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DOI: 10.1055/s-2001-11140
Aktueller Stand multimodaler Therapiekonzepte beim Pankreaskarzinom
Publication History
Publication Date:
31 December 2001 (online)
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Hintergrund
Das Karzinom der exokrinen Bauchspeicheldrüse stellt mit etwa 3 - 6 % aller Krebstodesfälle in Industrieländern die viert- oder fünfthäufigste Todesursache dar [1], wobei die Inzidenz auch in europäischen Ländern bis Ende der achtziger Jahre stetig zugenommen hat [2].
Trotz überzeugender Fortschritte in der chirurgischen Behandlung dieser Krebserkrankung ist die Prognose nach wie vor deprimierend schlecht. In der in diesem Zusammenhang wahrscheinlich meistzitierten Sammelstatistik, deren fortbestehende Gültigkeit heute gelegentlich angezweifelt wird, scheint nur jeder zehnte Krebs resektabel, wobei nur 0,4 % der so operierten Patienten 5 weitere Jahre überleben [3].
Unter dem Begriff „Pankreaskarzinom” wird in der Regel wegen nahezu identischer operativer Therapieverfahren nicht nur das eigentliche, duktale Adenokarzinom der Bauchspeicheldrüse verstanden. Trotz signifikant besserer Prognose werden unter dem Sammelbegriff „periampulläres Karzinom” zusätzlich die deutlich selteneren Duodenal-, Papillen- und distalen Choledochuskarzinome subsumiert und teilweise analog zum duktalen Pankreaskarzinom in Studien oder Publikationen behandelt. Hiervon kann auch in der vorliegenden Übersichtsarbeit nicht wesentlich abgewichen werden, wobei den Autoren durchaus bewusst ist, dass die verschiedenen Tumorentitäten u. U. nicht vergleichbar sind.
Nichts desto weniger wird anhand der o. g. Prognose der Erkrankung nach alleiniger Resektion, so überhaupt möglich, doch die dringende Notwendigkeit einer Therapieoptimierung deutlich. Ziel dieser Übersicht ist es, stattgehabte und mögliche Verbesserungen in der Behandlung des Bauchspeicheldrüsenkrebses aufzuzeigen. Hierbei soll der Schwerpunkt nicht auf die zahlenmäßig wahrscheinlich häufigere palliative Therapie beim metastasierten oder irresektablen Tumor gelegt werden. Vielmehr soll hauptsächlich erörtert werden, ob und auf welche Weise die Prognose des potentiell kurativ zu behandelnden Krebses in einem multimodalen Konzept aus chirurgischer, onkologischer und radiotherapeutischer Behandlung zu verbessern sein könnte.
Literatur
- 1 Gold E B, Cameron J L. Chronic pancreatitis and pancreatic cancer. New Engl J Med. 1993; 328 1485-1486
-
2 Andren-Sandberg A, Bäckmann P L.
Demographics of pancreatic cancer. In: Beger HG, Büchler MW, Schoenberg MH (eds) Cancer of the pancreas. Ulm; Universitätsverlag 1996 - 3 Gudjohnsson B. Cancer of the pancreas. Cancer. 1987; 60 2284-2303
- 4 Crile G. The advantages of bypass operations over radical pancreatoduodenectomy in the treatment of pancreas carcinoma. Surg Gynecol Obstet. 1970; 130 1049-1053
- 5 Bramhall S R, Allum W H, Jones A G, Allwood A, Cummings C, Neoptolemus J P. Treatment and survival in 13560 patients with pancratic cancer, and incidence of the disease, in the West Midlands: an epidemiological study. Br J Surg. 1995; 82 111-115
- 6 Roder J D, Stein H J, Hüttl W, Siewert J R. Pylorus-preserving versus standard pancreaticoduodenectomy: an analysis of 110 pancreatic and periampullary carcinomas. Br J Surg. 1992; 79 152-155
- 7 Miedema B W, Sarr M G, van Heerden J A, Nagorney D M, McIllrath D C, Ilstrup D. Complications following pancreaticoduodenectomy: current management. Arch Surg. 1992; 127 945-950
- 8 Klinkenbijl J HG, Jeekel J, Schmitz P IM, Rambout P AR, Nix G AJJ, Bruining H A, van Blankenstein M. Carcinoma of the pancreas and periampullary region: palliation versus cure. Br J Surg. 1993; 80 1575-1578
