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Gallstone Disease Pathophysiology and Therapeutic Approaches
Editors w. Swobodnik, H. Ditschuneit, and R. D. Soloway
With 99 Figures and 43 Tables
Springer-Verlag Berlin Heidelberg New York London Paris Tokyo Hong Kong
Swobodnik, w. Abteilung Innere Medizin II, Gastroenterologie und Ernahrungswissenschaften, Universitatsklinikum Ulm, Robert-Koch-StraBe 8, D-7900 Ulm, FRG
Soloway, R. D. Division of Gastroenterology, 4.106 McCullough, G-64, University of Texas Medical Branch at Galveston, Galveston TX 77550, USA
Ditschuneit, H. Abteilung Innere Medizin II, Gastroenterologie und Ernahrungswissenschaften, Universitatsklinikum Ulm, Robert-Koch-StraBe 8, D-7900 Ulm, FRG
ISBN -13 :978-3-540-50965-3 e-ISBN -13 :978-3-642-74619-2 DOl: 10.1007/978-3-642-74619-2
This work is subject to copyright. All rights are reserved, whether the whole or part of the material is concerned, specifically those of translation, reprinting, reuse of illustrations, broadcasting, reproduction by photocopying machine or similar means, and storage in data banks.
Under § 54 of the German Coypright Law, where copies are made for other than private use, a fee is payable to Verwertungsgesellschaft Wort, Munich.
© Springer-Verlag, Berlin Heidelberg 1990
Product Liability: The publisher can give no guarentee for information about drug dosage and application thereof contained in this book. In every individual case the respective user must check its accuracy by consulting other pharmaceutical literature.
The use of registered names, trademarks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use.
2127/3321-543210 - Printed on acid-free paper
Preface
The nonsurgical management of gallstone disease has drawn widespread clinical interest during the last decade as ultrasound surveys have indicated that cholelithiasis is predominantly an asymptomatic condition and much more prevalent than previously thought. This book presents an overview of the pathophysiologic and pathobiochemical principles of gallstone formation and the consequences for clinical therapeutic regimens. New information concerning the balance between vesicular and micellar transport of cholesterol, early cholesterol nucleation, and the influence of inhibiting and promoting compounds for cholesterol nucleation as well as information concerning the effects of changes in gallbladder motility and gallbladder mucosal function is reviewed. In order to make further progress in developing treatments which facilitate gallstone dissolution and in preventing disease, it is necessary to integrate this new data into our thinking.
Methods of treatment such as systemic litholysis of cholesterol gallbladder stones with bile acid preparations and mechanical fragmentation of stones either by extracorporal shock waves or intracorporal laser systems are carefully described and separate discussions of direct contact litholysis of cholesterol stones with ether preparations and the local litholytic treatment of calcified pigment stones are included. New therapeutic applications of HMG-CoA-reductase inhibitors and nonsteroidal anti-inflammatory drugs are also critically reviewed. Finally, for the interested reader an evaluation of prophylactic treatment against stone recurrence after successful conservative treatment and an appraisal of alternative management strategies supplement the information on the conservative treatment of gallstones.
Contents
Pathobiochemistry and Pathophysiology of Gallstone Development: Importance for Clinical Decision Processses
Increased Biliary Lithogenicity Through Cholesterol Supersaturation M. C. Carey . . . . . . . . . . . . . . . . . . . . . . . . . 3
Nucleation and Aggregation of Cholesterol Crystals in the Early Phase of Gallstone Genesis G. Salvioli, R. Lugli, and M. Pellati . . . . . . . . . . . . . . . 11
Modulation of the Edge Tension of Lipid Membranes by Cholate and Cholesterol and the Micelle-Vesicle Transition in Model Bile Systems P. Fromherz. . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 27
Pigment Gallstones and Secondary Calcification of Gallstones R. D. Soloway, 1. G. Wu, and D. F. Xu . . . . . . . . . . 35
The Influence of the Gallbladder Epithelium on Gallstone Formation B. F. Smith . . . . . . . . . . . . . . . . . . . . . . . . . 47
Biliary Proteins and Their Role as Nucleating Inhibitors/Promotors P. R. C. Harvey and S. M. Strasberg . . . . . . . . . . . . . . 55
Neurohormonal Aspects of Gallbladder Contractility in Gallstone Disease: The Role of Cholecystokinin U. G. Kliippelberg, X. Molero, H. Y. Gaisano, and L. 1. Miller. . . . . . 67
Environmental Factors and Gallstones 1. G. Wechsler . . . . . . . . . . . . . . . . . .
