ISSN 1001-5256
CN 22-1108/R
Issue 10
Oct.  2018
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Comprehensive guidelines for the diagnosis and treatment of pancreatic cancer (2018 version)

DOI: 10.3969/j.issn.1001-5256.2018.10.011
  • Published Date: 2018-10-20
  • Pancreatic cancer ranks the fifth leading cause of cancer-related death, while the incidence has increased in the recent years.Although available diagnosis and treatment have failed to significantly improve patients' outcome, some advances have been made along with the understanding of the new concepts from oncology over the past several years. Pancreatic Cancer Committee of Chinese Anti-Cancer Association worked out this latest edition of“The Clinical Practice Guidelines for Pancreatic Cancer ( version 2018) ”based on current situation to standardize and improve the diagnosis and treatment of pancreatic cancer in China. This guideline shows algorithms for the diagnosis involving classification and staging, the systematic treatment including surgical resection, systemic chemotherapy and radiation therapy, and the whole-course management model for patients with pancreatic cancer. Different from previous consensus, this guideline contains the discussions and recommendations of 19 hot-issues in the clinical practice for pancreatic cancer in a question-oriented form, such as selection of biopsy and specimen sites, clinical diagnostic criteria for pancreatic cancer, assessment of resectable pancreatic cancer, indications and methods of preoperative biliary drainage, application of laparoscopic surgery, effect of expanding resection on patients' outcomes, dissection of group 16 th lymph node in standard pancreaticoduodenectomy, prognostic value of serum tumor markers, and neoadjuvant therapy in patients with resectable pancreatic cancer, etc. This guideline aims to raise a better comprehensive understanding of the diagnosis and treatment of pancreatic cancer for specialists, and further improving and standardizing the clinical practice in different medical institutions.


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  • [1] SIEGEL RL, MILLER KD, JEMAL A.Cancer statistics, 2018[J].CA Cancer J Clin, 2018, 68 (1) :7-30.
    [2]CHEN W, ZHENG R, BAADE PD, et al.Cancer statistics in China, 2015[J].CA Cancer J Clin, 2016, 66 (2) :115-132.
    [3]CHEN W, SUN K, ZHENG R, et al.Cancer incidence and mortality in China, 2014[J].Chin J Cancer Res, 2018, 30 (1) :1-12.
    [4]LI D, MORRIS JS, LIU J, et al.Body mass index and risk, age of onset, and survival in patients with pancreatic cancer[J].JAMA, 2009, 301 (24) :2553-2562.
    [5]BAGNARDI V, ROTA M, BOTTERI E, et al.Alcohol consumption and site-specific cancer risk:A comprehensive dose-response meta-analysis[J].Br J Cancer, 2015, 112 (3) :580-593.
    [6]CAMARA SN, YIN T, YANG M, et al.High risk factors of pancreatic carcinoma[J].J Huazhong Univ Sci Technolog Med Sci, 2016, 36 (3) :295-304.
    [7]GHIORZO P, FORNARINI G, SCIALLERO S, et al.CDKN2A is the main susceptibility gene in Italian pancreatic cancer families[J].J Med Genet, 2012, 49 (3) :164-170.
    [8]ZHEN DB, RABE KG, GALLINGER S, et al.BRCA1, BRCA2, PALB2, and CDKN2A mutations in familial pancreatic cancer:A PAC-GENE study[J].Genet Med, 2015, 17 (7) :569-577.
    [9]PORUK KE, GAY DZ, BROWN K, et al.The clinical utility of CA 19-9 in pancreatic adenocarcinoma:Diagnostic and prognostic updates[J].Curr Mol Med, 2013, 13 (3) :340-351.
    [10]LUO G, LIU C, GUO M, et al.CA19-9-Low&Lewis (+) pancreatic cancer:A unique subtype[J].Cancer Lett, 2017, 385:46-50.
    [11]LIAO WC, TU YK, WU MS, et al.Blood glucose concentration and risk of pancreatic cancer:Systematic review and dose-response meta-analysis[J].BMJ, 2015, 350:g7371.
