛÙÔ˘, ÌÔÚ› ‰Â Ó· ˘ÔÏÔÁÈÛÙ› ηٿ ÚÔÛ¤ÁÁÈÛË Ì ÙË ¯Ú‹ÛË Ù˘ ‚·ıÌÔÏÔÁ›·˜ MELD12. ŒÙÛÈ, Ô ·ÓÙ›ÛÙÔȯԘ ·ÛıÂÓ‹˜ ¤¯ÂÈ, ¯ˆÚ›˜ ıÂÚ·›·, ÂÙ‹ÛÈ· ÂÈ‚›ˆÛË 80%, ÂÊfiÛÔÓ Â›Ó·È

ÎÈÚÚˆÙÈÎfi˜ ÛÙ·‰›Ô˘ ∞ ηٿ Child. O ›‰ÈÔ˜ ·ÛıÂÓ‹˜ ¤¯ÂÈ, ¯ˆÚ›˜ ıÂÚ·›·, ÂÙ‹ÛÈ· ÂÈ‚›ˆÛË 20%, ÂÊfiÛÔÓ Â›Ó·È ÎÈÚÚˆÙÈÎfi˜ ÛÙ·‰›Ô˘ μ ηٿ Child27. ∏ ÚÔ‚ÏÂfiÌÂÓË ÂÈ‚›ˆÛË ÂÓfi˜ ·ÛıÂÓÔ‡˜ Ì ∏∫∫ Î·È Î›ÚÚˆÛË ÌÔÚ› 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. Ÿˆ˜ ÚԷӷʤÚıËÎÂ, Ë ÚfiÁÓˆÛË Ù˘ ÂÈ‚›ˆÛ˘ ‡ÛÙÂÚ· ·fi ÙËÓ ¯ÂÈÚÔ˘ÚÁÈ΋ Â¤Ì‚·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‹˜ ÂÈ‚›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‹˜ ÂÈ‚›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˜ ıÂÚ·›˜ ™ÙȘ ÂÚÈÔ¯ÈΤ˜, ÌË ¯ÂÈÚÔ˘ÚÁÈΤ˜ ıÂÚ·›˜ ÙÔ˘ ∏∫∫ Û˘ÌÂÚÈÏ·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· ¯ÚËÛÈÌÔÔÈÔ‡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 Ë·ÙÂÎÙÔÌ‹ ‹ Û ÌÂÙ·ÌfiÛ¯Â˘ÛË (Û˘Ó‹ıˆ˜ ÏfiÁˆ ¿ÚÓËÛ˘ ÙÔ˘ ·ÚÚÒÛÙÔ˘), fiÛÔÈ ˘Ô‚¿ÏÔÓÙ·È Û ıÂÚÌÈ΋ ηٷÛÙÚÔÊ‹ Ì ڷ‰ÈÔ·̷ٷ, ÂȉÂÈÎÓ‡Ô˘Ó ÂÙ‹ÛÈ· Î·È ÙÚÈÂÙ‹ ÂÈ‚›ˆÛË 100% Î·È 72.7% ·ÓÙ›ÛÙÔȯ· 28. ∂ÈϤÔÓ, ·ÛıÂÓ›˜ Ì ΛÚÚˆÛË ÛÙ·‰›Ô˘ μ ηٿ Child, ÔÈ ÔÔ›ÔÈ ‰ÂÓ Ô‰ËÁÔ‡ÓÙ·È Û Ë·ÙÈ΋ ÌÂÙ·ÌfiÛ¯Â˘ÛË ·ÏÏ¿ ˘Ô‚¿ÏÔÓÙ·È Û ηٷÛÙÚÔÊ‹ Ì ڷ‰ÈÔ·̷ٷ, ¤¯Ô˘Ó ÂÙ‹ÛÈ· Î·È ÙÚÈÂÙ‹ ÂÈ‚›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¿ ÂÈ‚›ˆÛ˘ Â›Ó·È 4 ÂηÙÔÛÙ¿. ∞ÛıÂÓ›˜ Ì ΛÚÚˆÛË ÛÙ·‰›Ô˘ ∞ ηٿ Child, ÔÈ ÔÔ›ÔÈ ‰ÂÓ Ô‰ËÁÔ‡ÓÙ·È Û Ë·ÙÂÎÙÔÌ‹ ‹ Û ÌÂÙ·ÌfiÛ¯Â˘ÛË ·ÏÏ¿ ˘Ô‚¿ÏÔÓÙ·È Û ·ÚÙËÚÈ·Îfi ¯ËÌÂÈÔÂÌ‚ÔÏÈÛÌfi, ÂȉÂÈÎÓ‡Ô˘Ó ÂÙ‹ÛÈ· Î·È ‰ÈÂÙ‹ ÂÈ‚›ˆÛË 82% Î·È 63% ·ÓÙ›ÛÙÔȯ· 30 . ∂ÈϤÔÓ, ·ÛıÂÓ›˜ Ì ΛÚÚˆÛË ÛÙ·‰›Ô˘ μ ηٿ Child, ÔÈ ÔÔ›ÔÈ ‰ÂÓ Ô‰ËÁÔ‡ÓÙ·È Û Ë·ÙÈ΋ ÌÂÙ·ÌfiÛ¯Â˘ÛË ·ÏÏ¿ ˘Ô‚¿ÏÔÓÙ·È Û ·ÚÙËÚÈ·Îfi ¯ËÌÂÈÔÂÌ‚ÔÏÈÛÌfi, ¤¯Ô˘Ó ÂÙ‹ÛÈ· Î·È ÙÚÈÂÙ‹ ÂÈ‚›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¿ ÂÈ‚›ˆÛ˘.

iv. ∏ Ê˘ÛÈ΋ ÈÛÙÔÚ›· ÙÔ˘ ∏∫∫ ‡ÛÙÂÚ· ·fi Û˘ÛÙËÌ·ÙÈΤ˜ ıÂÚ·›˜ ∏ ÌÔÓ·‰È΋ Û˘ÛÙËÌ·ÙÈ΋ ıÂÚ·›· Ô˘ ·ԉ‰ÂÈÁ̤ӷ ·˘Í¿ÓÂÈ ÙËÓ ÂÈ‚›ˆÛË ÙˆÓ ÎÈÚÚˆÙÈÎÒÓ ·ÛıÂÓÒÓ Ì ∏∫∫ Â›Ó·È Ë ¯Ú‹ÛË Ù˘ ÛÔÚ·ÊÂÓ›‰Ë˜ (sorafenib). ™˘ÁÎÂÎÚÈ̤ӷ, Ë ÂÈ‚›ˆÛË ·ÛıÂÓÒÓ Ì ΛÚÚˆÛË ÛÙ·‰›Ô˘ ∞ ηٿ Child Î·È ∏∫∫, ÔÈ ÔÔ›ÔÈ ‰ÂÓ Âȉ¤¯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 ÂÈ‚›ˆÛË ·ÓÙ›ÛÙÔȯˆÓ Ë·ÙÔ·ıÒÓ Ô˘ Ï·Ì‚¿ÓÔ˘Ó ·ÚËÁÔÚÈ΋ ÌfiÓÔ ıÂÚ·›·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‹˜ ÂÈ‚›ˆÛË ÙˆÓ ·ÚÚÒÛÙˆÓ ·˘ÙÒÓ ·Ó¤Ú¯ÂÙ·È ÛÙÔ 61%. ™ÙËÓ ›‰È· ‚¿ÛË ‰Â‰Ô̤ӈÓ, Ë ÂÓÙ·ÂÙ‹˜ ÂÈ‚›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%. Ÿˆ˜ ·Ó·Ê¤ÚıËΠ·Ú·¿Óˆ, Â›Ó·È ‰˘Ó·Ùfi Ó· ÂÈϤÁÔÓÙ·È ·ÛıÂÓ›˜ Ì ‚¿ÛË Û˘ÁÎÂÎÚÈ̤ӷ ˘ÔÏÔÁÈÛÙÈο ÂÚÁ·Ï›·, ¤ÙÛÈ ÒÛÙ ӷ ÂÈÙ˘Á¯¿ÓÂÙ·È Ë ÂÈı˘ÌËÙ‹ ÂÓÙ·ÂÙ‹˜ ÂÈ‚›ˆÛË. O˘ÛÈ·ÛÙÈο ‰ËÏ·‰‹, ·ÔÎÏ›ÔÓÙ·˜ ÔÚÈṲ̂ÓÔ˘˜ ·ÛıÂÓ›˜ ·fi ÙË Ï›ÛÙ· ·Ó·ÌÔÓ‹˜, “ηٷÛ΢¿˙Ô˘Ì” ÙËÓ ÂÈı˘ÌËÙ‹ ηÌ‡ÏË Ê˘ÛÈ΋˜ ÈÛÙÔÚ›·˜ ÙÔ˘ ·ÚÚÒÛÙÔ˘ Ì ∏∫∫ ‡ÛÙÂÚ· ·fi ÌÂÙ·ÌfiÛ¯Â˘ÛË ‹·ÙÔ˜. ™˘ÁÎÂ-

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ÎÚÈ̤ӷ, fiÙ·Ó ÙËÚÔ‡ÓÙ·È ÔÈ ÚÔ¸Ôı¤ÛÂȘ ÌÂÙ·ÌfiÛ¯Â˘Û˘ ηٿ Milan ‹ ηٿ UCSF, Ë ÚÔ‚ÏÂfiÌÂÓË ÂÓÙ·ÂÙ‹˜ ÂÈ‚›ˆÛË ˘ÂÚ‚·›ÓÂÈ ÙÔ 70%. ŸÙ·Ó ÙËÚÔ‡ÓÙ·È ÔÈ ÚÔ¸Ôı¤ÛÂȘ ηٿ Barcelona, Ë ÚÔ‚ÏÂfiÌÂÓË ÂÓÙ·ÂÙ‹˜ ÂÈ‚›ˆÛË ÊÙ¿ÓÂÈ ÛÙÔ 50%. ŸÙ·Ó ‰ÂÓ Ù›ıÔÓÙ·È Î¿ÔȘ ÚÔ¸Ôı¤ÛÂȘ ÌÂÙ·ÌfiÛ¯Â˘Û˘, Ë ÚÔ‚ÏÂfiÌÂÓË ÂÓÙ·ÂÙ‹˜ ÂÈ‚›ˆÛË Â›Ó·È 11,2%, ÂÓÒ Ë ÏÂÈÔ„ËÊ›· ÙˆÓ ˘ÔÙÚÔÒÓ 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‹ Â¤Ì‚·ÛË ÁÈ·Ù›, ·Ó Î·È ¤¯Ô˘Ó ¤Ó‰ÂÈÍË (‚ÂÏÙ›ˆÛË ÂÈ‚›ˆÛ˘), ‰ÂÓ ÏËÚÔ‡Ó Ù· ÎÚÈÙ‹ÚÈ· (ÂÈ‚›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˘. ∂ÈϤÔÓ, ·ÎfiÌ· Î·È ·˘ÙÔ› Ô˘ Â›Ó·È ÂÓÙfi˜ ÙˆÓ ÚÔ¸Ôı¤ÛÂˆÓ Î·Ù¿ Milan, ÂÎ›ÙÔ˘Ó ·˘ÙÒÓ Ì ڢıÌfi 4% ÙÔ Ì‹Ó·35. ŸÏÔÈ ·˘ÙÔ› ÔÈ ·ÛıÂÓ›˜ ÌÔÚÔ‡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·‰ÈÔÔ›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·‰ÈÔÔ›ËÛË ÙˆÓ fiÁÎˆÓ Ô˘ ÍÂÂÚÓÔ‡Ó ÙȘ ‰Â‰Ô̤Ó˜ ÁÈ· ÙÔ ÂοÛÙÔÙ ΤÓÙÚÔ Ú¸Ôı¤ÛÂȘ ÌÂÙ·ÌfiÛ¯Â˘Û˘ (Milan, UCSF, ÎÙÏ) ÂÈÙ˘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‹˜ ÂÈ‚›ˆÛË ·ÛıÂÓÒÓ ‡ÛÙÂÚ· ·fi ÌÂÙ·ÌfiÛ¯Â˘ÛË ‹·ÙÔ˜ Ô˘ ·ÎÔÏÔ‡ıËÛ ˘ÔÛÙ·‰ÈÔÔ›ËÛË Ì TACE, RFA ‹ Û˘Ó‰˘·ÛÌfi ÙÔ˘˜ ·Ó‹Ïı ÛÙÔ 69%, ÛËÌ·ÓÙÈο ˘„ËÏfiÙÂÚÔ ·fi ÙÔ 31% ÙˆÓ ·ÛıÂÓÒÓ ¯ˆÚ›˜ ˘ÔÛÙ·‰ÈÔÔ›ËÛË. ΔÔ fiÊÂÏÔ˜ ÛÙËÓ ÂÈ‚›ˆÛË ·fi ÙËÓ ˘ÔÛÙ·‰ÈÔÔ›ËÛË ‹Ù·Ó ÌÂÁ·Ï‡ÙÂÚÔ ÛÙÔ˘˜ ·ÚÚÒ-

88

¢. μƒOÃπ¢∏™, ¢. Δ∞∫OÀ¢∞™

ÛÙÔ˘˜ ÂÎÙfi˜ ÚÔ¸Ôı¤ÛÂˆÓ Î·Ù¿ Milan36. ∂ÈϤÔÓ, ˘ÔÛÙ·‰ÈÔÔ›ËÛË Ì Ë·ÙÂÎÙÔÌ‹ (·Ó Â›Ó·È Ú·ÁÌ·ÙÔÔÈ‹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·‰ÈÔÔ›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· ¯ÚËÛÈÌÔÔÈËıÔ‡Ó ·ÏÏÔ‡) Û ·ÛıÂÓ›˜ Ô˘ ÍÂÂÚÓÔ‡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˜ ÍÂÂÚ¿ÛÂÈ ÙËÓ ¿ÌÂÛË ÌÂÙÂÁ¯ÂÈÚËÙÈ΋ ÂÚ›Ô‰Ô (30 Ë̤Ú˜), ÙfiÙÂ Ë ÂÓÙ·ÂÙ‹˜ ÂÈ‚›ˆÛË Â›Ó·È Û˘ÁÎÚ›ÛÈÌË Ì ·˘Ù‹ ÙˆÓ ÏËÙÒÓ ÌË ÔÚÈ·ÎÒÓ ÌÔÛ¯Â˘Ì¿ÙˆÓ.

H ¯Ú‹ÛË ÌÔÛ¯Â˘Ì¿ÙˆÓ ·fi Û˘ÁÁÂÓ‹ ˙ÒÓÙ· ‰fiÙË Û ·ÛıÂÓ›˜ Ô˘ ÍÂÂÚÓÔ‡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‚ÏÂfiÌÂÓË ÂÓÙ·ÂÙ‹˜ ÂÈ‚›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¤˜ ÂÈÏÔΤ˜ Ù˘ Â¤Ì‚·Û˘ ÛÙËÓ ÔÔ›· ı· ˘Ô‚ÏËıÔ‡Ó, ÌÔÚÔ‡Ó Ó· ÚÔÛʤÚÔ˘Ó ÌfiÛ¯Â˘Ì·, ·ÎfiÌ· Î·È ·Ó Â›Ó·È ¯·ÌËÏfiÙÂÚË Ë ÚÔ‚ÏÂfiÌÂÓË ÂÈ‚›ˆÛË ÙÔ˘ Ï‹ÙË38.

H ¯Ú‹ÛË ÓÔÌÔÁÚ·ÌÌ¿ÙˆÓ Â˘¤ÏÈÎÙˆÓ ÎÚÈÙËÚ›ˆÓ Û ·ÛıÂÓ›˜ Ô˘ ÍÂÂÚÓÔ‡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 ÌÔÚ› ·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˘ ÂËÚ¿˙Ô˘Ó ÙËÓ ¤Î‚·ÛË Ù˘ ÌÂÙ·ÌfiÛ¯Â˘Û˘ Î·È Ó· ηٷÛÙÚÒÛÂÈ ÓÔÌÔÁÚ¿ÌÌ·Ù· ÂÓÙ·ÂÙÔ‡˜ ÂÈ‚›ˆÛ˘ ÁÈ· οı ÌÈ· ·fi ·˘Ù¤˜. ΔÔ È·ÙÚÈÎfi Û˘Ì‚Ô‡ÏÈÔ, ˘ÔÏÔÁ›˙ÔÓÙ·˜ ·fi Ù· ÓÔÌÔÁÚ¿ÌÌ·Ù· ÙËÓ ÚÔ‚ÏÂfiÌÂÓË ÂÓÙ·ÂÙ‹ ÂÈ‚›ˆÛË ÁÈ· ÙÔ Û˘ÁÎÂÎÚÈ̤ÓÔ ·ÛıÂÓ‹ Î·È Û˘ÁÎÚ›ÓÔÓÙ¿˜ ÙËÓ Ì ÙË Ì¤ÛË ÂÓÙ·ÂÙ‹ ÂÈ‚›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‚ÏÂfiÌÂÓ˜ ÂÈ‚ÈÒÛÂȘ: ·) Èڛ˜ ıÂÚ·¢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‚ÏÂfiÌÂÓË ÂÈ‚›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. ∫·ÙfiÈÓ Û˘ÁÎÚ›ÓÔÓÙ·È Ë ÚÔ‚ÏÂfiÌÂÓË ÂÈ‚›ˆÛË ‡ÛÙÂÚ· ·fi Ë·ÙÈ΋ ÌÂÙ·ÌfiÛ¯Â˘ÛË ÁÈ· ∏∫∫ Ì ÙËÓ ÂÈ‚›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·‰ÈÔÔ›ËÛË, Û˘Ó‹ıˆ˜ Ì ¯ËÌÂÈÔÂÌ‚ÔÏÈÛÌfi. ∞Ó, ‡ÛÙÂÚ· ·fi ¢ڇ È·ÙÚÈÎfi Û˘Ì‚Ô‡ÏÈÔ, ·ÔÊ·ÛÈÛı› fiÙÈ Ë ˘ÔÛÙ·‰ÈÔÔ›ËÛË Ô‰‹ÁËÛ Û ÛËÌ·ÓÙÈ΋ ·‡ÍËÛË Ù˘ ÚÔ‚ÏÂfiÌÂÓ˘ ÂÈ‚›ˆÛ˘ ‡ÛÙÂÚ· ·fi ÌÂÙ·ÌfiÛ¯Â˘ÛË ÁÈ· ∏∫∫ (ÌÂÁ·Ï‡ÙÂÚË ·fi ÙËÓ ÂÈ‚›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·‰ÈÔÔ›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 ıÂÚ·›·.

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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.

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¢. 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 Ë·ÙÔ΢ÙÙ·ÚÈÎfi ηÚΛÓÔ ÂÎÙfi˜ ÎÚÈÙËÚ›ˆÓ MÈÏ¿ÓÔ˘ °.Ã. ™ˆÙËÚfiÔ˘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 Ë·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 ÙÔÈÎÔ‡˜ 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 Ë·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 ÂÚÈÙÒÛÂȘ 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. ™ÎÔfi˜ Ù˘ ·ÚÔ‡Û˘ ÌÂϤÙ˘ Â›Ó·È Ë ·Ó·ÛÎfiËÛË ·ÔÙÂÏÂÛÌ¿ÙˆÓ ÌÂÙ·ÌfiÛ¯Â˘Û˘ ‹·ÙÔ˜ Û ·ÛıÂÓ›˜ Ì Ë·ÙÔ΢ÙÙ·ÚÈÎfi ηÚΛÓÔ ÂÎÙfi˜ ÎÚÈÙËÚ›ˆÓ ªÈÏ¿ÓÔ˘. ∏ ·Ó·ÛÎfiËÛË ·˘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˘ ¶·ÓÂÈÛÙËÌÈ·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 Â› 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˘ Â›ÙˆÛ˘ ÙÔ˘ Ë·ÙÔ΢ÙÙ·ÚÈÎÔ‡ ηÚΛÓÔ˘ ·ÎfiÌË Î·È ÛÙȘ ‰˘ÙÈΤ˜ ¯ÒÚ˜2. ∏ ÌÂÙ·ÌfiÛ¯Â˘ÛË ‹·ÙÔ˜ ¤¯ÂÈ ϤÔÓ Â˘Ú¤ˆ˜ ·Ó·ÁÓˆÚÈÛÙ› ˆ˜ Ë Î·Ï‡ÙÂÚË ıÂÚ·¢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 ÔÔ›ˆÓ ηÓ›˜>3cm, ·Ô˘Û›· ·ÁÁÂȷ΋˜ ‰È‹ıËÛ˘) ·fi ÙÔ˘˜ Mazzafero Î·È Û˘ÓÂÚÁ¿Ù˜ ÙÔ 19964 Û˘ÓÂÙ¤ÏÂÛ Û ÔÛÔÛÙ¿ 5ÂÙÔ‡˜ ÂÈ‚›ˆÛ˘ ÌÂٷ͇ ÙˆÓ ·ÛıÂÓÒÓ Ì Ë·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 Ë·ÙÔ΢ÙÙ·ÚÈÎfi ηÚΛÓÔ. ∏ ÂÊ·ÚÌÔÁ‹ Ù˘ ÙÌËÌ·ÙÈ΋˜ ÌÂÙ·ÌfiÛ¯Â˘Û˘ ‹·ÙÔ˜ ·fi و̷ÙÈÎfi ‰fiÙË Û ÂÓ‹ÏÈΘ ·ÛıÂÓ›˜ Ì Ë·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˘ Â¤ÙÚ„·Ó ÙËÓ Ú·ÁÌ·ÙÔÔ›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 ÂÈÏÔ-

ªÂÙ·ÌfiÛ¯Â˘ÛË ‹·ÙÔ˜ ˆ˜ ıÂÚ·›· ÂÎÏÔÁ‹˜ Û ÎÈÚÚˆÙÈÎÔ‡˜ ·ÛıÂÓ›˜ Ì Ë·ÙÔ΢ÙÙ·ÚÈÎfi ηÚΛÓÔ Ÿˆ˜ ÚԷӷʤÚıËÎÂ, Ë ÌÂÙ·ÌfiÛ¯Â˘ÛË ‹·ÙÔ˜ ¤¯ÂÈ ϤÔÓ Â˘Ú¤ˆ˜ ·Ó·ÁÓˆÚÈÛÙ› ˆ˜ Ë Î·Ï‡ÙÂÚË ıÂÚ·¢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›· ÚÔÔÙÈ΋ ÌÂϤÙË Ô˘ ‰ÈÂÓÂÚÁ‹ıËΠÛÙÔ ªÂÙ·ÌÔÛ¯Â˘ÙÈÎfi Ì·˜ ∫¤ÓÙÚÔ Û ·ÛıÂÓ›˜ Ì Ë·ÙÔ΢ÙÙ·ÚÈÎfi ηÚΛÓÔ Û ¤‰·ÊÔ˜ ΛÚÚˆÛ˘ ÂÚÂ˘Ó‹Û·ÌÂ Û˘ÁÎÚÈÙÈο Ù· ·ÔÙÂϤÛÌ·Ù· ÙÚÈÒÓ ıÂÚ·¢ÙÈÎÒÓ ÌÂıfi‰ˆÓ ˆ˜ «ÌÔÓÔıÂÚ·›·˜», 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‡. Ÿˆ˜ Ê·›ÓÂÙ·È ÛÙËÓ ∂ÈÎfiÓ· 1, ÔÈ Î·Ì‡Ï˜ ÂÈ‚›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¿ ÂÈ‚›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‹ ÂÈ‚›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˜ ÂÈ‚›ˆÛ˘ (ηٿ Kaplan-Meier) ·Ó¿ ÔÌ¿‰· ÌÂϤÙ˘.

ÓˆÙ¤Úˆ ·ÔÙÂϤÛÌ·Ù· 3 ‰È·ÊÔÚÂÙÈÎÒÓ ÌÂıfi‰ˆÓ «ÌÔÓÔıÂÚ·›·˜» Û ÎÈÚÚˆÙÈÎÔ‡˜ ·ÛıÂÓ›˜, ‰Â›¯ÓÔ˘Ó Î·ı·Ú¿ fiÙÈ Ë ÌÂÙ·ÌfiÛ¯Â˘ÛË ‹·ÙÔ˜ ·ÔÙÂÏ› ÙËÓ Î·Ï‡ÙÂÚË ıÂÚ·›· ÁÈ· ÙÔÓ Ë·ÙÔ΢ÙÙ·ÚÈÎfi ηÚΛÓÔ ·fi ÔÁÎÔÏÔÁÈ΋ ¿Ô„Ë. ∞fi ÌÂÙ·ÌÔÛ¯Â˘ÙÈ΋ ¿Ô„Ë, ÂÂȉ‹ ÙÔ Úfi‚ÏËÌ· Ù˘ Â¿ÚÎÂÈ·˜ ÔÚÁ¿ÓˆÓ ÚÔ˜ ÌÂÙ·ÌfiÛ¯Â˘ÛË ÂȉÂÈÓÒÓÂÙ·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 ˘fiÏÔÈˆÓ, ÌË Î·ÚÎÈÓÔ·ıÒÓ, ÎÈÚÚˆÙÈÎÒÓ ·ÛıÂÓÒÓ.

