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4 Childhood Seizure and Epilepsy
Partial seizure (.ocal seizure) (4)
Partial ËÃ×Í focal seizure ໚¹ÍÒ¡Òêѡ«Ö§à¡Ô´¨Ò¡¡Ò÷ÕÁ¡ÃÐáÊä¿¿‡Ò·ÕÁÒ¡¼Ô´»¡µÔà¡Ô´¢Ö¹
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2. Complex partial seizure (CPS) ¼ÙŒ»†Ç¨ÐÁÕ impairment of consciousness «Öè§
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Generalized seizure (4)
Generalized seizure ໚¹ÍÒ¡Òêѡ·Õà¡Ô´¢Ö¹¨Ò¡¡ÒÃà»ÅÕ¹á»Å§¢Í§¡ÃÐáÊä¿¿‡Ò·Õè¡Ãеع
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·ÕäÁ‹¨Òà¾Òзբҧ㴢ŒÒ§Ë¹Ö§¢Í§Ã‹Ò§¡Ò generalized seizure ẋ§Í͡໚¹ 4 ¡ÅØÁãË‹æ 䴌ᡋ
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1. Tonic-clonic seizure (grand mal) ¼Ù»Ç¨ÐÁÕ¤ÇÒÁÃÙÊ¡µÑÇ·ÕŴŧ ËÇÁ¡ÑºÍÒ¡ÒÃà¡Ãç§ áÅÐ/
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ËÃ×Í¡Ãеء¢Í§ÅíÒµÑÇ, ᢹ¢Ò â´Â·ÑèÇä»ÍÒ¡Òêѡ¨ÐàÃÔèÁµŒ¹´ŒÇÂÍÒ¡ÒÃà¡Ãç§ (tonic phase) áÅŒÇ
µÒÁÁÒ´ŒÇÂÍÒ¡ÒáÃеء (clonic phase) ª‹Ç§·ÕèÁÕÍÒ¡Òêѡ¼ÙŒ»†ÇÂÍÒ¨ÁÕÍÒ¡Ò÷ҧÃкº»ÃÐÊÒ·
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.irst line drug in partial seizure : Phenytoin, phenobarbital,carbamazepine,
valproic acid
Primary generalized tonic-clonic seizure : Phenytoin, phenobarbital, carbamazepine,
valproic acid
Absence, myoclonic, atonic seizure : Valproic acid
Infantile spasm : Vigabatrin, ACTH
2. ¤ÇÃàÃÔÁÂҡѹªÑ¡´ŒÇÂÂÒª¹Ô´à´ÕÂÇ¡‹Í¹ (monotherapy)
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7. ã¹àǪ»¯Ôºµ·Ç仹ÔÂÁãËŒÂҡѹªÑ¡á¡‹¼»ÇµԴµ‹Í¡Ñ¹à»š¹ÃÐÂÐàÇÅÒ¹Ò¹ 2 »‚¡Í¹¾Ô¨ÒóÒ
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37.
10 Childhood Seizure and Epilepsy
µÒÃÒ§·Õè 3 ¢¹Ò´áÅФÇÒÁ¶Õè¢Í§¡ÒÃãËŒÂҡѹªÑ¡·Õè㪌º‹ÍÂã¹»ÃÐà·Èä·Â
Drug Initial dose Maintenance dose .requency Therapeutic level Metabolism
(mg/kg/day) (mg/kg/day) (mg/L)
Phenobarbital 3-5 3-8 bid, hs 10-40 Hepatic
Phenytoin 5 5-8 bid, hs 10-20 Hepatic
Carbamazepine 10-15 10-30 tid, bid (CR) 4-12 Hepatic
Valproic acid 10-15 30-60 tid, bid (chrono) 50-120 Hepatic
Topiramate 1 5-9 bid - Renal 70%
Levetiracetam 10 20-60 bid - Renal 70%
Lamotrigine 0.5 5-10 bid - Renal 70%
Oxcarbazepine 10 20-50 bid - Renal 70%
ÊÃØ»
âäÅÁªÑ¡ã¹à´ç¡à»š¹âä·Ò§ÊÁͧ·Õ¾ºä´ŒºÍÂã¹àǪ»¯ÔºµÔ ᾷ¤ÇÃÁÕ¤ÇÒÁÃÙ·à¡ÕÂÇ¢ŒÍ§¡Ñº
è ‹ Ñ Œ Õè è
ÍÒ¡Òêѡ áÅÐâäÅÁªÑ¡ãËŒ´Õ ÁÕ¤ÇÒÁÊÒÁÒö·Õ¨Ð«Ñ¡»ÃÐÇÑµÔ µÃǨËҧ¡Ò àÅ×͡ʋ§¡ÒõÃǨ¾ÔàÈÉ
è
Í×¹æ 䴌͋ҧàËÁÒÐÊÁà¾×ÍÇÔà¤ÃÒÐËÇÒ¼Ù»ÇÂÁÕÍÒ¡ÒêѡËÃ×ÍäÁ‹ ¶ŒÒÁÕÍÒ¡Òêѡ໚¹ÍÒ¡Òêѡª¹Ô´ã´
è è ‹ Œ †
¨Óà»ç¹µéͧãËé¡ÒÃÃÑ¡ÉÒËÃ×ÍäÁè ËÃ×ͨѴà¢éÒà»ç¹¡ÅØÁ epileptic syndrome ª¹Ô´ã´ä´éËÃ×ÍäÁè ¤ÇÃÁÕ¤ÇÒÁ-
è
ÃÙ㹡ÒÃàÅ×Í¡ÂҡѹªÑ¡·ÕàËÁÒÐÊÁ¡ÑºÍÒ¡Òêѡ·Õ¼»ÇÂÁÕ ¤Ç÷ÃÒº¶Ö§¼Å¢ŒÒ§à¤Õ§¢Í§ÂÒµ‹Ò§æ·ÕÍÒ¨¨Ð
Œ è è ÙŒ † è
à¡Ô´¢Ö¹ áÅФÇÃ͸ԺÒÂâäàº×ͧµŒ¹ãˌᡋ¼»Ç à¾×ÍãËŒ¼»ÇÂËÃ×ͼٻ¡¤ÃͧàËç¹¶Ö§¤ÇÒÁÊíÒ¤Ñ㹡ÒÃ
é é ÙŒ † è ÙŒ † Œ
ÃÑ¡ÉÒ áÅШÐä´Œ»¯ÔºµµÇãËŒ¶¡µŒÍ§µ‹Íä»
Ñ Ô Ñ Ù
àÍ¡ÊÒÃ͌ҧÍÔ§
1. Obeid M, Mikati MA. Expanding spectrum of paroxysmal events in children: Potential mimickers of epilepsy.
Pediatr Neurol. 2007;37:309-16.
2. Baulac M. Epilepsy. In: Schapira AHV, Byrne E, editors. Neurology and clinical neuroscience. Philadelphia:
Mosby Elsevier; 2007. p.673-718
3. The Commission on Classification and Terminology of the International League Against Epilepsy. Proposal for
revised clinical and electroencephalographic classification of epileptic seizures. Epilepsia. 1981;22:489-501.
4. Holmes GL, Nordli DR. Generalized, focal and multifocal seizure. In: Swaiman K., Ashwal S, .erriero DM,
editors. Pediatric neurology: principles and practice. Philadelphia: Mosby Elsevier; 2006. p. 1019-54.
5. The Commission on Classification and Terminology of the International League Against Epilepsy. Proposal for
revised classification of epilepsies and epileptic syndromes. Epilepsia. 1989;30:389-99.
6. Roger J, Bureau M, Dravet C, Genton P, Tassinari CA, Wolf P. Epileptic syndromes in infancy, childhood and
adolescence. 3rd ed. London: John Libbey; 2002.
7. Arzimanoglou A, Guerrini R, Aicardi J. Aicardi’s epilepsy in children. 3rd ed. Philadelphia: Lippincott William &
Wilkins; 2004.
38.
àǪÈÒʵ÷¹Âؤ 2553
Ñ 11
8. Hirtz D, Ashwal S, Berg A, et al. Practice parameter: evaluating a first nonfebrile seizure in children: report of
the quality standards subcommittee of the American Academy of Neurology, The Child Neurology Society,
and The American Epilepsy Society. Neurology. 2000;55:616-23.
9. Browne TR, Holmes GL. Epilepsy. N Engl J Med. 2001;344:1145-51.
10. Hirtz D, Berg A, Bettis D, et al. Practice parameter: treatment of the child with a first unprovoked seizure:
Report of the Quality Standards Subcommittee of the American Academy of Neurology and the Practice
Committee of the Child Neurology Society. Neurology. 2003;60:166-75.
11. Shinnar S, Berg AT, Moshe SL, et al. The risk of seizure recurrence after a first unprovoked afebrile seizure in
childhood: an extended follow-up. Pediatrics. 1996;98:216-25.
12. Brodie M, Dichter M. Antiepileptic drugs. N Engl J Med. 1996;334(3):168-75.
13. Dichter M, Brodie M. New antiepileptic drugs. N Engl J Med. 1996;334(24):1583-90.
14. Practice parameter: a guideline for discontinuing antiepileptic drugs in seizure-free patients – summary statement.
Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 1996;47(2):
600-2.
àǪÈÒʵ÷¹Âؤ 2553
Ñ 19
4. American Academy of Pediatrics, American College of Obstetricians and Gynecologists. Guidelines for perinatal
care. 6th ed. Elk Grove Village, IL:AAP; Washington DC: ACOG; 2007: 235-7.
5. American Academy of Pediatrics Section on Breastfeeding. Breastfeeding and the use of human milk. Pediatrics.
2005;115:496–506.
6. Lester BM. Definition and diagnosis of colic. In: Sauls HS, Redfern DE, eds. Colic and excessive cry. Report
of the 105th Ross Conference on Pediatric Research. Columbus: Abbot Laboratories, 1997.
7. World Health Organization. Evidence for the ten steps to successful breastfeeding. Geneva: World Health
Organization, Division of Child Health and Development, 1998. http://www.who.int/nutrition/publications/
evidence_ten_step_eng.pdf
àǪÈÒʵ÷¹Âؤ 2553
Ñ º··Õè 35
4
Cultivated Epithelial Cell in Ophthalmology, When and How?
ÃͧÈÒʵÃÒ¨ÒàᾷÂËÔ§ÀÔ¹ÔµÒ µÑ¹¸ØÇ¹ÔµÂ
¼ÙŒª‹ÇÂÈÒʵÃÒ¨ÒàᾷÂËÔ§³Ñ°¾Ã à·ÈÐÇÔºØÅ
ÀÒ¤ÇÔªÒ¨Ñ¡ÉØÇ·ÂÒ ¤³Ðá¾·ÂÈÒʵÃÈÃÃÒª¾ÂÒºÒÅ ÁËÒÇÔ·ÂÒÅÑÂÁËÔ´Å
Ô ÔÔ
ÃͧÈÒʵÃÒ¨Òà´Í¡àµÍû˜·ÁÒ à͡⾸Ôì
ÀÒ¤ÇÔªÒÇÔ·ÂÒÀÙÁ¤Á¡Ñ¹ ¤³Ðá¾·ÂÈÒʵÃÈÃÃÒª¾ÂÒºÒÅ ÁËÒÇÔ·ÂÒÅÑÂÁËÔ´Å
Ô ØŒ ÔÔ
¼ÙŒª‹ÇÂÈÒʵÃÒ¨Òà¹ÒÂá¾·ÂÁ§¤Å ÍØÂ»ÃÐàÊÃÔ°¡ØÅ
ÀÒ¤ÇÔªÒ¾ÂÒ¸ÔÇ·ÂÒ ¤³Ðá¾·ÂÈÒʵÃÈÃÃÒª¾ÂÒºÒÅ ÁËÒÇÔ·ÂÒÅÑÂÁËÔ´Å
Ô ÔÔ
WHEN? àÁ×èÍäè֧¨íÒ໚¹µŒÍ§·íÒ¡ÒÃÃÑ¡ÉÒ´ŒÇ cultivated epithelial cell
Background
Corneal limbal epithelial stem cell ËÃ×Í à«Åŵ¹¡íÒà¹Ô´¢Í§¼ÔÇ¡ÃШ¡µÒ໚¹à«ÅÅ··Ò˹ŒÒ·Õè
Œ Õè í
ÊÌҧà«ÅżǡÃШ¡µÒ (corneal epithelial cell) à«ÅʾºÍÂÙ·ºÃÔàdzÃ͵‹Í¢Í§µÒ´íҡѺµÒ¢ÒÇ
Ô Õé ‹ Õè
(limbus; áÊ´§ã¹ÀÒ¾·Õè 1) áÅÐ໚¹»˜¨¨ÑÂ˹֧·ÕÊÒ¤Ñ㹡Ò䧤ÇÒÁãʢͧ¡ÃШ¡µÒ (cornea) â´Â
è èí
¨Ð¤Í¡ѹäÁ‹ãËŒà«ÅŢͧàÂ×ÍºØµÒ (conjunctiva) ÃØ¡à¢ŒÒÁÒ㹡ÃШ¡µÒ(1)
é è
ÀÒ¾·Õè 1 áÊ´§µíÒá˹‹§¢Í§ limbus «Öè§ÁÕ corneal epithelial stem cell ÍÂÙ‹
ÍÒ¡Ò÷ҧ¤ÅÔ¹¡
Ô
ËÒ¡ corneal limbal stem cell àÊ×ÍÁÊÀҾ仨зíÒãËŒà¡Ô´ÀÒÇÐ corneal limbal stem cell
è
deficiency(1,2) «Ö§ÁռŷíÒãËŒÁàÊŒ¹àÅ×Í´áÅÐà«ÅŢͧàÂ×ͺصÒÃØ¡à¢ŒÒÁÒã¹¼ÔǢͧ¡ÃШ¡µÒ à¡Ô´á¼ÅËÅØ´
è Õ è
Å͡໚¹æ ËÒÂæ ¡ÃШ¡µÒ¢Ø¹ áÅеÒÁÑÇŧ «Ö§¾ºä´Œã¹ÀÒÇÐÀÙÁᾌ·µÒÍÂ‹Ò§ÃØ¹áç ¡ÅØÁÍÒ¡ÒÃ
‹ è Ô Õè ‹
Stevens Johnson ÍѹµÃÒ¨ҡÊÒÃà¤ÁÕ àª‹¹ ¡Ã´ ËÃ×Í´‹Ò§à¢ŒÒµÒ ¡ÒõԴàª×Í·Õ¡ÃШ¡µÒ µÒ·Õ䴌ú
é è è Ñ
63.
36 Cultivated Epithelial Cell in Ophthalmology, When and How?
¡Òü‹ÒµÑ´ËÅÒÂæ ¤Ãѧ(3) ¼Ù»Ç¨ÐÁÕÍÒ¡ÒõÒÁÑÇŧ ᾌáʧ äÁ‹ÊºÒÂµÒ «Ö§ËÒ¡à¡Ô´ÀÒÇдѧ¡Å‹ÒǹÕé
é Œ † è
¡ÒÃÃÑ¡ÉÒâ´Â¡Òü‹ÒµÑ´à»ÅÕ¹¡ÃШ¡µÒµÒÁ»¡µÔà¾Õ§Í‹ҧà´ÕÂÇ (corneal transplantation ËÃ×Í
è
penetrating keratoplasty) ¨ÐäÁ‹ÁâÍ¡ÒÊ»ÃÐʺ¼ÅÊíÒàÃç¨ÃÐÂÐÂÒÇä´ŒàÅ ´Ñ§¹Ñ¹¨Ö§¨íÒ໚¹µŒÍ§·íÒ¡ÒÃ
Õ é
ÃÑ¡ÉÒºÒ§»ÃСÒÃà¾×Í¿„¹¿ÙÊÀÒ¾¢Í§¡ÃШ¡µÒ¡‹Í¹
è œ (4)
¡ÒÃÃÑ¡ÉÒᵋà´ÔÁ
㹼ٻǷÕ໚¹ corneal limbal stem cell deficiency â´ÂÃͺ¡ÃШ¡µÒ ᵋà´ÔÁ¨Ð·íÒ¡ÒÃ
Œ † è
ÃÑ¡ÉÒâ´ÂÇÔ¸Õ»ÅÙ¡¶‹ÒÂà«ÅŵŒ¹¡íÒà¹Ô´ (stem cell) â´ÂµÃ§ (in vivo corneal limbal stem cell
transplantation)(2, 4) «Ö§ÍҨ㪌à«ÅŢͧ¼Ù»ÇÂàͧËÃ×ͨҡ¼ÙºÃÔ¨Ò¤ ´Ñ§¹Õé
è Œ † Œ
1. Autograft ã¹ÃÒ·Õ໚¹ corneal limbal stem cell deficiency ¢Í§µÒ¢ŒÒ§à´ÕÂÇ ÂѧÁÕà«ÅÅ·Õè
è
»¡µÔã¹µÒÍÕ¡¢ŒÒ§Ë¹Ö§ ¨ÐÊÒÁÒö㪌à«Åŵ¹¡íÒà¹Ô´¨Ò¡µÒ¢ŒÒ§·Õ»¡µÔ¢Í§¼Ù»ÇÂàͧ â´ÂàÍÒà¹×ÍàÂ×Í
è Œ è Œ † é è
ºÃÔàdzÃ͵‹Í¢Í§µÒ´íÒáÅеҢÒÇ (limbus) ÁÒ»ÅÙ¡¶‹ÒÂâ´ÂµÃ§
2. Allograft ã¹ÃÒ·յҷѧÊͧ¢ŒÒ§à»š¹ corneal limbal stem cell deficiency ÍҨ㪌à«ÅÅ
è é
¨Ò¡ÒµÔ àÃÕÂ¡Ç‹Ò living related corneal limbal allograft ËÃ×ͨҡµÒ¼ÙºÃÔ¨Ò¤ (allograft) â´Â¹íÒʋǹ
Œ
·Õ໚¹Ã͵‹Í¢Í§µÒ´íҡѺµÒ¢ÒÇÁÒ»ÅÙ¡¶‹ÒÂâ´ÂµÃ§
è
WHY? ·íÒäÁµŒÍ§ãªŒ cultivated epithelial cell 㹡ÒÃÃÑ¡ÉÒ·Ò§µÒ
¡Ò÷íÒ in vivo corneal limbal stem cell transplantation »˜ËÒ·Õ¾º¤×Í ËÒ¡¹íÒà«Åż͹
è ÙŒ ×è
ÁÒ»ÅÙ¡¶‹Ò (allograft) ¨ÐÁÕâÍ¡ÒÊà¡Ô´»¯Ô¡ÃÂÒµ‹ÍµŒÒ¹ (rejection) ÊÙ§ áÅеŒÍ§ÃѺ»ÃзҹÂÒ¡´
ÔÔ
ÀÙÁµÒ¹·Ò¹ (immunosuppressive drug) Í‹ҧµ‹Íà¹×ͧà¾×Í»‡Í§¡Ñ¹äÁ‹ãËŒà¡Ô´»¯Ô¡ÃÂҴѧ¡Å‹ÒÇ ã¹¡Ã³Õ
Ô Œ è è ÔÔ
¼Ù»ÇÂ໚¹âä·ÕµÒ¢ŒÒ§à´ÕÂÇ «Ö§¨Ð㪌à«ÅŨҡµÒ¢ŒÒ§·Õ»¡µÔ¢Í§¼Ù»ÇÂÁÒ»ÅÙ¡¶‹Ò ËÃ×ͼٻÇ·Õ໚¹âä
Œ † è è è Œ † Œ † è
·ÕµÒ·Ñ§Êͧ¢ŒÒ§áÅеŒÍ§¡ÒÃ㪌à«ÅŨҡµÒ¢Í§ÒµÔ ᾷ¨ÐäÁ‹ÊÒÁÒö¹íÒà«ÅŨҡµÒ¢ŒÒ§·Õ»¡µÔ
è é è
ÍÍ¡ÁÒ䴌㹻ÃÔÁÒ³ÁÒ¡æ ºÒ§¤Ãѧ»ÃÔÁÒ³¢Í§à«ÅŨ§äÁ‹à¾Õ§¾Í·Õ¨Ð»ÅÙ¡¶‹ÒÂà¾×Í»‡Í§¡Ñ¹¾Ñ§¼×´·Õ¨Ð
é Ö è è è
ÃØ¡à¢ŒÒ¡ÃШ¡µÒä´Œ ã¹ÃÐÂÐÂÒÇ
ä´ŒÁÕ¤ÇÒÁ¾ÂÒÂÒÁ㹡Ò䌹ËÒÇÔ¸ÕãËÁ‹ã¹¡ÒûÅÙ¡¶‹ÒÂà«ÅŵŒ¹¡íÒà¹Ô´¢Í§¼ÔÇ¡ÃШ¡µÒ
á·¹¡ÒÃ㪌à¹×éÍàÂ×èÍä»»ÅÙ¡¶‹ÒÂãˌᡋ¼ÙŒ»†ÇÂâ´ÂµÃ§ ᵋ¨Ð¹íÒà«ÅÅ·Õ赌ͧ¡ÒÃÁÒà¾ÒÐàÅÕé§ã¹ËŒÍ§
»¯Ôºµ¡Òá‹Í¹ ¨¹ä´Œ»ÃÔÁÒ³áÅÐÅѡɳеÒÁ·ÕµÍ§¡Òà ËÅѧ¨Ò¡¹Ñ¹¨Ö§¹íÒà«ÅÅ´§¡Å‹ÒÇÁÒ»ÅÙ¡¶‹ÒÂ
Ñ Ô è Œ é Ñ
ãˌᡋ¼»ÇÂÀÒÂËÅѧ 㹡ÒäѴàÅ×Í¡à«ÅÅ·¨Ð¹íÒÁÒà¾ÒÐàÅÕ§ ã¹»˜¨¨Øº¹ÁÕ 2 ª¹Ô´¤×Í
ÙŒ † Õè é Ñ
1. à«ÅŢͧ¡ÃШ¡µÒ (corneal epithelium)
2. à«ÅŢͧàÂ×ͺØã¹Ã‹Ò§¡Ò (mucosal epithelium)
è
64.
