/.5]: (043.3) (476)

Transcription

1 ..» /.5]: (043.3) (476) :,, ,

2 » : : :,,,,,,, «-..»,,,,,, «-» «4» «..» (223040,,., NArtemova@omr.med.by, ). «..» «5» 2014., 2.

3 ( ),, ; -, ;., [Rivkees S.A. et al., 2011; Vaisman F. et al., 2011].,, - (, % ), ( 20 % ) ( ).,., [.., 2008; Dinauer C.A. et al., 2008; Machens A. et al., 2010; Enomoto Y. et al., 2012].,, (, ). -.,,,,., ( ),,,,. 3

4 , (,,, ) « » (. 20, 21, 22, 24, 25) (« »,. 4.2, 4.3, 6.1). ( ), : ( , );. : ( : ); : «( )» ( , ); «, ( ) 4

5 ,». : «,,» )» ( , );,. : ( , ); : (International science and technology center ISTC) B-550 Thyroid pathologies in Chernobyl area; study of thyroid cancer and other thyroid pathologies in Belarus following Chernobyl accident ( ); B-736 Childhood visualized cancer-registry; development and demonstration of the methodology and information technology for making the diagnosis of childhood cancer on the basis of the visualized findings of the primary diagnostic complex ( ); B-1910 Epidemiological analysis of pediatric cancer based on spatio-temporal clustering of incidence and mortality for survival improvement within the long-term post-chernobyl period ( ). INTAS : "Disclosing intrinsic relations between ultrasonic and histological images for improving thyroid cancer diagnosis after the Chernobyl reactor accident" ( ) CRDF BEM MK-08: "Development of methods, algorithms and software for the analysis of angiogenic activity of thyroid cancer" ( )..,,

6 2.,,,,,. 3., ,, ( 19 ),. 226,, ( ) 23,. :,,, ( ),,,,., 1.,,. - 6

7 ( = 0,010),, = 0,011). 2. ( ). (3 14 ) (15 18 ) (65,3 51,4 %, = 0,0003). (, = 0,0007) (14,6 % 6,7 %, < 0,0001)., ( = 3,91; 95 % = 1,54 13,25).,, ( = 1,65; 95 % = 1,08 2,58), ( = 3,09; 95 % = 1,91 5,23), ( = 1,69; 95 % = 1,06 2,51). 3.,,,. : (p < 0,001), (p = 0,030), (p = 0,034)., (p = 0,013) (p = 0,007), (p < 0,001) (p = 0,006). 4. (51 %),. ( ( = 0,018) ( = 0,047), ( ( = 0,003)). 7

8 -,.,, -,,,.,,,.,,,, :..,...,..,...,... ).,,. ( : , (2009) G 01N 33/48, A 61B 10/00 /.,.,. ; 8

9 ; ; ; : , (2006) G 01N 33/48, A 61B 10/00 /.,.,.,. ; ; ; ), /.,.,. ), : /.,. ) :, ,.,. «Radiation-induced thyroid cancer: 20 years after Chernobyl», ,,. «,,», 3 4, 2007.,.,. «,, ,.,., 30 1, 2010.,.,. «,», ,.,. IV,, ,.,. 9

10 VI, ,.,. 36 th Annual Meeting of the European Thyroid Association, September 8 12, 2012, Pisa, Italy. I, ,., Project on nuclear hazard research and related tasks: the International workshop on radiation and thyroid cancer, February 21 23, 2014, Tokyo, Japan. «:», ,.,.. 79 : ( ) 5, 36. 9, 4. 14, 5. 2, 1, 2.,, 39, ,,, 5,, ,,, 1327 ( 19 ), ,,, 10

11 , (,, )., 936 -, , 86,8 % (1078),.,,, (, ). 23 (10 13 ). 210 (92,9 % (226) ) ,. (Pathology and genetics of tumours of endocrine organs, 2004)., (ptnm),., - ( ), -,.,,. RET/PTC ( ). RET/PTC1 RET/PTC3 1,5 %. BRAF T1799A 11

12 . T1799A 15 BRAF., 19.,. (,, ).. 2,0 2, ,,,.,.., 131 I ). 6,. :,,, 12

13 .,. : (,,, ), Akaike :. R; R < 0,05.,,., 7,4 23,1 ( 15,4 ), 2,2 27,1 ( 6,6 ).» ( ), -., 13