∂Ê·ÚÌÔÛÈÌfiÙËÙ· ÙˆÓ ÎÚÈÙËÚ›ˆÓ ÙÔ˘ ªÈÏ¿ÓÔ˘: ∞ÎÙÈÓÔÏÔÁÈ΋ Î·È ·ıÔÏÔÁÔ·Ó·ÙÔÌÈ΋ ·Ó·ÛÎfiËÛË ŒÓ· ÂÚÒÙËÌ· Ô˘ ‡ÏÔÁ· ÁÂÓÓ¿Ù·È ÛÙÔÓ ¤ÌÂÈÚÔ 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˘, fiÔ˘ Ë ‰È·ÊÔÚÈ΋ ‰È¿ÁÓˆÛË ·Ó¿ÌÂÛ· Û Ë·ÙÔ΢ÙÙ·ÚÈÎfi ηÚΛÓÔ Î·È ·Ó·ÁÂÓÓËÙÈÎfi fi˙Ô ·ÔÙÂÏ› ÚfiÎÏËÛË ·ÎfiÌË Î·È ÁÈ· ÙÔÓ ¤ÌÂÈÚÔ ·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 ÏÂÙ¤˜ 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 ·ÓÂ·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˜ ÂÈ‚›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 Ë·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·, ‰ÈÂ›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 ϤÔÓ 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’ Â¤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 ÂÈÚÚÂ‹˜ 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˘ÙÔÈ΋ Î·È Î·Ù¿ ‰Â‡ÙÂÚÔÓ ‰ÂÔÓÙÔÏÔÁÈο ÂÏÂÁ¯fiÌÂÓË.

∞ÔÙÂϤÛÌ·Ù· Ù˘ ÌÂÙ·ÌfiÛ¯Â˘Û˘ ‹·ÙÔ˜ Û ÎÈÚÚˆÙÈÎÔ‡˜ ·ÛıÂÓ›˜ Ì Ë·ÙÔ΢ÙÙ·ÚÈÎfi ηÚΛÓÔ ÂÎÙfi˜ ÎÚÈÙËÚ›ˆÓ ªÈÏ¿ÓÔ˘ ∞Ó¿Ï˘ÛË ÙˆÓ ÚÒÙˆÓ 100 ÌÂÙ·ÌÔÛ¯Â˘Ì¤ÓˆÓ ÎÈÚÚˆÙÈÎÒÓ ·ÛıÂÓÒÓ Ì Ë·ÙÔ΢ÙÙ·ÚÈÎfi ηÚΛÓÔ ÛÙÔ ¶·ÓÂÈÛÙËÌÈ·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· ÂÈÏÔÁ‹˜ 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 ÂÈ‚›ˆÛË ÛÙÔ ¯ÚfiÓÔ Î·È ÛÙËÓ 5ÂÙ›· 76% Î·È 54% ·ÓÙ›ÛÙÔȯ·, Û ۇÁÎÚÈÛË Ì ÂÈ‚›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 ÂÈ‚›ˆÛË ·fi ÙÔ˘˜ ·ÛıÂÓ›˜ Ô˘ Ï‹ÚˆÓ·Ó ·˘Ù¿ Ù· ÎÚÈÙ‹ÚÈ·, ¯ˆÚ›˜ fï˜ Ë ‰È·ÊÔÚ¿ ÛÙËÓ ÂÈ‚›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·ÛÎfiËÛË Ù˘ ÛËÌ·Û›·˜ ÙˆÓ ÎÚÈÙËÚ›ˆÓ ÙÔ˘ ªÈÏ¿ÓÔ˘ ˆ˜ ÚÔÁÓˆÛÙÈÎÔ‡ ‰Â›ÎÙË ™Â Ì›· Û˘ÛÙËÌ·ÙÈ΋ ‚È‚ÏÈÔÁÚ·ÊÈ΋ ·Ó·ÛÎfiËÛË 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΋ ÂÈ‚›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 ÂÈ‚›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· ÂÈ‚›ˆÛË ∞fi ÙȘ 92 ÌÂϤÙ˜ Ô˘ Û˘ÌÂÚÈÏ‹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˘ ÂÈ‚›ˆÛ˘ ÁÈ· ·ÛıÂÓ›˜ ÂÓÙfi˜ Î·È ÂÎÙfi˜ ÎÚÈÙËÚ›ˆÓ ªÈÏ¿ÓÔ˘. ∂ÓÓ¤· ÂÍ ·˘ÙÒÓ ‹Ù·Ó ÌË ÛÙ·ÙÈÛÙÈο ÛËÌ·ÓÙÈΤ˜, ÂÓÒ ÔÈ ˘fiÏÔÈ˜ 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 ÂÈ‚›ˆÛË ·Ó¤‰ÂÈÍ ÛÙ·ÙÈÛÙÈο ηχÙÂÚË ÂÈ‚›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˘ÌÂÚÈÏ‹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 ˘fiÏÔÈ˜ ÂÙ¿ ‹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· ÂÈ‚›ˆÛË ∞fi ÙȘ 92 ÌÂϤÙ˜ Ô˘ Û˘ÌÂÚÈÏ‹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˘ ÂÈ‚›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 ÂÈ‚›ˆÛË Û‡Ìʈӷ Ì ÙË Ì¤ıÔ‰Ô ÙÔ˘ Tippet ‰ÂÓ ·Ó¤‰ÂÈÍ ÛÙ·ÙÈÛÙÈο ÛËÌ·ÓÙÈΤ˜ ‰È·ÊÔÚ¤˜ ÛÙËÓ ÂÈ‚›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˘ÌÂÚÈÏ‹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). ™˘ÌÂÚ·ÛÌ·ÙÈο, ÂÓÒ ˘ÔÏÔÁ›ÛÙËΠÚÔÁÓˆÛÙÈ΋ ÛËÌ·ÓÙÈÎfiÙËÙ· ÙˆÓ ÎÚÈÙËÚ›ˆÓ ÙÔ˘ ªÈÏ¿ÓÔ˘ ÛÙË Ì¤Ù·-·Ó¿Ï˘ÛË ÙˆÓ ÌÔÓÔ·Ú·ÁÔÓÙÈÎÒÓ ÌÂÏÂÙÒÓ ÙfiÛÔ ÁÈ· ÂÈ‚›ˆÛË, fiÛÔ Î·È ÁÈ· ˘ÔÙÚÔ‹ ÙÔ˘ fiÁÎÔ˘, ‰ÂÓ ÂȂ‚·ÈÒıËΠÛÙË Ì¤Ù·-·Ó¿Ï˘ÛË ÙˆÓ ÔÏ˘·Ú·ÁÔÓÙÈÎÒÓ ÌÂÏÂÙÒÓ, Ô‡Ù ÁÈ· ÙËÓ ÂÈ‚›ˆÛË, Ô‡Ù ÁÈ· ÙËÓ ˘ÔÙÚÔ‹ ÙÔ˘ fiÁÎÔ˘, ÎÏÔÓ›˙ÔÓÙ·˜ ÙËÓ ÚÔÁÓˆÛÙÈ΋ ÛËÌ·Û›· ÙˆÓ ÎÚÈÙËÚ›ˆÓ ·˘ÙÒÓ ÛÙËÓ ÎÏÈÓÈ΋ ÙÔ˘˜ ÂÊ·ÚÌÔÁ‹.

™˘ÌÂÚ¿ÛÌ·Ù· ∏ ÌÂÙ·ÌfiÛ¯Â˘ÛË ‹·ÙÔ˜ ·ÔÙÂÏ› ÙËÓ Î·Ï‡ÙÂÚË ıÂÚ·›· 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˘. OˆÛ‰‹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 ¶·ÓÂÈÛÙ‹ÌÈÔ Ù˘ ∫·ÏÈÊfiÚÓÈ·˜/San Fransisco (UCSF, ÌÔÓ‹Ú˘ fiÁÎÔ˜≤6.5cm, 2-3 fiÁÎÔÈ ÂÎ ÙˆÓ ÔÔ›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˜, fiˆ˜ Ô ‚·ıÌfi˜ Ù˘ ‰È·ÊÔÚÔÔ›ËÛ˘ ÙÔ˘ fiÁÎÔ˘, ÌÔÚÔ‡Ó Ó· ¯ÚËÛÈÌÔÔÈËıÔ‡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˜ ¯ÚËÛÈÌÔÔÈÔ‡ÌÂÓÔÈ Ê·Ú̷΢ÙÈÎÔ› ·Ú¿ÁÔÓÙ˜ Â›Ó·È Î˘Ú›ˆ˜ Ë ÂÓ‰ÔÊϤ‚È· ¯ÔÚ‹ÁËÛË ÚÔÛÙ·Î˘ÎÏ›Ó˘ fiˆ˜ 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 ıÂÚ·›· Ë ÂÚÈÂÁ¯ÂÈÚËÙÈ΋ ıÓËÙfiÙËÙ· ÛÙÔ˘˜ ·ÛıÂÓ›˜ ·˘ÙÔ‡˜ Â›Ó·È ˘„ËÏfiÙÂÚË Î·È fiÙÈ Ë ˘Ï·ÈÔÓ¢ÌÔÓÈ΋ ˘¤ÚÙ·ÛË ÌÔÚ› Ó· ·Ú·Ì›ÓÂÈ Ë Ó· ÚˆÙÔÂÌÊ·ÓÈÛÙ› ·ÎfiÌË Î·È ÌÂÙ¿ ÙË ÌÂÙ·ÌfiÛ¯Â˘ÛË Î¿ÓÔÓÙ·˜ ÂÈÙ·ÎÙÈ΋ ÙËÓ Â·ÁÚ‡ÓËÛË Î·È ÙÔÓ Ì·ÎÚÔ¯ÚfiÓÈÔ ¤ÏÂÁ¯Ô ÙˆÓ ·ÛıÂÓÒÓ ·˘ÙÒÓ.

H Ó¢ÌÔÓÈ΋ ˘¤ÚÙ·ÛË Û ·ÛıÂÓ›˜ Ì Ë·ÙÈ΋ ·ÓÂ¿ÚÎÂÈ· ÙÂÏÈÎÔ‡ ÛÙ·‰›Ô˘ ‹ ·ÏÏÈÒ˜ ˘Ï·ÈÔÓ¢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˘ ÂÌϤÎÔÓÙ·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› ÏÔÈfiÓ 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·ÙÔÔÈÂ›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.

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¢ÈÂÁ¯ÂÈÚËÙÈ΋ ÓÂÊÚÈ΋ ‰˘ÛÏÂÈÙÔ˘ÚÁ›· ÛÙË ÌÂÙ·ÌfiÛ¯Â˘ÛË ‹·ÙÔ˜ ∞. §·Ì·‰·Ú›Ô˘

∞. ∂π™∞°ø°∏

ÎÙËÚ›˙ÂÙ·È ·fi ÓÂÊÚÈ΋ ·ÓÂ¿ÚÎÂÈ· – ÏÂÈÙÔ˘ÚÁÈ΋˜ ·ÈÙÈÔÏÔÁ›·˜ – Î·È ÛÔ‚·Ú¤˜ ‰È·Ù·Ú·¯¤˜ Ù˘ Û˘ÛÙËÌ·ÙÈ΋˜ ΢ÎÏÔÊÔÚ›·˜, ÔÈ Ôԛ˜ 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 ∏.¡.™. ÌÔÚ› Ó· ÂΉËψı› ¯ˆÚ›˜ ÚÔÊ·Ó‹ ·ÈÙ›·, Û˘Ó‹ıˆ˜ fï˜ ˘ÚÔ‰ÔÙÂ›Ù·È ·fi ÔÚÈṲ̂ÓÔ˘˜ ·Ú¿ÁÔÓÙ˜, fiˆ˜ 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›· ÂÙÈÎÔ‡3,4. ∏ ‰È¿ÁÓˆÛË Ù›ıÂÙ·È Ì ·ÔÎÏÂÈÛÌfi fiÏˆÓ ÙˆÓ ¿ÏÏˆÓ ·ÈÙ›ˆÓ Ô˘ ÚÔηÏÔ‡Ó ÓÂÊÚÈ΋ ·ÓÂ¿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˜ ÂÈ‚›ˆÛ˘ 15 Ë̤Ú˜). ΔÔ ∏.¡.™. Ù‡Ô˘ – 2, Â›Ó·È ÈÔ Î·ÏfiËı˜ (̤ÛÔ˜ fiÚÔ˜ ÂÈ‚›ˆÛ˘ 6 Ì‹Ó˜), ¯·Ú·ÎÙËÚ›˙ÂÙ·È ·fi ˘ÔÙÚÔÈ¿˙ÔÓÙ· ·ÛΛÙË Ô˘ ‰ÂÓ ·ÓÙ·ÔÎÚ›ÓÂÙ·È ÛÙË ‰ÈÔ˘ÚËÙÈ΋ ·ÁˆÁ‹ Î·È ÌÔÚ› ÔÔÙ‰‹ÔÙ ӷ ÌÂÙ·¤ÛÂÈ Û هÔ˘ – 13,4. Δ· ÙÂÏÂ˘Ù·›· ¯ÚfiÓÈ·, ¤¯Ô˘Ó ‰ÔÎÈÌ·ÛÙ› Ì ηϿ ·ÔÙÂϤÛÌ·Ù· ‰È¿ÊÔÚ˜ ıÂÚ·›˜ (·ÁÁÂÈÔÛ˘Û·ÛÙÈο Ê¿Ú̷η ·Ó¿ÏÔÁ· Ù˘ ‚·ÛÔÚÂÛÛ›Ó˘, TIPS, MARS), Ô˘ ‚ÂÏÙÈÒÓÔ˘Ó ÙË ÓÂÊÚÈ΋ ÏÂÈ-

∏ ÓÂÊÚÈ΋ ·ÓÂ¿ÚÎÂÈ· Â›Ó·È Û˘¯Ó‹ ÂÈÏÔ΋ ÙˆÓ ·ÛıÂÓÒÓ Ì ÙÂÏÈÎÔ‡ ÛÙ·‰›Ô˘ Ë·ÙÈ΋ ÓfiÛÔ (Δ.™.∏.¡.), Ô˘ ˘Ô‚¿ÏÏÔÓÙ·È Û ÔÚıÔÙÔÈ΋ ÌÂÙ·ÌfiÛ¯Â˘ÛË ‹·ÙÔ˜ (O.ª.∏.). ŸÏ˜ ÔÈ ÌÂϤÙ˜ ‰Â›¯ÓÔ˘Ó fiÙÈ ÙfiÛÔ Ë ÔÍ›· ÓÂÊÚÈ΋ ·ÓÂ¿ÚÎÂÈ· (O.¡.∞.) Ô˘ ÌÔÚ› Ó· ÂΉËψı› ηٿ ÙËÓ ÂÚÈÂÁ¯ÂÈÚËÙÈ΋ ÂÚ›Ô‰Ô Ù˘ ÌÂÙ·ÌfiÛ¯Â˘Û˘ fiÛÔ Î·È Ë ¯ÚfiÓÈ· ÓÂÊÚÈ΋ ·ÓÂ¿ÚÎÂÈ· (Ã.¡.∞.) Ô˘ ·Ó·Ù‡ÛÛÂÙ·È Ì·ÎÚÔÚfiıÂÛÌ· – ΢ڛˆ˜ ·fi ÙË ¯Ú‹ÛË ÙˆÓ ·Ó·ÛÙÔϤˆÓ Ù˘ ηÏÛÈÓ¢ڛÓ˘ – ÂËÚ¿˙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˘ ÌÔÚ› Ó· ÚÔÎÏËı› ·fi ÔÏϤ˜ ÓfiÛÔ˘˜ ‹ ηٷÛÙ¿ÛÂȘ, Ô˘ ÂËÚ¿˙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‡˜, fiˆ˜ 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 Ë·Ù›Ùȉ· μ, ÌÔÚ› Ó· ÂΉËψı› ÌÂÌ‚Ú·Ó҉˘ ˘ÂÚÏ·ÛÙÈ΋ ÛÂÈÚ·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, ÂËÚ¿˙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 ÂÈÙ˘¯‹ ÌÂÙ·ÌfiÛ¯Â˘ÛË ‹·ÙÔ˜2-4. ™‡Ìʈӷ Ì ‰È¿ÊÔÚ˜ ÌÂϤÙ˜, Ô ¯ÚfiÓÔ˜ χÛ˘ ÙÔ˘ ∏.¡.™. ÌÂÙ¿ ·fi ÂÈÙ˘¯‹ 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˘ ÂÈ‚›ˆÛ ̷ÎÚÔÚfiıÂÛÌ· ¯ˆÚ›˜ ıÂÚ·›· ÓÂÊÚÈ΋˜ ˘ÔηٿÛÙ·Û˘ ÌÂÙ¿ ÙËÓ O.ª.∏., Î˘Ì·›ÓÂÙ·È ·fi 58 % ¤ˆ˜ 77 %4,5.

3. OÍ›· ÓÂÊÚÈ΋ ·ÓÂ¿ÚÎÂÈ· ∏ O.¡.∞., ˘fi ÙËÓ ¤ÓÓÔÈ· Ù˘ ÔÍ›·˜ Ì›ˆÛ˘ ÙÔ˘ Ú˘ıÌÔ‡ ÛÂÈÚ·Ì·ÙÈ΋˜ ‰È‹ıËÛ˘ (GFR) Ô˘ ÌÔÚ› Ó· ÚÔηϤÛÂÈ ·˙ˆı·ÈÌ›·, Û˘Ó‰¤ÂÙ·È Ì ıÓËÙfiÙËÙ· ¿Óˆ ·fi 60 % Î·È Â›Ó·È Û˘¯Ó‹ ÂÈÏÔ΋ 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.¡.∞. ÌÔÚ› 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 ·ÓÙÈÌÂÙÒÈÛË ÏÔÈÌÒÍÂˆÓ fiˆ˜ ÔÈ ·ÌÈÓÔÁÏ˘ÎÔÛ›‰Â˜, Ë ·ÌÊÔÙÂÚÈΛÓË μ, ÔÈ ÂÓÈÎÈÏϛӘ, ÔÈ ÎÂÊ·ÏÔÛÔÚ›Ó˜, ÔÈ ÛÔ˘ÏÊÔÓ·Ì›‰Â˜ Î·È Ë ÚÈÊ·ÌÈΛÓË. ∂›Û˘, ÂÓÔ¯ÔÔÈÂ›Ù·È Ë ¯ÔÚ‹ÁËÛË ÙˆÓ ·Ó·ÛÙÔϤˆÓ ÙÔ˘ ÌÂÙ·ÙÚÂÙÈÎÔ‡ ÂÓ˙‡ÌÔ˘ Ù˘ ·ÁÁÂÈÔÙÂÓÛ›Ó˘, ÙˆÓ ÌË ÛÙÂÚÔÂȉÒÓ ·ÓÙÈÊÏÂÁÌÔÓˆ‰ÒÓ Ê·ÚÌ¿ÎˆÓ Û˘ÌÂÚÈÏ·Ì‚·ÓÔÌ¤ÓˆÓ Î·È ÙˆÓ ·Ó·ÛÙÔϤˆÓ Ù˘ COX-2, Ù˘ ÈÓÙÂÚÊÂÚfiÓ˘ Î·È Ù˘ ÈÓÙÂÚÏ¢ΛÓ˘ 2. ∏ O.¡.∞. ÌÔÚ› ·ÛÊ·ÏÒ˜ Ó· ÂΉËψı› Î·È ÛÙ· Ï·›ÛÈ· ¤Ó·Ú͢ ‹ Âȉ›ӈÛ˘ Ë·ÙÔÓÂÊÚÈÎÔ‡ Û˘Ó‰ÚfiÌÔ˘. ªÂ ‚¿ÛË Ù· ·ÓˆÙ¤Úˆ, Â›Ó·È ÚÔÊ·Ó¤˜ fiÙÈ ÔÈ Èı·ÓfiÙËÙ˜ ÂΉ‹ÏˆÛ˘ O.¡.∞. ÔÔÈ·‰‹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.

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°. 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.¡.∞. ∏ Â›ÙˆÛË 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 ÂÂÈÛÔ‰›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 ıÂÚ·›· ˘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 ÂÈϤÔÓ, 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˘ (΢ÎÏÔÛÔÚ›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΋ ·ÓÙÈÌÂÙÒÈÛË Î·È ÂÈÏÔΤ˜ ∂Âȉ‹ ÔÏÏ¿ ·fi Ù· ·›ÙÈ· Î·È ÙÔ˘˜ ·Ú¿ÁÔÓÙ˜ ÎÈÓ‰‡ÓÔ˘ ÚfiÎÏËÛ˘ O.¡.∞. ÂȉÚÔ‡Ó ‹ ÂȉÂÈÓÒÓÔÓÙ·È ‰ÈÂÁ¯ÂÈÚËÙÈο, ¤¯Ô˘Ó ‰ÔÎÈÌ·ÛÙ› Î·È ÌÂÏÂÙËı› ‰È¿ÊÔÚ· ıÂÚ·¢ÙÈο Û¯‹Ì·Ù· Ì ÛÙfi¯Ô ÙËÓ ÚfiÏË„Ë Î·È ‚ÂÏÙ›ˆÛË Ù˘ ÌÂÙÂÁ¯ÂÈÚËÙÈ΋˜ ÓÂÊÚÈ΋˜ ‰˘ÛÏÂÈÙÔ˘ÚÁ›·˜.

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∞. §∞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˘ Â¤Ì‚·Û˘, Ú·ÁÌ·ÙÔÔÈÂ›Ù·È ˘Ô¯ÚˆÙÈÎfi˜, ÚÔÛˆÚÈÓfi˜ ·ÔÎÏÂÈÛÌfi˜ Ù˘ ˘Ï·›·˜ Î·È Ù˘ οو ÎÔ›Ï˘ ÊϤ‚·˜. O ¯ÂÈÚÈÛÌfi˜ ·˘Ùfi˜ ÂÌÔ‰›˙ÂÈ ÙËÓ ·Ô¯¤Ù¢ÛË Ù˘ ÛÏ·¯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 ‰˘ÛÚ·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 ÙÚfiÔ, 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 ÙÚÔÔÔÈËÌ¤ÓˆÓ ¯ÂÈÚÔ˘ÚÁÈÎÒÓ Ù¯ÓÈÎÒÓ, Ô˘ ‰ÂÓ Î·ıÈÛÙÔ‡Ó ϤÔÓ ·Ó·Áη›· ÙË ¯Ú‹ÛË ÙÔ˘. ∂›Û˘, ÔÈ ÌÂϤÙ˜ ‰ÂÓ ˘ÔÛÙËÚ›˙Ô˘Ó ÙËÓ Â˘ÓÔ˚΋ Â›‰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˜ ¯ÚËÛÈÌÔÔÈË̤ÓÔ 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 ÂÛÂÈڷ̤ÓÔ ÛˆÏËÓ¿ÚÈÔ Î·È Ì ·˘Ùfi ÙÔÓ ÙÚfiÔ Ù· ÍÂϤÓÂÈ ·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˘˜ Â›‰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 ÓÂÊÚÔÚÔÛٷ٢ÙÈ΋ 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΋ ·ÓÂ¿ÚÎÂÈ·, ÁÈ·Ù› ÚÔηÏ› ·fiÙÔÌË ·‡ÍËÛË ÙÔ˘ ÂÓ‰·ÁÁÂÈ·ÎÔ‡ fiÁÎÔ˘. ∂›Û˘, Ë ¯ÔÚ‹ÁËÛ‹ Ù˘ ÌÔÚ› 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 ÛÎÔfi 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‡˜ ÂÈ‚·Ú˘ÓÙÈÎÔ‡˜ ·Ú¿ÁÔÓÙ˜ ÎÈÓ‰‡ÓÔ˘ ÚfiÎÏËÛ˘ O.¡.∞. (Ì·˙È΋ ·ÈÌÔÚÚ·Á›·, ÌÂÁ¿Ï˘ ¯ÚÔÓÈ΋˜ ‰È¿ÚÎÂÈ·˜ ˘fiÙ·ÛË, ÛÔ‚·Ú¤˜ ·ÚÚ˘ı̛˜, Î.·.). ∂ÈϤÔÓ ÛÙȘ ÌÂϤÙ˜ ·˘Ù¤˜, Ë ¯ÔÚ‹ÁËÛË Ù˘ ÓÙÔ·Ì›Ó˘ Û˘Óԉ¢fiÙ·Ó ·fi ÙË Û˘Á¯ÔÚ‹ÁËÛË Î·È ¿ÏÏˆÓ ‰˘ÓËÙÈο ÓÂÊÚÔÚÔÛٷ٢ÙÈÎÒÓ ·Ú·ÁfiÓÙˆÓ (Ì·ÓÓÈÙfiÏ˘ ‹ /Î·È ÊÔ˘ÚÔÛÂÌ›‰Ë˜) ‹ ÂÊ·ÚÌÔÁ‹ ÙÔ˘ Û˘ÛÙ‹Ì·ÙÔ˜ V-VB18,19. ™˘ÓÂÒ˜, 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΋˜ ÂÈÛÙÚÔÊ‹˜, Ô˘ ·ÔÙÂÏÔ‡Ó ÛËÌ·ÓÙÈο ÏÂÔÓÂÎÙ‹Ì·Ù· ÛÙËÓ ¿ÌÂÛË Î·È ·ÔÙÂÏÂÛÌ·ÙÈ΋ ·ÓÙÈÌÂÙÒÈÛË 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 ΢ÎÏÔÛÔÚ›ÓË ∞, ¤¯ÂÈ ‰Âȯı› Ë ÓÂÊÚÔÚÔÛٷ٢ÙÈ΋ ‰Ú¿ÛË Ù˘ ÊÔ˘ÚÔÛÂÌ›‰Ë˜ ηٿ ÙËÓ ÚÒ˚ÌË ÌÂÙÂÁ¯ÂÈÚËÙÈ΋ ÂÚ›Ô‰Ô. ∂Âȉ‹ Ë ÓÂÊÚÔÙÔÍÈÎfiÙËÙ· Ù˘ ΢ÎÏÔÛÔÚ›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˚΋ Â›‰Ú·ÛË ÛÙË ‚ÂÏÙ›ˆÛË Ù˘ ÓÂÊÚÈ΋˜ ·ÈÌ·ÙÈ΋˜ ÚÔ‹˜23.

