World Journal of Surgery

, Volume 27, Issue 10, pp 1075–1084 | Cite as

Treatment of Pancreatic Cancer: Challenge of the Facts

  • Hans G. Beger
  • Bettina Rau
  • Frank Gansauge
  • Bertram Poch
  • Karl-Heinz Link
Editorial Update

Abstract

Adenocarcinoma of the pancreas is associated with the worst survival of any form of gastrointestinal malignancy. In spite of the progress in surgical treatment, resulting in increasing resection rates and a decrease in treatment-related morbidity and mortality, the true figures of cure are even today below 3%. The dissemination of pancreatic cancer behind the local tissue compartments restricts the short-term (< 3 years) and long-term outcome for patients who have undergone resection. By histological evaluation, less than 15% of the patients undergoing R0 resection have a pN0 status, more than 60% suffer from lymph angiosis carcinomatosa, and more than 50% suffer extrapancreatic nerve plexus infiltration. Hematoxylin and eosin–negative lymph nodes were found to be cancer positive when reverse transcriptase polymerase chain reaction (RT- PCR) or immunostaining was applied to the HE-negative lymph nodes. Cancer of the uncinate process has a very poor prognosis because there are no early symptoms; vessel wall involvement occurs early and frequently; a high association of liver metastasis exists as well. Surgery offers a low success rate, but it provides the only chance of cure. Ductal pancreatic cancer is diagnosed in more than 95% of the cases in an advanced stage; potentially curative resection can be performed only in about 10%–15% of these patients. Major contributions of surgery to improved treatment results are the reduction of surgical morbidity—e.g., early postoperative local and systemic complications—and a decrease of hospital mortality below 3%–5%. In most recently published prospective trials, R0 resection has been reported to result in an increase in short-term survival beyond that recorded for patients with residual tumor. However, R0 resection fails to improve long-term survival. In many published R0 series, standard tissue resection of pancreatic head cancer with the Kausch-Whipple procedure failed to include remote cancer cell–positive tissues in the operative specimen; e.g., N2-lymph nodes, nerve plexus, and perivascular extrapancreatic and retropancreatic tissues were not excised. Cancer recurrence after so-called R0 resection with curative intent is frequently the consequence of cancer left behind. Thus, long-term survival (> 5 years) is observed in a very small group of patients, contradicting the published 5-year actuarial survival rates of 20%–45% for resected patients. The assessment of clinical benefit from surgical or medical cancer treatment should therefore be based on several end points, not only on actuarial survival. Publication of actuarial survival figures must include the number of observed (actual) survivals, the definition of the subset of patients followed after resection, and the total number of patients in the study group; anything less is misleading. In reporting pancreatic cancer treatment trial results after oncological resections, more convincing primary end points to evaluate treatment efficacy are median survival (in months), actual survival at 1–5 years, and progression-free survival (in months). In series with multimodality treatment, clinical benefit response as well as quality of life measurements using the EORTC Quality of Life index C30 (QLQ-C30) are of importance in evaluating survival data. Adjuvant treatment improves survival after oncological resection; however, the short-term and long-term benefit after adjuvant chemotherapy in R0 as well as in R1-2 resected patients has not yet been underscored by data from controlled clinical trials. The survival benefit (median survival time) of adjuvant chemotherapy or radiochemotherapy has been demonstrated to be 6–10 months. Therefore, after oncological resection of pancreatic cancer each patient should be offered adjuvant treatment. A neoadjuvant treatment protocol for pancreatic cancer, however, has not been established.

