S3-Guideline “Exocrine Pancreatic Carcinoma” 2007

G. Adler; T. Seufferlein; S. C. Bischoff; H.-J. Brambs; S. Feuerbach; G. Grabenbauer; S. Hahn; V. Heinemann; W. Hohenberger; J. M. Langrehr; M. P. Lutz; O. Micke; H. Neuhaus; P. Neuhaus; H. Oettle; P. M. Schlag; R. Schmid; W. Schmiegel; K. Schlottmann; J. Werner; B. Wiedenmann; I. Kopp

doi:10.1055/s-2008-1027420

Zeitschrift für Gastroenterologie, Table of Contents

Z Gastroenterol 2008; 46(5): 449-482
DOI: 10.1055/s-2008-1027420

Guideline

S3-Guideline “Exocrine Pancreatic Carcinoma” 2007[1]

Results of an Evidence-Based Consensus Conference (13. - 14.10.2006)S3-Leitlinie „Exokrines Pankreaskarzinom” 2007G. Adler¹ , T. Seufferlein¹ , S. C. Bischoff¹ , H.-J Brambs¹ , S. Feuerbach¹ , G. Grabenbauer¹ , S. Hahn¹ , V. Heinemann¹ , W. Hohenberger¹ , J. M. Langrehr¹ , M. P. Lutz¹ , O. Micke¹ , H. Neuhaus¹ , P. Neuhaus¹ , H. Oettle¹ , P. M. Schlag¹ , R. Schmid¹ , W. Schmiegel¹ , K. Schlottmann¹ , J. Werner¹ , B. Wiedenmann¹ , I. Kopp¹

