Diagnostik und Therapie des Pankreaskarzinoms

ZUSAMMENFASSUNG

Das Pankreaskarzinom weist eine weltweit steigende Inzidenz auf, wobei die Gründe hierfür bis dato nicht bekannt sind. Die NCCN-Leitlinie von 2017 empfiehlt zur Diagnose und Beurteilung der Resektabilität des pankreatischen duktalen Adenokarzinoms (PDAC) die Computertomografie (CT) als primäre Bildgebung. Bei fehlendem Nachweis und Verdacht eines Tumors wird die Magnetresonanztomografie (MRT) zur Abklärung kleiner Tumoren sowie zur Diagnostik einer eventuellen Lebermetastasierung empfohlen. Durch den Einsatz von neoadjuvanten Chemotherapieregimes konnte die Anzahl der insgesamt resezierbaren Tumoren deutlich gesteigert und somit auch die Prognose dramatisch verbessert werden. Inzwischen sind neue Therapiekonzepte etabliert, die zu einer signifikanten Verbesserung der Prognose beim inoperablen Pankreaskarzinom in der palliativen Situation geführt haben. Im Rahmen der Erkrankung mit einem Pankreaskarzinom kann es zu einer Verlegung der Gallenwege und konsekutiv zu Cholestase und Cholangitis kommen. In einem solchen Fall sollte, sofern möglich, der Galleabfluss wiederhergestellt werden. Eine adäquate Therapieoption stellt hierbei die Durchführung einer ERCP mit Stentanlage dar. Auch bei Obstruktion des Duodenums ist eine endoskopische Stentanlage zur Wiederherstellung der Passage eine Option.