Different Therapeutic Approaches to Gallstone Disease
Is Therapeutic Intervention Necessary in Gallstone Disease? The Surgeon's Point of View B.S. Ashby ................. .
Surgical Therapy for Acute Gallstone Complications W Oettinger, K. Orth, and B. Leibl ...... .
Therapeutic Interventions in Patients with Gallbladder Stones: The Internist's View G. Paumgartner .................... .
Acute Biliary Pancreatitis P. Malfertheiner . . . .
87
95
99
103
109
VIIl
Systemic Litholysis with Bile Acids
Principles of Gallstone Dissolution with Chenodeoxycholic Acid, Ursodeoxycholic Acid, and the Combination of Both Bile Acids A. Stiehl ..................... .
Systemic Litholysis with Bile Acids: Ursodeoxycholic Acid W Kurtz ..................... .
Combination Therapy of Chenodeoxycholic Acid and Ursodeoxycholic Acid M. Podda, M. Zuin, M. L. Petroni, E. Bertolini, A. Crosignani,
Contents
115
121
and G. Grandinetti. . . . . . . . . . . . . . . . . . . . . . . . .. 127
Results of an Index-Controlled Combination Therapy with Ursodeoxycholic and Chenodeoxycholic Acid P. Janowitz, W Swobodnik, 1. G. Wechsler, S. Fischer, 1. Tudyka, and H. Ditschuneit . . . . ~ . . . . . . . . . . . . . . . . . . . . .. 135
Extracorporeal Schock- Wave-Lithotripsy
Physical Basis of Lithotriptors U. Faust ............. .
Extracorporeal Shock-Wave Lithotripsy of Gallstones G. Paumgartner, M. Sackmann, 1. Holl, and T. Sauerbruch
Administration of Second-Generation Extracorporeal Shock Waves without Waterbath for Fragmentation of Extra- and Intrahepatic Bile Duct Stones M. Staritz, A. Rambow, A. Floth, P. Mildenberger, M. Goebel, T. Junginger,
147
161
R. Hohenfellner, M. Thelen, and K.-H. Meyer zum Biischenfelde . . . .. 165
Piezoelectric Lithotripsy of Gallbladder Stones C. Ell, W Kerze1, H. T. Schneider, W Domschke, and E. G. Hahn 171
Biliary Shock-Wave Lithotripsy: Experience of the First 3 Years in 612 Patients L. Greiner and C. Jakobeit . . . . . . . . . . . . . . . . . . . . . .. 177
Laser Lithotripsy
Laser Lithotripsy: Basic Physics R. Steiner and Th. Meier . . .
Laser Lithotripsy: Clinical Applications C. Ell, 1. Hochberger, E. G. Hahn, and L. Demling .
Local Litholysis
Local Litholytic Agents: Dissolution of Cholesterol Biliary Tract Stones with Methyl tert-Butyl Ether
195
201
1. L. Thistle, B. T. Petersen, 1. E. McCullough, C. E. Bender, and A.1. LeRoy. 205
Local Litholysis of Calcified Pigment Stones W Swobodnik . . . . . . . . . . . . . . . . . 211
Local Litholysis of Intrahepatic Calculi K. Draese, 1. Schopohl, C. E. Zockler, and S. Martin 217
Contents IX
New Therapeutic Trends
Reduction of Biliary Cholesterol Saturation by Inhibition of Cholesterol Synthesis: New Therapeutic Consequences? K. von Bergmann, T. Heinemann, and D. Liitjohann . . . . . . . . . . .. 225
Gallstone Prevention by Alteration of Gallbladder Mucin Secretion via Prostaglandin Synthesis Inhibition B. F. Smith and J. T. LaMont .. . . . . . . . . . . . . . . . . . . .. 231
Gallstone Prevention After Successful Treatment R. H. Dowling . . . . . . . . . . . . . . . .