àǪÈÒʵ÷¹Âؤ 2553
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HOW? ¨Ð㪌 cultivated epithelial cell ÁÒÃÑ¡ÉÒ䴌͋ҧäÃ
Corneal epithelial cell culture
¡ÒÃà¾ÒÐàÅÕ§â´Â㪌 corneal limbal stem cell à¾×Íà¾ÔÁ¨íҹǹ¢Í§ stem cell ¡‹Í¹¹íÒä»
é è è
»ÅÙ¡¶‹ÒÂãËŒÁÕ»ÃÔÁÒ³ÁÒ¡¾Í¡Ñº¤ÇÒÁµŒÍ§¡ÒÃáÅÐÅ´âÍ¡ÒÊ¡ÒÃà¡Ô´»¯Ô¡ÔÃÔÂÒµ‹ÍµŒÒ¹à¹×éÍàÂ×èÍ â´Â
·íÒ¡ÒÃà¾ÒÐàÅÕ§à«ÅÅã¹ËŒÍ§»¯Ôºµ¡Òú¹àÂ×ÍááŌǨ֧¹íÒ¡ÅѺ任ÅÙ¡¶‹ÒÂãˌᡋ¼»Ç ÊÒÁÒö
é Ñ Ô è ÙŒ †
à¾ÒÐàÅÕ§à«ÅŨҡ¢¹Ò´ 2 ÁÁ. ໚¹ 2 «Á. ã¹àÇÅÒ 2 - 4 ÊÑ»´ÒË ·íÒãËŒ¡Ò÷íÒ¼‹ÒµÑ´ª¹Ô´ autograft
é
໚¹ä»Í‹ҧÁÕ»ÃÐÊÔ·¸ÔÀÒ¾ÁÒ¡¢Ö¹ â´ÂÊÒÁÒöà¾ÔÁ»ÃÔÁÒ³à«ÅÅãËŒà¾Õ§¾Í·Õ¨Ð¤ÅØÁ¼ÔÇ¡ÃШ¡µÒ
é è è
·Ñ§ËÁ´ä´Œ áÅÐã¹¡Ã³Õ allograft ¡ÒÃà¾ÒÐàÅÕ§à«Åš͹¹íÒä»»ÅÙ¡¶‹Ò¨зíÒãËŒâÍ¡ÒÊà¡Ô´»¯Ô¡ÃÂÒ
é é ‹ ÔÔ
µ‹ÍµŒÒ¹ (graft rejection) ¹ŒÍ¡NjҡÒü‹ÒµÑ´áººà´ÔÁ à¹×ͧ¨Ò¡à«ÅÅ·¹ÒÁÒ»ÅÙ¡¶‹ÒÂÁÕà¾Õ§à«ÅÅ
è Õè í
ªÑ¹¼ÔÇ෋ҹѹ
é é
¡ÒÃà¾ÒÐàÅÕé§áÅлÅÙ¡¶‹ÒÂà«ÅÅÁÕÃÒ§ҹ¤ÃÑé§áá㹻‚ ¤.È. 1997 ·Õè»ÃÐà·ÈÍÔµÒÅÕ
¨Ò¡ÃÒ§ҹµ‹Ò§»ÃÐà·È¾ºÇ‹Ò»ÃÐʺ¼ÅÊíÒàÃ稻ÃÐÁҳÌÍÂÅÐ 75(5) áÅÐãËŒ¼Å´Õ¡Ç‹Ò¡ÒûÅÙ¡¶‹ÒÂ
à«ÅÅâ´ÂµÃ§ ʋǹ㹻ÃÐà·Èä·Â ¤³Ðá¾·ÂÈÒʵÃÈÃÃÒª¾ÂÒºÒÅâ´Â¤ÇÒÁËÇÁÁ×ͧ͢ÀÒ¤ÇÔªÒ
ÔÔ
¨Ñ¡ÉØÇ·ÂÒ ÀÒ¤ÇÔªÒÇÔ·ÂÒÀÙÁ¤Á¡Ñ¹ ÀÒ¤ÇÔªÒ¾ÂÒ¸ÔÇ·ÂÒ áÅÐÈÙ¹Âà¹×ÍàÂ×ͪÕÇÀÒ¾¡ÃØ§à·¾Ï ä´Œ·Ò¡ÒÃ
Ô Ô ØŒ Ô é è í
à¾ÒÐàÅÕ§ corneal limbal stem cell ã¹ËŒÍ§»®Ôºµ¡ÒÃáÅлÅÙ¡¶‹ÒÂãˌᡋ¼»Ç·ѧ allograft áÅÐ
é Ñ Ô ÙŒ † é
autograft ÊíÒàÃç¨à»š¹¤Ãѧáá㹻ÃÐà·Èä·Âã¹»‚ ¾.È. 2550 â´Âä´Œ¼ÒµÑ´·íÒ cultivated corneal epithelial
é ‹
transplantation ·Ñ§ËÁ´ÃÇÁ 14 ÃÒÂ
é
¨Ò¡¡ÒõÃǨµÔ´µÒÁ¼ÙŒ»†Ç¾ºÇ‹ÒÁÕ¡ÒÃÍÑ¡àʺ¢Í§µÒŴŧ à«ÅÅ·Õè»ÅÙ¡¶‹ÒÂÊÒÁÒö
¤§ÊÀÒ¾ÍÂÙä´Œâ´ÂäÁ‹ËÅØ´ÅÍ¡ ¼Å¡ÒõÃǨÊͺ·Ò§¾ÂÒ¸ÔÇ·ÂÒ·Õè 1 à´×͹ËÅѧ¼‹ÒµÑ´ ¾ºÇ‹ÒäÁ‹Áà«ÅÅ
‹ Ô Õ
¢Í§àÂ×ͺصÒÃØ¡ÅéÒࢌÒÁÒ㹺ÃÔàdz¢Í§¡ÃШ¡µÒ ¡Ò÷íÒઋ¹¹Õ໚¹¡ÒÃàµÃÕÂÁ¤ÇÒÁ¾ÃŒÍÁãËŒ¡ÃШ¡µÒ
è í é
à¾×Íà¾ÔÁâÍ¡Òʷըм‹ÒµÑ´à»ÅÕ¹¡ÃШ¡µÒãËŒ»ÃÐʺ¤ÇÒÁÊíÒàÃç¨ã¹Í¹Ò¤µÊÙ§¢Ö¹
è è è è é
Mucosal epithelial cell culture
㹼ٻǷÕÁ¾ÂÒ¸ÔÊÀÒ¾¢Í§µÒ·Ñ§Êͧ¢ŒÒ§ ઋ¹¡ÅØÁÍÒ¡Òà Stevens Johnson ËÃ×͵ҷѧÊͧ
Œ † è Õ é ‹ é
¢ŒÒ§ä´ŒÃºÍѹµÃÒ¨ҡÊÒÃà¤ÁÕ ËÒ¡¨íÒ໚¹µŒÍ§·íÒ cultivated corneal epithelial transplantation á¾·Â
Ñ
¨ÐäÁ‹ÊÒÁÒö·íÒâ´Â㪌à«ÅŢͧ¼Ù»ÇÂàͧ䴌 µŒÍ§ãªŒà»š¹ allograft «Ö§¾º»˜ËÒÇ‹ÒÂѧ¨íÒ໚¹µŒÍ§ãªŒÂÒ
Œ † è
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à«ÅŢͧàÂ×ͺػҡ (oral mucosal epithelium) ¾ºÇ‹Ò໚¹à«ÅÅ·àËÁÒÐÊÁ à¹×ͧ¨Ò¡ÁÕšɳÐ
è Õè è Ñ
¢Í§ differentiation µèÒ áº‹§à«ÅÅàÃçÇ äÁ‹ÁÕ keratin áÅÐÁÕ¤ÇÒÁªØÁª×¹àÁ×͹íÒÁÒà¾ÒÐàÅÕ§º¹àÂ×Íá
í ‹ é è é è
ÅѡɳРrugae ¢Í§ mucosa ¨ÐËÒÂä» áÅÐÁÕšɳÐà«ÅŤŌÒ corneal epithelium ´Ñ§¹Ñ¹ Kinoshita
Ñ é
áÅФ³Ð ¨Ö§ä´Œ¹Òà«ÅŢͧàÂ×ͺػҡÁÒ㪌»ÅÙ¡¶‹Ò·յҼٻÇ àÃÕÂ¡Ç‹Ò cultivated oral mucosal
(6)
í è è Œ †
epithelial transplantation (COMET) «Ö§ÃÒÂ§Ò¹Ç‹Ò ÊÒÁÒö·íÒãˌŴ¡ÒÃÍÑ¡àÊºã¹µÒ Å´àÊŒ¹àÅ×Í´·Õè
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38 Cultivated Epithelial Cell in Ophthalmology, When and How?
äÁ‹ãª‹à«ÅŢͧ¡ÃШ¡µÒàÁ×èÍ»ÅÙ¡¶‹ÒÂà«ÅÅáÅŒÇ ÊÑ¡ÃÐÂÐ˹Ö觨ÐÁÕàÊŒ¹àÅ×Í´¡ÅѺࢌÒÁÒã¹µÒã¹Ê‹Ç¹
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¡ÒÃà¾ÒÐàÅÕé§ corneal limbal stem cell
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system «Ö§¤×Í¡ÒÃÇÒ§ªÔ¹à¹×Í·ÕÁà«ÅÅ·§ªÔ¹º¹àÂ×Íá (amniotic membrane)(7-10) ËÃ×Í substrate Í×¹
è é é è Õ Ñé é è è
ઋ¹ fibrin gel ¡Ñº suspension culture system(11-14) «Ö§¨Ð‹ÍÂà«ÅÅãˌ໚¹à«ÅÅà´ÕÂÇæ ¡‹Í¹ áŌǨ֧
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ÇÒ§à«Åź¹ substrate ËÃ×Í amniotic membrane «Ö§ã¹ºÒ§ÃÒ§ҹ¨Ð㪌 3T3 feeder layer ໚¹µÑÇ
è
¡ÃеعãËŒà«ÅÅâµä´ŒàÃçÇ ¡ÒùíÒ amniotic membrane ÁÒ㪌 à¹×ͧ¨Ò¡ amniotic membrane ÁÕ growth
Œ è
factor µ‹Ò§æ ·ÕªÇÂãËŒà«ÅÅà¨ÃÔàµÔºâµä´Œ´Õ
è ‹ (15)
·Õ褳Ðá¾·ÂÈÒʵÃÈÔÃÔÃÒª¾ÂÒºÒŠʋǹ¡ÒÃà¾ÒÐàÅÕé§à«ÅŹÑé¹à¾ÒÐàÅÕ駺¹ amniotic
membrane áÅÐÁÕ¢¹µÍ¹´Ñ§µ‹Í仹Õé
Ñé
¡ÒÃà¾ÒÐàÅÕé§ corneal limbal stem cell
໚¹¡ÒÃàÅÕ§à«ÅÅẺ explants â´Â¹íÒ limbal tissue ·ÕÂÍ´ŒÇ dispase ÁÒàÅÕ§º¹àÂ×Í
é è ‹ é è
á amniotic membrane (AM) ·Õ¢´ epithelium cell ÍÍ¡ËÁ´ àÅÕ§ã¹ÍÒËÒÃàÅÕ§à«ÅÅ (keratinocyte
è Ù é é
growth medium: KGM) à¾ÒÐàÅÕ§㹠CO2 incubator ÍØ³ËÀÙÁÔ 37 C ÀÒÂ㵌ÊÀÒÇзÕÁ¡Ò«¤Òú͹
é í è Õ
ä´Í͡䫴ÃÍÂÅÐ 5 ໚¹àÇÅÒ 2-3 ÊÑ»´ÒË
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Ô Œ é è è é é Œ Õ Ô
â´Â ¡ÒÃÂŒÍÁÊÕ hematoxylin & eosin (H&E) áÅÐÈÖ¡ÉҤسÊÁºÑµ¢Í§ epithelial differentiation marker
Ô
(cytokeration K (CK) 12 and CK3) áÅÐ stem cell marker (ABCG2) ´ŒÇÂÇÔ¸Õ reverse transcription-
polymerase chain reaction (RT-PCR) áÅÐ immunoperoxidase áÅŒÇÈÖ¡ÉÒÇ‹Òà«ÅÅ·àÅÕ§䴌Á¤³ÊÁºÑµÔ
Õè é Õ Ø
¢Í§â¤Ã§ÊÌҧáÅÐá͹µÔਹ¤ÅŒÒ¡Ѻ corneal limbal stem cell ËÃ×ÍäÁ‹ «Ö§Åѡɳдѧ¡Å‹ÒǤ×Í
è
1. à«ÅÅÁûËҧ¤‹Í¹¢ŒÒ§¡ÅÁ¶Ö§àËÅÕÂÁ «ÑÂâµ¾ÅÒÊÁµÔ´ÊÕá´§ ¹ÔÇà¤ÅÕÂʵԴÊÕ¹Òà§Ô¹â»Ã‹§
ÕÙ è éí
àÁ×ÍÂŒÍÁ´ŒÇÂÊÕ H&E (ÀÒ¾·Õè 2)
è
2. ÂŒÍÁµÔ´á͹µÔਹ p63, AE1/AE5 «Ö§áÊ´§Ç‹Òà«ÅÅÁ¤³ÊÁºÑµà»š¹ stem cell áÅÐÂŒÍÁ
è Õ Ø Ô
µÔ´ CK12 㹪ѹº¹¢Í§à«ÅÅ áÊ´§Ç‹Òà«ÅÅ·à¾ÒÐàÅÕ§໚¹à«ÅŢͧ corneal epithelium(16-18)
é Õè é
3. à«ÅÅ·à¾ÒÐàÅÕ§ÀÒÂ㵌ÊÀÒÇдѧ¡Å‹ÒÇàÁ×Í·´ÊͺÇÔ¸Õ RT-PCR ¾ºÇ‹ÒÁÕ¡ÒÃáÊ´§ÍÍ¡¢Í§
Õè é è
ABCG2 CK 3 áÅÐ CK12 «Ö§Â×¹ÂѹNjÒ໚¹à«ÅŢͧ¡ÃШ¡µÒ·Õ·Ò˹ŒÒ·Õ໚¹ stem cell
è è í è
66.
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ÀÒ¾·Õè 2 áÊ´§ÀÒ¾·Ò§¾ÂÒ¸ÔÇÔ·ÂÒ ¢Í§¡ÒÃà¾ÒÐàÅÕé§ Corneal Limbal stem cell : (A) ÂŒÍÁÊÕ
H&E, (B) ÂŒ Í Á immunohistochemistry áÊ´§¶Ö § á͹µÔ à ¨¹·Õè á Ê´§ÍÍ¡ áÅÐ
äÁ‹áÊ´§ÍÍ¡º¹¼ÔÇà«ÅÅ ÂŒÍÁ p63 áÊ´§¶Ö§¡ÒÃ໚¹ stem cell, (C) ÂŒÍÁ CK12
µÔ ´ à«ÅÅ ªÑé ¹ º¹ áÊ´§¶Ö § à«ÅÅ ·Õè á º‹ § µÑ Ç à¨ÃÔ àµÔ º âµä´Œ à »š ¹ à«ÅÅ ¢ ͧ corneal
epithelium
¡ÒÃà¾ÒÐàÅÕé§ oral mucosal epithelium
´íÒà¹Ô¹¡ÒÃà¾ÒÐàÅÕ§ human oral mucosal epithelial cell ã¹ÍÒËÒÃàÅÕ§à«ÅÅã¹ÊÀÒÇзÕäÁ‹
é é è
ÁÕ serum áÅÐ feeder cell ໚¹àÇÅÒ 2-3 ÊÑ»´ÒË áÅŒÇÈÖ¡ÉҤسÊÁºÑµ¢Í§ epithelial differentiation
Ô
marker (cytokeration K (CK) 12 and CK3) áÅÐ stem cell marker (ABCG2) ´ŒÇÂÇÔ¸Õ reverse
transcription-polymerase chain reaction (RT-PCR) à«ÅÅ·à¾ÒÐàÅÕ§ÀÒÂ㵌ÊÀÒÇдѧ¡Å‹ÒÇÁÕ¡ÒÃ
Õè é
áÊ´§ÍÍ¡¢Í§ CK3 áÅÐ ABCG2 ᵋäÁ‹áÊ´§ÍÍ¡¢Í§ CK12 «Ö§áÊ´§Ç‹Ò໚¹à«ÅÅ·¤ÅŒÒ¡ÃШ¡µÒ
è Õè
ᵋäÁ‹ãª‹à«ÅŢͧ¡ÃШ¡µÒ
¡Ò÷íÒ¼‹ÒµÑ´á¡‹¼ÙŒ»†ÇÂ
¡Ò÷íÒ¼‹ÒµÑ´ CCET áÅÐ COMET ÁÕËÅÑ¡¡ÒÃà´ÕÂǡѹ¤×Í ÅÍ¡¾Ñ§¼×´·Õ¤ÅØÁ ocular surface
è
ÍÍ¡ ·Ñ§ã¹Ê‹Ç¹¢Í§ cornea áÅÐ conjunctiva ÇÒ§¹éÒÂÒ 0.02% mitomycin C à¾×Í»‡Í§¡Ñ¹¡ÒáÅѺ
é í è
໚¹«éҢͧ¾Ñ§¼×´ ¨Ò¡¹Ñ¹ÇÒ§àÂ×Íá·ÕÁà«ÅŢͧ corneal epithelium ËÃ×Í oral mucosal epithelium
í é è è Õ
ÍÂÙ‹ àÂ纵Դ¡Ñº sclera áÅÐ cornea ʋǹ·ÕÅÍ¡¾Ñ§¼×´ÍÍ¡áÅŒÇ(6-8, 10, 19,20) «Ö§¨Ð¾ºÇ‹ÒÊÒÁÒö·íÒãËŒÁÕ
è è
à«ÅŤŨÁá¼Åä´Œ·§ËÁ´ËÃ×Íà¡×ͺ·Ñ§ËÁ´µÑ§áµ‹ËÅѧ¼‹ÒµÑ´ ã¹ÃÒ·Õà¹×Í¡ÃШ¡µÒ¢Ø¹ ËÅѧ¨Ò¡á¼ÅµÔ´´Õ
Ñé é é è é ‹
¡ÒÃÍÑ¡àʺŴŧ ᵋ¡ÃШ¡µÒÂѧ¢Ø¹ÍÂÙ‹ ¨Ð·íÒ¡ÒÃà»ÅÕ¹¡ÃШ¡µÒµ‹Íä»
‹ è
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àÍ¡ÊÒÃ͌ҧÍÔ§
1. Li DQ, Tseng SC. Differential regulation of keratinocyte growth factor and hepatocyte growth factor/scatter
factor by different cytokines in human corneal and limbal fibroblasts. J Cell Physiol. 1997;172(3):361-72.
2. Dua HS, Azuara-Blanco A. Limbal stem cells of the corneal epithelium. Surv Ophthalmol. 2000;44(5):415-25.
3. Puangsricharern V, Tseng SC. Cytologic evidence of corneal diseases with limbal stem cell deficiency.
Ophthalmology. 1995;102(10):1476-85.
4. Prabhasawat P. Corneal limbal stem cells. Siriraj Med J. 2006;58:728-9.
5. Shortt AJ, Secker GA, Notara MD, Limb GA, Khaw PT, Tuft SJ, et al. Transplantation of ex vivo cultured limbal
epithelial stem cells: a review of techniques and clinical results. Surv Ophthalmol. 2007;52(5):483-502.
6. Nakamura T, Inatomi T, Sotozono C, Amemiya T, Kanamura N, Kinoshita S. Transplantation of cultivated
autologous oral mucosal epithelial cells in patients with severe ocular surface disorders. Br J Ophthalmol. 2004
;88(10):1280-4.
7. Koizumi N, Inatomi T, Suzuki T, Sotozono C, Kinoshita S. Cultivated corneal epithelial stem cell transplantation
in ocular surface disorders. Ophthalmology. 2001;108(9):1569-74.
8. Nakamura T, Inatomi T, Sotozono C, Koizumi N, Kinoshita S. Successful primary culture and autologous
transplantation of corneal limbal epithelial cells from minimal biopsy for unilateral severe ocular surface disease.
Acta Ophthalmol Scand. 2004;82(4):468-71.
9. Grueterich M, Espana EM, Touhami A, Ti SE, Tseng SC. Phenotypic study of a case with successful
transplantation of ex vivo expanded human limbal epithelium for unilateral total limbal stem cell deficiency.
Ophthalmology. 2002;109(8):1547-52.
10. Sangwan VS, Matalia HP, Vemuganti GK, .atima A, Ifthekar G, Singh S, et al. Clinical outcome of autologous
cultivated limbal epithelium transplantation. Indian J Ophthalmol. 2006;54(1):29-34.
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expanded stem cell allograft for ocular surface reconstruction. Ophthalmology. 2005;112(3):470-7.
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15. Prabhasawat P, Tseng SC. Impression cytology study of epithelial phenotype of ocular surface reconstructed
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42 Cultivated Epithelial Cell in Ophthalmology, When and How?
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70.
àǪÈÒʵ÷¹Âؤ 2553
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1. Hyams SW, Neumann E. Peripheral retina in myopia. With particular reference to retinal breaks. Br J Ophthalmol
1969;53(5):300-6.
2. Mirshahi A, Schopfer D, Gerhardt D, et al. Incidence of posterior vitreous detachment after laser in situ
keratomileusis. Graefes Arch Clin exp Ophthalmol 2006;244:149-53.
3. Hernandez-Verdejo JL, Teus MA, Roman JM, Boliver G. Porcine model to compare real-time intraocular
pressure during LASIK with a mechanical microkeratome and femtosecond laser. Invest Ophthalmol Vis Sci
2007;48:68-72.
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3. Murphree AL. Intraocular retinoblastoma: The case for a new group classification. Ophthalmol Clin North Am
2005;18:41–53.
4. Chantada G, Doz ., Antoneli CB, et al. A proposal for an international retinoblastoma staging system. Pediatr
Blood Cancer 2006;47:801-5.
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factors and treatment outcomes of retinoblastoma in pediatric patients: a single-institution study. Jpn J Ophthalmol
2009;53:35-9.
6. Murphree AL, Villablanca JG, Deegan W. 3rd, et al. Chemotherapy plus local treatment in the management
of intraocular retinoblastoma. Arch Ophthalmol 1996;114:1348-56.
7. RamaChandran S, Ariffin H. Secondary acute myeloid leukemia after etoposide therapy for haemophagocytic
lymphohistiocytosis. Pediatr Blood Cancer 2009;53:488-90.
8. Chan HS, DeBoer G, Thiessen JJ, et al. Combining cyclosporin with chemotherapy controls intraocular
retinoblastoma without requiring radiation. Clin Cancer Res 1996;2:1499-508.
9. Colombo D, .lori L, Altomare G, Aste N, Sgarbi S. Clinical outcome evaluation following cyclosporine a
treatment in moderate to severe psoriasis: a retrospective study. Int J Immunopathol Pharmacol 2010; 23:363-
7.
10. Kaneko A, Suzuki S. Eye-preservation treatment of retinoblastoma with vitreous seeding. Jpn J Clin Oncol
2003; 33:601-7.
11. Abramson DH, .rank CM, Dunkel IJ. A phase I/II study of subconjunctival carboplatin for intraocular
retinoblastoma. Ophthalmology 1999; 106:1947-50.
12. Yamane T, Kaneko A, Mohri M. The technique of ophthalmic arterial infusion therapy for patients with
intraocular retinoblastoma. Int J Clin Oncol 2004; 9:69-73.
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1. Manzi S., Shannon M. Drug interaction-a review. Clin Ped Emerg Med. 2005;6:93-102.
2. Piscitelli CS, Gallicano DK. Interaction among drugs for HIV and opportunistic infections. N Engl J Med.
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9. Jick H. Drugs-remarkably toxic. N Engl J of Med 1974;291(16):824-8.
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Massachusetts: IHI; 2004.
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110 PET/CT for Cancer in Head and Neck Region : Thyroid and Nonthyroid Carcinoma
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9. Weintraud M, Lundblad M, Kettner SC, Willschke H, Kapral S, L?nnqvist PA, et al. Ultrasound versus
landmark-based technique for ilioinguinal-iliohypogastric nerve blockade in children: the implications on plasma
levels of ropivacaine. Anesth Analg. 2009;108(5):1488-92.
10. Walker KJ, McGrattan K, Aas-Eng K, Smith A.. Ultrasound guidance for peripheral nerve blockade. Cochrane
Database Syst Rev. 2009;(4):CD006459.
11. Karthikesalingam A, Walsh SR, Markar SR, Sadat U, Tang TY, Malata CM. Continuous wound infusion of
local anaesthetic agents following colorectal surgery: systematic review and meta-analysis.World J Gastroenterol.
2008;14:5531-5.
12. Krotz ., Schiele TM, Klauss V, Sohn HY. Selective COX-2 inhibitors and risk of myocardial infarction. J Vasc
Res. 2005;42:312–24.
13. Lynn AM, Bradford H, Kantor ED, Seng K, Salinger DH, Chen J, et al. Postoperative ketorolac tromethamine
use in infants aged 6–18 months: the effect on morphine usage, safety assessment, and stereo-specific
pharmacokinetics. Anesth Analg. 2007;104:1040–51.
14. Papacci p, de .rancisci G, Iacobucci T, Giannantonio C, de Carolis MP, Zecca E. Use of intravenous ketorolac
in the neonate and premature babies. Pediatr Anesth. 2004;14:487–92.
15. Tucker A, Kim Y, Nadeson R et al. Investigation of potentiation of analgesic effects of fentanyl by ketamine
in humans: a double blinded, randomized, placebo controlled, crossover study of experimental pain. BMC
Anesthesiol. 2005;5:2–14.
16. Granry JC, Dube L, Turroques H et al. Ketamine: new uses for an old drug. Curr Opin Anaesthesiol.
2000;13:299–302.
17. Grande LA, O’Donnell BR, .itzgibbon DR et al. Ultra-low dose ketamine and memantine treatment for pain in
an opiodtolerant oncology patient. Anesth Analg. 2008;107:1380–83.
18. Hocking G, Cousins MJ. Ketamine in chronic pain management: an evidence-based review. Anesth Analg.
2003;97:1730–39.
19. Gurnani A, Sharma PK, Rautela RS et al. Analgesia for acute musculoskeletal trauma: low-dose subcutaneous
infusion of ketamine. Anaesth Intens Care. 1996;24:32–6.
156.
àǪÈÒʵ÷¹Âؤ 2553
Ñ 129
20. Dal D, Celebi N, Gaye E et al. The efficacy of intravenous or peritonsillar infiltration of ketamine for postoperative
pain relief in children following adenotonsillectomy. Pediatr Anesth. 2007;17:263–9.
21. Aspinall RL, Mayor A. A prospective randomized controlled study of the efficacy of ketamine for postoperative
pain relief in children after adenotonsillectomy. Paediatr Anaesth. 2001;11: 333–6.
22. Palmer GM, Chen SP, Smith KR, Hardikar W. Introduction and audit of intravenous paracetamol at a tertiary
paediatric teaching hospital. Anaesth Intensive Care. 2007;35:702–6
23. Murat I, Baujard C, .oussat C, et al. Tolerance and analgesic efficacy of a new i.v. paracetamol solution in
children after inguinal hernia repair. Paediatr Anaesth. 2005;15:663–70.