2.5. ™˘Ó‰˘·Ṳ̂ÓË ıÂÚ·›· (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 ÓÂÊÚÔÚÔÛٷ٢ÙÈ΋ ‰Ú¿ÛË ÙÔ˘ ηıÂÓfi˜ ÌÂÌÔӈ̤ӷ Â›Ó·È ÂÏ¿¯ÈÛÙË ÛÙÔ˘˜ ·ÛıÂÓ›˜ Ô˘ ˘Ô‚¿ÏÏÔÓÙ·È Û O.ª.∏. ∏ Ì·ÓÓÈÙfiÏË ÍÂϤÓÂÈ 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˘. ™˘ÓÂÒ˜, Ë Û˘Ó‰˘·Ṳ̂ÓË ¯ÔÚ‹ÁËÛË Î·È ÙˆÓ ÙÚÈÒÓ Ê·ÚÌ¿ÎˆÓ Â›Ó·È Èı·ÓfiÓ Ó· ¤¯ÂÈ ¤Ó· ηχÙÂÚÔ ·ıÚÔÈÛÙÈÎfi, ÓÂÊÚÔÚÔÛٷ٢ÙÈÎfi ·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 ÙÚÈÏ‹ ·ÁˆÁ‹, Ù· ÌÂÙÂÁ¯ÂÈÚËÙÈο Â›‰· 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, Â·Ó‹Ïı·Ó ÛÙȘ ‚·ÛÈΤ˜ ÙÈ̤˜ ÂÚ› ÙËÓ ¤‚‰ÔÌË ÌÂÙÂÁ¯ÂÈÚËÙÈ΋ Ë̤ڷ24. ™˘ÓÂÒ˜, Ù· ·ÔÙÂϤÛÌ·Ù· ·˘Ù¿ ‰Â›¯ÓÔ˘Ó fiÙÈ Î·È Ô ÙÚÈÏfi˜ Û˘Ó‰˘·ÛÌfi˜ – Ì·ÓÓÈÙfiÏË, ÓÙÔ·Ì›ÓË, ÊÔ˘ÚÔÛÂÌ›‰Ë – ·ÛΛ ÂÏ¿¯ÈÛÙË ÓÂÊÚÔÚÔÛÙ·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 ÛÎÔfi 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΋ ÓÂÊÚÔÚÔÛٷ٢ÙÈ΋ ‰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 ÛÎÔfi ÙË Û‡ÁÎÚÈÛË ÙˆÓ ‰‡Ô ·Ú·ÁfiÓÙˆÓ ÛÙËÓ ÚfiÏË„Ë Ù˘ ‚Ï¿‚˘ ·fi ÙËÓ ÈÛ¯·ÈÌ›· – Â·Ó·ÈÌ¿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 ÌÔÚ› 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΋ Â¤Ì‚·ÛË ‰ÂÓ ¤‰ÂÈÍ ÙË ÓÂÊÚÔÚÔÛٷ٢ÙÈ΋ ‰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 ¿ÓıÚˆÔ, ÌÂÙ·ÙÚ¤ÂÙ·È Û ÌÂÙ·‚Ôϛ٘ Ô˘ ÌÔÚÔ‡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 fiˆ˜ Ë ‚Ï¿‚Ë ÈÛ¯·ÈÌ›·˜ – Â·Ó·ÈÌ¿ÙˆÛ˘, fiˆ˜ Û˘Ì‚·›ÓÂÈ Î·Ù¿ ÙËÓ Ë·ÙÈ΋ ÌÂÙ·ÌfiÛ¯Â˘ÛË. ∏ ¡-·ÎÂÙ˘Ï΢ÛÙ½ÓË ·Ú·Ì¤ÓÂÈ Ë Î‡ÚÈ· ıÂÚ·›· ÛÙËÓ ·ÓÙÈÌÂÙÒÈÛË Ù˘ Ë·ÙÔÙÔÍÈÎfiÙËÙ·˜ Ô˘ ÚÔηÏ› Ë ·Ú·ÎÂÙ·ÌfiÏË. §fiÁˆ Ù˘ Ë·ÙÔÚÔÛٷ٢ÙÈ΋˜ Ù˘ ‰Ú¿Û˘, ¤¯ÂÈ ¯ÔÚËÁËı› Û ·ÚÎÂÙ¤˜ ÎÏÈÓÈΤ˜ ÌÂϤÙ˜ Û ·ÛıÂÓ›˜ Ì Δ.™.∏.¡., Ô˘ ˘Ô‚¿ÏÏÔÓÙ·È Û Ë·ÙÈ΋ ÌÂÙ·ÌfiÛ¯Â˘ÛË Ì ÛÎÔfi 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 ÂÂÌ‚·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΋ ÓÂÊÚÔÚÔÛÙ·Û›· ‰ÂÓ ÂÈÙ˘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 ÂÈı˘ÌËÙ‹, ‰ÈfiÙÈ ı· ‚ÔËı‹ÛÂÈ ÙË ÛˆÛÙ‹ ·ÓÙÈÌÂÙÒÈÛË ·˘ÙÒÓ ÙˆÓ ·ÛıÂÓÒÓ Û ÔÏϤ˜ ηÙ¢ı‡ÓÛÂȘ, fiˆ˜ Ë ‰È·¯Â›ÚÈÛË Ù˘ ıÂÚ·›·˜ ˘ÔηٿÛÙ·Û˘ Ù˘ ÓÂÊÚÈ΋˜ ÏÂÈÙÔ˘ÚÁ›·˜, Ë ÙÚÔÔÔ›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‰ÈÔÓ¢ÌÔÓÈ΋ ·Ú¿Î·Ì-

„Ë. ™ÙÔ˘˜ ·ÛıÂÓ›˜ Ô˘ Ù· Â›‰· ÙˆÓ ‚ÈÔ‰ÂÈÎÙÒÓ ·˘ÙÒÓ ‚Ú¤ıËÎ·Ó ·˘ÍË̤ӷ, ÂΉËÏÒıËΠÔÍ›· ÓÂÊÚÈ΋ ‚Ï¿‚Ë – ÔÚÈ˙fiÌÂÓË ˆ˜ ¿Óˆ ·fi 50% ·‡ÍËÛË ÙˆÓ ÂÈ¤‰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΋ ıÂÚ·›· Ì ·Ó·ÛÙÔÏ›˜ Ù˘ ηÏÛÈÓ¢ڛÓ˘ (΢ÎÏÔÛÔÚ›ÓË ∞, tacrolimus). ªÂ ‰Â‰Ô̤ÓÔ fiÙÈ Ë ·ÓÙÈÌÂÙÒÈÛË Ù˘ ÓÂÊÚÈ΋˜ ·ÓÂ¿ÚÎÂÈ·˜ – ÔÍ›·˜ ‹ ¯ÚfiÓÈ·˜ – ·Ú·Ì¤ÓÂÈ ˘ÔÛÙËÚÈÎÙÈ΋ Î·È fi¯È ıÂÚ·¢ÙÈ΋ (ÂÎÙfi˜ Î·È ·Ó Ô ·ÛıÂÓ‹˜ ˘Ô‚ÏËı› Û ÂÈÙ˘¯‹ ÓÂÊÚÈ΋ ÌÂÙ·ÌfiÛ¯Â˘ÛË), Â›Ó·È ÛËÌ·ÓÙÈÎfi Ë ¤Ú¢ӷ Ó· ÂÛÙÈ¿ÛÂÈ Û ‰‡Ô ·ÚÈ· ‰›·: ÛÙËÓ Â͇ÚÂÛË ÓÂÊÚÔÚÔÛٷ٢ÙÈÎÒÓ ·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΋ ·ÓÂ¿ÚÎÂÈ· Î·È ·˘Ùfi ‰ÂÓ Â›Ó·È ¿ÓÙ· ÂÊÈÎÙfi Û ÂÂÌ‚¿ÛÂȘ fiˆ˜ Ë O.ª.∏. Î·È ÛÙËÓ Â͇ÚÂÛË ·ÍÈfiÈÛÙˆÓ ‚ÈÔ‰ÂÈÎÙÒÓ, Ô˘ Ó· ÚԂϤ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·¯ÈÛÙÔÔÈÔ‡ÓÙ·È ÔÈ ·Ú¿ÁÔÓÙ˜ Ô˘ ÙËÓ ÚÔηÏÔ‡Ó.

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25. Planinsic RM, et al. Dopamine, furosemide and mannitol infusions and changes in serum creatinines after liver transplantation. Liver Transpl Surg. 1997; 3:C40.

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∏ ÔÚıÔÙÔÈ΋ ÌÂÙ·ÌfiÛ¯Â˘ÛË ‹·ÙÔ˜ (O.ª.∏.) ·ÔÙÂÏ› ÙËÓ ıÂÚ·›· ÂÎÏÔÁ‹˜ Û ·ÛıÂÓ›˜ Ì ÔÍ›· ‹ ¯ÚfiÓÈ· Ë·ÙÈ΋ ·ÓÂ¿ÚÎÂÈ· ÙÂÏÈÎÔ‡ ÛÙ·‰›Ô˘. ∂›Ó·È ÌÈ· ÛÔ‚·Ú‹ ¯ÂÈÚÔ˘ÚÁÈ΋ Â¤Ì‚·ÛË Ô˘ ¤¯ÂÈ ÂÍÂÏȯı› ÛËÌ·ÓÙÈο ·fi ÙËÓ ÚÒÙË ª.∏. Û ¿ÓıÚˆÔ ÙÔ 1963 ·fi ÙÔÓ Starzl1. ¢˘ÛÙ˘¯Ò˜, Ô ÚÒÙÔ˜ ·˘Ùfi˜ ·ÛıÂÓ‹˜ η٤ÏËÍ ·fi ·Î·Ù¿Û¯ÂÙË ·ÈÌÔÚÚ·Á›·, ÁÂÁÔÓfi˜ Ô˘ ¤‰ÂÈÍ fiÙÈ Ë ÂÈÏÔ΋ ·˘Ù‹ ı· ·ÔÙÂÏÔ‡Û ÛËÌ·ÓÙÈÎfi ·›ÙÈÔ ÓÔÛËÚfiÙËÙ·˜ Î·È ıÓËÙfiÙËÙ·˜ Ù· ÂfiÌÂÓ· ¯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· ÛËÙÈÎÒÓ ÂÂÈÛÔ‰›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·. ∂ÈϤÔÓ, 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 ϤÔÓ fi¯È ÌfiÓÔ Ì ÙȘ ÎÏ·ÛÛÈΤ˜ ıÂÚ·›˜ ˘ÔηٿÛÙ·Û˘ Ì ÊÚ¤ÛÎÔ Î·Ù„˘Á̤ÓÔ Ï¿ÛÌ·

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∞˘ÍË̤ӷ Â›‰· ·Ú·ÁfiÓÙˆÓ VIII Î·È vWf

∂ËÚ·Ṳ̂ÓË ÏÂÈÙÔ˘ÚÁÈ- ∂Ï·Ùو̤ӷ Â›‰· ÚˆÙ½ÎfiÙËÙ· ÙˆÓ ·ÈÌÔÂÙ·Ï›ˆÓ Ó˘ C, ÚˆÙ½Ó˘ S Î·È ·ÓÙÈıÚÔÌ‚›Ó˘ ∞˘ÍË̤ÓË ·Ó·ÛÙÔÏ‹ ∂Ï·Ùو̤ӷ Â›‰· Ï·ÛÌÈ·ÈÌÔÂÙ·Ï›ˆÓ ·fi ÙÔ ÓÔÁfiÓÔ˘ ÓÈÙÚÈÎfi ÔÍ›‰ÈÔ, ÙËÓ ÚÔÛÙ·Î˘ÎÏ›ÓË πππ Î·È ÙËÓ ·2-·ÓÙÈÏ·ÛÌ›ÓË ∂Ï·Ùو̤ÓË Û˘ÁΤÓÙÚˆÛË ∞˘ÍË̤ӷ Â›‰· 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¿ Â›‰· ·2-·ÓÙÈÏ·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 ‹Ș ‰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· ˘ÔËÎÙÈ΋ ηٿÛÙ·ÛË18,19. ¶Ú¤ÂÈ Ó· ÛËÌÂȈı› fiÙÈ ÔÈ ·ÛıÂÓ›˜ Ì Ë·ÙÔ΢ÙÙ·ÚÈÎfi ηÚΛÓÔ Î·È ¯ÔÏÔÛÙ·ÙÈ΋ ΛÚÚˆÛË ‚Ú›ÛÎÔÓÙ·È Û ˘ÂÚËÎÙÈ΋ ηٿÛÙ·ÛË (fiˆ˜ ·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˘ Â¤Ì‚·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 Ë·ÙÈ΋ ·ÓÂ¿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 Â›‰· ÙÔ˘ ÂÓÂÚÁÔÔÈËÙ‹ ÙÔ˘ Ï·ÛÌÈÓÔÁfiÓÔ˘ (tissue – plasminogen activator t-PA)18,19. O t-PA ÂÓÂÚÁÔÔÈ› ÙËÓ ÌÂÙ·ÙÚÔ‹ ÙÔ˘ Ï·ÛÌÈÓÔÁfiÓÔ˘ Û Ï·ÛÌ›ÓË Ô˘ Ì ÙËÓ ÛÂÈÚ¿ Ù˘ ηٷχÂÈ ÙËÓ ·Ô‰fiÌËÛË Ù˘ ÈÓÈ΋˜ ÙÔ˘ ıÚfiÌ‚Ô˘ ÛÙ· ÚÔÈfiÓÙ· ‰È¿Û·Û‹˜ Ù˘. Δ· ·˘ÍË̤ӷ Â›‰· ÙÔ˘ t-PA ÔÊ›ÏÔÓÙ·È Î˘Ú›ˆ˜ ÛÙËÓ ·‰˘Ó·Ì›· Ë·ÙÈ΋˜ οı·ÚÛ˘ ÙÔ˘22. ∂ÈϤÔÓ, 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-·ÓÙÈÏ·ÛÌ›Ó˘ Î·È Ù· ·˘ÍË̤ӷ Â›‰· 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˘ Â¤Ì‚·Û˘ Î·È ÚÔηÏ› ÛÔ‚·Ú¤˜ ‰È·Ù·Ú·¯¤˜ Ù˘ ·ÈÌfiÛÙ·Û˘. ª¤Û· Û ÌÂÚÈο ÏÂÙ¿ ·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 ·ÈÌÔÂÙ·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 ·ÈÌÔÂÙ·Ï›ˆÓ ÌÂٷ͇ Ù˘ ·ÚÙËÚȷ΋˜ Î·È ÊÏ‚È΋˜ ΢ÎÏÔÊÔÚ›·˜ ÛÙÔ Ó¤Ô ‹·Ú23. O ‚·ıÌfi˜ Ù˘ ÂÏ¿ÙÙˆÛ˘ ÙˆÓ ·ÈÌÔÂÙ·Ï›ˆÓ Ê·›ÓÂÙ·È Ó· Û¯ÂÙ›˙ÂÙ·È Ì ÙËÓ ‚·Ú‡ÙËÙ· Ù˘ ‚Ï¿‚˘ ·fi ÙËÓ ÈÛ¯·ÈÌ›· – Â·Ó·ÈÌ¿ÙˆÛË ÙÔ˘ ‹·ÙÔ˜. Δ· ·ÈÌÔÂÙ¿ÏÈ· ÚÔÛÎÔÏÏÒÓÙ·È ÛÙÔ ÂÓ‰Ôı‹ÏÈÔ ÙˆÓ ÂÓ‰ÔË-

·ÙÈÎÒÓ ·ÁÁ›ˆÓ Î·È ÂÈÙ›ÓÔ˘Ó ÙËÓ ‚Ï¿‚Ë ·˘Ù‹ ̤ۈ Ù˘ ÚfiÎÏËÛ˘ ·fiÙˆÛ˘ ÙˆÓ ÂÓ‰ÔıËÏÈ·ÎÒÓ Î˘ÙÙ¿ÚˆÓ 24. ∏ ÂÓ‰ÔË·ÙÈ΋ ηٷÎÚ¿ÙËÛË ÙˆÓ ·ÈÌÔÂÙ·Ï›ˆÓ, Ë Á¤ÓÂÛË ıÚÔÌ‚›Ó˘ ÛÙÔ ÂÓÂÚÁÔÔÈË̤ÓÔ ÂÓ‰Ôı‹ÏÈÔ ÙÔ˘ ÌÔۯ‡̷ÙÔ˜, Ë ÂÍ·ÁÁ›ˆÛË ·ÈÌÔÂÙ·Ï›ˆÓ ÛÙÔ˘˜ ¯ÒÚÔ˘˜ ÙÔ˘ Disse Î·È Ë ·˘ÍË̤ÓË Ê·ÁÔ΢ÙÙ¿ÚˆÛË ÙÔ˘˜ ·fi Ù· ·ÙÙ·Ú· Kuppfer ¤¯Ô˘Ó ÂÓÔ¯ÔÔÈËı› ÁÈ· ÙË ıÚÔÌ‚ÔÂÓ›·. ∂ÈϤÔÓ, ηٿ ÙËÓ Ê¿ÛË ·˘Ù‹ ·Ú·ÙËÚÂ›Ù·È ·˘ÍË̤ÓË ÈÓˆ‰fiÏ˘ÛË ÏfiÁˆ ÙˆÓ ·˘ÍËÌ¤ÓˆÓ ÂÈ¤‰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˘ ‰˘ÛÚ·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 Ë·Ú›ÓË ·fi ÙÔ ÈÛ¯·ÈÌÈÎfi ÂÓ‰Ôı‹ÏÈÔ ÙÔ˘ ÌÔۯ‡̷ÙÔ˜, ÛÙÔ 25-95% ÙˆÓ ÂÚÈÙÒÛˆÓ25. ∞˘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 ÂÚÈÙÒÛÂȘ ·˘Ù¤˜ ¤¯ÂÈ ¯ÚËÛÈÌÔÔÈËı› Ë ÚˆÙ·Ì›ÓË ˆ˜ ·Ó·ÛÙÚÔʤ·˜ Ù˘ ‰Ú¿Û˘ Ù˘ Ë·Ú›Ó˘. ¶Ú¤ÂÈ Ó· ÙÔÓÈÛÙ› fiÙÈ Î·È ¿ÏÏÔÈ ·Ú¿ÁÔÓÙ˜ fiˆ˜ Ë ÌÂÙ·‚ÔÏÈ΋ ÔͤˆÛË, Ë ˘ÔıÂÚÌ›·, Ë ¯·ÌËÏ‹ Û˘ÁΤÓÙÚˆÛË ÈÔÓÈṲ̂ÓÔ˘ Ca Û˘ÓÂÈÎÔ˘ÚÔ‡Ó ÛÙȘ ‰È·Ù·Ú·¯¤˜ ËÎÙÈÎÔ‡ Ì˯·ÓÈÛÌÔ‡ ÛÙËÓ Ê¿ÛË ·˘Ù‹.

4) ªÂÙÂÁ¯ÂÈÚËÙÈ΋ Ê¿ÛË ∏ ıÚÔÌ‚ÔÂÓ›· 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 ·ÈÌÔÂÙ·Ï›ˆÓ ÌÂÙ¿ ÙËÓ Â·Ó·ÈÌ¿ÙˆÛË, ÊÙ¿ÓÂÈ ÛÙÔ Ó·‰›Ú 2 Ì 3 Ë̤Ú˜ ÌÂÙ¿ (ÛÔ‚·Ú‹ ıÚÔÌ‚ÔÂÓ›· < 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· Â›‰· ıÚÔÌ‚ÔÔÈËÙ›Ó˘ ·˘Í¿ÓÔ˘Ó ·fi ÙËÓ ÚÒÙË Ì¤Ú· Î·È ÙËÓ 5Ë Ì¤Ú· ·Ú¯›˙Ô˘Ó Ó· ΢ÎÏÔÊÔÚÔ‡Ó Ó¤· ·ÈÌÔÂÙ¿ÏÈ·. ∏ Û˘ÁΤÓÙÚˆÛ‹ ÙÔ˘˜ ÊÙ¿ÓÂÈ ÛÂ Ê˘ÛÈÔÏÔÁÈο Â›‰· 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˘ ÔÈÛıÔÂÚÈÙÔÓ·›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·˜ ÂȉÂÈÓÒÓÔÓÙ·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. EÈϤÔÓ, 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 ·ÈÌÔÂÙ·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 ·ÓÙÈÌÂÙÒÈÛË ÙˆÓ ÛÔ‚·ÚÒÓ ·ÈÌÔÚÚ·ÁÈÒÓ Î·Ù¿ ÙË ‰È¿ÚÎÂÈ· Ù˘ O.ª.∏. fiˆ˜ 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 ıÂÚ·›· ÙˆÓ ‰È·Ù·Ú·¯ÒÓ Ù˘ ·ÈÌfiÛÙ·Û˘ ¤¯Ô˘Ó ¯ÚËÛÈÌÔÔÈËı› ÔÈ ÎÏ·ÛÛÈΤ˜ Ù¯ÓÈΤ˜ ˘ÔηٿÛÙ·Û˘ ÙˆÓ ·Ú·ÁfiÓÙˆÓ (ÊÚ¤ÛÎÔ Î·Ù„˘Á̤ÓÔ Ï¿ÛÌ· FFP, ÎÚ˘ÔηıÈ˙‹Ì·Ù·), ·ÈÌÔÂÙ·Ï›ˆÓ ηıÒ˜ Î·È ·Ó·ÛÙÔÏ‹˜ Ù˘ ÈÓˆ‰fiÏ˘Û˘ Ì ·ÓÙÈ-ÈÓˆ‰ÔÏ˘ÙÈÎÔ‡˜ ·Ú¿ÁÔÓÙ˜ (Â-·ÌÈÓÔηÚÔ˚Îfi Ô͇, ·ÚÔÙÈÓ›ÓË, ÙÚ·ÓÍÂÓ·ÌÈÎfi Ô͇). ΔËÓ ÙÂÏÂ˘Ù·›· ÂÙ·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 ÂÓÂÚÁÔÔÈË̤ÓË 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

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Factor, TF ) Î·È ÂÓÂÚÁÔÔ›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‡ÌÏÔÎÔ FVIIa – ÈÛÙÈÎÔ‡ ·Ú¿ÁÔÓÙ· Ô˘ Û¯ËÌ·Ù›˙ÂÙ·È ÂÓÂÚÁÔÔÈ› Ì ÙËÓ ÛÂÈÚ¿ ÙÔ˘ ÙÔÓ ·Ú¿ÁÔÓÙ· Ã Ô ÔÔ›Ô˜ ÂÓÂÚÁÔÔÈ› ·ÚÁ¿ ÙËÓ ÚÔıÚÔÌ‚›ÓË Î·È ·Ú¿ÁÔÓÙ·È Ù· ÚÒÙ· ÌfiÚÈ· ıÚÔÌ‚›Ó˘. H ıÚÔÌ‚›ÓË Â›Ó·È ˘‡ı˘ÓË ÁÈ· ÙËÓ ÌÂÁÈÛÙÔÔ›ËÛË Ù˘ ÂÓÂÚÁÔÔ›ËÛ˘ Ù˘ ‹Í˘, ÙÔÓ Û¯ËÌ·ÙÈÛÌfi Ù˘ ÈÓÈ΋˜ Î·È ÁÈ· ÙËÓ ÛÙ·ıÂÚÔÔÈ‹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‡ÌÏÔÎÔ FVIIa – ÈÛÙÈÎÔ‡ ·Ú¿ÁÔÓÙ·, ÂÓÂÚÁÔÔÈ› ÙÔÓ ·Ú¿ÁÔÓÙ· IX Ô ÔÔ›Ô˜ Ì ÙËÓ ÛÂÈÚ¿ ÙÔ˘, ·ÚÔ˘Û›· ÂÓÂÚÁÔÔÈËÌ¤ÓˆÓ ·ÈÌÔÂÙ·Ï›ˆÓ, ÚÔηÏ› ·Ú·ÁˆÁ‹ ıÚÔÌ‚›Ó˘. ‚) Û‡Ó‰ÂÛË Ì ٷ ÂÓÂÚÁÔÔÈË̤ӷ ·ÈÌÔÂÙ¿ÏÈ· Î·È ÂÓÂÚÁÔÔ›ËÛË ÙÔ˘ ·Ú¿ÁÔÓÙ· Ã. O rFVIIa ÌÔÚ› Ó· ÂÓÂÚÁÔÔÈ‹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 ÌÔÚ› Ó· Û˘Ó‰Âı› ¿ÌÂÛ· Ì ٷ ÂÓÂÚÁÔÔÈË̤ӷ ·ÈÌÔÂÙ¿ÏÈ· Î·È Ó· ÂÓÂÚÁÔÔÈ‹ÛÂÈ ÙÔÓ ·Ú¿ÁÔÓÙ· Ã Ô ÔÔ›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‚ÔÂÓ›· Ô˘ ·ÈÌÔÚÚ·ÁÔ˘Ó Ô rFVIIa Â›Ó·È ·ÔÙÂÏÂÛÌ·ÙÈÎfi˜ ÛÙËÓ ÂÏ¿ÙÙˆÛË Ù˘ ·ÈÌÔÚÚ·Á›·˜32,33. ™Â ÌÈ· ÚfiÛÊ·ÙË ÌÂϤÙË, ·ԉ›¯ıËΠfiÙÈ Ô rFVIIa ÛÙÔ˘˜ ıÚÔÌ‚ÔÂÓÈÎÔ‡˜ ·ÛıÂÓ›˜ ÂÈÙ·¯‡ÓÂÈ ÙËÓ Á¤ÓÂÛË ıÚÔÌ‚›Ó˘, ÙËÓ ÂÓÂÚÁÔÔ›ËÛË ÙˆÓ ·ÈÌÔÂÙ·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‚ÔÂÓ›· (·ÚÈıÌfi ·ÈÌoÂÙ·Ï›ˆÓ < 20 x 109/lt) , o rFVIIa ‰ÂÓ ‚ÂÏÙ›ˆÛ ÙËÓ ÛÙ·ıÂÚfiÙËÙ· ÙÔ˘ ıÚfiÌ‚Ô˘ ÂÓÒ Û ÌÂÁ·Ï‡ÙÂÚ˜ ÙÈ̤˜ ·ÈÌÔÂÙ·Ï›ˆÓ Ë ÛÙ·ıÂÚfiÙËÙ· ÙÔ˘ ıÚfiÌ‚Ô˘ ‹Ù·Ó Ê˘ÛÈÔÏÔÁÈ΋. ∏ ·Ú·Ù‹ÚËÛË ·˘Ù‹ ¤¯ÂÈ ÛËÌ·Û›· ÁÈ· ÙÔ˘˜ ÎÈÚÚˆÙÈÎÔ‡˜ ıÚÔÌ‚ÔÂÓÈÎÔ‡˜ ·ÛıÂÓ›˜ ÌÈ· Î·È Ë ¯ÔÚ‹ÁËÛË rFVIIa ı· Ô‰ËÁ‹ÛÂÈ ÛÙËÓ ‰ËÌÈÔ˘ÚÁ›· ÛÙ·ıÂÚÒÓ ıÚfiÌ‚ˆÓ Î·È ÂÔ̤ӈ˜ Û ÂÚÈÔÚÈÛÌfi ÙˆÓ ·ÈÌÔÚÚ·ÁÈÒÓ ÛÙÔ˘˜ ·ÛıÂÓ›˜ Ì > 20 x 109/lt ·ÈÌÔÂÙ¿ÏÈ·.