- 9 Klempnauer J, Ridder G J, Bektas H, Pichlmayr R. Extended resections of ductal pancreatic cancer - impact on operative risk and prognosis. Oncology. 1996; 53 47-53
- 10 Schönberg M H, Gansauge F, Kunz R. Wertigkeit der pyloruserhaltenden Duodenopankreatektomie beim duktalen Pankreaskarzinom. Chirurg. 1997; 68 1262-1267
- 11 Trede M, Saeger H D, Schwall G, Rumstadt B. Resection of pancreatic cancer - surgical achievements. Langenbecks Arch Surg. 1998; 383 121-128
- 12 Yeo C J, Cameron J L, Sohn T A, Lillemoe K D, Pitt H A, Talamini M A, Hruban R H, Ord S E, Sauter P K, Coleman J, Zahurak M L, Grochow L B, Abrams R A. Six hundred fifty consecutive pancreaticoduodenectomies in the 1990s. Ann Surg. 1997; 226 248-260
- 13 Pedrazzoli S, DiCarlo V, Dionigi R, Mosca F, Pederzoli P, Pasquali C, Kläppel G, Dhaene K, Michelassi F. and the lymphadenectomy study group . Standard versus extended lymphadenectomy associated with pancreatoduodenectomy in the surgical treatment of adenocarcinoma of the head of the pancreas. Ann Surg. 1998; 228 508-517
- 14 Mosca F, Giuliantti P C, Balestracci T, DiCandio G D, Pitrabissa A, Sbrana F, Rossi G. Long-term survival in pancreatic cancer: pylorus-preserving versus Whipple pancreatoduodenectomy. Surgery. 1997; 122 553-566
- 15 Gordon T A, Burleyson G P, Tielsch J M, Cameron J L. The effects of regionalisation on cost and outcome for one general high-risk surgical procedure. Ann Surg. 1995; 221 43-49
- 16 Birkmeyer J D, Finlayson S RG, Tosteson A NA, Sharp S M, Warshaw A L, Fisher E S. Effect of hospital volume on in-hospital mortality with pancreaticoduodenectomy. Surgery. 1999; 125 250-256
- 17 Harmon J W, Tang G D, Gordon T A, Bowman H M, Chiotti M A, Kaufman H S, Bender J S, Duncan M D, Magnusson T H, Lillemoe K d, Cameron J L. Hospital volume can serve as a surrogate for surgeon volume for achieving excellent outcomes in colorectal resection. Ann Surg. 1999; 230 404-413
- 18 Yeo C J, Camreon J L, Lillemoe K D, Sitzmann J V, Hruban R H, Goodman S N, Dooley W C, coleman J, Pitt H A. Pancraticoduodenectomy for cancer of the head of the pancreas. 201 patients. Ann Surg. 1995; 221 721-733
- 19 Gall F P, Kessler H, Hermanek P. Surgical treatment of ductal pancreatic carcinoma. Eur J Surg Oncol. 1991; 17 173-181
- 20 Geer R J, Brenan M F. Prognostic indicators of survival after resection of pancreatic adenocarcinoma. Am J Surg. 1993; 165 68-72
- 21 Baumel H, Huguier M, Fabre J M. Palliative treatment of cancers of the head of the pancreas. Surgery versus endoscopy. Ann Chir. 1995; 49 110-115
- 22 Sperti C, Pasquali C, Picoli A, Pedrazzoli S. Survival after resection for ductal adenocarcinoma of the pancreas. Br J Surg. 1996; 83 625-631
- 23 Sener S F, Fremgen A, Menck H R, Winchester D P. Pancreatic cancer: A report of treatment and survival trends for 100313 patients diagnosed from 1985 - 1995, using the national cancer database. J Am Coll Surg. 1999; 189 1-7
- 24 Nitecki S, Sarr M G, Colby T V, van Heerden J A. Long term survival after resection for ductal adenocarcinoma of the pancreas. Is it really improving?. Ann Surg. 1995; 221 59-66
- 25 Birkmeyer J D, Warshaw A L, Finlayson S R, Grove M R, Tosteson A NA. Relationship between hospital volume and late survival after pancreaticoduodenectomy. Surgery. 1999; 126 178-183
- 26 Fortner J G. Regional pancreatectomy for cancer of the pancreas, ampulla, and other related sites. Ann Surg. 1984; 199 418-425
- 27 Ihse I, Anderson H, Andren S. Total pancreatectomy for cancer of the pancreas: is it appropriate?. World J Surg. 1996; 20 288-293