24. Capici ., Ingelmo PM, Davidson A, et al. Randomized controlled trial of duration of analgesia following
intravenous or rectal acetaminophen after adenotonsillectomy in children. Br J Anaesth. 2008;100:251–5.
25. Palmer GM , Atkins M, Anderson BJ, Smith KR, Culnane TJ,McNally CM, et al.I.V. acetaminophen
pharmacokinetics in neonates after multiple doses. Br J Anaesth.2008;101(4):523–30.
26. Grond S, Sablotzki A. Clinical pharmacology of tramadol. Clin Pharmacokinet. 2004;43:879–923.
27. Allegaert K, Anderson BJ, Verbesselt R, Debeer A, de Hoon J, Devlieger H,et al. Tramadol disposition in the
very young: an attempt to assess in vivo cytochrome P-450 2D6 activity. Br J Anaesth.2005;95(2):231–9.
28. Kitson R, Carr B. Tramadol and severe serotonin syndrome. Anaesthesia. 2005;60(9):934-5
158.
àǪÈÒʵ÷¹Âؤ 2553
Ñ º··Õè 131
19
Outcome Improvement in Neuroanesthesia
: Neuro-interventional Perspective
Assistant Professor Anchalee Churojana
Department of Radiology, .aculty of Medicine Siriraj Hospital, Mahidol University
Interventional Neuroradiology is a treatment modality of vascular diseases of central
nervous system (CNS) and head & neck region with certain overlapped aspects with neurosurgery,
head & neck surgery and vascular surgery, by means of endovascular access to deliver
therapeutic agents such as embolic materials, sclerosing and chemotherapeutic drugs including
mechanical devices. The purpose of the procedure is either definite treatment or preoperative
devascularization.
It can be broadly grouped as
1. Embolization procedure: with the purpose to occlude vessels in the diseases with
abnormal vascular channels or high vascularization. Those diseases are arteriovenous
malformations (AVMs), arteriovenous fistulas, carotid-cavernous fistulas, intracranial aneurysms,
traumatic aneurysms and preoperative devascularization of tumors.
Diseases Embolic agent Comment
AVMs N-butyl cyanoacrylate (NBCA
or Glue)
Carotid-cavernous fistulas Detachable balloon
(CC.s)
Aneurysms Detachable coils May need nondetachable
balloon or stent-assisted
coiling
Arteriovenous fistulas NBCA or coils depending on size of fistulas
Dural arteriovenous shunts NBCA and/or fibered coils Usually NBCA using fpr
or detachable coils transarterial feeder occlusion
and coils using for dural sinus
or venous packing
Preoperative tumor Particles (polyvinyl alcohols
embolizations or PVA)
159.
132 Outcome Improvement in Neuroanesthesia : Neuro-interventional Perspective
1. Dilatation procedure: with purpose to open up the narrowed arteries, or perform
angioplasty with or without stenting in the occluded vascular disease including mechanical
thrombectomy or clot retrieval in acute embolic stroke.
2. Transarterial infusion: with the purpose for intraarterial thrombolysis in acute stroke
or chemotherapy in certain cancers such as transophthalmic artery chemo-infusion for
retinoblastoma, palliative transarterial chemo-infusion for nasopharyngeal cancer.
3. Percutaneous or direct puncture: mostly used in AVMs or venous malformations
with extracranial locations for delivering liquid embolic or sclerosing agents directly. In our
practice, NBCA is used in AVMs and Bleomycin is used as sclerosing drug.
Currently, Interventional Neuroradiology is increasingly performed with the administration
of anesthesia. In this point of view, several important concerns from anesthesiologists should
be included1
! Maintenance of the patient’s immobility to reduce motion artifact, general anesthesia
is preferred to facilitate visualization of small vessels and prevent patient movement.
! Proper monitoring: blood pressure, PaCO2 in case of the possibility of unexpected
neurological complications and anaphylactic reactions, particularly from contrast
media.
! Anticoagulant therapy and monitoring.
! Rapid recovery from anesthesia and sedation during the procedure to facilitate
neurological testing, such as in internal carotid artery sacrification.
! Management of sudden unexpected complication such as hemorrhage or vascular
occlusion.
! Guiding the medical care and treatment of critical ill patients during the procedure
and transportation.
! Smooth recovery from anesthesia after procedure to prevent risk of complications
such as balloon displacement during strong coughing, vascular injury at puncture
site during non-purposeful movement.
General care
! Intravenous access should be on the left arm with adequate extension tube from the
image intensifier or when the patient is draped.
! Increased systemic blood pressure in patient whose femoral pulse can’t be palpated
due to hypotension.
160.
àǪÈÒʵ÷¹Âؤ 2553
Ñ 133
! Intraprocedural heparinization and control activated clotting time including
postoperative protamine reversal.
! Awareness of allergic reaction particularly with contrast media.
Special care
! Pediatric patients: keep warm to the patients, contrast medium and drug dose-
limitation, intraarterial & intravenous fluid overload. Post embolization for vein of
Galen malformation and high flow AVM usually need to maintain head in semi-upright
position to minimize venous congestion.
! Controlled systemic hypotension may be required during embolization of high flow
fistulas or intracranial AVMs to reduce the flow across the lesions to achieve good
deposition of embolic agents.2
! The patient must be awake for the balloon occlusion test procedure, as continuous
neurological examination to assess the effects of occlusion. However, rapid wake-up
of the patient is requested in the case of unplanned or accidental arterial occlusion.
! Concerning of sudden hypotension or vago-vagal reflex during carotid balloon
angioplasty
! Adequate heparinization in the case of transarterial device delivery such as coiling
aneurysm or balloon application.
! Preoperative antiplatelet administration for all stenting procedure.
Neurovascular complication management
! Catheter-induced vasospasm: may need transarterial Nimodipine infusion which results
to systemic hypotension.
! Arterial occlusion: may be caused by fly-away of embolic agents to normal arteries,
malposition of device such as coils or stent, and thromboembolism. In this event,
the arterial pressure should be raised to increase collateral blood flow and maintain
normocarbia. Mechanical thrombectomy or infusion of thrombolytic agent may be
needed. Antiplatelet agents, such as Abciximab, have also shown promising results.
However, occlusion from NBCA or glue is always permanent. If arterial luminal
narrowing or occlusion occurred from catheter-induced dissection, systemic
heparinization is recommended and the procedure must be terminated.
161.
134 Outcome Improvement in Neuroanesthesia : Neuro-interventional Perspective
! Venous outlet occlusion: usually results from spillage of glue during embolization of
AVMs or fistula into draining veins. If stasis of contrast media in the venous outlet
is observed in post-embolization angiogram, embolization of feeding arteries as much
as possible is recommended to minimize the venous congestion. During post
procedural period, the patient needs to have maintenance of modest hypotension
and sedation.
! Hemorrhage: results from arterial rupture by catheter or guide-wire perforation or abrupt
rise in mean arterial pressure during test injection in the small artery or fragile
aneurysm. Visualization of extravasation of contrast media is the only clue for the
diagnosis, however, some patients may have sudden onset of bradycardia. Immediate
reversal of heparin is required (1 mg protamine for each 100 units of heparin given).
Lowering of the systemic arterial pressure may be needed. PaCO2 should be
maintained between 4.5 and 5.0 kPa.2 Endovascular treatment should be performed
without hesitation depending on each cause. Aneurysm rupture should be rapidly
packed by coils as much as possible. Arterial perforation can be glued vigorously at
the tip of microcatheter. Intraoperative CT scan is recommended for assessment
and preparing for postoperative management. Emergency craniotomy may be required
if endovascular embolization fails.
In conclusion, interventional neuroradiological procedures have been expanding in the
treatment of CNS, including head and neck, diseases. The type of anesthetic administration,
general anesthesia or intravenous sedation, is determined by the goal of each procedure together
with the experience of the radiology-anesthesia team.3 The anesthesiologists have a crucial role
in facilitating procedures, monitoring of the patients and involvement of complication management.
Thus, understanding of specific interventional neuroradiological procedures and their potential
complications are important. Good relationship with communication and planning between
radiologists and anesthesiologists in the team of interventional neuroradiology are key factors
of smooth procedure with good patient’s outcome.
References
1. Hashimoto T, Gupta DK, Young WL. Interventional neuroradiology-anesthetic considerations. Anesthesiology
Clinics of North America. 2002;20(2):347-59.
2. Varma MK, Price K, Jayakrishnan Y, et al. Anaesthetic considerations for interventional neuroradiology. BJA
2007;99(1):75-85.
3. Derbent A, Oran I, Parildar M, et al. Adverse effects of anesthesia in interventional radiology. Diagn Interv
Radiol 2005;11:109-112.
àǪÈÒʵ÷¹Âؤ 2553
Ñ 141
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12. Brent J. .omepizole for ethylene glycol and methanol poisoning. N Engl J Med 2009;360(21):2216-23.
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Clin North Am 2007;25(2):309-31; abstract viii.
14. Lheureux P, Penaloza A, Gris M. Pyridoxine in clinical toxicology: a review. Eur J Emerg Med 2005;12(2):
78-85.
144 ¡ÒÃÍÍ¡¡íÒÅѧËÅѧ¡Ò÷íÒËѵ¶¡ÒÃËÃ×ͼ‹ÒµÑ´ËÑÇã¨
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è Õ è è
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è
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THR= %(HRmax- HRrest) + HRrest
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¢ÂѺ¢ŒÍµ‹Í (range of motion exercise) ËÃ×ÍÂ×´àÊŒ¹Â×´ÊÒ (stretching) ¡‹Í¹¡ÒÃÂ×¹à´Ô¹
(µÒÃÒ§·Õè 5) (5) â´Â·ÑÇ仨нƒ¡ãËŒ¼»ÇÂà´Ô¹ÍÍ¡¡íÒÅѧ䴌 10-15 ¹Ò·Õ áŌǨÐËÑ´ãËŒ¢¹Å§
è ÙŒ † Öé
ºÑ¹ä´ ËÃ×Í ·íÒ¡Ô¨¡ÃÃÁä´Œã¹ÃдѺ»ÃÐÁÒ³ 3-4 METs ¡‹Í¹ãËŒ¨íÒ˹‹ÒÂÍÍ¡¨Ò¡
âç¾ÂÒºÒÅËÃ×Í¡ÅѺºŒÒ¹ à¾ÃÒСԨÇѵûÃШíÒÇѹʋǹãË‹¨ÐÁÕÃдѺ¾Åѧ§Ò¹»ÃÐÁÒ³
3 - 4 METs
175.
148 ¡ÒÃÍÍ¡¡íÒÅѧËÅѧ¡Ò÷íÒËѵ¶¡ÒÃËÃ×ͼ‹ÒµÑ´ËÑÇã¨
µÒÃÒ§·Õè 2 áÊ´§à¡³±¡ÒèѴÃдѺ¤ÇÒÁàÊÕ§¢Í§ American Association of Cardiovascular
è
and Pulmonary Rehabilitation (AACVPR)(4)
Low Risk Moderate Risk High Risk
! No significant left ! Moderately impaired left ! Decreased left ventricular
ventricular dysfunction ventricular function function (E. of < 40%)
(E. of > 50%) (E. = 40% - 49%) ! Survivor of cardiac arrest or
! No resting or exercise- ! Signs/symptoms including sudden death
induced complex angina at moderate levels ! Complex ventricular
arrhythmias of exercise (5 – 6.9 METs) arrhythmias at rest or with
! Uncomplicated Ml; CABGs; or in recovery exercise
angioplasty, atherectomy, ! MI or cardiac surgery
or stent; complicated by cardiogenic
! Absence of CH., or shock. CH., and/or
signs/symptoms of signs/symptoms of
postevent ischemia postevent/procedure
! Normal hemodynamics ischemia
with exercise or recovery ! Abnormal hemodynamics
! Asymptomatic including with exercise (especially flat
absence of angina with or decreasing SBP or
exertion or recovery chronotropic incompetence
! .unctional capacity of > 7 with increasing workload)
METs ! Signs/symptoms including
! Absence of clinical angina pectoris at low levels
depression of exercise (< 5.0 METs) or
in recovery
! .unctional capacity of < 5.0
METs
! Clinically significant
depression
Low-risk classification is Moderate risk is assumed for Highest-risk classification is
assumed when each of the patients who do not meet the assumed with the presence of
descriptors in the category is classification of either high or any one of the descriptors
present low risk included in this category
ËÁÒÂà赯 MI = myocardial infarction; CABGs = coronary artery bypass surgery;
CH. = congestive heart failure; SBP = systolic blood pressure
176.
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µÒÃÒ§·Õè 3 ¢ŒÍËŒÒÁ㹡ÒÃÍÍ¡¡íÒÅѧ(4)
! Unstable angina
! SBP ¢³Ð¾Ñ¡ > 180 mm Hg ËÃ×Í DBP ¢³Ð¾Ñ¡ > 110 mm Hg ·Ñ§¹ÕµÍ§¾Ô¨ÒóÒ
é é Œ
໚¹ÃÒÂæ´ŒÇÂ
! Orthostatic blood pressure drop > 20 mm Hg ·ÕÁÍÒ¡ÒÃ
è Õ
! Critical aortic stenosis
! Acute systemic illness or fever
! Uncontrolled atrial or ventricular arrhythmias
! Uncontrolled sinus tachycardia (> 120 beats per minute)
! Uncompensated congestive heart failure
! Third-degree A-V block (without pacemaker)
! Active pericarditis or myocarditis
! Recent embolism
! Thrombophlebitis
! Resting ST displacement (> 2mm); > 3 mm if patient is taking digitalis
! Uncontrolled diabetes (resting blood glucose > 400 mg/dL)
! Severe orthopedic problems that would prohibit exercise
! Other metabolic problems such as acute thyroiditis, hypo- or hyperkalemia,
hypovolemia, etc.
µÒÃÒ§·Õè 4 âäËÃ×ÍÀÒÇзÕè·íÒãËŒà¡Ô´¡ÒÃàºÕè§ູ¢Í§á¹Ç·Ò§ËÃ×Íâ»Ãá¡ÃÁ·ÕèÇÒ§äÇŒ(4)
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ÊÀҾËҧ¡ÒÂ͋͹áÍ ºÍººÒ§ (frailty) ÀÒÇÐàÅ×Í´ÍÍ¡ËÅѧ¼‹ÒµÑ´
âääµàÃ×ÍÃѧ
é ÀÒÇÐËÑÇã¨àµŒ¹¼Ô´»¡µÔ
âäËÅÍ´àÅ×Í´ÊÁͧ »Í´ÍÑ¡àʺµÔ´àª×Íé
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Ñ 151
µÒÃÒ§·Õè 6 ¡Òõͺʹͧµ‹Í¡ÒÃÍÍ¡¡íÒÅѧ·Õ躋§ªÕéãËŒËÂØ´ÍÍ¡¡íÒÅѧã¹ÃÐÂмٌ»†ÇÂã¹(4)
! HR > 130 bpm or > 30 bpm above pre-exercise level
! Diastolic BP > 110 mm Hg
! Decrease in systolic BP > 10 mm Hg
! Significant ventricular or atrial arrhythmias
! Second- or third-degree heart block
! Signs/symptoms of exercise intolerance including angina pectoris and marked dyspnea
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àÍ¡ÊÒÃ͌ҧÍÔ§
1. American College of Sports Medicine. ACSM’s guidelines for exercise testing and prescription. 7th ed. Lippincott
Williams & Wilkins; 2006.
2. Jolliffe JA, Rees K, Taylor RS, Thompson D, Oldridge N, Ebrahim S. Exercise-based rehabilitation for coronary
heart disease. Cochrane Database Syst Rev. 2001(1):CD001800.
180.
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3. Taylor RS, Brown A, Ebrahim S, Jolliffe J, Noorani H, Rees K, et al. Exercise-based rehabilitation for patients
with coronary heart disease: systematic review and meta-analysis of randomized controlled trials. Am J Med
2004;116(10):682-92.
4. American Association of Cardiovascular and Pulmonary Rehabilitation. Guidelines for cardiac rehabilitation and
secondary prevention programs. 3rd ed. Champaign,IL: Human Kinetics; 1999.
5. Pollock ML, Gomes PS. Exercise prescription. In: Wenger NK, Smith LK, .roelicher ES, Comoss PM, editors.
Cardiac rehabilitation: a guide to practice in the 21st century. New York: Marcel Dekker; 1999. p. 49-65.
6. Haskell WL, Lee IM, Pate RR, Powell KE, Blair SN, .ranklin BA, et al. Physical activity and public health:
updated recommendation for adults from the American College of Sports Medicine and the American Heart
Association. Circulation 2007;116(9):1081-93.
7. Nelson ME, Rejeski WJ, Blair SN, Duncan PW, Judge JO, King AC, et al. Physical activity and public health
in older adults: recommendation from the American College of Sports Medicine and the American Heart
Association. Circulation 2007;116(9):1094-105.
182.
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168 Whiplash Injury
»Ç´ÃعáçµÑ§áµ‹àÃÔÁµŒ¹ (higher initial pain intensity) ໚¹»˜¨¨Ñ·ժ´à¨¹·Õº§ºÍ¡¶Ö§¡Òÿ„¹µÑÇáÅÐ
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ËÒ¨ҡâ䪌ÒáÅзíÒãËŒ»Ç´àÃ×ÍÃѧ ʋǹÍÒÂØ à¾ÈËÔ§ angular deformity of cervical spine, rear-end
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recovery) ¤Ô´ã¹á§‹Åº (negative thinking) ÇÔµ¡¡Ñ§ÇÅ (anxiety) ÁÕá¹Ç⹌Á¨Ð¡ÅÒÂ໚¹»˜ËÒàÃ×ÍÃѧ é
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fistulotomy in the surgical management of high anal fistula. Br J Surg 1998;85:243-5.
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188 Hepatocellular Carcinoma : Management in the New Era
10. Yao .Y, .errell L, Bass NM, et al. Liver transplantation for hepatocellular carcinoma: expansion of the tumor
size limits does not adversely impact survival. Hepatology 2001;33:1394-403.
11. Lewis AL, Gonzalez MV, Leppard SW, et al. Doxorubicin eluting beads – 1: Effects of drug loading on bead
characteristics and drug distribution. J Master Sci 2007;18: 1691-9.
12. Lammar J, Malagari K, Vogl T, et al. Prospective randomized study of Doxorubicin-Eluting-Bead embolization
in the treatment of hepatocellular carcinoma: Result of the PRECISION V Study. Cardiovasc Intervent Radiol
2010;33:41-52.
13. Li YY, Sha WH, Zhou YJ, Nie YQ. Short and long term efficacy of high intensity focused ultrasound therapy
for advanced hepatocellular carcinoma. J Gastroentero Hepato 2007;22:2148-2154.
14. Wu ., Wang ZB, Chen WZ, et al. Advanced hepatocellular carcinoma: treatment with high-intensity focused
ultrasound ablation combined with transcatheter arterial embolization. Radiology 2005;235:659-67.
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30
Robotic Surgery for General Surgeons :
.utute or .antasy
Vitoon Chinswangwatanakul, MD., PhD.
Thawatchai Akaraviputh, MD.
Attaporn Trakarnsanga, MD.
Asada Metasate, MD., PhD.
Thanyadej Nimmanwudipong, MD.
Naraong Lertakyamanee, MD.
Department of Surgery, .aculty of Medicine Siriraj Hospital, Mahidol University
Robotic surgery is one of the innovations by the end of the last century. The word
‘robot’, described for the first time by Karel Capek in 1921, was named after the Czeck word
‘robota’ which means ‘forced labor’. The rapid advances of mechanical engineering in combination
with computer science has led to the fundamental establishment in robotic surgery.
History of robotic surgical machines
In 1993, the first robotic-assisted machine was launched named AESOP® Endoscope
Positioner which provided the stability of endoscope positioning.1
The next machine called HERMES® O.R. Control Center was a computer-driven system
which allowed surgeons to control extra devices by voice. The HERMES voice-activated device
control system could control 28 different devices from tables, cameras, to lighting systems and
electrosurgical units. It offers direct control and eliminates the various interfaces between surgeon
and other personnel in order to adjust the surgical equipments.
In 1998, ZEUS® Surgical System is made up of a surgeon console and three
table-mounted robotic arms, which provide visualization during performing endoscopic surgical
tasks. (.igure 1) The ZEUS system assists surgeons to increase dexterity of the surgical
procedures. Surgeon could control the right and left arms of ZEUS, with a real-time articulation
of the surgical instruments, meanwhile the third camera arm incorporated with the AESOP®
provides magnified, steady visualization of the operative field. In 1999, ZEUS made history in
225.
198 Robotic Surgery for General Surgeons : .uture or .antasy
the world's first robotic-assisted beating-heart bypass surgery, by Douglas Boyd. This milestone
indicated a new era of minimally invasive surgery.2
.igure 1. The ZEUS® Surgical System.3
In 2000, da Vinci Surgical System® was launched by Intuitive Surgical, after merging
with Computer Motion. It consists of an ergonomically designed surgeon’s console, a patient-
side cart with four interactive robotic arms, the high-performance 3-D InSite® Vision System and
EndoWrist® Instruments. (.igure 2) The surgeon’s hand movements are scaled, filtered and
effectively translated into precise movements of the EndoWrist® Instruments. The da Vinci
Surgical System® is now the only commercially available technology that can provide surgeons
with the spontaneous control, wider range of motion, fine tissue manipulation capability and 3-D
visualization, through tiny typical incisions of minimally invasive surgery.4
In 2001, the SOCRATESTM
.igure 2. The da Vinci Surgical System®.5
226.
àǪÈÒʵ÷¹Âؤ 2553
Ñ 199
Telecollaboration system synergized a number of systems including Zeus, AESOP,
and HERMES. It allows remotely located surgeons to receive a live endoscopic video image of
the operative field. The audio and video links the operating room with the remote station. The
SOCRATESTM system controls the operative site's AESOP endoscope camera view of the
operative site while communicating with HERMES OR control to provide securely remote control
of networked surgical devices. The safety features allow surgeon to halt all movements initiated
by the collaborating surgeon via voice-activated commands.6
Table 1. Computer Motion systems that all are now owned by Intuitive Surgical.6
Equipment Costs Company Equipment Descriptions
da Vinci Surgical $1 million Intuitive Robot-assistant, with arms to
System Surgical connect surgical instruments
Zeus Robot Surgical $975,000 Computer Robot-assistant, with arms
System Motion* to connect surgical instruments
Aesop 3000 $80,000 Computer Voice-controlled endoscope-
Motion* positioning robot
Hermes Control Center n/a Computer Centralized system used to
Motion* network an intelligent OR
Socrates Robotic n/a Computer Allows shared control of
Telecollaboration System Motion* Aesop 3000 from different locations
*.ormer Computer Motion systems that are now owned by Intuitive Surgical.
Sources: from Journal of Healthcare Management 46:4 July/August 2003.
What sort of operations we can do...
The U.S. .ood and Drug Administration (US .DA) has cleared the da Vinci® Surgical
System for use in urological surgical procedures, general laparoscopic surgical procedures,
gynecologic laparoscopic surgical procedures, transoral otolaryngology surgical procedures
restricted to benign and malignant tumors classified as T1 and T2, general thoracoscopic surgical
procedures, and thoracoscopically assisted cardiotomy procedures.7-8 The system can also be
employed with adjunctive mediastinotomy to perform coronary anastomosis during cardiac
revascularization. The da Vinci® System has been successfully used in the following procedures,
among others:
227.
200 Robotic Surgery for General Surgeons : .uture or .antasy
Table 2 The procedures have been successfully performed by da Vinci® System.7
Surgical Specialties Procedures
Urology Radical prostatectomy, pyeloplasty,
cystectomy, nephrectomy, ureteral reimplantation
Gynecology Hysterectomy, myomectomy and
sacrocolpopexy
Cardiothoracic Surgery Internal mammary artery mobilization and
cardiac tissue ablation
Mitral valve repair, endoscopic atrial septal
defect closure
Mammary to left anterior descending coronary
artery anastomosis for cardiac revascularization
with adjunctive mediastinotomy
Gastrointestinal Surgery Cholecystectomy, Nissen fundoplication, Heller
myotomy, gastric bypass, donor nephrectomy,
adrenalectomy, splenectomy and bowel resection
Otolaryngology Oropharyngeal, laryngeal and hypopharyngeal
resections; floor of mouth and oral cavity
resections
In September 2000, .DA Approved the da Vinci® robotic surgery for the following operative
procedures :-
! Cholecystectomy
! Antireflux procedures
! Heller’s cardiomyotomy
! Distal pancreatectomy
! Gastrojejunostomy
! Esophagectomy
! Gastric bypass
! Gastric banding
! Pyloroplasty
! Colectomy
! Adrenalectomy
! Splenectomy
228.