    [12]XU J, CAO Z, LIU W, et al.Plasma miRNAs effectively distinguish patients with pancreatic cancer from controls:A multicenter study[J].Ann Surg, 2016, 263 (6) :1173-1179.
    [13]XU L, LI Q, XU D, et al.hsa-miR-141 downregulates TM4SF1to inhibit pancreatic cancer cell invasion and migration[J].Int JOncol, 2014, 44 (2) :459-466.
    [14]MELO SA, LUECKE LB, KAHLERT C, et al.Glypican-1 identifies cancer exosomes and detects early pancreatic cancer[J].Nature, 2015, 523 (7559) :177-182.
    [15]COHEN JD, JAVED AA, THOBURN C, et al.Combined circulating tumor DNA and protein biomarker-based liquid biopsy for the earlier detection of pancreatic cancers[J].Proc Natl Acad Sci U SA, 2017, 114 (38) :10202-10207.
    [16]MA L, TIAN X, GUO H, et al.Long noncoding RNA H19 derived miR-675 regulates cell proliferation by down-regulating E2F-1in human pancreatic ductal adenocarcinoma[J].J Cancer, 2018, 9 (2) :389-399.
    [17]LI W, ZHANG X, LU X, et al.5-Hydroxymethylcytosine signatures in circulating cell-free DNA as diagnostic biomarkers for human cancers[J].Cell Res, 2017, 27 (10) :1243-1257.
    [18]AL-HAWARY MM, FRANCIS IR, CHARI ST, et al.Pancreatic ductal adenocarcinoma radiology reporting template:Consensus statement of the society of abdominal radiology and the American pancreatic association[J].Gastroenterology, 2014, 146 (1) :291-304.
    [19]TIRKES T, SANDRASEGARAN K, SANYAL R, et al.Secretinenhanced MR cholangiopancreatography:Spectrum of findings[J].Radiographics, 2013, 33 (7) :1889-1906.
    [20]XU HX, CHEN T, WANG WQ, et al.Metabolic tumour burden assessed by18F-FDG PET/CT associated with serum CA19-9 predicts pancreatic cancer outcome after resection[J].Eur J Nucl Med Mol Imaging, 2014, 41 (6) :1093-1102.
    [21]CANTO MI, GOGGINS M, HRUBAN RH, et al.Screening for early pancreatic neoplasia in high-risk individuals:A prospective controlled study[J].Clin Gastroenterol Hepatol, 2006, 4 (6) :766-781.
    [22]OKASHA HH, NAGA MI, ESMAT S, et al.Endoscopic ultrasound-guided fine needle aspiration versus percutaneous ultrasoundguided fine needle aspiration in diagnosis of focal pancreatic masses[J].Endosc Ultrasound, 2013, 2 (4) :190-193.
    [23]LI JH, HE R, LI YM, et al.Endoscopic ultrasonography for tumor node staging and vascular invasion in pancreatic cancer:A meta-analysis[J].Dig Surg, 2014, 31 (4-5) :297-305.
    [24]BAILEY P, CHANG DK, NONES K, et al.Genomic analyses identify molecular subtypes of pancreatic cancer[J].Nature, 2016, 531 (7952) :47-52.
    [25]WADDELL N, PAJIC M, PATCH AM, et al.Whole genomes redefine the mutational landscape of pancreatic cancer[J].Nature, 2015, 518 (7540) :495-501.
    [26]DU Y, ZHAO B, LIU Z, et al.Molecular subtyping of pancreatic cancer:Translating genomics and transcriptomics into the clinic[J].J Cancer, 2017, 8 (4) :513-522.
    [27]FERRONE CR, LEVINE DA, TANG LH, et al.BRCA germline mutations in Jewish patients with pancreatic adenocarcinoma[J].JClin Oncol, 2009, 27 (3) :433-438.