14 , (73,7 %) (11,1 %). 12, (n = 504),, pt3-t4, 166 (32,9 %), 320 (63,5 %)., ( 10 ), - (11 14 ) (15 18 ).,, (3,8 4,9 8,7 %, = 0,044), (2,5 8,0 14,5 %, < 0,001). (29,3 22,3 13,5 % ), (19,7 29,9 38,6 %, < 0,001). (21,7 16,2 10,4 % ), (1,3 6,0 9,9 %, < 0,001). (46,5 33,5 32,8 %, = 0,006), (25,5 20,1 15,2 %, = 0,015), (95,5 85,2 79,5 %, < 0,001) (2,5 13,7 22,7 %, < 0,001). (21,7 11,5 6,7 %, < 0,001), (82,8 82,0 71,8 %, < 0,001). : ( = 2,79; 95 % : 1,80 4,37), ( = 2,94; 95 % : 1,70 5,28), (, = 3,13; 95 % : 1,66 6,02). ) = 3,40; 95 % : 2,20 5,30), = 3,63; 95 % : 1,89 7,23) ( = 3,78; 95 % : 2,52 5,71). ( = 9,48; 95% : 3,50 30,73). 14

15 ( = 2,19; 95 % = 0,94 5,10), ( = 2,26; 95 % : 1,48 3,45), ( = 2,36; 95 % : 1,17 5,09), ( = 2,94; 95 % : 1,95 4,48), ( = 3,55; 95 % : 1,93 4,97). ( = 23,41; 95 % = 11,66 50,84).,. (, )., ( 10 ) ( = 5,03; 95 % = 2,65 9,69), - (11 14 ) = 2,43; 95 % = 1,39 4,32). ( : = 1,98; 95 % = 1,23 3,19), (,, = 3,47; 95 % = 1,79 7,33), ( : = 2,21; 95 % = 1,18 4,37). ( = 2,20; 95 % = 1,26 3,93), ( = 1,77; 95 % = 1,09 2,90) = 1,88; 95 % = 1,13 3,11). ( = 6,08; 95 % = 3,43 11,31) ,. ( = 2,93; 95 % = 1,39 6,21) ( = 1,81; 95 % = 1,04 3,14). ( 1), 5 ( ), 6 ( ). 15

16 ). 10, D). 1 ( ) (C, D) ( ) (B, D),,, (,, ). Grey,,.,, (,, p < 0,001), ( = 0,044), (p < 0,001) ( = 0,046). ( ) - ( < 0,001), ( = 0,005). 16

17 = 0,019), ( = 0,024), ( = 0,010) (p < 0,001),.,, ( < 0,001), (p = 0,011), = 0,013), ( = 0,002).,,. (, : = 5,34; 95 % = 1,30 21,8), ( = 8,68; 95 % = 2,75 27,4) ( = 9,26; 95 % = 2,74 31,2).,., (, ), 5 6, ( ),.»,,,., 23,. 4,7 ± 2,8 ( 1 12 ). ( ) 9,2 ± 3,3 ( 4 16 ). (,, ), 17

18 ( ). :, ( ; 91,3 %) -, VI II V. ( 1 3) 0,3 7, ,6. 99,3 ( 18,1 186,6.).., (73,8 %) (11,1 %).» - : (47,8 % 26,1 % 10 ) ( 52,2 % 21,7 % 10 )., ( = 4,32; 95 % : 1,29 12,70), ( = 3,43; 95 % : 1,38 8,94), ( = 3,22; 95 % : 1,17 9,98), ( = 2,42; 95 % : 0,89 6,27), ( = 2,15; 95 % : 0,92 5,18),»,.,,, 10 ( = 6,29; 95 % : 1,72 30,87).,, = 3,03; 95 % : 1,08 8,14), ( = 4,89; 95 % : 1,34 31,53), ( = 0,22; 95 % : 0,03 0,84).,, 18

19 . -..,. -» () ) ),» »,,., (56,5 20,4 % ; = 0,0006).., (14 56 ; = 0,0436),,,,,.» = 0,0108) ( = 0,0351). ( ),,,» ( = 0,0014). 19

20 ,», -,,., : , , , ,., ( ),. - ( ) (15 20 ),,,., (11,2 ± 3,3 ),,, 15,8 ± 11,8, (p < 0,0001),, (38,6 %), (65,5 %) 3-4 N1a (37,0 %). ( = 0,0006) 14,1 %. (42,9 %) (19,1 %), (86,5 %) (10,2 %). (41,1 %), (22,9 %) (94,0 %), (67,1 %) (19,7 %) (4 9, 10 15, ) 20