àǪÈÒʵ÷¹Âؤ 2553
Ñ 201
Robotic surgery in gastrointestinal surgery : Siriraj experience
We started to perform the first case of robotic-assisted laparoscopic esophagomyotomy
on November, 30th 2007. Since then, 11 different types of laparoscopic gastrointestinal surgery
were carried out with the successful rate over 84%. (Table 2) The principle of case selection
has been based on the most benefits surgeons could gain from robotic-assisted devices. The
need for tissue dissection in depth, differentiation of delicated tissue (such as sympathetic
nerve plexus) or use of intracorporeal suturing and anastomosis were the reason to choose
robotic-assisted laparoscopic approach. The most complex surgical procedure we performed
was pancreaticoduodenectomy. Even though the successful rate on such a complex surgery
was only 50%, all of the last 3 cases was uneventfully successful. The more procedures we
have performed, the more experience we have received. To overcome the learning curve, we
have to establish a good surgical team work, because the complex procedures certainly extend
the operative time which cause the stress and fatigue to a single surgeon. Thus, we switched
the surgical operator every 1-2 hours among 3 surgeons. This work as team approach led to
nonstop operation with the most effective result. We demonstrated the shorter operative time
by this technique.
Table 3 The variety of surgical procedures performed in the Division of General Surgery,
Department of Surgery, .aculty of medicine Siriraj Hospital.
Procedures Attempt .ailure
Esophagomyotomy 18 0
Pancreaticoduodenectomy 6 3
Low Anterior Resection 6 1
Nissen .undoplication 5 1
Partial Gastrectomy 2 0
Hepatectomy 2 1
Cholecystectomy 2 0
Hepaticojejunostomy 1 0
Abdominoperineal Resection 1 0
Sigmoidectomy and Rectopexy 1 0
Partial Duodenectomy 1 1
Total 45 7
229.
202 Robotic Surgery for General Surgeons : .uture or .antasy
Conclusion
Robotic surgery is now accepted as an alternative for selected surgical procedures.
This is just a dawn of the new era for future surgery. We believe this innovation from the end of
the last century would certainly establish a milestone of robotic surgery for the benefit of mankind.
References
1. Sackier JM, Wang Y. Robotically assisted laparoscopic surgery: from concept to development. Surg Endosc
1994;8:63-6.
2. Ballantyne GH. Robotic surgery, telerobotic surgery, telepresence, and telementoring: Review of early clinical
results. Surg Endosc 2002;6:1389-402.
3. http://library.thinkquest.org/03oct/00760/Zeus%20System.htm (Accessed on 17 July 2010)
4. http://www.intuitivesurgical.com/products/davinci_surgicalsystem/index.aspx (Accessed on 17 July 2010)
5. http://www.intuitivesurgical.com/www/site1/products/robotic/4th-Arm_259X319.jpg (Accessed on 17 July 2010)
6. http://www.frost.com/prod/servlet/market-insight-top.pag?docid=4453859 (Accessed on 17 July 2010)
7. Talamini MA, Chapman S, Horgan S, Melvin WS. A prospective analysis of 211 robotic-assisted surgical
procedures. Surg Endosc 2003;17:1521–4.
8. Watanabe G. Are You Ready to Take Off as a Robo-surgeon? Surg Today 2010;40:491–3.
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4. Mirels H. Metastatic disease in long bones: A prosposed scoring system for diagnosing impending pathologic
fractures. Clin Orthop 1989;249:256-64.
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6. Malawer MM and Sugarbaker PH. Treatment of Metastatic Bone Disease in Musculoskeletal Cancer Surgery.
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7. Lewis VO. Surgical Management of Upper Extremity Metastatic Disease in Schwartz HS editor. Orthopaedic
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2007: 375-82.
8. Weber KL, Randall RL, Grossman S, Parvizi J. Management of Lower-Extremity Bone Metastasis. J Bone
Joint Surg Am. 2006;88:11-9.
230 Practical Management of Dysfunctional Uterine Bleeding
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240 Practical Management of Dysfunctional Uterine Bleeding
14. Vilos GA, Tureanu V, Garcia M, Abu-Rafea B. The levonorgestrel intrauterine system is an effective treatment
in women with abnormal uterine bleeding and anticoagulant therapy. J Minim Invasive Gynecol. 2009;16:
480-4.
15. Hill D, Maher P. Treatment of menorrhagia by endometrial ablation. Med J Aust. 1990;152:564-5.
16. .raser IS, Angsuwathana S, Mahmoud ., Yezerski S. Short and medium term outcomes after rollerball
endometrial ablation for menorrhagia. Med J Aust. 1993;158:454-7.
17. .raser IS. The dysfunctional uterus: dysmenorrrhea and dysfunction uterine bleeding. In: Shearman RP,
editor. Clinical reproductive endocrinology. New york: Churchill Livingstone; 1985. 579-98.
18. Jutras ML, Cowan BD. Abnormal bleeding in the climacteric. Obstet Gynecol Clin North Am 1990;17:409-25.
19. Lacey JV, Jr., Chia VM. Endometrial hyperplasia and the risk of progression to carcinoma. Maturitas. 2009;63:
39-44.
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264 ¡ÒÃ䴌¹º¡¾Ã‹Í§ã¹à´ç¡â´ÂÀÒ¾ÃÇÁáÅСÒäѴ¡Ãͧ¡ÒÃ䴌¹ã¹à´ç¡ááà¡Ô´
Ô Ô
àÍ¡ÊÒÃ͌ҧÍÔ§
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cholesteatoma ËÇÁ´ŒÇ «Ö§ÊÒÁÒö·íÒÅÒ¡Ãд١ÃÙ»¤ŒÍ¹ ·Ñ§ â¡Å¹ä´Œ ÃÇÁ¶Ö§ÍÒ¨¹íÒä»ÊÙÀÒÇÐá·Ã¡
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«Ö§¨Ð·íÒãËŒà¡Ô´ cholesteatoma µÒÁÁÒä´Œ ËÃ×ÍÍÒ¨à¡Ô´¡ÒÃῺµÑǢͧᡌÇËٺҧʋǹ (atelectasis)
è
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é Ñé Ô
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1. Teele DW, Klein JO, Rosner B. Epidemiology of otitis media during the first seven years of life in children in
greater Boston: a prospective, cohort study. J Infect Dis. 1989;160(1):83-94.
2. Tos M. Epidemiology and natural history of secretory otitis. Am J Otol. 1984;5(6):459-62.
3. Paradise JL, Rockette HE, Colborn DK, Bernard BS, Smith CG, Kurs-Lasky M, et al. Otitis media in 2253
Pittsburgh-area infants: prevalence and risk factors during the first two years of life. Pediatrics. 1997;99(3):
318-33.
4. Casselbrant ML, Mandel EM. Epidemiology. In: Rosenfeld RM, Bluestone CD, editors. Evidence-based otitis
media. 2nd ed. Hamilton, Ontario: BC Decker Inc; 2003. p. 147-62.
5. Rosenfeld RM, Culpepper L, Doyle KJ, Grundfast KM, Hoberman A, Kenna MA, et al. Clinical practice
guideline: Otitis media with effusion. Otolaryngol Head Neck Surg. 2004;130(5 Suppl):S95-118.
6. Diagnosis and management of acute otitis media. Pediatrics. 2004;113(5):1451-65.
7. Germiller JA. Hearing loss in children. In: Wetmore R., editor. Pediatric Otolaryngology. 1st ed. Philadelphia:
Mosby; 2007. p. 60-76.
8. Rosenfeld RM, Bluestone CD. Clinical pathway for otitis media with effusion. In: Rosenfeld RM, Bluestone
CD, editors. Evidence-based otitis media. 2nd ed. Hamilton(ON): BC Decker;2003. p. 303-24.
9. Bluestone CD. Role in management of otitis media. In: Bluestone CD, editor. Eustachain tube: structure,
function , role in otitis media. 1st ed. Ontario: BC Decker; 2005. p. 145-76.
10. Rosenfeld RM, Kay D. Natural history of untreated otitis media. Laryngoscope. 2003;113(10):1645-57.
11. Williamson IG, Dunleavey J, Bain J, Robinson D. The natural history of otitis media with effusion—a three-year
study of the incidence and prevalence of abnormal tympanograms in four South West Hampshire infant and
first schools. J Laryngol Otol. 1994;108(11):930-4.
272 ¡ÒÃÊÙàÊÕ¡ÒÃ䴌¹㹼ٻÇÂà´ç¡¨Ò¡ÊÒà˵طҧ¾Ñ¹¸Ø¡ÃÃÁ
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âä¢Í§â¤ÃâÁâ«Á·Õ辺º‹Í·ÕèÊØ´¤×Í ¡ÅØ‹ÁÍÒ¡ÒôÒǹ (Down syndrome) «Ö觨оº
conductive hearing loss ä´Œ¶§ÃŒÍÂÅÐ 60-80 ¨Ò¡¤ÇÒÁ¼Ô´»¡µÔ¢Í§ËÙª¹¡ÅÒ§ »˜¨¨Ñ·շÒãËŒÁ¤ÇÒÁ
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2. ¡ÅØÁÍÒ¡Ò÷ÕÁ¤ÇÒÁ¼Ô´»¡µÔ¢Í§ÈÕÃÉÐáÅÐãºË¹ŒÒ (Craniofacial syndromes)
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syndromes) ·Õ¾ºº‹ÍÂ䴌ᡋ¡ÅØÁÍÒ¡Òà Crouzon áÅÐ¡ÅØÁÍÒ¡Òà Apert «Ö§¡ÅØÁÍÒ¡ÒÃàËŋҹÕÁ¡ÒÃ
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receptor 2 (.G.R2) ·Ñ§ 2 ¡ÅØÁÍÒ¡ÒùըÐÁÕ conductive hearing loss ËÇÁ¡Ñº¡Òû´àÃçǡNjҡíÒ˹´
é ‹ é
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craniosynostosis ·Õ¾º sensorineural hearing loss ä´Œ¤Í Muenke syndrome «Ö§à¡Ô´¨Ò¡¡ÒáÅÒÂ
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tomography, CT) ¢Í§¡Ãд١ temporal âä¹Õ໚¹âä¾Ñ¹¸Ø¡ÃÃÁ ·Õ¶Ò·ʹẺÂÕ¹´ŒÍ áÅÐà¡Ô´¨Ò¡
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nonsyndromic hearing loss ·Õè¶‹Ò·ʹẺÂÕ¹´ŒÍ à¡Ô´¨Ò¡¡ÒáÅÒ¾ѹ¸Ø ¢Í§ÂÕ¹ GJB2
(connexin 26)(7) ¡ÒáÅÒ¾ѹ¸Ø·¾ºº‹Í·Õʴ㹪ÒǵÐÇѹµ¡¢Í§ÂÕ¹ GJB2 ¤×Í ¡ÒâҴËÒÂä»
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1. Jariengprasert C, Lertsukprasert K, Kasemsuwan L ,et al. Newborn hearing screening using otoacoustic
emission (OAEs): a 1-year study at Ramathibodi Hospital. Thai J Otolaryngol Head Neck Surg 2003;4:27–41.
2. Davis A, Parving A. Toward appropriate epidemiology data on childhood hearing disability: comparative
European study of birth cohorts 1982–88. J Audiol Med. 1994;3:35–47.
3. Marazita ML, Ploughman LM, Rawlings B, Remington E, Arnos KS, Nance WE. Genetic epidemiological
studies of early-onset deafness in the U.S. school-age population. Am J Med Genet. 1993;46:486–91.
4. Toriello HV, Reardon W, Gorlin R., editors. Hereditary hearing loss and its syndrome, 2nd ed. New York:
Oxford University Press, 2004.
5. Kochhar A, Hildebrand MS, Smith RJ. Clinical aspects of hereditary hearing loss. Genet Med. 2007;9:393-408.
6. .alk RE, Honrubia D, .ischel-Ghodsian N. Hereditary hearing loss and deafness. In: Rimoin DL, Connor JM,
Pyeritz RE, Korf BR, editors. Emery and Rimoin’s principles and practice of medical genetics, 5th ed. Philadelphia:
Churchill Livingstone; 2007. p.3265-303.
7. Estivill X, .ortina P, Surrey S, Rabionet R, Melchionda S, D’Agruma L, et al. Connexin-26 mutations in
sporadic and inherited sensorineural deafness. Lancet. 1998;351:394–8.
8. Snoeckx RL, Huygen PL, .eldmann D, Marlin S, Denoyelle ., Waligora J, et al. GJB2 mutations and degree
of hearing loss: a multicenter study. Am J Hum Genet. 2005;77:945-57.
9. Ohtsuka A, Yuge I, Kimura S, Namba A, Abe S, Van Laer L,et al. GJB2 deafness gene shows a specific
spectrum of mutations in Japan, including afrequent founder mutation. Hum Genet. 2003; 112:329–33.
10. .ischel-Ghodsian N. Mitochondrial mutations and hearing loss: paradigm for mitochondrial genetics. Am J Hum
Genet. 1998;62:15-9.
11. Wattanasirichaigoon D, Limwongse C, Jariengprasert C, Yenchitsomanus PT, Tocharoenthanaphol C,
Thongnoppakhun W, et al. High prevalence of V37I genetic variant in the connexin-26 (GJB2) gene among
non-syndromic hearing-impaired and control Thai individuals. Clin Genet. 2004;66:452-60.
296 ¡Òû‡Í§¡Ñ¹âäËÅÍ´àÅ×Í´ÊÁͧ·Ñ§¡‹Í¹áÅÐËÅѧ¡Òü‹ÒµÑ´
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Benefit (B) / I : B >>> R IIa : B >> R IIb : B ? R III : R > B
Risk (R)
Level A Multiple RCT* Some conflict Greater conflict Multiple RCT*
(3-5 trials)
Level B Single RCT* or Some conflict Greater comflict Single RCT* or
(2-3 trials) none RCT* none RCT*
Level C Expert opinion Expert opinion Expert opinion Expert opinion
(1-2 trials)
Summary Indicated Reasonable May be or unclear Not indicated
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43
Scrub Typhus in Thailand
Yupin Suputtamongkol
Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University,
Human rickettsioses, known to occur in Thailand, include mainly scrub typhus and
murine typhus. Scrub typhus is caused by Orientia tsutsugamushi, an obligate intracellular
Gram-negative bacterium that has a different cell wall structure and genetic makeup from those
of rickettsiae.(1) It is transmitted to humans by the bite of the larval stage of trombiculid mites
(chiggers). Endemic areas of scrub typhus include rural areas of South-East Asia throughout the
Asia Pacific rim and Northern Australia. More than a billion people are at risk of infection and
about one million cases occur annually.(2) In Thailand the report incidence of scrub typhus has
increased during the previous decade.(2, 3) Clinical manifestations of this infection varies widely
from a mild and self-limited febrile illness to a more severe course which may be fatal.2 Scrub
typhus is recently recognized as a common cause of acute undifferentiated fever both in
indigenous population and ill travelers returning from the tropics. (2, 3)
Despite the availability of low cost and effective antibiotic treatment, scrub typhus
continues to cause significant morbidity and mortality in otherwise healthy adults and children.
The greatest challenge to clinician is early diagnosis of this infection, when antibiotic therapy is
most effective. The purpose of this presentation is to summarize the epidemiologic data using
new molecular tools, clinical manifestations and management of scrub typhus.
Epidemiology of scrub typhus in Thailand
Scrub typhus was first reported in human from central region of Thailand in 1952(4) and
O. tsutsugamushi was first isolated from rodent trapped from the same area in
1955.(5)Leptotrombidium deliensis is the primary vector of O. tsutsugamushi. However several
other species have been implicated as vectors such as L. Chiangraiensis, L. imphalum and
Blankaartia acuscutellaris.(6)
Nationwide seroepidemiological studies indicate that O. tsutsugamushi infection is
widespread in Thailand. The seropositivity rates of O. tsutsugamushi among soldiers and patients
325.
298 Scrub Typhus in Thailand
with acute febrile illness varied from 5.4% to 21%. These surveys have found high point
prevalence, varied from 13-31% of inhabitants in suburban Bangkok, to 59 -77% of inhabitants of
3 villages in the northern and northern region respectively.(7) According to the unpublished
records of the Public Health Ministry of Thailand, fewer than 100 cases of scrub typhus were
reported annually before 1983, 750–900 cases/year were reported between 1988 and 1991, and
3,000- 5,000 cases/year has been reported since 2001.
We conducted an epidemiological and clinical study of 1,663 patients with acute
undifferentiated fever, between October 2000 and March 2003 in 6 hospitals in rural Thailand;
four hospitals in the northeastern region, one hospital in the central region and one hospital in
the southern region. There were 268 (16.1%) patients with laboratory confirmed scrub typhus.(8)
The diagnosis of scrub typhus was made by PCR (101 out of 141 patients tested) or by indirect
immunofluorescent antibody (IFA) for combined Karp, Kato, and Gilliam strain of O.
tsutsugamushi (74 patients by a fourfold rising in titer to 1:400, 76 patients by a single titer to
1:400, 17 patients by a fourfold rising in titer or stable titers of at least 1:200). Blood culture
for aerobic bacteria and serological tests for leptospirosis, dengue infection were negative in all
of these patients. Scrub typhus, murine typhus, and SFG rickettsioses were diagnosed in
7.8%, 2.4%, and 5% respectively in the subgroup analysis of these patients who presented
with severe manifestations in our recent publication.(9)
Clinical features
The clinical presentations of scrub typhus are nonspecific. In our clinical study the
median duration of fever was 7 days in patients with scrub typhus. Headache, generalized
myalgia, and calf pain were very common. The classic manifestation of scrub typhus, includes
generalized lymphadenopathy, maculopapular rash and splenomegaly were not common in this
case series. Eschar was detected in 56 (20.9%) patients. Complications such as hepatic
dysfunction (defined as jaundice or total bilirubin 2.5 mg/dl, or high AST and/ or ALT level to
more than 120 IU, or high alkaline phosphatase level to more than 350 IU, or mixed abnormalities),
renal dysfunction (defined as oliguria or abnormal urea and/ or creatinine level), hypotension
(defined as systolic BP <90 mmHg on admission), congestive heart failure, or pulmonary
involvement (defined as abnormal chest radiography) were common in scrub typhus. Only 32%
of patients with scrub typhus did not have any complication on admission.
Hepatic dysfunction was the most common complication. Pulmonary involvement was
found in approximately half of study group. The chest radiographic abnormalities were similar to
those previously reported, except that hilar lymphadenopathy was not as common as previously
326.
àǪÈÒʵ÷¹Âؤ 2553
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reported. Cardiac involvement defined by cardiomegaly or cardiac to thoracic ratio > 0.5 on PA
chest radiography or > 0.6 on AP chest radiography (36/119, 30.3%) or congestive heart failure
(23/119, 19.3%) were common abnormal radiographic findings in this study group. However this
finding was not associated with hypotension on admission. Approximately 12% of the patients
presented with multi-organ dysfunction mimic community-acquired septicemia in this case series.
Overall seven patients with scrub typhus died in this case series. The causes of dead
in all except one patient were multi-organ failure including respiratory failure. ARDS was not a
prominent cause of death in this study. The cause of death (bleeding hepatoma) was unrelated
to scrub typhus in one patient. Scrub typhus was not included in the differential diagnosis
therefore no effective treatment was given in four out of six patients who died. In addition scrub
typhus was diagnosed in 18 out of 51 (35.3%) of patients who presented with septic shock in
one of the study hospital between November 2001 and January 2002. The mortality was 16.7%
in this subgroup of scrub typhus with septic shock.(10)
Conclusion
Scrub typhus is presented with nonspecific symptoms and signs. Eschar is the only
clinical sign that differentiated scrub typhus from other infectious disease. Severe scrub typhus
can manifest as multi-organ dysfunction mimic septicemia from other causes and leptospirosis.
Unaware of the diagnosis of severe scrub typhus in these patients could lead to delay diagnosis
and high mortality.
Awareness that scrub typhus is a prominent cause of acute undifferentiated fever in
adults in Thailand improves the probability of an accurate clinical diagnosis. Early recognition
and appropriate treatment reduce morbidity and mortality. Results from recent clinical studies
from Thailand indicate that rational antimicrobial therapy would be doxycycline in mild cases
and a combination of either cefotaxime or ceftriaxone and doxycycline in severe cases.
Azithromycin could be considered as an alternative treatment when ever doxycycline allergy is
suspected. This would be either curative, or have no ill-effect, in the majority of instances.
Failure to improve or defervesce within the next 48 hours would indicate the need to a thorough
reevaluation of clinical findings and initial laboratory investigation results and a need to change
antibiotic.
327.
300 Scrub Typhus in Thailand
References
1. Tamura A, Ohashi N, Urakami H, Miyamura S. Classification of Rickettsia tsutsugamushi in a new genus,
Orientia gen. nov., as Orientia tsutsugamushi comb nov. Int J Syst Bacteriol 1995;45:589-91.
2. Watt G, Parola P. Scrub typhus and tropical rickettsioses. Curr Opin Infect Dis 2003;16:429-36.
3. Suttinont C, Losuwanaluk K, Niwatayakul K, Hoontrakul S, Intaranongpai W, Silpasakorn S, et al. Causes of
acute, undifferentiated, febrile illness in rural Thailand: results of a prospective observational study. Ann Trop
Med Parasitol 2006;100: 363-70.
4. Trishnanda M, Vasuvat C, Harinasuta C. Investigation of scrub typhus in Thailand. J Trop Med Hyg 1964;67:215-9.
5. Traub R, Johnson P, Mirsse M, Elbel R. Isolation of Rickettsia tsutsugamushi from rodents from Thailand. Am
J Trop Med Hyg 1954;3:356-9.
6. Lerdthusnee K, Khuntirat B, leepitakrat W, Tanskul P, Monkanna T, Khlaimanee N, et al. 2003. Vector
competence of Leptotrombidium Chiangraiensis chiggers and transmission efficacy and isolation of Orientia
tsutsugamushi. Ann N Y Acad Sci 2003;990:25-35.
7. Strickman D, Tanskul P, Eamsila C, Kelly DJ. Prevalence of antibodies to rickettsiae in the human population
of suburban Bangkok. Am J Trop Med Hyg 1994;5:149- 53.
8. Suputtamongkol Y, Suttinont C, Niwatayakul K, Hoontrakul S, Limpaiboon R, Chierakul W, et al. Epidemiology
and clinical aspects of rickettsioses in Thailand. Ann N Y Acad Sci 2009;1166:172- 9.
9. Suputtamongkol Y, Niwattayakul K, Suttinont C, Losuwanaluk K, Limpaiboon R, Chierakul W, et al. An open,
randomized, controlled trial of penicillin, doxycycline, and cefotaxime for patients with severe leptospirosis. Clin
Infect Dis 2004;39:1417-24.
10. Thap LC, Suparanond W, Treeprasertsook S, et al. Septic shock secondary to scrub typhus: characteristics
and complications. Southeast Asian Trop Med Public Health 2002;33:780- 6.
328.
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44
Molecular Epidemiology of Scrub Typhus in Thailand
Patimaporn Wongprompitak
Department of Immunology, .aculty of Medicine Siriraj Hospital, Mahidol University,
Scrub typhus is widely distributed in Asia Pacific region. This disease is caused by
Orientia tsutsugamushi infection. O. tsutsugamushi is an obligatory intracellular Gram-negative
bacteria. The pathogenesis of scrub typhus in humans is various, depending on the geographic
area because of an infection with the different strain of O. tsutsugamushi. The geographic
distribution study of the existing strains of O. tsutsugamushi will be beneficial for the epidemiology
and control of this disease. Several strains of O. tsutsugamushi have been reported in different
countries. The Gilliam, Karp, Kato, TA678, TA686, TA716, and TA763 strains have been
identified in South-East Asia and Australia by indirect immunofluorescence (I.) using polyclonal
and monoclonal antibodies. The Karp and Gilliam strains were the most prevalent in China,
Korea and Thailand. (1)
Molecular identification of scrub typhus in Thailand
Genetic analysis of the antigenic protein encoding gene of O. tsutsugamushi, the 56-
kDa protein, 22?kDa protein and the 47?kDa protein, were used for genotypic identification.(1)
The molecular methods including PCR, restriction fragment-length polymorphism (R.LP), and
nucleotide sequencing of specific PCR products were used for direct comparison of products
from the same genes of O. tsutsugamushi. The previous study, a nested PCR based on the
56?kDa protein encoding gene and DNA sequencing of a 487 base pair PCR product were
performed to identify O. tsutsugamushi isolated from scrub typhus patients.(2) DNA from 62
seropositive patients with scrub typhus were extracted. Karp was reported to be the most
prevalent in Thailand with 97% (60/62) of positive samples, followed by Kato (3%; 2/62). Recently,
the entire OR. of the 56-kDa protein encoding gene of each isolates were characterized by
nucleotide sequencing, followed by phylogenetic analysis. (3) The majority isolates in Thailand
was Karp strain (65.2%), then Gilliam (26.1%), TA763 (4.3%) and others (4.3%).