Intermittent Bile Acid Therapy as an Alternative Therapeutic Strategy T. C. Northfield and R. P. lazrawi
Subject Index . . . . . . . . .
237
239
249
Contributors
Ashby, B.S. Department of Surgery, Southend Hospital, Prittlewell Chase, Southend, SSO ORY, U.K.
Bender, C. E. Division of Gastroenterology, Mayo Clinic, Rochester, MN 55905, USA
von Bergmann, K. Abteilung Klinische Pharmakologie, Medizinische Klinik, UniversiHit Bonn, Sigmund-Freud-StraBe 25, 5300 Bonn 1, FRG
Bertolini, E. Institute of Internal Medicine, University of Milan, Via Pace 9, 20122 Milan, Italy
Carey, M.C. Department of Medicine, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115, USA
Crosignani, A. Institute of Internal Medicine, University of Milan, Via Pace 9, 20122 Milan. Italy
Demling, L. Medizinische Klinik I mit Poliklinik, UniversiHit Erlangen-Niirnberg, KrankenhausstraBe 12, 8520 Erlangen, FRG
Ditschuneit. H. Abteilung Innere Medizin II, Gastroenterologie und Erniihrungswissenschaften, Universitiitsklinikum Ulm, Robert-Koch-StraBe 8, 7900 Ulm, FRG
Domschke, W. Medizinische Klinik I mit Poliklinik, Universitiit Erlangen-Niirnberg, KrankenhausstraBe 12. 8520 Erlangen, FRG
Dowling, R. H. Gastroenterology Unit, Guy's Hospital, Guy's Tower, London SE1 9RT, UK
Draese, K. Chirurgische Klinik, Krankenhaus Bad Oeynhausen, WielandstraBe 28, 4970 Bad Oeynhausen, FRG
Ell, C. Medizinische Klinik I mit Poliklinik, Universitiit Erlangen-Niirnberg, KrankenhausstraBe 12, 8250 Erlangen, FRG
Faust, U. Institut fUr Biomedizinische Technik der Universitiit Stuttgart, SeidenstraBe 36, 7000 Stuttgart 1, FRG
XII Contributors
Fischer, S. Abteilung Innere Medizin II, Gastroenterologie und Erni.i.hrungswissenschaften, Universiti.i.tsklinikum Ulm, Robert-Koch-Stral3e 8, 7900 Ulm, FRG
Floth, A. Urologische Klinik, Universiti.i.t Mainz, Langenbeckstral3e 1, 6500 Mainz, FRG
Frenzel, F. Abteilung fUr Gastroenterologie, Ferdinand-Sauerbruch-Klinikum, Arrenberger Stral3e 20-56, 5600 Wuppertal1, FRG
Fromherz, P. Abteilung fUr Biophysik der Universiti.i.t Ulm, Oberer Eselsberg, 7900 Ulm, FRG
Gaisano, H. Y. Gastroenterology Research Unit., Mayo Clinic and Foundation, Rochester, MN 55905, USA
Goebel, M. Radiologische Klinik, Universiti.i.t Mainz, Langenbeckstral3e 1, 6500 Mainz, FRG
Grandinetti, G. Institute of Internal Medicine, University of Milan, Via Pace 9, 20122 Milan, Italy
Greiner, L. Abteilung fur Gastroenterologie, Ferdinand-Sauerbruch-Klinikum, Arrenberger Stral3e 20-56,5600 Wuppertal1, FRG
Hahn, E.G. Medizinische Klinik I mit Poliklinik, Universiti.i.t Erlangen-Nurnberg, Krankenhausstral3e 12, 8520 Erlangen, FRG
Harvey, P. R. C. Department of Surgery and Research Institute, Mount Sinai Hospital, University of Toronto, 600 University Ave., Toronto, Ontario M5G 1X5, Canada
Heinemann, T. Abteilung Klinische Pharmakologie, Medizinische Klinik, Universiti.i.t Bonn, Sigmund-Freud-Stral3e 25,5300 Bonn 1, FRG
Hochberger, J. Medizinische Klinik I mit Poliklinik, Universiti.i.t Erlangen-Nurnberg, Krankenhausstral3e 12, 8520 Erlangen, FRG
Hohenfellner, R. Urologische Klinik, Universitat Mainz, Langenbeckstral3e 1, 6500 Mail1Z, FRG
Holl, J. Medizinische Klinik II, Universitat Munchen, Klinikum Grol3hadern, Marchioninistral3e 15, 8000 Munchen 70, FRG
Jakobeit, C. Abteilung fur Gastroenterologie, Ferdinand-Sauerbruch-Klinikum, Arrenberger Stral3e 20-56, 5600 Wuppertal 1, FRG
Janowitz, P. Abteilung Innere Medizin II, Gastroenterologie und Erni.i.hrungswissenschaften, Universitatsklinikum Ulm, Robert-Koch-Stral3e 8, 7900 Ulm, FRG
Contributors
Jazrawi, R. P. Department of Biochemical Medicine, St. George's Hospital Medical School, Cranmer Terrace, London SW17 ORE, UK
Junginger, T. Chirurgische Klinik, Universitiit Mainz, LangenbeckstraBe 1, 6500 Mainz, FRG
Kerzel, M.