- 28 Sarr M G, Behrens K E, van Herden J A. Total pancreatectomy. An objective analysis of its use in pancreatic cancer. Hepatogastroenterology. 1993; 40 418-421
- 29 Trede M, Schwall G, Säger H D. Survival after pancreaticoduodenectomy. 118 consecutive patients with mortality. Ann Surg. 1990; 211 447-458
- 30 Trede M. Tratment of pancreatic carcinoma: the surgeon's dilemma. Br J Surg. 1987; 74 79-80
- 31 Keck H, Knoop M, Langrehr J M, Hennecken V, Neuhaus P. Erweiterte partielle Duodenopankreatektomie nach Kausch-Whipple durch Resektion tumorinfiltrierter Gefäßabschnitte. Zentralbl Chir. 1995; 120 809-814
- 32 Takahashi S, Ogota Y, Tsuzuki T. Combined resection of the pancreas and portal vein for pancreatic cancer. Br J Surg. 1994; 81 1190-1193
- 33 Ishikawa O, Ohhigaashi H, Sasakai Y, Kabuto T, Fukuda I, Furukawa H, Imaoka S, Iwananga T. Practical usefulness of lymphatic and connective tissue clearance for the carcinoma of the pancreatic head. Ann Surg. 1988; 208 215-220
- 34 Mukaiya M, Hirata K, Satoh T, Kimura M, Yamashiro K, Ura H, Okikawa I, Denno R. Lack of survival benefit of extended lymph node dissection for ductal adenocarcinoma of the head of the pancreas: retrospective multi-institutional analysis in Japan. World J Surg. 1998; 22 248-253
- 35 Hirata K, Sato T, Mukaiya M, Yamashiro K, Kimura M, Sasakai K, Denno R. Results of 1001 pancreatic resections for invasive ductal adenocarcinoma of the pancreas. Arch Surg. 1997; 132 771-776
- 36 Yeo C J, Cameron J L, Sohn T A, Coleman J, Sauter P K, Hruban R H, Pitt H A, Lillemoe K D. Pancrearticoduodenectomy with and without extended retroperitoneal lymphadenectomy for periampullary adenocarcinoma. Comparison of morbidity and mortality and short-term outcome. Ann Surg. 1999; 5 613-624
- 37 Henne-Bruns D, Vogel I, Lüttges J, Klöppel G, Kremer B. Ductal adenocarcinoma of the pancreas head: Survical after regional and extended lymphadenectomy. Hepatogastroenterology. 1998; 45 855-866
- 38 Sperti C, Pasquali C, Piccoli A, Pedrazzoli S. Recurrence after resection for ductal adenocarcinoma. World J Surg. 1997; 21 195-220
- 39 Klinkenbijl J H, Jeekel J, Sahmoud T, van Pel R, Courveur M L, Veenhof C H, Arnaud J P, Gonzalez D G, de Witt L T, Hennipman A, Wils J. Adjuvant radiotherapy and 5-Fluorouracil after curative resection of cancer of the pancreas and periampullary region. Ann Surg. 1999; 230 776-784
- 40 Kayahara M, Nagakawa T, Ueno K, Ohta T, Takeda T, Miyazaki I. An evaluation of radical resection for pancreatic cancer based on the mode of recurrence by autopsy and diagnostic imaging. Cancer. 1993; 72 2118-2123
- 41 Kompaki R, Wadler S, Peters M S, Byhardt R W, Order S, Gallagher M J, Herskovic M D, Pederson J. High-dose local irradiation plus prophylactic hepatic irradiation and chemotherapy for inoperable adenocarcinoma of the pancreas. Cancer. 1992; 69 2807-2813
- 42 Sindelar W, Kinsella T. Studies of intraoperative radiotherapy in carcinoma of the pancreas. Ann Oncol. 1999; 10 (4) 226-230
- 43 Roldan G E, Gunderson L L, Nagorney D M, Martin J K, Illstrup D M, Holbrook M A, Kvols L K, McIllrath D C. External beam vs. intraoperative and external beam irradiation for locally advanced pancreatic cancer. Cancer. 1988; 16 1110-1116
- 44 Whittington R, Solin L, Mohihuddin M. Multimodality therapy of localized unresectable pancreatic adenocarcinoma. Cancer. 1984; 54 1991-1998
- 45 Shipley W U, Wood W C, Tepper J C, Warshaw A L, Orlow E L, Kaufman S D, Battit G E, Nardi G L. Intraoperative iradiation for patients with unresectable pancreatic carcinoma. Ann Surg. 1984; 200 289-296
