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Zentralbl Chir 2003; 128(10): 821-830
DOI: 10.1055/s-2003-44336
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© Georg Thieme Verlag Stuttgart · New York

Aktueller Stand der Pankreastransplantation: Indikation, operative Technik, Immunsuppression, Komplikationen und Ergebnisse

Pancreas Transplantation: A Survey on Indications, Surgical Techniques, Immunosuppression, Complications and OutcomeO. Drognitz1 , U. T. Hopt1
  • 1Klinik und Poliklinik für Chirurgie, Abteilung für Allgemein- und Viszeralchirurgie, Universitätsklinikum Freiburg
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Publication History

Publication Date:
20 November 2003 (online)

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Zusammenfassung

Die klinische Pankreastransplantation hat seit ihrer Einführung im Jahr 1966 eine bemerkenswerte Entwicklung durchgemacht. Fortschritte im Bereich der operativen Technik, der Organkonservierung und der Immunsuppression haben das Patientenüberleben und die Transplantatfunktionsrate dramatisch verbessert. Die 1-Jahres-Pankreasfunktionsrate beträgt heutzutage 83 % nach simultaner Pankreas-/Nierentransplantation (SPK) und 78 % nach alleiniger Pankreastransplantation bei einem 1-Jahres-Patientenüberleben von 95 % bzw. 97 %. Dabei bestehen zwischen den Ergebnissen der nordamerikanischen und der europäischen Zentren keine wesentlichen Unterschiede. Dennoch ist die Akzeptanz der Pankreastransplantation in Deutschland immer noch geringer als in den USA. Die SPK gilt als Therapie der Wahl für Typ-1-Diabetiker mit terminaler Niereninsuffizienz. Viele nordamerikanische Zentren plädieren sogar seit längerem für eine Simultantransplantation vor Eintritt der Dialysepflichtigkeit. Die erfolgreiche Pankreastransplantation führt neben einer signifikanten Verbesserung der Lebensqualität zu einer nahezu vollständigen Normalisierung des Glukosemetabolismus. Das Fortschreiten der diabetischen Spätschäden wird hierdurch im Langzeitverlauf verhindert. Darüber hinaus wird das Langzeitüberleben der Patienten mit Typ-1-Diabetes und terminalem Nierenversagen durch eine Reduzierung der kardiovaskulär-bedingten Todesfälle erhöht. Das 10-Jahres-Patientenüberleben nach SPK beträgt ü ber 70 %. Damit existiert kein alternatives Therapieverfahren mit einer vergleichbaren Lebenserwartung. Allerdings sind Morbidität und Mortalität nach SPK im ersten Jahr höher als nach alleiniger Nierentransplantation. Die Ergebnisse nach solitärer Pankreastransplantation haben sich ebenfalls deutlich verbessert; die Methode ist jedoch nach wie vor auf Patienten mit funktionierenden Eigennieren beschränkt, die unter einem raschen Fortschreiten der diabetischen Spätschäden oder unter einem schlecht einzustellenden Diabetes mit einer dadurch bedingten massiven Einschränkung ihrer Lebensqualität leiden.

Abstract

Since its introduction in 1966, pancreas transplantation has undergone considerable progress. Refinements in surgical technique, better organ preservation solutions, and more potent immunosuppressive therapies have improved patient and graft-survival rates dramatically. Survival rates for patient and pancreas at 1 year approach 95 and 83 %, resp., for simultaneous pancreas and kidney transplantation, and 97 and 78 %, resp., for pancreas alone. US pancreas graft and patient survival rates do not significantly differ from the results of the European centers. However, there is still a hesitant acceptance of combined pancreas-kidney transplantation in Germany. Combined pancreas-kidney transplantation is nowadays the treatment of choice in carefully selected patients with type 1 insulin-dependent diabetes mellitus and end-stage renal failure. Many US centers even advocate combined transplantation in diabetic patients at a pre-uremic stage. Pancreas transplantation significantly improves quality of life and provides excellent long-term glycemic control which halts or even ameliorates secondary diabetic complications such as microangiopathy and neuropathy. In addition, there is increasing evidence that successful pancreas transplantation significantly prolongs patient survival mainly by a reduction of cardiovascular-related mortality. Current 10-year patient survival rate after SPK exceeds 70 %. For diabetics with end-stage renal disease there is no alternative treatment available with comparable live expectancy. However, morbidity and mortality after SPK is still higher than for kidney transplantation alone in the first year. Outcome of isolated pancreas transplantation is also improving but this technique is still restricted to non-uremic patients with severe diabetic complications or with brittle diabetes and severe impairment of quality of life.

