ﻣﻌﺮﻓﻲ ﻳﻚ ﻣﻮرد ﺑﻴﻤﺎر ﻣﺒﺘﻼ ﺑﻪ ﻛﺎرﺳﻴﻨﻮم ﻧﻮرواﻧﺪوﻛﺮﻳﻦ ﻧﺎزوﻓﺎرﻧﻜﺲ

ﺗﻤﭙــﺎﻧﻮﻣﺘﺮي ﭘــﺲ از درﻣــﺎن در ﻫــﺮ دو ﺳــﻤﺖ، A-type و اودﻳﻮﻣﺘﺮي، ﻣﺆﻳﺪ ﻣﺨﺘﺼﺮSNHL

(Sensory neural hearing loss) در ﻓﺮﻛﺎﻧﺲﻫﺎي ﺑﺎﻻ ﺑﻮد( ﻣﻨﻄﺒﻖ ﺑﺎ Presbycusis ). ﺑﻴﻤـﺎر ﺗﺎ ﻳﻚ ﺳﺎل ﭘﺲ از ﭘﺎﻳﺎن درﻣﺎن، ﻫﻤﭽﻨﺎن ﺑـﺪون ﺷـﻮاﻫﺪ ﻋـﻮد ﻛﻠﻴﻨﻴﻜــﻲ و ﭘــﺎراﻛﻠﻴﻨﻴﻜﻲ و داراي ﺣــﺎل ﻋﻤــﻮﻣﻲ ﺧــﻮب ﺑــﻮد (disease-free).

ﺑﺤﺚ

ﻧﺎزوﻓﺎرﻧﻜﺲ، ﺑﺨﺸﻲ از ﺳﻴﺴﺘﻢ ﺗﻨﻔﺴﻲ اﺳﺖ ﻛﻪ در ﭘﺸﺖ و ﺑﺎﻻي ﻛﺎم ﻧﺮم واﻗﻊ ﺷـﺪه و ﻣـﺸﺘﻤﻞ ﺑـﺮ دﻳـﻮارهﻫـﺎي ﻗـﺪاﻣﻲ، ﺧﻠﻔﻲ و ﺟﺎﻧﺒﻲ ﻣﻲﺑﺎﺷﺪ. ﭘﻮﺷـﺶ ﺑﺨـﺶ ﻋﻤـﺪه ﻧﺎزوﻓـﺎرﻧﻜﺲ، اﭘﻴﺘﻠﻴﻮم اﺳﻜﻮاﻣﻮس ﻣﻄﺒﻖ اﺳﺖ. ﺑﻘﻴﻪ ﻧﺎزوﻓﺎرﻧﻜﺲ، ﺑﺎ اﭘﻴﺘﻠﻴﻮم اﺳﺘﻮاﻧﻪاي ﻣﮋﻛﺪار ﻣﻔﺮوش ﺷـﺪه اﺳـﺖ. ﻣﻤﻜـﻦ اﺳـﺖ ﻧـﻮاﺣﻲ ﻣﺤﺪودي از اﭘﻴﺘﻠﻴﻮم ﺑﻴﻨﺎﺑﻴﻨﻲ(Transitional) ﻫﻢ وﺟﻮد داﺷـﺘﻪ ﺑﺎﺷﺪ.(11و12)

ﺳﻴﺴﺘﻢ ﻧﻮرواﻧﺪوﻛﺮﻳﻦ ﻣﺠﺎري ﺗﻨﻔﺴﻲ، ﻣﺘﺸﻜﻞ از ﺳﻠﻮﻟﻬﺎي اﭘﻴﺘﻠﻴﺎل اﻧـﺪوﻛﺮﻳﻦ اﺧﺘـﺼﺎص ﻳﺎﻓﺘـﻪ راه ﻫـﻮاﻳﻲ اﺳـﺖ ﻛـﻪ ﺑـﺎ ﻓﻴﺒﺮﻫﺎي ﻋﺼﺒﻲ ﻫﻤﺮاﻫﻲ دارﻧﺪ. اﻳـﻦ ﺳـﻠﻮﻟﻬﺎ در ﻣﺠـﺎري زﻳـﺮ ﻣﺨﺎﻃﻲ واﻗﻊ ﺷﺪه اﻧﺪ.(13-15) اﻳﻦ ﺳـﻠﻮﻟﻬﺎي اﭘﻴﺘﻠﻴـﺎل ﻣـﻲﺗﻮاﻧﻨـﺪ، ﻣﻨﻔــﺮد(Solitary) ﻳــﺎ ﺑــﻪ ﺻــﻮرت ﻣﺠﺘﻤــﻊﻫــﺎﻳﻲ ﺑــﻪ ﻓــﺮم Neuroepithlial Body ﺑﺎﺷﻨﺪ ﻛﻪ ﭘﺮوﻟﻴﻔﺮاﺳﻴﻮن اﻳﻦ ﺳﻠﻮﻟﻬﺎي ﻧﻮرواﻧﺪوﻛﺮﻳﻦ و ﻧﻮرواﭘﻴﺘﻠﻴـﺎل ﺑـﺎدي، در ﺗـﺮﻣﻴﻢ و ﺟـﺎﻳﮕﺰﻳﻨﻲ ﺳـــﻠﻮﻟﻬﺎي اﭘﻴﺘﻠﻴـــﺎل راه ﻫـــﻮاﻳﻲ و ﭘﻴـــﺪاﻳﺶ ﺗﻮﻣﻮرﻫـــﺎي ﻧﻮرواﻧﺪوﻛﺮﻳﻦ دﺧﺎﻟﺖ دارد.(14-16)