-
46 Tepper J E, Noyes D, Krall J M.
Intraoperative radiation therapy of pancreatic carcinoma. A report of RTOG-8505. In: Abe M, Takahashi M (eds) Intraoperative radiation therapy. Proceedings of the third international symposium on intraoperative radiation therapy. New York; Pergamonn Press 1991: 231-233 - 47 Yasue M, Sakamoto J, Yasui K, Morimoto T, Miyashi S, Kurimotot K, Kuno N, Kido C, Kawasumi C, Nakamura S, Uchiyama Y, Morita K. A randomized trial of intraoperative radiation therapy (IORT) vs. IORT plus chemotherapy (MTX-5FU) for adenocarcinoma of the pancreas. Cancer Res ther Control. 1993; 3 283-289
- 48 Ouchi K, Sugawara T, Ono H, Fujiya T, Kamiyama Y, Kakugawa Y, Mikuni J, Yamanami H. Palliative Operation for cancer of the head of the pancreas: significance of pancreaticoduodenectomy and intraoperative radiation therapy for survival and quality of life. World J Surg. 1998; 22 413-417
- 49 Zerbi A, Fossati V, Parolini D, Carlucci M, Parolini D, Carlucci M, Balzano G, Bordogna G, Staudacher G, Di Carlo V. Intraoperative radiation therapy adjuvant to resection in the treatment of pancreatic cancer. Cancer. 1994; 73 2930-2935
- 50 Heijmans H J, Hoekstra H J, Mehta D M. Is adjuvant intraoperative radiotherapy (IORT) for resectable and unresectable pancratic carcinoma worthwhile?. Hepatogastroenterology. 1989; 36 474-477
- 51 Hiraoka T. Extended radical resection of cancer of the pancreas with intra-operative radiotherapy. Balliere Clin Gastroenterol. 1990; 4 985-993
- 52 Kasperk R, Klever P, Andreopoulos D, Schumpelick V. Intraoperative radiotherapy for pancreatic carcinoma. Br J Surg. 1995; 82 1259-1261
- 53 Beger H G, Gansauge F, Bücler M W, Link K H. Intraarteriel adjuvant chemotherapy after pancreaticoduodebectomy for pancreatic cancer: significant reduction in occurrence of liver metastasis. WorlsdJ Surg. 1999; 23 946-949
- 54 Ishikawa O, Ohigashi H, Imaoka S, Sasaki Y, Kameyama M, Kakamori S, Kabuto T, Furukawa H. Regional chemotherapy to prevent hepatic metastasis after resection of pancreatic cancer. Hepato-Gastroenterology. 1997; 44 1541-1546
- 55 Ozaki H, Kinoshita T, Kosuge T, Egawa S, Kishi K. Effectiveness of multimodality treatment for resectable pancreatic cancer. Int J Pancreatol. 1990; 7 195-200
-
56 Birk D, Beger H G.
Kommentar: Diagnostik und Therapie des exokrinen Pankreaskarzionoms. In: Junginger T, Hossfeld DK, Müller RP (Hrsg) Leitlinien zur Diagnostik und Therapie von Tumoren des Gastrointestinaltraktes und der Schilddrüse. Stuttgart; Demeter Verlag 1999 - 57 Palmer K P, Kerr M, Knowles G. Chemotherapy prolongs survival and quality of life in inoperable pancreatic carcinoma. Br J Surg. 1994; 81 882-885
- 58 Glimelius B, Hoffman K, Sjöden P O, Jacobsen G, Sellstrom H, Enander L K, Linne T, Svensson C. Chemotherapy improves survival and quality of life in advanced pancreatic and biliary cancer. Ann Oncol. 1996; 7 593-600
- 59 Burris H A, Moore M J, Andersen J, Green M R, Rothenberg M L, Modiano M R, Cripps M C, Portenoy R K, Storniolo A M, Tarassoff P, Nelson R, Dorr F A, Stephens C D, von Hoff D D. 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
- 60 Moertel C G, Frytak S, Hahn R G, O'Connell M J, Reitemeier R J, Rubin J, Schutt A J, Weiland L H, Childs D S, Holbrook M A, Lavin P T, Livstone E, Spiro H, Knowlton A, Kalser M, Barkin J, Lessner H, Mann-Kaplan R, Ramming K, Douglas H O, Thomas P, Nave H, Bateman J, Lokich J, Brooks J, Chaffey J, Corson J M, Zamcheck N, Novak J W. Gastrointestinal Tumour Study Group: therapy of locally unresectable pancreatic carcinoma: a randomised comparison of high dose radiation alone (6000 rads), moderate dose radiation (4000 rads + 5-fluorouracil) and high dose radiation + 5-fluorouracil. Cancer. 1981; 48 1705-1710