Schlüsselwörter

Pankreastransplantation - Indikation - operative Technik - Komplikationen - Immunsuppression - Lebensqualität - Langzeitüberleben - diabetische Spätschäden - Typ-I-Diabetes - terminale Niereninsuffizienz

Key words

Pancreas transplantation - indication - surgical technique - complications - immunosuppressive therapy - quality of life - long-term survival - secondary diabetic complications - type I diabetes - end-stage renal disease

Literatur

  • 1 Adang E M, Engel G L, van Hooff J P, Kootstra G. Comparison before and after transplantation of pancreas-kidney and pancreas-kidney with loss of pancreas - a prospective controlled quality of life study.  Transplantation. 1996;  62 754-758
    PubMedGoogle Scholar
  • 2 Becker B N, Brazy P C, Becker Y T, Odorico J S, Pintar T J, Collins B H, Pirsch J D, Leverson G E, Heisey D M, Sollinger H W. Simultaneous pancreas-kidney transplantation reduces excess mortality in type 1 diabetic patients with end-stage renal disease.  Kidney Int. 2000;  57 2129-2135
    CrossrefPubMedGoogle Scholar
  • 3 Belzer F O, D'Alessandro A M, Hoffmann R M, Knechtle S J, Reed A, Pirsch J D, Kalayoglu M, Sollinger H W. The use of UW solution in clinical transplantation. A 4-year experience.  Ann Surg. 1992;  215 579-583
    CrossrefPubMedGoogle Scholar
  • 4 Bruce D S, Newell K A, Josephson M A, Woodle E S, Piper J B, Millis J M, Seaman D S, Carnrike C L, Huss E, Thistlethwaite J R. Long-term outcome of kidney-pancreas transplant recipients with good graft function at one year.  Transplantation. 1996;  62 451-456
    PubMedGoogle Scholar
  • 5 Bruce D S, Sollinger H W, Humar A, Sutherland D E, Light J A, Kaufman D B, Alloway R R, Lo A, Stratta R J. Multicenter survey of daclizumab induction in simultaneous kidney-pancreas transplant recipients.  Transplantation. 2001;  72 1637-1643
    PubMedGoogle Scholar
  • 6 Bundesärztekammer (Köln) .www.bundesaerztekammer.de. 
    Google Scholar
  • 7 Busing M, Heimes M, Martin D, Schulz T, Dehof S, Kozuschek W. Simultaneous pancreas-/kidney transplantation - the Bochum experience.  Exp Clin Endocrinol Diabetes. 1997;  105 92-97
    PubMedGoogle Scholar
  • 8 Chariat M N, Erren M, Chariat M, Deng M, Wolters H H, Dietl K H. Basiliximab in the therapy of acute rejection after organ transplantation.  Transplant Proc. 2001;  33 2380
    CrossrefPubMedGoogle Scholar
  • 9 Cheung A T, Perez R V, Chen P C. Improvements in diabetic microangiopathy after successful simultaneous pancreas-kidney transplantation: a computer-assisted intravital microscopy study on the conjunctival microcirculation.  Transplantation. 1999;  68 927-932
    PubMedGoogle Scholar
  • 10 Chow V C, Pai R P, Chapman J R, O'Connell P J, Allen R D, Mitchell P, Nankivell B J. Diabetic retinopathy after combined kidney-pancreas transplantation.  Clin Transplant. 1999;  13 356-362
    PubMedGoogle Scholar
  • 11 Cook K, Sollinger H W, Warner T, Kamps D, Belzer F O. Pancreaticocystostomy: an alternative method for exocrine drainage of segmental pancreatic allografts.  Transplantation. 1983;  35 634-636
    CrossrefPubMedGoogle Scholar
  • 12 D'Alessandro A M, Stratta R J, Sollinger H W, Kalayoglu M, Pirsch J D, Belzer F O. Use of UW solution in pancreas transplantation.  Diabetes. 1989;  38 (Suppl 1) 7-9
    PubMedGoogle Scholar
  • 13 Deutsche Stiftung Organtransplantation (DSO) .www.dso.de. 
    Google Scholar
