Pancreatic Cancer ( ) The Lancet, vol378, August 13, 2011 Audrey Vincent, PhD, Johns Hopkins Sol Goldman Joseph Herman, Rich Schulick, Ralph H Hruban,

Size: px

Start display at page:

Download "Pancreatic Cancer ( ) The Lancet, vol378, August 13, 2011 Audrey Vincent, PhD, Johns Hopkins Sol Goldman Joseph Herman, Rich Schulick, Ralph H Hruban,"

らむすえがら
7 years ago
Views:

1 Pancreatic Cancer () The Lancet, vol378, August 13, 2011 Audrey Vincent, PhD, Johns Hopkins Sol Goldman Joseph Herman, Rich Schulick, Ralph H Hruban, Michael Goggins, H23.9 The Lancet Johns Hopkins Sol Goldman high volume the Lancet NEJM low volume center 16.3% 16 high volume center Hospital volume and surgical mortality in the United States, NEJM,April11, high volume center CT CT Johns Hopkins 64 1/19

2 (sporadic) BRCA2breast cancer 2 PALB2 AKB48 Johns Hopikins BRCA2 Oxana Yablonskaya 3 Oxana 1 BRCA BRCA2 DNA 1 BRCA2 1 BRCA2 80 5% 10 NHK Johns Hopkins 2/19

3 Chicago Center for Jewish Genetic Disorders BRCA2 BRCA1, BRCA2 O O 10 metastatic subclone % CA19-9 CA19-9 ( 37 ) IU/ml 3 CT MRI 3/19

4 CT ERCP CT 2cm T1T2 2cm SMA SMA 20 SMA high volume center gemcitabine, fluorouracil gemcitabine () Gemcitabine () gemcitabine+fluorouracil fluorouracil TS1 CTCA19-9mutant DNA gemcitabine erlotinib, fluorouracil, capecitabine Erlotinib() EGFR(epidermal growth factor receptor) gemcitabinepaclitaxel Paclitaxel taxan taxus Taxan supportive care CT ablasion 4/19

5 PEG The Lancet, 38 the Lancet, O 4. metformin BRCA2PALB BRCA metastatic subclone % CT 18. MRI 19. CA IU/ml 20. CT 21. ERCP SMA SMA T1 T2 2cm 5/19

6 high volume 28. gemcitabinefluorouracil gemcitabine() 31. gemcitabinefluorouracil 32. gemcitabine fluorouracil, erlotinib, capecitabine 33. gemcitabine+paclitaxel CTCA19-9mutantDNA 36. CT ablasion 37. PEG 38. Pancreatic Cancer () The Lancet, vol378, August 13, 2011 H23.9 Audrey Vincent, PhD, Johns Hopkins Sol Goldman Joseph Herman, Rich Schulick, Ralph H Hruban, Michael Goggins, non-invasive precursors of malignant disease /19

7 pancreatic ductal adenocarcinoma chlorynated hydrocarbon solvents, nickel Helicobacter pylori Metformin familial pancreatic cancer sporadic 50 BRCA2 517% 10% BRCA2 PALB2 (partner and localizer of BRCA2) 3% BRCA2 PALB2 Fanconi DNA BRCA2-PALB2-FanconiDNA PARP inhibitor alkylating agents CDKN2A familial atypical multiple-mole melanoma germline STK11 Peutz-Jeghers syndrome 7/19

8 PRSS1 Lynch syndrome (hereditary non-polyposis colon cancer) O BRCA2breast cancer susceptibility gene PALB2 chemoprevention BRCA2 Atypical multiple-mole melanoma CDKN2A ( pancreatic ductal adenocarcinoma) pancreatic intraepithelial neoplasia intraductal papillary mucinous neoplasm mucinous cystic neoplasms 24 exomes KRAS CDKN2A, TP53, SMAD4, BRCA2telomere KRAS telomere pancreatic intraepithelial neoplasia Telomere TP53, SMAD4, BRCA2 pancreatic intraepithelial neoplasia, BRAF, MYB, AKT2, EGFR 8/19

9 MAP2K4, STK11, TFFBR1, TGFBR2, ACVR1B, ACVR2A, FBXW7, EP300 PIK3CG, DGKA, STK33, TTK, PRKCG driver mutation Intraductal papillary mucinous neoplasm intraepithelial neoplasia SMAD4 driver gene epigenetic DNA methylation non-coding RNA RNA DNA MethylationCH3 gene silencing CDKN2A DNA gene silencing MLH1 CDH1 CDKN1C, RELN, SPARC,TFPI2 aberrant gene silencing promotor hypomethylation SFN, MSLN,S100A4 RNA micro RNA expression micro RNA mir-21, mir-34,mir155, mir-200 Micro RNA molecular clock 10 metastatic subclone driver gene 9/19

10 cancer-associated fibroblasts KRAS1, RB1, CDKN2A, TP53, SMAD4, TGB1 Hedgehog, NOTCH, AKT1-PI3K-MTOR, BRCA2-PALB2-Fanconi T regulatory lymphocytes () mesothelin tumor-initiating cell, cancer stem cell pancreatic intraepithelial neoplasia noninvasive intraductal papillary mucinous neoplasm mucinous cystic neoplasm CAPS intraductal papillary mucinous neoplasm 10/19