21 , 1,5:1, 1,8:1 2,7:1 ( = 0,0655)., (34,5 < 40,3 < 58,0 %, = 0,0006), (34,2 < 43,1 < 45,7 %; = 0,0069)., , ( :14,1 < 11,0 < 2,5 %; = 0,0006)., (2,8 < 7,6 < 11,0 %, = 0,0014), (3,5 < 12,4 < 16,9 %, p < 0,0001)., , :,, < 0,0001), < 0,0001) ( = 0,0703), ( = 0,0015) ( < 0,0001).,,.,, (,.) ( ),,,. ( = 0,4346), ( = 0,5651), = 0,7292), ( = 0,1962), ( = 0,8272), = 0,8468), ( = 0,1172).,,. 21

22 ,.,,,,. :,,,..,,, :,.,, ( ± 96,9 ± 0,9 %, 16,2 ). (7), (6), (, ), (,, )., : (, )., 87,3 ± 7,2 % ( 8,6 ). ( 10, ); :. 3,8 52,9 10,1, 16,4 ± 16,0). 22

23 , 87,8 ± 1,6 % ( 15,4 ), 76,7 ± 7,8 % ( 6,6 ). : 92,3 ± 0,9 % ( 15,4 ) 85,1 ± 6,2 % ( 6,6 ). -, » RET/PTC1 RET/PTC3, T1799A BRAF 41, 10, ( ). 17 (, )., 14 19, 1987,,,. 41 RET/PTC 16 (39,0 %).» RET/PTC 4 10 (40,0 %), RET/PTC1 (10,0 %), RET/PTC3 (30,0 %). RET 41,1 % (7 17), RET/PTC1 4 (23,5 %), RET/PTC3 (17,6 %). RET/PTC1 (14,3 %), RET/PTC3 (21,4 %),. RET/PTC 35,7 % (5 14). RET/PTC.. RET/PTC- RET/PTC,, 23

24 . RET/PTC 3-4 (p = 0,0003) (p = 0,0306). RET/PTC (93,8 %) RET/PTC (72,0 %), (p = 0,1201). ( ), RET (p = 0,0058). BRAF T1799A 3 17 (17,6 %) 3 14 (21,4 %). (n = 10)., T1799A 0 21,4 %, 14,6 %. T1799A 15 9,1 % 25,0 % ,7 15,4 %. RET/PTC T1799A BRAF 22 (53,7 %)..., RET/PTC, T1799A BRAF,., RET BRAF. ( 10 ), - (11 14 ) (15 18 ), RET/PTC- (75,0 38,9 31,6 % ) BRAF (0 11,1 21,1 % ). RET 24

25 (p = 0,0093),, pt3,., RET/PTC.,, RET/PTC, BRAF T1799A..,. < 0,001, 13,6 ± 3,1 ) 14 (55,7 %)», (60,7 %). ( = 0,0004):,,, 1:1,8, 1:3,5. 10 ( ,6 %; = 0,0083). = 0,0001) (12 14; 85,7 %)., ( = 0,0028)., : 31,2 %», 52,2 %» ( = 0,0001). 38,5 %, 28,6 % < 0,0001). (35,4 %) (87,6 %) ( = 0,0167 < 0,0001 ).» ( = 0,0484), < 0,0001). 25

26 ,,,»,,,.,».,,», ( ),., 10 16,., ( = 2,07; 95 % : 1,38 3,13). ( = 1,86; 95 % : 1,25 2,81), = 0,32; 95 % : 0,21 0,48)., = 0,86; 95 % : 0,79 0,93). ( = 0,81; 95 % : 0,75 0,88), ( = 0,91; 95 % : 0,86 0,97) ( = 0,88; 95 % : 0,84 0,93)., ( = 1,12; 95 % : 1,04 1,21)., ( = 0,005 = 0,023 ) ( = 0,008 = 0,029 ). : = 3,09; 95 % : 1,91 5,23., ( = 0,22; 95 % : 0,03 0,84)». 26

27 463 (172, 291 ) 6 15, ,479., ( ). (,,, ) ( 97),.. (51 %),,. ( 11 = 1,59; 95 % : 1,04 2,43), ( = 7,77; 95 % : 3,34 20,64), ( = 1,85; 95 % : 1,23 2,78). ( = 2,13; 95 % : 1,23 3,77), ( = 4,13; 95 % : 1,58 12,29), ( = 1,72; 95 % : 1,15 2,58).,,, = 0,018) ( = 0,047) ( ,6 %; = 0,0083) 27