ﻛﺎرﺳﻴﻨﻮم ﻧﻮرواﻧﺪوﻛﺮﻳﻦ ﺑـﻴﺶ از 100 ﺳـﺎل ﭘـﻴﺶ، ﺑـﺮاي اوﻟﻴﻦ ﺑﺎر، ﺗﻮﺳﻂ Lubarsch ﺷﺮح داده ﺷﺪ.(17) در ﺳﺎل 1907 ﺑــﻪ ﻣﻨﻈــﻮر اﻓﺘــﺮاق ﮔﺮوﻫــﻲ از ﻧﺌﻮﭘﻼﺳــﻢﻫــﺎي رودهاي ﻛــﻪ اﻟﮕﻮﻫﺎي ﻣﻮرﻓﻮﻟﻮژﻳﻚ ﻣﺘﻔﺎوت و ﻋﻤـﺪﺗﺎً ﺧـﻮشﺧـﻴﻢ داﺷـﺘﻨﺪ، وﻟﻲ از آدﻧﻮﻛﺎرﺳﻴﻨﻮم، ﻣﻬﺎﺟﻢﺗﺮ ﺑﻮدﻧﺪ، Oberndorfer از ﻟﻐـﺖ «ﻛﺎرﺳـﻴﻨﻮﻳﻴﺪ» اﺳـﺘﻔﺎده ﻛـﺮد.(18 )ﭘـﺲ از آن ﻛﺎرﺳـﻴﻨﻮمﻫـﺎي ﻧﻮرواﻧـــﺪوﻛﺮﻳﻦ را ﺟﺰﺋـــﻲ از ﻧﺌﻮﭘﻼﺳـــﻢﻫـــﺎي ﺳﻴـــﺴﺘﻢ Amine precursor uptake & decarboxylation)APUD )ﻃﺒﻘﻪﺑﻨﺪي ﻛﺮدﻧﺪ.(1).

در ﺣﺎل ﺣﺎﺿﺮ اﻳﻦ ﻧﺌﻮﭘﻼﺳﻢﻫﺎ، ﺟﺰﺋـﻲ از ﺳﻴﺴﺘﻢ Solitary ﻧﻮرواﻧﺪوﻛﺮﻳﻦ ﻣﺸﺘﻤﻞ ﺑـﺮ ارﮔـﺎنﻫـﺎي ﻏﻴـﺮ ﺣﺎوي ﺳﻠﻮﻟﻬﺎي APUD ﺑﻪ ﺷﻤﺎر ﻣﻲروﻧﺪ.(1)