  • 14 Diabetes Control and Complications Trial Research Group . The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus.  N Engl J Med. 1993;  329 977-986
    Google Scholar
  • 15 Drognitz O, Benz S, Pfeffer F, Schareck W, Hopt U T. Reduction of acute rejection episodes after simultaneous pancreas- kidney transplantation with Tacrolimus and Mycophenolate mofetil (Abstract).  Acta Diabetol. 2000;  37 149
    PubMedGoogle Scholar
  • 16 Drognitz O, Pfeffer F, Benz S, Becker H D, Schareck W, Hopt U T. Long-term follow up of 78 simultaneous pancreas-kidney transplants (Abstract).  Acta Diabetol. 2002;  36 210-211
    PubMedGoogle Scholar
  • 17 Esmatjes E, Ricart M J, Fernandez-Cruz L, Gonzalez- Clemente J M, Saenz A, Astudillo E. Quality of life after successful pancreas-kidney transplantation.  Clin Transplant. 1994;  8 75-78
    PubMedGoogle Scholar
  • 18 Fernandez B M, Esmatjes E, Ricart M J, Casamitjana R, Astudillo E, Fernandez C L. Successful pancreas and kidney transplantation: a view of metabolic control.  Clin Transplant. 1998;  12 582-587
    PubMedGoogle Scholar
  • 19 Fiorina P, La Rocca E, Venturini M, Minicucci F, Fermo I, Paroni R, D'Angelo A, Sblendido M, di Carlo V, Cristallo M, Del Maschio A, Pozza G, Secchi A. Effects of kidney-pancreas transplantation on atherosclerotic risk factors and endothelial function in patients with uremia and type 1 diabetes.  Diabetes. 2001;  50 496-501
    PubMedGoogle Scholar
  • 20 Friedman A L, Friedman E A. Pancreas Transplantation for Type 2 Diabetes at U. S. Transplant Centers.  Diabetes Care. 2002;  25 1896
    PubMedGoogle Scholar
  • 21 Gaber A O, el Gebely S, Sugathan P, Elmer D S, Hathaway D K, McCully R B, Shokouh-Amiri M H, Burlew B S. Early improvement in cardiac function occurs for pancreas-kidney but not diabetic kidney-alone transplant recipients.  Transplantation. 1995;  59 1105-1112
    PubMedGoogle Scholar
  • 22 Gaber A O, Shokouh-Amiri H, Grewal H P, Britt L G. A technique for portal pancreatic transplantation with enteric drainage.  Surg Gynecol Obstet. 1993;  177 417-419
    PubMedGoogle Scholar
  • 23 Gonin J M. Maintenance immunosuppression: new agents and persistent dilemmas.  Adv Ren Replace Ther. 2000;  7 95-116
    PubMedGoogle Scholar
  • 24 Greger B, Koller M, Rothmund M. Information deficits and hesitant acceptance of combined pancreas- kidney transplantation in Germany. A survey at German dialysis centers.  Dtsch Med Wochenschr. 2002;  127 1375-1381
    PubMedGoogle Scholar
  • 25 Gruessner A C, Sutherland D E. Analysis of United States (US) and non-US pancreas transplants reported to the United network for organ sharing (UNOS) and the international pancreas transplant registry (IPTR) as of October 2001.  Clin Transpl. 2001;  41-72
    PubMedGoogle Scholar
  • 26 Gruessner R W, Dunn D L, Gruessner A C, Matas A J, Najarian J S, Sutherland D E. Recipient risk factors have an impact on technical failure and patient and graft survival rates in bladder-drained pancreas transplants.  Transplantation. 1994;  57 1598-1606
    PubMedGoogle Scholar
  • 27 Gruessner R W, Sutherland D E, Troppmann C, Benedetti E, Hakim N, Dunn D L, Gruessner A C. The surgical risk of pancreas transplantation in the cyclosporine era: an overview.  J Am Coll Surg. 1997;  185 128-144
    PubMedGoogle Scholar
  • 28 Hathaway D K, Abell T, Cardoso S, Hartwig M S, el Gebely S, Gaber A O. Improvement in autonomic and gastric function following pancreas-kidney versus kidney- alone transplantation and the correlation with quality of life.  Transplantation. 1994;  57 816-822