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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΋ ‹ Â›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˜ ÂÂÌ‚¿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 ·ÓıÚÒÔ˘˜, ¤Ó·˜ ÌÂÁ¿ÏÔ˜ ·ÚÈıÌfi˜ ÌÂÏÂÙÒÓ Ì ÌÈÎÚfi ·ÚÈıÌfi ·ÛıÂÓÒÓ ¤¯Ô˘Ó ·Ó·Ê¤ÚÂÈ ÈηÓÔÔÈËÙÈ΋, ·ÔÙÂÏÂÛÌ·ÙÈ΋ Î·È ·ÛÊ·Ï‹ ¯Ú‹ÛË ÙÔ˘ rFVIIa Û ‰È¿ÊÔÚ˜ ÎÏÈÓÈΤ˜ ηٷÛÙ¿ÛÂȘ Ì ÌÂÁ¿Ï˜ ·ÒÏÂȘ ·›Ì·ÙÔ˜ fiˆ˜ Û ·ÛıÂÓ›˜ Ì Ë·ÙÈ΋ ·ÓÂ¿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¿‰· fiÔ˘ Ë ¯Ú‹ÛË ÙÔ˘ rFVIIa Èı·ÓÒ˜ Ó· ÌÔÚÔ‡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 ÔÔ›ÔÈ ¤Ï·‚·Ó rFVIIa Û ‰fiÛË 80Ìg/kg ÚÈÓ ÙËÓ ¤Ó·ÚÍË Ù˘ Â¤Ì‚·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¤˜ Â›Û˘ ·Ú·Ù‹ÚËÛ·Ó, Ì ÙË ¯Ú‹ÛË Ù˘ ıÚÔÌ‚ÔÂÏ·ÛÙÔÁÚ·Ê›·˜ (thromboelastography, TEG), fiÙÈ Ë ¯ÔÚ‹ÁËÛË ÙÔ˘ rFVIIa ÂÈÙ¿¯˘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˘¯·ÈÔÔÈË̤Ó˜, ‰ÈϤ˜Ù˘ÊϤ˜, ÂÏÂÁ¯fiÌÂÓ˜ Ì ÂÈÎÔÓÈÎfi Ê¿ÚÌ·ÎÔ (placebo-controlled) ÌÂϤÙ˜. ™ÙËÓ ÚÒÙË, ÂϤÁ¯Ô˘ ‰fiÛ˘ ÌÂϤÙË, 82 ·ÛıÂÓ›˜ Ù˘¯·ÈÔÔÈ‹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 ÂÂÈÛÔ‰›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΋ Â¤Ì‚·ÛË Î·È Ô ¯ÚfiÓÔ˜ ÚÔıÚÔÌ‚›Ó˘ Â·ÓÂÚ¯fiÙ·Ó ÛÙ· ÚÔ Ù˘ ¯ÔÚ‹ÁËÛ˘ Â›‰· ̤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˘ Â·Ó¤Ú¯ÔÓÙ·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 Â·Ó·ÈÌÔÚÚ·Á›· Î·È Û ÌÂÙ·ÁÁ›ÛÂȘ ·›Ì·ÙÔ˜ Ì ÙËÓ ›‰È· Û˘¯ÓfiÙËÙ· fiˆ˜ Î·È ÛÙËÓ placebo ÔÌ¿‰· (›Ó·Î·˜ 2). ™Â ÌÈ· ¿ÏÏË ÔÏ˘ÎÂÓÙÚÈ΋ ÌÂϤÙË, 183 ·ÛıÂÓ›˜ Ù˘¯·ÈÔÔÈ‹ıËÎ·Ó Û 3 ÔÌ¿‰Â˜ Î·È ¤Ï·‚·Ó placebo, 80 ‹ 120 Ìg/kg rFVIIa ·ÓÙ›ÛÙÔȯ·. OÈ ‰fiÛÂȘ Â·Ó·Ï·Ì‚·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˘ Â¤Ì‚·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 ·ԉ›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. AÔÙÂϤÛÌ·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)

ÂÂÈÛfi‰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.: oÚıÔÙÔÈ΋ ÌÂÙ·ÌfiÛ¯Â˘ÛË ‹·ÙÔ˜, ∏.∞.: Ë·ÙÈ΋ ·ÓÂ¿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 ¯ÚËÛÈÌÔÔÈ‹ıËÎ·Ó ÌÂÁ·Ï‡ÙÂÚ˜ ‰fiÛÂȘ rFVIIa Î·È Û Â·Ó·Ï·Ì‚·ÓfiÌÂÓ˜ ‰fiÛÂȘ. ∫·È Û ·˘Ù‹Ó ÙËÓ ÌÂϤÙË fiˆ˜ Î·È ÛÙËÓ ÚÔËÁÔ‡ÌÂÓË, ‰ÂÓ ˘‹ÚÍ ÛÙ·ÙÈÛÙÈο ÛËÌ·ÓÙÈ΋ ‰È·ÊÔÚ¿ ÛÙËÓ Û˘¯ÓfiÙËÙ· ÙˆÓ ıÚÔÌ‚ÔÂÌ‚ÔÏÈÎÒÓ ÂÂÈÛÔ‰›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˘¯·ÈÔÔÈ‹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 ÌÔÚ› Ó· ¯ÚËÛÈÌÔÔÈËı› ÛÙËÓ ª.∏. Œ¯Ô˘Ì ÛÙË ‰È¿ıÂÛ‹ Ì·˜ ¤Ó· Ê¿ÚÌ·ÎÔ Ô˘ ¤¯ÂÈ ·ԉ›ÍÂÈ Û ÔÏϤ˜ (in vitro Î·È ÎÏÈÓÈΤ˜) ÌÂϤÙ˜ fiÙÈ ¤¯ÂÈ ÛËÌ·ÓÙÈ΋ ÚÔËÎÙÈ΋ ‰Ú·ÛÙËÚÈfiÙËÙ·. ŸÌˆ˜ ̤¯ÚÈ ÙÒÚ· ‰ÂÓ ¤¯ÂÈ ·Ô‰Âȯı› Ó· ÚÔηÏ› ÛËÌ·ÓÙÈ΋ ÂÏ¿ÙÙˆÛË Ù˘ ·ÈÌÔÚÚ·ÁÈ΋˜ ‰È¿ıÂÛ˘ Î·È Î·Ù’ Â¤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˘¯·ÈÔÔÈË̤Ó˜ ÌÂϤÙ˜ Ô˘ ¤ÁÈÓ·Ó Û ·ÛıÂÓ›˜ Ô˘ ˘Ô‚¿ÏÏÔÓÙ·È Û ª.∏. ·¤Ù˘¯·Ó Ó· ·ԉ›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΋ ·ÓÂ¿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‚ÔÂÓ›· ñ ˘Ï·›· ˘¤ÚÙ·ÛË ñ Û˘Ó˘¿Ú¯Ô˘Û· ÓÂÊÚÈ΋ ·ÓÂ¿ÚÎÂÈ· ñ ¯ÂÈÚÔ˘ÚÁÈ΋ Ù¯ÓÈ΋ ñ ·Ó·ÈÛıËÛÈÔÏÔÁÈ΋ ·ÓÙÈÌÂÙÒÈÛË. ŸÏÔÈ ·˘ÙÔ› ÔÈ ·Ú¿ÁÔÓÙ˜ Ô˘ÛÈ·ÛÙÈο ÌÂÙ·‚¿ÏÏÔ˘Ó ÙÔÓ ·ÈÌÔÚÚ·ÁÈÎfi ΛӉ˘ÓÔ Î·È ‰È·ÊÔÚÔÔÈÔ‡Ó ÙËÓ ·Ó¿ÁÎË ÁÈ· ıÂÚ·›·47. ª›· ÚfiÛÊ·ÙË ÌÂϤÙË, ¯ÚËÛÈÌÔÔÈÒÓÙ·˜ 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΋˜ ·ÓÂ¿ÚÎÂÈ·˜ Ì ÛÎÔfi Ó· ·Ó·ÚÔÛ‰ÈÔÚÈÛÙ› Ë ÔÌ¿‰· ·ÛıÂÓÒÓ Ô˘ ¯Ú‹˙Ô˘Ó ıÂÚ·›·˜ Ì ÚÔËÎÙÈÎÔ‡˜ ·Ú¿ÁÔÓÙ˜48. H ¯Ú‹ÛË ÙÔ˘ rFVIIa ‰ÂÓ ÚÔÙ›ÓÂÙ·È ˆ˜ Ù˘ÊÏ‹ ıÂÚ·›· 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 ÂÈÏÔÁ‹ ÙˆÓ ˘Ô„ËÊ›ˆÓ ÚÔ˜ ÌÂÙ·ÌfiÛ¯Â˘ÛË ¤¯ÂÈ Ô‰ËÁ‹ÛÂÈ Û ÂÂÌ‚¿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· ıÂÚ·¢ÙÈο ̤۷ ¤¯Ô˘Ó ·ÔÙ‡¯ÂÈ Î·È Ë ¯Ú‹ÛË ÙÔ˘ rFVIIa ·ÔÙÂÏ› ÙËÓ ıÂÚ·›· ‰È¿ÛˆÛ˘ (rescue therapy)51.

OÈ ‰‡Ô ·˘Ù¤˜ ÌÂÁ¿Ï˜ Ù˘¯·ÈÔÔÈË̤Ó˜ 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· Â·Ó·ÈÌÔÚÚ·Á›·41,42. ∞˘Ùfi ÛËÌ·›ÓÂÈ fiÙÈ ÙfiÛÔ Ë ‰fiÛË ÙÔ˘ rFVIIa Ô˘ ¯ÔÚËÁ‹ıËΠfiÛÔ Î·È Ô ÙÚfiÔ˜ ¯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 ˘ÔıÂÚ·¢ÙÈ΋ Û˘ÁΤÓÙÚˆÛË ÛÙÔ Ï¿ÛÌ·. ∏ ıˆڛ· ·˘Ù‹ ÂÓÈÛ¯‡ÂÙ·È ·fi ÙÔ ÁÂÁÔÓfi˜ fiÙÈ ÛÙËÓ ‰Â‡ÙÂÚË ÌÂϤÙË fiÔ˘ ¯ÔÚËÁÔ‡ÓÙ·Ó rFVIIa Û Â·Ó·Ï·Ì‚·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 ÂÈÏÔΤ˜ Ù˘ Î·È ·›ÙÈÔ ÛËÌ·ÓÙÈ΋˜ ÓÔÛËÚfiÙËÙ·˜ Î·È ıÓËÙfiÙËÙ·˜. O ÂÓÂÚÁÔÔÈË̤ÓÔ˜ ·Ú¿ÁÔÓÙ·˜ VIIa ·ÔÙÂÏ› ¤Ó· ıÂÚ·¢ÙÈÎfi ̤ÛÔ ÁÈ· ıÂÚ·›· ‰È¿ÛˆÛ˘ ÛÙȘ ÂÚÈÙÒÛÂȘ ÛÔ‚·Ú‹˜ ·ÈÌÔÚÚ·Á›·˜ Û ·ÛıÂÓ›˜ Ô˘ ˘Ô‚¿ÏÏÔÓÙ·È Û ÔÚıÔÙÔÈ΋ 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˜.

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METAMO™XEY™Eπ™ 2008

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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.

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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.

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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.

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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.

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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.

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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).

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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.

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45. Lodge JP, Jonas S, Jones RM et al. Efficacy and safety of repeated perioperative doses of recombinant factor

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KÂÚ·˘ÓÔ‚fiÏÔ˜ Ë·Ù›Ùȉ· ∂. ∫·Ùۛη

5-26 ‚‰ÔÌ¿‰Â˜, ÌÂÙ¿ ÙËÓ ÂÌÊ¿ÓÈÛË ›ÎÙÂÚÔ˘ (ÂÈ‚›ˆÛË 14 %).

∏ ÎÂÚ·˘ÓÔ‚fiÏÔ˜ Ë·Ù›Ùȉ· ‹ ÔÍ›· Ë·ÙÈ΋ ·ÓÂ¿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›·˜ Â› ·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΋ ·ÓÂ¿ÚÎÂÈ· Ô˘ Û˘¯Ó¿ ÚÔηÏ› ÙÔ ı¿Ó·ÙÔ. ∏ ıÓËÛÈÌfiÙËÙ· ÚÈÓ ÙË ‰˘Ó·ÙfiÙËÙ· ‰ÈÂÓ¤ÚÁÂÈ·˜ ÌÂÙ·ÌfiÛ¯Â˘Û˘ ‹·ÙÔ˜ ÍÂÂÚÓÔ‡Û ÙÔ 80%. ™‹ÌÂÚ·, Ì ÙË ÌÂÙ·ÌfiÛ¯Â˘ÛË ‹·ÙÔ˜, Ë ÂÈ‚›ˆÛË Êı¿ÓÂÈ Ì¤¯ÚÈ Î·È ÙÔ 80%.

∞Èٛ˜ ∫‡ÚȘ ·Èٛ˜ Ù˘ ÔÍ›·˜ Ë·ÙÈ΋˜ ·ÓÂ¿ÚÎÂÈ·˜ Â›Ó·È Ê¿Ú̷η (.¯. ·Ú·ÎÂÙ·ÌfiÏË) Ë·Ù›Ùȉ· μ Î·È Ë·Ù›Ùȉ· non ∞ non μ, ÏÈ҉˜ ‹·Ú Ù˘ ·ËÛ˘, ÌÂÙ·‚ÔÏÈο ÓÔÛ‹Ì·Ù·. ∏ ·Ó·ÁÓÒÚÈÛË Ù˘ ·ÈÙ›·˜ Ù˘ O.∏.∞. Â›Ó·È ÛËÌ·ÓÙÈ΋ ηıÒ˜ Ë ·ÈÙÈÔÏÔÁ›· ÂËÚ¿˙ÂÈ ÙËÓ ÚfiÁÓˆÛË ·ÏÏ¿ Î·È ÙËÓ ·ÓÙÈÌÂÙÒÈÛË.

∫ÏÈÓÈΤ˜ Û˘Ó¤ÂȘ ∫·Ú‰È·ÁÁÂÈ·Îfi Û‡ÛÙËÌ· – ∞ÓÙÈÌÂÙÒÈÛË

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 ·ÓÙÈÌÂÙÒÈÛË 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· ÍÂÂÚÓ¿ Ù· 10 cm H2O. ŸÙ·Ó Ë ¯ÔÚ‹ÁËÛË ˘ÁÚÒÓ ‰ÂÓ Â›Ó·È ·ÔÙÂÏÂÛÌ·ÙÈ΋ ÛÙËÓ ·ÓÙÈÌÂÙÒÈÛË Ù˘ ˘fiÙ·Û˘, Ë ¯ÔÚ‹ÁËÛË ÈÓÔÙÚfiˆÓ ‚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 ÓÙÔÂÍ·Ì›Ó˘, ÂÓfi˜ Ê·ÚÌ¿ÎÔ˘ Ì ÓÙÔ·ÌÈÓÂÚÁÈ΋ Î·È ‚-·‰ÚÂÓÂÚÁÈ΋ ‰Ú¿ÛË. ∏ ÓÙÔÂÍ·Ì›ÓË ·˘Í¿ÓÂÈ ÙË ÛÏ·Á¯ÓÈ΋ Î·È ÓÂÊÚÈ΋ ÚÔ‹

O fiÚÔ˜ ÎÂÚ·˘ÓÔ‚fiÏÔ˜ Ë·ÙÈ΋ ·ÓÂ¿ÚÎÂÈ· ¯ÚËÛÈÌÔÔÈ‹ıËΠÚÒÙË 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˘, Â› ·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·‰ÈÔÔ›ËÛË Ù˘ O.∏.∞. ‚·ÛÈṲ̂ÓË Û ̛· ·Ó·‰ÚÔÌÈ΋ ÌÂϤÙË 539 ·ÛıÂÓÒÓ. OÈ O’Grady Î·È Û˘Ó. ¯ÚËÛÈÌÔÔ›ËÛ·Ó ÙÔ˘˜ fiÚÔ˘˜: ˘ÂÚÔÍ›·, ÔÍ›· Î·È ˘ÔÍ›· Ë·ÙÈ΋ ·ÓÂ¿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˘ (ÂÈ‚›ˆÛË 36%). ∏ ÔÍ›· Ë·ÙÈ΋ ·ÓÂ¿ÚÎÂÈ· ÂÚÈÏ·Ì‚¿ÓÂÈ ·ÛıÂÓ›˜ Ô˘ ·Ó·Ù‡ÛÛÔ˘Ó ÂÁÎÂÊ·ÏÔ¿ıÂÈ· 8-28 Ë̤Ú˜ ÌÂÙ¿ ÙËÓ ÂÌÊ¿ÓÈÛË ÈÎÙ¤ÚÔ˘ (ÂÈ‚›ˆÛË 7%). ∏ ˘ÔÍ›· ÌÔÚÊ‹ ÂÚÈÁÚ¿ÊÂÈ ÙËÓ ÂÌÊ¿ÓÈÛË ÂÁÎÂÊ·ÏÔ¿ıÂÈ·˜

115

116

∂. ∫∞Δ™π∫∞

Î·È ‚ÂÏÙÈÒÓÂÈ ÙËÓ ·ÚÔ¯‹ Ô͢ÁfiÓÔ˘. ∂ÈϤÔÓ, Ë ·ÓÙÈÊÏÂÁÌÔÓ҉˘ ‰Ú¿ÛË Ù˘ ÌÂÙÚÈ¿˙ÂÈ ÙËÓ Û˘ÁÎfiÏÏËÛË ÙˆÓ Ï¢ÎÔ΢ÙÙ¿ÚˆÓ ÛÙË ÌÈÎÚÔ·ÁÁÂȷ΋ ÛÏ·Á¯ÓÈ΋ ΢ÎÏÔÊÔÚ›·.

∫.¡.™.

OÈ ÈÔ Û˘¯Ó¤˜ ÂÈÏÔΤ˜ 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 ıÂÚ·›· ·˘ÙÒÓ ÙˆÓ ÂÈÏÔÎÒÓ.

·) ∂ÁÎÂÊ·ÏÔ¿ıÂÈ· ∏ Ë·ÙÈ΋ ÂÁÎÂÊ·ÏÔ¿ıÂÈ· Â›Ó·È ·ÔÙ¤ÏÂÛÌ· ·ÓÂ¿ÚÎÂÈ·˜ ‚ÈÔÌÂÙ·ÊÔÚ¿˜ Î·È ·¤ÎÎÚÈÛ˘ ÙÔÍÈÓÒÓ Ô˘ Ê˘ÛÈÔÏÔÁÈο Ú·ÁÌ·ÙÔÔÈÂ›Ù·È ·fi ÙÔ ‹·Ú. ™ÙÔ Ï¿ÛÌ· ·ÓȯÓ‡ÔÓÙ·È ·˘ÍË̤ӷ Â›‰· ·Ì̈ӛ·˜, ÌÂÚηÙ·ÓÒÓ, ÏÈ·ÚÒÓ ÔͤˆÓ, ·ÌÈÓÔͤˆÓ ·ÚˆÌ·ÙÈÎÔ‡ ‰·ÎÙ‡ÏÈÔ˘, Ô˘ÛÈÒÓ ·ÚfiÌÔÈˆÓ Ì ÙȘ ‚ÂÓ˙ԉȷ˙Â›Ó˜, Á-·ÌÈÓÔ‚Ô˘Ù˘ÚÈÎÔ‡ ÔͤԘ, ÁÏÔ˘Ù·Ì›Ó˘ Î·È ÙÔÍÈÎÒÓ ÌÂÙ¿ÏÏˆÓ (.¯. „¢‰¿ÚÁ˘ÚÔ˘, ¯·ÏÎÔ‡, Ì·ÁÓËÛ›Ô˘). ∂ÈϤÔÓ, ·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˘ÌÂÚÈÊÔÚ¿, 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˘ÌÂÚÈÊÔÚ¿ – 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 ÂÈÏÂÎÙÈ΋ ‰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 ) ∞ÓÙÈÌÂÙÒÈÛË ∞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·ÙÔÔÈÂ›Ù·È Ì ÙËÓ ÙÔÔı¤ÙËÛË Î·ıÂÙ‹Ú· ÛÙÔ ÂÁÎÂÊ·ÏÈÎfi ·Ú¤Á¯˘Ì·, ‹ ÛÙÔÓ ÂÈÛÎÏËÚ›‰ÈÔ ‹ ÛÙÔÓ ˘ÔÛÎÏËÚ›‰ÈÔ ¯ÒÚÔ. OÈ ÂÈÛÎÏËÚ›‰ÈÔÈ Î·ıÂÙ‹Ú˜ ¤¯Ô˘Ó ÏÈÁfiÙÂÚ˜ ÂÈÏÔΤ˜ (3,8%) ·fi ÙÔ˘˜ ˘ÔÛÎÏËÚ›‰ÈÔ˘˜ (20%) Î·È ÙÔ˘˜ ·ÚÂÁ¯˘Ì·ÙÈÎÔ‡˜ (22%). ∏ ΢ÚÈfiÙÂÚË ÂÈÏÔ΋ Â›Ó·È Ë ÂÁÎÂÊ·ÏÈ΋ ·ÈÌÔÚÚ·Á›·. ™ÙȘ ÂÚÈÙÒÛÂȘ Ô˘ ÙÔ INR> 1,5, ‹ Ù· ·ÈÌÔÂÙ¿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 ÙÔÔı¤ÙËÛË ÙÔ˘ ÂÓ‰ÔÎÚ¿ÓÈÔ˘ ηıÂÙ‹Ú·. ªË ÂÂÌ‚·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˘ ıÂÚ·›·˜ 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 Ï‹ÚË Ó¢ÚÔÏÔÁÈ΋ ·Ó¿ÓË„Ë ÌÂÙ¿ ·fi ·Ú·ÙÂٷ̤ÓË ∂∫¶ (>35mmHg ÁÈ· 24-38h) Î·È ÂËÚ·Ṳ̂ÓË ∂.¶.¢. ·ÓıÂÎÙÈ΋ ÛÙË Î·ıÈÂڈ̤ÓË ıÂÚ·›·.