ﻗــﺒﻼً ﺗﻮﻣﻮرﻫــﺎي ﻛﺎرﺳــﻴﻨﻮﻳﻴﺪ ﺑﺮاﺳــﺎس ﻣﻨــﺸﺄ اﺣﺘﻤــﺎﻟﻲ ﺟﻨﻴﻨــﻲ (از ﺑﺨــﺸﻬﺎي ﻣﺨﺘﻠــﻒ Genitourinary tract)GUT)) ﻃﺒﻘﻪﺑﻨﺪي ﻣـﻲﺷﺪﻧـــﺪ.(19) در ﺣـﺎل ﺣﺎﺿـﺮ ﻋـﻼوه ﺑـﺮ ﻣﻨـﺸﺄ ﺗﻮﻣﻮر، ﺑﻪ وارﻳﺎﺳﻴﻮنﻫﺎي ﻫﻴﺴﺘﻮﻟﻮژﻳﻚ در ﺗﻘﺴﻴﻢﺑﻨـﺪي آﻧﻬـﺎ ﺗﻮﺟﻪ ﻣـﻲﺷـــﻮد.(20) در ﺗﻘـﺴﻴﻢﺑﻨـــﺪي ﺟﺪﻳـــﺪ، ﺗﻮﻣﻮرﻫـﺎي ﺗﻴﭙﻴــــﻚ، ﺗﻮﻣﻮرﻫــــﺎي ﻧﻮرواﻧﺪوﻛﺮﻳــــﻦ ﺧــﻮب ﺗﻤــﺎﻳﺰ ﻳﺎﻓﺘــﻪ (well-differentiated) ﻧﺎﻣﻴﺪه ﻣﻲﺷﻮﻧﺪ. اﻳﻦ ﺗﻮﻣﻮرﻫـﺎ، ﺣـﺎوي ﺳﻠﻮﻟﻬﺎي ﻛﻮﭼﻚ ﺑﺎ ﻫﺴﺘﻪﻫﺎي ﮔﺮد و ﻣﻨﻈﻢ ﻫﺴﺘﻨﺪ.(21)

ﺗﻮﻣﻮرﻫـﺎي داراي آﺗﻴﭙـﻲ ﻫـﺴﺘﻪاي اﻓـﺰاﻳﺶ ﻳﺎﻓﺘـﻪ، ﻓﻌﺎﻟﻴـﺖ ﻣﻴﺘـــﻮزي ﺑـــﺎﻻ ﻳـــﺎ ﻧـــﻮاﺣﻲ ﻧﻜـــﺮوز، در ﮔﺬﺷـــﺘﻪ ﺑـــﻪ ﻧـــﺎم ﻛﺎرﺳـــﻴﻨﻮﻳﻴﺪﻫﺎي آﺗﻴﭙﻴـــﻚ ﻳـــﺎ آﻧﺎﭘﻼﺳﺘﻴـــــﻚ ﻧﺎﻣﮕـــــﺬاري ﻣـــﻲﺷﺪﻧـــــﺪ ﻛـــــﻪ اﻣـــــﺮوزه ﺗﺤـــﺖ ﻋﻨـــﻮان ﻛﺎرﺳـــﻴﻨﻮم ﻧﻮرواﻧﺪوﻛﺮﻳﻦ ﺧﻮب ﺗﻤﺎﻳﺰ ﻳﺎﻓﺘﻪ(well-differentiated ) ﻳـﺎ ﻛـﻢ ﺗﻤﺎﻳﺰ ﻳﺎﻓﺘﻪ(Poorly-differentiated ) ﻃﺒﻘﻪﺑﻨﺪي ﻣﻲﺷﻮﻧﺪ. ﺑﺮوز ﻛﻠــﻲ ﺗﻮﻣﻮرﻫــﺎي ﻛﺎرﺳــﻴﻨﻮﻳﻴﺪ در آﻣﺮﻳﻜــﺎ ﺣــﺪود 1-2 در 100000 ﮔــﺰارش ﺷــﺪه اﺳــﺖ.(22و 23 ) ﺑﻄــﻮر ﻛﻠــﻲ ﻛﺎرﺳــﻴﻨﻮم ﻧﻮرواﻧﺪوﻛﺮﻳﻦ، ﭘـﺎﺗﺮن Basic organoid دارد و ﺑـﺎ ﻗﺮارﮔﻴـﺮي ﭘـﺮيواﺳـﻜﻮﻟﺮ ﺳـﻠﻮﻟﻬﺎي اﭘﻴﺘﻠﻴـﺎل ﺑـﺎ درﺟـﺎت ﻣﺨﺘﻠـﻒ ﺗﻤـﺎﻳﺰ ﻣﻮرﻓﻮﻟﻮژﻳﻚ ﻣﺸﺨﺺ ﻣﻲﺷـﻮد، ﻛـﻪ اﻳـﻦ ﺗﻮﻣـﻮر را از ﺳـﺎﻳﺮ ﻛﺎرﺳﻴﻨﻮمﻫﺎ و آدﻧﻮﻛﺎرﺳﻴﻨﻮمﻫﺎ، ﺑﺪون ﺗﻮﺟﻪ ﺑﻪ ﻣﻨﺸﺄ آﻧﻬﺎ در ارﮔﺎنﻫﺎي ﻣﺨﺘﻠﻒ، ﻣﺘﻤﺎﻳﺰ ﻣﻲﻛﻨﺪ.(24)