References

  1. 1.
    Hruban, RH, Offerhaus, GJA, Kern, SE 2001

    Familial pancreatic cancer

    Cameron, JL eds. Pancreatic CancerBC Decker, Inc.Hamilton, London, Ontario2536
    Google Scholar
  2. 2.
    Gudjonsson, B 1987Cancer of the pancreas. 50 years of surgeryCancer602284PubMedGoogle Scholar
  3. 3.
    Tsuchiya, R, Oribe, T, Noda, T 1985Size of the tumor and other factors influencing prognosis of carcinoma of the head of the pancreasAm. J. Gastroenterol.80459PubMedGoogle Scholar
  4. 4.
    Cameron, JL, Crist, DW, Sitzmann, JV,  et al. 1991Factors influencing survival after pancreaticoduodenectomy for pancreatic cancerAm. J. Surg.161120PubMedGoogle Scholar
  5. 5.
    Nagakawa, T, Kayahara, M, Ohta, T,  et al. 1991Patterns of neural and plexus extensive invasion of human pancreatic cancer and experimental cancerInt. J. Pancreatol.10113PubMedGoogle Scholar
  6. 6.
    Ishikawa, O 1996Surgical technique, curability and postoperative quality of life in an extended pancreatectomy for adenocarcinoma of the pancreasHepatogastroenterology.43320PubMedGoogle Scholar
  7. 7.
    Geer, RJ, Brennan, MF 1993Prognostic indicators for survival after resection of adenocarcinoma of the pancreasAm. J. Surg.16568PubMedGoogle Scholar
  8. 8.
    Yeo, C, Abrams, R, Grochow, L,  et al. 1997Pancreaticoduodenectomy for pancreatic adenocarcinoma: postoperative adjuvant chemoradiation improves survivalAnn. Surg.225621CrossRefPubMedGoogle Scholar
  9. 9.
    Birk, D, Fortnage, G, Formentini, A,  et al. 1998Small carcinoma of the pancreas. Factors of prognostic relevanceJ Hepatol. Biliary Pancreat. Surg.23234Google Scholar
  10. 10.
    Beger, HG, Gansauge, F, Birk, D 2001

