Pankreatischer Hyperinsulinismus – Wandel des Krankheitsbildes mit spezifischen Unterschieden auch bei sporadischen Erkrankungsformen (Eigene Erfahrung an 144 operierten Patienten von 1986–2009)

Zusammenfassung

Der pankreatogene Hyperinsulinismus wurde in früheren Jahren fast synonym mit einem gutartigen oder bösartigen Insulinom gleich gesetzt und nur die familiären Formen z. B. im Rahmen des MEN-1-Syndroms wurden getrennt davon betrachtet. So konzentrierte sich die chirurgische Therapie fast ausschließlich auf die Technik der Operation, mit dem Vergleich offener und minimal-invasiver Verfahrensweisen. Mit Diagnose von Patienten, die an einem sporadischen Hyperinsulinismus ohne Insulinom (non-insulinoma pancreatogenic hypoglycemia syndrome = NIPHS) leiden, wurde nun klinisch wie auch pathologisch (Insulinomatose) eine zusätzliche Gruppe von Patienten definiert, die das bisherige diagnostische und operative Vorgehen erweitert hat. Anhand der eigenen Erfahrung an 144 operierten Patienten der letzten 22 Jahre mit 16 Patienten, die an NIPHS litten, und anhand der Literatur wird dargestellt, welche Voraussetzungen heute an die Chirurgie des pankreatogenen Hyperinsulinismus gestellt werden müssen.

Abstract

The diagnoses of pancreatogenic hyperinsulinism and insulinoma (benign or malignant) were almost synonomously used during the last decades. Only familial forms of hyperinsulinism, i. e., in patients with multiple endocrine neoplasia type 1 were separately discussed. The surgical literature concentrated on technical questions, comparing open and minimal invasive techniques. The clinical diagnosis of patients with pancreatogenic hypo­glycaemia syndrome (NIPHS) and the pathological diagnosis of insulinomatosis has now opened up new questions in the diagnosis and therapy of pancreatogenic hyperinsulinism. On the basis of our experience from 144 patients oper­ated on for pancreatogenic hyperinsulinism during the last 22 years with 16 NIPHS patients and with the help of the relevant literature, we explain the prerequisites that surgical therapy has to fulfil in the treatment of patients with pancreatogenic hyperinsulinism today.

Schlüsselwörter

endokrine Chirurgie - pankreatischer Hyperinsulinismus - neuroendokrine Tumoren - Insulinom - NIPHS

Key words

endocrine surgery - pancreatic hyperinsulininsm - neuroendocrine tumours - insulinoma - NIPHS