ﺑﺮﺧــﻲ از ﻓﺎﻛﺘﻮرﻫــﺎي ﭘــﻴﺶﺑﻴﻨــﻲ ﻛﻨﻨــﺪه ﺑــﺪﺧﻴﻤﻲ ﺗﻮﻣــﻮر ﻧﻮرواﻧﺪوﻛﺮﻳﻦ ﺑﻪ ﻗﺮار زﻳﺮ اﺳﺖ:

1. اﻧﺪازه ﺗﻮﻣﻮر(ﺑﺎﻻي 2 ﺳﺎﻧﺘﻲﻣﺘﺮ)
2. ﺗﻬﺎﺟﻢ ﺑﻪ ﺑﺎﻓﺘﻬﺎي اﻃﺮاف
3. ﺗﻬﺎﺟﻢ ﺑﻪ ﺧﺎرج از زﻳﺮ ﻣﺨﺎط
4. ﻧﻜﺮوز
5. آﺗﻴﭙـــﻲ واﺿـــﺢ ﺳـــﻠﻮﻟﻲ ﺑـــﺎ ﺑـــﻴﺶ از دو ﻣﻴﺘـــﻮز در hpf( ﺑﺰرﮔﻨﻤﺎﻳﻲ زﻳﺎد ﻋﺪﺳﻲ)
6. ﻓﻘـــﺪان Chranogen immunoreactvity و ﺗﻮﻟﻴـــﺪ ﻫﻮرﻣﻮن
7. ﺗﺠﻤﻊ ﭘﺮوﺗﺌﻴﻦ ﻫﺴﺘﻪاي P53

ﻛﺎرﺳـﻴﻨﻮم ﻧﻮرواﻧــﺪوﻛﺮﻳﻦ در ﺑـﺴﻴﺎري از اﺣـﺸﺎء اﻧــﺴﺎن ﮔــﺰارش ﺷــﺪه اﺳــﺖ. در رﻳــﻪ، اﻳــﻦ ﺗﻮﻣﻮرﻫــﺎ ﺑــﻪ دو دﺳــﺘﻪ ﺗﻮﻣﻮرﻫﺎي ﺑﺎ ﺳﻠﻮل ﻛﻮﭼﻚ و ﺑﺰرگ ﺗﻘﺴﻴﻢ ﻣﻲﺷﻮﻧﺪ و اﻟﻔـﺎظ ﻛﺎرﺳﻴﻨﻮﻳﻴﺪ آﺗﻴﭙﻴﻚ ﻳـﺎ Oat cell carcinoma ﺣـﺬف ﺷـﺪه اﻧـﺪ.

ﻛﺎرﺳﻴﻨﻮم small-cell رﻳـﻪ، ﺑـﺴﻴﺎر ﺑـﺪﺧﻴﻢ ﺑـﻮده و ﭘﺮوﮔﻨـﻮز ﺑــﺴﻴﺎر ﺑــﺪي دارد.(25و26 ) در اﻧــﺴﺎن در ﻣﺘــﻮن ﭼــﺎپ ﺷــﺪه، ﮔﺰارﺷﻲ از ﻛﺎرﺳﻴﻨﻮم ﻧﻮرواﻧﺪوﻛﺮﻳﻦ از ﻧﺎزوﻓـﺎرﻧﻜﺲ وﺟـﻮد ﻧﺪارد.

در ﺳﺎل 2002، ﺑــﺮاي اوﻟﻴﻦ ﺑﺎر ﻛﺎرﺳﻴﻨﻮم ﻧﻮرواﻧﺪوﻛﺮﻳﻦ در ﻧﺎزوﻓﺎرﻧﻜــــﺲ ﻳــــﻚ ﺳــــﮓ ﺑﻴﻤــــﺎر 9 ﺳﺎﻟــــﻪ ﮔــﺰارش ﺷﺪ.(27)