    Lymph node dissection

    Cameron, JL eds. Pancreatic CancerBC Decker, Inc.Hamilton, London, Ontario123132
    Google Scholar
  11. 11.
    Ishikawa, O, Ohigashi, H, Sasaki, Y,  et al. 1997Practical grouping of positive lymph nodes in pancreatic head cancer treated by an extended pancreatectomySurgery121244249PubMedGoogle Scholar
  12. 12.
    Hirai, I, Murakami, G, Kimura, W,  et al. 2001Origin of the thoracic duct and pancreaticoduodenal lymphatic pathways to the para-aortic lymph nodesJ. Hepatobiliary. Pancreat. Surg.8441448CrossRefPubMedGoogle Scholar
  13. 13.
    Tsuchiya, R, Takatoshi, N, Harada, N,  et al. 1986Collective review of small carcinomas of the pancreasAnn. Surg.2037781PubMedGoogle Scholar
  14. 14.
    Hermanek, P 1991Staging of exocrine pancreatic carcinomaEur. J. Surg. Oncol.17167172PubMedGoogle Scholar
  15. 15.
    Takahashi, T, Ishikara, H, Kato, H,  et al. 1992Intra-pancreatic, extratumoral perineural invasionActa Pathol. Jpn.4299103PubMedGoogle Scholar
  16. 16.
    Nakao, A, Harada, A, Nonami, T,  et al. 1996Clinical significance of carcinoma invasion of the extrapancreatic nerve plexus in pancreatic cancerPancreas12357361PubMedGoogle Scholar
  17. 17.
    Kayahara, M, Nagakawa, T, Futagami, F,  et al. 1996Lymphatic flow and neural plexus invasion associated with carcinoma of the body and tail of the pancreasCancer782485CrossRefPubMedGoogle Scholar
  18. 18.
    Heeckt, P, Safi, F, Binder, T,  et al. 1992Free intraperitoneal tumor cells in pancreatic cancer—significance for clinical course and therapyChirurgie782485Google Scholar
  19. 19.
    Ando, N, Nakao, A, Nomoto, S,  et al. 1997Defection of mutant K-ras in dissected paraaortic lymph nodes of patients with pancreatic adenocarcinomaPancreas15374378PubMedGoogle Scholar
  20. 20.
    Hosch, SB, Knoefel, WT, Metz, S,  et al. 1997Early lymphatic tumor cell dissemination in pancreatic cancer: frequency and prognostic significancePancreas15154159PubMedGoogle Scholar
  21. 21.
    Demuere, MJ, Doffek, KM, Komoiowski, RA,  et al. 1998Adenocarcinoma of the pancreas. Detection of occult metastases in regional lymph nodes by PCR-based assayCancer8313281334CrossRefPubMedGoogle Scholar
  22. 22.
    Mühling B, Dehner C, Steiger. Micrometastasis in pancreatic head cancer: use of polymerase chain reaction for precise tumor staging. J. Gastrointest. Surg., in pressGoogle Scholar
  23. 23.
    Juhl, H, Stritzel, M, Wroblewski, A,  et al. 1994Immunocytological detection of micrometastatic cellsInt. J. Cancer57330335PubMedGoogle Scholar
  24. 24.
    Inoue, S, Nakao, A, Kasai, Y,  et al. 1995Detection of hepatic micrometastasis in pancreatic adenocarcinoma patients by two-stage polymerase chain reaction/restriction fragment length polymorphism analysisJpn. J. Cancer Res.86626630PubMedGoogle Scholar
  25. 25.
    Soeth, E, Röder, C, Juhl, H,  et al. 1996The detection of disseminated tumor cells in bone marrow from colorectal-cancer patients by a cytokeratin-20-specific nested reverse-transcriptase-polymerase-chain reaction is related to the stage of diseaseInt. J. Cancer69278282CrossRefPubMedGoogle Scholar
  26. 26.
    Thorban, S, Roder, JD, Pantel, K,  et al. 1996Immunocytochemical detection of isolated epithelial tumor cells in bone marrow of patients with pancreatic carcinomaAm. J. Surg.172297298CrossRefPubMedGoogle Scholar
  27. 27.
    Kayahara, M, Nagakawa, T, Konishi, I,  et al. 1991Clinicopathological study of pancreatic carcinoma with particular reference to the invasion of the extrapancreatic neural plexusInt. J. Pancreatol.10105111PubMedGoogle Scholar
  28. 28.
    Nagakawa, T, Kayahara, M, Ueno, K,  et al. 1992A clinicopatholgic study on neural invasion in cancer of the pancreatic headCancer69930935PubMedGoogle Scholar
  29. 29.
    Ohigashi, H, Ishikawa, O, Sasaki, Y,  et al. 2000K-ras point mutation in the nerve plexus around superior mesenteric artery in resectable adenocarcinoma of the pancreatic headArch. Surg.13514501455CrossRefPubMedGoogle Scholar
  30. 30.
    Birk, D, Fortnage, G, Formentini, A,  et al. 1998Carcinoma of the pancreas arising from the uncinate processBr. J. Surg.85498CrossRefPubMedGoogle Scholar
  31. 31.