ÁI) ∞ÓÙÈÌÂÙÒÈÛË ª·ÓÓÈÙfiÏË: ÃÔÚËÁÂ›Ù·È Û Â·Ó·Ï·Ì‚·ÓfiÌÂÓ˜ ÂÊ¿·Í ‰fiÛÂȘ (0,5-1gr/kgr) ‰È·ÙËÚÒÓÙ·˜ ÙËÓ ÔÛ̈ÙÈÎfiÙËÙ· ÙÔ˘ Ï¿ÛÌ·ÙÔ˜ οو ·fi 320mOsm/lt. £ÂÈÔÂÓÙ¿ÏË: ÃÚËÛÈÌÔÔÈÂ›Ù·È Û ÂÚÈÙÒÛÂȘ fiÔ˘ 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). ∂ÈϤÔÓ, ‰Ú· Î·È ˆ˜ Û·ÛÌÔÏ˘ÙÈÎfi. ∞ÓÂÈı‡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·. ÀÂÚ·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 ıÂÚ·›· 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. ∂ÈϤÔÓ, Ì ÙËÓ ˘ÔıÂÚÌ›· ÂÏ·ÙÙÒıËÎ·Ó Ù· Â›‰· ·Ì̈ӛ·˜ ÛÙÔ ·›Ì· ηıÒ˜ Î·È Ë ÂÁÎÂÊ·ÏÈ΋ ÚfiÛÏË„Ë ·Ì̈ӛ·˜. ∏ Ù¯ÓÈ΋ ·˘Ù‹ Ì ÂÈÙ˘¯›· 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 ıÂÚ·›· 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 ÂÈ‚›ˆÛ‹ ÙÔ˘˜, ÂÎÙfi˜ ·Ó Ú·ÁÌ·ÙÔÔÈËı› ÌÂÙ·ÌfiÛ¯Â˘ÛË ‹·ÙÔ˜ ̤۷ Û 12-24 ÒÚ˜.

¢È·Ù·Ú·¯¤˜ ÛÙËÓ ‹ÍË ÙÔ˘ ·›Ì·ÙÔ˜ ΔÔ ‹·Ú Â›Ó·È ˘‡ı˘ÓÔ ÁÈ· ÙË Û‡ÓıÂÛË ÙˆÓ ·Ú·ÁfiÓÙˆÓ Ù˘ ‹Í˘ Î·È ÂÔ̤ӈ˜ ‰È·Ù·Ú·¯¤˜ ÛÙËÓ ‹ÍË ÂÌÊ·Ó›˙ÔÓÙ·È ¿ÌÂÛ· ÛÙËÓ O.∏.∞. ∞ÈÌÔÚÚ·Á›Â˜ ÂΉËÏÒÓÔÓÙ·È Î˘Ú›ˆ˜ ·fi ÙÔ ·ÓÒÙÂÚÔ ÂÙÈÎfi, ·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 ·ÈÌÔÂÙ·Ï›ˆÓ, ÂÏ·Ùو̤ӷ Â›‰· ÙˆÓ ·Ú·ÁfiÓÙˆÓ Î·È ÙˆÓ ·Ó·ÛÙÔϤˆÓ Ù˘ ‹Í˘, ÈÓˆ‰fiÏ˘ÛË Î·È ‰È¿¯˘ÙË ÂÓ‰·ÁÁÂȷ΋ ‹ÍË. O ·ÚÈıÌfi˜ ÙˆÓ ·ÈÌÔÂÙ·Ï›ˆÓ ÂÏ·ÙÙÒÓÂÙ·È Ú·Á‰·›· ›Ù ÏfiÁˆ ηٷÛÙÚÔÊ‹˜ ÙÔ˘˜ ›Ù ÏfiÁˆ ÂÏ·Ùو̤Ó˘ Ë·ÙÈ΋˜ Û‡ÓıÂÛ˘ Ù˘ ıÚÔÌ‚ÔÔÈËÙ›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· Â›‰· ÙÔ˘ ·Ú¿ÁÔÓÙ· VIII Â›Ó·È Û˘Ó‹ıˆ˜ ·˘ÍË̤ӷ. Δ· Â›‰· 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· Â›‰· 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˘ ÈÛÙÔÔÈÂ›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 ÂÚÈÙÒÛˆÓ, 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 ·ÓÙÈÌÂÙÒÈÛË 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 ·ÓÙÈÌÂÙÒÈÛË 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·¯¤˜ ÀÔÁÏ˘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 ÂÈÏÔÁ‹ 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 «ÂÈΛӉ˘Ó· ÛÙ¿‰È·» Ù˘ Â¤Ì‚·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 ÚÔÔÊfiÏ˘ ‹ ıÂÈÔÂÓÙ¿Ï˘ Î·È Ë ¯ÔÚ‹ÁËÛË Í˘ÏÔη˝Ó˘ ÁÈ· ÙË ‰È·ÛˆÏ‹ÓˆÛË. ∏ ÚÔÔÊfiÏË 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·ÙÔÔÈÂ›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˘ Â¤Ì‚·Û˘ Â›Ó·È ·ÚfiÌÔȘ Ì’·˘Ù¤˜ ÙˆÓ ·ÛıÂÓÒÓ Ì ¯ÚfiÓÈ· Ë·ÙÈ΋ ·ÓÂ¿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 ÂÚÈÙÒÛÂȘ ·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΋ ·ÓÂ¿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΋ ·ÓÂ¿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΋˜ £ÂÚ·›·˜ ª.∞. ¶·Û·ÎÈÒÙÔ˘

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Û˜ (SGOT/SGPT) Â›Ó·È ·˘ÍË̤Ó˜ ÙȘ ÚÒÙ˜ 2-3 ̤Ú˜, Â·Ó¤Ú¯ÔÓÙ·È ‰Â ÛÙ·‰È·Î¿ ÛÙ· Ê˘ÛÈÔÏÔÁÈο Â›‰·, ÂÊ’ fiÛÔÓ ‰ÂÓ ÚÔ·ÙÔ˘Ó ÚÔ‚Ï‹Ì·Ù·.

OÈ ·ÛıÂÓ›˜ Ô˘ ¤¯Ô˘Ó ˘Ô‚ÏËı› Û ÔÚıÔÙÔÈ΋ ÌÂÙ·ÌfiÛ¯Â˘ÛË ‹·ÙÔ˜ ¯ÚÂÈ¿˙ÔÓÙ·È ÓÔÛËÏ›· ÙÔ˘Ï¿¯ÈÛÙÔÓ 24-48 ÒÚ˜ ÛÙË ªÔÓ¿‰· ∂ÓÙ·ÙÈ΋˜ £ÂÚ·›·˜ (ª∂£). ∏ ·Ê·›ÚÂÛË ÙÔ˘ ÙÚ·¯ÂÈÔۈϋӷ ÚÔ¸Ôı¤ÙÂÈ ÙËÓ ÔÌ·Ï‹ ÏÂÈÙÔ˘ÚÁ›· ÙÔ˘ ÌÔۯ‡̷ÙÔ˜ Î·È ÙÔ ÈηÓÔÔÈËÙÈÎfi 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 ÂÈ‚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 Ùˆ¯‹ ¤Î‚·ÛË Î·È ·˘ÍË̤ÓË ıÓËÛÈÌfiÙËÙ·1. ¶¿ÓÙˆ˜, ˘¿Ú¯Ô˘Ó ÂӉ›ÍÂȘ fiÙÈ Ë ÚÒÈÌË-Û¯ÂÙÈο- ·ԉȷۈϋӈÛË 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·, ÂÂȉ‹ ÂÏ·ÙÙÒÓÂÈ ÙȘ ·Ó¿ÁΘ ÁÈ· ÌÂÙ¿ÁÁÈÛË, ÂϤÁ¯ÔÓÙ·˜ ÙËÓ ·ÈÌÔÚÚ·Á›· Î·È ÌÂÈÒÓÔÓÙ·˜ ÙȘ ·Ó¿ÁΘ ÁÈ· ÈÓfiÙÚÔË 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˘ Â¤Ì‚·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΋ ·ÓÂ¿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 ÂÈÏÔÎÒÓ ·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˘ ÔÔ›·˜ ÌÔÚ› 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·ÈÔÓ¢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 fiˆ˜ ·ÎÚÈ‚Ò˜ Î·È Û ÔÔÈÔÓ‰‹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 ÂËÚ¿˙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΋˜ ·ÓÂ¿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· Â›‰¿ 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¿-

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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΋˜ ÂÈÙÚ¤Ô˘Ó ÙËÓ ÌÂÙ·ÌfiÛ¯Â˘ÛË, ÙfiÙ ıˆÚÂ›Ù·È ··Ú·›ÙËÙË Ë ÙÔÔı¤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 (ÂÈÛÓÂfiÌÂÓÔ˘ 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 ÔÔ›Ô ÚÔÙ›ÓÂÙ·È ·fi ‰È¿ÊÔÚÔ˘˜ ÂÚ¢ÓËÙ¤˜ Î·È ÙÔ˘ ÔÔ›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΋ ·ÓÂ¿ÚÎÂÈ· ¤¯Ô˘Ó ‰˘ÛÌÂÓ‹ ¤Î‚·ÛË, fiˆ˜ ı¿Ó·ÙÔ˜ ‹ ·Ó¿ÁÎË ÁÈ· Â·Ó·ÌÂÙ·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¯ÔÔÈÔ‡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 ÔÔ›· 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

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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 ‰ÈÏ¿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·. ∏ ıÂÚ·›· ÛÙË ª∂£ ÂÚÈÏ·Ì‚¿ÓÂÈ ·ÈÌÔ‰˘Ó·ÌÈ΋ Î·È ·Ó·Ó¢ÛÙÈ΋ ˘ÔÛÙ‹ÚÈÍË, ‰ÈfiÚıˆÛË Ù˘ ÔͤˆÛ˘ Î·È ÙˆÓ ÏÔÈÒÓ 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 ÂÈÏÔÎÒÓ Î˘Ì·›ÓÂÙ·È ·fi 8-14%10. ∂ÌÊ·Ó›˙ÔÓÙ·È Û˘Ó‹ıˆ˜ ÙËÓ ÚÒÙË ÌÂÙÂÁ¯ÂÈÚËÙÈ΋ ̤ڷ, ·Ó Î·È ÌÔÚ› Ó· ÂÌÊ·ÓÈÛıÔ‡Ó ÌÂÚÈΤ˜ ‚‰ÔÌ¿‰Â˜ ÌÂÙ¿ ÙËÓ Â¤Ì‚·ÛË. ∏ ıÚfiÌ‚ˆÛË Â›Ó·È Ë ϤÔÓ ÚÒÈÌË ÂÈÏÔ΋, ÂÓÒ Ë ÛÙ¤ÓˆÛË Î·È ÙÔ „¢‰Ô·Ó‡ڢÛÌ· Û¯ËÌ·Ù›˙ÔÓÙ·È ·ÚÁfiÙÂÚ·. ∏ ÎÏÈÓÈ΋ ÂÈÎfiÓ· ÔÈΛÏÏÂÈ ·fi ·Û˘Ìو̷ÙÈ΋ ·‡ÍËÛË ÙˆÓ Ë·ÙÈÎÒÓ ÂÓ˙‡ÌˆÓ ̤¯ÚÈ ÔÍ›· ÎÂÚ·˘ÓÔ‚fiÏÔ Ë·ÙÈ΋ ·ÓÂ¿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˘Ìو̷ÙÔÏÔÁ›·, Ì ÂÈÎfiÓ· ·ÛΛÙË Î·È ÎÈÚÛÔÚÚ·Á›·˜. ∏ ·ÓÙÈÌÂÙÒÈÛË Û˘Ó›ÛÙ·Ù·È Û ıÚÔÌ‚ÂÎÙÔÌ‹ Î·È ·Ó·ıÂÒÚËÛË Ù˘ ·Ó·ÛÙfïÛ˘, ÂÊ’ fiÛÔÓ ‰È·ÁÓˆÛı› ÂÁη›Úˆ˜ ·˘Ù‹ Ë ÂÈÏÔ΋.

OÈ ÂÈÏÔΤ˜ ·fi Ù· ¯ÔÏËÊfiÚ· ÚÔ·ÙÔ˘Ó ÛÙÔ 15% ÂÚ›Ô˘ ÙˆÓ ·ÛıÂÓÒÓ Ì ÔÚıÔÙÔÈ΋ ÌÂÙ·ÌfiÛ¯Â˘ÛË ‹·ÙÔ˜11. ∞fi ·˘Ù¤˜, Ë ÈÔ Û˘ÓËıÈṲ̂ÓË Â›Ó·È Ë ‰È·Ê˘Á‹ ¯ÔÏ‹˜ , fiÔ˘ Ù· Û˘ÌÙÒÌ·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 ıÂÚ·›· Û˘Ó›ÛÙ·Ù·È Â›Ù ÛÙËÓ ÂÓ‰ÔÛÎÔÈ΋ ÙÔÔı¤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‰ÔÛÎÔÈο ‹ ̤ۈ Ù˘ ÂÂÌ‚·ÙÈ΋˜ ·ÎÙÈÓÔÏÔÁ›·˜, ÂÓÒ Ë ¯ÂÈÚÔ˘ÚÁÈ΋ ·ÔηٿÛÙ·ÛË Â›Ó·È, οÔȘ 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΋ ıÂÚ·›· 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 ÂÈÏÔÎÒÓ 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˜ ÌÔÚ› Ó· ·-

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ª. ¶∞™∞∫πøΔ√À

ڷ̤ÓÂÈ ÛÙ·ıÂÚ‹ Û ÔÏÏÔ‡˜ ·ÛıÂÓ›˜, ÛÙÔ˘˜ ÔÔ›Ô˘˜ ¤¯Ô˘Ó ‚ÚÂı› ÂÛÙȷΤ˜ ‹ ‹Ș 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·ÔÚÚÈÙÈ΋ ·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· ÂÂÈÛfi‰È· Ù˘ ÚÒÈÌ˘ ÔÍ›·˜ ·fiÚÚȄ˘ ‰ÂÓ ÂËÚ¿˙Ô˘Ó ·ÚÓËÙÈο ÙÔ ÌfiÛ¯Â˘Ì· ‹ ÙËÓ ¤Î‚·ÛË ÙÔ˘ ·ÛıÂÓÔ‡˜16. Δ· ÂÂÈÛfi‰È· Ù˘ ·ÒÙÂÚ˘ ΢ÙÙ·ÚÈ΋˜ ·fiÚÚȄ˘ Û˘¯Ó¿ Û˘Ó‰¤ÔÓÙ·È Ì ¯·ÌËÏ¿ Â›‰· ΢ÎÏÔÛÔÚ›Ó˘ ‹ tacrolimus ÛÙÔ ·›Ì·, fiˆ˜ Â›Û˘ Î·È Ì ¯·ÌËÏ‹ ÂÈ‚›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· ÂÂÈÛfi‰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 ÂÂÈÛfi‰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· ÂÂÈÛfi‰ÈÔ ·ÒÙÂÚ˘ ÔÍ›·˜ ·fiÚÚȄ˘, Ô˘ ÂÌÊ·Ó›ÛıËÎ·Ó ÙÔÓ ÚÒÙÔ ¯ÚfiÓÔ, ÂÓÒ ˘‹ÚÍ·Ó Î·È ÂÚÈÙÒÛÂȘ ·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¿ Â›‰· ·ÓÔÛÔηٷÛÙ·ÏÙÈÎÒÓ Ô˘ ·ÓȯÓ‡ıËÎ·Ó ÛÙÔ ·›Ì·, ˘¿Ú¯Ô˘Ó Î·È ¿ÏÏÔÈ ·Ú¿ÁÔÓÙ˜ Ô˘ ÂÓÔ¯ÔÔÈÔ‡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 ÔÔ›· ·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˘ÌÙÒÌ·Ù· Ô˘ ÂÌÊ·Ó›˙ÔÓÙ·È ÛÙÔ˘˜ ·ÛıÂÓ›˜ Ì ·fiÚÚÈ„Ë, fiˆ˜ ˘ÚÂÙfi˜, ηÎÔ˘¯›·, ÎÔÈÏȷο ¿ÏÁË, Ë·ÙÔÌÂÁ·Ï›·, ÛÏËÓÔÌÂÁ·Ï›·, ÂȉÂÈÓÔ‡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·ÓÛÂÙȉ¿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 ÔÔÈ·‰‹ÔÙ ¿ÏÏË ‰˘ÛÏÂÈÙÔ˘ÚÁ›· ÙÔ˘ Ë·ÙÈÎÔ‡ ÌÔۯ‡̷ÙÔ˜ Î·È ‰ÂÓ Û˘Ó‰¤ÂÙ·È Ì ÙË ‚·Ú‡ÙËÙ· ÙˆÓ ·ÔÚÚÈÙÈÎÒÓ ÂÂÈÛÔ‰›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 ÂÈ¤‰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 ¯ÚËÛÈÌÔÔÈÔ‡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˘˜ ÂÈÏÔÎÒÓ 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 ÂÈÏÔΤ˜, 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 ÂÈı‹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 ·ÍÈfiÈÛÙË fiÙ·Ó ¤¯Ô˘Ó ÏËÊı› ÙÔ˘Ï¿¯ÈÛÙÔÓ ‰‡Ô ÈÛÙÔÙÂÌ¿¯È· ·fi ‰‡Ô ‰È·ÊÔÚÂÙÈο Â›‰·, 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 ÔÔ›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, fiÔ˘ ·ԉ›¯ıËΠfiÙÈ ‰ÂÓ Û˘Ì‚·‰›˙ÂÈ Ì ÙËÓ ·¿ÓÙËÛË ÙÔ˘ ·ÛıÂÓÔ‡˜ ÛÙ· ÎÔÚÙÈÎÔÛÙÂÚÔÂȉ‹ ‹/Î·È Ì ÙËÓ ÂÈ‚›ˆÛË ÙÔ˘ ÌÔۯ‡̷ÙÔ˜24.

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¢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· ÌÔÚ› Ó· ·ÓÙ·Ó·ÎÏÔ‡Ó Ù¯ÓÈο ‹ ÏÂÈÙÔ˘ÚÁÈο ÚÔ‚Ï‹Ì·Ù·, fiˆ˜ 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· ÌÔÚ› 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· ÔÔ›· 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˘ ΢ÎÏÔÛÔÚ›Ó˘, Ì·˙È΋ ·ÈÌÔÚÚ·ÁÈ΋ Ó¤ÎÚˆÛË Î·È ·Û˘Ì‚·ÙfiÙËÙ· ÔÌ¿‰·˜ ·›Ì·ÙÔ˜-·ÈÌfiÏ˘ÛË.

£ÂÚ·›· OÈ ˘„ËϤ˜ ‰fiÛÂȘ ÎÔÚÙÈÎÔÛÙÂÚÔÂȉÒÓ Â›Ó·È, Û˘Ó‹ıˆ˜, Ë ÚÒÙË ıÂÚ·¢ÙÈ΋ ·ÓÙÈÌÂÙÒÈÛË Ù˘ ÔÍ›·˜ ΢ÙÙ·ÚÈ΋˜ ·fiÚÚȄ˘. OÈ ‰fiÛÂȘ Ù˘ ÌÂı˘ÏÚ‰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˘ ıÂÚ·›·˜ Â›Ó·È ÈÔ ·ÔÙÂÏÂÛÌ·ÙÈ΋ ÛÙËÓ ·fiÚÚÈ„Ë Î·È Û˘Ó‰¤ÂÙ·È Ì ÏÈÁfiÙÂÚ˜ ÏÔÈÌÒÍÂȘ ·fi fiÙÈ Ë ¯ÔÚ‹ÁËÛË ÌÂı˘ÏÚ‰ÓÈ˙ÔÏfiÓ˘ 1000mg ÁÈ· 3 ̤Ú˜25. ¶ÂÚ›Ô˘, ÙÔ 70-80% ÙˆÓ ÂÚÈÙÒÛÂˆÓ ÔÍ›·˜ ΢ÙÙ·ÚÈ΋˜ ·fiÚÚȄ˘ ·ÓÙÈÌÂÙˆ›˙ÔÓÙ·È ÂÈÙ˘¯Ò˜ Ì ÙȘ ˘„ËϤ˜ ‰fiÛÂȘ ÎÔÚÙÈÎÔÛÙÂÚÔÂȉÒÓ, ÂÓÒ ÌÈ· ‰Â‡ÙÂÚË Û˘Ó‰ڛ· Â›Ó·È ··Ú·›ÙËÙË ÛÙȘ ÂÌ̤ÓÔ˘Û˜ ÂÚÈÙÒÛÂȘ. ∏ ‚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, fiˆ˜ ÛÙÔÌ·ÙÈ΋˜ Ì˘ÎËÙ›·Û˘, Ïԛ̈͢ ·fi ΢ÙÙ·ÚÔÌÂÁ·ÏÔ˚fi, ·Û¤ÚÁÈÏÏÔ, Ó¢ÌÔÓÔ·ÛÙË carinii Î·È ·ıÔÁfiÓ· ‚·ÎÙËÚ›‰È·. ÕÏϘ ‰˘ÓËÙÈΤ˜ ÂÈÏÔΤ˜ Â›Ó·È Ë ˘-

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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˜. ∏ ·ÓÙÈÌÂÙÒÈÛË ÙˆÓ ·Ú·¿Óˆ ÂÚÈÏ·Ì‚¿ÓÂÈ ÙË ¯ÔÚ‹ÁËÛË ·Ó·ÛÙÔϤˆÓ Ù˘ ·ÓÙÏ›·˜ ÚˆÙÔÓ›ˆÓ, ÙÚÈÌÂıÔÚ›Ì˘-ÛÔ˘ÏÊÔÌÂıÔÍ·˙fiÏ˘ Î·È Û˘¯Ófi ¤ÏÂÁ¯Ô Ù˘ ÁÏ˘Îfi˙˘ ÙÔ˘ ·›Ì·ÙÔ˜.

∏·Ù›Ùȉ· C ∏ ·ÓÙÈÌÂÙÒÈÛË Ù˘ ÔÍ›·˜ ΢ÙÙ·ÚÈ΋˜ ·fiÚÚȄ˘ Û ·ÛıÂÓ›˜ Ì Ë·Ù›Ùȉ· C (HCV) ··ÈÙ› ȉȷ›ÙÂÚË ÚÔÛÔ¯‹. ∏ ıÂÚ·›· Ì ÎÔÚÙÈÎÔÛÙÂÚÔÂȉ‹ ÂÈÙ·¯‡ÓÂÈ ÙËÓ ÂͤÏÈÍË Ù˘ HCV, ÌÂ Û˘Ó¤ÂÈ· ÙËÓ ·˘ÍË̤ÓË ıÓËÛÈÌfiÙËÙ·26. ∂ÈϤÔÓ, 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·ÔÚÚÈÙÈ΋ ıÂÚ·›· 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· ıÂÚ·¢ÙÈο Û¯‹Ì·Ù· Ô˘ ·ÓÙÈÌÂÙˆ›˙Ô˘Ó ÙËÓ ÂÈÏÔ΋ ·˘Ù‹, fiˆ˜ 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∞™ ∏ ÔÚıÔÙÔÈ΋ ÌÂÙ·ÌfiÛ¯Â˘ÛË ‹·ÙÔ˜ ·Ú·Ì¤ÓÂÈ Ë Ì¤ıÔ‰Ô˜ ÂÎÏÔÁ‹˜ ÁÈ· ÙËÓ ‚·ÚÈ¿ Ë·ÙÈ΋ ·ÓÂ¿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˘ ÔÔ›·˜ ‚·ÛÈ΋ ȉÈfiÙËÙ· Â›Ó·È Ë Û‡Ó‰ÂÛ‹ Ù˘ Ì ÙȘ ÙÔ͛Ә ÙÔ˘ ·›Ì·ÙÔ˜28. ∏ ·ÓıÚÒÂÈÔ˜ ·Ï‚Ô˘Ì›ÓË ÙÔ˘ ÔÚÔ‡ Â›Ó·È ¤Ó·˜ ÈÛ¯˘Úfi˜ ·ÓÙÈÔÍÂȉˆÙÈÎfi˜ ÌÂÙ·ÊÔÚ¤·˜ Ê·ÚÌ¿ÎˆÓ Î·È ÂÓ‰ÔÁÂÓÒÓ ·ÓÈfiÓÙˆÓ, fiˆ˜ ¯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, ÏÔÈfiÓ, ‰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 ÔÔ›Ô ¯ÚËÛÈÌÔÔÈ› ¤Ó· ‰È¿Ï˘Ì· ÂÌÏÔ˘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), fiÔ˘ Ù· ˘ÁÚ¿ Ù˘ ‰È‹ıËÛ˘ ÂÌÏÔ˘Ù›˙ÔÓÙ·È Ì ·Ï‚Ô˘Ì›ÓË 4.4%. ™˘ÌÂÚ·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΋ ·ÓÂ¿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΋ ÂÈÏÔÁ‹ Ù˘ ÌÂıfi‰Ô˘ Ô˘ ı· ÂÊ·ÚÌÔÛı›.

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METAMO™XEY™Eπ™ 2008

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17. Wiesner RH, et al. Acute hepatic allograft rejection: incidence, risk factors, impact and outcome. Hepatology 28:638, 1995.