329.
302 Molecular Epidemiology of Scrub Typhus in Thailand
Identification of O. tsutsugamushi in scrub typhus patients
O. tsutsugamushi infection can be identified by serological tests but patient sera often
cross-react with the antigens from different strains. Recently, nested polymerase chain reaction
(PCR) was used for the identification of scrub typhus strains using gene encoding the specific
56-kDa protein of O. tsutsugamushi. In this study, genotypic identification of O. tsutsugamushi
in Thailand was investigated by genetic analysis using nucleotide sequencing and phylogenetic
analysis. The samples from patient with febrile illness were collected and selected for O.
tsutsugamushi infection using PCR amplification of specific 16S rRNA gene. The 56-kDa protein
encoding gene of these samples was amplified and analyzed for nucleotide sequences. The
nucleotide sequences of hypervariable region (VDI-IV) in this gene were compared with the
reference strains in Genbank database and phylogenetic tree was constructed (figure 1). There
were 4 major groups which related to O. tsutsugamushi strains (Karp, Gilliam, TA763 and
Kato). The most prevalent strain of O. tsutsugamushi in Thailand was Karp (43.8%; 28/64),
followed by Gilliam (34.4%; 22/64), TA763 (12.5%; 8/64) and Kato (4.7%; 3/64).
Application in the future
The result of this study might be useful for developing the method for strain identification.
The nucleotide sequences alignment of hypervarible region in 56 KDa encoding gene will be
performed and strain specific primers will be selected for strain identification using nested PCR
amplification. The information of molecular epidemiology of scrub typhus could be also useful
for prevention and controlling of the disease in Thailand.
References
1. Kelly DJ, .uerst PA, Ching WM, Richards AL. Scrub typhus: the geographic distribution of phenotypic and
genotypic variants of Orientia tsutsugamushi. Clin Infect Dis 2009;48:S203-30.
2. Blacksell SD, Luksameetanasan R, Kalambaheti T, Aukkanit N, Paris DH, McGready R, et al. Genetic typing
of the 56-kDa type-specific antigen gene of contemporary Orientia tsutsugamushi isolates causing human scrub
typhus at two sites in north-eastern and western Thailand. .EMS Immunol Med Microbiol 2008;52:335-42.
3. Manosroi J, Chutipongvivate S, Auwanit W, Manosroi A. Determination and geographic distribution of Orientia
tsutsugamushi serotypes in Thailand by nested polymerase chain reaction. Diagn Microbiol Infect Dis 2006;55:185-
90.
330.
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.igure 1 Dendrogram representing the genetic relationships of samples from scrub
typhus patients (represented in G alphabet followed by number (Gxx)) and
reference O. tsutsugamushi strains based on the nucleotide sequence of the
56-kDa protein encoding gene demonstrating the relationships between O.
tsutsugamushi strains.
332.
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45
Recent Advances in the Diagnosis of Scrub Typhus
Wei-Mei Ching
Viral and Rickettsial Diseases Naval Medical Research Center
Diagnosis of scrub typhus is generally based on the clinical presentation and the history
of a patient. However, differentiating scrub typhus from other acute tropical febrile illnesses
such as leptospirosis, murine typhus, malaria, dengue fever, and viral hemorrhagic fevers can
be difficult because of the similarities in these signs and symptoms. Besides the isolation of
the causative agent Orientia from patient blood as the confirmatory test, many modern
technologies have been applied in the development of diagnostic assays. Recent advances in
the diagnosis of scrub typhus are briefly described below, with emphasis on the activities
carried out in my laboratory.
Immuno-detection
The early serological assays include Weil-Felix test (1916), indirect immunofluorescent
antibody test (IFA, 1963), indirect immunoperoxidase (IIP, 1982), passive hemagglutination
assay (1993), dipstick dot –blot assay (1995) and ELISA (1997). Almost all of the assays use
whole cell grown in egg yolk sac or tissue culture as the antigen. Due to the intracellular nature
of Orientia and the hazardous procedures which require biosafety level 3 (BSL3) facilities and
practices for large scale production, not many diagnostic laboratories have the ability to culture
and purify O. tsutsugamushi. It was not until 1993, Kim et. el.1 developed the first recombinant
antigen of the outer membrane protein, the 56 kDa antigen, which comprises 10-15% of the total
bacterial protein. This protein is an ideal antigen to be used in sero-diagnosis because sera from
95–99% of patients with scrub typhus recognize this variable 56 kDa antigen of O. tsutsugamushi.
The availability of recombinant Orientia protein antigens that can be produced and
purified in large amounts and have similar antigenic properties as Orientia-derived antigens has
opened up a new avenue to develop low cost rapid assays. However, O. tsutsugamushi exhibits
considerable antigenic strain variation and the antigenic differences depend largely on the outer
membrane protein, that varies in size from 53 to 63 kDa. In order to develop a more broadly
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306 Recent Advances in the Diagnosis of Scrub Typhus
reactive diagnostic reagent, we produced t truncated recombinant protein of the 56 kDa antigen
(r56) from three prototype strains (Karp, Gilliam, and Kato). The combination of these three r56
(Tri-r56) in ELISA performed as well as the combination of whole cell antigens from the same
strains in IFA. Table 1 shows Tri- r56 in ELISA has the same sensitivity as IFA for IgM detection.
The results for IgG are also in very good agreement (data not shown).
Table 1 Combination of r56 from three strains in ELISA can detect IgM as early as IFA
The collaborative efforts of AccessBio and the DoD Laboratory at the Naval Medical
Research Center culminated in the development of a CareStartTM Scrub Typhus Combo Test
Device.This device was evaluated at the DoD Laboratorywith sera collected in Taiwan (Table 2)
and sera collected in the tropical environment of the Lao People’s Democratic Republic (Laos)
and Thailand (Table 3). Both evaluations have suggested that this test kit is sensitive (>90%)
and specific (>90%) for early diagnosis (IgM detection) as compared to IFA. On the basis of
data from stored patient samples, the AccessBio scrub typhus IgM rapid assay appears to
provide accurate results for the diagnosis of acute scrub typhus in a tropical setting where
scrub typhus is endemic.2 The ease of use and low cost of test kit have enhanced its
commercial applicability in the mostly underdeveloped endemic countries
Table 2 The performance of CareStartTM Scrub Typhus Combo Test Device (using the
mixture of recombinant antigen r56 from three proto type strains) as compared to current gold
standard IFA using whole cell lyaste (mixture of three proto type strains).
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Table 2A DoD laboratory evaluation of CareStartTM Scrub Typhus Combo for IgM detection.
Comparison between the results of IgM of CareStartTM Scrub Typhus Combo and IFA IgM
Specificity Specificity % Sensitivity Sensitivity % Agreement %
Site 1: Access Bio 93/94 98.9% 18/19 94.7% 98.2%
Site 2: NMRC 91/112 81.3% 93/98 94.9% 87.6%
Total 184/206 89.3% 111/117 94.9% 91.3%
Table 2B DoD laboratory evaluation of CareStartTM Scrub Typhus Combo for IgG
detection
Comparison between the results of total antibody of CareStartTM Scrub Typhus Combo and IFA total antibody
Specificity Specificity % Sensitivity Sensitivity % Agreement %
Site 1: Access Bio 92/94 97.9% 19/19 100% 98.2%
Site 2: NMRC 38/40 95% 117/120 97.5% 96.9%
Total 130/134 97% 136/139 97.7% 97.8%
Table 3 Overall diagnostic accuracy and sensitivity of the AccessBio scrub typhus
Combo for detection of IgM and total antibodies compared to the results of the
gold standard assay, IFA
Antibody Sensitivity Specificity PPV NPV
IgM 96.8 (92.0–99.1) 93.3 (86.7–97.3) 94.5 (89.1–97.8) 96.1 (90.3–98.9)
Total antibody 97.6 (93.1–99.5) 71.4 (61.8–79.8) 80.3 (73.0–86.3) 96.2 (89.2–99.2)
To encompass a broader spectrum of antigenic variations, we have produced the r56
from strain TA763, chigger isolate Lc-1, and four chimeric r56s based on the sequences of Karp
and TA763 in the variable regions. Three of these chimeric r56s (C1, C2, and C3) were as
reactive as either Karpr56 or TA763r56 against 14 strain specific sera from infected mice3,
suggesting that the chimeric r56 exibited broader reactivity as compared to their parent r56,
either from Karp or TA763.
Nucleic acid detection
The value of serological assays for diagnosis of acute infection inclinical settings has
its limitations. This is because the earliest detection of antibodies is at least 4-5 days after the
onset of illness. In addition, there are high background titers in endemic populations. Therefore
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308 Recent Advances in the Diagnosis of Scrub Typhus
antigen detection is important for early diagnosis. However, the amount of Orientia in scrub
typhus patients during bacteremia is very low (5-10 organisms/ul). The immuno-capture assay is
not sensitive enough without an additional step for sample concentration. With the advent of
polymerase chain reaction (PCR), Furuya et al. first demonstrated that amplification of the 56-
kDa protein gene was a reliable method for early diagnosis (1991). Later on, PCR, nested PCR,
and quantitative PCR against different target genes such as 16S RNA, 60 kDa GroEL heat
shock protein and 47 kDa HtrA1 gene were developed. The use of nucleic acid amplification
has provided sufficient sensitivity. However, this approach requires sample processing (DNA
extraction), sophisticated instrumentation, expensive temperature sensitive reagents, and
extensive training of the end user. Its application is suitable for hospital centers with high
complexity laboratories, but not for rudimentary point-of-care centers such as doctors offices in
endemic rural areas. Another potential disadvantage is that false positives due to DNA
contamination are often observed.
Recently, Paris et al. described a new nucleic acid based assay using LAMP (loop-
mediated isothermal amplification) for the detection of Orientia (2008)(4). LAMP assay is quick,
easy to perform without the need of a thermal cycler for amplification. The Bst DNA polymerase
used in LAMP provides an additional advantage due to its insensitivity to blood borne components
including myoglobin, heme-blood protein complexes and immunoglobin, which inhibit the Taq
polymerase used in PCR. Thus much simpler sample preparation and reaction conditions are
required for LAMP compared to conventional PCR or real-time, quantitative PCR. Primers against
the Orientia specific region of groEL gene were designed using the Primer Explorer software of
Eiken (http://primerexplorer.jp/e/). The LAMP assay was carried out in a single tube 65C for 90
min for DNAs extracted from cultured Orientia, or Orientia infected buffy coat and whole blood
of confirmed scrub typhus patient. The detection limits were about 5 to 10 fold less than that of
qPCR. The results were in 100% agreement with those of the gold standard IFA. Therefore
LAMP assay has a very high potential to be used in rural areas.
We have sequenced the 47 kDa antigen gene from 25 disparate strains previously
selected to cover the wide range of strain variation. The 25 strains included six proto type
strains, all but one of human origin and were isolated from different locations throughout the
Asia-Pacific-Australia endemic region. LAMP primers against the conserved region of 47kDa
gene were designed. The assay has been performed isothermally at 60?C for 60 or 90 minutes.
The detection limit is consistently around 200 copies/ 25uL reaction with occasional detection
of as few as 10 copies/25uL reaction. The sensitivity of this LAMP assay was similar to that of
real-time PCR experiments using the same primers and to that of the LAMP assay using GroEL
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gene as the target. So far this LAMP assay has been shown to detect at least 6 immunologically
and biologically disparate strains (Karp, Kato, Gilliam, TA763, TH11811, and TH1812) which
cover the major clades of prevalent strains of Orientia with similar sensitivity.(5)
Host response gene profile: the next generation diagnosis tool
It has been hypothesized that (1) a unique set of early response genes for a specific
rickettsial pathogen can be defined in vitro by using the high-throughput cDNA microarray
technology. (2) The expression profile of these unique sets of genes can be detected in patient
blood cells. (3) The characterization of these unique genes can be used to differentiate rickettsial
infections as well as infections caused by other agents. The proof of this hypothesis will
undoubtedly lead to the development of diagnostic kits using cDNA microarrays containing
genes that change significantly in their expression level in response to infection. Furthermore,
the cDNA microarray technology could be used as a true multiplex diagnostic platform to
differentiate various infections. The application of this approach for early diagnosis is remarkable.
It can detect the infection of a particular pathogen long before the onset of symptoms, and
much earlier than the current method of nucleic acid based real-time PCR and antigen based
serology tests. Unlike the host responses monitored by microarray technology, antigen detection
assays require adequate amounts of bacterial DNA or antigen; achieved only through infection
for a few days or more, for optimal detection. Moreover, antibody detection assays usually
requires 5-10 days for the host to develop a significant enough immune response to detect
specific IgM and IgG antibodies. Gene profile signatures related to the time course of impending
illness can be especially helpful for physicians to treat patients properly.
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310 Recent Advances in the Diagnosis of Scrub Typhus
As Orientia is an obligate intracellular pathogen, organisms disseminate from the skin
to target organs strongly suggest that they may enter the peripheral circulation. Walsh et al.
presented the evidence that Orientia was present in circulating white blood cells (mostly
mononuclear cells) of humans with acute scrub typhus (2001)(5). For determination of host
response genes that play a role in infection, we performed the in vitro study described below.
Freshly isolated peripheral blood mononuclear cells (PBMC) from healthy donors were
infected with Orientia and samples were collected at 1 h, 4 h, 8 h or 18 h post infection. The
gene expression profiles were monitored by cDNA microarray. Among the 7489 genes 658
genes were up or down regulated upon infection. Semi-quantitative PCR using specific primers
that flank the mRNA splicing sites of these 658 genes were carried out to verify microarray
results using glyceraldehyde 3-phosphate dehydrogenase (GAPDH) as the reference gene. Among
these 658 genes, 22 genes were confirmed to beup or down regulated (Table 4). Quantitative
PCR using 18S rRNA as the reference further confirmed two genes (NM_001547 and NM_006187)
exhibited significant increase of expression Analysis of these 22 genes and the specific increase
of both NM_001547 and NM_006187 suggest the list of 22 genes appears to be unique for O.
tsutsugamushi infection and has the potential for use in differentiating infections caused by
viruses, bacteria, parasites and other pathogens.(6)
Table 4. List of genes confirmed by semi-quantitative PCR
Accessionnumber Name of Genes Biological processes
NM_000530 myelin protein zero (Charcot-Marie-Tooth neuropathy 1B) (MPZ), Signal transduction
NM_000595 lymphotoxin alpha (TNF superfamily, member 1) (LTA), Signal transduction
NM_000801 FK506 binding protein 1A, 12kDa (FKBP1A), transcript variant 12B Signal transduction
NM_001547 interferon-induced protein with tetratricopeptide repeats 2 (IFIT2), Cell growth and/or maintenance
NM_001838 chemokine (C-C motif) receptor 7 (CCR7), Signal transduction
NM_002498 NIMA (never in mitosis gene a)-related kinase 3 (NEK3), transcript variant 1, Signal transduction
NM_002922 regulator of G-protein signalling 1 (RGS1), Signal transduction
NM_002946 replication protein A2, 32kDa (RPA2), Nucleotide and nucleic acid
metabolism
NM_002983 chemokine (C-C motif) ligand 3 (CCL3), Immune response
NM_003205 transcription factor 12 (HTF4, helix-loop-helix transcription Nucleotide and nucleic acid
factors 4) (TCF12), transcript variant 3 metabolism
NM_003404 tyrosine 3-monooxygenase/tryptophan 5-monooxygenase Signal transduction
activation protein, beta polypeptide (YWHAB), transcript variant 1
NM_003906 MCM3 minichromosome maintenance deficient 3 (S. cerevisiae) Signal transduction
associated protein (MCM3AP),
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Accessionnumber Name of Genes Biological processes
NM_004551 NADH dehydrogenase (ubiquinone) Fe-S protein 3, 30kDa Metabolism, Energy pathways
(NADH-coenzyme Q reductase) (NDUFS3),
NM_005082 tripartite motif-containing 25 (TRIM25), Nucleotide and nucleic acid
metabolism
NM_005623 chemokine (C-C motif) ligand 8 (CCL8), Signal transduction
NM_006187 2'-5'-oligoadenylate synthetase 3, 100kDa (OAS3), Immune response
NM_007215 polymerase (DNA directed), gamma 2, accessory subunit Nucleotide and nucleic acid
(POLG2), metabolism
NM_015369 TP53TG3 protein (TP53TG3), transcript variant 1 Regulation of cell cycle
NM_021991 junction plakoglobin (JUP), transcript variant 2 Cell adhesion
NM_033340 caspase 7, apoptosis-related cysteine peptidase (CASP7), Apoptosis
transcript variant beta
NM_080657 radical S-adenosyl methionine domain containing 2 (RSAD2), Immune response
NM_152998 enhancer of zeste homolog 2 (Drosophila) (EZH2), transcript Nucleotide and nucleic acid
variant 2 metabolism
Bolded genes are down-regulated
In summary, recent advances in the diagnosis of scrub typhus are exciting. Significant
progress has has already been made in rapid serological test and nucleic acid based molecular
detection. The establishment of host responsive gene profile specific to Orientia infection may
provide the opportunity for early diagnosis at the onset of illness.
References
1. Kim IS, Seong SY, Woo SG, Choi MS, and Chang WH. High-level expression of a 56-kilodalton protein gene
(bor56) of Rickettsia tsutsugamushi Boryong and its application to enzyme-linked immunosorbent assays. J.
Clin Microbiol 1993;1:598-605.
2. Blacksell SD, Jenjaroen K, Phetsouvanh R, Wuthiekanun V, Day NP, Newton PN, Ching WM. Accuracy of
AccessBio Immunoglobulin M and Total Antibody Rapid Immunochromatographic Assays for the Diagnosis of
Acute Scrub Typhus Infection. Clin Vaccine Immunol 2010;17:263-6.
3. Chao CC, Zhang Z, Huber E, and Ching WM. Cross reactivity of various 56 kDa recombinant protein
antigens with sera from Orientia tsutsugamushi infected mice. 5th International Conference on Rickettsiae and
Rickettsial Diseases, May 18-20, 2008, Marseille, France.
4. Paris DH, Blacksell SD, Newton PN, and Day NPJ. Simple, rapid and sensitive detection of Orientia tsutsugamushi
by loop-isothermal DNA amplification. Trans R Soc Trop Med Hyg 2008;102:1239-46.
339.
312 Recent Advances in the Diagnosis of Scrub Typhus
5. Chao CC, Huber E, Chen HW, and Ching WM. Detection of Orientia tsutsugamushi DNA using loop-mediated
isothermal amplification: a rapid and sensitive alternative to real-time PCR, 24th Meeting of the American
Society for Rickettsiology, July 31 – Aug 3, 2010, Skamania Lodge, Stevenson, Washington, USA.
6. Chao CC, Li X, Hammamieh R, O’Leary B, Jett M and Ching WM. Identification of human peripheral
leukocyte early response genes following infection with Orientia tsutsugamushi by DNA microarray and real-
time PCR. Accepted by Chao CC The Open Infectious Diseases Journal, 2010.
340.
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46
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1. Muangpaisan W, Praditsuwan R, Assanasen J, Srinonprasert V, Assantachai P, Intalapaporn S, et al. Caregiver
burden and needs of dementia caregivers in Thailand: a cross-sectional study. J Med Assoc Thai 2010;93(5):601-
7.
2. Brookmeyer R, Johnson E, Ziegler-Graham K, Arrighi HM. .orecasting the global burden of Alzheimer’s
disease. Alzheimers Dement 2007;3(3):186-91.
3. Muangpaisan W, Assantachai P, Intalapaporn S, Richardson K, Brayne C. Health expectancies in the older
Thai population. Arch Gerontol Geriatr 2010;(Article in Press).
4. Jitapunkul S, Chansirikanjana S, Thamarpirat J. Undiagnosed dementia and value of serial cognitive impairment
screening in developing countries: a population-based study. Geriatr Gerontol Int 2009;9(1):47-53.
5. ÇÕÃÈÑ¡´Ôì àÁ×ͧä¾ÈÒÅ. ÀÒÇÐÊÁͧàÊ×ÍÁã¹¼ÙʧÍÒÂØáÅСÒû‡Í§¡Ñ¹. ã¹: »ÃÐàÊÃÔ° ÍÑÊÊѹµªÑÂ, ºÃóҸԡÒÃ. »˜ËÒÊØ¢ÀÒ¾
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·Õ¾ºº‹ÍÂã¹¼ÙʧÍÒÂØ. ¡Ãا෾ÁËÒ¹¤Ã: ºÃÔÉ·ÂÙà¹Õ¹ ¤ÃÕàͪѹ ¨íÒ¡Ñ´; 2552. ˹ŒÒ 125-57.
è ŒÙ Ñ è è
6. Mitchell AJ, Shiri-.eshki M. Temporal trends in the long term risk of progression of mild cognitive impairment:
a pooled analysis. J Neurol Neurosurg Psychiatry 2008;79(12):1386-91.
7. Gatz M, Prescott CA, Pedersen NL. Lifestyle risk and delaying factors. Alzheimer Dis Assoc Disord 2006;20(3
Suppl 2):S84-8.
8. Borenstein AR, Copenhaver CI, Mortimer JA. Early-life risk factors for Alzheimer disease. Alzheimer Dis Assoc
Disord 2006;20(1):63-72.
9. Bendlin BB, Carlsson CM, Gleason CE, Johnson SC, Sodhi A, Gallagher CL, et al. Midlife predictors of
Alzheimer’s disease. Maturitas 2010;65(2):131-7.
10. .licker L. Life style interventions to reduce the risk of dementia. Maturitas 2009;63(4):319-22.
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Antidepressants: Antihypertensives:
- Amitriptyline, Doxepin - Doxazosin
- Daily fluoxetine - Reserpine at doses >0.25 mg
- Clonidine
Long-acting benzodiazepines: Cardiac drug: Digoxin
- .lurazepam, Chlordiazepoxide, Diazepam (should not exceed >0.125 mg/d except
and Chlorazepate treating atrial arrhythmias)
399.
372 Harmonized Care for Older Patients : .ocus on Hospitalized Patients
ÂÒ·ÕèÁÕ¤ÇÒÁàÊÕè§ÊÙ§µ‹Í¼ÙŒÊÙ§ÍÒÂØ ÂÒ·ÕèÁÕ¤ÇÒÁàÊÕè§µ‹Í¼ÙŒÊÙ§ÍÒÂØ ᵋ¹ŒÍ¡NjÒ
Doses of short-acting benzodiazepines: Antiplatelet aggregation: Short-acting
daily doses greater than dipyridamole
- Lorazepam 3 mg, Alprazolam 2 mg, Antimigraine: Ergot mesyloids
Temazepam 15 mg, Triazolam 0.25 mg H2 receptor blockers: Cimetidine
Barbiturates (except phenobarbital) Antianemics: .errous sulfate >325 mg/d
Antipsychotics: Thioridazine
Opioids: Pentazocine, Meperidine
Antihypertensives:
Methyldopa, Short acting nifedipine
Antiarrhythmics: Disopyramide
Hypoglycemics: Chlorpropamide
Antiplatelet aggregating agents:
Ticlopidine
Muscle relaxants and antispasmodics:
Methocarbamol, Carisoprodol,
Chlorzoxazone, Cyclobenzaprine,
Orphenadrine and Oxybutynin
Gastrointestinal antispasmodic drugs:
Dicyclomine,Hyoscyamine, Propantheline,
Belladonna alkaloids, and Clidinium-
chlordiazepoxide (Librax)
Anticholinergics and antihistamines:
Chlorpheniramine, Diphenhydramine,
Hydroxyzine, Cyproheptadine, Promethazine
and Diphenhydramine
NSAIDs: Indomethacin
Long-term use of full-dosage, longer half
-life, non–COX-selective NSAIDs:
Naproxen and Piroxicam
Laxatives: Mineral oil
Long-term use of stimulant laxatives:
Bisacodyl, Cascara sagrada except
in the presence of opiate analgesic use
ËÁÒÂà赯 ´Ñ´á»Å§¨Ò¡ .ick DM, Cooper JW, Wade WE, et al(16)
384 Harmonized Care for Older Patients : .ocus on Cognition
àÍ¡ÊÒÃ͌ҧÍÔ§
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412.