¹Department of Internal Medicine I, University Medical Center Ulm

Abstract

Full Text

References

1 Adler G, Seufferlein T, Bischoff S C. et al . S3-Guidelines “Exocrine pancreatic cancer” 2007. Z Gastroenterol. 2007; 45 487-523
2 Glade M J. Food, nutrition, and the prevention of cancer: a global perspective. American Institute for Cancer Research/World Cancer Research Fund, American Institute for Cancer Research, 1997. Nutrition. 1999; 15 523-526
3 Fernandez E, La Vecchia C, Decarli A. Attributable risks for pancreatic cancer in northern Italy. Cancer Epidemiol Biomarkers Prev. 1996; 5 23-27
4 Ji B T, Chow W H, Gridley G. et al . Dietary factors and the risk of pancreatic cancer: a case-control study in Shanghai China. Cancer Epidemiol Biomarkers Prev. 1995; 4 885-893
5 Soler M, Chatenoud L, La Vecchia C. et al . Diet, alcohol, coffee and pancreatic cancer: final results from an Italian study. Eur J Cancer Prev. 1998; 7 455-460
6 Nkondjock A, Krewski D, Johnson K C. et al . Dietary patterns and risk of pancreatic cancer. Int J Cancer. 2005; 114 817-823
7 Nothlings U, Wilkens L R, Murphy S P. et al . Meat and fat intake as risk factors for pancreatic cancer: the multiethnic cohort study. J Natl Cancer Inst. 2005; 97 1458-1465
8 Michaud D S, Giovannucci E, Willett W C. et al . Dietary meat, dairy products, fat, and cholesterol and pancreatic cancer risk in a prospective study. Am J Epidemiol. 2003; 157 1115-1125
9 Michaud D S, Skinner H G, Wu K. et al . Dietary patterns and pancreatic cancer risk in men and women. J Natl Cancer Inst. 2005; 97 518-524
10 Hine R J, Srivastava S, Milner J A. et al . Nutritional links to plausible mechanisms underlying pancreatic cancer: a conference report. Pancreas. 2003; 27 356-366
11 Bueno M esquita HB, Maisonneuve de P, Runia S. et al . Intake of foods and nutrients and cancer of the exocrine pancreas: a population-based case-control study in The Netherlands. Int J Cancer. 1991; 48 540-549
12 Lyon J L, Slattery M L, Mahoney A W. et al . Dietary intake as a risk factor for cancer of the exocrine pancreas. Cancer Epidemiol Biomarkers Prev. 1993; 2 513-518
13 Fraser G E. Associations between diet and cancer, ischemic heart disease, and all-cause mortality in non-Hispanic white California Seventh-day Adventists. Am J Clin Nutr. 1999; 70 532S-538S
14 Mills P K, Beeson W L, Abbey D E. et al . Dietary habits and past medical history as related to fatal pancreas cancer risk among Adventists. Cancer. 1988; 61 2578-2585
15 Chan J M, Wang F, Holly E A. Vegetable and fruit intake and pancreatic cancer in a population-based case-control study in the San Francisco bay area. Cancer Epidemiol Biomarkers Prev. 2005; 14 2093-2097
16 Negri E, La Vecchia C, Franceschi S. et al . Vegetable and fruit consumption and cancer risk. Int J Cancer. 1991; 48 350-354
17 Larsson S C, Hakansson N, Naslund I. et al . Fruit and vegetable consumption in relation to pancreatic cancer risk: a prospective study. Cancer Epidemiol Biomarkers Prev. 2006; 15 301-305
18 Vainio H, Weiderpass E. Fruit and vegetables in cancer prevention. Nutr Cancer. 2006; 54 111-142
19 Lin Y, Tamakoshi A, Hayakawa T. et al . Nutritional factors and risk of pancreatic cancer: a population-based case-control study based on direct interview in Japan. J Gastroenterol. 2005; 40 297-301
20 Stolzenberg-Solomon R Z, Pietinen P, Taylor P R. et al . Prospective study of diet and pancreatic cancer in male smokers. Am J Epidemiol. 2002; 155 783-792
21 Zhang J, Zhao Z, Berkel H J. Animal fat consumption and pancreatic cancer incidence: evidence of interaction with cigarette smoking. Ann Epidemiol. 2005; 15 500-508
22 Anderson K E, Sinha R, Kulldorff M. et al . Meat intake and cooking techniques: associations with pancreatic cancer. Mutat Res. 2002; 506 - 507 225-231
23 Anderson K E, Kadlubar F F, Kulldorff M. et al . Dietary intake of heterocyclic amines and benzo(a)pyrene: associations with pancreatic cancer. Cancer Epidemiol Biomarkers Prev. 2005; 14 2261-2265
24 Ghadirian P, Baillargeon J, Simard A. et al . Food habits and pancreatic cancer: a case-control study of the Francophone community in Montreal, Canada. Cancer Epidemiol Biomarkers Prev. 1995; 4 895-899
25 Fernandez E, Chatenoud L, La Vecchia C. et al . Fish consumption and cancer risk. Am J Clin Nutr. 1999; 70 85-90
26 Michaud D S, Liu S, Giovannucci E. et al . Dietary sugar, glycemic load, and pancreatic cancer risk in a prospective study. J Natl Cancer Inst. 2002; 94 1293-1300
27 Silvera S A, Rohan T E, Jain M. et al . Glycemic index, glycemic load, and pancreatic cancer risk (Canada). Cancer Causes Control. 2005; 16 431-436
28 Schernhammer E S, Hu F B, Giovannucci E. et al . Sugar-sweetened soft drink consumption and risk of pancreatic cancer in two prospective cohorts. Cancer Epidemiol Biomarkers Prev. 2005; 14 2098-2105
29 Lin Y, Tamakoshi A, Kawamura T. et al . Risk of pancreatic cancer in relation to alcohol drinking, coffee consumption and medical history: findings from the Japan collaborative cohort study for evaluation of cancer risk. Int J Cancer. 2002; 99 742-746
30 Michaud D S, Giovannucci E, Willett W C. et al . Coffee and alcohol consumption and the risk of pancreatic cancer in two prospective United States cohorts. Cancer Epidemiol Biomarkers Prev. 2001; 10 429-437
31 Silverman D T. Risk factors for pancreatic cancer: a case-control study based on direct interviews. Teratog Carcinog Mutagen. 2001; 21 7-25
32 Brown L M. Epidemiology of alcohol-associated cancers. Alcohol. 2005; 35 161-168
33 Ye W, Lagergren J, Weiderpass E. et al . Alcohol abuse and the risk of pancreatic cancer. Gut. 2002; 51 236-239
34 Talamini G, Bassi C, Falconi M. et al . Alcohol and smoking as risk factors in chronic pancreatitis and pancreatic cancer. Dig Dis Sci. 1999; 44 1303-1311
35 MacMahon B, Yen S, Trichopoulos D. et al . Coffee and cancer of the pancreas. N Engl J Med. 1981; 304 630-633
36 Gullo L, Pezzilli R, Morselli-Labate A M. Coffee and cancer of the pancreas: an Italian multicenter study. The Italian Pancreatic Cancer Study Group. Pancreas. 1995; 11 223-229
37 Lyon J L, Mahoney A W, French T K. et al . Coffee consumption and the risk of cancer of the exocrine pancreas: a case-control study in a low-risk population. Epidemiology. 1992; 3 164-170
38 Harnack L J, Anderson K E, Zheng W. et al . Smoking, alcohol, coffee, and tea intake and incidence of cancer of the exocrine pancreas: the Iowa Women’s Health Study. Cancer Epidemiol Biomarkers Prev. 1997; 6 1081-1086
39 Qiu D, Kurosawa M, Lin Y. et al . Overview of the epidemiology of pancreatic cancer focusing on the JACC Study. J Epidemiol. 2005; 15 (Suppl 2) S157-167
40 Tavani A, La Vecchia C. Coffee and cancer: a review of epidemiological studies, 1990 - 1999. Eur J Cancer Prev. 2000; 9 241-256
41 La Vecchia C, Negri E, Franceschi S. et al . Tea consumption and cancer risk. Nutr Cancer. 1992; 17 27-31
42 Nagano J, Kono S, Preston D L. et al . A prospective study of green tea consumption and cancer incidence, Hiroshima and Nagasaki (Japan). Cancer Causes Control. 2001; 12 501-508
43 Hemminki K, Dong C, Vaittinen P. Cancer risks to spouses and offspring in the Family-Cancer Database. Genet Epidemiol. 2001; 20 247-257
44 Hemminki K, Jiang Y. Cancer risks among long-standing spouses. Br J Cancer. 2002; 86 1737-1740
45 Nilsen T I, Vatten L J. A prospective study of lifestyle factors and the risk of pancreatic cancer in Nord-Trondelag, Norway. Cancer Causes Control. 2000; 11 645-652
46 Berrington de Gonzalez A, Sweetland S, Spencer E. A meta-analysis of obesity and the risk of pancreatic cancer. Br J Cancer. 2003; 89 519-523
47 Michaud D S, Giovannucci E, Willett W C. et al . Physical activity, obesity, height, and the risk of pancreatic cancer. Jama. 2001; 286 921-929