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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 ·ÓÙÈÌÂÙÒÈÛË ÛÔ‚·Ú‹˜ Û‹„˘ Î·È ÛËÙÈÎÔ‡ 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 ηÙËÁÔÚÈÔÔÈ› Â›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˘ ÛËÙÈÎÔ‡ ÛÔÎ ¯ÚËÛÈÌÔÔÈÔ‡ÓÙ·È ÔÈ ÔÚÈÛÌÔ› fiˆ˜ ‰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 ÛËÙÈÎÔ‡˜ ·ÛıÂÓ›˜. Œ¯ÂÈ ‚ÚÂı› fiÙÈ ÙÔ 39,8%ÙˆÓ ·ÛıÂÓÒÓ Ì ÔÍ›· Ë·ÙÈ΋ ·ÓÂ¿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. ∏ ·ÓÙÈÌÂÙÒÈÛË Ù˘ ÛÔ‚·Ú‹˜ Û‹„˘ Î·È ÙÔ˘ ÛËÙÈÎÔ‡ ÛÔÎ ·Ó·Ê¤ÚÂÙ·È ÛÙËÓ: 1. ·Ú¯È΋ ·Ó·˙ˆÔÁfiÓËÛË 2. ·ÈÌÔ‰˘Ó·ÌÈ΋ ˘ÔÛÙ‹ÚÈÍË Î·È ÛÙËÓ 3. ˘ÔÛÙËÚÈÎÙÈ΋ ıÂÚ·›·

OÈ ‰Â›ÎÙ˜ ÂÈ‚›ˆÛ˘ ÌÂÙ¿ ÌÂÙ·ÌfiÛ¯Â˘ÛË ‹·ÙÔ˜ Û˘Ó¯Ҙ ‚ÂÏÙÈÒÓÔÓÙ·È ·˘Í¿ÓÔÓÙ·˜ ÙÔ ÔÛÔÛÙfi ÂÙ‹ÛÈ·˜ ÂÈ‚›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 ·ÓÙÈÌÂÙÒÈÛË ÙˆÓ ÏÔÈÌÒÍÂˆÓ Î·È ÛÙË ‚ÂÏÙ›ˆÛË ÙˆÓ ¯ÂÈÚÔ˘ÚÁÈÎÒÓ Ù¯ÓÈÎÒÓ1. ∏ ÓÔÛËÚfiÙËÙ· fï˜ Î·È Ë ıÓËÙfiÙËÙ· Ô˘ ÔÊ›ÏÂÙ·È ÛÙË ÛËÙÈΤ˜ ÂÈÏÔΤ˜ ·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· ÛËÙÈÎfi ÂÂÈÛfi‰ÈÔ3. ∏ ÛÔ‚·Ú‹ Û‹„Ë Î·È ÙÔ ÛËÙÈÎfi ÛÔÎ ·ÔÙÂÏÔ‡Ó ÙÂÚ¿ÛÙÈÔ Úfi‚ÏËÌ· ÛÙÔ ¯ÒÚÔ Ù˘ ˘Á›·˜, ·ÊÔÚÒÓÙ·˜ ÂηÙÔÌ̇ÚÈ· ·ÓıÚÒÔ˘˜ ·ÁÎÔÛÌ›ˆ˜ Î·È Ì ıÓËÙfiÙËÙ· ÙÔ˘Ï¿¯ÈÛÙÔÓ 25%4. ∏ ıÓËÙfiÙËÙ· Ù˘ ÛÔ‚·Ú‹˜ Û‹„˘ Û ¢·›ÛıËÙ˜ ÔÌ¿‰Â˜ ·ÛıÂÓÒÓ, fiˆ˜ ·ÛıÂÓÒÓ Ì ÔÍ›· Ë·ÙÈ΋ ·ÓÂ¿ÚÎÂÈ· ·Ó¤Ú¯ÂÙ·È Û 59%, ÂÓÒ ÙÔ˘ ÛËÙÈÎÔ‡ ÛÔÎ Û 98%5. ΔÔ 2004, ‰ÈÂıÓ‹˜ ÔÌ¿‰· ÂȉËÌfiÓˆÓ ÛÙË ‰È¿ÁÓˆÛË Î·È ·ÓÙÈÌÂÙÒÈÛË ÙˆÓ ÏÔÈÌÒÍÂˆÓ Î·È Ù˘ Û‹„˘, ·ÓÙÈÚÔÛˆ‡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˘ ÛËÙÈÎÔ‡ 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˘ ÛËÙÈÎÔ‡ ÛÔÎ7. ¶Ú¤ÂÈ fï˜ Ó· ÂÈÛËÌ·Óı›, fiÙÈ ÔÈ Î·Ù¢ı˘ÓÙ‹ÚȘ Ô‰ËÁ›Â˜ ‰ÂÓ ·ÓÙÈηıÈÛÙÔ‡Ó ÙÔ ÎÏÈÓÈÎfi ÎÚÈÙ‹ÚÈÔ Î·È Ë ·ÓÙÈÌÂÙÒÈÛË Î¿ı ·ÛıÂÓ‹ Ú¤ÂÈ Ó· ÂÍ·ÙÔÌÈ·ÂÙ·È. ∏ ÔÈfiÙËÙ· ÙÂÎÌËÚ›ˆÛ˘ ÙˆÓ Ô‰ËÁÈÒÓ ·˘ÙÒÓ ‚·Û›ÛÙËΠÛÙÔ Û‡ÛÙËÌ· GRADE Ô˘ ηÙËÁÔÚÈÔÔÈ› ÙËÓ ÙÂÎÌËÚ›ˆÛË ˆ˜ ˘„ËÏ‹

1. ∞ƒÃπ∫∏ ∞¡∞∑øO°O¡∏™∏ ÃÚËÛÈÌÔÔÈÔ‡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%

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¶›Ó·Î·˜ 1. OÚÈÛÌÔ› Û‹„˘, ÛÔ‚·Ú‹˜ Û‹„˘ Î·È ÛËÙÈÎÔ‡ ÛÔÎ ø˜ Û‹„Ë ÔÚ›˙ÂÙ·È Ì›· ÂȂ‚·ÈˆÌ¤ÓË ‹ Èı·Ó‹ Ïԛ̈ÍË Ì ¤Ó· ‹ ÂÚÈÛÛfiÙÂÚ· ·fi Ù· ·Ú·Î¿Ùˆ: °ÂÓÈÎÔ› ‰Â›ÎÙ˜ ¶˘ÚÂÙfi˜ (ÂÛˆÙÂÚÈ΋ ıÂÚÌÔÎÚ·Û›· >38,3Ô C) ÀÔıÂÚÌ›· (ÂÛˆÙÂÚÈ΋ ıÂÚÌÔÎÚ·Û›· <36Ô C) ∫·Ú‰È·Î‹ Û˘¯ÓfiÙËÙ· >90/ÏÂÙfi ‹ >2 SD ¿Óˆ ·fi ÙË Ê˘ÛÈÔÏÔÁÈ΋ Û˘¯ÓfiÙËÙ· Δ·¯‡ÓÔÈ· ¢È·Ù·Ú·¯¤˜ ÂÈ¤‰Ô˘ Û˘Ó›‰ËÛ˘ ™ËÌ·ÓÙÈÎfi Ô›‰ËÌ· ‹ ıÂÙÈÎfi ÈÛÔ˙‡ÁÈÔ ˘ÁÚÒÓ (>20 mL/kg Û 24 ÒÚ˜) ÀÂÚÁÏ˘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˘ÎÔÂÓ›· (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‚ÔÂÓ›· (PLT <100.000/ÌL) ÀÂÚ¯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˜ ÛËÙÈÎfi ÛÔÎ ÔÚ›˙ÂÙ·È Ë ÔÍ›· ΢ÎÏÔÊÔÚÈ΋ ·ÓÂ¿ÚÎÂÈ· Ô˘ ‰ÂÓ ÌÔÚ› 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 ÂÈÙ˘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 Â›‰· ˘„ËÏfiÙÂÚ· (12-15 mmHg) Û ÂÚÈÙÒÛÂȘ 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 ÙÔÔıÂÙË̤ÓÔ˜ >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˜, fiˆ˜ 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˜ ‹ ËÌÈÔÛÔÙÈΤ˜ 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‹˜ fiˆ˜ Ë ÚÔηÏÛÈÙÔÓ›ÓË, ·Ó Î·È ¯Ú‹ÛÈÌÔÈ ‰ÂÓ Â›Ó·È ÂȉÈÎÔ›.

1Á. ∞ÓÙÈ‚ÈÔÙÈ΋ ıÂÚ·›·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˘ ÛËÙÈÎÔ‡ 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‹ Â·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‰ÂÙÂÚÔÂÓÈÎÔ‡˜ ·ÛıÂÓ›˜ (2D) ÃÔÚ‹ÁËÛË Û˘Ó‰È·ÛÌÔ‡ ·ÓÙÈ‚ÈÔÙÈÎÒÓ ≤3-5 ̤Ú˜ Î·È ·ÔÎÏÈ̿ΈÛË ·Ó·ÏfiÁˆ˜ ÂӉ›ÍÂˆÓ (2D) ¢È¿ÚÎÂÈ· ıÂÚ·›·˜ ¤ˆ˜ 7-10 ̤Ú˜, ÂÚÈÛÛfiÙÂÚ˜ Û ·ÚÁ‹ ·ÓÙ·fiÎÚÈÛË ‹ ÛÂ Ì˘ÎËÙÈ·ÛÈΤ˜ ÏÔÈÌÒÍÂȘ ‹ Û ·ÓÔÛÔ·ÓÂ¿ÚÎÂȘ, fiˆ˜ Ô˘‰ÂÙÂÚÔÂÓ›· (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 ÂÚÈÙÒÛÂȘ ÛÔ‚·Ú‹˜ Û‹„˘ Î·È ÛËÙÈÎÔ‡ ÛÔÎ Î·È ÙÔ ÎÏÈÓÈÎfi ÎÚÈÙ‹ÚÈÔ Û ·˘Ù¤˜ ÙȘ ÂÚÈÙÒÛÂȘ ·ÔÎÙ¿ ηıÔÚÈÛÙÈ΋ ÛËÌ·Û›·. ∏ ÎÚ›ÛÈÌË ÚÒÙË ÂÈÏÔÁ‹ ·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 fiˆ˜: – 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 – ÂȉËÌÈÔÏÔÁ›· ·ÓÙÔ¯‹˜ ÛÙË Û˘ÁÎÂÎÚÈ̤ÓË ª∂£ ∂ȉÈÎfiÙÂÚ·, ÔÈ ÏÔÈÌÒ‰ÂȘ ÂÈÏÔΤ˜ ÌÂÙ¿ ÌÂÙ·ÌfiÛ¯Â˘ÛË ‹·ÙÔ˜ Â›Ó·È ÛËÌ·ÓÙÈÎfiٷ٘ ÁÈ·Ù› ÂËÚ¿˙Ô˘Ó ¿ÌÂÛ· ÙËÓ ÂÈ‚›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 ÂÈÏÔÁ‹ ¯ÔÏÈ΋˜ ·Ó·ÛÙfïÛ˘ Ù‡Ô˘ Roux-en-Y, ÔÈ ÔÏÏ·Ϥ˜ ¯ÂÈÚÔ˘ÚÁÈΤ˜ ÂÂÌ‚¿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 ÌÔÚÔ‡Ó Ó· ηÙËÁÔÚÈÔÔÈËıÔ‡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 fiˆ˜ ‡·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· ÌÔÚ› Ó· ÔÊ›ÏÔÓÙ·È Û ‰È·Ê˘Á‹ ¯ÔÏ‹˜ ÂÓÒ ÂÓ‰ÔË·ÙÈο ÌÔÚ› Ó· Û¯ÂÙ›˙ÔÓÙ·È Ì ıÚfiÌ‚ˆÛË Ë·ÙÈ΋˜ ·ÚÙËÚ›·˜3. ∞ÓÙÈ‚ÈÔÙÈο Ô˘ ¯ÚËÛÈÌÔÔÈÔ‡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

ÌÂÈÚÈ΋ ıÂÚ·›· ÛÙËÓ ·Ú¯È΋ ÌÂÙÂÁ¯ÂÈÚËÙÈ΋ ÂÚ›Ô‰Ô Ú¤ÂÈ Ó· ηχÙÔ˘Ó Gram ıÂÙÈÎÔ‡˜ ÎfiÎÎÔ˘˜, Gram ·ÚÓËÙÈο ‚·ÎÙ‹ÚÈ· Î·È ·Ó·ÂÚfi‚È·. ¶ÚÔÙ›ÓÂÙ·È ÌÈ· ÎÂÊ·ÏÔÛÔÚ›ÓË 3˘ ÁÂÓÈ¿˜ ‹ ÊıÔÚÈÔÎÈÓÔÏfiÓË Ì ÈÂÚ·ÎÈÏÏ›ÓË/Ù·˙ÔÌ·ÎÙ¿ÌË ‹ ·ÌÈÎÈÏÏ›ÓË/ÛÔ˘ÏÌ·ÎÙ¿ÌË3. Δ· ÙÂÏÂ˘Ù·›· ¯ÚfiÓÈ· ÂÈÎÚ·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 ÎÏÂÌÛȤÏÏ· 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, ÌÔÚ› 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·ÓÂ¿ÚÎÂÈ·˜ Ô˘ ÚÔηÏ› Ô ÌÂÁ·ÏÔ΢ÙÙ·ÚÔ˚fi˜. ∞·ÈÙÔ‡Ó ıÂÚ·›· ÁÈ· 2-4 ‚‰ÔÌ¿‰Â˜ ̤¯ÚÈ ÙËÓ ·ÚÓËÙÈÎÔÔ›ËÛË ÙˆÓ ·ÔÙÂÏÂÛÌ¿ÙˆÓ. §ÔÈÌÒÍÂȘ ·fi ·Û¤ÚÁÈÏÏÔ ÌÔÚÔ‡Ó Â›Û˘ Ó· ÂÌÊ·ÓÈÛÙÔ‡Ó ·˘Ù‹ ÙË ¯ÚÔÓÈ΋ ÂÚ›Ô‰Ô. ∞ÓÙÈÚÔÛˆÂ‡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 ·ÓıÚÒÈÓÔ ÂÚËÙÔ˚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 ÈηÓÔÔÈËÙÈ΋ ÏÂÈÙÔ˘ÚÁ›· ÙÔ˘ ÌÔۯ‡̷ÙÔ˜. ∞˘ÙÔ› ÔÈ ·ÛıÂÓ›˜ Û˘Ó‹ıˆ˜ ·Ó·Ù‡ÛÔ˘Ó ÏÔÈÌÒÍÂȘ Ù˘ ÎÔÈÓfiÙËÙ·˜ fiˆ˜ Î·È Ô ÁÂÓÈÎfi˜ ÏËı˘ÛÌfi˜, Â›Ó·È fï˜ ÈÔ ÂÈÚÚÂ›˜ ÛÙËÓ ·Ó¿Ù˘ÍË ÏÔÈÌÒÍÂˆÓ ·fi ÏÂÁÈÔÓ¤ÏÏ·22. ÃÚfiÓȘ ÈÔÁÂÓ›˜ ÏÔÈÌÒÍÂȘ ÌÔÚ› Ó· Ô‰ËÁ‹ÛÔ˘Ó Û ÂÈÏÔΤ˜ ÛÙËÓ ·ÒÙÂÚË ·˘Ù‹ ÌÂÙ·ÌÔÛ¯Â˘ÙÈ΋ ÂÚ›Ô‰Ô. π‰È·›ÙÂÚË ÚÔÛÔ¯‹ ¯ÚÂÈ¿˙ÂÙ·È Û ·ÛıÂÓ›˜ Ì ÌËÓÈÁÁ›Ùȉ· Ô˘ ÌÔÚ› 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· ÂÓÙÔÈÛÙ› fiÛÔ ÙÔ ‰˘Ó·ÙfiÓ ÁÚËÁÔÚfiÙÂÚ· (fiˆ˜

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˘ ÛËÙÈÎÔ‡ ÛÔÎ (1B) ∂ÎÙ›ÌËÛË ·Ó ··ÈÙÔ‡ÓÙ·È ¿ÏÏÔÈ ¯ÂÈÚÈÛÌÔ›, fiˆ˜ ·ÚÔ¯¤Ù¢ÛË ·ÔÛÙ‹Ì·ÙÔ˜ (1C) ÕÌÂÛË ·ÓÙÈÌÂÙÒÈÛË, ÌÂÙ¿ ÙËÓ ÂÈÙ˘¯‹ ·Ú¯È΋ ·Ó·˙ˆÔÁfiÓËÛË(1C) (ÂÍ·›ÚÂÛË: Ë ÂÈÌÔÏ˘Ṳ̂ÓË ·ÁÎÚ·ÙÈ΋ Ó¤ÎÚˆÛË, fiÔ˘ Ë ¯ÂÈÚÔ˘ÚÁÈ΋ ·ÓÙÈÌÂÙÒÈÛË Â›Ó·È Î·Ï‡ÙÂÚ· Ó· ηı˘ÛÙÂÚ‹ÛÂÈ) (2B) °È· ¤ÏÂÁ¯Ô ÂÛÙ›·˜ ÂÈÏÔÁ‹ ¯ÂÈÚÈÛÌÔ‡ Ì ÙËÓ ÌÂÁ·Ï‡ÙÂÚË ·ÔÙÂÏÂÛÌ·ÙÈÎfiÙËÙ· Î·È ÙȘ ÏÈÁfiÙÂÚ˜ ÂÈÏÔΤ˜ (fiˆ˜ ‰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 ÂÈıÂÙÈ΋˜ 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 ÏÂÙ¿. ªÂÁ·Ï‡ÙÂÚË Î·È ÁÚËÁÔÚfiÙÂÚË ¯ÔÚ‹ÁËÛËÌÔÚ› 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 ȤÛÂȘ 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΋˜ ·ÓÂ¿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˘ ÂÈÏÔÁ‹˜ Ë ÓÔÚ·‰ÚÂÓ·Ï›ÓË Î·È Ë ÓÙÔ·Ì›ÓË (1C) ∏ ·‰ÚÂÓ·Ï›ÓË, Ë Ê·ÈÓ˘ÏÂÊÚ›ÓË, ‹ Ë ‚·ÛÔÚÂÛÛ›ÓË ‰ÂÓ Ú¤ÂÈ Ó· ¯ÔÚËÁÔ‡ÓÙ·È Û·Ó ·ÁÁÂÔÛ˘Û·ÛÙÈο ÚÒÙ˘ ÂÈÏÔÁ‹˜ ÛÙÔ ÛËÙÈÎfi ÛÔÎ (2C) ÃÚ‹ÛË ·‰ÚÂÓ·Ï›Ó˘ Û·Ó ÂfiÌÂÓË ÂÈÏÔÁ‹ Û ÛËÙÈÎfi ÛÔÎ fiÔ˘ Ë ·ÚÙËÚȷ΋ ›ÂÛË ‰ÂÓ ·ÓÙ·ÔÎÚ›ÓÂÙ·È ÛÙË ¯ÔÚ‹ÁËÛË ÓÔÚ·‰ÚÂÓ·Ï›Ó˘ ‹ ÓÙÔ·Ì›Ó˘ (2μ) ¢ÂÓ Ú¤ÂÈ Ó· ¯ÚËÛÈÌÔÔÈÂ›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· ÙÔÔıÂÙÂ›Ù·È ÂÓ‰Ô·ÚÙËÚÈ·Îfi˜ ηıÂÙ‹Ú·˜ ̤ÙÚËÛ˘ ∞¶ fiÙ·Ó ·˘Ùfi Â›Ó·È ÂÊÈÎÙfi (1D) ™ÙÔ ÛËÙÈÎfi ÛÔÎ Ë ·˘ÙÔÚÚ‡ıÌÈÛË ÙÔ˘ ÙfiÓÔ˘ ÙˆÓ ·ÁÁ›ˆÓ ÌÔÚ› 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 ÌÔÚ› 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 ÂÈÙ›ÓÂÈ ÙËÓ ·ÓÔÛÔηٷÛÙÔÏ‹35. ™Â ÚfiÛÊ·ÙË ÔÏ˘ÎÂÓÙÚÈ΋, Ù˘¯·ÈÔÔÈË̤ÓË, ‰ÈÏ‹-Ù˘ÊÏ‹ ÌÂϤÙË Ê¿ÓËΠfiÙÈ Ë ¯ÔÚ‹ÁËÛË ÌÈÎÚ‹˜ ‰fiÛ˘ ‚·ÛÔÚÂÛÛ›Ó˘ ¤Ó·ÓÙÈ Ù˘ ÓÔÚ·‰ÚÂÓ·Ï›Ó˘, ‰ÂÓ ‚ÂÏÙÈÒÓÂÈ ÙË ÂÈ‚›ˆÛË34.

2Á. πÓfiÙÚÔ·36 ÃÚ‹ÛË ‰Ô‚Ô˘Ù·Ì›Ó˘ Û ·ÛıÂÓ›˜ Ì ηډȷ΋ ‰˘ÛÏÂÈÙÔ˘ÚÁ›· (·‡ÍËÛË ȤÛÂˆÓ 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 Â›‰· (1μ) O ÛËÙÈÎfi˜ ·ÛıÂÓ‹˜ Ô˘ ·Ú·Ì¤ÓÂÈ ˘ÔÙ·ÛÈÎfi˜ ÌÂÙ¿ ÙËÓ ·Ó¿Ù·ÍË Ì ˘ÁÚ¿ ÌÔÚ› Ó· ¤¯ÂÈ ¯·ÌËÏ‹, Ê˘ÛÈÔÏÔÁÈ΋ ‹ ˘„ËÏ‹ ηډȷ΋ ·ÚÔ¯‹. ŒÙÛÈ Ë ¯Ú‹ÛË ÈÓÔÙÚÔÔ˘/·ÁÁÂÈÔÛ˘Û·ÛÙÈÎÔ‡ ·Ú¿ÁÔÓÙ·, fiˆ˜ 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 ÛËÙÈÎfi ÛÔÎ ÌÂÙ¿ ÌÂÙ·ÌfiÛ¯Â˘ÛË ‹·ÙÔ˜, ÂÂȉ‹ ÌÔÚ› Ó· ÚÔ˘‹Ú¯Â ˘ÂÚ‰˘Ó·ÌÈ΋ ΢ÎÏÔÊÔÚ›· ÚÈÓ ÙËÓ ÂÌÊ¿ÓÈÛË ÙÔ˘ ÛËÙÈÎÔ‡ ÛÔÎ, Ë ÂÎÙ›ÌËÛË Ù˘ ηډȷ΋˜ ·ÚÔ¯‹˜ Û·Ó ·fiÏ˘ÙË ÙÈÌ‹ ‰ÂÓ Â›Ó·È ·ÛÊ·Ï‹˜. ™’ ·˘Ù¤˜ ÙȘ ÂÚÈÙÒÛÂȘ 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 ÛËÙÈÎfi ÛÔÎ fiÙ·Ó Ë ˘fiÙ·ÛË ÂÈ̤ÓÂÈ ·Ú¿ ÙËÓ ·Ó¿Ù·ÍË Ì Â·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 ÂÓÙfiÈÛË ÙˆÓ ·ÛıÂÓÒÓ Ì ÛËÙÈÎfi ÛÔÎ Ô˘ ı· Ï¿‚Ô˘Ó ˘‰ÚÔÎÔÚÙÈ˙fiÓË (2B) ∏ ˘‰ÚÔÎÔÚÙÈ˙fiÓË Â›Ó·È ÚÔÙÈÌÒÙÂÚË ·fi ÙË ‰ÂÍ·ÌÂı·˙fiÓË (2B) ∏ ÊıÔÚÈÔ¸‰ÚÔÎÔÚÙÈ˙fiÓË ÌÔÚ› Ó· Û˘ÌÂÚÈÏËÊı› ÚÔ·ÈÚÂÙÈο (2C) ∏ ıÂÚ·›· Ì ÛÙÂÚÔÂȉ‹ ÌÔÚ› Ó· ·ÔÛ˘Úı›, ·Ó ‰ÂÓ ··ÈÙÔ‡ÓÙ·È ϤÔÓ ·ÁÁÂÈÔÛ˘Û·ÛÙÈο (2D) ∏ ‰fiÛË ˘‰ÚÔÎÔÚÙÈ˙fiÓ˘ Ú¤ÂÈ Ó· Â›Ó·È ≤300 mg/24ˆÚÔ (1A) ¢ÂÓ Ú¤ÂÈ Ó· ¯ÚËÛÈÌÔÔÈÔ‡ÓÙ·È ÎÔÚÙÈÎÔÛÙÂÚÔÂȉ‹ ÁÈ· ıÂÚ·›· Û‹„˘ ·Ó ‰ÂÓ ˘¿Ú¯ÂÈ ÛÔÎ, ÂÎÙfi˜ ·Ó ˘¿Ú¯Ô˘Ó ÂӉ›ÍÂȘ ÈÛÙÔÚÈÎÔ‡ ·‰ÚÂÓÂÚÁÈ΋˜ ·ÓÂ¿ÚÎÂÈ·˜ (1D) ∏ ¯Ú‹ÛË ÂÙÔÌȉ¿Ù˘ Â›Ó·È ÚÔÙÈÌÒÙÂÚÔ Ó· ·ÔʇÁÂÙ·È Î·Ù¿ ÙË ‰È·‰Èηۛ· Ù˘ ‰È·ÛˆÏ‹ÓˆÛ˘, ÁÈ·Ù› ÌÔÚ› Ó· ηٷÛÙ›ÏÂÈ ÙÔÓ ˘Ôı·Ï·ÌÔ-˘ÔÊ˘ÛÈÔ-ÂÈÓÂÊÚȉÈÎfi ¿ÍÔÓ·40. ∏ Û¯ÂÙÈ΋ ÂÈÓÂÊÚȉÈ΋ ·ÓÂ¿ÚÎÂÈ· Â›Ó·È Û˘ÓËıÈṲ̂ÓË Û ·ÛıÂÓ›˜ Ì Ë·ÙÈ΋ ÓfiÛÔ, ÊÙ¿ÓÔÓÙ·˜ ÛÙÔ 33% ÙˆÓ ·ÛıÂÓÒÓ Ì ÔÍ›· Ë·ÙÈ΋ ·ÓÂ¿ÚÎÂÈ· Î·È ÙÔ 65% ÙˆÓ ¯ÚfiÓÈˆÓ Ë·ÙÔ·ıÒÓ Ì ۋ„Ë. ™Â ·ÛıÂÓ›˜ ÌÂÙ¿ ÌÂÙ·ÌfiÛ¯Â˘ÛË ‹·ÙÔ˜ ÛÙÔ˘˜ ÔÔ›Ô˘˜ ¯ÚËÛÈÌÔÔÈÂ›Ù·È ÚˆÙfiÎÔÏÏÔ ÂχıÂÚÔ ÎÔÚÙÈÎÔÂȉÒÓ, Û¯ÂÙÈ΋ ÂÈÓÂÊÚȉÈ΋ ·ÓÂ¿ÚÎÂÈ· ˘¿Ú¯ÂÈ Û ÔÛÔÛÙfi ¤ˆ˜ Î·È 92%, ·ÎfiÌ· Î·È Û ·Ô˘Û›· Û‹„˘41.