    CrossrefPubMedGoogle Scholar
  • 29 Hathaway D K, Hartwig M S, Crom D B, Gaber A O. Identification of quality-of-life outcomes distinguishing diabetic kidney-alone and pancreas-kidney recipients.  Transplant Proc. 1995;  27 3065-3066
    PubMedGoogle Scholar
  • 30 Hopt U T, Busing M, Schareck W D, Becker H D. The bladder drainage technique in pancreas transplantation - the Tübingen experience.  Diabetologia. 1991;  34 (Suppl 1) S 24-S 27
    PubMedGoogle Scholar
  • 31 Hopt U T, Busing M, Schareck W D, Becker H D. The management of exocrine pancreatic secretion - a central problem of allogeneic pancreas transplantation.  Chirurg. 1992;  63 186-192
    PubMedGoogle Scholar
  • 32 Hopt U T, Drognitz O. Pancreas organ transplantation. Short and long-term results in terms of diabetes control.  Langenbecks Arch Surg. 2000;  385 379-389
    PubMedGoogle Scholar
  • 33 International Pancreas Transplant Registry (IPTR) .www.iptr.umn.edu/database.htm. 
    Google Scholar
  • 34 Jordan M L, Shapiro R, Gritsch H A, Egidi F, Khanna A, Vivas C A, Scantlebury V P, Fung J J, Starzl T E, Corry R J. Long- term results of pancreas transplantation under tacrolimus immunosuppression.  Transplantation. 1999;  67 266-272
    PubMedGoogle Scholar
  • 35 Kaufman D B, Leventhal J R, Koffron A J, Gallon L G, Parker M A, Fryer J P, Abecassis M M, Stuart F P. A prospective study of rapid corticosteroid elimination in simultaneous pancreas-kidney transplantation: comparison of two maintenance immunosuppression protocols: tacrolimus/mycophenolate mofetil versus tacrolimus/sirolimus.  Transplantation. 2002;  73 169-177
    PubMedGoogle Scholar
  • 36 Kaufman D B, Leventhal J R, Stuart J, Abecassis M M, Fryer J P, Stuart F P. Mycophenolate mofetil and tacrolimus as primary maintenance immunosuppression in simultaneous pancreas-kidney transplantation: initial experience in 50 consecutive cases.  Transplantation. 1999;  67 586-593
    PubMedGoogle Scholar
  • 37 Kelly W D, Lillehei R C, Merkel F K, Idezuki Y, Goetz F C. Allotransplantation of the pancreas and duodenum along with the kidney in diabetic nephropathy.  Surgery. 1967;  61 827-837
    PubMedGoogle Scholar
  • 38 Kim S I, Elkhammas E A, Henry M L, Davies E A, Bumgadner G L, Ferguson R M. Outcome of combined kidney/pancreas transplantation in recipients with coronary artery disease.  Transplant Proc. 1995;  27 3071
    PubMedGoogle Scholar
  • 39 Koch M, Gradaus F, Schoebel F C, Leschke M, Grabensee B. Relevance of conventional cardiovascular risk factors for the prediction of coronary artery disease in diabetic patients on renal replacement therapy.  Nephrol Dial Transplant. 1997;  12 1187-1191
    PubMedGoogle Scholar
  • 40 Konigsrainer A, Foger B H, Miesenbock G, Patsch J R, Margreiter R. Pancreas transplantation with systemic endocrine drainage leads to improvement in lipid metabolism.  Transplant Proc. 1994;  26 501-502
    PubMedGoogle Scholar
  • 41 La Rocca E, Fiorina P, di Carlo V, Astorri E, Rossetti C, Lucignani G, Fazio F, Giudici D, Cristallo M, Bianchi G, Pozza G, Secchi A. Cardiovascular outcomes after kidney-pancreas and kidney-alone transplantation.  Kidney Int. 2001;  60 1964-1971
    CrossrefPubMedGoogle Scholar
  • 42 Lo A, Stratta R J, Alloway R R, Egidi M F, Shokouh-Amiri M H, Grewal H P, Gaber L W, Gaber A O. Initial clinical experience with interleukin-2 receptor antagonist induction in combination with tacrolimus, mycophenolate mofetil and steroids in simultaneous kidney-pancreas transplantation.  Transpl Int. 2001;  14 396-404