48 Patel A V, Rodriguez C, Bernstein L. et al . Obesity, recreational physical activity, and risk of pancreatic cancer in a large U. S. Cohort. Cancer Epidemiol Biomarkers Prev. 2005; 14 459-466
49 Rapp K, Schroeder J, Klenk J. et al . Obesity and incidence of cancer: a large cohort study of over 145 000 adults in Austria. Br J Cancer. 2005; 93 1062-1067
50 Larsson S C, Permert J, Hakansson N. et al . Overall obesity, abdominal adiposity, diabetes and cigarette smoking in relation to the risk of pancreatic cancer in two Swedish population-based cohorts. Br J Cancer. 2005; 93 1310-1315
51 Berrington de Gonzalez A, Spencer E A, Bueno-de-Mesquita H B. et al . Anthropometry, physical activity, and the risk of pancreatic cancer in the European prospective investigation into cancer and nutrition. Cancer Epidemiol Biomarkers Prev. 2006; 15 879-885
52 Silverman D T, Swanson C A, Gridley G. et al . Dietary and nutritional factors and pancreatic cancer: a case-control study based on direct interviews. J Natl Cancer Inst. 1998; 90 1710-1719
53 Stolzenberg-Solomon R Z, Pietinen P, Taylor P R. et al . A prospective study of medical conditions, anthropometry, physical activity, and pancreatic cancer in male smokers (Finland). Cancer Causes Control. 2002; 13 417-426
54 Hanley A J, Johnson K C, Villeneuve P J. et al . Physical activity, anthropometric factors and risk of pancreatic cancer: results from the Canadian enhanced cancer surveillance system. Int J Cancer. 2001; 94 140-147
55 Coughlin S S, Calle E E, Patel A V. et al . Predictors of pancreatic cancer mortality among a large cohort of United States adults. Cancer Causes Control. 2000; 11 915-923
56 Lin Y, Tamakoshi A, Kawamura T. et al . A prospective cohort study of cigarette smoking and pancreatic cancer in Japan. Cancer Causes Control. 2002; 13 249-254
57 Yun Y H, Jung K W, Bae J M. et al . Cigarette smoking and cancer incidence risk in adult men: National Health Insurance Corporation Study. Cancer Detect Prev. 2005; 29 15-24
58 Chiu B C, Lynch C F, Cerhan J R. et al . Cigarette smoking and risk of bladder, pancreas, kidney, and colorectal cancers in Iowa. Ann Epidemiol. 2001; 11 28-37
59 Bonelli L, Aste H, Bovo P. et al . Exocrine pancreatic cancer, cigarette smoking, and diabetes mellitus: a case-control study in northern Italy. Pancreas. 2003; 27 143-149
60 Duell E J, Holly E A, Bracci P M. et al . A population-based, case-control study of polymorphisms in carcinogen-metabolizing genes, smoking, and pancreatic adenocarcinoma risk. J Natl Cancer Inst. 2002; 94 297-306
61 Miyasaka K, Kawanami T, Shimokata H. et al . Inactive aldehyde dehydrogenase-2 increased the risk of pancreatic cancer among smokers in a Japanese male population. Pancreas. 2005; 30 95-98
62 Wang L, Miao X, Tan W. et al . Genetic polymorphisms in methylenetetrahydrofolate reductase and thymidylate synthase and risk of pancreatic cancer. Clin Gastroenterol Hepatol. 2005; 3 743-751
63 Villeneuve P J, Johnson K C, Mao Y. et al . Environmental tobacco smoke and the risk of pancreatic cancer: findings from a Canadian population-based case-control study. Can J Public Health. 2004; 95 32-37
64 Alguacil J, Pollan M, Gustavsson P. Occupations with increased risk of pancreatic cancer in the Swedish population. Occup Environ Med. 2003; 60 570-576
65 Alguacil J, Porta M, Benavides F G. et al . Occupation and pancreatic cancer in Spain: a case-control study based on job titles. PANKRAS II Study Group. Int J Epidemiol. 2000; 29 1004-1013
66 Laakkonen A, Kauppinen T, Pukkala E. Cancer risk among Finnish food industry workers. Int J Cancer. 2006; 118 2567-2571
67 Fryzek J P, Garabrant D H, Harlow S D. et al . A case-control study of self-reported exposures to pesticides and pancreas cancer in southeastern Michigan. Int J Cancer. 1997; 72 62-67
68 Ji B T, Silverman D T, Stewart P A. et al . Occupational exposure to pesticides and pancreatic cancer. Am J Ind Med. 2001; 39 92-99
69 Ojajarvi I A, Partanen T J, Ahlbom A. et al . Occupational exposures and pancreatic cancer: a meta-analysis. Occup Environ Med. 2000; 57 316-324
70 Ojajarvi A, Partanen T, Ahlbom A. et al . Risk of pancreatic cancer in workers exposed to chlorinated hydrocarbon solvents and related compounds: a meta-analysis. Am J Epidemiol. 2001; 153 841-850
71 Weiderpass E, Vainio H, Kauppinen T. et al . Occupational exposures and gastrointestinal cancers among Finnish women. J Occup Environ Med. 2003; 45 305-315
72 Yassi A, Tate R B, Routledge M. Cancer incidence and mortality in workers employed at a transformer manufacturing plant: update to a cohort study. Am J Ind Med. 2003; 44 58-62
73 Ji J, Hemminki K. Socioeconomic and occupational risk factors for pancreatic cancer: a cohort study in Sweden. J Occup Environ Med. 2006; 48 283-288
74 Bjelakovic G, Nikolova D, Simonetti R G. et al . Antioxidant supplements for prevention of gastrointestinal cancers: a systematic review and meta-analysis. Lancet. 2004; 364 1219-1228
75 Bjelakovic G, Nikolova D, Simonetti R G. et al . Antioxidant supplements for preventing gastrointestinal cancers. Cochrane Database Syst Rev CD 004 183. 2004;
76 Harris R E, Beebe-Donk J, Doss H. et al . Aspirin, ibuprofen, and other non-steroidal anti-inflammatory drugs in cancer prevention: a critical review of non-selective COX-2 blockade (review). Oncol Rep. 2005; 13 559-583
77 Jacobs E J, Connell C J, Rodriguez C. et al . Aspirin use and pancreatic cancer mortality in a large United States cohort. J Natl Cancer Inst. 2004; 96 524-528
78 Coogan P F, Rosenberg L, Palmer J R. et al . Nonsteroidal anti-inflammatory drugs and risk of digestive cancers at sites other than the large bowel. Cancer Epidemiol Biomarkers Prev. 2000; 9 119-123
79 Homma T, Tsuchiya R. The study of the mass screening of persons without symptoms and of the screening of outpatients with gastrointestinal complaints or icterus for pancreatic cancer in Japan, using CA 19-9 and elastase-1 or ultrasonography. Int J Pancreatol. 1991; 9 119-124
80 Kim J E, Lee K T, Lee J K. et al . Clinical usefulness of carbohydrate antigen 19-9 as a screening test for pancreatic cancer in an asymptomatic population. J Gastroenterol Hepatol. 2004; 19 182-186
81 McWilliams R R, Rabe K G, Olswold C. et al . Risk of malignancy in first-degree relatives of patients with pancreatic carcinoma. Cancer. 2005; 104 388-394
82 Klein A P, Brune K A, Petersen G M. et al . Prospective risk of pancreatic cancer in familial pancreatic cancer kindreds. Cancer Res. 2004; 64 2634-2638
83 Bartsch D K, Sina-Frey M, Lang S. et al . CDKN2A germline mutations in familial pancreatic cancer. Ann Surg. 2002; 236 730-737
84 McFaul C D, Greenhalf W, Earl J. et al . Anticipation in familial pancreatic cancer. Gut. 2006; 55 252-258
85 Tersmette A C, Petersen G M, Offerhaus G J. et al . Increased risk of incident pancreatic cancer among first-degree relatives of patients with familial pancreatic cancer. Clin Cancer Res. 2001; 7 738-744
86 Brentnall T A. Management strategies for patients with hereditary pancreatic cancer. Curr Treat Options Oncol. 2005; 6 437-445
87 Canto M I, Goggins M, Yeo C J. et al . Screening for pancreatic neoplasia in high-risk individuals: an EUS-based approach. Clin Gastroenterol Hepatol. 2004; 2 606-621
88 Canto M I, Goggins M, Hruban R H. et al . Screening for early pancreatic neoplasia in high-risk individuals: a prospective controlled study. Clin Gastroenterol Hepatol. 2006; 4 766-781; quiz 665
89 Giardiello F M, Brensinger J D, Tersmette A C. et al . Very high risk of cancer in familial Peutz-Jeghers syndrome. Gastroenterology. 2000; 119 1447-1453
90 Lim W, Olschwang S, Keller J J. et al . Relative frequency and morphology of cancers in STK11 mutation carriers. Gastroenterology. 2004; 126 1788-1794
91 Lynch H T, Brand R E, Hogg D. et al . Phenotypic variation in eight extended CDKN2A germline mutation familial atypical multiple mole melanoma-pancreatic carcinoma-prone families: the familial atypical mole melanoma-pancreatic carcinoma syndrome. Cancer. 2002; 94 84-96