XIII
Medizinische Klinik I mit Poliklinik, Universitiit Erlangen-Niirnberg, KrankenhausstraBe 12, 8520 Erlangen, FRG
Kliippelberg, U. G. Gastroenterology Research Unit, Mayo Clinic and Foundation, Rochester, MN 55905, USA (present address: Innere Medizin II, Klinikum GroBhadern der Universitiit Miinchen, MarchioninistraBe 15, 8000 Miinchen 70, FRG)
Kurz, W Medizinische Klinik 1, Zentralkrankenhaus Reinkenheide, PostbrookstraBe, 2850 Bremerhaven, FRG
LaMont, J. T. Section of Gastroenterology, University Hospital, Boston University Medical Center, Boston, MA 02118, USA
Leibl, B. Abteilung fUr Allgemeine Chirurgie, Universitiit Ulm, SteinhovelstraBe 9, 7900 Ulm, FRG
LeRoy, A.J. Division of Gastroenterology, Mayo Clinic, Rochester, MN 55905, USA
Lugli, R. Patologia Speciale Medica, Universita di Modena, Viale Vittorio Veneto 9, 41100 Modena, Italy
Liitjohann, D. Abteilung Klinische Pharmakologie, Medizinische Klinik, Universitiit Bonn, Sigmund-Freud-StraBe 25, 5300 Bonn 1, FRG
Malfertheiner, P. Abteilung Innere Medizin II, Universitiit UIm, Robert-Koch-StraBe 8, 7900 Ulm, FRG
Martin, S. Chirurgische Klinik, Krankenhaus Bad Oeynhausen, WielandstraBe 28, 4970 Bad Oeynhausen, FRG
McCullough, J. E. Division of Gastroenterology, Mayo Clinic, Rochester, MN 55905, USA
Meier, T. Institut fUr Lasertechnologien in der Medizin, Universitiit Ulm, HelmholtzstraBe 12, 7900 Ulm, FRG
Merz, B. Abteilung fUr Gastroenterologie, Ferdinand-Sauerbruch-Klinikum, Arrenberger StraBe 20-56, 5600 Wuppertall, FRG
Meyer zum Biischenfelde, K.-H. I. Medizinische Klinik und Poliklinik, Universitiit Mainz, LangenbeckstraBe 1, 6500 Mainz, FRG
XIV Contributors
Mildenberger, P. Radiologische Klinik, Universitat Mainz, LangenbeckstraBe 1, 6500 Mainz, FRG
Miller, L. 1. Gastroenterology Research Unit, Mayo Clinic and Foundation, Rochester, MN 55905, USA
Molero, x. Gastroenterology Research Unit, Mayo Clinic and Foundation, Rochester, MN 55905, USA
Northfield, T. C. Department of Biochemical Medicine, St. George's Hospital Medical School, Cranmer Terrace, London SW17 ORE, UK
Oettinger, W. Abteilung fUr Allgemeine Chirurgie, Universitat Ulm, SteinhovelstraBe 9, 7900 Ulm, FRG
Orth, K. Abteilung fUr Allgemeine Chirurgie, Universitat Ulm, SteinhovelstraBe 9, 7900 Ulm, FRG
Paumgartner, G. Medizinische Klinik II, Universitat Munchen, Klinikum GroBhadern, MarchioninistraBe 15, 8000 Munchen 70, FRG
Pellati, M. Patologia Speciale Medica, Universita di Modena, Viale Vittorio Veneto 9, 41100 Modena, Italy
Petersen, B. T. Division of Gastroenterology, Mayo Clinic, Rochester, MN 55905, USA
Petroni, M. L. Institute of Internal Medicine, University of Milan, Via Pace 9, 20122 Milan, Italy