2Â. ∂ÓÂÚÁÔÔÈË̤ÓË ·ÓıÚÒÈÓË 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‚ÔÂÓ›· Â›Ó·È ÂÚÈÛÛfiÙÂÚÔ ÚÔ‚ÏËÌ·ÙÈ΋, ÁÈ·Ù› ·˘Í¿ÓÂÈ ÙÔÓ Î›Ó‰˘ÓÔ ·ÈÌÔÚÚ·ÁÈÎÒÓ ÂÈÏÔÎÒÓ. ∏ ¯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· Â›‰· Û ÂȉÈΤ˜ ηٷÛÙ¿ÛÂȘ (Ì˘Ôηډȷ΋ ÈÛ¯·ÈÌ›·, ÛÔ‚·Ú‹ ˘ÔÍ›·, ÔÍ›· ·ÈÌÔÚÚ·Á›·, ΢·ÓˆÙÈ΋ ηډȷ΋ ÓfiÛÔ˜ ‹ Á·Ï·ÎÙÈ΋ ÔͤˆÛË) ∏ ÂÚ˘ıÚÔÔÈËÙ›ÓË ‰ÂÓ Ú¤ÂÈ Ó· ¯ÚËÛÈÌÔÔÈÂ›Ù·È Û ·Ó·ÈÌ›· Û¯ÂÙÈ˙fiÌÂÓË Ì ۋ„Ë. ªÔÚ› Ó· ¯ÚËÛÈÌÔÔÈËı› Û ¿ÏϘ ÂȉÈΤ˜ ηٷÛÙ¿ÛÂȘ fiˆ˜ ÓÂÊÚÈ΋ ·ÓÂ¿ÚÎÂÈ· (2B) ¢ÂÓ Ú¤ÂÈ Ó· ¯ÚËÛÈÌÔÔÈÂ›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 ÂÂÌ‚·ÙÈ΋ ·Ú¤Ì‚·ÛË (2D) ¢ÂÓ ··ÈÙÂ›Ù·È ıÂÚ·›· Ì ·ÓÙÈıÚÔÌ‚›ÓË (1B) ÃÔÚ‹ÁËÛË ·ÈÌÔÂÙ·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 ‹ ÂÂÌ‚·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 ˘ÂÚηÓ›· 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΋ ÙÂÏÈÎÔÂÎÓ¢ÛÙÈ΋ ›ÂÛË (PEEP) ÁÈ· ·ÔÊ˘Á‹ Û‡ÌÙ˘Í˘ ÙˆÓ Î˘„ÂÏ›‰ˆÓ ÛÙÔ Ù¤ÏÔ˜ Ù˘ ÂÎÓÔ‹˜ (1C) ÃÚ‹ÛË ÚËÓÔ‡˜ ı¤Û˘ Û ·ÛıÂÓ›˜ Ô˘ ·ÂÚ›˙ÔÓÙ·È Ì ÌÂÁ¿ÏË Û˘ÁΤÓÙÚˆÛË ÂÈÛÓÂÔ̤ÓÔ˘ 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, ÔfiÙ ٛıÂÓÙ·È ÌÂٷ͇ 30-450 (1C) ªË ÂÂÌ‚·ÙÈÎfi˜ Ì˯·ÓÈÎfi˜ ·ÂÚÈÛÌfi˜ ¯ÚËÛÈÌÔÔÈÂ›Ù·È Û ÂÚÈÔÚÈṲ̂ÓÔ ·ÚÈıÌfi ·ÛıÂÓÒÓ Ì ̤ÙÚÈ· ¤ˆ˜ ÛÔ‚·Ú‹ ˘ÔÍ·ÈÌÈ΋ ·Ó·Ó¢ÛÙÈ΋ ·ÓÂ¿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 ÂÈΛӉ˘ÓË ÂÈÏÔ΋ ¡· ··ÈÙ› ¯·ÌËÏ‹ ·Ó·Ó¢ÛÙÈ΋ ˘ÔÛÙ‹ÚÈÍË ¡· ··ÈÙ› ˘ÎÓfiÙËÙ˜ ÂÈÛÓÂÔ̤ÓÔ˘ Ô͢ÁfiÓÔ˘ ¯·ÌËϤ˜ Ô˘ Ó· ÌÔÚÔ‡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 ˘ÂÚηÓ›· 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 Â›Ù¢ÍË ÚÔηıÔÚÈṲ̂ÓÔ˘ ÂÈ¤‰Ô˘ ηٷÛÙÔÏ‹˜ (‚¿ÛÂÈ Îϛ̷η˜), Ì ‰˘Ó·ÙfiÙËÙ· ηıËÌÂÚÈÓ‹˜ ÂÏ¿ÙÙˆÛ˘ ‹ ‰È·ÎÔ‹˜ ÙÔ˘˜ ÁÈ· Â›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 ¯ÚËÛÈÌÔÔÈÂ›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·ıÂÚÔÔ›ËÛË ÛÙË ª∂£) (1B) ¶ÚÔÛ¿ıÂÈ· ‰È·Ù‹ÚËÛ˘ ÂÈ¤‰ˆÓ ÁÏ˘Îfi˙˘ <150 mg/dL ¯ÚËÛÈÌÔÔÈÒÓÙ·˜ 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·ıÂÚÔÔÈËı›) 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˙˘ ÂËÚ¿˙ÂÙ·È ·fi ‰È¿ÊÔÚÔ˘˜ ·Ú¿ÁÔÓÙ˜, fiˆ˜ Ô Ù‡Ô˜ Î·È ÙÔ ÌÔÓÙ¤ÏÔ Ù˘ Û˘Û΢‹˜ Ô˘ ¯ÚËÛÈÌÔÔÈÂ›Ù·È Î·È Ô ·ÈÌ·ÙÔÎÚ›Ù˘ ÙÔ˘ ·ÛıÂÓ‹ (1B) ¶ÚfiÛÊ·Ù·, ÔÏ˘ÎÂÓÙÚÈ΋, Ù˘¯·ÈÔÔÈË̤ÓË ÌÂϤÙË ¤‰ÂÈÍ fiÙÈ Ë ÂÓÙ·ÙÈ΋ ÈÓÛÔ˘ÏÈÓÔıÂÚ·›· Ì ÛÙfi¯Ô ÙËÓ Â˘ÁÏ˘Î·ÈÌ›· Û ·ÛıÂÓ›˜ Ì ÛÔ‚·Ú‹ Û‹„Ë Ô‰ËÁ› Û 4Ï·ÛÈ·ÛÌfi ÙˆÓ ÂÂÈÛÔ‰›ˆÓ ˘ÔÁÏ˘Î·ÈÌ›·˜, ¯ˆÚ›˜ Ó· ‚ÂÏÙÈÒÓÂÈ ÙËÓ ÂÈ‚›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˘ Â¤Ì‚·Û˘ ηٿ ÙËÓ ¿ÌÂÛË Î˘Ú›ˆ˜ ÌÂÙ·ÌÔÛ¯Â˘ÙÈ΋ ÂÚ›Ô‰Ô, ηıÈÛÙÔ‡Ó Ôχ ÈÔ ‰‡ÛÎÔÏË ÙË Ú‡ıÌÈÛË ÙˆÓ ÂÈ¤‰ˆÓ ÁÏ˘Îfi˙˘, ȉ›ˆ˜ ·Ó ÔÈ ·ÛıÂÓ›˜ ·˘ÙÔ› ÂÈÏ·ÎÔ‡Ó Ì ۋ„Ë.

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ªÂ Ù· Ó¤· - Û˘ÌʈÓË̤ӷ ‰ÈÂıÓÒ˜ - ÎÚÈÙ‹ÚÈ· ÔÈ ÂfiÌÂÓ˜ ÌÂϤÙ˜ ı· ηٷϋÍÔ˘Ó Û ÈÔ ·ÍÈfiÈÛÙ· ÔÛÔÛÙ¿. ¶¿ÓÙˆ˜, ˆ˜ ÙÒÚ· Ë Û˘¯ÓfiÙËÙ· Ù˘ ÛÔ‚·Ú‹˜ O¡∞ Ô˘ ¯ÚÂÈ¿˙ÂÙ·È ıÂÚ·›· 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 ÛËÙÈ΋ ηٷÏËÍ›·, 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˘ÎÏÔÛÔÚ›Ó˘ ‹Ù·Ó Ù· ·›ÙÈ· Ù˘ fi„ÈÌ˘ (2Ë – 4Ë Â‚‰ÔÌ¿‰· ÌÂÙ¿ ÙË ÌÂÙ·ÌfiÛ¯Â˘ÛË).

∏ ÓÂÊÚÈ΋ ·ÓÂ¿ÚÎÂÈ· ·Ú·Ì¤ÓÂÈ Ì›· Û˘¯Ó‹ ÂÈÏÔ΋ 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‹ Â›ÙˆÛË ÙfiÛÔ Ù˘ ÔÍ›·˜ ÓÂÊÚÈ΋˜ ·ÓÂ¿ÚÎÂÈ·˜ fiÛÔ Î·È Ù˘ ¯ÚfiÓÈ·˜ ÓÂÊÚÈ΋˜ ÓfiÛÔ˘ ÛÙËÓ ÂÈ‚›ˆÛË ÙˆÓ ÌÂÙ·ÌÔÛ¯Â˘Ì¤ÓˆÓ ·ÛıÂÓÒÓ. £· ·Ó·Ï‡ÛÔ˘Ì ٷ ·›ÙÈ·, ÙË Û˘¯ÓfiÙËÙ·, ÙË ıÂÚ·›·, 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΋ ·ÓÂ¿ÚÎÂÈ· (O¡∞) Ô˘ ÂÌÊ·Ó›˙ÂÙ·È Û ·ÛıÂÓ›˜ ÌÂÙ¿ ·fi ÔÚıÔÙÔÈ΋ 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·ÊÔÚÔÔ›ËÛË ÙˆÓ ÎÚÈÙËÚ›ˆÓ Ô˘ ¯ÚËÛÈÌÔÔÈÔ‡ÓÙ·È ÁÈ· Ó· ÔÚ›ÛÔ˘Ó ÙËÓ O¡∞. ¶ÚfiÛÊ·Ù·, ÌÈ· ‰ÈÂıÓ‹˜ ÂÈÙÚÔ‹ ÂȉÈÎÒÓ Î·Ù¤ÏËÍ ÛÙËÓ Ù·ÍÈÓfiÌËÛË ÙˆÓ ÛÙ·‰›ˆÓ Ù˘ ÓÂÊÚÈ΋˜ ÚÔÛ‚ÔÏ‹˜ Î·È ÛÙËÓ ÂÈÛ·ÁˆÁ‹ ÎÚÈÙËÚ›ˆÓ, ÙˆÓ ÁÓˆÛÙÒÓ ϤÔÓ 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˘ ÌÔÚ› 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·ÓÂ¤Ì‚·ÛË. øÛÙfiÛÔ Û ÔÏ˘·Ú·ÁÔÓÙÈ΋ ·Ó¿Ï˘ÛË ·‰›¯ıËÛ·Ó ˆ˜ ÛËÌ·ÓÙÈÎÔ› ·ÓÂÍ¿ÚÙËÙÔÈ ÚÔÁÓˆÛÙÈÎÔ› ·Ú¿ÁÔÓÙ˜ ÔÈ ·Ú·Î¿Ùˆ: ÔÏÏ·Ϥ˜ 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 ÌÔÚÔ‡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· ÙÚÔÔÔÈ‹ÛÔ˘Ì ηٿÏÏËÏ· ÙËÓ ·ÓÔÛÔηٷÛÙÔÏ‹ Î·È Ó· ¯ÚËÛÈÌÔÔÈ‹ÛÔ˘Ì ٷ ‰È·ı¤ÛÈÌ· Ù¯ÓÈο ̤۷ Ì ÙÔÓ ϤÔÓ ÔÚıÔÏÔÁÈÎfi ÙÚfiÔ. Ÿˆ˜ Ê·›ÓÂÙ·È ÛÙÔ Û¯‹Ì· 1 ·fi ÙËÓ ÌÂϤÙË ÙˆÓ Parikh et al11, Ù· Â›‰· 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 ηډÈÔÓ¢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 ÌÔÚ› 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΋ ÂËÚ¿˙ÂÈ ‰˘ÛÌÂÓ¤ÛÙÂÚ· ÙËÓ ÂÈ‚›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. ∂›‰· biomarkers.

48

138

Ã. ∫À¢ø¡∞

ÛËÌÂÈÒÓÂÙ·È Ë ‰ÈÏ¿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%). ¶ÚÔÏËÙÈο, Ë ÂÈÏÔÁ‹ ‰ÔÙÒÓ ·ÏÏ¿ Î·È ÏËÙÒÓ ¯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· ÌÔÚÔ‡Û·Ó Ó· ÏËÊıÔ‡Ó ÁÈ· ÙËÓ ·ÔÊ˘Á‹ ÂÁηٿÛÙ·Û˘ O¡∞. ŸÛÔÓ ·ÊÔÚ¿ ÙËÓ ÂÌÊ¿ÓÈÛË Ã¡∞ Û ϋÙ˜ 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 ÂÈ‚·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΋ ·ÓÂ¿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· ÂËÚ¿˙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΋ ÛÂÈÚ·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‡ ÛÂÈÚ·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΋ ·ÓÂ¿ÚÎÂÈ· (ÔÚÈ˙fiÌÂÓÔ˜ ˆ˜ GFR<29ml/min/1.73m2) ‹Ù·Ó 18.1%, Ô ÔÔ›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 ÂÈ‚›ˆÛË. OÈ Gonwa et al23 η٤ÁÚ·„·Ó 13ÂÙ‹ ÂÈ‚›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‹ ÂÈ‚›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 ÏÔÈfiÓ, Â›Ó·È ·Ó·Áη›· ÎÈ ·˘Ùfi ÂÚÈÏ·Ì‚¿ÓÂÈ ·fi ÙË Ì›· ÙËÓ ÂÈıÂÙÈ΋ ·ÓÙÈÌÂÙÒÈÛË Ù˘ ˘¤ÚÙ·Û˘, Ù˘ ˘ÂÚÏÈȉ·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˘ÎÏÔÛÔÚ›ÓË Î·È ÙÔ tacrolimus, ·ÔÙÂÏÔ‡Ó ÈηÓÔ‡˜ ·ÓÔÛÔηٷÛÙ·ÏÙÈÎÔ‡˜ ·Ú¿ÁÔÓÙ˜ Ô˘ ¯ÚËÛÈÌÔÔÈÔ‡ÓÙ·È ÛÙË ÌÂÙ·ÌfiÛ¯Â˘ÛË ‹·ÙÔ˜ Î·È ·ÚÔ˘ÛÈ¿˙Ô˘Ó ·ÚfiÌÔÈÔ Ì˯·ÓÈÛÌfi ‰Ú¿Û˘, ·ÏÏ¿ Î·È ÙÔÓ ›‰ÈÔ ÙÚfiÔ ÚÔÛ‚ÔÏ‹˜ ÙÔ˘ ÓÂÊÚÔ‡. £ÂˆÚÔ‡ÓÙ·È ϤÔÓ 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 ÛÂÈÚ·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 «ÚÔÛÂÈÚ·Ì·ÙÈ΋» ÏfiÁˆ ÔÍ›·˜, ‰ÔÛÔÂÍ·ÚÙÒÌÂÓ˘ - ·ÏÏ¿ ·ÓÙÈÛÙÚÂÙ‹˜ ·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 ÓÔÚÂÈÓÂÊÚ›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˘ ΢ÎÏÔÛÔÚ›Ó˘ Î·È ‰Ë ÙËÓ ÂÓ‰ÔÊϤ‚È·, ÂÓÒ Â‡ÎÔÏ· Â·Ó¤Ú¯ÂÙ·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 ÌÔÚ› Ó· ÚÔηϤÛÂÈ ‰È¿ÌÂÛË ›ÓˆÛË Ì ÂÁηÙÂÛÙË̤ÓË ¯ÚfiÓÈ· ÓÂÊÚÈ΋ ÓfiÛÔ. ™Â Â›Â‰Ô ÌÈÎÚÔ΢ÎÏÔÊÔÚ›·˜ Ë ›ÓˆÛË ÚÔ¿ÁÂÙ·È ·fi ÌfiÚÈ·, fiˆ˜ ‚-ÙÚÔÔÔÈËÙÈÎÔ‡ ·˘ÍËÙÈÎÔ‡ ·Ú¿ÁÔÓÙ·, ÂÓ‰ÔıËÏ›Ó˘ -1 Î·È ÔÛÙÂÔÔÓÙ›Ó˘ 26. ¶·ÏÈfiÙÂÚ˜ ÌÂϤÙ˜ ÙˆÓ Fisher Î·È Platz 10-17 ‰ÂÓ ¤‰ÂÈ¯Ó·Ó ·ÍÈÔÛËÌ›ˆÙË ‰È·ÊÔÚ¿ ÛÙË ÓÂÊÚÔÙÔÍÈÎfiÙËÙ· ÌÂٷ͇ ΢ÎÏÔÛÔÚ›Ó˘ Î·È tacrolimus Û ·ÛıÂÓ›˜ Ì Oª∏. ŸÌˆ˜ ÛÙË ‰ËÌÔÛ›Â˘ÛË ÙÔ˘ Pham26 ÙÔ˘ 2003 ·ԉ›¯ıËΠ̠5ÂÙ‹ ·Ú·ÎÔÏÔ‡ıËÛË fiÙÈ ÌË ‰È·‚ËÙÈÎÔ› ·ÛıÂÓ›˜ Ì Oª∏ ›¯·Ó ηχÙÂÚË ÓÂÊÚÈ΋ ÏÂÈÙÔ˘ÚÁ›· Ì tacrolimus ·ãfiÙÈ Ì ΢ÎÏÔÛÔÚ›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˘ÎÏÔÛÔÚ›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·, fiˆ˜ ÁÈ· ·Ú¿‰ÂÈÁÌ· Ô Gonwa Ô˘ ·ÓÙÈηıÈÛÙ¿ ÙËÓ Î˘ÎÏÔÛÔÚ›ÓË Û ·ÛıÂÓ›˜ Ì Ë·ÙÔÓÂÊÚÈÎfi Û‡Ó‰ÚÔÌÔ ‹ ̤ÙÚÈ· ÓÂÊÚÈ΋ ·ÓÂ¿ÚÎÂÈ· Ì ÙÔ Û˘Ó‰˘·ÛÌfi ·˙·ıÂÈÔÚ›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, fiˆ˜ 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· ·ÓıÚÒÈÓË ·ÓÔÛÔÛÊ·ÈÚ›ÓË G1 Ô˘ ÌÏÔοÚÂÈ ÙËÓ ·Ï˘Û›‰· · ÙˆÓ ˘Ô‰Ô¯¤ˆÓ Ù˘ interleukin 2 ÛÙ· ÂÓÂÚ-

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ÁÔÔÈË̤ӷ Δ ÏÂÌÊÔ·ÙÙ·Ú·. ¢ÂÓ ·Ú·ÙËÚ‹ıËÎ·Ó ÂÈÏÔΤ˜ 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, ÔfiÙÂ 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. ÃÚËÛÈÌÔÔÈ‹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΋ ·ÓÂ¿ÚÎÂÈ· ¯ÔÚ‹ÁËÛ·Ó MMF Ì ÛÙ·‰È·Î‹ Ì›ˆÛË Ù˘ ΢ÎÏÔÛÔÚ›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 ·ԉ‰ÂÈÁ̤ÓË Ì ‚ÈÔ„›· CNI-related ¯ÚfiÓÈ· ÓÂÊÚÈ΋ ÓfiÛÔ, Ë ¤Ó·ÚÍË MMF ÛÙË ı¤ÛË Î˘ÎÏÔÛÔÚ›Ó˘ ‹ tacrolimus ‰ÂÓ Â·Ó¤ÊÂÚ ÙË ÓÂÊÚÈ΋ ÏÂÈÙÔ˘ÚÁ›·, Ô‡Ù ·fi ÙËÓ ¿ÏÏË ·‡ÍËÛ ٷ ÂÂÈÛfi‰È· ·fiÚÚȄ˘. ∞Ó Î·È Î¿ÔÈ· ΤÓÙÚ· ÂÈ̤ÓÔ˘Ó Ó· ÙÔ ‰ÔÎÈÌ¿˙Ô˘Ó ˆ˜ ÌÔÓÔıÂÚ·›· 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·˘ÙÔÔÈ‹ıËΠÚÒÙ· ˆ˜ ·ÓÙÈÌÈÎÚÔ‚È·Îfi Ê¿ÚÌ·ÎÔ Ù˘ ηÙËÁÔÚ›·˜ ÙˆÓ Ì·ÎÚÔÏȉÒÓ, ·ÏÏ¿ ·ÚÁfiÙÂÚ· ·Ó·ÁÓˆÚ›ÛÙËÎ·Ó ÔÈ ·ÓÔÛÔÙÚÔÔÔÈËÙÈΤ˜ 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΋˜ ·ÓÂ¿ÚÎÂÈ·˜ Ì ٷ˘Ùfi¯ÚÔÓË ‰È·ÎÔ‹ ÙˆÓ CNI, ‚ÂÏÙ›ˆÛ ÙË ÓÂÊÚÈ΋ ÏÂÈÙÔ˘ÚÁ›· ¯ˆÚ›˜ ÂÌÊ¿ÓÈÛË ·fiÚÚȄ˘37. ŸÌˆ˜ ÙÔ FDA ÚÔÂȉÔÔ›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¿ ÌÔÚ› Ó· ¯ÔÚËÁËı› 6 Ì‹Ó˜ ÌÂÙ¿38,39. ∞ÓÙÈÎÚÔ˘fiÌÂÓ˜ ÌÂϤÙ˜ ˘ÔÛÙËÚ›˙Ô˘Ó ÙË ¯Ú‹ÛË ÙÔ˘, ÁÈ·Ù› ‰ÂÓ ÂȂ‚·›ˆÛ·Ó ·˘ÍË̤ÓË Â›ÙˆÛË ÛÙË ıÚfiÌ‚ˆÛË Ù˘ Ë·ÙÈ΋˜ ·ÚÙËÚ›·˜40,41.