92 Rulyak S J, Brentnall T A, Lynch H T. et al . Characterization of the neoplastic phenotype in the familial atypical multiple-mole melanoma-pancreatic carcinoma syndrome. Cancer. 2003; 98 798-804
93 Vasen H F, Gruis N A, Frants R R. et al . Risk of developing pancreatic cancer in families with familial atypical multiple mole melanoma associated with a specific 19 deletion of p16 (p16-Leiden). Int J Cancer. 2000; 87 809-811
94 Friedenson B. BRCA1 and BRCA2 pathways and the risk of cancers other than breast or ovarian. MedGenMed. 2005; 7 60
95 Asperen C Jvan, Brohet R M, Meijers-Heijboer E J. et al . Cancer risks in BRCA2 families: estimates for sites other than breast and ovary. J Med Genet. 2005; 42 711-719
96 Thompson D, Easton D F. Cancer Incidence in BRCA1 mutation carriers. J Natl Cancer Inst. 2002; 94 1358-1365
97 Lilley M, Gilchrist D. The hereditary spectrum of pancreatic cancer: the Edmonton experience. Can J Gastroenterol. 2004; 18 17-21
98 Aarnio M, Sankila R, Pukkala E. et al . Cancer risk in mutation carriers of DNA-mismatch-repair genes. Int J Cancer. 1999; 81 214-218
99 Geoffroy-Perez B, Janin N, Ossian K. et al . Cancer risk in heterozygotes for ataxia-telangiectasia. Int J Cancer. 2001; 93 288-293
100 Giardiello F M, Offerhaus G J, Lee D H. et al . Increased risk of thyroid and pancreatic carcinoma in familial adenomatous polyposis. Gut. 1993; 34 1394-1396
101 Couch F J, Johnson M R, Rabe K. et al . Germ line Fanconi anemia complementation group C mutations and pancreatic cancer. Cancer Res. 2005; 65 383-386
102 Howes N, Lerch M M, Greenhalf W. et al . Clinical and genetic characteristics of hereditary pancreatitis in Europe. Clin Gastroenterol Hepatol. 2004; 2 252-261
103 Lowenfels A B, Maisonneuve P, DiMagno E P. et al . Hereditary pancreatitis and the risk of pancreatic cancer. International Hereditary Pancreatitis Study Group. J Natl Cancer Inst. 1997; 89 442-446
104 Kimmey M B, Bronner M P, Byrd D R. et al . Screening and surveillance for hereditary pancreatic cancer. Gastrointest Endosc. 2002; 56 S82-86
105 Bansal P, Sonnenberg A. Pancreatitis is a risk factor for pancreatic cancer. Gastroenterology. 1995; 109 247-251
106 Karlson B M, Ekbom A, Josefsson S. et al . The risk of pancreatic cancer following pancreatitis: an association due to confounding?. Gastroenterology. 1997; 113 587-592
107 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
108 Malka D, Hammel P, Maire F. et al . Risk of pancreatic adenocarcinoma in chronic pancreatitis. Gut. 2002; 51 849-852
109 Talamini G, Falconi M, Bassi C. et al . Incidence of cancer in the course of chronic pancreatitis. Am J Gastroenterol. 1999; 94 1253-1260
110 Chari S T, Leibson C L, Rabe K G. et al . Probability of pancreatic cancer following diabetes: a population-based study. Gastroenterology. 2005; 129 504-511
111 Coughlin S S, Calle E E, Teras L R. et al . Diabetes mellitus as a predictor of cancer mortality in a large cohort of US adults. Am J Epidemiol. 2004; 159 1160-1167
112 Huxley R, Ansary-Moghaddam A, Berrington de Gonzalez A. et al . Type-II diabetes and pancreatic cancer. A meta-analysis of 36 studies. Br J Cancer. 2005; 92 2076-2083
113 Stolzenberg-Solomon R Z, Graubard B I, Chari S. et al . Insulin, glucose, insulin resistance, and pancreatic cancer in male smokers. Jama. 2005; 294 2872-2878
114 Wideroff L, Gridley G, Mellemkjaer L. et al . Cancer incidence in a population-based cohort of patients hospitalized with diabetes mellitus in Denmark. J Natl Cancer Inst. 1997; 89 1360-1365
115 Calle E E, Murphy T K, Rodriguez C. et al . Diabetes mellitus and pancreatic cancer mortality in a prospective cohort of United States adults. Cancer Causes Control. 1998; 9 403-410
116 Chow W H, Gridley G, Nyren O. et al . Risk of pancreatic cancer following diabetes mellitus: a nationwide cohort study in Sweden. J Natl Cancer Inst. 1995; 87 930-931
117 Silverman D T, Schiffman M, Everhart J. et al . Diabetes mellitus, other medical conditions and familial history of cancer as risk factors for pancreatic cancer. Br J Cancer. 1999; 80 1830-1837
118 Everhart J, Wright D. Diabetes mellitus as a risk factor for pancreatic cancer. A meta-analysis. Jama. 1995; 273 1605-1609
119 Gullo L, Pezzilli R, Morselli-Labate A M. Diabetes and the risk of pancreatic cancer. Italian Pancreatic Cancer Study Group. N Engl J Med. 1994; 331 81-84
120 Rousseau M C, Parent M E, Pollak M N. et al . Diabetes mellitus and cancer risk in a population-based case-control study among men from Montreal, Canada. Int J Cancer. 2006; 118 2105-2109
121 Bjornsson E, Ismael S, Nejdet S. et al . Severe jaundice in Sweden in the new millennium: causes, investigations, treatment and prognosis. Scand J Gastroenterol. 2003; 38 86-94
122 Reisman Y, Gips C H, Lavelle S M. et al . Clinical presentation of (subclinical) jaundice - the Euricterus project in The Netherlands. United Dutch Hospitals and Euricterus Project Management Group. Hepatogastroenterology. 1996; 43 1190-1195
123 Watanabe I, Sasaki S, Konishi M. et al . Onset symptoms and tumor locations as prognostic factors of pancreatic cancer. Pancreas. 2004; 28 160-165
124 Balthazar E J. Pancreatitis associated with pancreatic carcinoma. Preoperative diagnosis: role of CT imaging in detection and evaluation. Pancreatology. 2005; 5 330-344
125 Mujica V R, Barkin J S, Go V L. Acute pancreatitis secondary to pancreatic carcinoma. Study Group Participants. Pancreas. 2000; 21 329-332
126 Adamek H E, Albert J, Breer H. et al . Pancreatic cancer detection with magnetic resonance cholangiopancreatography and endoscopic retrograde cholangiopancreatography: a prospective controlled study. Lancet. 2000; 356 190-193
127 Hanninen E L, Ricke J, Amthauer H. et al . Magnetic resonance cholangiopancreatography: image quality, ductal morphology, and value of additional T 2- and T 1-weighted sequences for the assessment of suspected pancreatic cancer. Acta Radiol. 2005; 46 117-125
128 Forsmark C E, Lambiase L, Vogel S B. Diagnosis of pancreatic cancer and prediction of unresectability using the tumor-associated antigen CA 19-9. Pancreas. 1994; 9 731-734
129 Nazli O, Bozdag A D, Tansug T. et al . The diagnostic importance of CEA and CA 19-9 for the early diagnosis of pancreatic carcinoma. Hepatogastroenterology. 2000; 47 1750-1752
130 Ritts R E, Nagorney D M, Jacobsen D J. et al . Comparison of preoperative serum CA 19-9 levels with results of diagnostic imaging modalities in patients undergoing laparotomy for suspected pancreatic or gallbladder disease. Pancreas. 1994; 9 707-716
131 Tessler D A, Catanzaro Jr A, Velanovich V. et al . Predictors of cancer in patients with suspected pancreatic malignancy without a tissue diagnosis. Am J Surg. 2006; 191 191-197
132 Agarwal B, Abu-Hamda E, Molke K L. et al . Endoscopic ultrasound-guided fine needle aspiration and multidetector spiral CT in the diagnosis of pancreatic cancer. Am J Gastroenterol. 2004; 99 844-850
133 Klapman J B, Chang K J, Lee J G. et al . Negative predictive value of endoscopic ultrasound in a large series of patients with a clinical suspicion of pancreatic cancer. Am J Gastroenterol. 2005; 100 2658-2661
134 Varadarajulu S, Wallace M B. Applications of endoscopic ultrasonography in pancreatic cancer. Cancer Control. 2004; 11 15-22
135 David O, Green L, Reddy V. et al . Pancreatic masses: a multi-institutional study of 364 fine-needle aspiration biopsies with histopathologic correlation. Diagn Cytopathol. 1998; 19 423-427
136 Bipat S, Phoa S S, Delden O M. et al . Ultrasonography, computed tomography and magnetic resonance imaging for diagnosis and determining resectability of pancreatic adenocarcinoma: a meta-analysis. J Comput Assist Tomogr. 2005; 29 438-445
