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271 60 20XX7Stage 1 20XX12 1715 271 20XX 5 7 Stage 20XX 5 7 Stage 20XX 1 13 20XX 1 13 15 10 11 12 10 11 BSC 12 271 271 20XX 5 7 Stage 20XX 5 7 Stage 20XX 1 13 20XX 1 13 15 15 10 12 11 BSC 271 10 12 11 BSC 271 Gifu University Hospital Cancer Center 11

20XX 5 7 20XX 1 Stage 13 20XX5 6 Group5 7 10 12 11 BSC 15 271 20 HBV 121/70mmHg 88 36.5 SpO 2 97% Performance Status (PS) : 0 271 WBC Neutro. Mono. Lymph. Eosino. Baso. RBC Hb Hct MCV MCH MCHC PLT PT% PT-INR APTT 7980 /L 71.3 % 5.9 % 19.4 % 2.9 % 0.5 % 394 10 4 /L 8.8 g/dl 30.7 % 77.9 fl 22.3 pg 28.7 % 34.4 10 4 /L 85 % 1.03 26.2 sec. TP Alb CK T-Bil AST ALT LDH ALP GTP ChE AMY Cre BUN UA Na K 6.7 g/dl 3.9 g/dl 72 IU/L 0.6 mg/dl 27 IU/L 12 IU/L 244 IU/L 259 IU/L 15 IU/L 221 IU/L 128 IU/L 0.78 mg/dl 13.7 mg/dl 2.9 mg/dl 139 meq/l 4.6 meq/l Cl 106 meq/l Glu 104 mg/dl CRP 0.68 mg/dl 271 CEA CA19-9 20.5 ng/ml 16.9 U/mL AFP 12816.1 ng/ml PIVKA-II 424 mau/ml CYFRA 1.9 ng/ml SCC 0.7 ng/ml NSE 12.2 ng/ml HBs 1809.03 IU/mL HBs <0.1 miu/ml HBe <0.50 S/CO (-) HBe 99 % (+) HBc HBV-DNA 437.0 COI (+) 2.4 Log copy/ml 271 adenocarcinoma, Group5 tub2 (>por) 5 271 271 12 Gifu University Hospital Cancer Center

XP/CT adenocarcinoma, Group5 tub2 (>por) HER2 3+ HER2Human Epidermal Growth Factor Receptor Type 2 HER2 20% 271 S9/1025mm 271 CT CT S58mm 271 S813mm 271 PET-CT HER2 Stage [ UM, L, type5, tub2(>por), ct4a, cn3a, cm1 (LYM, PUL), ch1] HER2 3+ HBV 271 271 Gifu University Hospital Cancer Center 13

271 271 20XX 5 7 Stage S-1 1 HER2 20XX 1 271 10 12 11 BSC 271 20XX 5 7 Stage 20XX 5 7 Stage S-1 1 HER2 S-1 1 HER2 2 2 20XX 1 20XX 1 10 12 11 BSC 271 10 12 11 BSC 271 14 Gifu University Hospital Cancer Center

20XX 5 7 Stage 20XX 5 7 Stage S-1 1 HER2 S-1 1 HER2 20XX 1 Cre 2.72 1eGFR50-60mL/min. 4 20XX 1 4 1 10 12 11 BSC 271 10 12 11 BSC 271 20XX 5 7 Stage 20XX 5 7 Stage S-1 1 HER2 S-1 1 HER2 4 4 1 PD 1 PD 20XX 1 20XX 1 S-1 3 10 12 11 BSC 271 10 12 11 BSC 271 20XX 5 7 Stage 20XX 5 7 Stage S-1 1 HER2 S-1 1 HER2 4 4 1 PD 1 PD 20XX 1 S-1 3 PRSD 20XX 1 S-1 7 10 12 11 BSC 271 10 12 11 BSC 271 Gifu University Hospital Cancer Center 15