    Gordon, TA, Burleyson, G, Tielsch, JM,  et al. 1995The effects of regionalization on cost and outcome for one high-risk general surgical procedureAnn. Surg.2214349PubMedGoogle Scholar
  32. 32.
    Liebermann, MD, Killborn, H, Lindsey, M,  et al. 1995Relation of perioperative deaths to hospital volume among patients undergoing pancreatic resection for malignancyAnn. Surg.222638645PubMedGoogle Scholar
  33. 33.
    Gouma, DJ, Geenen, RCI, Gulik, THM 2000Rates of complications and death after pancreaticoduodenectomy: risk factors and the impact of hospital volumeAnn. Surg.232786794CrossRefPubMedGoogle Scholar
  34. 34.
    Bramhall, SR, Allum, WH, Jones, AG,  et al. 1995Treatments and survival in 13.560 patients with pancreatic cancer, and incidence of the disease, in the West Midlands: an epidemiological studyBr. J. Surg.82111115PubMedGoogle Scholar
  35. 35.
    Neoptolemos, JP, Russel, RCG, Bramhale, S,  et al. 1997Low mortality following resection for pancreatic and periampullary tumours in 1026 patientsBr. J. Surg.841370PubMedGoogle Scholar
  36. 36.
    Gordon, TA, Bowman, HM, Bass, EB,  et al. 1999Complex gastrointestinal surgery: impact of provider experience on clinical and economic outcomesJ. Am. Coll. Surg.1894656CrossRefPubMedGoogle Scholar
  37. 37.
    Scand J Finnish Surg Society Annual Meeting. (1996) 17-45Google Scholar
  38. 38.
    Birkmeyer, JD, Finlayson, SRG, Tosteson, ANA,  et al. 1999Effect of hospital volume on in-hospital mortality with pancreaticoduodenectomySurgery125250256CrossRefPubMedGoogle Scholar
  39. 39.
    Howard, J 1968Pancreaticoduodenectomy: forty-one consecutive Whipple resections without an operative mortalityAnn. Surg.168629640PubMedGoogle Scholar
  40. 40.
    Beger HG, Gansauge F, Ramadani M, et al. Morbidity and mortality after pancreatic head resection— monoinstitutional results of 1200 patients. Ann. Surg. 2003, in pressGoogle Scholar
  41. 41.
    Pedrazzoli, S, Carlo, V, Dionigi, R,  et al. 1998Standard versus extended lymphadenectomy associated with pancreaticoduodenectomy in the surgical treatment of adenocarcinoma of the head of the pancreasAnn. Surg.228508517CrossRefPubMedGoogle Scholar
  42. 42.
    Yeo, CL, Cameron, JL, Lillemoe, KD,  et al. 2002Pancreaticoduodenectomy with or without distal gastrectomy and extended retroperitoneal lymphadenectomy for periampullary adenocarcinomaAnn. Surg.236355368CrossRefPubMedGoogle Scholar
  43. 43.
    Pedrazzoli, S, Beger, HG, Obertop, H,  et al. 1999A surgical and pathological based classification of resective treatment of pancreatic cancerDig. Surg.16337345CrossRefPubMedGoogle Scholar
  44. 44.
    Tsuchiya, R, Karada, N, Tsunoda, T,  et al. 1988Long-term survivors after operation on carcinoma of the pancreasInt. J. Pancreatol.3401406PubMedGoogle Scholar
  45. 45.
    Trede, M, Schwall, G, Seger, HD 1990Survival after pancreatoduodenectomy. 118consecutive resections without an operative mortalityAnn. Surg.211447458PubMedGoogle Scholar
  46. 46.
    Nagakawa, T, Kayahar, M, Ohta, T,  et al. 1991Patterns of neural and plexus invasion of human pancreatic cancer and experimental cancerInt. J. Pancreatol.10113119PubMedGoogle Scholar
  47. 47.
    Takahashi, S, Ogata, Y, Miyazaki, H,  et al. 1995Aggressive surgery for pancreatic duct cell cancer: feasibility, validity, limitationsWorld J. Surg.19653660PubMedGoogle Scholar
  48. 48.
    Klempnauer, J, Ridder, GJ, Pichlmayr, R 1995Prognostic factors after resection of ampullary carcinoma: multivariate survival analysis in comparison with ductal cancer of the pancreatic headBr. J. Surg.8216861691Google Scholar
  49. 49.
    Yeo, CL, Sohn, TA, Caeron, JL,  et al. 1998Periampullary adenocarcinoma: analysis of 4-year survivorsAnn. Surg.227821831CrossRefPubMedGoogle Scholar
  50. 50.
    Takahashi, T, Nizno, N, Ishikura, H,  et al. 1997Predictive factors for long-term survival in patients with pancreatic carcinomaHepatogastroenterology.4414631468PubMedGoogle Scholar
  51. 51.
    Nitecki, S, Sarr, MG, Thomas, VC,  et al. 1995Long-term survival after resection for ductal adenocarcinoma of the pancreas. Is it really improving?Ann. Surg.2215966PubMedGoogle Scholar
  52. 52.
    Hanyu, F, Imaizumi, T 1996

