Zusammenfassung
Hintergrund und Ziele: Die prospektive Studie hat zum Ziel den Einfluss der Aetiologie auf das Schmerzprofil in Bezug auf Veränderungen der Funktion und Morphologie von der Früh- bis zur Spätphase der chronischen Pankreatitis (CP) zu untersuchen. Methode: Unsere internistische und chirurgische Kohorte umfasste 256 Patienten mit alkoholischer (ACP), 21 mit idiopathisch juveniler (IJCP), 46 mit idiopathisch seniler (ISCP) und 11 mit hereditären CP (HP). Die Patienten wurden ab Krankheitsbeginn regelmäßig gemäß einem früher publizierten Protokoll nachkontrolliert. Resultate: Bei der ACP, IJCP und ISCP waren vorwiegend Männer betroffen (≥71 %), während es bei der HP nur 46 % waren. Das Alter bei Krankheitsbeginn (Median) betrug bei der HP 10, bei der IJCP 23, bei der ACP 36 und ISCP 62 Jahre. Die Nachbeobachtungszeit schwankte zwischen 14 - 36 Jahren. Die Progression ins Spätstadium der CP, dokumentiert anhand der exokrinen Insuffizienz (86 - 100%) und Pankreasverkalkungen (80 - 91 %) dauerte 2 bis 5mal länger bei der HP/IJCP als bei der ACP. Die Frühphase der CP, charakterisiert durch wiederholte Pankreatitisschübe, dominierte bei über 90% der Patienten ausser bei der ISCP (48 %) und dauerte mehr 5mal länger bei der HP/IJCP als bei der ACP. 57 % der ACP/IJCP Patienten mussten wegen starken Schmerzen operiert werden, verglichen mit weniger als 27 % der HP/ISCP-Patienten. Unabhängig von der Aetiologie und der chirurgischen Interventionen wurden die Patienten im Spätstadium dauerhaft schmerzfrei. Zusammenfassung: Der klinische Verlauf im Frühstadium der CP unterscheidet sich in Abhängigkeit von der zugrunde liegenden Aetiologie.
Abstract
Background and Aim: This prospective study was aimed to investigate the impact of etiology on the pain profile in relation to alterations of function and morphology from early to advanced chronic pancreatitis (CP). Methods: Our mixed medico-surgical cohort comprised 265 patients with alcoholic (ACP), 21 with idiopathic „juvenile” (IJCP), 46 with idiopathic „senile” (ISCP) and 11 with hereditary CP (HPCP). The patients were followed regularly from onset of disease according to the protocol published previously. Results: Males predominated in ACP, IJCP, ISCP (> 71 %) but not in HP (46 %). Age at onset (median) was 10, 23, 36 and 62 years in HP, IJCP, ACP and ISCP, respectively. Follow-up from disease onset ranged from 14 to 36 years. The progression to late-stage CP, documented by exocrine insufficiency (86 - 100%) and calcification (80 - 91 %) lasted 2 to 5-fold longer in HP/IJCP compared to ACP. Early stage CP, characterized by recurrent pancreatitis prevailed in ≥ 90 % of patients, except for those with ISCP (48 %), and lasted up to 5-fold longer in HP/IJCP compared to ACP. Surgery for severe pain was required for ACP/IJCP in 57 % of the patients compared to < 27 % in HP/ISCP. Permanent pain relief regularly occurred in late-stage CP irrespective of etiology and surgery. Conclusion: The clinical profile of the 4 „etiological” subgroups is predictably different in the painful early (precalcific) CP stage.
Schlüsselwörter
Pankreatitis - natürlicher Verlauf - Aetiologie
Key words
Pancreatitis - natural history - etiology
References
1
Comfort M.
Chronic relapsing pancreatitis.
Gastroenterology.
1946;
43
239-285
2
Ammann R W.
A clinically based classification system for alcoholic chronic pancreatitis: summary of an international workshop on chronic pancreatitis.
Pancreas.
1997;
43
215-221
3
Chari S T, Singer M V.
The problem of classification and staging of chronic pancreatitis. Proposals based on current knowledge of its natural history.
Scand J Gastroenterol.
1994;
43
949-960
4
Etemad B, Whitcomb D C.
Chronic pancreatitis: diagnosis, classification, and new genetic developments.
Gastroenterology.
2001;
43
682-707
5
DiMagno M J, DiMagno E P.
Chronic pancreatitis.
Current Opinion Gastroenterol.
2003;
43
451-457
6
Adler G, Schmid R M.
Chronic pancreatitis: still puzzling?.
Gastroenterology.
