Pankreaskarzinom

Zusammenfassung

Das Adenokarzinom des Pankreas ist trotz erheblicher Fortschritte im Bereich der Epidemiologie, Molekulargenetik und Diagnostik unverändert durch eine extrem schlechte Prognose gekennzeichnet. Die vorliegende Arbeit versucht, durch eine kritische Analyse der umfangreichen Datenlage Empfehlungen zum diagnostischen und therapeutischen Vorgehen zu entwickeln.

Ein kosteneffizienter diagnostischer Algorithmus bei klinischem Verdacht auf ein Pankreaskarzinom besteht im initialen Einsatz des abdominellen Ultraschalls, der bei Fehlen von Fernmetastasen oder uneindeutigem Befund von einem MRT in „One-stop-Technik” gefolgt wird. Potenziell resektable Patienten sind einer explorativen Laparotomie zuzuführen.

In frühen Tumorstadien ist eine Resektion unter kurativer Zielsetzung möglich und aufgrund der verbesserten Operationstechnik in erfahrenen Zentren gerechtfertigt. Möglicherweise führt eine adjuvante Chemotherapie zu einer Prognoseverbesserung.

Bei irresektablem lokal fortgeschrittenen Tumor können eine kombinierte Radiochemotherapie oder Chemotherapie indiziert sein. Bei Vorliegen von Fernmetastasen kann eine systemische Chemotherapie mit Gemcitabine das Überleben geringfügig verbessern und bei ausgewählten Patienten zu einem klinischen Benefit führen. Den therapeutischen Grundpfeiler in jedem Stadium stellt eine an Symptomen orientierte supportive Behandlung dar.

Die aktuelle Datenlage macht deutlich, dass der Entwicklung innovativer therapeutischer und diagnostischer Strategien herausragende Bedeutung zukommt.

Abstract

Despite considerable progress in the areas of epidemiology and molecular genetics, pancreatic cancer is still characerized by a dismal prognosis. The current overwiev attempts a critical analysis of the published data resulting in recommendations for diagnostic and therapeutic algorithms.

The diagnostic work-up of suspected pancreatic cancer patients includes an initial abdominal ultrasound which in case of ambiguous results or the absence of distant metastases is followed by „one-stop-MRI” and explorative laparotomy.

Locally confined tumour disease should proceed to resective surgery which however results in cure only in a minority of resected patients even in specialized centers. Adjuvant chemotherapy might be of some benefit in terms of survival. Locally advanced but irresectable disease can be considered for combined radiochemotherapy. Systemic chemotherapy with Gemcitabine results in marginal benefit of overall survival and may offer clinical benefit to a subgroup of patients. Best supportive care still remains the mainstay of irresectable disease.

This summary highlights the urgent need for the development of innovative diagnostic and therapeutic strategies.

Übersicht - Pankreaskarzinom - Diagnostik - adjuvant - Chemotherapie - Lebensqualität - Palliation

Review - pancreatic cancer - diagnosis - adjuvant therapy - chemotherapy - quality of life - palliation