137 Dewitt J, Devereaux B M, Lehman G A. et al . Comparison of endoscopic ultrasound and computed tomography for the preoperative evaluation of pancreatic cancer: a systematic review. Clin Gastroenterol Hepatol. 2006; 4 717-725; quiz 664
138 Romagnuolo J, Bardou M, Rahme E. et al . Magnetic resonance cholangiopancreatography: a meta-analysis of test performance in suspected biliary disease. Ann Intern Med. 2003; 139 547-557
139 Pakzad F, Groves A M, Ell P J. The role of positron emission tomography in the management of pancreatic cancer. Semin Nucl Med. 2006; 36 248-256
140 Schachter P P, Avni Y, Shimonov M. et al . The impact of laparoscopy and laparoscopic ultrasonography on the management of pancreatic cancer. Arch Surg. 2000; 135 1303-1307
141 Vollmer C M, Drebin J A, Middleton W D. et al . Utility of staging laparoscopy in subsets of peripancreatic and biliary malignancies. Ann Surg. 2002; 235 1-7
142 Waaij L A, Dullemen H M, Porte R J. Cyst fluid analysis in the differential diagnosis of pancreatic cystic lesions. A pooled analysis. Gastrointest Endosc. 2005; 62 383-389
143 Fong van der Y, Blumgart L H, Fortner J G. et al . Pancreatic or liver resection for malignancy is safe and effective for the elderly. Ann Surg. 1995; 222 426-434; discussion 434 - 437
144 Lightner A M, Glasgow R E, Jordan T H. et al . Pancreatic resection in the elderly. J Am Coll Surg. 2004; 198 697-706
145 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; discussion 328 - 330
146 American College of Physicians . Guidelines for assessing and managing the perioperative risk from coronary artery disease associated with major noncardiac surgery. Ann Intern Med. 1997; 127 309-312
147 Wagner M, Redaelli C, Lietz M. et al . Curative resection is the single most important factor determining outcome in patients with pancreatic adenocarcinoma. Br J Surg. 2004; 91 586-594
148 Fuhrman G M, Leach S D, Staley C A. et al . Rationale for en bloc vein resection in the treatment of pancreatic adenocarcinoma adherent to the superior mesenteric-portal vein confluence. Pancreatic Tumor Study Group. Ann Surg. 1996; 223 154-162
149 Leach S D, Lee J E, Charnsangavej C. et al . Survival following pancreaticoduodenectomy with resection of the superior mesenteric-portal vein confluence for adenocarcinoma of the pancreatic head. Br J Surg. 1998; 85 611-617
150 Sasson A R, Hoffman J P, Ross E A. et al . En bloc resection for locally advanced cancer of the pancreas: is it worthwhile?. J Gastrointest Surg. 2002; 6 147-157; discussion 157 - 158
151 Nakao A, Takeda S, Inoue S. et al . Indications and techniques of extended resection for pancreatic cancer. World J Surg. 2006; 30 976-982; discussion 983 - 984
152 Varadhachary G R, Tamm E P, Abbruzzese J L. et al . Borderline resectable pancreatic cancer: definitions, management, and role of preoperative therapy. Ann Surg Oncol. 2006; 13 1035-1046
153 Siriwardana H P, Siriwardena A K. Systematic review of outcome of synchronous portal-superior mesenteric vein resection during pancreatectomy for cancer. Br J Surg. 2006; 93 662-673
154 Carrere N, Sauvanet A, Goere D. et al . Pancreaticoduodenectomy with mesentericoportal vein resection for adenocarcinoma of the pancreatic head. World J Surg. 2006; 30 1526-1535
155 Riediger H, Makowiec F, Fischer E. et al . Postoperative morbidity and long-term survival after pancreaticoduodenectomy with superior mesenterico-portal vein resection. J Gastrointest Surg. 2006; 10 1106-1115
156 Bachellier P, Nakano H, Oussoultzoglou P D. et al . Is pancreaticoduodenectomy with mesentericoportal venous resection safe and worthwhile?. Am J Surg. 2001; 182 120-129
157 Li B, Chen F Z, Ge X H. et al . Pancreatoduodenectomy with vascular reconstruction in treating carcinoma of the pancreatic head. Hepatobiliary Pancreat Dis Int. 2004; 3 612-615
158 Settmacher U, Langrehr J M, Husmann I. et al . Reconstruction of visceral arteries with homografts in excision of the pancreas. Chirurg. 2004; 75 1199-1206
159 Schwarz R E. Technical considerations to maintain a low frequency of postoperative biliary stent-associated infections. J Hepatobiliary Pancreat Surg. 2002; 9 93-97
160 Gerke H, White R, Byrne M F. et al . Complications of pancreaticoduodenectomy after neoadjuvant chemoradiation in patients with and without preoperative biliary drainage. Dig Liver Dis. 2004; 36 412-418
161 Jagannath P, Dhir V, Shrikhande S. et al . Effect of preoperative biliary stenting on immediate outcome after pancreaticoduodenectomy. Br J Surg. 2005; 92 356-361
162 Martignoni M E, Wagner M, Krahenbuhl L. et al . Effect of preoperative biliary drainage on surgical outcome after pancreatoduodenectomy. Am J Surg. 2001; 181 52-59; discussion 87
163 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; discussion 267 - 268
164 Targarona E M, Garau J, Munoz-Ramos C. et al . Single-dose antibiotic prophylaxis in patients at high risk for infection in biliary surgery: a prospective and randomized study comparing cefonicid with mezlocillin. Surgery. 1990; 107 327-334
165 Kujath P, Bouchard R, Scheele J. et al . Current perioperative antibiotic prophylaxis. Chirurg. 2006; 77 490, 492-498
166 Connor S, Alexakis N, Garden O J. et al . Meta-analysis of the value of somatostatin and its analogues in reducing complications associated with pancreatic surgery. Br J Surg. 2005; 92 1059-1067
167 Bassi C, Dervenis C, Butturini G. et al . Postoperative pancreatic fistula: an international study group (ISGPF) definition. Surgery. 2005; 138 8-13
168 Finlayson C, Hoffman J, Yeung R. et al . Intraoperative ultrasound does not improve detection of liver metastases in resectable pancreatic cancer. Am J Surg. 1998; 175 99-101
169 Kolecki R, Schirmer B. Intraoperative and laparoscopic ultrasound. Surg Clin North Am. 1998; 78 251-271
170 Warshaw A L, Fernandez-del Castillo C. Pancreatic carcinoma. N Engl J Med. 1992; 326 455-465
171 Konishi M, Kinoshita T, Nakagohri T. et al . Prognostic value of cytologic examination of peritoneal washings in pancreatic cancer. Arch Surg. 2002; 137 475-480
172 Yachida S, Fukushima N, Sakamoto M. et al . Implications of peritoneal washing cytology in patients with potentially resectable pancreatic cancer. Br J Surg. 2002; 89 573-578
173 Diener M K, Knaebel H P, Heukaufer C. et al . A Systematic Review and Meta-analysis of Pylorus-preserving Versus Classical Pancreaticoduodenectomy for Surgical Treatment of Periampullary and Pancreatic Carcinoma. Ann Surg. 2007; 245 187-200
174 Christein J D, Kendrick M L, Iqbal C W. et al . Distal pancreatectomy for resectable adenocarcinoma of the body and tail of the pancreas. J Gastrointest Surg. 2005; 9 922-927
175 Shimada K, Sakamoto Y, Sano T. et al . Prognostic factors after distal pancreatectomy with extended lymphadenectomy for invasive pancreatic adenocarcinoma of the body and tail. Surgery. 2006; 139 288-295
176 Shoup M, Conlon K C, Klimstra D. et al . Is extended resection for adenocarcinoma of the body or tail of the pancreas justified?. J Gastrointest Surg. 2003; 7 946-952; discussion 952
177 Pedrazzoli S, DiCarlo V, Dionigi R. et al . Standard versus extended lymphadenectomy associated with pancreatoduodenectomy in the surgical treatment of adenocarcinoma of the head of the pancreas: a multicenter, prospective, randomized study. Lymphadenectomy Study Group. Ann Surg. 1998; 228 508-517
178 Farnell M B, Pearson R K, Sarr M G. et al . A prospective randomized trial comparing standard pancreatoduodenectomy with pancreatoduodenectomy with extended lymphadenectomy in resectable pancreatic head adenocarcinoma. Surgery. 2005; 138 618-628; discussion 628 - 630
179 Yeo C J, Cameron J L, Lillemoe K D. et al . Pancreaticoduodenectomy with or without distal gastrectomy and extended retroperitoneal lymphadenectomy for periampullary adenocarcinoma, part 2: randomized controlled trial evaluating survival, morbidity, and mortality. Ann Surg. 2002; 236 355-366; discussion 366 - 368