    [28]CONNOR AA, DENROCHE RE, JANG GH, et al.Association of distinct mutational signatures with correlates of increased immune activity in pancreatic ductal adenocarcinoma[J].JAMA Oncol, 2017, 3 (6) :774-783.
    [29]CHANTRILL LA, NAGRIAL AM, WATSON C, et al.Precision medicine for advanced pancreas cancer:The individualized molecular pancreatic cancer therapy (IMPa CT) trial[J].Clin Cancer Res, 2015, 21 (9) :2029-2037.
    [30]COLLISSON EA, SADANANDAM A, OLSON P, et al.Subtypes of pancreatic ductal adenocarcinoma and their differing responses to therapy[J].Nat Med, 2011, 17 (4) :500-503.
    [31]MOFFITT RA, MARAYATI R, FLATE EL, et al.Virtual microdissection identifies distinct tumor-and stroma-specific subtypes of pancreatic ductal adenocarcinoma[J].Nat Genet, 2015, 47 (10) :1168-1178.
    [32]National Comprehensive Cancer Network.NCCN clinical practice guidelines in oncology (NCCN guidelines) :Pancreatic adenocarcinoma[EB/OL].[2018-04-27].https://www.nccn.org/professionals/physician_gls/pdf/pancreatic.pdf.
    [33]LIU L, XU HX, HE M, et al.A novel scoring system predicts postsurgical survival and adjuvant chemotherapeutic benefits in patients with pancreatic adenocarcinoma:Implications for AJCC-TNM staging[J].Surgery, 2018, 163 (6) :1280-1294.
    [34]SHI S, HUA J, LIANG C, et al.Proposed modification of the 8th edition of the AJCC staging system for pancreatic ductal adenocarcinoma[J].Ann Surg, 2018.[Epub ahead of print]
    [35]SHEN BY, SHI YS.Present situation and prospect of Da Vinci robot-assisted pancreatic surgery[J].Chin J Dig Surg, 2017, 16 (8) :797-799. (in Chinese) 沈柏用, 施昱晟.达芬奇机器人手术系统辅助胰腺手术的现状与展望[J].中华消化外科杂志, 2017, 16 (8) :797-799.
    [36]ZHANG H, WU X, ZHU F, et al.Systematic review and meta-analysis of minimally invasive versus open approach for pancreaticoduodenectomy[J].Surg Endosc, 2016, 30 (12) :5173-5184.
    [37]CAO F, LI J, LI A, et al.Radical antegrade modular pancreatosplenectomy versus standard procedure in the treatment of left-sided pancreatic cancer:A systemic review and meta-analysis[J].BMC Surg, 2017, 17 (1) :67.
    [38]TAKAHASHI H, AKITA H, TOMOKUNI A, et al.Preoperative Gemcitabine-based chemoradiation therapy for borderline resectable pancreatic cancer:Impact of venous and arterial involvement status on surgical outcome and pattern of recurrence[J].Ann Surg, 2016, 264 (6) :1091-1097.
    [39]FRIGERIO I, REGI P, GIARDINO A, et al.Downstaging in stage IV pancreatic cancer:A new population eligible for surgery?[J].Ann Surg Oncol, 2017, 24 (8) :2397-2403.
    [40]OETTLE H, NEUHAUS P, HOCHHAUS A, et al.Adjuvant chemotherapy with gemcitabine and long-term outcomes among patients with resected pancreatic cancer:The CONKO-001 randomized trial[J].JAMA, 2013, 310 (14) :1473-1481.
    [41]KHORANA AA, MANGU PB, BERLIN J, et al.Potentially curable pancreatic cancer:American society of clinical oncology clinical practice guideline update[J].J Clin Oncol, 2017, 35 (20) :2324-2328.
    [42]KHORANA AA, MANGU PB, BERLIN J, et al.Potentially curable pancreatic cancer:American society of clinical oncology clinical practice guideline[J].J Clin Oncol, 2016, 34 (21) :2541-2556.