Literatur

• 1 Arbeitsgemeinschaft Bevölkerungsbezogener Krebsregister in Deutschland . Krebs in Deutschland. 3. erweiterte, aktualisierte Ausgabe. Saarbrücken, 2002. 
• 2 Lowenfels A B, Maisonneuve P, Cavallini G. et al . Pancreatitis and the risk of pancreatic cancer. International Pancreatitis Study Group.  N Engl J Med. 1993;  328 1433-1437
• 3 Lowenfels A B, Maisonneuve P, DiMagno E P. et al . Hereditary pancreatitis and the risk of pancreatic cancer. International Hereditary Pancreatitis Study Group [see comments].  J Natl Cancer Inst. 1997;  89 442-446
• 4 Everhart J, Wright D. Diabetes mellitus as a risk factor for pancreatic cancer. A meta-analysis.  JAMA. 1995;  273 1605-1609
• 5 Permert J, Larsson J, Westermark G T. et al . Islet amyloid polypeptide in patients with pancreatic cancer and diabetes.  N Engl J Med. 1994;  330 313-318
• 6 Schneider G, Schmid R M. Genetic alterations in pancreatic carcinoma.  Mol Cancer. 2003;  2 15
• 7 Hruban R H, Adsay N V, Albores-Saavedra J. et al . Pancreatic intraepithelial neoplasia: a new nomenclature and classification system for pancreatic duct lesions.  Am J Surg Pathol. 2001;  25 579-586
• 8 Klöppel G, Luttges J. WHO-classification 2000: exocrine pancreatic tumors.  Verh Dtsch Ges Pathol. 2001;  85 219-228
• 9 DiMagno E P, Reber H A, Tempero M A. AGA technical review on the epidemiology, diagnosis, and treatment of pancreatic ductal adenocarcinoma. American Gastroenterological Association.  Gastroenterology. 1999;  117 1464-1484
• 10 Bohmig M, Wiedenmann B, Rosewicz S. Diagnose und Staging des Pankreaskarzinoms.  Dtsch Med Wochenschr. 2001;  126 113-116
• 11 Harrison L E, Brennan M F. Portal vein resection for pancreatic adenocarcinoma.  Surg Oncol Clin N Am. 1998;  7 165-181
• 12 Lopez H E, Amthauer H, Hosten N. et al . Prospective evaluation of pancreatic tumors: accuracy of MR imaging with MR cholangiopancreatography and MR angiography.  Radiology. 2002;  224 34-41
• 13 Gress F G, Hawes R H, Savides T J. et al . Role of EUS in the preoperative staging of pancreatic cancer: a large single-center experience.  Gastrointest Endosc. 1999;  50 786-791
• 14 Saleh M M, Norregaard P, Jorgensen H L. et al . Preoperative endoscopic stent placement before pancreaticoduodenectomy: a meta-analysis of the effect on morbidity and mortality.  Gastrointest Endosc. 2002;  56 529-534
• 15 Sohn T A, Yeo C J, Cameron J L. et al . Do preoperative biliary stents increase postpancreaticoduodenectomy complications?.  J Gastrointest Surg. 2000;  4 258-267
• 16 Griffin J F, Smalley S R, Jewell W. et al . Patterns of failure after curative resection of pancreatic carcinoma.  Cancer. 1990;  66 56-61
• 17 Neoptolemos J P, Dunn J A, Stocken D D. et al . Adjuvant chemoradiotherapy and chemotherapy in resectable pancreatic cancer: a randomised controlled trial.  Lancet. 2001;  358 1576-1585
• 18 Bakkevold K E, Arnesjo B, Dahl O. et al . Adjuvant combination chemotherapy (AMF) following radical resection of carcinoma of the pancreas and papilla of Vater - results of a controlled, prospective, randomised multicentre study.  Eur J Cancer. 1993;  29A 698-703
• 19 Lim J E, Chien M W, Earle C C. Prognostic factors following curative resection for pancreatic adenocarcinoma: a population-based, linked database analysis of 396 patients.  Ann Surg. 2003;  237 74-85
• 20 Yeo C J, Abrams R A, Grochow L B. et al . Pancreaticoduodenectomy for pancreatic adenocarcinoma: postoperative adjuvant chemoradiation improves survival. A prospective, single-institution experience.  Ann Surg. 1997;  225 621-633
• 21 Kalser M H, Ellenberg S S. Pancreatic cancer. Adjuvant combined radiation and chemotherapy following curative resection.  Arch Surg. 1985;  120 899-903
• 22 Klinkenbijl J H, Jeekel J, Sahmoud T. et al . Adjuvant radiotherapy and 5-fluorouracil after curative resection of cancer of the pancreas and periampullary region: phase III trial of the EORTC gastrointestinal tract cancer cooperative group.  Ann Surg. 1999;  230 776-782
• 23 Klaassen D J, MacIntyre J M, Catton G E. et al . Treatment of locally unresectable cancer of the stomach and pancreas: a randomized comparison of 5-fluorouracil alone with radiation plus concurrent and maintenance 5-fluorouracil - an Eastern Cooperative Oncology Group study.  J Clin Oncol. 1985;  3 373-378
• 24 Lionetto R, Pugliese V, Bruzzi P. et al . No standard treatment is available for advanced pancreatic cancer [see comments].  Eur J Cancer. 1995;  31A 882-887
• 25 Burris H A, Moore M J. et al . Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial.  J Clin Oncol. 1997;  15 2403-2413