11 1cm CAP3 CT27% 93 MRI81% pancreatic intraepithelial neoplsasia fine-needle aspiration silent chachexia panniculitis CTtri-phasic pancreatic-protocol CT 80 accuracy 3 CT CT MRI resectable borderline resectable locally advanced metastatic 11/19

12 X CT PET CT CT CA U/ml unresectability CT fine-needle aspiration ERCP 20 nonneoplastic reactive cell local or resectable 10 median 1723 Stage 0 (Tis, N0, M0 : carcinoma in situ, ) Stage 1A (T1,N0, M0: 2cm ) Stage 1B (T2, N0, M0: 2cm ) Stage 2A (T3, N0,M0: celiac A, SMA ) Stage 2B T1,N1,M0. 2cm T2,N1,M0: 2cm T3,N1,M0: celiac A,SMA Borderline resectable: 10 median20 Stage3 (T4,anyN,M0: celiac A SMA ) celiac A SMA 180 Locally advanced or unresectable ( 30 median814 ) Stage3 (T4,anyN,M0: celiac A SMA ) celiac A SMA /19

13 Metastatic ( 60 median 4-6 ) Stage4 (anyt, anyn,m1 : T, N ) MSW a. low volume high volume gastric emptying R0 negative resection SMV tattooing CA /19

14 b. R0 (negative resection) R1 margin R2 resection SMV T3 pancreatic ductal adenocarcinoma variants colloid carcinoma (intestinal- type intraductal papillary mucinous neoplasm ) medullary cancer (microsatellite instability ) adenosquamous tumor hepatoid carcinoma signet-ring cell cancer undifferentiated carcinoma undifferentiated carcinoma with osteoclast-like giant cells ductal adenocarcinoma SMAD4 SPARC c. Adjuvant and neoadjuvant treatment 12 CT CA19-9 GITSGCONKO-001RTOG-9704 GISTG flluorouracil chemoradiation ESPAC-1 RTOG-9704 fluorouracil chemoradiation gemcitabine fluorouracil ESPAC-3 Gemcitbine fluorouracil 14/19

15 CONKO-001 Gemcitabine median chemoradiation R0 resectiion R0 R1() median R1 resection R0 resection R1 resection neoadjuvant therapyr0 resection d. median 3-6 median 9-15 gemcitabine() gemcitabine locally advanced disease chemoradiation 30 resectable patient 15/19

16 The National Comprehensive Cancer Network Fluorouracil 50 60Gy 4 gemcitabine Fluorouracil gemcitabine radiosensitiser gemcitbine fluorouracil e Gy Gy/ Fluorouracil capecitabine (oral fluoropyrimidine) radiosesnsitizer 45Gy 5 15Gy neoadjuvant chemoradiotherapy borderline ml ml intensity-modulated radiation therapystereotactic body radiation therapy f. gemcitabine() gemcitabine () fluorouracil (5FU) gemcitabine ()capecitabine () Gemcitabine gemcitabine+fluorouracil+folinic acid+irinotecan+oxaliplatin 11 gemcitabine 6.8 gemcitabine+erlotinib Erlotinib EGFR(epidermal growth factor receptor) gemcitabine FDA 16/19

17 erlotinib wild-type KRAS subgroup gemcitabine+erlotinib+bevacizmab gemcitabine+erlotinib progression-free survival gemcitabine+platinum- based drug/fluoropyrimidine 2 gemcitabine gemcitabine+paclitaxel Gemcitabine1000mg/m2 nanoparticle-formulated paclitaxel (125mg/m2) phase3 trial oxaliplatin+fluorouracil+folinic acid second-line treatment Gemcitabine fluorouracil+folinic acid CONKO-003 trial g. CT RECIST(response evaluation criteria in solid tumours) criteria CT 2 CA19-9 mutant DNA h. olaparib BRCA2-PALB2-Fanconi DNA Poly (ADP-ribose) polymerase (PARP) inhibitors olaparib PARP DNA poly(adp-ribose) DNA histone 17/19

18 DNA, olaparib GDC-0449 GDC-0449 hedgehog pathway inhibitor phase 2 cryotherapy, photodynamic therapy, radiofrequency ablasion i. supportive care CT plexus ablasion biliary stenting Plastic stent Metal stent 20 PEG the Lancet, O 4. metformin BRCA2PALB BRCA /19

19 11. metastatic subclone % CT 18. MRI 19. CA IU/ml 20. CT 21. ERCP SMA SMA T1 T2 2cm high volume 28. gemcitabinefluorouracil gemcitabine() 31. gemcitabinefluorouracil 32. gemcitabine fluorouracil, erlotinib, capecitabine 33. gemcitabine+paclitaxel CTCA19-9mutantDNA 36. CT ablasion 37. PEG /19

食道がん化学放射線療法後のsalvage手術

食道がん化学放射線療法後のsalvage手術 2006 2 17 52 Daly JM, et al. J Am Coll Surg 2000;190:562-573 Esophageal Cancer: Results of an American College of Surgeons Patient Care Evaluation Study Daly JM, et al. J Am Coll Surg 2000;190:562-573