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àǪÈÒʵ÷¹Âؤ 2553
Ñ 439
Hemiballism
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è Õ è Ø
áÅÐÊÒÁÒö·íÒãËŒ¤¹ä¢ŒÁÕ exhaustion 䴌͋ҧÁÒ¡ ᵋÊǹãË‹ hemiballism ÁÑ¡¨ÐËÒÂä»àͧ ã¹
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¡Ã³Õ·Õè hemiballism äÁ‹ËÒÂä»àͧËÅѧ¡ÒõԴµÒÁ໚¹àÇÅÒ¹Ò¹¾ÍÊÁ¤Çà ÊÁ¤ÇþԨÒóҶ֧¡Òü‹Ò
µÑ´ «Öè§ÁÕÃÒ§ҹ¡ÒüšÒü‹ÒµÑ´·Õè´Õ·Ñ駨ҡ thalamotomy ààÅÐ pallidotomy ¼Å¡Òü‹ÒµÑ´¼ÙŒ»†ÇÂ
persistent hemiballism 1 ÃÒ´ŒÇÂÇÔ¸Õ pallidotomy ¾ºÇ‹Ò hemiballism ËÒÂä»ã¹¡ÒõԴµÒÁ 5 »‚
Tourette syndrome
»˜¨¨Øº¹ÁÕÃÒ§ҹ¼Å·Õ´¨Ò¡¡Òü‹ÒµÑ´ deep brain stimulation àോµÒàà˹‹§ target ¢Í§¡ÒÃ
Ñ è Õ í
¼‹ÒµÑ´ÂѧÁÕ¤ÇÒÁËÅÒÂËÅÒ¡ ÁÕÃÒ§ҹ¼Å¡Òü‹ÒµÑ´·Õè´Õ·Ñ駨ҡ anteromedial globus pallidus,
posterolateral globus pallidus, anterior limb of internal capsule, neuclear accumben ààÅÐ medial
thalamus «Ö§ÁÕÃÒ§ҹ¨íҹǹ¼Ù»ÇÂÁÒ¡·ÕÊ´ â´Â¨Ð target ·Õè centromedian parafasicular complex
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(CM-Pfc) ËÇÁ¡Ñº Ventral oraoanterior nucleus (VOa) ¢Í§ thalamus26 ¼Å¡Òü‹ÒµÑ´¼Ù»Ç 2 ÃÒÂ
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´ŒÇÂÇÔ¸Õ bilateral CM-Pfc-VOa deep brain stimulation ààÅÐÍÕ¡ 1 ÃÒ´ŒÇÂÇÔ¸Õ bilateral pallidal deep
brain stimulation ¾ºÇ‹Òª‹ÇÂãËŒ motor tics ààÅÐ vocal tics ´Õ¢¹Öé
àÍ¡ÊÒÃ͌ҧÍÔ§
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¹Í¡¨Ò¡¹Õé¼ÙŒà¢Õ¹ÁÕ¤ÇÒÁàËç¹Ç‹Ò 㹺ÃÔº·¢Í§Êѧ¤Áä·Â »˜¨¨Ñ·ÕèÊíÒ¤ÑÍÕ¡¢ŒÍ·Õè¤ÇùíÒÁÒ
¾Ô¨ÒÃ³Ò ¤×Í àÈÃɰ°Ò¹Ð¢Í§¼Ù»Ç ¡µÑÇÍ‹ҧઋ¹ ÂÒ fluoxetine áÁŒ¨ÐÁÕËÅÑ¡°Ò¹Ê¹ÑºÊ¹Ø¹ã¹¡ÒÃ
Œ †
ÃÑ¡ÉÒÍÒ¡ÒëÖÁàÈÃŒÒã¹ MTBI ¹ŒÍÂ¡Ç‹Ò sertraline ᵋ¼Å¢ŒÒ§à¤Õ§¹ŒÍÂà·‹Òæ¡Ñ¹ áÅÐÃÒ¤Ò¶Ù¡¡Ç‹Òà¡Ô¹
10 à·‹Ò á¾·Â¤ÇõŒÍ§àʹͷҧàÅ×Í¡Í×¹æ áÅÐãËŒ¢ÍÁÙÅ»ÃСͺ¡ÒõѴÊÔ¹ã¨á¡‹¼»ÇÂËÃ×ÍÒµÔ´ÇÂ
è Œ ÙŒ † Œ
áÁŒ·Ò§àÅ×Í¡Í×¹æ ¹Ñ¹ÍÒ¨ÁÕËÅÑ¡°Ò¹·Ò§ÇÔ·ÂÒÈÒʵÃÁÒʹѺʹع¹ŒÍ¡NjҡçµÒÁ á¹Ç¤ÇÒÁ¤Ô´¹ÕÊÍ´
è é é
¤ÅŒÍ§¡Ñº¹ÔÂÒÁ¡ÒÃ㪌ÂÒÍ‹ҧÊÁà˵ØÊÁ¼Å (rational drug use) ¢Í§Í§¤¡ÒÃ͹ÒÁÑÂâÅ¡·ÕÇÒ “Rational è‹
use of drugs requires that patients receive medications appropriate to their clinical needs, in
doses that meet their own individual requirements for an adequate period of time, and the
lowest cost to them and their community.” (14)
484.
àǪÈÒʵ÷¹Âؤ 2553
Ñ 457
µÒÃÒ§·Õè 2 ¡ÒÃ㪌ÂÒÃÑ¡ÉÒ neuropsychiatric symptoms ã¹¼ÙŒ»†Ç MTBI (11, 15-17)
Neuropsychiatric Symptoms ÂÒ ¢¹Ò´àÃÔÁµŒ¹ (mg/day) ¢¹Ò´ÂÒ໇ÒËÁÒ (mg/day)
è
Depression Sertraline 25 25 - 200
Citalopram 10 20 - 50
Fluoxetine 10 20 - 40
Amitriptyline a 10 - 25 75 - 250
Cognitive disturbance Methylphenidate 5 - 10 10 - 30 (0.25 - 0.3 mg/kg)
Donepezil 5 5 - 10
Rivastigmine 3 3 - 12
Bromocriptine 2.5 < 100
Aggressiveness b Propanolol 20 - 30 60 - 400
Pindolol 40 40 - 100
Buspirone 10 45 - 60
Sodium valproate 200 - 500 750 - 1,000
Carbamazepine 200 - 400 400 - 1200
Psychosis Olanzapine c 5 5 - 20
Haloperidol c 2-5 < 10
Mania Sodium valproate 200 - 500 750 - 1,000
Insomnia Trazodone 25 - 50 50 - 150
a
㪌Í‹ҧÃÐÁÑ´ÃÐÇѧ à¹×ͧ¨Ò¡ÂÒÅ´ seizure threshold
è
b
ÍÒ¨ÃÑ¡ÉÒâ´Â㪌ÂÒÃÑ¡ÉÒÍÒ¡Òà depression ã¹µÒÃҧ䴌ઋ¹¡Ñ¹
c
㪌¢¹Ò´µèÒáÅÐÃÐÂÐÊѹ෋ҷըÒ໚¹ à¹×ͧ¨Ò¡ÂҢѴ¢ÇÒ§¡Òÿ„¹¿Ù´Ò¹ cognition
í é èí è œ Œ
ÊÃØ»
Neuropsychiatric disorders ÊÒÁÒö¾ºä´ŒºÍ¶֧˹֧ã¹ÊÒÁ¢Í§¼Ù»Ç·ÕÁÕ mild traumatic
‹ è Œ † è
brain injury Ê‹§¼Å¡Ãзºµ‹ÍÊØ¢ÀÒ¾áÅФسÀÒ¾ªÕǵ¢Í§¼Ù»ÇÂáÅФÃͺ¤ÃÑÇä´ŒÁÒ¡ áÅÐ໚¹»˜ËÒ
Ô Œ †
·Ò§ÊÒ¸ÒÃ³ÊØ¢·ÕÊÒ¤Ñ ºØ¤Åҡ÷ҧ¡ÒÃᾷ¨§¤ÇÃཇÒÃÐÇѧ áÅлÃÐàÁÔ¹ÍÒ¡Òà à¾×ÍãËŒ¡ÒÃÃÑ¡ÉÒ
èí Ö è
á¡‹¼»ÇÂÍ‹ҧàËÁÒÐÊÁ
ÙŒ †
àÍ¡ÊÒÃ͌ҧÍÔ§
1. Suriyawongpaisal P, Kanchanasut S. Road traffic injuries in Thailand: Trends, selected underlying determinants
and status of intervention. Injury Control and Safety Promotion. 2003;10(1-2):95-104.
2. Massagli TL, Fann JR, Burington BE, Jaffe KM, Katon WJ, Thompson RS. Psychiatric illness after mild
traumatic brain injury in children. Arch Phys Med Rehabil. 2004;85(9):1428-34.
3. Schwarzbold M, Diaz A, Martins ET, Rufino A, Amante LN, Thais ME, et al. Psychiatric disorders and
traumatic brain injury. Neuropsychiatr Dis Treat. 2008;4(4):797-816.
485.
458 Neuropsychiatric Disorders after Mild Traumatic Brain Injury
4. Fann JR, Burington B, Leonetti A, Jaffe K, Katon WJ, Thompson RS. Psychiatric illness following traumatic
brain injury in an adult health maintenance organization population. Arch Gen Psychiatry. 2004;61(1):53-61.
5. Rogers JM, Read CA. Psychiatric comorbidity following traumatic brain injury. Brain Inj. 2007;21(13-14):1321-
33.
6. Petchprapai N, Winkelman C. Mild traumatic brain Injury: determinants and subsequent quality of life. a review
of the literature. Journal of Neuroscience Nursing. 2007;39(5):13.
7. Mild Traumatic Brain Injury Committee ACoRM, Head Injury Interdisciplinary Special Interest Group. Definition
of mild traumatic brain injury. Journal of Head Trauma Rehabilitation. 1993;8(3):86-7.
8. Silver JM, McAllister TW, Arciniegas DB. Depression and cognitive complaints following mild traumatic brain
injury. Am J Psychiatry. 2009;166(6):653-61.
9. Koponen S, Taiminen T, Kurki T, Portin R, Isoniemi H, Himanen L, et al. MRI findings and Axis I and II
psychiatric disorders after traumatic brain injury: a 30-year retrospective follow-up study. Psychiatry Res.
2006;146(3):263-70.
10. Bryant RA, O’Donnell ML, Creamer M, McFarlane AC, Clark CR, Silove D. The Psychiatric Sequelae of
Traumatic Injury. Am J Psychiatry. 2010;167(3):312-20.
11. Lombardi F. Pharmacological treatment of neurobehavioural sequelae of traumatic brain injury. European
Journal of Anaesthesiology. 2008;25(Suppl 42):131-6.
12. Guilmette TJ, Paglia MF. The public’s misconceptions about traumatic brain injury: a follow up survey. Archives
of Clinical Neuropsychology. 2004;19(2):183-9.
13. Swift TL, Wilson SL. Misconceptions about brain injury among the general public and non-expert health
professionals: an exploratory study. Brain Injury. 2001;15:149-65.
14. WHO. The Rational Use of Drugs: Report of the Conference of Experts. Geneva: WHO,1985.
15. Fann JR, Hart T, Schomer KG. Treatment for Depression after Traumatic Brain Injury: A Systematic Review.
Journal of Neurotrauma. 2009;26(12):2383-402.
16. Warden DL, Gordon B, McAllister TW, Silver JM, Barth JT, Bruns J, et al. Guidelines for the Pharmacologic
Treatment of Neurobehavioral Sequelae of Traumatic Brain Injury. Journal of Neurotrauma. 2006;23(10):1468-
501.
17. Silver JM, Yudofsky SC, Hales RE. Neuropsychiatric aspects of traumatic brain injury. In: Yudofsky SC, Hales
RE, editors. The American Psychiatric Publishing textbook of neuropsychiatry and behavioral neurosciences:
American Psychiatric Publishing; 2008. p. 595-648.
àǪÈÒʵ÷¹Âؤ 2553
Ñ 477
7. Yaquinto JJ, Harms SE, Siemers PT, .lamig DP, Griffey RH, .oreman ML. Arterial injury from penetrating
trauma: evaluation with single-acquisition fat-suppressed MR imaging. Am J Roentgenol. 1992;158(3):631-3.
8. Catalano C, .raioli ., Laghi A, Napoli A, Bezzi M, Pediconi ., et al. Infrarenal aortic and lower-extremity arterial
disease: diagnostic performance of multi-detector row CT angiography. Radiology. 2004;231(2):555-63.
9. Katz DS, Hon M. CT angiography of the lower extremities and aortoiliac system with a multi-detector row
helical CT scanner: promise of new opportunities fulfilled. Radiology. 2001;221(1):7-10.
10. Martin ML, Tay KH, .lak B, .ry PD, Doyle DL, Taylor DC, et al. Multidetector CT angiography of the aortoiliac
system and lower extremities: a prospective comparison with digital subtraction angiography. Am J Roentgenol.
2003;180(4):1085-91.
11. Ota H, Takase K, Igarashi K, Chiba Y, Haga K, Saito H, et al. MDCT compared with digital subtraction
angiography for assessment of lower extremity arterial occlusive disease: importance of reviewing cross-
sectional images. Am J Roentgenol. 2004;182(1):201-9.
12. Rubin GD, Schmidt AJ, Logan LJ, Sofilos MC. Multi-detector row CT angiography of lower extremity arterial
inflow and runoff: initial experience. Radiology. 2001;221(1):146-58.
13. .ishman EK, Horton KM, Johnson PT. Multidetector CT and three-dimensional CT angiography for suspected
vascular trauma of the extremities. Radiographics. 2008 ;28(3):653-65; discussion 65-6.
14. Rieger M, Mallouhi A, Tauscher T, Lutz M, Jaschke WR. Traumatic arterial injuries of the extremities: initial
evaluation with MDCT angiography. Am J Roentgenol. 2006;186(3):656-64.
15. Pieroni S, .oster BR, Anderson SW, Kertesz JL, Rhea JT, Soto JA. Use of 64-row multidetector CT angiography
in blunt and penetrating trauma of the upper and lower extremities. Radiographics. 2009;29(3):863-76.
488 Imaging of Trauma : Abdominal Trauma
àÍ¡ÊÒÃ͌ҧÍÔ§
1. Rhea JT. CT of Abdominal Trauma in Mann .A. Emergency radiology categorical course in diagnostic
radiology RSNA 2004 Syllabus, 2004:91-112
2. .eliciano DV, Mattox KL, Moore EE. Trauma, 6th ed. New York: McGraw-Hill companies, 2008:261-328
3. Korner M, Krotz MM, Degenhart C, et al. Current role of emergency US in patients with major trauma.
Radiographic 2008;28:225-44
4. Shanmuganathan K, Killeen KL. Imaging of abdominal trauma in Mirvis SE, Shanmuganathan K. Imaging of
trauma and critical care, 2nd ed. Philadelphia: WB Saunders, 2003:369-517
5. Yoon W, Jeong YY, Kim JK, et al. CT in blunt liver trauma. Radiographic 2005;25:87-104
6. Yaghmai V. Splenic trauma and surgery in Gore RM, Levine MS. Textbook of gastrointestinal radiology, 3rd ed.
Philadelphia: WB Saunders, 2008:2051-64
7. Alonso RC, Nacenta SB, Martinez PD, et al. Kidney in danger: CT findings of blunt and penetrating renal
trauma. Radiographics 2009; 2033-53
8. Dunnick NR, Sandler CM, Newhouse JH, et al. Urinary tract trauma in Textbook of uroradiology, 3rd ed.
Philadelphia: Lippincott Williams & Wilkins, 2001:451-83
9. Ramchandani P, Buckler PM. Imaging of genitourinary trauma. AJR 2009;192:1514-23
10. Vaccaro JP, Brody JM. CT cystography in the evaluation of major bladder trauma. Radiographic 2000;20:1373-
81
11. Brody JM, Leighton DB, Murphy BL, et al. CT of blunt trauma bowel and mesenteric injury: typical findings and
pitfalls in diagnosis. Radiographics 2000;20:1525-36
516.
àǪÈÒʵ÷¹Âؤ 2553
Ñ º··Õè 489
68
Traumatic Cerebrovascular Injury : Neurosurgical Perspective
ÍÒ¨Òà¹ÒÂá¾·ÂàÍ¡ÇØ²Ô ¨Ñ¹á¡ŒÇ1,2
ÍÒ¨Òà¹ÒÂᾷ·ÇÕÈÑ¡´Ôì àÍ×éͺØÒÇѲ¹1,2
ÃͧÈÒʵÃÒ¨ÒàᾷÂËÔ§ÍѪÅÕ ªÙâè¹2
1
ÀÒ¤ÇÔªÒÈÑÅÂÈÒʵà ¤³Ðá¾·ÂÈÒʵÃÈÔÃÔÃÒª¾ÂÒºÒÅ ÁËÒÇÔ·ÂÒÅÑÂÁËÔ´Å
2
ÀÒ¤ÇÔªÒÃѧÊÕÇ·ÂÒ ¤³Ðá¾·ÂÈÒʵÃÈÃÃÒª¾ÂÒºÒÅ ÁËÒÇÔ·ÂÒÅÑÂÁËÔ´Å
Ô ÔÔ
ÀÒÇÐ traumatic cerebrovascular injury ໚¹ÀÒÇзվºäÁ‹ºÍÂᵋÁ¤ÇÒÁÊíÒ¤Ñ «Ö§ÍÒ¨
è ‹ Õ è
·íÒãËŒ¼ÙŒ»†Ç¶֧ᡋªÕÇÔµ ¶ŒÒãËŒ¡ÒÃÃÑ¡ÉÒäÁ‹àËÁÒÐÊÁÍ‹ҧ·Ñ¹·‹Ç§·Õ ¢³Ð¹ÕéÂѧäÁ‹ÁÕ¡ÒÃÃÒ§ҹã¹
»ÃÐà·Èä·Â áµ‹ÍØºÑµÔ¡Òó¨Ò¡ÃÒ§ҹ¢Í§µ‹Ò§»ÃÐà·ÈÍÂÙ‹ÃÐËNjҧ 0.18-1.55 % ¢Í§¼ÙŒ»†ÇÂ
·ÕÃºÍØºµà赯 ¡ÒÃÃÑ¡ÉÒ¼Ù»ÇÂã¹¡ÅØÁ¹Õ§ÁÕ¤ÇÒÁ«Ñº«ŒÍ¹ÁÒ¡¢Ö¹à¹×ͧ¨Ò¡¼Ù»ÇÂÁÑ¡ÁÕ¡ÒúҴà¨çºÃкº
èÑ Ñ Ô Œ † ‹ é Ôè é è Œ †
Í׹ËÇÁ´ŒÇÂ
è
㹺·¤ÇÒÁ¹Õ¨Ð¤Ãͺ¤ÅØÁà¹×ÍËҴѧ¹Õé
é é
1. Classification of traumatic cerebrovascular injury
1.1 Anatomical consideration
1.2 Pathological consideration
2. ¡ÒôÙáżٻÇ·ÕÁÀÒÇÐ traumatic cerebrovascular injury (Evaluation and treatment
Œ † è Õ
option for traumatic cerebrovascular injury)
Classification of traumatic cerebrovascular injury
ã¹»˜¨¨Øº¹ÂѧäÁ‹Á¡ÒèíÒṡ traumatic cerebrovascular injury ·Õ໚¹·ÕÂÍÁÃѺ«Ö§ÍÒ¨à¹×ͧ
Ñ Õ è è è è
ÁÒ¨Ò¡¡ÒúҴà¨çºÁÕËÅÒ¡Åä¡áÅоÂÒ¸ÔÊÀÒ¾ÁÕä´ŒËÅÒ¡ËÅÒ 㹷Õè¹Õé¨Ð¢Í¨íÒṡ traumatic
cerebrovascular injury µÒÁËÑÇ¢ŒÍµ‹Ò§æ´Ñ§¹Õé
By mechanisms of injury
Penetrating cerebrovascular injury
Nonpenetrating cerebrovascular injury
Iatrogenic injury
Cranial injury with secondary cerebrovascular injury
517.
490 Traumatic Cerebrovascular Injury : Neurosurgical Perspective
By location of injury
Cervical portion injury
Skull base portion injury
Intracranial portion injury
By vascular type injury
Arterial system injury
Venous system and dural sinus injury
By arterial distribution
Carotid artery injury
Common carotid artery injury
Internal carotid artery injury
External carotid artery injury
Vertebral artery injury
By pathological finding
Arterial side
Occlusion
Dissection
.alse aneurysm
Arteriovenous fistula
Venous side
Dural tears
Compression of the pial vein and venous thrombosis
ã¹·Õè¹Õé¨Ð¢ÍÊÃØ»à»š¹ 2 ¨íҾǡà¾×èͧ‹Òµ‹Í¤ÇÒÁࢌÒ㨤×Í â´ÂµíÒá˹‹§¡ÒúҴà¨çº·Ò§
¡ÒÂÇÔÀÒ¤ (by anatomical consideration ) áÅÐ â´Â¾ÂÒ¸ÔÊÀÒ¾·Õà¡Ô´¢Ö¹ (by pathological finding)
è é
¡ÒÃẋ§â´ÂµíÒá˹‹§¡ÒúҴà¨çº·Ò§¡ÒÂÇÔÀÒ¤
ICA Relevant Regional Anatomy Remark
Cervical carotid artery Cervical spine Carotid dissection, Carotid
occlusion : Cerebral emboli
Petrous carotid artery Temporal bone, Ear ossicles, Carotid occlusion : Cerebral
Lower Cranial Nerve emboli
Cavernous carotid artery Cavernous sinus, Sphenoid sinus, .alse carotid aneurysm : massive
Cranial Nerve III, IV, V1, V2 epistaxis, Subarachnoid hemorrhage
(intradural extension)
àǪÈÒʵ÷¹Âؤ 2553
Ñ 493
¡ÒûÃÐàÁÔ¹¼ÙŒ»†Ç·ÕèʧÊÑÂÀÒÇÐ traumatic cerebrovascular injury
1. Basic and advanced trauma life support Âѧ໚¹¡ÒÃÃÑ¡ÉÒàº×ͧµŒ¹·ÕÁ¤ÇÒÁ¨íÒ໚¹
é è Õ
2. »ÃÐàÁÔ¹ neurological deficit
3. ¡ÒÃÊ׺¤Œ¹à¾ÔÁàµÔÁ
è
3.1 CT áÅÐ CTA
໚¹¡ÒÃÊ׺¤Œ¹·ÕÊÒÁÒöµÃǨËÒ¾ÂÒ¸ÔÊÀÒ¾¢Í§ÊÁͧáÅÐ ¡ÒúҴà¨çº¢Í§ËÅÍ´
è
àÅ×Í´ä´Œ¾ÃŒÍÁ¡Ñ¹ã¹ÃÐÂÐàÇÅÒÍѹÊÑé¹ ¹Í¡¨Ò¡¹ÕéµíÒá˹‹§¢Í§àÅ×Í´·ÕèÍÍ¡ËÃ×Í¡ÐâËÅ¡ÈÕÃÉзÕèᵡ
ÊÒÁÒöª‹ÇÂÇÒ§á¼¹¡ÒÃÃÑ¡ÉÒËÃ×Í»‡Í§¡Ñ¹ÀÒÇÐá·Ã¡«ŒÍ¹¨Ò¡¡Ò÷íÒ¼‹ÒµÑ´ CT áÅÐ/ËÃ×Í CTA Âѧ
ÁÕÊǹª‹ÇÂÊíÒËÃѺ¡ÒõԴµÒÁ¡ÒÃà»ÅÕ¹á»Å§ÀÒÂËÅѧ¡ÒÃÃÑ¡ÉÒ
‹ è
3.2 Cerebral angiogram
໚¹¡ÒÃÊ׺¤Œ¹·ÕÊÒÁÒöµÃǨËÒ ¡ÒúҴà¨çº¢Í§ËÅÍ´àÅ×Í´ä´Œ¾ÃŒÍÁ¡Ñ¹¡Ñº¡ÒÃ㪌
è
ÃѧÊÕÃÇÁÃÑ¡ÉÒä´Œã¹àÇÅÒà´ÕÂǡѹ ¹Í¡¨Ò¡¹Õ§ÊÒÁÒö»ÃÐàÁÔ¹ cerebral hemodynamic (cerebral blood
‹ éÑ
flow, collateral circulation and occlusion test)
3.3 MRI áÅÐ MRA
໚¹¡ÒÃÊ׺¤Œ¹·ÕèÊÒÁÒöµÃǨËÒ¾ÂÒ¸ÔÊÀÒ¾¢Í§ÊÁͧáÅСÒúҴà¨çº¢Í§ËÅÍ´
àÅ×Í´ä´Œ¾ÃŒÍÁ¡Ñ¹áµ‹¨Ò໚¹µŒÍ§ãªŒàÇÅÒ㹡ÒõÃǨ·Õ¹Ò¹áÅÐÍÒ¨äÁ‹àËÁÒÐÊÁ㹼ٻǷÕä´ŒÃºÍØºµÔà˵Ø
í è Œ † è Ñ
·ÕÍÒ¡ÒÃäÁ‹¤§·Õè
è
3.4 Transcranial Doppler ultrasound (TCD)
໚¹¡ÒÃÊ׺¤Œ¹·ÕÊÒÁÒöµÃǨËÒÍØºµ¡Òó¢Í§ÅÔÁàÅ×Í´ËÅØ´ÅÍÂã¹ÊÁͧ (cerebral
è Ñ Ô è
emboli) ¹Í¡¨Ò¡¹Õ§ÊÒÁÒö»ÃÐàÁÔ¹ cerebral hemodynamic (cerebral blood flow, collateral
é Ñ
circulation)
3.5 Brain SPECT without and with stress test
໚¹¡ÒÃÊ׺¤Œ¹·ÕÊÒÁÒö»ÃÐàÁÔ¹ cerebral hemodynamic (cerebral blood flow,
è
collateral circulation) ·Ñ§¹ÕÍҨ㪌ÃÇÁ¡Ñº¡ÒõÃǨÇԸ͹ઋ¹ balloon occlusion test
é é ‹ Õ ×è
¡ÒôÙáÅÃÑ¡ÉÒ¼ÙŒ»†ÇÂÁÕÀÒÇÐ traumatic cerebrovascular injury
Multidisciplinary team approach ÁÕ¤ÇÒÁÊíÒ¤ÑÍ‹ҧÂÔ§ »ÃСͺ´ŒÇ neurovascular team
è
(neurointerventionist neurosurgeon) trauma surgeon ¨Ñ¡ÉØá¾·Â á¾·ÂËÙ ¤Í ¨ÁÙ¡ ¡ÒÃÃÑ¡ÉÒÁÕ
ËÅÒÂÇÔ¸¢¹ÍÂÙ¡º¾ÂÒ¸ÔÊÀÒ¾áÅТŒÍÁÙŨҡ¡ÒÃÊ׺¤Œ¹µ‹Ò§æ´Ñ§·Õä´Œ¡Å‹ÒÇÁÒáŌǢŒÒ§µŒ¹ â´Â·ÑÇä»ÁÑ¡
Õ Öé ‹ Ñ è è
µŒÍ§ãªŒ¡ÒÃÃÑ¡ÉÒËÅÒÂÇÔ¸ÃÇÁ¡Ñ¹
Õ‹
Goal of treatment for arterial injury
1. »‡Í§¡Ñ¹ÀÒÇÐàÅ×Í´ÍÍ¡ (acute hemorrhage or hemorrhagic infarction)
2. »‡Í§¡Ñ¹ÀÒÇÐÊÁͧ¢Ò´àÅ×Í´ (acute or late cerebral infarction)
521.