- 61 Bakkevold K E, Arnesjo B, Dahl O, Kambestad B. 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; 29 698-703
- 62 Splinter T A, Obertop H, Jeckel J. Adjuvant chemotherapy after resection of adenocarcinoma of the ampullary region and the head of the pancreas. J Cancer Res Clin Oncol. 1989; 115 200-202
- 63 Bosset J F, Pavy J J, Gilet M, Mantion G, Pelissier E, Schraub S. Conventional external irradiation alone as adjuvant treatment in resectable pancreatic cancer: results of a prospective study. Radiother Oncol. 1992; 24 191-194
- 64 Link K H, Formentini A, Leder G, Fortnagel G, Sartori N, Schatz M, Beger H G. Resection and radiochemotherapy of pancreatic cancer - the future?. Langenbecks Arch Surg. 1998; 383 134-144
- 65 Kalser M H, Ellenberg S S. Pancreatic Cancer. Adjuvant combined radiation and chemotherapy following curative resection. Arch Surg. 1985; 120 899-903
- 66 Gastrointestinal Tumor Study Group. Further evidence of effective adjuvant combined radiation and chemotherapy following curative resection of pancreatic cancer. Cancer. 1987; 59 2006-2010
- 67 Whittington R, Bryer M P, Haller D G, Solin L J, Rosato F E. Adjuvant therapy of resected adenocarcinoma of the pancreas. Int Radiation Oncol Biol Phy. 1991; 21 1137-1143
- 68 Yeo C J, Abrams R A, Grochow L B, Sohn T A, Ord S E, Hruban R H, Zahurak M L, Dooley W C, Coleman J, Sauter P K, Pitt H A, Lillemoe K D, Cameron J L. Pancreaticoduodenectomy for pancreatic adenocarcinoma: postoperative adjuvant chemoradiation improves survival. Ann Surg. 1997; 5 621-636
- 69 Foo M L, Gunderson L L, Nagorney D M, McIllrath D C, van Heerden J A. Patterns of failure in grossly resected pancraetic ductal adenocarcinoma traeted with adjuvant irradiation and 5 fluorouracil. Int J Radiation Oncol Biol Phy. 1993; 26 483-489
- 70 Carr J A, Ajlouni M, Wollner I, Wong D, Velanovich V. Adenocarcinoma of the head of the pancreas: effects of surgical and non-surgical therapy on survival - a ten year experience. Am Surg. 1999; 65 1143-1149
- 71 Neoptolemus J P, et al. ASCO 2000, Abstract 923.
- 72 Neoptolemus J P, Kerr D J, Beger H G, Link K, Pedrazzoli P, Bassi C, Dervenis C, Fernandez-Cruz L, Lacaine F, Friess H, Büchler M. ESPAC-I trail progress report. Digestion. 1997; 58 570-577
- 73 Ghaneh P, Kawesha A, Howes N, Jones L, Neoptolemus J P. Adjuvant therapy for pancreatic cancer. World J Surg. 1999; 23 937-945
- 74 Tepper J, Nardi G, Suit H. Carcinoma of the pancreas; review of HGH experience from 1963 to 1973: analysis of surgical failure and implications on radiation therapy. Cancer. 1976; 37 1519-1524
- 75 Pilepich M V, Miller H H. Preoperative irradiation in carcinoma of the pancreas. Cancer. 1980; 46 1945-1949
- 76 Ishikawa O, Ohigashi H, Imaoka S, Sasaki Y, Iwananga T, Matayoshi Y, Inoue T. Is the long-term survival rate improved by peroperative irradiation prior to Whipple's procedure for adenocarcinoma of the pancreatic head?. Arch Surg. 1994; 129 1075-1080
- 77 Wanebo H J, Glicksman A S, Vezeridis M P, Clark J C, Tibbetts L, Koness J, Levy A L. Preoperative Chemotherapy, radiotherapy, and surgical resection of locally advanced pancreatic cancer. Arch Surg. 2000; 135 81-87
- 78 Sohn T A, Lillemoe K D, Cameron J L, Pitt H A, Huang J L, Hruban R H, Yeo W. Reexploration for periampullary carcinoma. Resectability, perioperative results, pathology, and long-term cure. Ann Surg. 1999; 229 393-400
- 79 Tyler D S, Evans D B. Reoperative Pancreaticoduodenectomy. Ann Surg. 1994; 219 21-221
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