20XX 5 7 Stage 20XX 5 7 Stage S-1 1 HER2 S-1 1 HER2 20XX 1 4 1 PD S-1 7 20XX 1 4 1 PD S-1 7 PD 10 12 11 BSC 271 10 12 11 BSC 271 20XX 5 7 Stage 2013 5 7 Stage S-1 1 HER2 S-1 1 HER2 20XX 1 4 1 PD S-1 7 PD 20XX 1 4 1 PD S-1 7 PD 6 S-1 3 6 S-1 3 PD 10 12 11 BSC 271 10 12 11 BSC 271 20XX 5 7 20XX 1 6 8 10 12 Stage S-1 1 HER2 1 PD 11 BSC S-1 7 PD S-1 3 PD 1 3 4 PS 2 271 0 1 2 3 20XX 5 7 20XX 1 6 8 10 12 Stage S-1 1 HER2 11 BSC 1 PD S-1 7 PD S-1 3 PD 1 3 PD 4 PS 271 0 1 2 3 2 16 Gifu University Hospital Cancer Center

Gifu University Hospital Cancer Center 17 271 20XX 7 20XX 1 6 8 10 1st 2nd 3rd 4th S-1 1 4 1 S-1 7 S-1 3 1 3 271 10 4 271 10 4 271 271 271 WBC Neutro. Mono. Lymph. Eosino. Baso. RBC Hb Hct MCV MCH MCHC PLT 7780 77.5 8.0 6.5 5.5 0.5 224 6.7 22.0 98.2 29.9 30.5 23.1 /L % % % % % 10 4 /L g/dl % fl pg % 10 4 /L PT% PT-INR APTT 110 0.91 28.7 % sec. TP Alb CK AST ALT LDH ALP GTP AMY Cre BUN UA Na K Cl T-Bil Glu CRP 4.3 2.2 39 69 18 557 340 65 60 0.89 14.6 5.5 137 3.9 105 0.4 102 3.94 g/dl g/dl IU/L IU/L IU/L IU/L IU/L IU/L IU/L mg/dl mg/dl mg/dl meq/l meq/l meq/l mg/dl mg/dl mg/dl

3IC 271 271 20XX 5 7 Stage 20XX 1 13 20XX6 10 11 BSC 12 271 20XX10 11 12 271 20XX10 11 12 20XX10 11 12 271 271 18 Gifu University Hospital Cancer Center

Gifu University Hospital Cancer Center 19 271 38 1426kcal5-7 ADLPS4 271 WBC Neutro. Mono. Lymph. Eosino. Baso. RBC Hb Hct MCV MCH MCHC PLT 14450 86.4 6.8 4.2 2.1 0.5 250 7.6 25.6 102.4 30.4 29.7 34.4 /L % % % % % 10 4 /L g/dl % fl pg % 10 4 /L PCT -D- 2.52 <0.8 <5.0 ng/ml TP Alb CK AST ALT LDH ALP GTP ChE Cre BUN Na K Cl T-Bil Glu CRP 4.9 1.9 157 155 35 2535 1022 496 77 0.67 22.1 149 3.5 116 0.7 105 28.51 g/dl g/dl IU/L IU/L IU/L IU/L IU/L IU/L IU/L mg/dl mg/dl meq/l meq/l meq/l mg/dl mg/dl mg/dl pg/ml pg/ml CT 271 271 BSC 31 271 IC 1 1 1 271 20XX11 12 500ml Na 3.3mg 200ml2 CTM 2g 2mg 50mg Na100mg PPI 1mg PIC 2500mL, 2 25%