    [43]LIU L, XU H, WANG W, et al.A preoperative serum signature of CEA+/CA125+/CA19-9≥1000 U/m L indicates poor outcome to pancreatectomy for pancreatic cancer[J].Int J Cancer, 2015, 136 (9) :2216-2227.
    [44]NEOPTOLEMOS JP, MOORE MJ, COX TF, et al.Effect of adjuvant chemotherapy with fluorouracil plus folinic acid or gemcitabine vs observation on survival in patients with resected periampullary adenocarcinoma:The ESPAC-3 periampullary cancer randomized trial[J].JAMA, 2012, 308 (2) :147-156.
    [45]NEOPTOLEMOS JP, PALMER DH, GHANEH P, et al.Comparison of adjuvant gemcitabine and capecitabine with gemcitabine monotherapy in patients with resected pancreatic cancer (ESPAC-4) :A multicentre, open-label, randomised, phase 3 trial[J].Lancet, 2017, 389 (10073) :1011-1024.
    [46]UESAKA K, BOKU N, FUKUTOMI A, et al.Adjuvant chemotherapy of S-1 versus gemcitabine for resected pancreatic cancer:A phase 3, open-label, randomised, non-inferiority trial (JASPAC 01) [J].Lancet, 2016, 388 (10041) :248-257.
    [47]RAHMA OE, DUFFY A, LIEWEHR DJ, et al.Second-line treatment in advanced pancreatic cancer:A comprehensive analysis of published clinical trials[J].Ann Oncol, 2013, 24 (8) :1972-1979.
    [48]SAHIN IH, ASKAN G, HU ZI, et al.Immunotherapy in pancreatic ductal adenocarcinoma:An emerging entity?[J].Ann Oncol, 2017, 28 (12) :2950-2961.
    [49]FENG M, XIONG G, CAO Z, et al.PD-1/PD-L1 and immunotherapy for pancreatic cancer[J].Cancer Lett, 2017, 407:57-65.
    [50]VON HOFF DD, ERVIN T, ARENA FP, et al.Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine[J].NEngl J Med, 2013, 369 (18) :1691-1703.
    [51]WANG-GILLAM A, LI CP, BODOKY G, et al.Nanoliposomal irinotecan with fluorouracil and folinic acid in metastatic pancreatic cancer after previous gemcitabine-based therapy (NAPOLI-1) :A global, randomised, open-label, phase 3 trial[J].Lancet, 2016, 387 (10018) :545-557.
    [52]CONROY T, DESSEIGNE F, YCHOU M, et al.FOLFIRINOXversus gemcitabine for metastatic pancreatic cancer[J].N Engl JMed, 2011, 364 (19) :1817-1825.
    [53]SUDO K, ISHIHARA T, HIRATA N, et al.Randomized controlled study of gemcitabine plus S-1 combination chemotherapy versus gemcitabine for unresectable pancreatic cancer[J].Cancer Chemother Pharmacol, 2014, 73 (2) :389-396.
    [54]GILL S, KO YJ, CRIPPS C, et al.PANCREOX:A randomized phase III study of fluorouracil/leucovorin with or without oxaliplatin for second-line advanced pancreatic cancer in patients who have received gemcitabine-based chemotherapy[J].J Clin Oncol, 2016, 34 (32) :3914-3920.
    [55]UENO H, IOKA T, IKEDA M, et al.Randomized phase III study of gemcitabine plus S-1, S-1 alone, or gemcitabine alone in patients with locally advanced and metastatic pancreatic cancer in Japan and Taiwan:GEST study[J].J Clin Oncol, 2013, 31 (13) :1640-1648.
    [56]CUNNINGHAM D, CHAU I, STOCKEN DD, et al.Phase III randomized comparison of gemcitabine versus gemcitabine plus capecitabine in patients with advanced pancreatic cancer[J].J Clin Oncol, 2009, 27 (33) :5513-5518.