494 Traumatic Cerebrovascular Injury : Neurosurgical Perspective
2.1 »‡Í§¡Ñ¹ÀÒÇÐÅÔÁàÅ×Í´ (emboli)
è
2.2 »‡Í§¡Ñ¹ÀÒÇÐàÅ×Í´ä»àÅÕ§ÊÁͧäÁ‹à¾Õ§¾Í (inadequate cerebral blood flow)
é
·Ò§àÅ×͡㹡ÒÃÃÑ¡ÉÒ
1. Conservative treatment and/or medical treatment
2. Endovascular treatment
3. Surgical treatment
¡ÒÃàÅ×Í¡ÇÔ¸¡ÒÃÃÑ¡ÉÒNjҨÐ㪌Ǹ㴹ѹ¢Ö¹ÍÂÙ¡ºËÅÒ»˜¨¨Ñ ઋ¹
Õ Ô Õ é é ‹ Ñ
1. µíÒá˹‹§¢Í§ÃÍÂâä (Location of pathology)
2. ÅѡɳТͧ¾ÂÒ¸ÔÊÀÒ¾ áÅСÒôíÒà¹Ô¹âä (Pathology and natural history)
3. Hemodynamic cerebral circulation áÅÐ cerebral reserve
4. ¤ÇÒÁàÊÕ§áÅмÅá·Ã¡«ŒÍ¹·ÕÍÒ¨à¡Ô´¢Ö¹¨Ò¡¡ÒÃÃÑ¡ÉÒᵋÅÐÇÔ¸Õ (Risk and benefit of
è è é
treatment option)
5. »ÃÐʺ¡Òó¢Í§á¾·Â¼·Ò¡ÒÃÃÑ¡ÉÒ
ÙŒ í
¡ÒÃÃÑ¡ÉÒ´ŒÇÂÇÔ¸¡ÒÃ㪌ÊÒÂÊǹ·Ò§ËÅÍ´àÅ×Í´ (Endovascular Treatment)
Õ
1. .low preservation procedure ઋ¹ ¡ÒÃãÊ‹ stent ËÃ×Í balloon à¾×ÍÍØ´µíÒá˹‹§¢Í§ÃÍÂÃÑÇ
è è
¢Í§àÊŒ¹àÅ×Í´á´§
2. .low disruption procedure ઋ¹ ¡ÒÃãÊ‹ coil, detachable balloon ËÃ×Í¡ÒÃÍØ´´ŒÇ¡ÒÇ
(glue embolization)
¡ÒÃÃÑ¡ÉÒ´ŒÇÂÇÔ¸¼ÒµÑ´ (Surgical treatment)
Õ ‹
â´Â¨Ðẋ§ÇÔ¸¡ÒÃÃÑ¡ÉÒ໚¹ 2 ÇÔ¸¤Í
Õ Õ ×
1. .low preservation procedure
2. .low disruption procedure without or with flow augmentation procedure
500 Interventional Radiology Management in Traumatic Patient
¼Å¡ÒÃÃÑ¡ÉÒ´ŒÇÂÇԸʹËÅÍ´àÅ×ʹ㹼ٻǷÕÁ¡ÒúҴà¨çº¢Í§äµ¹Ñ¹ä´Œ¼Å´ÕÁÒ¡ã¹»˜¨¨Øº¹
ÕØ Œ † è Õ é Ñ
ÃÒ§ҹ¤ÇÒÁÊíÒàÃ稻ÃÐÁÒ³ 84-100% ÀÒÇÐá·Ã¡«ŒÍ¹·ÕÍÒ¨à¡Ô´¢Ö¹¾ºä´Œ¹Í 䴌ᡋ ÍÒ¡ÒûǴ
(3)
è é Œ
post embolization syndrome ËÃ×ÍÀÒÇСÒâҴàÅ×Í´¢Í§äµ«Ö§â´Â·ÑÇ仼ٻǨÐäÁ‹ÁÍÒ¡ÒÃ
è è Œ † Õ
ÀÂѹµÃÒµ‹ÍÁŒÒÁ (Traumatic splenic injury)
ÁŒÒÁ໚¹ÍÇÑÂÇзվº¡ÒúҴà¨çºä´ŒºÍ¨ҡ¡ÒÃà¡Ô´Íغµà赯 áÅÐà¹×ͧ¨Ò¡à»š¹ÍÇÑÂÇзÕÁàÅ×Í´
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Œ † è Õ Ñ è
ª¹Ô´áÅеíÒá˹‹§¢Í§¡ÒÃà¡Ô´¾ÂÒ¸ÔÊÀÒ¾ ÃÇÁ·Ñ§ª‹ÇÂÇÒ§á¼¹¡ÒÃÃÑ¡ÉÒ ËÒ¡¾º¾ÂÒ¸ÔÊÀҾઋ¹¨Ø´
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è Ñ í Ñ
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Ñ Œ † è Õ
ºÒ´à¨çº¢Í§ÁŒÒÁÍÂ‹Ò§ÃØ¹áç·Ñ§ã¹º·ºÒ·¢Í§ preoperative surgical splenectomy áÅСÒÃÃÑ¡ÉÒ
é
ẺäÁ‹µÍ§¼‹ÒµÑ´ ËÅÑ¡¡Òâͧ¡ÒÃÍØ´ËÅÍ´àÅ×ʹẺ¹Õ¹¹ à¹×ͧÁÒ¨Ò¡ ÁŒÒÁ໚¹ÍÇÑÂÇзÕÁÕ collateral
Œ é Ñé è è
504 Interventional Radiology Management in Traumatic Patient
¼Å¡ÒÃÃÑ¡ÉÒ´ŒÇÂÇÔ¸¡ÒÃÍØ´ËÅÍ´àÅ×Í´¹Ñ¹ÍÂÙ·»ÃÐÁÒ³ 85-100%(7) áÅÐÀÒÇÐá·Ã¡«ŒÍ¹·Õà¡Ô´
Õ é ‹ Õè è
¢Ö¹¾ºä´Œ¹Í ઋ¹ non target embolization ËÃ×Í puncture site complication ໚¹µŒ¹
é Œ
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154:352–5.
2. Hagiwara A, Sakaki S, Goto H, et al. The Role of Interventional Radiology in the Management of Blunt Renal
Injury: A Practical Protocol J Trauma. 2001;51:526–31.
3. .lacker R, Paolini RM, Lima S. Management of traumatic hematuria by selective renal artery embolization. J
Urol 1984;132:662-7.
4. Drooz AT, Curtis AL, Allen TE, et al. Quality improvement guidelines for percutaneous transcatheter embolization.
J Vasc Interv Radiol 2004;14:S237-42.
5. Haan JM, Biffl W, Knudson M. Splenic embolization revisited: a multicenter review. J Trauma 2004;56:542-7.
6. .angio P, Asehnoune K, Edouard A, et al. Early embolization and vasopressor administration for management
of life-threatening hemorrhage from pelvic fracture. J Trauma 2005;58:978-84.
7. Teitelbaum GP, Reed RA, Larsen D, et al. Microcatheter embolization of non-neurologic traumatic vascular
lesions. J Vasc Interv Radiol 1993;4:149-54.
8. Michael J. Pentecost. Interventional therapies of hepatic malignancy. In: Stanley Baum, Michael J. Pentecost,
eds. Abrams’ Angiography Interventional radiology. Philadelphia: Lippincott Williams & Wilkins, 2006:516-35.
532.
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70
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(Snoring and Obstructive Sleep Disordered Breathing; OSDB)
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ÀÒ¤ÇÔªÒâʵ ¹ÒÊÔ¡ ÅÒÃÔ§«Ç·ÂÒ ¤³Ðá¾·ÂÈÒʵÃÈÃÃÒª¾ÂÒºÒÅ ÁËÒÇÔ·ÂÒÅÑÂÁËÔ´Å
Ô ÔÔ
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è è ‹ é
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è è è Õ è
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è é è è è é
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µ‹ÍÁ·ÍūԹ (tonsils) ⤹ÅÔ¹ (base of tongue) ¨¹¶Ö§ºÒ§Ê‹Ç¹¢Í§¡Å‹Í§àÊÕ§ (larynx) ·Ñ§¹ÕàÊÕ§¡Ã¹
é é é
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‹ Œ Õè Ñ
(sign) ·ÕÊÒ¤ÑÍ‹ҧ˹֧¢Í§¡ÅØÁâäÀÒÇÐËÒÂ㨼Դ»¡µÔ¢³ÐËÅѺª¹Ô´ÍØ´¡Ñ¹ (obstructive sleep-
èí è ‹ é
disordered breathing; OSDB) â´Ââä¡ÅØ‹Á¹ÕéËÒ¡àÃÕ§µÒÁÅíҴѺ¤ÇÒÁÃØ¹áç¨Ò¡¹ŒÍÂä»ÁÒ¡
¨Ð»ÃСͺ´ŒÇ ÀÒÇй͹¡Ã¹¸ÃÃÁ´Ò (primary snoring), ¡ÅØÁÍÒ¡Òèҡ·Ò§à´Ô¹ËÒÂã¨Ê‹Ç¹µŒ¹µÕº
‹
᤺ (upper airway resistance syndrome; UARS) ¡ÅØÁÍÒ¡ÒÃËÂØ´ËÒÂ㨢³ÐËÅѺª¹Ô´ÍØ´¡Ñ¹
‹ é
(obstructive sleep apnea (OSA) ËÃ×Í obstructive sleep apnea hypopnea syndrome; OSAHS)
áÅкҧ¤Ãѧ ÍÒ¨¨Ñ´ obesity hypoventilation (Pickwickian) syndrome ÃÇÁÍÂÙ´ÇÂ(1)
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3.2.1 ¡ÒÃʋͧ¡ÅŒÍ§ÀÒÂã¹·Ò§à´Ô¹ËÒÂã¨Ê‹Ç¹µŒ¹ (Upper airway endoscopy) ÊÒÁÒö
㪌䴌·§ flexible ËÃ×Í rigid endoscope â´Â·íÒã¹¢³Ð·Õ¼»ÇÂÍÂÙã¹·‹Ò¹Ñ§ËÃ×Í·‹Ò¹Í¹¡çä´Œ ¹Í¡¨Ò¡
Ñé è ÙŒ † ‹ è
¹Õ§ÍÒ¨µÃǨ㹼ٻǺҧÃÒ¢³Ð·ÕËÅѺ (sleep endoscopy) «Ö§¨Ðä´Œ¢ÍÁÙÅ·Õ໚¹¶Ù¡µŒÍ§ÁÒ¡¢Ö¹(31)
é Ñ Œ † è è Œ è é
3.2.2 ¡Òö‹ÒÂÀÒ¾ÃѧÊÕ (X-ray) ºÃÔàdz¡ÐâËÅ¡ÈÕÃÉРઋ¹ film lateral skull, lateral
cephalometry, ËÃ×Í panoramic view à¾×Í´Ùâ¤Ã§ÊÌҧ¡Ãд١ãºË¹ŒÒ ¢Ò¡ÃÃä¡Ã áÅÐà¹×ÍàÂ×ͧ͢·Ò§
è é è
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(jaw surgery) ໚¹µŒ¹
3.2.3 ¡ÒõÃǨ¾ÔàÈÉÍ×¹ æ ઋ¹ CT scan, MRI, fluoroscopy of airway ËÃ×Í acoustic
è
analysis »˜¨¨Øº¹Âѧ㪌ã¹à¾×ͧҹÇÔ¨Â໚¹ËÅÑ¡ ᵋäÁ‹¹ÂÁ㪌㹷ҧ»¯ÔºµÔ(32)
Ñ è Ñ Ô Ñ
3.3 ¡ÒõÃǨËÒâäµÒÁÃкº (Systemic assessment)
à¾×ÍËÒâäËÇÁáÅлÃÐàÁÔ¹ÀÒÇÐá·Ã¡«ŒÍ¹¨Ò¡ OSA ËÃ×Íà¾×ÍàµÃÕÂÁ¡Òü‹ÒµÑ´ ·Ñ§¹Õé
è è é
¤ÇþԨÒóÒÊ‹§µÃǨ 㹡óշʧÊÑÂ໚¹ÃÒÂæ ä» àª‹¹ ¡ÒõÃǨ CBC (complete blood count)
Õè
à¾×Í´ÙÀÒÇÐ polycythemia ¡Òö‹ÒÂÀÒ¾ x-ray ·Ãǧ͡à¾×Í»ÃÐàÁÔ¹ÀÒÇÐ right heart failure ËÃ×Í
è è
cor pulmonale ¡ÒõÃǨ arterial blood gas áÅСÒõÃǨà¡ÕÂǡѺµ‹ÍÁä¸ÃÍ´ ઋ¹ thyroid
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function test ໚¹µŒ¹
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Œ † è Õ é é é ‹ Ñ
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Œ † Œ
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é Õ Œ †
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Œ † Ñ è è é
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Ñ Ô Ø Ô é Œ † Öé
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1. ¡ÒÃÃÑ¡ÉÒẺ͹ØÃÑ¡É (Conservative treatment)
¡ÒÃÃÑ¡ÉÒ¡ÅØÁ¹Õ¤ÇÃ໚¹¾×¹°Ò¹·ÕÊÒ¤ÑÊíÒËÃѺ¼Ù»Ç·ءÃÒ äÁ‹ÇÒ¨ÐÁÕ¤ÇÒÁÃØ¹áçÃдѺ
‹ é é èí Œ † ‹
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1.1 ¡ÒÃÅ´¹éÒ˹ѡ (Weight reduction) àËÁÒÐÊíÒËÃѺ¼Ù·Íǹ (obesity) ËÃ×Í ¼Ù·ÁÕ
í Œ Õè Œ Œ Õè
¹éÒ˹ѡà¡Ô¹ (overweight) «Ö§¨Ðª‹ÇÂÅ´¤ÇÒÁÃØ¹áç¢Í§âäŧ䴌 à¹×ͧ¨Ò¡¡ÒÃÅ´¹éÒ˹ѡ¨Ðª‹ÇÂÅ´
í è (33)
è í
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é è
â´ÂÃÇÁ´Õ¢Öé¹ ·Ñé§¹ÕéÇÔ¸Õ¡Ò÷Õèä´ŒÊíҤѷÕèÊØ´ÊíÒËÃѺ¼Å´Õã¹ÃÐÂÐÂÒÇ µŒÍ§ÍÒÈѤÇÒÁµÑé§ã¨¨Ãԧ㹡ÒÃ
à»ÅÕè¹ÃٻẺ¡ÒÃ㪌ªÕÇÔµ (life style change) ·Ñé§¡ÒäǺ¤ØÁÍÒËÒà ÃÇÁ¶Ö§ ¡ÒÃÍÍ¡¡íÒÅѧ¡ÒÂ
·ÕàËÁÒÐÊÁ ໚¹µŒ¹
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é
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àǪÈÒʵ÷¹Âؤ 2553
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! Modafinil ÂÒµÑǹÕé㪌¡Ñ¹á¾Ã‹ËÅÒ ¡Åä¡¡ÒÃÍ͡ķ¸Ôì¤Ô´Ç‹Ò¹‹Ò¨Ðà¡Ô´¨Ò¡¡ÒÃà¾ÔèÁ
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! Tricyclic antidepressants áÅÐ selective serotonin reuptake inhibitor (SSRI)
! Sodium oxybate ໚¹ÂÒ·Õ໚¹ÃѺÃͧâ´Âͧ¤¡Òà .DA ã¹ÊËÃѰÍàÁÃÔ¡ÒÃ㹡ÒÃÃÑ¡ÉÒ
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1. Shipley KG, McAfee JG. Assessment in speech-language pathology. 3rded. Delmar learning: USA, 2004,
390-406
2. Crary MA, Groher ME. Introduction to adult swallowing disorders. Elsevier Science,USA, 2003.
3. Palmer JB, Drennan JC, Baba M. Evaluation and treatment of swallowing impairments. AA.P 2000; Apirl;15.
4. Burkhead LM, Sapienza CM, Rosenbek JC. Strength-training exercise in dysphagia rehabilitation: Principle,
procedures, and directions for future research. Dysphagia 2007;22 :251-265
5. Logemann JA. The role of exercise programs for dysphagia patients. Dysphagia 2005;20:139-140.
6. Johnson A., Jacobson BH. Medical speech-language pathology a practitioner’s guide. Thieme: New York,
1998.
7. McKinstry A, Tranter M, Sweeney J. Outcomes of dysphagia intervention in a pulmonary rehabilitation program.
Dysphagia 2010;25:104-11.
8. Speyer R, Baijens L, Heijnen M, Zwijnenberg I. Effects of therapy in oropharyngeal dysphagia by speech-
language therapist: a systematic review. Dysphagia 2010;25:40-6.
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ã¹·ÕÊ´¤ÇÃ䴌ú¡ÒõÃǨËÒ H. Pylori àÊÁÍ áÅÐËÒ¡¾ºÇ‹ÒÁÕ¡ÒõԴàª×Í ¤Ç÷íÒ¡ÒÃÃÑ¡ÉÒ à¾ÃÒÐä´Œ
èØ Ñ é
ÃѺ¡ÒÃÂÍÁÃѺNjҪ‹ÇÂÅ´âÍ¡ÒÊà¡Ô´ recurrent peptic ulcer 䴌͋ҧªÑ´à¨¹
References :
1. Grace H. Elta. Yamada Text book of Gastroenterology, 4th ed. 2003:698-723.
2. Christopher S. Huang,David R. Lichtenstein.Nonvariceal upper gastrointestinal bleeding.Gastroenterology clinics
of north America. 2003;32(4):1053-78.
3. Chen IC, Hung MS et al. Risk scoring systems to predict need for clinical intervention for patients with
nonvariceal upper gastrointestinal tract bleeding. Am J Emerg Med. 2007;25(7):774-9.
4. Robert A Enns,Yves M Gagnon et al. Validation of the Rockall scoring system for outcomes from non-variceal
upper gastrointestinal bleeding in a Canadian setting. World J Gastroenterology. 2006;12(28):7779-85.
581.
554 ÀÒÇÐàÅ×Í´Í͡㹷ҧà´Ô¹ÍÒËÒÃʋǹº¹
5. Hamid Hussain,Seth Lapin et al.Clinical scooring systems for determining the Prognosis of Gastrointestinal
bleeding. Gastroenterology clinics of north America. 2000;29(2):445-64.
6. Thomas J. Savides, Dennis M.Jensen.Therapeutic Gastroenterology clinics of north America Endoscopy for
Nonvariceal Gastrointestinal Bleeding. 2000;29(2):465-88.
7. Alan Barkun,Marc Bardou et al.Concensus Recommendation for Managing Patients with Nonvariceal Upper
Gastrointestinal Bleeding.Ann Intern Med. 2003;139:843-57.
8. Mitshell S. Cappell, David .rieddel.Medical Clinic of North America. 2008;92:491-509.
582.