500ml 500ml 200ml2 CTM 2g Na 3.3mg 200ml2 CTM 2g Na 3.3mg 2mg 2mg 50mg Na100mg 50mg Na100mg PPI 1mg PPI 1mg 2 25% 2500mL, 2 25% 2500mL, DNR 20XX11 PIC 12 271 20XX11 PIC 12 271 20XX 5 7 Stage 20XX 1 13 10 11 BSC 12 15 median survival time: MST 6-13 4, 2014 HER2trastuzumab ToGaXP/FPMST11.1trastuzumab MST13.8HER2MST16 Bang YJ, et al., Lancet, 2010; 376(9742): 687-697 4 17 271 271 50%10% 5% 121984-2000 0.5% 35101105, 1993. 40.8% Takakura K, et al : Metastatic tumors of central nervous system. Igaku-Shoin, Tokyo, 1982. 271 BSCkey person IC 271 20 Gifu University Hospital Cancer Center

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(total pain) (total pain) (total pain) 34 PPN:Kcal PPN:Kcal Gifu University Hospital Cancer Center 23

PPN:Kcal PPN:Kcal PPN:Kcal 24 Gifu University Hospital Cancer Center

40 20XX/12 2 3 CEA CA19-9 CT 4 data TP 6.7 mg/dl Alb 3.7 mg/dl AST 32 IU/L ALT 97 IU/L LDH 215 IU/L ALP 245 IU/L BUN 8.1 mg/dl Cre 0.51 mg/dl Na 141mEq/L K 4.2 meq/l Cl 106mEq/L CRP 0.90 mg/dl WBC 7270 /ul RBC 458X10 4 /ul Hb 11.4 g/dl Plt 35.7X10 4 /ul ICTP 11.2 ng/ml CEA 21.8 ng/ml CYFRA 5.6 ng/ml SCC 0.6 ng/ml ProGRP 37 ng/ml APTT 31s PT 13.9s INR 1.04 CT 20x/4 PET-CT Gifu University Hospital Cancer Center 25

T3N3M1b stage 20XX/4 8Gy 20XX/5 Performance status (PS) 4 20XX/5 20XX/4 CT 20XX/4 MRI T1 axial 20XX/4 MRI T2 coronal 20XX/5 26 Gifu University Hospital Cancer Center

20XX/5 20XX/5.. 8. 6. 6 8 9 Walker MS. J Med Econ. 2013 Brodowicz T. Ann Oncol. 2012 70-95 65-75 65-75 30-40 20-25 60 14-45 Coleman. Cancer Treat Rev 2001 Giordano. Cancer 2004 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% 2008 2009 2010 2011 2012 2008-2012 Gifu University Hospital Cancer Center 27

: : : : : : : EGF TGF-b FGFs BMPs IGFs RANKL PTHrP PGs IL-6 IL-1 RANKL Ca Ca ) 28 Gifu University Hospital Cancer Center

: performance status () 2003 Tomita K, et al. spine 2001 3-6 : Okano et al. Clin Calcium 2008 Normannno et al. dcrine-related Cancer 2005 Gifu University Hospital Cancer Center 29

6 8 9 20XX/5. 10 40 2 900 800 700 600 500 400 300 200 100 0 2011 0 5 10 15 20 25 4 9 14 19 24 29 30 35 40 45 50 55 60 65 70 75 80 85 34 39 44 49 54 59 64 69 74 79 84 12 10 8 6 4 2 0 2010 5 1015 2025303540455055606570758085 52541 520032005 0 10 20 30 40 50 60 70 80% 0 10 20 30 40 50 60 70 80 90% 2003-2005, 2013 22 EGFR EGFR 4 EGFR 1 EGFR 2 EGFR ON OFF 3 EGFR EGFR 5 4 3 2 1 0 4.5 2.2 1.4 1.6 1.61.7 1.3 1.4 1 1 1 1 5 4 3 2 1 0 3.7 4.2 1.51.5 1.3 1.3 1.4 1 1 1 1 1 0.7 1.1 1.7 1) Inoue M, et al. Pres Med. 38; 516-522, 2004 2) Sobue T, et al. Int J Cancer 99;245-251, 20023) Sasazuki S, et al. Int J Cancer 101; 560-566, 2002 4) Otani T, et al. Cancer Epidemiol Biomark Prev. 12; 1492-1500, 20035) Hanaoka T, et al. Int J Cancer 114; 317-322, 2005 30 Gifu University Hospital Cancer Center