    [57]OETTLE H, RIESS H, STIELER JM, et al.Second-line oxaliplatin, folinic acid, and fluorouracil versus folinic acid and fluorouracil alone for gemcitabine-refractory pancreatic cancer:Outcomes from the CONKO-003 trial[J].J Clin Oncol, 2014, 32 (23) :2423-2429.
    [58]ZHU CP, SHI J, CHEN YX, et al.Gemcitabine in the chemoradiotherapy for locally advanced pancreatic cancer:A meta-analysis[J].Radiother Oncol, 2011, 99 (2) :108-113.
    [59]HUGUET F, GIRARD N, GUERCHE CS, et al.Chemoradiotherapy in the management of locally advanced pancreatic carcinoma:Aqualitative systematic review[J].J Clin Oncol, 2009, 27 (13) :2269-2277.
    [60]JIN Z, DU Y, LI Z, et al.Endoscopic ultrasonography-guided interstitial implantation of iodine 125-seeds combined with chemotherapy in the treatment of unresectable pancreatic carcinoma:A prospective pilot study[J].Endoscopy, 2008, 40 (4) :314-320.
    [61]DU Y, JIN Z, MENG H, et al.Long-term effect of gemcitabinecombined endoscopic ultrasonography-guided brachytherapy in pancreatic cancer[J].J Interv Gastroenterol, 2013, 3 (1) :18-24.
    [62]JONES WE 3rd, SUH WW, ABDEL-WAHAB M, et al.ACR appropriateness criteriaresectable pancreatic cancer[J].Am J Clin Oncol, 2017, 40 (2) :109-117.
    [63]KATZ MH, CRANE CH, VARADHACHARY G.Management of borderline resectable pancreatic cancer[J].Semin Radiat Oncol, 2014, 24 (2) :105-112.
    [64]LIU Z, LUO G, GUO M, et al.Lymph node status predicts the benefit of adjuvant chemoradiotherapy for patients with resected pancreatic cancer[J].Pancreatology, 2015, 15 (3) :253-258.
    [65]HERMAN JM, SWARTZ MJ, HSU CC, et al.Analysis of fluorouracil-based adjuvant chemotherapy and radiation after pancreaticoduodenectomy for ductal adenocarcinoma of the pancreas:Results of a large, prospectively collected database at the Johns Hopkins Hospital[J].J Clin Oncol, 2008, 26 (21) :3503-3510.
    [66]BALABAN EP, MANGU PB, KHORANA AA, et al.Locally advanced, unresectable pancreatic cancer:American society of clinical oncology clinical practice guideline[J].J Clin Oncol, 2016, 34 (22) :2654-2668.
    [67]HURT CN, FALK S, CROSBY T, et al.Long-term results and recurrence patterns from SCALOP:A phase II randomised trial of gemcitabine-or capecitabine-based chemoradiation for locally advanced pancreatic cancer[J].Br J Cancer, 2017, 116 (10) :1264-1270.
    [68]KARAKAS Y, LACIN S, YALCIN S.Recent advances in the management of pancreatic adenocarcinoma[J].Expert Rev Anticancer Ther, 2018, 18 (1) :51-62.
    [69]LUCENTEFORTE E, LA VECCHIA C, SILVERMAN D, et al.Alcohol consumption and pancreatic cancer:A pooled analysis in the international pancreatic cancer case-control consortium (PanC4) [J].Ann Oncol, 2012, 23 (2) :374-382.
    [70]HONG GB, ZHOU JX, SUN HB, et al.Continuous transarterial infusion chemotherapy with gemcitabine and 5-Fluorouracil for advanced pancreatic carcinoma[J].Asian Pac J Cancer Prev, 2012, 13 (6) :2669-2673.
    [71]CHEN Y, WANG XL, WANG JH, et al.Transarterial infusion with gemcitabine and oxaliplatin for the treatment of unresectable pancreatic cancer[J].Anticancer Drugs, 2014, 25 (8) :958-963.
    [72]FEARON K, STRASSER F, ANKER SD, et al.Definition and classification of cancer cachexia:An international consensus[J].Lancet Oncol, 2011, 12 (5) :489-495.