180 Brugge W R, Lauwers G Y, Sahani D. et al . Cystic neoplasms of the pancreas. N Engl J Med. 2004; 351 1218-1226
181 Brugge W R, Lewandrowski K, Lee-Lewandrowski E. et al . Diagnosis of pancreatic cystic neoplasms: a report of the cooperative pancreatic cyst study. Gastroenterology. 2004; 126 1330-1336
182 Sedlack R, Affi A, Vazquez-Sequeiros E. et al . Utility of EUS in the evaluation of cystic pancreatic lesions. Gastrointest Endosc. 2002; 56 543-547
183 Salvia R, Fernandez-del Castillo C, Bassi C. et al . Main-duct intraductal papillary mucinous neoplasms of the pancreas: clinical predictors of malignancy and long-term survival following resection. Ann Surg. 2004; 239 678-685; discussion 685 - 687
184 Bassi C, Salvia R, Molinari E. et al . Management of 100 consecutive cases of pancreatic serous cystadenoma: wait for symptoms and see at imaging or vice versa?. World J Surg. 2003; 27 319-323
185 Hirano S, Kondo S, Ambo Y. et al . Outcome of duodenum-preserving resection of the head of the pancreas for intraductal papillary-mucinous neoplasm. Dig Surg. 2004; 21 242-245
186 Takada T, Yasuda H, Amano H. et al . Simultaneous hepatic resection with pancreato-duodenectomy for metastatic pancreatic head carcinoma: does it improve survival?. Hepatogastroenterology. 1997; 44 567-573
187 Mann O, Strate T, Schneider C. et al . Surgery for advanced and metastatic pancreatic cancer - current state and perspectives. Anticancer Res. 2006; 26 681-686
188 Shrikhande S V, Kleeff J, Reiser C. et al . Pancreatic resection for M 1 pancreatic ductal adenocarcinoma. Ann Surg Oncol. 2007; 14 118-127
189 Friess H, Kleeff J, Silva J C. et al . The role of diagnostic laparoscopy in pancreatic and periampullary malignancies. J Am Coll Surg. 1998; 186 675-682
190 Urbach D R, Swanstrom L L, Hansen P D. The effect of laparoscopy on survival in pancreatic cancer. Arch Surg. 2002; 137 191-199
191 Santoro E, Carlini M, Carboni F. Laparoscopic pancreatic surgery: indications, techniques and preliminary results. Hepatogastroenterology. 1999; 46 1174-1180
192 Cioc A M, Ellison E C, Proca D M. et al . Frozen section diagnosis of pancreatic lesions. Arch Pathol Lab Med. 2002; 126 1169-1173
193 Luttges J, Zamboni G, Kloppel G. Recommendation for the examination of pancreaticoduodenectomy specimens removed from patients with carcinoma of the exocrine pancreas. A proposal for a standardized pathological staging of pancreaticoduodenectomy specimens including a checklist. Dig Surg. 1999; 16 291-296
194 Compton C C, Henson D E. Protocol for the examination of specimens removed from patients with carcinoma of the exocrine pancreas: a basis for checklists. Cancer Committee, College of American Pathologists. Arch Pathol Lab Med. 1997; 121 1129-1136
195 Sakata E, Shirai Y, Yokoyama N. et al . Clinical significance of lymph node micrometastasis in ampullary carcinoma. World J Surg. 2006; 30 985-991
196 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
197 Stocken D D, Buchler M W, Dervenis C. et al . Meta-analysis of randomised adjuvant therapy trials for pancreatic cancer. Br J Cancer. 2005; 92 1372-1381
198 Neoptolemos J P, Stocken D D, Friess H. et al . A randomized trial of chemoradiotherapy and chemotherapy after resection of pancreatic cancer. N Engl J Med. 2004; 350 1200-1210
199 Penberthy D R, Rich T A, Shelton C H. et al . A pilot study of chronomodulated infusional 5-fluorouracil chemoradiation for pancreatic cancer. Ann Oncol. 2001; 12 681-684
200 Mallinson C N, Rake M O, Cocking J B. et al . Chemotherapy in pancreatic cancer: results of a controlled, prospective, randomised, multicentre trial. Br Med J. 1980; 281 1589-1591
201 Palmer K R, Kerr M, Knowles G. et al . Chemotherapy prolongs survival in inoperable pancreatic carcinoma. Br J Surg. 1994; 81 882-885
202 Glimelius B, Hoffman K, Sjoden P O. et al . Chemotherapy improves survival and quality of life in advanced pancreatic and biliary cancer. Ann Oncol. 1996; 7 593-600
203 Yip D, Karapetis C, Strickland A. et al . Chemotherapy and radiotherapy for inoperable advanced pancreatic cancer. Cochrane Database Syst Rev 3 CD 002 093. 2006;
204 Burris H A3 rd, Moore M J, Andersen 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
205 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
206 Louvet C, Labianca R, Hammel P. et al . Gemcitabine in combination with oxaliplatin compared with gemcitabine alone in locally advanced or metastatic pancreatic cancer: results of a GERCOR and GISCAD phase III trial. J Clin Oncol. 2005; 23 3509-3516
207 Heinemann V, Quietzsch D, Gieseler F. et al . Randomized phase III trial of gemcitabine plus cisplatin compared with gemcitabine alone in advanced pancreatic cancer. J Clin Oncol. 2006; 24 3946-3952
208 Herrmann R, Bodoky G, Rushstaller T. et al . Gemcitabine (G) plus capecitabine (C) versus G alone in locally advanced or metastatic pancreatic cancer: a randomized phase III study of the Swiss Group for Clinical Cancer Research (SAKK) and the Central European Cooperative Oncology Group (CECOG). J Clin Oncol. 2005; 23 A4010
209 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 E 2297. J Clin Oncol. 2002; 20 3270-3275
210 Van Cutsem E, Velde H, Karasek P. et al . Phase III trial of gemcitabine plus tipifarnib compared with gemcitabine plus placebo in advanced pancreatic cancer. J Clin Oncol. 2004; 22 1430-1438
211 Tempero M, Plunkett W, Van Ruiz H aperen V. 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
212 Poplin E, Levy D, Berlin J. et al . Phase III trial of gemcitabine (30 min infusion) versus gemcitabine (fixed-dose rate infusion (FDR) versus gemcitabine + oxaliplatin (GEMOX) in patients with advanced pancreatic cancer (E6201). J Clin Oncol. 2006; 24 LBA4004
213 Maisey N, Chau I, Cunningham D. et al . Multicenter randomized phase III trial comparing protracted venous infusion (PVI) fluorouracil (5-FU) with PVI 5-FU plus mitomycin in inoperable pancreatic cancer. J Clin Oncol. 2002; 20 3130-3136
214 Ducreux M, Rougier P, Pignon J P. et al . A randomised trial comparing 5-FU with 5-FU plus cisplatin in advanced pancreatic carcinoma. Ann Oncol. 2002; 13 1185-1191
215 Lutz M P, Koniger M, Muche R. et al . A phase II study of weekly 24-h infusion of high-dose 5-fluorouracil in advanced pancreatic cancer. Z Gastroenterol. 1999; 37 993-997
216 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
217 Ducreux M, Mitry E, Ould-Kaci M. et al . Randomized phase II study evaluating oxaliplatin alone, oxaliplatin combined with infusional 5-FU, and infusional 5-FU alone in advanced pancreatic carcinoma patients. Ann Oncol. 2004; 15 467-473
218 Cunningham D, Chau I, Stocken D D. et al . Phase III randomized comparison of gemcitabine (GEM) vs. gemcitabine plus capecitabine (Gem-CAP) in patients with advanced pancreatic cancer. Eur J Cancer. 2005; 3 PS11
219 Di Costanzo F, Carlini P, Doni L. et al . Gemcitabine with or without continuous infusion 5-FU in advanced pancreatic cancer: a randomised phase II trial of the Italian oncology group for clinical research (GOIRC). Br J Cancer. 2005; 93 185-189
220 Riess M, Helm A, Niedergethmann I. et al . A randomised prospective, multicentre phase III trial of gemcitabine, 5-fluorouracil (5-FU), folinic acid vs. gemcitabine alone in patients with advanced pancreatic cancer. J Clin Oncol. 2005; 23 A1092
221 Moore M J, 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; 15 1960-6
222 Kindler H L, Friberg G, Singh D A. et al . Phase II Trial of Bevacizumab Plus Gemcitabine in Patients With Advanced Pancreatic Cancer. J Clin Oncol. 2005; 23 8033-8040
223 Kindler H, Niedzwiecki D, Hollis D. et al . A double-blind, placebo controlled, randomized phase III trial of gemcitabine (G) plus bevacizumab (B) versus gemcitabine plus placebo (P) in patients with advanced pancreatic cancer (PC): a preliminary analysis of Cancer and Leukemia Group B (CALGB) 80 303. Proceedings of the ASCO Gastrointestinal Cancers Symposium. 2007; A108