28 (12 14; 85,7 %; = 0,0001)., (p = 0,0028) [4, 33, 35, 36, 39, 40, 41, 47, 48, 50, 53, 54]. 2 ( 10 ), - (11 14 ) (15 18 ) RET/PTC- (75,0 38,9 31,6 % ) BRAF- (0 11,1 21,1 % ). RET (p = 0,0093).,, ( = 0,91; 95 % : 0,86 0,97) ( = 0,88; 95 % : 0,84 0,93). ( = 0,86; 95 % : 0,79 0,93) ( = 0,81; 95 % : 0,75 0,88) [5, 36, 39, 40, 41, 50, 68]. 3 : ), ( ) ( 10,9 91 % (95 % = 80,0 96,0 %)). -, - 97,8 ± 0,6 %, 97,0 ± 0,7 % 97,0 ± 0,7 %, 92,8 ± 1,5 %, 88,3 ± 1,9 %, 84,5 ± 2,2 % [5, 18, 32, 36, 50, 54, 70]. 4 ( 11, = 1,59; 95 % : 1,04 2,43), ( = 7,77; 95 % : 3,34 20,64) ( = 1,85; 95 % : 1,23 2,78)., ( = 2,13; 95 % : 1,23 3,77), ( = 1,72; 95 % : 1,15 2,58), ( = 1,53; 95 % : 1,02 2,29).,, ( = 5,39; 95 % = 2,43 13,67), ( = 1,65; 95 % = 1,11 2,47), 28

29 ( = 4,1; 95 % = (1,55 12,91) ( = 2,02; 95 % = (1,22 3,38) [49, 67]. 1.,., [1, 2, 3, 5, 9, 17, 21, 22, 31, 32, 34, 37, 40, 41, 45, 46, 47, 75, 76, 77, 78, 79]. 2, :,,,., (,, 10 ), [5, 41, 50, 52, 54]. 3 ( 10 ),, ( 10 ).,, [5, 41, 50, 52, 54]. 4,, ;, [49, 67]. 29

30 ( ) 1.,. /.,.,.. :, : 3. /.,.,.,.,.,.,.. :, : , /.,.,.,.,. // :,,, /.,.,.., ,. : /.,.. :, Papillary thyroid cancer in childhood and adolescence with specific consideration of patients after radiation exposure / Yu. Demidchik, M. Fridman, K.W. Schmid, Chr. Reiners, J. Biko, S. Mankovskaya // Updates in the Understanding and Management of Thyroid Cancer / ed. by Thomas J. Fahey. INTECH, P , /.,.,.,. // ,. /.,.,. // /.,.,.,.,. //

31 9.,. /.,.,. // ,. /.,. // ,. /.,.,. // ,. - /.,. // ,. /. // ,. /.,. // ,. :,, /.,. // ,. : /.,. // ,.» /. // ,. /. // ,. : (2004) 31

32 /.,. // ,. : /. // ,. /. // ,. : /.,.,. // ,. /.,. // ,. /.,.,. // ,. : /. // ,. /.,.,. // i i /.,.,.,. // ,. /.,. // i /.,.,.,., // ,. 20 /. // /.,.,.,. //

33 32.,. : /.,.,. // ,. /.,.,. // Joint analysis of histological and ultrasound images to learn state of thyroid gland / A. Nedzved, B. Zalesky, S. Ablameyko, V. Drozd, M. Fridman // Machine graphics and vision Vol. 16, 3/ :, /.,.,.,.,.,.,. // /.,.,.,.,. // : /.,.,.,.,.,.,. // /.,.,.,.,. // The usual ultrasonographic features of thyroid cancer are less frequent in small tumors that develop after a long latent period after the Chernobyl radiation release accident / V.M. Drozd, M.L. Lushchik, O.N. Polyanskaya, M.V. Fridman, Y.E. Demidchik, A.P. Lyshchik, J. Biko, C. Reiners, Y. Shibata, V.A. Saenko, S. Yamashita // Thyroid Vol. 19, ,. :,, /. // ,. /.,. // Ars medica , : 33

34 /. // Ars medica /.,.,.,. // ,. : /. // Ars medica /.,.,.,., // : /.,.,.,.,.,., K.W. Schmid // Clinical and pathologic features of sporadic papillary thyroid carcinoma registered in years in children and adolescents of Belarus / M. Fridman, N. Savva, O. Krasko, A. Zborovskaya, S. Mankovskaya, K.W. Schmid, Y. Demidchik // Thyroid Vol. 22, 10. P » /.,.,.,.,. //... i ,. : /. // Ars medica /.,.,.,.,.,., K.W. Schmid // , :, /.,.,.,.,. //