3 1520 8085 5060 2530 XCT X CT 1. 2. 3. X 1. 2.CT 3. 4. X EGFR EML4-ALKVEGF 20155 A B AB B Gifu University Hospital Cancer Center 31

CBDCA, 2 CDDP, 1 PTX PEM, 3 110 46 46 EGFR CDDP, 1 CDDP, 1 CDDP, 1 DOC, 2 GEM, 610 VNR, 8610 CDDP CPT-11, 1, 81590 2, 3090 150mg11 250mg11 40mg11 46 46 46 46 46 3 EGFR 1 2 3 4 EGFR EGFR 32 Gifu University Hospital Cancer Center

30Gy /10 2024Gy/46 12Gy/2 8Gy/1 30Gy/10 Gifu University Hospital Cancer Center 33

1/3 4 34 Gifu University Hospital Cancer Center

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stage 5 7 46 5 6) 14 Gifu University Hospital Cancer Center 37

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ᒱ㜧 㸳 ࡀ ᆅᇦ㐃ᦠ ࢫ がん地域連携パスのパンフレット がんセンターホームページの次の URL からダウンロードが可能です https://hosp.gifu-u.ac.jp/center/gan/img/renkeipasu_leaflet.pdf 66 Gifu University Hospital Cancer Center

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US 1 2 3 1 2 3 6 4 5 6 4 5 6 5.12 cm 3 0.55 cm 3 78 Gifu University Hospital Cancer Center

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⒆ ⒆ ษ㝖ࡋ ᘓ ษ㝖 ๓ ᚋ 図 2 脛骨近位部の骨肉腫例 持続動注療法後に最小範囲で腫瘍を切除し 切除した腫瘍骨を温熱処理し て腫瘍細胞を死滅させた後 もとに戻して関節を再建しました Gifu University Hospital Cancer Center 81

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先進的がん診断の取り組み 分子生物学的コンパニオン診断の実践 病理部 ඛ㐍 ࡀ デ ࠕศᏊ Ꮫ ࢥ デ ᐇ㊶ 㒊 病理部では 分子生物学的解析をもとにしたコンパニオン診断への取り組みをすすめています 病理診断では 一般的に組織 細胞の形態学的変化を観察する病理形態学的診断が用いられます コンパニオン診断とは 染色体や遺伝子の発現の変化を特異的に解析し 病理形態学的診断の裏 付けとするもので FISH, DISH や PCR, RT-PCR, real time PCR といった方法があります た とえば 乳腺や消化管の腺がんにおける増殖レセプターをコードする HER2 遺伝子の過剰な増 幅を調べるのに 図 1 に示すように免疫組織化学で HER2 蛋白の発現が強く認められる場合 さらに DISH 法で HER2 の異常な増幅がないか解析します また 染色体の転座によって融合 遺伝子が悪性腫瘍を発生させることが最近知られており 図 2 に示すように 腫瘍特異的な融合 遺伝子の検出を FISH 法で解析しています さらに 融合遺伝子を RT-PCR で増幅し その塩 基配列を確認して診断確定に役立てています 今後 パラフィン包埋切片ベースで定量的 RTPCR を行って 遺伝子の発現量の異常を解析することも視野に入れ 環境整備 技術の習得を すすめていきます また がん登録実務者研修会にも講師を派遣するなど 都道府県がん診療連携拠点病院事業に も協力しています 図 3 図 1 A 胃腺がんの組織像 B 同 HER2 免疫組織化学染色 C 同 DISH による HER2 遺伝子増幅の解析 図 2 A FISH による融合遺伝子の検出 B,C FISH による染色体転座 図3 がん登録実務者研修会の一コマ 宮崎副部長 Gifu University Hospital Cancer Center 85

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