Literatur

• 1 Friesen S R. The endocrine gut and pancreas. In: Welbourn RB, ed. The history of endocrine surgery. New York: Praeger Publishers; 1990: 236–267
• 2 Wilder R M, Allan F N, Robertson H E. Carcinoma of the islands of the pancreas. Hyperinsulinism and hypoglycaemia.  JAMA. 1927;  89 348-355
• 3 Wilder R M, Allan F N, Power M H et al. Dysinsulinism due to islet cell ­tumor of the pancreas, with operation and cure.  JAMA. 1929;  93 674-679
• 4 Marks V, Teale J D. Tumours producing hypoglycaemia.  Endocrine-Related Cancer. 1998;  5 111-129
• 5 Langer P, Bartsch D, Fendrich V et al. Minimal-invasive operative treatment of organic hyperinsulinism.  Dtsch Med Wochenschr. 2005;  130 514-518
• 6 Anlauf M, Schlenger R, Perren A et al. Microadenomatosis of the endocrine pancreas in patients with and without the multiple endocrine neoplasia type 1 syndrome.  Am J Surg Pathol. 2006;  30 560-574
• 7 Saddig C, Goretzki P E, Starke A AR. Differentiation of insulin secretion pattern in insulinoma.  World J Surg. 2008;  32 918-929
• 8 Doppman J L, Miller D L, Chang R et al. Localization of insulinomas to ­regions of the pancreas by intra-arterial stimulation with calcium.  Ann Intern Med. 1995;  123 269-273
• 9 Brown C K, Bartlett D L, Doppman J L et al. Intraarterial calcium stimulation and intraoperative ultrasonography in the localization and resection of insulinomas.  Surgery. 1997;  122 1189-1193
• 10 Kann P H, Rothmund M, Zielke A. Endoscopic ultrasound imaging of ­insulinomas: limitations and clinical relevance.  Exp Clin Endocrinol Diabetes. 2005;  113 471-474
• 11 Guettier J M, Karn A, Chang R et al. Localization of insulinomas to ­regions of the pancreas by intraarterial calcium stimulation: the NIH experience.  J Clin Endocrinol Metab. 2009;  94 1074-1080
• 12 Rappeport E D, Hansen C P, Kjaer A et al. Multidetector computed tomography and neuroendocrine pancreaticoduodenal tumors.  Acta Radiologica. 2006;  47 248-256
• 13 Hellman P, Goretzki P E, Simon D et al. Therapeutic experience in 65 cases with organic hyperinsulinism.  Langenbecks Arch Chir. 2000;  385 329-336
• 14 Wiesli P, Brändler M, Schwegler B et al. A plasma concentration below 2.5 mmol / l is not an appropriate criterion to end the 72 h fast.  J Intern Med. 2002;  252 504-509
• 15 Gouya H, Vignaux O, Augui J et al. CT, endosonography, and acombined protocol for preoperative evaluation of pancreatic insulinomas.  Am J Radiology. 2003;  181 987-992
• 16 Kar P, Price P, Sawers S et al. Insulinomas may present with normo­glycemia after prolonged fasting but glucose-stimulated hypoglycaemia.  J Clin Endocrinol Metab. 2006;  91 4733-4736
• 17 O’Riordain D S, O’Brien T, van Heerden J A et al. Surgical management of insulinoma associated with multiple endocrine neoplasia type 1.  World J Surg. 1994;  18 488-493
• 18 Cupisti K, Höppner W, Dotzenrath C et al. Lack of MEN 1 gene mutations in 27 sporadic insulinomas.  Eur J Clin Invest. 2000;  30 325-329
• 19 Schaaf L, Pickel J, Zinner K et al. Developing effective screening strategies in multiple endocrine neoplasia type 1 (MEN 1) on the basis of clinical and sequencing data of German patients with MEN 1.  Exp Clin Endocrinol Diabetes. 2007;  115 509-517
• 20 Kaplan E L, Lee C H. Recent advances in the diagnosis and treatment of insulinomas.  Surg Clin North Am. 1979;  59 119-129
• 21 Kaczirek K, Soleiman A, Schindl M et al. Nesidioblastosis in adults: a challenging cause of organic hyperinsulinism.  Eur J Clin Invest. 2003;  33 488-492
• 22 Service G J, Thompson G B, Service F J et al. Hyperinsulinemic hypoglycemia with nesidioblastosis after gastric-bypass surgery.  N Engl J Med. 2005;  353 249-254
• 23 Anlauf M, Wieben D, Perren A et al. Persistent hyperinsulinemic hypoglycemia in 15 adults with diffuse nesidioblastosis: diagnostic criteria, incidence, and characterization of beta-cell changes.  Am J Surg Pathol. 2005;  29 524-533
• 24 Starke A, Saddig C, Kirch B et al. Islet hyperplasia in adults: challenge to preoperatively diagnose non-insulinoma pancreatogenic hypoglycemia syndrome.  World J Surg. 2006;  30 670-679
• 25 Goretzki P E, Starke A. Diffuse nesidioblastosis in adults and insuli­noma: can they be associated?.  Am J Surg Pathol. 2006;  30 919-921
• 26 Won J G, Tseng H S, Yang A H et al. Clinical features and morphological characterizatin of 10 patients with noninsulinoma pancreatogenous hypoglycemia syndrome (NIPHS).  Clin Endocrinol (Oxf). 2006;  65 566-578
• 27 Anlauf M, Bauersfeld J, Raffel A et al. Insulinomatosis – a multicentric insulinoma disease that frequently causes early recurrent hyperinsu­linemic hypoglycaemia.  Am J Surg Pathol. 2009;  33 339-346
• 28 Caneiro D M, Levi J U, Irvin G L. Rapid insulin assay for intraoperative confirmation of complete resection of insulinomas.  Surgery. 2002;  132 937-942
• 29 Gimm O, König E, Thanh P N et al. Intra-operative quick insulin assay to confirm complete resection of insulinomas guided by selective arterial calcium injections (SACI).  Langenbeck’s Arch Surg. 2007;  392 679-684
• 30 Placzkowski K A, Vella A, Thompson G B et al. Secular trends in the presentation and management of functioning insulinoma at the Mayo Clinic, 1987–2007.  J Clin Endocrinol Metab. 2009;  94 1069-1073
• 31 Simon D, Starke A, Goretzki P E et al. Reoperation for organic hyperinsulinism: indications and operative strategy.  World J Surg. 1998;  22 666-671
• 32 Rindi G, Klöppel G, Ahlmann H et al. TNM staging of foregut (neuro)endocrine tumors: a consensus proposal including a grading system.  Virchows Arch. 2006;  449 395-401
• 33 Starke A, Saddig C, Mansfeld L et al. Malignant metastatic insulinoma – postoperative treatment and follow-up.  World J Surg. 2005;  29 789-793
• 34 Ayav A, Bresler L, Brunaud L et al. Laparoscopic approach for solitary ­insulinoma: a multicenter study.  Langenbecks Arch Surg. 2005;  390 134-140
• 35 Toniato A, Meduri F, Foletto M et al. Laparoscopic treatment of benign insulinomas localized in the body and tail of the pancreas: a single center study.  World J Surg. 2006;  30 1916-1919
• 36 Fernandez-Cruz L, Blanco L, Cosa R et al. Is laparoscopic resections adequate in patients with neuroendocrine pancreatic tumors?.  World J Surg. 2008;  32 904-917