    CrossrefPubMedGoogle Scholar
  • 43 Lo A, Stratta R J, Hathaway D K, Egidi M F, Shokouh-Amiri M H, Grewal H P, Winsett R, Trofe J, Alloway R R, Gaber A O. Long-term outcomes in simultaneous kidney-pancreas transplant recipients with portal-enteric versus systemic-bladder drainage.  Am J Kidney Dis. 2001;  38 132-143
    PubMedGoogle Scholar
  • 44 Marcelli D, Spotti D, Conte F, Tagliaferro A, Limido A, Lonati F, Malberti F, Locatelli F. Survival of diabetic patients on peritoneal dialysis or hemodialysis.  Perit Dial Int. 1996;  16 (Suppl 1) S 283-S 287
    PubMedGoogle Scholar
  • 45 Matas A J, McHugh L, Payne W D, Wrenshall L E, Dunn D L, Gruessner R W, Sutherland D E, Najarian J S. Long-term quality of life after kidney and simultaneous pancreas-kidney transplantation.  Clin Transplant. 1998;  12 233-242
    PubMedGoogle Scholar
  • 46 McAlister V C, Gao Z, Peltekian K, Domingues J, Mahalati K, MacDonald A S. Sirolimus-tacrolimus combination immunosuppression.  Lancet. 2000;  355 376-377
    CrossrefPubMedGoogle Scholar
  • 47 Navarro X, Sutherland D E, Kennedy W R. Long-term effects of pancreatic transplantation on diabetic neuropathy.  Ann Neurol. 1997;  42 727-736
    CrossrefPubMedGoogle Scholar
  • 48 Nghiem D D, Corry R J. Technique of simultaneous renal pancreatoduodenal transplantation with urinary drainage of pancreatic secretion.  Am J Surg. 1987;  153 405-406
    CrossrefPubMedGoogle Scholar
  • 49 Odorico J S, Becker Y T, Groshek M, Werwinski C, Becker B N, Pirsch J D, Sollinger H W. Improved solitary pancreas transplant graft survival in the modern immunosuppressive era.  Cell Transplant. 2000;  9 919-927
    PubMedGoogle Scholar
  • 50 Orsenigo E, Castoldi R, Socci C, Cristallo M, Fiorina P, La Rocca E, Invernizzi L, Secchi A, di Carlo V. Advantages and disadvantages of enteric versus bladder diversion in simultaneous kidney-pancreas transplantation.  Chir Ital. 2002;  54 429-436
    PubMedGoogle Scholar
  • 51 Otsu I, Nozawa M, Tsuchida H, Hirose K. The point of no return in rat diabetic nephropathy: effects of pancreatic transplantation.  Transplant Proc. 1992;  24 857-858
    PubMedGoogle Scholar
  • 52 Pfeffer F, Busing M, Zink R, Gwodzinski A, Makowiec F, Renn W, Hopt U T. High graft survival and excellent endocrine function after pancreas transplantation: effect of a standardized protocol.  Transplant Proc. 1994;  26 471-472
    PubMedGoogle Scholar
  • 53 Pfeffer F, Nauck M A, Erb M, Benz S, Hopt U T. Absence of severe hyperinsulinemia after pancreas/kidney transplantation with peripheral venous drainage.  Transplant Proc. 1997;  29 645-646
    CrossrefPubMedGoogle Scholar
  • 54 Piehlmeier W, Bullinger M, Kirchberger I, Land W, Landgraf R. Evaluation of the quality of life of patients with insulin-dependent diabetes mellitus before and after organ transplantation with the SF 36 health survey.  Eur J Surg. 1996;  162 933-940
    PubMedGoogle Scholar
  • 55 Robertson R P, Sutherland D E, Kendall D M, Teuscher A U, Gruessner R W, Gruessner A. Metabolic characterization of long-term successful pancreas transplants in type I diabetes.  J Investig Med. 1996;  44 549-555
    PubMedGoogle Scholar
  • 56 Robertson R P, Sutherland D E, Lanz K J. Normoglycemia and preserved insulin secretory reserve in diabetic patients 10-18 years after pancreas transplantation.  Diabetes. 1999;  48 1737-1740