Podda, M. Chair of Internal Medicine, University of Milan, Via A. di Rudini 8, 20142 Milan, Italy
Rambow, A. I. Medizinische Klinik und Poliklinik, Universitat Mainz, LangenbeckstraBe 1, 6500 Mainz, FRG
Sackmann, M. Medizinische Klinik II, Universitat Munchen, Klinikum GroBhadern, MarchioninistraBe 15, 8000 Munchen 70, FRG
Salvioli, G. Patologia Speciale Medica, Universita di Modena, Viale Vittorio Veneto 9, 41100 Modena, Italy
Sauerbruch, T. Medizinische Klinik II, Universitat Munchen, Klinikum GroBhaderm. MarchioninistraBe 15, 8000 Munchen 70, FRG
Schneider, H. T. Medizinische Klinik I mit Poliklinik, Universitat Erlangen-Nurnberg, KrankenhausstraBe 12, 8520 Erlangen, FRG
Contributors
Schopohl, J. Chirurgische Klinik, Krankenhaus Bad Oeynhausen, WielandstraBe 28, 4970 Bad Oeynhausen, FRG
Smith, B. F.
xv
Section of Gastroenterology and Hepatology, Boston City Hospital, Boston University Medical Center, 818 Harrison Avenue, Boston. MA 021118, USA
Soloway, R. D. Division of Gastroenterology, 4.106 McCullough, G-64, University of Texas Medical Branch at Galveston, Galveston TX 77550, USA
Staritz, M. I. Medizinische Klinik und Poliklinik, Universitat Mainz, LangenbeckstraBe 1, 6500 Mainz, FRG
Steiner, R. Institut fUr Lasertechnologien in der Medizin, Universitat Ulm, HelmholtzstraBe 12, 7900 Ulm, FRG
Stiehl, A. Medizinische Klinik, Klinikum der Universitat Heidelberg, Bergheimer StraBe 58, 6900 Heidelberg 1, FRG
Strasberg, S. M. Department of Surgery and Research Institute, Mount Sinai Hospital, University of Toronto, 600 University Ave., Toronto, Ontario M5G 1X5, Canada
Swobodnik, W. Abteilung Innere Medizin II, Gastroenterologie und Ernahrungswissenschaften, Universitatsklinikum Ulm, Robert-Koch-StraBe 8, 7900 Ulm, FRG
Thelen, M. Radiologische Klinik, Universitat Mainz, LangenbeckstraBe 1, 6500 Mainz, FRG
Thistle, J. L. Division of Gastroenterology, Mayo Clinic, Rochester, MN 55905, USA
Tudyka, J. Abteilung Innere Medizin II, Gastroenterologie und Ernahrungswissenschaften, Universitatsklinikum Ulm, Robert-Koch-StraBe 8, 7900 Ulm, FRG
Wechsler, J. G. Abteilung Innere Medizin II, Gastroenterologie und Ernahrungswissenschaften, Universitatsklinikum Ulm, Robert-Koch-StraBe 8, 7900 Ulm, FRG
Wenzel, H. Abteilung fUr Gastroenterologie, Ferdinand-Sauerbruch-Klinikum, Arrenberger StraBe 20-56, 5600 Wuppertal1, FRG
Wu,J.G. Department of Chemistry, Beijing University, Beijing 100871, People's Republic of China
Xu, D.F. Section of Polymer Chemistry, Sinica Academica, Beijing 100871, People's Republic of China
XVI Con tri butors
Z6ckler, C. E. Chirurgische Klinik, Krankenhaus Bad Oeynhausen, Wielandstra13e 28, 4970 Bad Oeynhausen, FRG
Zuin, M. Institute of Internal Medicine, University of Milan, Via Pace 9, 20122 Milan, Italy