• 26 Bramhall S R, Rosemurgy A, Brown P D. et al . Marimastat as first-line therapy for patients with unresectable pancreatic cancer: a randomized trial.  J Clin Oncol. 2001;  19 3447-3455
• 27 Moore M J, Hamm J, Dancey J. et al . Comparison of gemcitabine versus the matrix metalloproteinase inhibitor BAY 12 - 9566 in patients with advanced or metastatic adenocarcinoma of the pancreas: a phase III trial of the National Cancer Institute of Canada Clinical Trials Group.  J Clin Oncol. 2003;  21 3296-3302
• 28 Storniolo A M, Enas N H, Brown C A. et al . An investigational new drug treatment program for patients with gemcitabine: results for over 3000 patients with pancreatic carcinoma.  Cancer. 1999;  85 1261-1268
• 29 Colucci G, Giuliani F, Gebbia V. et al . Gemcitabine alone or with cisplatin for the treatment of patients with locally advanced and/or metastatic pancreatic carcinoma: a prospective, randomized phase III study of the Gruppo Oncologia dell’Italia Meridionale.  Cancer. 2002;  94 902-910
• 30 Berlin J D, Catalano P, Thomas J P. et al . Phase III study of gemcitabine in combination with fluorouracil versus gemcitabine alone in patients with advanced pancreatic carcinoma: Eastern Cooperative Oncology Group Trial E2297.  J Clin Oncol. 2002;  20 3270-3275
• 31 Tempero M, Plunkett W, Ruiz V H. et al . Randomized phase II comparison of dose-intense gemcitabine: thirty-minute infusion and fixed dose rate infusion in patients with pancreatic adenocarcinoma.  J Clin Oncol. 2003;  21 3402-3408
• 32 Rothenberg M L, Moore M J, Cripps M C. et al . A phase II trial of gemcitabine in patients with 5-FU-refractory pancreas cancer.  Ann Oncol. 1996;  7 347-353
• 33 Bramhall S R, Schulz J, Nemunaitis J. et al . A double-blind placebo-controlled, randomised study comparing gemcitabine and marimastat with gemcitabine and placebo as first line therapy in patients with advanced pancreatic cancer.  Br J Cancer. 2002;  87 161-167
• 34 Watanapa P, Williamson R C. Surgical palliation for pancreatic cancer: developments during the past two decades.  Br J Surg. 1992;  79 8-20
• 35 Smith A C, Dowsett J F, Russell R C. et al . Randomised trial of endoscopic stenting versus surgical bypass in malignant low bileduct obstruction.  Lancet. 1994;  344 1655-1660
• 36 Speer A G, Cotton P B, Russell R C. et al . Randomised trial of endoscopic versus percutaneous stent insertion in malignant obstructive jaundice.  Lancet. 1987;  2 57-62
• 37 Prat F, Chapat O, Ducot B. et al . A randomized trial of endoscopic drainage methods for inoperable malignant strictures of the common bile duct.  Gastrointest Endosc. 1998;  47 1-7
• 38 Kim H S, Lee D K, Kim H G. et al . Features of malignant biliary obstruction affecting the patency of metallic stents: a multicenter study.  Gastrointest Endosc. 2002;  55 359-365
• 39 Barkin J S, Goldberg R I, Sfakianakis G N. et al . Pancreatic carcinoma is associated with delayed gastric emptying.  Dig Dis Sci. 1986;  31 265-267
• 40 Lillemoe K D, Cameron J L, Hardacre J M. et al . Is prophylactic gastrojejunostomy indicated for unresectable periampullary cancer? A prospective randomized trial.  Ann Surg. 1999;  230 322-328
• 41 Yim H B, Jacobson B C, Saltzman J R. et al . Clinical outcome of the use of enteral stents for palliation of patients with malignant upper GI obstruction.  Gastrointest Endosc. 2001;  53 329-332
• 42 Grahm A L, Andren-Sandberg A. Prospective evaluation of pain in exocrine pancreatic cancer.  Digestion. 1997;  58 542-549
• 43 Lillemoe K D, Cameron J L, Kaufman H S. et al . Chemical splanchnicectomy in patients with unresectable pancreatic cancer. A prospective randomized trial.  Ann Surg. 1993;  217 447-455
• 44 Wigmore S J, Plester C E, Richardson R A. et al . Changes in nutritional status associated with unresectable pancreatic cancer.  Br J Cancer. 1997;  75 106-109
• 45 McMillan D C, Wigmore S J, Fearon K C. et al . A prospective randomized study of megestrol acetate and ibuprofen in gastrointestinal cancer patients with weight loss.  Br J Cancer. 1999;  79 495-500
• 46 McGeer A J, Detsky A S, O’Rourke K. Parenteral nutrition in cancer patients undergoing chemotherapy: a meta-analysis.  Nutrition. 1990;  6 233-240
• 47 Bruno M J, Haverkort E B, Tijssen G P. et al . Placebo controlled trial of enteric coated pancreatin microsphere treatment in patients with unresectable cancer of the pancreatic head region.  Gut. 1998;  42 92-96
• 48 Kelsen D P, Portenoy R K, Thaler H T. et al . Pain and depression in patients with newly diagnosed pancreas cancer.  J Clin Oncol. 1995;  13 748-755
• 49 Passik S D, Breitbart W S. Depression in patients with pancreatic carcinoma. Diagnostic and treatment issues.  Cancer. 1996;  78 615-626