ﺗﻮﻣﻮرﻫﺎي ﻛﺎرﺳﻴﻨﻮﻳﻴﺪ از ﻧﻈﺮ ﻫﻴﺴﺘﻮﻟﻮژﻳﻚ ﺑﺎ واﻛﻨﺶﻫﺎي ﻣﺜﺒﺖ ﻧﺴﺒﺖ ﺑﻪ رﻧﮕﻬﺎي ﻧﻘﺮه ﻣﺸﺨﺺ ﻣﻲﺷﻮﻧﺪ. در ﺑﺮرﺳﻲ ﺑﺎ ﻣﻴﻜﺮوﺳــﻜﻮپ اﻟﻜﺘﺮوﻧــﻲ، ﺑــﻪ ﺻــﻮرت ﻣــﺸﺨﺺ، ﺣــﺎوي ﮔﺮاﻧﻮلﻫـﺎي ﻣﺘﻌـﺪد Neurosecretory ﻣﺤـﺪود ﺷـﺪه ﺑـﺎ ﻏـﺸﺎ ﻫﺴﺘﻨﺪ ﻛﻪ ﺣﺎوي ﻫﻮرﻣﻮنﻫـﺎ و آﻣـﻴﻦﻫـﺎي ﺑﻴﻮﻟﻮژﻳـﻚ ﻣﺘﻌـﺪد ﻫﺴﺘﻨــﺪ، ﻛــﻪ ﻳﻜـﻲ از ﺷـﻨﺎﺧﺘﻪ ﺷـﺪهﺗـﺮﻳﻦ آﻧﻬـﺎ، ﺳـﺮوﺗﻮﻧﻴﻦ اﺳــــﺖ. ﻣــــﻮارد دﻳﮕــــﺮي ﻫﻤﭽــــﻮن ﻛﻮرﺗﻴﻜــــﻮﺗﺮوﭘﻴﻦ(28)، ﻫﻴـــﺴﺘﺎﻣﻴﻦ(29) ، دوﭘـــﺎﻣﻴﻦ(30)، (31)ﻣـــﺎدهP ، ﻧﻮروﺗﻨـــﺴﻴﻦ(24)، ﭘﺮوﺳـﺘﺎﮔﻼﻧﺪﻳﻦﻫـﺎ(32)و ﻛـﺎﻟﻴﻜﺮﺋﻴﻦ(33)، ﻧﻴـﺰ از اﻳـﻦ ﺗﻮﻣﻮرﻫـﺎ ﺗﺮﺷﺢ ﻣﻲﮔﺮدﻧﺪ. ﻋﺎﻣﻞ ﭘﻴـﺪاﻳﺶ ﺳـﻨﺪرم ﻛﺎرﺳـﻴﻨﻮﻳﻴﺪ، ﻛـﻪ ﺑـﻪ ﺻــﻮرت ﻓﻼﺷﻴﻨــــﮓ، وﻳﺰﻳﻨــﮓ، اﺳــﻬﺎل اﭘﻴﺰودﻳــﻚ و ﺣﺘــﻲ ﻧﺎرﺳﺎﻳﻲ درﻳﭽﻪاي ﻗﻠﺒﻲ ﺳﻤﺖ راﺳـﺖ ﭘﺪﻳـﺪار ﻣـﻲﺷـﻮد، آزاد ﺷﺪن ﺳﺮوﺗﻮﻧﻴﻦ و ﺳﺎﻳﺮ ﻣﻮاد Vasoactive ﺑـﻪ داﺧـﻞ ﺟﺮﻳـﺎن ﺧﻮن ﺳﻴـﺴﺘﻤﻴﻚ اﺳـﺖ. در رﻧـﮓآﻣﻴـﺰي اﻳﻤﻮﻧﻮﻫﻴـﺴﺘﻮﺷﻴﻤﻲ (Immunohistochemistry=IHC)، واﻛﻨﺶ ﺑﻪ آﻧﺘـﻲﺑـﺎديﻫـﺎي NSE، (Neural cell adhesion molecule)N-CAM، S-100 و ﻛﺮوﻣﻮﮔﺮاﻧﻴﻦ A، ﺑﺮاﺳﺎس ﻣﺤـﻞ ﻣﻨـﺸﺄ ﺗﻮﻣـﻮر ﻛﺎرﺳـﻴﻨﻮﻳﻴﺪ، ﻣﺘﻔــﺎوت اﺳــﺖ وﻟــﻲ واﻛــﻨﺶ ﺑــﻪ Synaptophysin در %100 ﻣــﻮارد وﺟــﻮد دارد.(10) اﻓﺘــﺮاق ﺗﻮﻣﻮرﻫــﺎي ﻛﺎرﺳــﻴﻨﻮﻳﻴﺪ از ﻣــــﻮاردي ﻫﻤﭽــــﻮن Undiff.carcinoma ﻧﺎزوﻓــــﺎرﻧﻜﺲ و Olfactory neuroblastoma ﺑــــﻪ واﺳﻄــــﻪ IHC اﻣﻜﺎﻧﭙــﺬﻳﺮ اﺳﺖ.