224 Reni M, Passoni P, Bonetto E. et al . Final results of a prospective trial of a PEFG (Cisplatin, Epirubicin, 5-Fluorouracil, Gemcitabine) regimen followed by radiotherapy after curative surgery for pancreatic adenocarcinoma. Oncology. 2005; 68 239-245
225 Lutz M P, Van Cutsem E, Wagener T. et al . Docetaxel plus gemcitabine or docetaxel plus cisplatin in advanced pancreatic carcinoma: randomized phase II study 40 984 of the European Organisation for Research and Treatment of Cancer Gastrointestinal Group. J Clin Oncol. 2005; 23 9250-9256
226 Shepard R C, Levy D E, Berlin J D. et al . Phase II study of gemcitabine in combination with docetaxel in patients with advanced pancreatic carcinoma (E1298). A trial of the eastern cooperative oncology group. Oncology. 2004; 66 303-309
227 Ridwelski K, Fahlke J, Kuhn R. et al . Multicenter phase-I/II study using a combination of gemcitabine and docetaxel in metastasized and unresectable, locally advanced pancreatic carcinoma. Eur J Surg Oncol. 2006; 32 297-302
228 Jacobs A D, Otero H, Picozzi V J. et al . Gemcitabine combined with docetaxel for the treatment of unresectable pancreatic carcinoma. Cancer Invest. 2004; 22 505-514
229 Ulrich-Pur Jr H, Raderer M, Verena K ornek G. et al . Irinotecan plus raltitrexed vs raltitrexed alone in patients with gemcitabine-pretreated advanced pancreatic adenocarcinoma. Br J Cancer. 2003; 88 1180-1184
230 Tsavaris N, Kosmas C, Skopelitis H. et al . Second-line treatment with oxaliplatin, leucovorin and 5-fluorouracil in gemcitabine-pretreated advanced pancreatic cancer: A phase II study. Invest New Drugs. 2005; 23 369-375
231 Reni M, Pasetto L, Aprile G. et al . Raltitrexed-eloxatin salvage chemotherapy in gemcitabine-resistant metastatic pancreatic cancer. Br J Cancer. 2006; 94 785-791
232 Demols A, Peeters M, Polus M. et al . Gemcitabine and oxaliplatin (GEMOX) in gemcitabine refractory advanced pancreatic adenocarcinoma: a phase II study. Br J Cancer. 2006; 94 481-485
233 Oettle H, Arnold D, Esser M. et al . Paclitaxel as weekly second-line therapy in patients with advanced pancreatic carcinoma. Anticancer Drugs. 2000; 11 635-638
234 Burris 3 rd H A, Rivkin S, Reynolds R. et al . Phase II trial of oral rubitecan in previously treated pancreatic cancer patients. Oncologist. 2005; 10 183-190
235 Mitry E, Ducreux M, Ould-Kaci M. et al . Oxaliplatin combined with 5-FU in second line treatment of advanced pancreatic adenocarcinoma. Results of a phase II trial. Gastroenterol Clin Biol. 2006; 30 357-363
236 Willett C G, Czito B G, Bendell J C. et al . Locally advanced pancreatic cancer. J Clin Oncol. 2005; 23 4538-4544
237 Moertel C G, Childs D S, Reitemeier R J. et al . Combined 5-fluorouracil and supervoltage radiation therapy of locally unresectable gastrointestinal cancer. Lancet. 1969; 2 865-867
238 Moertel C G, Frytak Jr S, Hahn R G. et al . Therapy of locally unresectable pancreatic carcinoma: a randomized comparison of high dose (6000 rads) radiation alone, moderate dose radiation (4000 rads + 5-fluorouracil), and high dose radiation + 5-fluorouracil: The Gastrointestinal Tumor Study Group. Cancer. 1981; 48 1705-1710
239 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
240 Cohen L, Woodruff K H, Hendrickson F R. et al . Response of pancreatic cancer to local irradiation with high-energy neutrons. Cancer. 1985; 56 1235-1241
241 Cohen S J, Dobelbower Jr R, Lipsitz S. et al . A randomized phase III study of radiotherapy alone or with 5-fluorouracil and mitomycin-C in patients with locally advanced adenocarcinoma of the pancreas: Eastern Cooperative Oncology Group study E 8282. Int J Radiat Oncol Biol Phys. 2005; 62 1345-1350
242 Gastrointestinal Tumor Study Group . Treatment of locally unresectable carcinoma of the pancreas: comparison of combined-modality therapy (chemotherapy plus radiotherapy) to chemotherapy alone. J Natl Cancer Inst. 1988; 80 751-755
243 Shinchi H, Takao S, Noma H. et al . Length and quality of survival after external-beam radiotherapy with concurrent continuous 5-fluorouracil infusion for locally unresectable pancreatic cancer. Int J Radiat Oncol Biol Phys. 2002; 53 146-150
244 McGinn C J, Zalupski M M, Shureiqi I. et al . Phase I trial of radiation dose escalation with concurrent weekly full-dose gemcitabine in patients with advanced pancreatic cancer. J Clin Oncol. 2001; 19 4202-4208
245 Kachnic L A, Shaw J E, Manning M A. et al . Gemcitabine following radiotherapy with concurrent 5-fluorouracil for nonmetastatic adenocarcinoma of the pancreas. Int J Cancer. 2001; 96 132-139
246 Crane C H, Abbruzzese J L, Evans D B. et al . Is the therapeutic index better with gemcitabine-based chemoradiation than with 5-fluorouracil-based chemoradiation in locally advanced pancreatic cancer?. Int J Radiat Oncol Biol Phys. 2002; 52 1293-1302
247 Rocha L ima CM, Green M R, Rotche R. et al . Irinotecan plus gemcitabine results in no survival advantage compared with gemcitabine monotherapy in patients with locally advanced or metastatic pancreatic cancer despite increased tumor response rate. J Clin Oncol. 2004; 22 3776-3783
248 Chauffert B, Mornex F, Bonnetain F. et al . Phase III trial comparing initial chemoradiotherapy (intermittent cisplatin and infusional 5-FU) followed by gemcitabine vs. gemcitabine alone in patients with locally advanced non metastatic pancreatic cancer: A FFCD-SFRO study. J Clin Oncol. 2006; 24 A4008
249 Huguet F, Andre T, Hammel P. et al . Impact of chemoradiotherapy after disease control with chemotherapy in locally advanced pancreatic adenocarcinoma in GERCOR Phase II and III studies. J Clin Oncol. 2007; 20 326-331
250 Sa Cunha A, Rault A, Laurent C. et al . Surgical resection after radiochemotherapy in patients with unresectable adenocarcinoma of the pancreas. J Am Coll Surg. 2005; 201 359-365
251 Fisher B J, Perera F E, Kocha W. et al . Analysis of the clinical benefit of 5-fluorouracil and radiation treatment in locally advanced pancreatic cancer. Int J Radiat Oncol Biol Phys. 1999; 45 291-295
252 Furuse J, Kinoshita T, Kawashima M. et al . Intraoperative and conformal external-beam radiation therapy with protracted 5-fluorouracil infusion in patients with locally advanced pancreatic carcinoma. Cancer. 2003; 97 1346-1352
253 Brunner T B, Grabenbauer G G, Kastl S. et al . Preoperative Chemoradiation in Locally Advanced Pancreatic Carcinoma: A Phase II Study. Onkologie. 2000; 23 436-442
254 Ikeda M, Okada S, Tokuuye K. et al . A phase I trial of weekly gemcitabine and concurrent radiotherapy in patients with locally advanced pancreatic cancer. Br J Cancer. 2002; 86 1551-1554
255 Talamonti M S, Catalano P J, Vaughn D J. et al . Eastern Cooperative Oncology Group Phase I trial of protracted venous infusion fluorouracil plus weekly gemcitabine with concurrent radiation therapy in patients with locally advanced pancreas cancer: a regimen with unexpected early toxicity. J Clin Oncol. 2000; 18 3384-3389
256 Brunner T B, Grabenbauer G G, Klein P. et al . Phase I trial of strictly time-scheduled gemcitabine and cisplatin with concurrent radiotherapy in patients with locally advanced pancreatic cancer. Int J Radiat Oncol Biol Phys. 2003; 55 144-153
257 Micke O, Hesselmann S, Bruns F. et al . Results and follow-up of locally advanced cancer of the exocrine pancreas treated with radiochemotherapy. Anticancer Res. 2005; 25 1523-1530
258 Xiong H Q, Rosenberg A, LoBuglio A. et al . Cetuximab, a monoclonal antibody targeting the epidermal growth factor receptor, in combination with gemcitabine for advanced pancreatic cancer: a multicenter phase II Trial. J Clin Oncol. 2004; 22 2610-2616
259 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