    PubMedGoogle Scholar
  • 57 Schleicher E, Nerlich A. The role of hyperglycemia in the development of diabetic complications.  Horm Metab Res. 1996;  28 367-373
    PubMedGoogle Scholar
  • 58 Secchi A, Caldara R, La Rocca E, Fiorina P, di Carlo, V. Cardiovascular disease and neoplasms after pancreas transplantation.  Lancet. 1998;  352 65
    PubMedGoogle Scholar
  • 59 Shapiro A M, Lakey J R, Ryan E A, Korbutt G S, Toth E, Warnock G L, Kneteman N M, Rajotte R V. Islet transplantation in seven patients with type 1 diabetes mellitus using a glucocorticoid-free immunosuppressive regimen.  N Engl J Med. 2000;  343 230-238
    CrossrefPubMedGoogle Scholar
  • 60 Smets Y F, Westendorp R G, van der Pijl J W, de Charro F T, Ringers J, de Fijter J W, Lemkes H H. Effect of simultaneous pancreas-kidney transplantation on mortality of patients with type-1 diabetes mellitus and end-stage renal failure.  Lancet. 1999;  353 1915-1919
    CrossrefPubMedGoogle Scholar
  • 61 Sollinger H W, Odorico J S, Knechtle S J, D'Alessandro A M, Kalayoglu M, Pirsch J D. Experience with 500 simultaneous pancreas-kidney transplants.  Ann Surg. 1998;  228 284-296
    CrossrefPubMedGoogle Scholar
  • 62 Stratta R J, Gaber A O, Shokouh-Amiri M H, Reddy K S, Alloway R R, Egidi M F, Grewal H P, Gaber L W, Hathaway D. Evolution in pancreas transplantation techniques: simultaneous kidney-pancreas transplantation using portal-enteric drainage without antilymphocyte induction.  Ann Surg. 1999;  229 701-708
    CrossrefPubMedGoogle Scholar
  • 63 Stratta R J, Taylor R J, Ozaki C F, Bynon J S, Miller S A, Baker T L, Lykke C, Krobot M E, Langnas A N, Shaw B W. The analysis of benefit and risk of combined pancreatic and renal transplantation versus renal transplantation alone.  Surg Gynecol Obstet. 1993;  177 163-171
    PubMedGoogle Scholar
  • 64 Stratta R J, Taylor R J, Sindhi R, Sudan D, Jerius J T, Gill I S. Analysis of early readmissions after combined pancreas-kidney transplantation.  Am J Kidney Dis. 1996;  28 867-877
    PubMedGoogle Scholar
  • 65 Sudan D, Sudan R, Stratta R. Long-term outcome of simultaneous kidney-pancreas transplantation: analysis of 61 patients with more than 5 years follow-up.  Transplantation. 2000;  69 550-555
    PubMedGoogle Scholar
  • 66 Sutherland D E, Gruessner R W, Dunn D L, Matas A J, Humar A, Kandaswamy R, Mauer S M, Kennedy W R, Goetz F C, Robertson R P, Gruessner A C, Najarian J S. Lessons learned from more than 1 000 pancreas transplants at a single institution.  Ann Surg. 2001;  233 463-501
    CrossrefPubMedGoogle Scholar
  • 67 Tyden G, Bolinder J, Solders G, Brattstrom C, Tibell A, Groth C G. Improved survival in patients with insulin-dependent diabetes mellitus and end-stage diabetic nephropathy 10 years after combined pancreas and kidney transplantation.  Transplantation. 1999;  67 645-648
    PubMedGoogle Scholar
  • 68 Wilczek H E, Jaremko G, Tyden G, Groth C G. Evolution of diabetic nephropathy in kidney grafts. Evidence that a simultaneously transplanted pancreas exerts a protective effect.  Transplantation. 1995;  59 51-57
    PubMedGoogle Scholar

Dr. med. Oliver Drognitz

Universitätsklinikum Freiburg

Klinik und Poliklinik für Chirurgie

Abteilung für Allgemein- und Viszeralchirurgie

Hugstetter Straße 55

79106 Freibug im Breisgau

Phone: 07 61/2 70 28 06

Fax: 07 61/2 70 28 04

Email: oliverdrognitz@web.de