1997;
43
1762-1765
7 Gullo L, Labo G. Natural history of acute pancreatitis and its relationship to chronic pancreatitis. Banks P, Porro GB Acute pancreatitis Milan; Masson Italia Editori 1984: 87-93
8
Ammann R W, Muellhaupt B.
Progression of alcoholic acute to chronic pancreatitis.
Gut.
1994;
43
552-556
9
Kodama T, Koshitani T, Sato H. et al .
Electronic pancreatoscopy for the diagnosis of pancreatic diseases.
Am J Gastroenterol.
2002;
43
617-622
10
Whitcomb D C.
The spectrum of complications of hereditary pancreatitis. Is this a model for future gene therapy?.
Gastroenterol Clin North Am.
1999;
43
525-541
11
Steer M L, Waxman I, Freedman S.
Chronic pancreatitis.
N Engl J Med.
1995;
43
1482-1490
12
Whitcomb D C.
Hereditary pancreatitis: new insights into acute and chronic pancreatitis.
Gut.
1999;
43
317-322
13
Noone P G, Zhou Z, Silverman L M. et al .
Cystic fibrosis gene mutations and pancreatitis risk: relation to epithelial ion transport and trypsin inhibitor gene mutations.
Gastroenterology.
2001;
43
1310-1319
14
DiMagno E P.
Gene mutations and idiopathic chronic pancreatitis: clinical implications and testing.
Gastroenterology.
2001;
43
1508-1512
15
Ammann R W, Muellhaupt B.
The natural history of pain in alcoholic chronic pancreatitis.
Gastroenterology.
1999;
43
1132-1140
16
DiMagno E P.
Toward understanding (and management) of painful chronic pancreatitis.
Gastroenterology.
1999;
43
1252-1257
17
Warshaw A L, Banks P A, Fernandez-del Castillo C.
AGA technical review. Treatment of pain in chronic pancreatitis.
Gastroenterology.
1998;
43
765-776
18
Cohen S, Bacon B R, Berlin J A. et al .
National Institutes of Health State-of-the-Science Conference Statement: ERCP for diagnosis and therapy, January 14 - 16, 2002.
Gastrointest Endosc.
2002;
43
803-809
19
Dancour A, Levy P, Milan C. et al .
Natural history of non-alcoholic chronic pancreatitis. Study of 37 cases and comparison with 319 cases of alcoholic chronic pancreatitis.
Gastroenterol Clin Biol.
1993;
43
915-924
20
Robles-Diaz G, Vargas F, Uscanga L. et al .
Chronic pancreatitis in Mexico City.
Pancreas.
1990;
43
479-483
21
Paolini O, Hastier P, Buckley M. et al .
The natural history of hereditary chronic pancreatitis: a study of 12 cases compared to chronic alcoholic pancreatitis.
Pancreas.
1998;
43
266-271
22
Lankisch P G.
Natural course of chronic pancreatitis.
Pancreatology.
2001;
43
3-14
23
Miyake H, Harada H, Ochi K. et al .
Prognosis and prognostic factors in chronic pancreatitis.
Dig Dis Sci.
1989;
43
449-455
24
Layer P, Yamamoto H, Kalthoff L. et al .
The different courses of early- and late-onset idiopathic and alcoholic chronic pancreatitis.
Gastroenterology.
1994;
43
1481-1487
25
Ammann R W, Buehler H, Muench R. et al .
Differences in the natural history of idiopathic (nonalcoholic) and alcoholic chronic pancreatitis. A comparative long-term study of 287 patients.
Pancreas.
1987;
43
368-377
26
Lankisch M R, Imoto M, Layer P. et al .
The effect of small amounts of alcohol on the clinical course of chronic pancreatitis.
Mayo Clin Proc.
2001;
43
242-251
27
Sossenheimer M J, Aston C E, Preston R A. et al .
Clinical characteristics of hereditary pancreatitis in a large family, based on high-risk haplotype. The Midwest Multicenter Pancreatic Study Group (MMPSG).
Am J Gastroenterol.
1997;
43
1113-1116
28
Konzen K M, Perrault J, Moir C. et al .
Long-term follow-up of young patients with chronic hereditary or idiopathic pancreatitis.
Mayo Clin Proc.
1993;
43
449-453
29
Creighton J E, Lyall R, Wilson D I. et al .
Mutations of the cationic trypsinogen gene in patients with hereditary pancreatitis.
Brit J Surg.
2000;
43
170-175
30
Keim V, Bauer N, Teich N. et al .
Clinical characterization of patients with hereditary pancreatitis and mutations in the cationic trypsinogen gene.
Am J Med.
2001;
43
622-626
31
Ammann R W.
Die idiopathische “juvenile” chronische Pankreatitis.