در ﺑﻴﻤﺎر ﻣـﻮرد ﺑﺤـﺚ، وﺟـﻮد اﻧـﺴﺪاد ﻣﻜـﺎﻧﻴﻜﻲ در ﻧﺎﺣﻴـﻪ ﻧﺎزوﻓــﺎرﻧﻜﺲ(ﻧﺎﺷــﻲ از ﺗــﻮده ﻛﺎرﺳــﻴﻨﻮﻣﺎﺗﻮ)، ﺗﻮﺟﻴــﻪ ﻛﻨﻨــﺪه اﻧﺴﺪاد ﺑﻴﻨﻲ وي ﻣﻲﺑﺎﺷﺪ ﻛﻪ ﺑﺎ رﺷﺪ ﺗﻮده ﺑﺘﺪرﻳﺞ ﺣﺎﻟﺖ داﻳﻤﻲ ﺑﺨــﻮد ﮔﺮﻓﺘــﻪ اﺳــــﺖ و ﺑــﻪ ﻋﻠــﺖ ﻣﺎﻫﻴــﺖ ﻧﺌﻮﭘﻼﺳــﺘﻴﻚ ﺑــﻪ درﻣﺎنﻫﺎي ﻣﻌﻤﻮل ﭘﺎﺳـــﺦ ﻧـﺪاده اﺳـﺖ. ﻳﻜـﻲ از ﻋﻼﻳـﻢ ﻗﺎﺑـﻞ ﺗﻮﺟـﻪ در وي، وﺟـﻮد ﻛﺎﻫـــﺶ ﺷـﻨﻮاﻳﻲ و اﺣـﺴﺎس tinnitus ﺑﻮده اﺳﺖ ﻛﻪ ﺑﺎ اﻧـﺴﺪاد ﻣﻜـﺎﻧﻴﻜﻲ ﺷـﻴﭙﻮر اﺳـﺘﺎش دو ﻃـﺮف ﺑﻮﻳﮋه ﺳﻤﺖ ﭼـﭗ و ﭘﻴـﺪاﻳﺶ اوﺗﻴـﺖ ﻣﻴـﺎﻧﻲ ﺳـﺮوز دو ﻃﺮﻓـﻪ (serous otitis media=SOM) ﺗﻮﺟﻴـﻪﭘـﺬﻳﺮ اﺳـﺖ. ﮔـﻮاه اﻳـﻦ ﻣﻄﻠﺐ، رﻓﻊ ﻣﺸﻜﻞ ﺑﻴﻤﺎر ﻫﻢ ﺑﻪ ﺻﻮرت Subjective و ﻫـﻢ ﺑـﻪ ﺻﻮرت )Objectiveﻃﺒﻴﻌﻲ ﺷـﺪن ﺗﻤﭙـﺎﻧﻮﻣﺘﺮي و رﻓـﻊ ﻛـﺎﻫﺶ ﺷﻨﻮاﻳﻲ ﻫﺪاﻳﺘﻲ دو ﻃﺮﻓﻪ) ﭘﺲ از درﻣﺎن اﺳﺖ.

در ﻣــﻮرد درﻣــﺎن ﺗﻮﻣﻮرﻫــﺎي ﻧﻮرواﻧــﺪوﻛﺮﻳﻦ، ﻛﻤــﻮﺗﺮاﭘﻲ ﺳــﻴﻤﻴﺘﻴﻚ ﻣﻤﻜــﻦ اﺳــﺖ ﺑــﺎ وارﻳﺎﻧــﺖﻫــﺎي ﻣﻬــﺎﺟﻢ ﺗﻮﻣــﻮر ﻛﺎرﺳﻴﻨﻮﻳﻴﺪ، ﻣﺆﺛﺮﺗﺮ و ﺳﻮدﻣﻨﺪﺗﺮ از ﺳـﺎﻳﺮ درﻣـﺎنﻫـﺎ ﺑﺎﺷـﺪ.

ﺗﺮﻛﻴﺐ cisplatin و Etoposide (رژﻳﻤﻲ ﻛـﻪ ﻋﻤﻮﻣـﺎً در درﻣـﺎن Small-cell lung cancer ﺑﻜـﺎر ﻣـﻲرود)، در ﺑﻴﻤـﺎران ﻣﺒـﺘﻼ ﻛﺎرﺳﻴﻨﻮم ﻧﻮرواﻧﺪوﻛﺮﻳﻦ ﭘﺎﺳـﺨﻲ ﺑـﻪ ﻣﻴـﺰان %67 ﺑـﻪ دﻧﺒـﺎل داﺷــﺘﻪ اﺳــﺖ.(34) ﺑــﺮ ﻋﻜــﺲ، ﺑﻴﻤــﺎران ﻣﺒــﺘﻼ ﺑــﻪ ﺗﻮﻣﻮرﻫــﺎي ﻛﺎرﺳﻴﻨﻮﻳﻴﺪ ﺗﻴﭙﻴﻚ، ﺑﻪ اﻳﻦ ﺷﻜﻞ از درﻣـﺎن، ﭘﺎﺳﺦ ﻧﻤﻲدﻫﻨﺪ.