35 52. /.,.,.,. // : 936 /.,.,.,. // Initial presentation and late results of treatment of post-chernobyl papillary thyroid carcinoma in children and adolescents of Belarus / M. Fridman, N. Savva, O. Krasko, S. Mankovskaya, Branovan D.I., K.W. Schmid, Y. Demidchik // J. Clin. Endocrinol. Metab. [Electronic resource] Mode of access : Date of access : ,. /.,. //, /. «..-..»., ,. : /.,. // :..-..,. 75-,, : 2. /., ,. /. //,, : ,, /., ,. /.,.,. // :..-.., ,, , ,. /.,. // : 35

36 ..-.., ,, , ,. - /.,. // :..-..,, /... ; [...]., ,. /.,. // :..-..,, /... ; [...]., ,. /.,.,.,. // :..-..,, /... ; [...]., , /.,.,.,. // : 4-,, , ,. /.,.,. // :..-.,., 24 25, /..... ;..-..., Early diagnosis of thyroid cancer following the Chernobyl accident: ultrasound features with respect to latent period and tumor size / V.M. Drozd, M.L. Lushchik, O.N. Polyanskaya, M.V. Fridman, Y.E. Demidchik, A.P. Lyshchik, J. Biko, C. Reiners, Y. Shibata, V.A. Saenko, S. Yamashita //, :..-..,, /.»,...., «..» ;...,..,..,...,

37 66.» : /.,.,.,.,.,. // :..-..,, , / ;..., , /.,.,.,.,. // :..-..,, / ;..., ,. : /.,.,. // VI :.,, / «..».., ,. /.,.,. // :.,, /....., , /.,.,.,.,., Kurt W. Schmid,. // XVI,, , Fridman, M.V. Pathological characteristics of sporadic thyroid cancer in Belarus / M. Fridman, S. Mankovskaya, Yu. Demidchik // VII,,, /.., Conventional papillary thyroid carcinoma in children and adolescents / M. Fridman, S. Mankovskaya, N. Savva, O. Krasko, K.W. Schmid, Y. Demidchik // The 36th Annual Meeting of the European Thyroid Association, Pisa, Italy, 8 12 Sept Eur. Thyroid J Vol. 1, Suppl.1. P /.,.,.,.,. // I, 37

38 , XXI Vol. 5, ,. BRAFT1799A, RET/PTC 1,3 /.,.,. // : :..-..,, / ;..., ,. : /....,.. ;.,. //, [ ] : : ( 73.00) // :... /.,.,.,.,.,.,.,.,.,.,.,.,.,.,.,.,.,.,.,.,.,.,.,.,.,.,.,.,.,.,.,.,.,.,.,.,.,.,., P.M.,.,.,.,.,.,. ; ;...,.., ,. /.,.,.. :, : , (2009) G 01N 33/48, A 61B 10/00 /.,.,. ; 38

39 ; ; [ ] // : : : , (2006) G 01N 33/48, A 61B 10/00 /.,.,.,. ; ; ; ] // : :

40 :,, :,,. :,,. : 1078 ( 19 ),. 226,, ( ) 23,. :,,. :,. -,., ( ),. : -,,.,. :. 40

41 :,, :,, :,,. : 1078 ( 19 ),. 226,, ( ) 23,. :,,. :.,., ( ),. : -,,.,. :. 41

42 Summary Fridman Michael V. Papillary thyroid cancer in children and adolescents: diagnosis, treatment, prognosis Keywords: papillary carcinoma, thyroid, children and adolescents Objective: to improve the results of treatment of children and adolescents with radiogenic and "sporadic" forms of papillary thyroid cancer, basing on the certain key characteristics associated with clinical features of this disease. Subjects: 1078 children and adolescents (under 19 years) with papillary thyroid carcinoma associated with the consequences of the Chernobyl accident. Comparison group made up of 226 patients operated in the same age range who lacked were not irradiated and 23 patients who developed thyroid cancer after treatment for the first malignancy. Methods: morphological, molecular biological, statistics. Results: the latent period of radiogenic papillary cancer has a direct influence on the formation of the phenotype of the tumor and its clinical behavior. Age at surgery plays a key role in molecular biology and clinical and morphological manifestations of carcinoma, with a more aggressive course of the disease correlates with the younger age of the patients. Performing total thyroidectomy with extended lymph node dissection, supplemented by courses of radioiodine therapy (if indicated), reduces the likelihood of relapse. Recommendations: the heterogeneity of radiogenic thyroid papillary carcinomas and the evolution of the clinical and morphological manifestations of the disease should be considered when planning treatment tactics. For radiogenic carcinomas search for extrathyroid extension, nodal disease and internal organs metastases is vital. The entire arsenal of imaging techniques and the use of core biopsy to assess the morphological features associated with the spread of tumor and recurrence risks is mandated. Scope: oncology. 42