• Literatur

• 1 Iglesias-Garcia J, Lindkvist B, Larino-Noia J. et al. Differential diagnosis of solid pancreatic masses: contrast-enhanced harmonic (CEH-EUS), quantitative-elastography (QE-EUS), or both?. United European Gastroenterol 2017; 5: 236-246
• 2 Puli SR, Singh S, Hagedorn CH. et al. Diagnostic accuracy of EUS for vascular invasion in pancreatic and periampullary cancers: a meta-analysis and systematic review. Gastrointest Endosc 2007; 65: 788-797
• 3 Chen J, Yang R, Lu Y. et al. Diagnostic accuracy of endoscopic ultrasound-guided fine-needle aspiration for solid pancreatic lesion: a systematic review. J Cancer Res Clin Oncol 2012; 138: 1433-1441
• 4 Lidsky ME, Sun Z, Nussbaum DP. et al. Going the Extra Mile: Improved Survival for Pancreatic Cancer Patients Traveling to High-volume Centers. Ann Surg 2016; 266: 333-338
• 5 Dasari BV, Pasquali S, Vohra RS. et al. Extended Versus Standard Lymphadenectomy for Pancreatic Head Cancer: Meta-Analysis of Randomized Controlled Trials. J Gastrointest Surg 2015; 19: 1725-1732
• 6 Fang JZ, Lu CD, Wu SD. et al. Portal vein/superior mesenteric vein resection in pancreatic cancer treatment in the elderly. Medicine (Baltimore) 2017; 96: e7335
• 7 Jegatheeswaran S, Baltatzis M, Jamdar S. et al. Superior mesenteric artery (SMA) resection during pancreatectomy for malignant disease of the pancreas: a systematic review. HPB (Oxford) 2017; 19: 483-490
• 8 Lahat G, Sever R, Lubezky N. et al. Pancreatic cancer: surgery is a feasible therapeutic option for elderly patients. World J Surg Oncol 2011; 9: 10
• 9 Petrucciani N, Debs T, Nigri G. et al. Pancreatectomy combined with multivisceral resection for pancreatic malignancies: is it justified? Results of a systematic review. HPB (Oxford) 2018; 20: 3-10
• 10 Verbeke C, Lohr M, Karlsson JS. et al. Pathology reporting of pancreatic cancer following neoadjuvant therapy: challenges and uncertainties. Cancer Treat Rev 2015; 41: 17-26
• 11 Ferrone CR, Marchegiani G, Hong TS. et al. Radiological and surgical implications of neoadjuvant treatment with FOLFIRINOX for locally advanced and borderline resectable pancreatic cancer. Ann Surg 2015; 261: 12-17
• 12 Oettle H, Post S, Neuhaus P. et al. Adjuvant chemotherapy with gemcitabine vs observation in patients undergoing curative-intent resection of pancreatic cancer: a randomized controlled trial. Jama 2007; 297: 267-277
• 13 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. Lancet 2017; 389: 1011-1024
• 14 Conroy T, Hammel P, Hebbar M. et al. Unicancer GI PRODIGE 24/CCTG PA.6 trial: A multicenter international randomized phase III trial of adjuvant mFOLFIRINOX versus gemcitabine (gem) in patients with resected pancreatic ductal adenocarcinomas. 2018. ASCO. Abstract #: LBA 4001
• 15 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 Clin Oncol 2013; 31: 1640-1648
• 16 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). Lancet 2016; 388: 248-257
• 17 Janssen QP, Buettner S, Suker M. et al. Neoadjuvant FOLFIRINOX in patients with (borderline) resectable pancreatic cancer: A systematic review and patient-level meta-analysis. 2018. ASCO. Abstract #: c16207
• 18 Dhir M, Zenati MS, Hamad A. et al. FOLFIRINOX Versus Gemcitabine/Nab-Paclitaxel for Neoadjuvant Treatment of Resectable and Borderline Resectable Pancreatic Head Adenocarcinoma. Ann Surg Oncol 2018; 25: 1896-1903
• 19 Okada KI, Hirono S, Kawai M. et al. Phase I Study of Nab-Paclitaxel plus Gemcitabine as Neoadjuvant Therapy for Borderline Resectable Pancreatic Cancer. Anticancer Res 2017; 37: 853-858
• 20 Schwarz L, Vernerey D, Bachet JB. et al. Resectable pancreatic adenocarcinoma neo-adjuvant FOLF(IRIN)OX-based chemotherapy – a multicenter, non-comparative, randomized, phase II trial (PANACHE01-PRODIGE48 study). BMC Cancer 2018; 18: 762
• 21 Turner K, Narayanan S, Attwood K. et al. Neoadjuvant FOLFIRINOX and/or gemcitabine/nab-paclitaxel for advanced pancreatic adenocarcinoma. J Clin Oncol 2017; 35: 473
• 22 Mokdad AA, Minter RM, Zhu H. et al. Neoadjuvant Therapy Followed by Resection Versus Upfront Resection for Resectable Pancreatic Cancer: A Propensity Score Matched Analysis. J Clin Oncol 2017; 35: 515-522
• 23 Gillen S, Schuster T, Meyer Zum Buschenfelde C. et al. Preoperative/neoadjuvant therapy in pancreatic cancer: a systematic review and meta-analysis of response and resection percentages. PLoS Med 2010; 7: e1000267
• 24 Kunzmann V, Martens UM, Alguel H. et al. Secondary resectability in locally advanced pancreatic cancer (LAPC) after nab-paclitaxel/gemcitabine- versus FOLFIRINOX-based induction chemotherapy: Interim results of a randomized phase II AIO trial (NEOLAP). 2018. ASCO. Abstract #: 348
• 25 Stirrups R. Chemoradiotherapy for pancreatic adenocarcinoma. Lancet Oncol 2018. DOI: https://doi.org/10.1016/S1470-2045(18)30358-9
• 26 Conroy T, Desseigne F, Ychou M. et al. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med 2011; 364: 1817-1825
• 27 Von Hoff DD, Ervin T, Arena FP. et al. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med 2013; 369: 1691-703
• 28 Dahan L, Phelip JM, Malicot KL. et al. FOLFIRINOX until progression, FOLFIRINOX with maintenance treatment, or sequential treatment with gemcitabine and FOLFIRI.3 for first-line treatment of metastatic pancreatic cancer: A randomized phase II trial (PRODIGE 35- PANOPTIMOX). ASCO 2018. Abstract # 4000
• 29 Portal A, Pernot S, Tougeron D. et al. Nab-paclitaxel plus gemcitabine for metastatic pancreatic adenocarcinoma after Folfirinox failure: an AGEO prospective multicentre cohort. Br J Cancer 2015; 113: 989-995
• 30 Haas M, Siveke JT, Schenk M. et al. Efficacy of gemcitabine plus erlotinib in rash-positive patients with metastatic pancreatic cancer selected according to eligibility for FOLFIRINOX: A prospective phase II study of the ‚Arbeitsgemeinschaft Internistische Onkologie’. Eur J Cancer 2017; 94: 95-103
• 31 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 Clin Oncol 2007; 25: 1960-1966
• 32 Pelzer U, Schwaner I, Stieler J. et al. Best supportive care (BSC) versus oxaliplatin, folinic acid and 5-fluorouracil (OFF) plus BSC in patients for second-line advanced pancreatic cancer: a phase III-study from the German CONKO-study group. Eur J Cancer 2011; 47: 1676-1681
• 33 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. Lancet 2016; 387: 545-557
• 34 Gebbia V, Maiello E, Giuliani F. et al. Irinotecan plus bolus/infusional 5-Fluorouracil and leucovorin in patients with pretreated advanced pancreatic carcinoma: a multicenter experience of the Gruppo Oncologico Italia Meridionale. Am J Clin Oncol 2010; 33: 461-464
• 35 Zaniboni A, Aitini E, Barni S. et al. FOLFIRI as second-line chemotherapy for advanced pancreatic cancer: a GISCAD multicenter phase II study. Cancer Chemother Pharmacol 2012; 69: 1641-1645
• 36 Toki MI, Syrigos KN, Saif MW. The role of biliary drainage in patients with pancreatic adenocarcinoma. Jop 2014; 15: 128-131
• 37 Grimm IS, Baron TH. Biliary Stents for Palliation of Obstructive Jaundice: Choosing the Superior Endoscopic Management Strategy. Gastroenterology 2015; 149: 20-22
• 38 Baron TH, Grimm IS. Relief of obstructive jaundice from pancreatic cancer: the end of the plastic stent era?. Gut 2016; 65: 191-192
• 39 Tol JA, van Hooft JE, Timmer R. et al. Metal or plastic stents for preoperative biliary drainage in resectable pancreatic cancer. Gut 2015; 65: 1981-1987
• 40 Adams MA, Anderson MA, Myles JD. et al. Self-expanding metal stents (SEMS) provide superior outcomes compared to plastic stents for pancreatic cancer patients undergoing neoadjuvant therapy. J Gastrointest Oncol 2012; 3: 309-313
• 41 Watanapa P, Williamson RC. Surgical palliation for pancreatic cancer: developments during the past two decades. Br J Surg 1992; 79: 8-20
• 42 Shah A, Fehmi A, Savides TJ. Increased rates of duodenal obstruction in pancreatic cancer patients receiving modern medical management. Dig Dis Sci 2014; 59: 2294-2298
• 43 Hosono S, Ohtani H, Arimoto Y. et al. Endoscopic stenting versus surgical gastroenterostomy for palliation of malignant gastroduodenal obstruction: a meta-analysis. J Gastroenterol 2007; 42: 283-290