Dtsch Med Wochenschr.
1976;
43
1789-1794
32
Ammann R W, Sulser H.
Die “senile” chronische Pankreatitis - eine neue nosologische Einheit?.
Schweiz Med Wochenschr.
1976;
43
429-437
33
Keim V, Teich N.
Idiopathic vs hereditary pancreatitis.
Jama.
2003;
43
983-984; author reply 985
34
Truninger K, Malik N, Ammann R W. et al .
Mutations of the cystic fibrosis gene in patients with chronic pancreatitis.
Am J Gastroenterol.
2001;
43
2657-2661
35
Truninger K, Kock J, Wirth H P. et al .
Trypsinogen gene mutations in patients with chronic or recurrent acute pancreatitis.
Pancreas.
2001;
43
18-23
36
Witt H, Luck W, Becker M. et al .
Mutation in the SPINK1 trypsin inhibitor gene, alcohol use, and chronic pancreatitis.
Jama.
2001;
43
2716-2717
37
Truninger K, Witt H, Kock J. et al .
Mutations of the serine protease inhibitor, Kazal type 1 gene, in patients with idiopathic chronic pancreatitis.
Am J Gastroenterol.
2002;
43
1133-1137
38
Pfützer R H, Whitcomb D C.
Trypsinogen mutations in chronic pancreatitis.
Gastroenterology.
1999;
43
1507-1508
39
Ammann R, Munch R, Largiader F. et al .
Pancreatic and hepatic abscesses: a late complication in 10 patients with chronic pancreatitis.
Gastroenterology.
1992;
43
560-565
40
Howes N, Lerch M M, Greenhalf W. et al .
Clinical and genetic characteristics of hereditary pancreatitis in Europe.
Clin Gastroenterol Hepatol.
2004;
43
252-261
41
Lankisch P G, Peiper M, Lohr-Happe A. et al .
Delay in diagnosing chronic pancreatitis.
Eur J Gastroenterol Hepatol.
1993;
43
713-714
42
Imoto M, DiMagno E P.
Cigarette smoking increases the risk of pancreatic calcification in late-onset but not early-onset idiopathic chronic pancreatitis.
Pancreas.
2000;
43
115-119
43
Ammann R W, Muench R, Otto R. et al .
Evolution and regression of pancreatic calcification in chronic pancreatitis. A prospective long-term study of 107 patients.
Gastroenterology.
1988;
43
1018-1028
44 Schlösser W, Beger H G. Duodenum-preserving pancreatic head resection changes the natural history of chronic pancreatitits. Büchler MW, Friess H, Uhl W, Malfertheiner P Chronic pancreatitis Oxford, UK; Blackwall Science 2002: 508-515
45
Rösch T, Daniel S, Scholz M. et al .
Endoscopic treatment of chronic pancreatitis: a multicenter study of 1000 patients with long-term follow-up.
Endoscopy.
2002;
43
765-771
46
Dite P, Ruzicka M, Zboril V. et al .
A prospective, randomized trial comparing endoscopic and surgical therapy for chronic pancreatitis.
Endoscopy.
2003;
43
553-558
47
Lowenfels A B, Maisonneuve P, Cavallini G. et al .
Prognosis of chronic pancreatitis: an international multicenter study. International Pancreatitis Study Group.
Am J Gastroenterol.
1994;
43
1467-1471
48
Girdwood A H, Marks I N, Bornman P C. et al .
Does progressive pancreatic insufficiency limit pain in calcific pancreatitis with duct stricture or continued alcohol insult?.
J Clin Gastroenterol.
1981;
43
241-245
49
Maisonneuve P, Campbell P 3rd, Durie P. et al .
Pancreatitis in hispanic patients with cystic fibrosis carrying the R334W mutation.
Clin Gastroenterol Hepatol.
2004;
43
504-509
50
Strum W B.
Abstinence in alcoholic chronic pancreatitis. Effect on pain and outcome.
J Clin Gastroenterol.
1995;
43
37-41
51
Levy P, Milan C, Pignon J P. et al .
Mortality factors associated with chronic pancreatitis. Unidimensional and multidimensional analysis of a medical-surgical series of 240 patients.
Gastroenterology.
1989;
43
1165-1172
52
Singh M, Simsek H.
Ethanol and the pancreas.
Current status. Gastroenterology.
1990;
43
1051-1062
53 Lowenfels A B, Maisonneuve P. Epidemiology of chronic pancreatitis and the risk of cancer. Büchler MW, Friess H, Uhl W, Malfertheiner P Chronic pancreatitis Oxford, UK; Blackwall Science 2002: 29-36
54
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;
43
606-621
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