àǪÈÒʵ÷¹Âؤ 2553
Ñ º··Õè 555
75
Management of Esophageal Varices and
Esophageal Variceal Hemorrhage
¼ÙŒª‹ÇÂÈÒʵÃÒ¨ÒàᾷÂËÔ§ÈÔÇоà äªÂ¹ØÇѵÔ
ÍÒ¨ÒàᾷÂËÔ§¹¹·ÅÕ à¼‹ÒÊÇÑÊ´Ôì
ÍÒ¨Òà¹ÒÂá¾·ÂÊØ¾¨¹ ¹ÔèÁ͹§¤
ÀÒ¤ÇÔªÒÍÒÂØÃÈÒʵà ¤³Ðá¾·ÂÈÒʵÃÈÔÃÔÃÒª¾ÂÒºÒÅ ÁËÒÇÔ·ÂÒÅÑÂÁËÔ´Å
ÀÒÇÐ portal hypertension (PH) ¤×Í ÀÒÇзÕèÁÕ¤‹Ò¤ÇÒÁᵡµ‹Ò§ÃÐËNjҧ¤ÇÒÁ´Ñ¹ã¹
ËÅÍ´àÅ×Í´´íÒ portal áÅÐËÅÍ´àÅ×Í´´íÒãË‹ (inferior vena cava) à¡Ô¹ 5 mmHg â´Â»¡µÔ
¤ÇÒÁᵡµ‹Ò§ÃÐËNjҧ¤ÇÒÁ´Ñ¹ã¹ËÅÍ´àÅ×Í´´íÒ¾Í÷Š(portal pressure gradient) ¨ÐÍÂÙÃÐËNjҧ
Ñ ‹
1-5 mm Hg ¹Í¡¨Ò¡¹Õã¹ÀÒÇÐ PH ÂѧÁÕ¡ÒÃà»ÅÕ¹àÊŒ¹·Ò§äËÅàÇÕ¹¢Í§àÅ×Í´â´Â¡ÒÃÊÌҧ portal
é è
systemic collaterals ¢Ö¹ÁÒ໚¹·Ò§ÅÑ´¢Í§àÅ×Í´«Ö§¨Ð·íÒãËŒÁ¡ÒÃäËÅàÇÕ¹¢Í§àÅ×Í´¨Ò¡ portal system
é è Õ
ࢌÒä»ÊÙÃкº¡ÒÃäËÅàÇÕ¹ systemic â´ÂµÃ§â´ÂàÅ×Í´¨ÐäÁ‹¼Ò¹µÑº àÊŒ¹àÅ×Í´ collaterals ·Õà¡Ô´¢Ö¹
‹ ‹ è é
䴌ᡋàÊŒ¹àÅ×Í´¢Í´ã¹ËÅÍ´ÍÒËÒÃ-¡ÃÐà¾ÒÐÍÒËÒà (gastroesophageal varices) àÁ×ÍÁÕ portal pressure
è
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é è é èØ
Esophageal varices and esophageal variceal hemorrhage
¤ÇÒÁªØ¡¢Í§àÊŒ¹àÅ×Í´¢Í´ã¹ËÅÍ´ÍÒËÒâͧ¼ÙŒ»†Ç·ÕèÁÕÀÒÇеѺá¢ç§·Õèä´ŒµÃǨʋͧ¡ÅŒÍ§
·Ò§à´Ô¹ÍÒËÒÃʋǹµŒ¹ (esophagogastroduodenoscopy, EGD) »ÃÐÁҳÌÍÂÅÐ 30-40 áÅоº
àÊŒ¹àÅ×Í´¢Í´ã¹ËÅÍ´ÍÒËÒö֧ 60% ã¹¼ÙŒ»†ÇµѺá¢ç§ÃÐÂÐÊØ´·ŒÒ (decompensated cirrhosis)
¨Ò¡¡ÒÃÈÖ¡ÉÒ¡ÒÃà¡Ô´¢Í§àÊŒ¹àÅ×Í´ã¹ËÅÍ´ÍÒËÒà (esophageal varices, EV) â´Â Groszmann áÅÐ
¤³Ð¾ºÇ‹Ò¤‹Ò hepatic venous pressure gradient (HVPG) ·ÕÁÒ¡¡Ç‹Ò 10 mmHg ໚¹»˜¨¨Ñº‹§ºÍ¡
è
(predictor) ·ÕÊÒ¤Ñ㹡ÒÃà¡Ô´ EV
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Ñ Ô Œ †
µ‹Í»‚áÅÐàÊŒ¹àÅ×Í´¢Í´¢¹Ò´àÅç¡ (small EV) ¨Ðâµ¢Ö¹¢ÂÒµÑÇ໚¹¢¹Ò´ãË‹ (large EV) ã¹ÍѵÃÒ
é
ÃŒÍÂÅÐ 5-30 µ‹Í»‚ âÍ¡ÒÊ·Õà¡Ô´àÊŒ¹àÅ×Í´ÍÍ¡¨Ò¡àÊŒ¹àÅ×Í´¢Í´áµ¡»ÃÐÁҳÌÍÂÅÐ 15 µ‹Í»‚ àÁ×Íà¡Ô´
è è
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Œ † Ñ Ô
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Œ † è Ô
àÅ×Í´ÍÍ¡«éÒä´ŒÀÒÂã¹ 6 ÊÑ»´ÒËáÅÐÃŒÍÂÅÐ 40-60 ¢Í§¼Ù»ÇÂ¡ÅØÁ¹Õ¨ÐàÊÕªÕǵ䴌 ´Ñ§¹Ñ¹¡Òû‡Í§¡Ñ¹
í Œ † ‹ é Ô é
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Œ † ‹ é Ñ Ô è
àÅ×Í´ÍÍ¡â´ÂµÃ§
¡ÒÃ㪌ÂÒ non-selective ß-blocker ઋ¹ propranolol ¤ÇÃà¾ÔÁ¢¹Ò´ÂÒ¨¹ÊÒÁÒöŴªÕ¾¨Ãŧ
è
ÃŒÍÂÅÐ 25 ËÃ×ÍÁÕ͵ÃҢͧªÕ¾¨Ã 50-55 ¤Ãѧ/¹Ò·Õ ʋǹ nadolol 䴌ú¤ÇÒÁ¹ÔÂÁÁÒ¡¢Ö¹à¹×ͧ¨Ò¡ãËŒ
Ñ é Ñ é è
¡Ô¹ÇѹÅФÃѧ䴌·ÒãËŒÊдǡ¡Ñº¼Ù»Ç (ᵋÂÒ¹ÕäÁ‹Áã¹»ÃÐà·Èä·Â) ã¹ÃÒ·ÕÁ¼Å¢ŒÒ§à¤Õ§¢Í§ÂÒËÃ×Í
é í Œ † é Õ è Õ
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Œ
¨Ðª‹ÇÂÅ´ portal pressure ä´Œ´Õ¢Öé¹àÁ×èÍà·Õº¡Ñº¡ÒÃ㪌 propranolol Í‹ҧà´ÕÂÇ Ê‹Ç¹¡ÒáíҨѴ
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è Õ Õè Ø Œ † è Ñ í é è Ñ é
ãËŒ·Ò TIPS ʋǹ¡Ò÷íÒ¡Òü‹ÒµÑ´ shunt ¹Ñ¹ ¾ºÇ‹Òª‹ÇÂÅ´âÍ¡ÒÊà¡Ô´àÅ×Í´ÍÍ¡«éÒᵋäÁ‹ä´ŒÅ´ÍѵÃÒ
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·ÕÁÀÒÇÐàÅ×Í´ÍÍ¡«éÒ¤ÇþԨÒóҡÒÃà»ÅÕ¹µÑº (liver transplantation) ËÇÁ´ŒÇÂ
è Õ í è
568 Embolization for Upper Gastrointestinal Hemorrhage
¢Í§¡ÒÃÃÑ¡ÉÒ´ŒÇÂÇÔ¸¡ÒÃÍØ´¡Ñ¹ËÅÍ´àÅ×Í´àÁ×Íà·Õº¡Ñº¡ÒÃʋͧ¡ÅŒÍ§àÍç¹â´Ê⤻ËÃ×Í¡Òü‹ÒµÑ´¤×Í
Õ é è
äÁ‹ÊÒÁÒö·íÒä´Œá¾Ã‹ËÅÒÂã¹âç¾ÂÒºÒÅ·ÑÇæ ä» Â¡àÇŒ¹Ê¶ÒºÑ¹·Ò§¡ÒÃá¾·ÂãË‹æ ËÃ×ÍâçàÃÕ¹
è
á¾·Âà·‹Ò¹Ñé¹ ¡ÒÃÃÑ¡ÉÒÀÒÇÐàÅ×Í´Í͡㹷ҧà´Ô¹ÍÒËÒäÇ÷íÒ¡ÒÃÍØ´¡Ñé¹ËÅÍ´àÅ×ʹËÇÁ¡Ñº
¡ÒÃʋͧ¡ÅŒÍ§àÍç¹â´Ê⤻ 㹡óբͧ¼Ù»Ç·ÕÁÕ massive arterial bleeding ¤Ç÷íÒ angiography
Œ † è
áÅÐ embolization ¡‹Í¹ ʋǹ¼Ù»Ç intermittent bleeding ¤ÇÃ䴌ú¡ÒÃʋͧ¡ÅŒÍ§àÍç¹â´Ê⤻¡‹Í¹
Œ † Ñ
´Ñ§¹Ñé¹ ¤ÇÒÁÊíÒàÃç¨ã¹¡ÒÃÃÑ¡ÉÒ¼ÙŒ»†Ç¨֧¢Öé¹ÍÂÙ‹¡Ñº¤ÇÒÁËÇÁÁ×͡ѹÍ‹ҧ´ÕÃÐËNjҧÍÒÂØÃá¾·ÂáÅÐ
ÈÑÅÂá¾·ÂÃкº·Ò§à´Ô¹ÍÒËÒà ËÇÁ¡ÑºÃѧÊÕᾷ´ҹÃѧÊÕÃÇÁÃÑ¡ÉÒ
Œ ‹
àÍ¡ÊÒÃ͌ҧÍÔ§
1. Baum ST. Arteriographic diagnosis and treatment of gastrointestinal bleeding. In: Baum ST, Pentecost MJ,
eds. Abram’s angiography interventional radiology. 2nd ed. Philadelphia, Pa: Lippincott, Williams & Wilkins,
2006;488-513.
2. Lee EW, Laberge JM. Differential diagnosis of gastrointestinal bleeding. Tech Vasc Interv Radiol 2005;7:112-
22.
3. Kuo W, Lee DE, Saad WE, Patel N, Sahler lG, Waldman DL. Superselective microcoil embolization for the
treatment of lower gastrointestinal hemorrhage. J Vasc Interv Radiol 2003;14:1503-9.
596.
àǪÈÒʵ÷¹Âؤ 2553
Ñ º··Õè 569
77
General Aspects of Tumor Microenvironment
Assistant Professor Peti Thuwajit, M.D. Ph.D.
Department of Immunology, .aculty of Medicine Siriraj Hospital, Mahidol University
Cancer is still a major problem in medicine. It is the leading cause of death in Thai
people within many years. Cancer cells could be developed from each cell type in the whole
body, especially epithelial cells. Normally epithelial cells could function as protector and
transporter, which supported by a various type of the cells beneath and nearby including connective
tissue cells, vascular cells and muscle cells. When tissues are going to pathological stage, the
immunological cells will infiltrate and play role in both promoting and repairing of the abnormal
conditions. This could be showing as inflammation and repairing processes, including fibrosis
and angiogenesis, even though the pathological stage is still exist. Carcinogenesis is one of the
inflammatory conditions which involved a numbers of cells. After epithelial cells turning to
malignant, the cancer cells will be going to infiltrate the underlying tissue layers and the cells
lying beneath become closer. They still have interaction with neighboring cells and environment
and also need supporting from their surrounding environment too.(1,2) On the other hand,
microenvironment in tumor area could suppress or destroy the cancer cells too.(1,2) The major
cells that play roles in tumor progression are including the resident cells and the infiltrated
migratory cell, for example, the circulating immunological cells. The most common resident cell
found in tumor microenvironment is fibroblast.(3) It could not only produce collagens and
extracellular matix for structural support but it could also produce a lot of peptides or small
signaling molecules that could affect tumor cell growth, survival and metastasis.(3,4) So the
control of fibroblast should be a target for cancer management.(5) Immunological cells are the
most abundant infiltrating cell in tumor microenvironment. Some of immunological cells are
residence, for example, macrophages and dendritic cells. The immunological cells which are
the major infiltrating cell in tumor microenvironment are including polymorphonuclear cells and
lymphocytes. One of the examples of the importance of immunological cells in tumor biology is
from the recent studies that showed the effect of NKG2D ligand expression in tumor biology.(6)
597.
570 General Aspects of Tumor Microenvironment
NKG2D is the lectin family receptor presented on membrane of many types of immune cells
including natural killer (NK) cells, cytotoxic T lymphocyte, !" T lymphocyte, macrophages and
some groups of helper T cell. The finding showed that regulation of NKG2D by NKG2D ligends
could affect the activity of NK cell and tumor survival. (6) In Thai people there are a polymorphism
of many types of NKG2D ligands have been reported.(7,8)
There are not only cells play role in tumor microenvironment, the extracellular matrix
molecules are also having the effect on tumor progression. Collagen could retard the migration
of cancer cells by its structure but it may promote epithelial-mesenchymal transition (EMT) and
stimulate cell migration by itself.(9) Small molecules which have cell signaling effects to tumor
cells are using this space for their actions. These small molecules could be proteins, peptides,
steroids, etc. They could regulate tumor cell growth, metastasis and also angiogenesis. Some
proteins could help tumor cells evade from immune system. One of the examples for this group
of protein is mucin. Mucin is a family of protein with heavy glycosylation. MUC1 is a mucin
found in many types of cancers, including cholangiocarcinoma. It has been hypothesized that
MUC1 production could protect tumor cells from the recognition by immune cell due to its
glycosylation as a barrier for detection.(10) In cholangiocarcinoma, MUC1 has been reported its
association with poor prognosis.(10,11) Unlike MUC1, MUC5AC and MUC6 are mucins found
increased expression in cholangiocarcinoma too but they did not show the association with
poor prognosis.(11-13) MUC6 seems to associate with good prognosis of cholangiocarcinoma in
one study.(13)
Trefoil factor family is a group of protein that could regulate the migration and invasion
in cancer metastasis process. T..1 and T..2 are found in cholangiocarcinoma but not show
association with survival of the patients.(12,13) However, due to their function, T..s are considered
as a target for study their roles in cancer metastasis. Another interesting protein is periostin, a
protein that could be produced from cancer cells and fibroblast in extracellular matrix and has
many effects to cancer including activation of cell growth, induce invasion and promote
angiogenesis. It has been reported the over-expression in cholangiocarcinoma with in vitro tumor
promoting effect.(14)
Tumor metastasis and angiogenesis are the hot topic for studying. Both processes are
needed tumor microenvironment for promoting their progression. So, tumor microenvironment
should involve in all steps of tumor progression and cells or molecules inside should be considered
as targets for studying and controlling of tumor progression. In this session will discuss about
tumor microenvironment in the current study and its propose as the target for cancer therapy.
598.
àǪÈÒʵ÷¹Âؤ 2553
Ñ 571
References
1. Mbeunkui ., Johann DJ Jr. Cancer and the tumor microenvironment: a review of an essential relationship.
Cancer Chemother Pharmacol. 2009;63(4):571-82.
2. Witz IP. The tumor microenvironment: the making of a paradigm. Cancer Microenviron. 2009;2 Suppl 1:
9-17.
3. Pietras K, Ostman A. Hallmarks of cancer: interactions with the tumor stroma. Exp Cell Res. 2010;316(8):1324-
31.
4. Chuaysri C, Thuwajit P, Paupairoj A, Chau-In S, Suthiphongchai T, Thuwajit C. Alpha-smooth muscle actin-
positive fibroblasts promote biliary cell proliferation and correlate with poor survival in cholangiocarcinoma.
Oncol Rep. 2009;21(4):957-69.
5. Plz?k J, Lacina L, Chovanec M, Dvor?nkov? B, Szabo P, Cada Z, Smetana K Jr. Epithelial-stromal interaction
in squamous cell epithelium-derived tumors: an important new player in the control of tumor biological properties.
Anticancer Res. 2010;30(2):455-62.
6. Champsaur M, Lanier LL. Effect of NKG2D ligand expression on host immune responses. Immunol Rev.
2010;235(1):267-85.
7. Romphruk AV, Romphruk A, Naruse TK, Raroengjai S, Puapairoj C, Inoko H, Leelayuwat C. Polymorphisms
of NKG2D ligands: diverse RAET1/ULBP genes in northeastern Thais. Immunogenetics. 2009;61(9):
611-7.
8. Jumnainsong A, Romphruk AV, Jearanaikoon P, Klumkrathok K, Romphruk A, Luanrattanakorn S, Leelayuwat
C. Association of polymorphic extracellular domains of MICA with cervical cancer in northeastern Thai population.
Tissue Antigens. 2007;69(4):326-33.
9. Medici D, Nawshad A. Type I collagen promotes epithelial-mesenchymal transition through ILK-dependent
activation of N.-kappaB and LE.-1. Matrix Biol. 2010;29(3):161-5.
10. Park SY, Roh SJ, Kim YN, Kim SZ, Park HS, Jang KY, Chung MJ, Kang MJ, Lee DG, Moon WS. Expression
of MUC1, MUC2, MUC5AC and MUC6 in cholangiocarcinoma: prognostic impact. Oncol Rep. 2009;22(3):
649-57.
11. Boonla C, Sripa B, Thuwajit P, Cha-On U, Puapairoj A, Miwa M, Wongkham S. MUC1 and MUC5AC mucin
expression in liver fluke-associated intrahepatic cholangiocarcinoma. World J Gastroenterol. 2005 28;11(32):4939-
46.
12. Thuwajit P, Chawengrattanachot W, Thuwajit C, Sripa B, May .E, Westley BR, Tepsiri NN, Paupairoj A,
Chau-In S. Increased T..1 trefoil protein expression in Opisthorchis viverrini-associated cholangiocarcinoma is
important for invasive promotion. Hepatol Res. 2007;37(4):295-304.
13. Thuwajit P, Chawengrattanachot W, Thuwajit C, Sripa B, Paupairoj A, Chau-In S. Enhanced expression of
mucin 6 glycoprotein in cholangiocarcinoma tissue from patients in Thailand as a prognostic marker for
survival. J Gastroenterol Hepatol. 2008;23(5):771-8.
14. Utispan K, Thuwajit P, Abiko Y, Charngkaew K, Paupairoj A, Chau-in S, Thuwajit C. Gene expression profiling
of cholangiocarcinoma-derived fibroblast reveals alterations related to tumor progression and indicates periostin
as a poor prognostic marker. Mol Cancer. 2010;9:13.
600.
àǪÈÒʵ÷¹Âؤ 2553
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78
Cancer-associated .ibroblasts in Tumor Progression
Assistant Professor Chanitra Thuwajit, Ph.D., M.D.
Department of Immunology .aculty of Medicine Siriraj Hospital, Mahidol University
Tumor progression requires a crosstalk between cancer cells and tumor microenvironment
via several interactions of both cell-to-cell and substance-to-cell manners. Among these interactions,
cancer-associated fibroblasts (CA.s) are the most attention both as recipients to the signals
from cancer cells, immune cells and extracellular matrix (ECM); and as producers of pro-
tumorigenic signals which can facilitate the progression and aggressiveness of the cancers.
The purpose of this talk is to introduce the importance of CA.s in cancer which have
been made during the last several years. These include the explanation of what CA.s originate
from, the specific characters and genetic status of CA.s, and roles of CA.s in particular in
cancer progression. The translational studies of using CA.s as therapeutic targets is of great
interest to mention herein. .inally, our data of CA.s in cholangiocarcinoma (CCA) which is
nowadays the major health problem in the North and Northeastern parts of the country will be
mentioned.
The origin of CA.s
CA.s are simply defined as fibroblasts found in cancers. They have specific characters
in particular the expression of activated fibroblast markers importantly !-smooth muscle actin
(!-SMA), fibroblast-activated protein (.AP). Several researches indicate distinct CA.s subsets
probably originated from different sources. There are three main explanations regarding the
origin of CA.s. Local fibroblasts or fibroblast precursors, stimulated by members of growth
factors and cytokines, have generally been considered as the major source of CA.s.
The experiment in mouse models demonstrated bone marrow-derived precursor cells in the
contribution of CA.s population.(1) Moreover, it has been suggested that CA.s are derived from
malignant epithelial cells or endothelial cells undergoing mesenchymal transitions. (2, 3)
601.
574 Cancer-associated .ibroblasts in Tumor Progression
The genetic alterations of CA.s
What is egg or chicken between the abnormalities of CA.s and the mutations occurred
in tumor cells is still not clear. The controversial results showed that characters of CA.s have
been maintained both in the absence and the presence of malignant cells. In case of CA.s
stability in the absence of malignant cells, the genetic and epigenetic alterations within CA.s
are involved. Using microdissected fibroblasts from breast cancer and head and neck squamous
cell carcinoma, p53 mutations and loss-of-heterozygosity are common events.(4, 5) Moreover,
epigenetic alterations in CA.s have been detected from fibroblasts isolated from breast and
prostate cancers.(6, 7)
Roles of CA.s in cancer progression
There is a complex interplay of reciprocal stromal-epithelial interactions resulting in
changes in the ECM and the tumor stroma. Carcinogenesis arises from the loss or breakdown
of this interaction rather than from epithelial or stromal mutation alone.(8) Several studies in
mouse models of genetically altered fibroblasts demonstrated a direct involvement of resident
fibroblasts in the initiation of cancer. However, many more research works so far have been
performed and indicated roles of CA.s in cancer progression. It is more than believable that
CA.s are sources of secreted growth factors, ECM-degrading proteases, invasive factors, and
angiogenic factors. .or example, CA.s are known to produce insulin-like growth factors in head
and neck cancer.(9) The ECM components such as various types of collagen have been
demonstrated the cross-link to the malignant cells which then cause integrin ligation leading to
PI3K and AKT survival signaling pathways. Matrix metalloproteases (MMPs), cathepsins, and
plasminogen activators are produced from CA.s and needed for cancer invasion and
metastasis.(10) To induce neovascular formation and the recruitment of endothelial progenitor
cells, CA.s are sources of vascular endothelial growth factors, fibroblast growth factor-2, and
stomal-derived factor-1.
Clinical implications of CA.s
The more evidence of CA.s in the progression of several cancers leading to the provincing
value of using CA.s in the clinical application. A key study regarding gene expression profile in
breast cancer revealed the significance of genes expressed in stromal cells as prognostic
predictors.(11) In addition, in colorectal cancer CA.s abundance has been shown to associate
with bad prognosis.(12, 13)
602.
àǪÈÒʵ÷¹Âؤ 2553
Ñ 575
CA.s can be the therapeutic targets through either the interfering with the recruitment
or expansion of CA.s in cancer tissues or the interfering with secreted CA.s-derived pro-
tumorigenic signals. Members of the platelet-derived growth factor (PDG.) family of growth
factors are well established regulator of tumor fibroblasts and pericytes.(14) Targeting of stromal
PDG. receptors, in experimental tumors, increase tumor drug uptake. In addition, inhibition of
stromal PDG. receptors induce anti-tumoral effects in cervix and colorectal cancers. Several
tyrosine kinase inhibitors with anti-PDG.R activity, such as imatinib, sorafenib, and sunitinib,
are presently approved and under clinical development.
Recently, CA.s have been proven to secrete CXCL14 chemokine(15), suggesting this
protein and its yet-to-be identified receptor as the targets for inhibition. Newly published studies
have been performed to find out the specific signal pathway in CA.s to be inhibited including a
recent finding of hedgehog-signaling as a novel pathway for anti-stromal therapy.(16) .inally,
immunotherapy-approached have been employed to target CA.s in particular .AP antibody are
the most attractive candidate drug with the committed effects in animal models.(17) Though
clinical studies are more needed, it is promising for targeting CA.s as the treatment in cancer
patients.
Cholangiocarcinoma-associated fibroblasts and role in cancer
progression
Our group has recently reported the in vitro tumorigenic effects of CA.s derived from
CCA patients through both contact and non-contact fashions.(18) In addition, the result supported
the previous findings in other cancers that the abundance of !-SMA positive fibroblasts correlated
to the short survival time of CCA patients. In order to identify the tumorigenic genes in CCA
fibroblasts, the gene expression profile of CA.s isolated from CCA patients undergone
hepatectomy was performed in comparison to that of normal fibroblasts.(19) Oligonucleotide
microarrays were used and certain genes involved in induction of cancer progression have been
proposed. Of most interest, periostin (PN) has been confirmed the expression in only CA.s
whereas no expressions in cancer cells or other stromal cells. In addition, patients who have
high level of PN had shorter survival time than the ones with low PN level. The in vitro studies
on roles of PN indicated the effects of PN to induce cancer cell proliferation and invasion.
Taken together, it is promising that in CCA, fibroblasts take part in cancer progression and
fibroblast-derived substances at least PN could be used as the poor prognostic markers. The
mechanism of action of PN on CCA cells and its effect in induction of MMPs are under
investigating in our lab. In addition, the other CA.s-derived substances in particular growth
603.
576 Cancer-associated .ibroblasts in Tumor Progression
factors, cytokines, chemokines represented from the oligonucleotide microarray and from the
study using protein chip assay (unpublished data) are of value to explore their roles in CCA. The
ultimate goal is to challenge targeting CA.s to attenuate tumorigenic induction and progression
in CCA patients.
References
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tumor-associated myofibroblasts and fibroblasts. Cancer Res. 2004;64(23):8492-5.
2. Radisky DC, Kenny PA, Bissell MJ. .ibrosis and cancer: do myofibroblasts come also from epithelial cells via
EMT? J Cell Biochem. 2007;101(4):830-9.
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a source for carcinoma-associated fibroblasts. Cancer Res. 2007;67(21):10123-8.
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mutations and nodal metastases. N Engl J Med. 2007;357(25):2543-51.
5. Weber ., Xu Y, Zhang L, Patocs A, Shen L, Platzer P, et al. Microenvironmental genomic alterations and
clinicopathological behavior in head and neck squamous cell carcinoma. JAMA. 2007;297(2):187-95.
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stromal cells of breast cancers. Nat Genet. 2005;37(8):899-905.
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methylation in prostate tumor-associated stromal cells. J Natl Cancer Inst. 2006;98(4):255-61.
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disease recurrence for colorectal cancer. Clin Cancer Res. 2007;13(7):2082-90.
13. Henry LR, Lee HO, Lee JS, Klein-Szanto A, Watts P, Ross EA, et al. Clinical implications of fibroblast
activation protein in patients with colon cancer. Clin Cancer Res. 2007;13(6):1736-41.
14. Ostman A, Heldin CH. PDG. receptors as targets in tumor treatment. Adv Cancer Res. 2007;97:247-74.
15. Augsten M, Hagglof C, Olsson E, Stolz C, Tsagozis P, Levchenko T, et al. CXCL14 is an autocrine growth
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16. Rudin CM, Hann CL, Laterra J, Yauch RL, Callahan CA, .u L, et al. Treatment of medulloblastoma with
hedgehog pathway inhibitor GDC-0449. N Engl J Med. 2009;361(12):1173-8.
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18. Chuaysri C, Thuwajit P, Paupairoj A, Chau-In S, Suthiphongchai T, Thuwajit C. Alpha-smooth muscle actin-
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