    [73]BEATTY GL, CHIOREAN EG, FISHMAN MP, et al.CD40 agonists alter tumor stroma and show efficacy against pancreatic carcinoma in mice and humans[J].Science, 2011, 331 (6024) :1612-1616.
    [74]RHIM AD, OBERSTEIN PE, THOMAS DH, et al.Stromal elements act to restrain, rather than support, pancreatic ductal adenocarcinoma[J].Cancer Cell, 2014, 25 (6) :735-747.
    [75]ROBERTS KJ, KERSHNER AM, BEACHY PA.The stromal niche for epithelial stem cells:A template for regeneration and a brake on malignancy[J].Cancer Cell, 2017, 32 (4) :404-410.
    [76]MOORE MJ, GOLDSTEIN D, HAMM J, et al.Erlotinib plus gemcitabine compared with gemcitabine alone in patients with advanced pancreatic cancer:A phase III trial of the National Cancer Institute of Canada Clinical Trials Group[J].J Clin Oncol, 2007, 25 (15) :1960-1966.
    [77]SCHULTHEIS B, REUTER D, EBERT MP, et al.Gemcitabine combined with the monoclonal antibody nimotuzumab is an active first-line regimen in KRAS wildtype patients with locally advanced or metastatic pancreatic cancer:A multicenter, randomized phase IIb study[J].Ann Oncol, 2017, 28 (10) :2429-2435.
    [78]MARTIN RC 2nd, KWON D, CHALIKONDA S, et al.Treatment of 200 locally advanced (stage III) pancreatic adenocarcinoma patients with irreversible electroporation:Safety and efficacy[J].Ann Surg, 2015, 262 (3) :486-494.
    [79] ZHAO YP.Attach importance to the multidisciplinary diagnosis and treatment of pancreatic cancer[J].Chin J Surg, 2016, 54 (11) :801-803. (in Chinese) 赵玉沛.重视胰腺癌的多学科诊疗[J].中华外科杂志, 2016, 54 (11) :801-803.
    [80]RIEMANN JF, EICKHOFF A.Pancreas:Preoperative biliary drainage for pancreatic cancer[J].Nat Rev Gastroenterol Hepatol, 2010, 7 (6) :308-309.
    [81]van der GAAG NA, RAUWS EA, van EIJCK CH, et al.Preoperative biliary drainage for cancer of the head of the pancreas[J].NEngl J Med, 2010, 362 (2) :129-137.
    [82]HARTWIG W, STROBEL O, HINZ U, et al.CA19-9 in potentially resectable pancreatic cancer:Perspective to adjust surgical and perioperative therapy[J].Ann Surg Oncol, 2013, 20 (7) :2188-2196.
    [83]O'BRIEN DP, SANDANAYAKE NS, JENKINSON C, et al.Serum CA19-9 is significantly upregulated up to 2 years before diagnosis with pancreatic cancer:Implications for early disease detection[J].Clin Cancer Res, 2015, 21 (3) :622-631.
    [84]KONDO S.Japanese pancreas society staging systems for pancreatic cancer//NEOPTOLEMOS JP, URRUTIA R, ABBRUZZESE J, et al.Pancreatic Cancer[M].New York:Springer, 2010:1035-1050.
    [85]LIU C, CHEN R, CHEN Y, et al.Should a standard lymphadenectomy during pancreatoduodenectomy exclude para-aortic lymph nodes for all cases of resectable pancreatic head cancer?A consensus statement by the Chinese Study Group for Pancreatic Cancer (CSPAC) [J].Int J Oncol, 2015, 47 (4) :1512-1516.
    [86]CAPELLO M, LEE M, WANG H, et al.Carboxylesterase 2 as a determinant of response to irinotecan and neoadjuvant FOLFIRINOXtherapy in pancreatic ductal adenocarcinoma[J].J Natl Cancer Inst, 2015, 107 (8) :djv132.
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