260 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
261 Beger H G, Link K H, Gansauge F. Adjuvant regional chemotherapy in advanced pancreatic cancer: results of a prospective study. Hepatogastroenterology. 1998; 45 638-643
262 Ghaneh P, Neoptolemos J P. Conclusions from the European Study Group for Pancreatic Cancer adjuvant trial of chemoradiotherapy and chemotherapy for pancreatic cancer. Surg Oncol Clin N Am. 2004; 13 567-587, vii-viii
263 Lohr M, Hoffmeyer A, Kroger J. et al . Microencapsulated cell-mediated treatment of inoperable pancreatic carcinoma. Lancet. 2001; 357 1591-1592
264 Mercadante S. Pain treatment and outcomes for patients with advanced cancer who receive follow-up care at home. Cancer. 1999; 85 1849-1858
265 Zech D F, Grond S, Lynch J. et al . Validation of World Health Organization Guidelines for cancer pain relief: a 10-year prospective study. Pain. 1995; 63 65-76
266 Marinangeli F, Ciccozzi A, Leonardis M. et al . Use of strong opioids in advanced cancer pain: a randomized trial. J Pain Symptom Manage. 2004; 27 409-416
267 Grahm A L, Andren-Sandberg A. Prospective evaluation of pain in exocrine pancreatic cancer. Digestion. 1997; 58 542-549
268 Caraceni A, Portenoy R K. Pain management in patients with pancreatic carcinoma. Cancer. 1996; 78 639-653
269 Ross G J, Kessler H B, Clair M R. et al . Sonographically guided paracentesis for palliation of symptomatic malignant ascites. Am J Roentgenol. 1989; 153 1309-1311
270 McNicol E, Strassels S, Goudas L. et al . Nonsteroidal anti-inflammatory drugs, alone or combined with opioids, for cancer pain: a systematic review. J Clin Oncol. 2004; 22 1975-1992
271 Carr D B, Goudas L C, Balk E M. et al . Evidence report on the treatment of pain in cancer patients. J Natl Cancer Inst Monogr. 2004; 32 23-31
272 Payne R, Mathias S D, Pasta D J. et al . Quality of life and cancer pain: satisfaction and side effects with transdermal fentanyl versus oral morphine. J Clin Oncol. 1998; 16 1588-1593
273 De Conno F, Ripamonti C, Saita L. et al . Role of rectal route in treating cancer pain: a randomized crossover clinical trial of oral versus rectal morphine administration in opioid-naive cancer patients with pain. J Clin Oncol. 1995; 13 1004-1008
274 Cherny N I. The management of cancer pain. CA Cancer J Clin. 2000; 50 70-116; quiz 117 - 120
275 Gilmer-Hill H S, Boggan J E, Smith K A. et al . Intrathecal morphine delivered via subcutaneous pump for intractable pain in pancreatic cancer. Surg Neurol. 1999; 51 6-11
276 Staats P S, Hekmat H, Sauter P. et al . The effects of alcohol celiac plexus block, pain, and mood on longevity in patients with unresectable pancreatic cancer: a double-blind, randomized, placebo-controlled study. Pain Med. 2001; 2 28-34
277 Eisenberg E, Carr D B, Chalmers T C. Neurolytic celiac plexus block for treatment of cancer pain: a meta-analysis. Anesth Analg. 1995; 80 290-295
278 Wong G Y, Schroeder D R, Carns P E. et al . Effect of neurolytic celiac plexus block on pain relief, quality of life, and survival in patients with unresectable pancreatic cancer: a randomized controlled trial. Jama. 2004; 291 1092-1099
279 Stefaniak T, Basinski A, Vingerhoets A. et al . A comparison of two invasive techniques in the management of intractable pain due to inoperable pancreatic cancer: neurolytic celiac plexus block and videothoracoscopic splanchnicectomy. Eur J Surg Oncol. 2005; 31 768-773
280 Arends J, Bodoky G, Bozzetti F. et al . ESPEN Guidelines on Enteral Nutrition: Non-surgical oncology. Clin Nutr. 2006; 25 245-259
281 Arends J, Zuercher G, Fietkau R. et al . DGEM Leitlinie Enterale Ernährung: Onkologie. Akt Ernähr Med. 2003; 28 61-68
282 Bjelakovic G, Nikolova D, Gluud L L. et al . Mortality in randomized trials of antioxidant supplements for primary and secondary prevention: systematic review and meta-analysis. Jama. 2007; 297 842-857
283 Wigmore S J, Falconer J S, Plester C E. et al . Ibuprofen reduces energy expenditure and acute-phase protein production compared with placebo in pancreatic cancer patients. Br J Cancer. 1995; 72 185-188
284 Gordon J N, Trebble T M, Ellis R D. et al . Thalidomide in the treatment of cancer cachexia: a randomised placebo controlled trial. Gut. 2005; 54 540-545
285 Jatoi A, Windschitl H E, Loprinzi C L. et al . Dronabinol versus megestrol acetate versus combination therapy for cancer-associated anorexia: a North Central Cancer Treatment Group study. J Clin Oncol. 2002; 20 567-573
286 Loprinzi C L, Kugler J W, Sloan J A. et al . Randomized comparison of megestrol acetate versus dexamethasone versus fluoxymesterone for the treatment of cancer anorexia/cachexia. J Clin Oncol. 1999; 17 3299-3306
287 Moss A C, Morris E, Mac Mathuna P. Palliative biliary stents for obstructing pancreatic carcinoma. Cochrane Database Syst Rev CD 004 200. 2006;
288 Hausegger K A, Thurnher S, Bodendorfer G. et al . Treatment of malignant biliary obstruction with polyurethane-covered Wallstents. Am J Roentgenol. 1998; 170 403-408
289 Isayama H, Komatsu Y, Tsujino T. et al . A prospective randomised study of “covered” versus “uncovered” diamond stents for the management of distal malignant biliary obstruction. Gut. 2004; 53 729-734
290 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
291 Urbach D R, Bell C M, Swanstrom L L. et al . Cohort study of surgical bypass to the gallbladder or bile duct for the palliation of jaundice due to pancreatic cancer. Ann Surg. 2003; 237 86-93
292 DiFronzo L A, Egrari S, O’Connell T X. Choledochoduodenostomy for palliation in unresectable pancreatic cancer. Arch Surg. 1998; 133 820-825
293 Aranha G V, Prinz R A, Greenlee H B. Biliary enteric bypass for benign and malignant disease. Am Surg. 1987; 53 403-406
294 Song H Y, Shin J H, Yoon C J. et al . A dual expandable nitinol stent: experience in 102 patients with malignant gastroduodenal strictures. J Vasc Interv Radiol. 2004; 15 1443-1449
295 Kaw M, Singh S, Gagneja H. et al . Role of self-expandable metal stents in the palliation of malignant duodenal obstruction. Surg Endosc. 2003; 17 646-650
296 Smith T J, Khatcheressian J, Lyman G H. et al . 2006 update of recommendations for the use of white blood cell growth factors: an evidence-based clinical practice guideline. J Clin Oncol. 2006; 24 3187-3205
297 Rizzo J D, Lichtin A E, Woolf S H. et al . Use of epoetin in patients with cancer: evidence-based clinical practice guidelines of the American Society of Clinical Oncology and the American Society of Hematology. J Clin Oncol. 2002; 20 4083-4107
298 Bokemeyer C, Aapro M S, Courdi A. et al . EORTC guidelines for the use of erythropoietic proteins in anaemic patients with cancer: 2006 update. Eur J Cancer. 2007; 43 258-270
299 Schuchter L M, Hensley M L, Meropol N J. et al . 2002 update of recommendations for the use of chemotherapy and radiotherapy protectants: clinical practice guidelines of the American Society of Clinical Oncology. J Clin Oncol. 2002; 20 2895-2903

1 Commissioned by the German Society for Digestive and Metabolic Diseases (DGVS) und the German Cancer Society (DKG). In cooperation with the Task Force Radiologic Oncology of the German Cancer Society (ARO), Pancreatectomy Team e. V., German Society for Surgery (DGCH), German Society for Hematology and Oncology (DGHO), German Society for Palliative MedicineGerman Society for Pathology (DGP), German Society for Radiooncology (DEGRO), German Society for Visceral Surgery (CAO-V)/Surgical Task Force Oncology (CAO-V), German Society for Radiology (DRG), German Joint Societies for Clinical Chemistry and Laboratory Medicine (DGKL) (Chairmen: G. Adler, T. Seufferlein, I. Kopp)

Prof. Dr. Guido Adler

Department of Internal Medicine I, University Medical Center

Robert-Koch-St. 8

89081 Ulm

Germany

Phone: ++ 49/7 31/50 04 45 00

Fax: ++ 49/7 31/50 04 45 02

Email: guido.adler@uniklinik-ulm.de