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∂›Ó·È ÏÔÈfiÓ ÏÔÁÈÎfi, ÏfiÁˆ Ù˘ ¤ÏÏÂȄ˘ ÌÂÁ¿ÏˆÓ ÚÔÔÙÈÎÒÓ Ù˘¯·ÈÔÔÈËÌ¤ÓˆÓ ÌÂÏÂÙÒÓ Î·È ÙˆÓ ·ÌÊÈÏÂÁfiÌÂÓˆÓ ·ÔÙÂÏÂÛÌ¿ÙˆÓ ÌÂÏÂÙÒÓ Ì ÌÈÎÚ¤˜ ÛÂÈÚ¤˜ ·ÛıÂÓÒÓ, Ë ·ÓÔÛÔηٷÛÙ·ÏÙÈ΋ ıÂÚ·›· Ó· ÚÔÛ‰ÈÔÚ›˙ÂÙ·È Ì ‚¿ÛË ÙȘ ·Ó¿ÁΘ ÙÔ˘ Û˘ÁÎÂÎÚÈ̤ÓÔ˘ ·ÚÚÒÛÙÔ˘. ŒÙÛÈ, ÌÔÚ› ·fi ÙË Ì›· Ù· ÌÔÓÔÎψÓÈο ·ÓÙÈÛÒÌ·Ù· ¤Ó·ÓÙÈ ÙˆÓ ˘Ô‰Ô¯¤ˆÓ Ù˘ interleukin 2 Ì ‰È·ÎÔ‹ Ù˘ ΢ÎÏÔÛÔÚ›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·ÓÂÓÂÚÁÔÔ›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‡˜ ¯ÚËÛÈÌÔÔÈÔ‡ÓÙ·È ÔÈ ·Ó·ÛÙÔÏ›˜ ÙÔ˘ ÌÂÙ·ÙÚÂÙÈÎÔ‡ 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΋˜ £ÂÚ·›·˜, fiÔ˘ Ï·Ì‚¿ÓÔÓÙ·È Ù· ··Ú·›ÙËÙ· ıÂÚ·¢ÙÈο ̤ÙÚ· ÁÈ· ÙËÓ ÚfiÏË„Ë Î·È ·ÓÙÈÌÂÙÒÈÛË Ù˘ ÓÂÊÚÈ΋˜ ·ÓÂ¿ÚÎÂÈ·˜. ∏ Â·Ú΋˜ ·ÔηٿÛÙ·ÛË ÙÔ˘ ÂÓ‰·ÁÁÂÈ·ÎÔ‡ fiÁÎÔ˘, Ë ·ÈÌÔ‰˘Ó·ÌÈ΋ ˘ÔÛÙ‹ÚÈÍË, Ë ÂÈıÂÙÈ΋ ıÂÚ·›· Û ÂÌÊ·ÓÈ˙fiÌÂÓË Û‹„Ë, Ë ¯Ú‹ÛË ÓÂÊÚÔÚÔÛٷ٢ÙÈÎÒÓ 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· ·ÍÈfiÈÛÙÔ˜ ‰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˘ ÌÔÚ› Ó· Û˘Ì‚¿ÏÏÔ˘Ó Û „¢‰Ò˜ ¯·ÌËÏ¿ Â›‰· 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˘ÂÙ›‰ÈÔ Ô˘ ·Ú¿ÁÂÙ·È Û fiÏÔ˘˜ ÙÔ˘˜ ˘Ú‹Ó˜ ÙˆÓ Î˘ÙÙ¿ÚˆÓ Û˘Ó¯Ҙ ̤۷ ÛÙÔ ¯ÚfiÓÔ, ÂÚÓ¿ ÙË ÛÂÈÚ·Ì·ÙÈ΋ ÌÂÌ‚Ú¿ÓË, Â·Ó·ÔÚÚÔÊ¿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 ÌÔÚ› Ó· ·ÔÙÂϤÛÂÈ ÙËÓ Ú·ÎÙÈ΋ ÙÔ˘ ̤ÏÏÔÓÙÔ˜ ÛÙË ª∂£47,48,49. ™ËÌ·ÓÙÈ΋ Â›Ó·È ÂÈϤÔÓ 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·, ÙÔÔı¤ÙËÛË ·ÈÌÔÛÙ·ÙÈÎÒÓ Á·˙ÒÓ Á‡Úˆ ·fi ÙÔ ÌfiÛ¯Â˘Ì· ÁÈ· ÙËÓ ·ÓÙÈÌÂÙÒÈÛË ‰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˘ - fiˆ˜ Û˘Ì‚·›ÓÂÈ ÛÙËÓ ·¯˘Û·ÚΛ· - fiÔ˘ ˘¿Ú¯ÂÈ ¯ÚfiÓÔ˜ ÁÈ· ·ÓÙÈÚÚfiËÛË53. ∏ ‰È·Ú΋˜ ·‡ÍËÛË Ù˘ IAP Ô‰ËÁ› Û Ì›ˆÛË Ù˘ ηډȷ΋˜ ·ÚÔ¯‹˜, Ù˘ ÛÏ·¯ÓÈ΋˜ Î·È Ë·ÙÈ΋˜ ·ÈÌ·ÙÈ΋˜ ÚÔ‹˜ Î·È ÙÔ˘ ‰Ú·ÛÙÈÎÔ‡ ·Ó·ÓÂfiÌÂÓÔ˘ fiÁÎÔ˘. O Ì˯·ÓÈÛÌfi˜ Ì ÙÔÓ ÔÔ›Ô Ë ˘„ËÏ‹ IAP ÚÔηÏ› ÓÂÊÚÈ΋ ·ÓÂ¿ÚÎÂÈ· ‰ÂÓ ¤¯ÂÈ Ï‹Úˆ˜ ‰È¢ÎÚÈÓÈÛÙ›, ·ÏÏ¿ ÁÓˆÚ›˙Ô˘Ì οÔÈÔ˘˜ ·ÈÙÈÔ·ıÔÏÔÁÈÎÔ‡˜ ·Ú¿ÁÔÓÙ˜ fiˆ˜ : 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 ÔÔ›Ô Â›Ó·È ÎÚ›ÛÈÌË ÁÈ· ÙÔ˘˜ ÓÂÊÚÔ‡˜, ‚Ú¤ıËΠ۠ÂÈÚ·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 ÛÂÈÚ·Ì·ÙÈ΋ ‰È‹ıËÛË Î·Ù¿ 25% Î·È ÂÈʤÚÂÈ ÔÏÈÁÔ˘-

METAMO™XEY™Eπ™ 2008

Ú›·55. ™Â ÌÈ· ÌÂϤÙË Ô˘ ·ÊÔÚ¿ ÂȉÈο ÙËÓ ÂÓ‰ÔÎÔÈÏȷ΋ ˘¤ÚÙ·ÛË Û ϋÙ˜ ‹·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 ÂËÚ¿˙ÂÈ Î¿ÔȘ ·ÈÌÔ‰˘Ó·ÌÈΤ˜ ·Ú·Ì¤ÙÚÔ˘˜, fiˆ˜ 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 ÌÔÚ› Ó· ·ÓÙ·Ó·ÎÏ¿ Û „¢‰Ò˜ ˘„ËϤ˜ ÙÈ̤˜ CVP Î·È PCWP57 Î·È Ó· ·Ú·Ï·Ó¿ ÙÔÓ ÎÏÈÓÈÎfi ÁÈ·ÙÚfi, Ô ÔÔ›Ô˜ ‰ÂÓ ·ÓÙÈÏ·Ì‚¿ÓÂÙ·È ÙËÓ ˘ÔÁηÈÌ›· Î·È ¿Ú· ‰ÂÓ ÙËÓ ·ÓÙÈÌÂÙˆ›˙ÂÈ Ì ·ÔÙ¤ÏÂÛÌ· ÙËÓ ÚÔÓÂÊÚÈ΋ ·˙ˆı·ÈÌ›·. ¶·Ú·ÙËÚ‹ıËΠÏÔÈfiÓ, ¿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΋˜ ·ÓÂ¿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 ·ÓÙÈÌÂÙÒÈÛË Ù˘ ÂÁηÙÂÛÙË̤Ó˘ ϤÔÓ O¡∞ ÛÙË ªÔÓ¿‰· Â›Ó·È Ô ¯ÚfiÓÔ˜ ¤Ó·Ú͢ Î·È Ô Ù‡Ô˜ Ù˘ ıÂÚ·›·˜ ÓÂÊÚÈ΋˜ ˘ÔηٿÛÙ·Û˘. ∏ ÂÈÏÔÁ‹ ·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 ·ԉ›ÍÂÈ ÙËÓ ˆÊ¤ÏÂÈ· Ù˘ ÚÒÈÌ˘ CRRT ÛÙËÓ ÚfiÁÓˆÛË ·ÛıÂÓÒÓ Ì ÔÏ˘ÔÚÁ·ÓÈ΋ ·ÓÂ¿ÚÎÂÈ· ÂÍ·ÈÙ›·˜ Û‹„˘59 ‹ ÌÂÙ¿ ·fi ÌÂÁ¿Ï˜ ¯ÂÈÚÔ˘ÚÁÈΤ˜ ÂÂÌ‚¿ÛÂȘ60. ∞˘Ùfi ÂÍËÁÂ›Ù·È ·fi ÙÔ fiÙÈ Ë ·ÚÁ‹ Î·È Û˘Ó¯‹˜ ̤ıÔ‰Ô˜ ÂÈÙÚ¤ÂÈ ÙËÓ ÛÙ·ıÂÚ‹ ·ÔÌ¿ÎÚ˘ÓÛË ÙˆÓ Ô˘Ú·ÈÌÈÎÒÓ ÙÔÍÈÓÒÓ Î·È ÙÔ˘ ÏÂÔÓ¿˙ÔÓÙÔ˜ ‡‰·ÙÔ˜ Î·È ÙËÓ ÙÈÙÏÔÔÈË̤ÓË ˆÚÈ·›· ·Ê˘‰¿ÙˆÛË ·Ó¿ÏÔÁ· Ì ÙËÓ ÂÌÊ¿ÓÈÛË ·ÈÌÔ‰˘Ó·ÌÈ΋˜ ·ÛÙ¿ıÂÈ·˜. ∂›Ó·È ÛËÌ·ÓÙÈÎfi fiÙÈ ‰ÂÓ ÂÈ‚·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΋ ·ÓÂ¿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΋ ‰˘ÛÚ·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˘ ÂÈÎÚ·ÙÔ‡Ó Û οı ÓÔÛÔÎÔÌÂ›Ô (·ÚÈıÌfi˜ ÓÔÛËÏ¢ÙÒÓ, ÂÍÔÈΛˆÛË ÙÔ˘ ÚÔÛˆÈÎÔ‡ 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 ϤÔÓ ÂËÚ¿˙ÂÙ·È ·fi ¿ÏÏÔ˘˜ ·Ú¿ÁÔÓÙ˜, fiˆ˜ ηډȷÁÁÂȷο ÓÔÛ‹Ì·Ù·, ÌÂÙ·‚ÔÏÈΤ˜ ‹ ·ÓÔÛÔÏÔÁÈΤ˜ ‰È·Ù·Ú·¯¤˜ Î·È ¯ÚfiÓÈ· ÓÂÊÚÈ΋ ·ÓÂ¿ÚÎÂÈ·. ∞ÊÔ‡ ‰È·Ó‡Ô˘Ì ÙËÓ 3Ë ‰ÂηÂÙ›· ÂÈÙ˘¯Ô‡˜ Oª∏, ÌÈ· ‰È·‰Èηۛ· Ô˘ ¤ÊÂÚ ÙËÓ Â·Ó¿ÛÙ·ÛË ÛÙËÓ ·ÓÙÈÌÂÙÒÈÛË ÙÔ˘ ÙÂÏÈÎÔ‡ ÛÙ·‰›Ô˘ Ë·ÙÈ΋˜ ·ÓÂ¿ÚÎÂÈ·˜, Ë ÚÔÛÔ¯‹ Ì·˜ Ú¤ÂÈ Ó· ÛÙÚ·Ê› ÛÙË ‚ÂÏÙ›ˆÛË Ù˘ ÔÈfiÙËÙ·˜ ˙ˆ‹˜ Î·È ÙË Ì·ÎÚfi¯ÚÔÓË ÂÈ‚›ˆÛË ÙˆÓ ·ÛıÂÓÒÓ ÎÈ ·˘Ùfi ÂȉÈο ÂÌÂÚȤ¯ÂÈ ÙËÓ ÚÔÛÙ·Û›· ÙÔ˘ ÓÂÊÚÔ‡.

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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 ÂÈÏÔÎÒÓ, ÔÏϤ˜ ·Ô ÙȘ Ôԛ˜ Ô‰ËÁÔ‡Ó ÙÔ ÌÂÙ·ÌÔÛ¯Â˘Ì¤ÓÔ ÛÙÔ ı¿Ó·ÙÔ.

OÈ ÂÈÏÔΤ˜ ÛÙË ª∏ Ô˘ ··ÈÙÔ‡Ó ¯ÂÈÚÔ˘ÚÁÈ΋ ‰ÈÂÚ‡ÓËÛË, ı· ÌÔÚÔ‡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˘ ÌÔÚÔ‡Ó Ó· ·ÚÔ˘ÛÈ·ÛıÔ‡Ó ÌÂÙ¿ ÙÔ ¤Ú·˜ Ù˘ ÓÔÛËÏ›·˜ ÙÔ˘ ·ÛıÂÓÔ‡˜ Î·È ÙËÓ ÂÈÛÙÚÔÊ‹ ÛÙÔ Û›ÙÈ ÙÔ˘. ¶ÚÔÎÂÈ̤ÓÔ˘ Ó· ‰Ôı› Ì›· ÛÊ·ÈÚÈ΋ ÂÈÎfiÓ·, ı· ·ÚÔ˘ÛÈ·ÛÙÔ‡Ó ÔÈ ÂÚÈÛÛfiÙÂÚÔ ÎÔÈÓ¤˜ ÂÈÏÔΤ˜ Ô˘ ÌÔÚÔ‡Ó Ó· ÂÈÛ˘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. ∏ ÂÈÌÂÏ‹˜ ·ÈÌfiÛÙ·ÛË Û˘¯Ó¿ ‰ÂÓ Â·ÚΛ ÁÈ· ÙËÓ ÚfiÏË„Ë ·˘Ù‹˜ Ù˘ ÂÈÏÔ΋˜ Î·È Ë ¯Ú‹ÛË ·ÈÌÔÛÙ·ÙÈÎÔ‡ ÂÈˆÌ·ÙÈÛÌÔ‡ 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 ÂÚÈÙÒÛÂȘ 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˘ fiˆ˜ ·˘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 ÂfiÌÂÓ˜ 4872 ÒÚ˜ ÌÂÙ¿ ÙË ÌÂÙ·ÌfiÛ¯Â˘ÛË, ÁÈ· ·ÔÌ¿ÎÚ˘ÓÛË ÙˆÓ Ï·ÎÔ‡ÓÙˆÓ ·›Ì·ÙÔ˜.

¶ÚÒ˚̘ ÃÂÈÚÔ˘ÚÁÈΤ˜ ªÂÙÂÁ¯ÂÈÚËÙÈΤ˜ ∂ÈÏÔΤ˜ OÈ ÂÈÏÔΤ˜ 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˜ ÂÈÏÔΤ˜, ÙËÓ ·ÈÌÔÚÚ·Á›· ·Ô ÙÔ ÂÙÈÎfi, ÙË ‰È¿ÙÚËÛË ÎÔ›ÏÔ˘ ÛÏ¿¯ÓÔ˘ ÙË ‰È·Ê˘Á‹ ·Ô ÙËÓ ·Ó·ÛÙfïÛË ÙˆÓ ¯ÔÏËÊfiÚˆÓ ‹ ÙÔ ¯ÔÏÔÂÚÈÙfiÓ·ÈÔ. Δ¤ÏÔ˜ Ò˜ ¯ÂÈÚÔ˘ÚÁÈ΋ ÂÈÏÔ΋ Ô˘ ··ÈÙ› ¿ÌÂÛË ¯ÂÈÚÔ˘ÚÁÈ΋ ·ÓÙÈÌÂÙÒÈÛË Ì ÙËÓ ¤ÓÓÔÈ· Ù˘ Â·Ó·ÌÂÙ·ÌfiÛ¯Â˘Û˘, Â›Ó·È Î·È Ë ÌË ÏÂÈÙÔ˘ÚÁ›· ÙÔ˘ ÌÔۯ‡̷ÙÔ˜. ∏ Û˘¯ÓfiÙËÙ· ·˘ÙÒÓ ÙˆÓ ÂÈÏÔÎÒÓ 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 ÂÈÏÔ‹ Ô˘ Û˘Ó‹ıˆ˜ ÂÈÛ˘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

∏ ÂÈÏÔ΋ ·˘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›·. ∏ ·ÓÙÈÌÂÙÒÈÛË Ù˘ ÂÈÏÔ΋˜ ·˘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 ÔÔ›Ô ‰È·ÁÓÒÛıËΠıÚfiÌ‚ˆÛË Ù˘ Ë·ÙÈ΋˜ ·ÚÙËÚ›·˜, ÂÊ fiÛÔÓ Á›ÓÂÈ Û¯Â‰fiÓ ¿ÌÂÛ· ÌÂÙ¿ ÙÔ Û˘Ì‚¿Ó, ÌÔÚ› 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˘ÌÏËڈ̷ÙÈ΋ ¤Á¯˘ÛË ıÚÔÌ‚ÔÏ˘ÙÈÎÒÓ Ô˘ÛÈÒÓ (¯, ÛÙÂÙÔÎÈÓ¿ÛË, Ô˘ÚÔÎÈÓ¿ÛË ÎÏ). ∏ ·ÔÙÂÏÂÛÌ·ÙÈÎfiÙËÙ· Ù˘ ÌÂıfi‰Ô˘ ·ÌÊÈÛ‚ËÙ›ٷÈ, ·Ó Î·È ÛÙË ‚È‚ÏÈÔÁÚ·Ê›· ·Ó·Ê¤ÚÔÓÙ·È ÂÈÙ˘¯Â›˜ ÚÔÛ¿ıÂȘ. ∏ ·ÓÙÈÌÂÙÒÈÛË Ù˘ ÂÈÏÔ΋˜ ·˘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˜ ÂÈÏÔΤ˜ Ú¤ÂÈ Ó· Û˘ÌÂÚÈÏËÊı› Ë ıÚfiÌ‚ˆÛË Ù˘ ˘Ï·›·˜ (1.5%-2%), Ë ÔÔ›· Û˘Ó‹ıˆ˜ ‰È·ÁÓÒÛÎÂÙ·È Ì ÌÂÁ·Ï‡ÙÂÚË Î·ı˘ÛÙ¤ÚËÛË ·fiÙÈ Ë ıÚfiÌ‚ˆÛË Ù˘ Ë·ÙÈ΋˜ ·ÚÙËÚ›·˜, ÂÂȉ‹ Ë ‚ÈÔ¯ËÌÈ΋ Ù˘ ÂÈÎfiÓ· ‰ÂÓ Â›Ó·È ÙfiÛÔ ¿ÌÂÛ· ıÔÚ˘‚҉˘. ∫·È Û ·˘Ù‹ ÙËÓ ÂÚ›ÙˆÛË ÌÔÚ› Ó· ÂȯÂÈÚËı› ¯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.

∂ÈÏÔΤ˜ ·Ô Ù· ¯ÔÏËÊfiÚ· OÈ ÂÈÏÔΤ˜ ·Ô Ù· ¯ÔÏËÊfiÚ· (10% ÛÙÔ˘˜ ÂÓ‹ÏÈΘ) ·ÔÙÂÏÔ‡Ó ÛËÌ·ÓÙÈÎfi Úfi‚ÏËÌ· ÛÙȘ ÂÚÈÛÛfiÙÂÚ˜ ÌÂÙ·ÌÔÛ¯Â˘ÙÈΤ˜ ÌÔÓ¿‰Â˜. ™ÙȘ ÂÈÏÔΤ˜ ·˘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 ¯ÔÏÔÂÙÈ΋ ·Ó·ÛÙfïÛË Î·È ÙÔ ¯ÔÏÔÂÚÈÙfiÓ·ÈÔ, ÙÔ ÔÔ›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΋

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·Ó·ÛÙfïÛË, ·ÔÙÂÏ› ¯·Ú·ÎÙËÚÈÛÙÈÎfi ‰È·Ê˘Á‹˜ ·Ô ÙËÓ ·Ó·ÛÙfïÛË ÙˆÓ ¯ÔÏËÊfiÚˆÓ. ∂ÊfiÛÔÓ ¤¯ÂÈ ÙÔÔıÂÙËı› ۈϋӷ˜ Kehr ÛÙË Ã-à ·Ó·ÛÙfïÛË Î·È ÌÂÙ¿ ·Ô ÂȂ‚·›ˆÛË ÌÂ Û˘ÚÈÁÁÔÁÚ·Ê›·,- Ô˘ ÌÔÚ› Ó· Á›ÓÂÈ Î·È ÂÈ Ù˘ ÎÏ›Ó˘-, Ë ¿ÌÂÛË ¯ÂÈÚÔ˘ÚÁÈ΋ ‰ÈÂÚ‡ÓËÛË ‰ÂÓ Â›Ó·È ··Ú·›ÙËÙË Î·È ÌÔÚ› Ó· ÚÔÁÚ·ÌÌ·ÙÈÛı› Ó· ‰ÈÂÓÂÚÁËı› Ì ÙȘ ηÏÏ›ÙÂÚ˜ ‰˘Ó·Ùfi Û˘Óı‹Î˜ ÁÈ· ÙÔÓ ·ÛıÂÓ‹. ™ÙȘ ÂÚÈÙÒÛÂȘ fï˜ Ù˘ ¯ÔÏÔÂÙÈ΋˜ ·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 ÂÈÏÔ΋ ·Ô ÙË ÏÂÈÙÔ˘ÚÁ›· ˆ˜ <ηÙ¢ı˘ÓfiÌÂÓÔ Û˘Ú›ÁÁÈÔ> Ù˘ ˘ÊË·ÙÈ΋˜ ·ÚÔ¯¤Ù¢Û˘, ÙfiÙÂ Â›Ó·È ··Ú·›ÙËÙË Ë ·ÓÙÈÌÂÙÒÈÛ‹ 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. ∏ ıÂÚ·›· ÂÍ·ÚÙ¿Ù·È ·Ô ÙË Ê‡ÛË Ù˘ ÂÈÏÔ΋˜ 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 ÙÔÔı¤ÙËÛË stent ÂÓÙfi˜ ÙÔ˘ ¯ÔÏˉfi¯Ô˘ fiÚÔ˘ ¤ˆ˜ ÙË ÌÂÙ·ÙÚÔ‹ Ù˘ ¯ÔÏˉԯÔ-¯ÔÏˉfi¯Ô (Ã-Ã) ·Ó·ÛÙfïÛ˘, Û ¯ÔÏÔÂÙÈ΋ ·Ó·ÛÙfïÛË (Roux-en-À). ™ÙȘ ÂÚÈÙÒÛÂȘ ‰È·Ê˘Á‹˜ ·Ô ÙËÓ ¯ÔÏÔÂÙÈ΋ ·Ó·ÛÙfïÛË, Û˘Ó‹ıˆ˜ ·ÚΛ Ë Û˘ÚÚ·Ê‹ ÙÔ˘ ÛËÌ›Ԣ ·Ô fiÔ˘ ·Ú·ÙËÚÂ›Ù·È Ë ‰È·Ê˘Á‹ ηÈ, Û ·ÎÚ·›Â˜ ÂÚÈÙÒÛÂȘ, Ë ÙÔÔı¤ÙËÛË ÂȉÈÎÔ‡ ۈϋÓÔ˜-ÎˉÂÌfiÓÔ˜ ÛÙËÓ ·Ó·ÛÙfïÛË, Ô ÔÔ›Ô˜ ÂÍÂÚ¯ÂÙ·È Ì¤Ûˆ Ù˘ ÚÔÛÈÔ‡Û˘ ¤ÏÈÎÔ˜ Ù˘ Rouxen-À ·Ô ÙÔ ÎÔÈÏÈ·Îfi ÙÔ›¯ˆÌ·.

∞ÈÌÔÚÚ·Á›· ·Ô ÙÔ ÂÙÈÎfi ™˘Ó‹ı˘ ÂÓÙfiÈÛË ·˘Ù‹˜ Ù˘ ·ÈÌÔÚÚ·Á›·˜ Â›Ó·È Ô ÛÙfiÌ·¯Ô˜ (Á·ÛÙÚÔÚÚ·Á›· ·Ô ÎÈÚÛÔ‡˜ ÙÔ˘ ıfiÏÔ˘/stress ulcer), Ë ¯ÔÏÔÂÙÈ΋ ·Ó·ÛÙfïÛË, ¤ÎÙÔÔÈ ÎÈÚÛÔ› ÛÙÔ ÏÂÙfi ¤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· ÂÓÙÔÈÛı› Î·È Ó· ÂÏÂÁ¯ı›.

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¢È¿ÙÚËÛË ÎÔ›ÏÔ˘ ÛÏ¿¯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˜. ∏ ·ÓÙÈÌÂÙÒÈÛË Â›Ó·È Ë Û˘Ó‹ı˘ ÂÁ¯ÂÈÚËÙÈ΋, fiˆ˜ 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· Â·Ó·ÌÂÙ·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 ¤ÎÙˆÛË Ù˘ ÏÂÈÙÔ˘ÚÁ›·˜ ÙÔ˘ Ë·ÙÈÎÔ‡ ÌÔۯ‡̷ÙÔ˜ ı· ··ÈÙ‹ÛÔ˘Ó Â·Ó·ÌÂÙ·ÌfiÛ¯Â˘ÛË.

™˘ÌÂÚ¿ÛÌ·Ù· ™ÙËÓ ¿ÌÂÛË ÌÂÙ·ÌÔÛ¯Â˘ÙÈ΋ ÂÚ›Ô‰Ô, Ô ·ÛıÂÓ‹˜ Ì ÌÂÙ·ÌfiÛ¯Â˘ÛË ‹·ÙÔ˜ ÌÔÚ› Ó· ÂÌÊ·Ó›ÛÂÈ ¤Ó·Ó ÛËÌ·ÓÙÈÎfi ·ÚÈıÌfi ÂÈÏÔÎÒÓ, Ô˘ fiϘ Â›Ó·È ·ÂÈÏËÙÈΤ˜ ÁÈ· ÙËÓ ÂÈ‚›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 ÂÂÌ‚¿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

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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-

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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

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23.11.2006 CMV Infect, Gancyclovir

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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

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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.

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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.