در ﻣــﻮرد اﺳــﺘﻔﺎده از رادﻳــﻮﺗﺮاﭘﻲ در درﻣــﺎن ﺗﻮﻣﻮرﻫــﺎي ﻛﺎرﺳﻴﻨﻮﻳﻴــــﺪ، ﻣﻄﺎﻟﻌــــﻪ وﺳﻴﻌــــﻲ اﻧﺠــﺎم ﻧــﺸﺪه اﺳــﺖ. External-Beam radiation ﻣﻲﺗﻮاﻧﺪ ﺑـﻪ Palliation ﻣـﺆﺛﺮ در ﻣﺘﺎﺳـﺘﺎزﻫﺎي اﺳـﺘﺨﻮاﻧﻲ و Central nervous system)CNS ) ﻛﻤﻚ ﻛﻨﺪ.(35)

اﺧﻴـــﺮاً اﺳﺘﻔـــــﺎده از آﻧـــﺎﻟﻮگﻫــــﺎي ﺳﻮﻣﺎﺗﻮﺳـــﺘﺎﺗﻴﻦ (Radiolabe led) ﺑــﻪ ﻣﻨﻈــﻮر Shrinkage ﺗﻮﻣــﻮر و ﺑﻬﺒــﻮد ﻛﻠﻴﻨﻴﻜﻲ، در ﺗﻌﺪاد ﻛﻤﻲ از ﺑﻴﻤﺎران ﻣﺒـﺘﻼ ﺑـﻪ ﻛﺎرﺳـﻴﻨﻮﻳﻴﺪﻫﺎي ﻣﺘﺎﺳــﺘﺎﺗﻴﻚ ﮔــﺰارش ﻧــﺸﺪه اﺳــﺖ(36و37) ؛ ﻟــﺬا ﻫﻨــﻮز ﺑــﺮاي ﺗﺼﻤﻴﻢﮔﻴﺮي در ﻣﻮرد اﺛﺮات ﻃﻮﻻﻧﻲ ﻣﺪت اﻳﻦ ﮔﻮﻧﻪ درﻣﺎنﻫـﺎ، ﺑﻪ ﻣﻄﺎﻟﻌﺎت و Trialﻫﺎي ﺑﻴﺶﺗﺮي ﻧﻴﺎز ﻫﺴﺖ.