    Extended radical surgery for carcinoma of the head of the pancreas—Japanese experience

    Beger, HGBüchler, MSchoenberg, MH eds. Cancer of the PancreasUniversitätsverlagUlm (Germany)389401
    Google Scholar
  53. 53.
    Tashiro, S, Kochino, R, Hiraoka, T,  et al. 1991Surgical indications and significance of portal vein resection in biliary and pancreatic cancerSurgery109481487PubMedGoogle Scholar
  54. 54.
    Ishikawa, O, Ohigashi, H, Imaoka, S,  et al. 1992Preoperative indications for extended pancreatectomy for locally advanced pancreas cancer involving the portal veinAnn. Surg.215231236PubMedGoogle Scholar
  55. 55.
    Allema, JH, Renders, ME, Gulik, TM,  et al. 1994Portal vein resection in patients undergoing pancreatoduodenectomy for carcinoma of the pancreatic headBr. J. Surg.8116421646Google Scholar
  56. 56.
    Takahashi, S, Ogata, Y, Tsuzuki, T 1994Combined resection of the pancreas and portal vein for pancreatic cancerBr. J. Surg.8111901193PubMedGoogle Scholar
  57. 57.
    Nakao, A, Harada, A, Nonami, T,  et al. 1995Clinical significance of portal vein invasion by pancreatic head carcinomaSurgery1175055PubMedGoogle Scholar
  58. 58.
    Roder, JD, Stein, HJ, Siewert, JR 1996Carcinoma of the periampullary region: who benefits from portal vein resection?Am. J. Surg.171170175CrossRefPubMedGoogle Scholar
  59. 59.
    Harrison, LE, Klimstra, DS, Murray, FB 1996Isolated portal vein involvement in pancreatic adenocarcinoma. A Contraindication for resection?Ann. Surg.224342349CrossRefPubMedGoogle Scholar
  60. 60.
    Evans, DB, Pisters, PWT, Lee, JE,  et al. 1998Preoperative chemoradiation strategies for localized adenocarcinoma of the pancreasJ. Hepatobil. Pancreat. Surg.5242250CrossRefGoogle Scholar
  61. 61.
    Launois, B, Franci, J, Bardayoglou, E,  et al. 1999Total pancreatectomy for ductal adenocarcinoma of the pancreas with special reference to resection of the portal vein and multicentric cancerWorld J. Surg.17122Google Scholar
  62. 62.
    Shibada, C, Kobari, M, Tsuchiya, T,  et al. 2001Pancreatectomy combined with superior mesenteric-portal vein resection for adenocarcinoma in pancreasWorld J. Surg.2510021005PubMedGoogle Scholar
  63. 63.
    Kawada M, Kondo S, Okushiba S, et al. (2003) “Re-evaluation on indication of radical pancreatectomy for pancreatic carcinoma—is portal vein infiltration a contraindication?” Langenbecks Arch. Surg., in pressGoogle Scholar
  64. 64.
    Griffin, JF, Smallay, SR, Jewel, W,  et al. 1990Patterns of failure after curative resection of pancreatic carcinomaCancer665661PubMedGoogle Scholar
  65. 65.
    Westerdahl, J, Andrew-Sandberg, A, Ihse, I 1993Recurrence of exocrine pancreatic cancer: local or hepatic?Hepatogastroenterology.40384PubMedGoogle Scholar
  66. 66.
    Kayahara, M, Nagakwa, T, Keno, K,  et al. 1993An evaluation of radical resection for pancreatic cancer based on the mode of recurrence as determined by autopsy and diagnostic imagingCancer722118PubMedGoogle Scholar
  67. 67.
    Sperti, C, Pasquali, C, Piccoli, A,  et al. 1996Survival after resection for ductal adenocarcinoma of the pancreasBr. J. Surg.83625631PubMedGoogle Scholar
  68. 68.
    Iacono, C, Bortolasi, L, Facci, E 1997Does extended pancreatico-duodenectomy increase operative morbidity and mortality vs. standard pancreatoduodenectomy?J. Gastrointest. Surg.1446453CrossRefPubMedGoogle Scholar
  69. 69.
    Gudjonsson, B 2002Survival statistics gone awry. Pancreatic cancer, a case in pointJ. Clin. Gastroenterol.35180184CrossRefPubMedGoogle Scholar
  70. 70.
    Glimelius B. Efficacy endpoints in pancreatic cancer trials: an expert’s view CRP. The Remedy Ltd, LondonGoogle Scholar
  71. 71.
    Storniolo, AM, Enas, NH, Brown, CA,  et al. 1999An investigational new drug treatment programme for patients with gemcitabineCancer8512611268PubMedGoogle Scholar
  72. 72.
    Klinkenbijl, JH, Jeekel, J, Sahmoud, T 1999Adjuvant radiotherapy and 5-fluorouracil after curative resection of cancer of the pancreas and periampullary region: phase III trial of the EORTC gastrointestinal tract cancer cooperative groupAnn. Surg.230776784CrossRefPubMedGoogle Scholar
  73. 73.
    Nguyten, TC, Sohn, TA, Cameron, JL,  et al. 2003Standard vs. radical pancreaticoduodenectomy for periampullary adenocarcinoma: a prospective, randomized trial evaluating quality of life in pancreaticoduodenectomy survivorsJ. Gastrointest. Surg.7111CrossRefPubMedGoogle Scholar
  74. 74.
    Kalser, MH, Ellenberg, SS 1985 Pancreatic cancer: adjuvant combined radiation and chemotherapy following curative resectionArch. Surg.120899903PubMedGoogle Scholar
  75. 75.
    GITSG1987Further evidence of effective adjuvant combined radiation and chemotherapy following curative resection of pancreatic cancerCancer5920062010Google Scholar
  76. 76.
    Yeo, CJ, Abrams, RA, Grochow, LB,  et al. 1997Pancreaticoduodenectomy for pancreatic adenocarcinoma: postoperative adjuvant chemoradiation improves survival. A prospective, single-institution experienceAnn. Surg.225621636CrossRefPubMedGoogle Scholar
  77. 77.
    Nukui, Y, Picozzi, VJ, Traverso, LW 2000Interferon-based adjuvant chemoradiation therapy improves survival after pancreaticoduodenectomy for pancreatic adenocarcinomaAm. J. Surg.179367371CrossRefPubMedGoogle Scholar
  78. 78.
    Neoptolemos, JP, Dunn, JA, Stocken, DD,  et al. 2001Adjuvant chemoradiotherapy and chemotherapy in resectable pancreatic cancer: a randomised controlled trialLancet35815761585CrossRefPubMedGoogle Scholar
  79. 79.
    Ishikawa, O, Ohigashi, H, Sasaki, Y,  et al. 1994Liver perfusion chemotherapy via both the hepatic artery and portal vein to prevent hepatic metastasis after extended pancreatectomy for adenocarcinoma of the pancreasAm. J. Surg.168361364PubMedGoogle Scholar
  80. 80.
    Tahakashi, S, Ogata, Y, Miyazaki, H,  et al. 1995Aggressive surgery for pancreatic duct cell cancer: feasibility, validity, limitationsWorld J. Surg.19653PubMedGoogle Scholar
  81. 81.
    Beger, HG, Gansauge, F, Büchler, MW,  et al. 1999Intraarterial adjuvant chemotherapy after pancreaticoduodenectomy for pancreatic cancer: significant reduction in occurrence of liver metastasisWorld J. Surg.23946949CrossRefPubMedGoogle Scholar
  82. 82.
    Zerbi, A, Fossati, U, Perolini, D,  et al. 1994Intraoperative radiation therapy adjuvant to resection in the treatment of pancreatic cancerCancer7329302935PubMedGoogle Scholar
  83. 83.
    Foo, ML, Gunderson, LG, Nagorney, DM,  et al. 1993Patterns of failure in grossly resected pancreatic ductal adenocarcinoma treated with adjuvant irradiation + 5 fluorouracilInt. J. Radiat. Oncol. Biol. Phys.26483489PubMedGoogle Scholar
  84. 84.
    Hiraoka, T 1990Extended radical resection of cancer of the pancreas with intraoperative radiotherapyBaillieres Clin. Gastroenterol.4985PubMedGoogle Scholar
  85. 85.
    Hosotani, R, Kogire, M, Arii, S,  et al. 1997Results of pancreatectomy with radiation therapy for pancreatic cancerHepatogastroenterology.4415281535PubMedGoogle Scholar
  86. 86.
    Farrell, TJ, Barbot, DJ, Rosato, FE 1997Pancreatic resection combined with intraoperative radiation therapy for pancreatic cancerAnn. Surg.2266669CrossRefPubMedGoogle Scholar
  87. 87.
    Jessup, JM, Steele, C, Mayer, RJ,  et al. 1993Neoadjuvant therapy for unresectable pancreatic adenocarcinomaArch. Surg.128559PubMedGoogle Scholar
  88. 88.
    Spitz, F, Abbruzzose, J, Janjan, N,  et al. 1997Preoperative and postoperative chemoradiation strategies in patients treated with pancreaticoduodenectomy for adenocarcinoma of the pancreasJ. Clin. Oncol.15928PubMedGoogle Scholar
  89. 89.
    Snady, H, Bruckner, H, Coopermann, A,  et al. 2000Survival advantage of combined chemoradiotherapy compared with resection as the initial treatment in patients with regional pancreatic carcinomaCancer89314CrossRefPubMedGoogle Scholar

Copyright information

© Société Internationale de Chirurgie 2003

Authors and Affiliations

  • Hans G. Beger
    • 1
  • Bettina Rau
    • 2
  • Frank Gansauge
    • 3
  • Bertram Poch
    • 3
  • Karl-Heinz Link
    • 4
  1. 1.Department of SurgeryUniversity of UlmSteinhoevelstrasse 9, D-89075 UlmGermany
  2. 2.Department of General, Visceral and Vascular SurgeryUniversity of the SaarlandKirrberger StraΒe 57, D-66421 Homburg/SaarGermany
  3. 3.Department of Visceral SurgeryIllertalklinikKrankenhausstrasse 7, D-89257 IllertissenGermany
  4. 4.Department of Surgery IIAsklepios Paulinen HospitalGeisenheimer Str. 10, D-65197 WiesbadenGermany

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