ﻓﻬﺮﺳﺖ ﻣﻨﺎﺑﻊ

1. Kulve MH, Mayer RJ. Carcinoid tumors. N Engl J Med 1999; 340: 858-68 .
2. Arnold R. Diagnosis and management of neuroendocrine tumors. United Eur gastroenterol week 2001; 8: 1-12.
3. Konno A, Nagata M, Nawko H. Immuno histo chemical diagnosis of a Merkel cell tumor in a dog. Vet pathol 1998; 35: 538-40.
4. Pantnaik AK. Canine and feline nasal and paranasal neoplasms. In: Reznik G. Morphology and orgin of nasal  tumor in animals and Man. 2 nd ed. Vol 2. Boca Raton, FL: CRC Press; 1983. p. 199-228.
5. Pantnaik AK. A morphologic and immunity to chemical study of hepatic neoplasms in cats. Vet pathol 1992; 29: 405-15.
6. Pantnaik AK, Erlandson RA, Lieberman PH. Esophageal neuroendocrine carcinoma in a cat. Vet pathol 1990; 27: 128-30.
7. Pantnaik AK, Hurivitz AI, Johnson GF. Canine intestinal adenocarcinomas and carcinoids. Vet pathol 1979; 17: 149-63.
8. Pantnaik AK, Lie barman PH, Hurvitz AJ, Johnen GF. Canine hepatic carcinoids. Vet pathol 1981; 18: 445-53.
9. Pantnaik AK, Liu SK, Johnson GF. Feline intestinal adenocarcinoma: A dinicopathlogic study of 22 cases. Vet pathol 1976; 13: 1-10.
10.  Al-khafaji B, Noffsinger AE, Miller MA, Devoe G, Stemmermann NU, Fenelglio-presser C. Immunohistologic analysis of GI and pulmonary carcinoid tumors. Hum pathol 1998; 29: 992-9.
11. Naga H. A morphological study of human epipharyngeal mucosa: 10 autopsy cases. Nippon Jibiinkoka Gakkai Kaiho 1996; 3: 417-43.
12. Nagai H, Takahashi H, Yaok. A morphological study of the human epipharyngeal Mucosa. Eur Arch otorhinolaryngol 1997; supp 1: 523-6.
13. Hauser-Kronberger C, Hacker GW, Franz P, Albegger K, Dietzeo. CGRP and substance p in intraepithelial neuronal structures of the human upper respiratory system. Regul pept 1997; 72: 79-85.
14. Scheuermann DW. Comparative histology of pulmonary neuroendocrine cell system in mammalian Lungs. Microsc Res Tech 1997; 37: 31-42.
15. Van lommel A, Bolle Tt, Fannes W, Lauweryns JM. The pulmonary neuroendocrine system: the past decade. Arch Histol cytol 1999; 62: 1-16.
16. Paladugu RR, Benfield JR, Pak HY, Ross RK, Teplitc RL. Broncho kulchitzky cell carcinomas: A new classification scheme for typical and atypical carcinoids.Cancer 1985; 55: 1303-10.
17. Lubarsch O. Ueber den primaren krebs des Ileum nebst Bemer Kungen uber das glichzeitige vorkommen von krebs und Tuberkulose virchows Arch. pathol Anat 1888; 13: 280-317.
18. Oberndorfers’ Karzinoide. Tumoren des dunndarms.Frank f z pathol 1907; 1: 426-34.
19. Williams ED, Sandler M. The classification of carcinoid tumors. Lancet 1963; 1: 238-9.
20. Capella C, Heitz PU, Hofler H, Solicia E, Kloppel G. Revised classification of neuroendocrine tumors of the lung, pancreas and gut. Virchows Arch 1995; 425:547-60.
21. Saga Tazawa K. Pathlogic analysis of carcinoids: histologic reevaluation of 62 cases. Cancer 1971; 28: 990-8.
22. Godwin J. Carcinoid Tumors: an analysis 2837 cases.Cancer 1975; 36: 560-9.
23. Modlin IM, Sandor A. An analysis of 8305 cases of carcinoid tumors. Cancer 1997; 79: 813-29.
24. Feldman JM, Odorisio TM. Role of neuropeptides and serotonin in the diagnosis of carcinoid tumors. Am J Med 1986; 81(suppl 6 B): 41-8.
25. Harkema JR, Jones SE, Naydan DK, Wilson DW. An atypical neuroendocrine carcinoma in the lung of a Beagle dog. Vet pathol 1992; 29: 175-9.
26. Junker K, Wiethege T, Muller KM. Pathology of small-cell lung cancer. J cancer Res clin oncol 2000; 7: 361-8.
27. Pantnaik AK, Ludwig LL, Erlandson RA. Neuroendocrine carcinoma of the nasopharynx in a dog. Vetpathol 2002; 39: 496-500.
28. Limper AH, Carpenter PC, Scheithauer B, Staats BA. The cushing syndrome induced by bronchial carcinoid tumors. Ann Intern Med 1992; 117: 209-14.
29. Pernow B, Waldenstrom J. Determition of Shydroytryxptamine,S-hydroxin-dole Acetic acid, and histamine in 33 cases of carcinoid Tumor(argentaffinoma). Am J Med 1957; 23: 16-25.
30. Feldman J. Increased dopamine production in patients with carcinoid tumors. Metabolism 1985; 34: 255-60.
31. Skrabanek P, Cannon D, Kirrane J, Powell D.Substance P Secretion by carcinoid tumors. Ir J Med Sa 1978; 147: 47-9.
32. Sandler H, Karim SM, Williams ED. Prostaglandins in amin-peptide-secreting tumors. Lancet 1968; 2: 1053-4.
33. Locas KJ, Feldman JM. Flushing in the carcinoid syndrome and plasma kallikein. Cancer 1986; 58: 2290-3.
34. Moertel CG, Kvols LK, O’Connell MJ, Rubin J. Treatment of neuroendocrine carcinomas with combined etoposid and cisplatin: evidence of Major Therapeutic activity in the anaplastic variants of these neoplasms. Cancer 1991; 68: 227-32.
35. Schupak KD, Wallner KE. The role of radiation therapy in the treatment of locally  unresectable or metastatic carcinoid tumors. Int J Radiat oncol Biol phys 1991; 20:465-89.
36. MC Carthy KE, Woltering EA, Espenan GD, Cronin M, Maloney TJ, Anthory LB. In situ radiotherapy with lll-In-pentereolide: initial observation and future directions. Cancer J Sci AM 1998; 4: 94-102.
37. Otte A, Mueller-Brand J, Dellas S, Nitzche EU, Herrmann R, Maeche HR. Yttrium-90 labelledsomatostatin-analogue for cancer treatment. Lancet 1998;351: 417-8.