Pankreas Cerrahisinin Endokrin Komplikasyonları ve Yönetimi
Özet
Pankreas cerrahisi, endokrin hücrelerin azalmasına bağlı olarak glukoz metabolizmasında önemli değişikliklere ve sıklıkla Tip 3c diyabet gelişimine yol açmaktadır. Langerhans adacıklarındaki beta, alfa ve delta hücreleri sırasıyla insülin, glukagon ve somatostatin salgılayarak kan şekerini dengeler. Parsiyel pankreatektomilerde diyabet riski rezeksiyon oranına, preoperatif HbA1c ve açlık kan glukozu seviyelerine göre değişmektedir. Distal pankreatektomide, alfa hücrelerinin bu bölgede yoğunlaşması nedeniyle hipoglisemi riski daha yüksekken; pankreatikoduodenektomide GLP-1 artışına bağlı olarak bu risk daha düşüktür. Total pankreatektomi ise mutlak insülin eksikliği, şiddetli malabsorbsiyon ve yüksek glisemik değişkenlikle karakterize "hassas" bir diyabet tablosuna neden olur. Son yıllarda, uzun etkili insülin analogları, insülin pompaları (yapay pankreas) ve modern enzim preparatlarındaki ilerlemeler total pankreatektomi sonrası hastaların yaşam kalitesini ve sağkalımını belirgin şekilde artırmıştır. Postoperatif dönemde HbA1c ve C-peptid takibi, erken insülin tedavisine başlanması açısından kritiktir. Ayrıca, diyetisyen ve endokrinolog iş birliğiyle yürütülen multidisipliner hasta eğitimleri, sık ve küçük öğünler içeren beslenme protokolleri glisemik kontrolü optimize etmede temel rol oynamaktadır.
Pancreatic surgery leads to significant alterations in glucose metabolism and frequently results in Type 3c diabetes due to the reduction of endocrine cells. Beta, alpha, and delta cells within the islets of Langerhans regulate blood glucose by secreting insulin, glucagon, and somatostatin, respectively. In partial pancreatectomies, the risk of diabetes varies based on the resection rate, preoperative HbA1c, and fasting glucose levels. Distal pancreatectomy carries a higher risk of hypoglycemia due to the dense concentration of alpha cells in the tail, whereas pancreaticoduodenectomy presents a lower risk owing to increased GLP-1 secretion. Total pancreatectomy results in absolute insulin deficiency, severe malabsorption, and a "brittle" diabetes scenario characterized by high glycemic variability. Recently, advancements in long-acting insulin analogs, insulin pumps (artificial pancreas), and modern pancreatic enzyme replacement therapies have significantly improved postoperative survival and quality of life. Postoperative monitoring of HbA1c and C-peptide levels is crucial for timely insulin therapy. Furthermore, multidisciplinary patient education led by endocrinologists and dietitians, combined with nutritional protocols featuring small, frequent meals, plays a pivotal role in optimizing long-term glycemic control.
Referanslar
Bonner-Weir, S. (1991). Anatomy of the islet of Langerhans. In: Samols E (ed.), The endocrine pancreas (15-27), New York: Raven Press.
Ramnanan CJ, Edgerton DS, Rivera N, et al Molecular characterization of insulin-mediated suppression of hepatic glucose production in vivo. Diabetes. 2010;59(6):1302–1311.
Kahn BB. Glucose transport: pivotal step in insulin action. Diabetes. 1996;45(11):1644–1654.
Slezak LA, Andersen DK. Pancreatic resection: effects on glucose metabolism. World J Surg. 2001;25(4):452–460.
Klover PJ, Mooney RA. Hepatocytes: critical for glucose homeostasis. Int J Biochem Cell Biol. 2004;36(5):753–758.
Reichlin S. Somatostatin (second of two parts). N Engl J Med. 1983; 309(25):1556–1563.
Beglinger C, Drewe J. Somatostatin and octreotide: physiological background and pharmacological application. Digestion. 1999;60(Suppl 2):2–8.
Paye F. The Pancreatic stump after pancreatoduodenectomy:the 'Achilles heel' revisited. J. Visc.Surg. 2010;147:e13–e20
Wang X, Misawa R, Zielinski MC, et al. Regional differences in islet distribution in the human pancreas-preferential beta-cell loss in the head region in patients with type 2 diabetes. PloS one. 2013;8(6):e67454.
Mezza T, Cefalo CM, Cinti F, et al. Endocrine and metabolic insights from pancreatic surgery. Trends in Endocrinology & Metabolism. 2020; 31(10):760-772.
W L, Nahm CB, Jamieson NB, et al. Risk factors for development of diabetes mellitus (Type 3c) after partial pancreatectomy: a systematic review. Clinical endocrinology. 2020;92(5):396-406.
Leahy JL, Bumbalo LM, Chen C, et al. Diazoxide causes recovery of beta-cell glucose responsiveness in 90% pancreatectomies diabetic rats. Diabetes. 1994;43:173–179
Liu YQ, Nevin PW, Leahy JL. β-Cell adaptation in 60% pancreatectomy rats that preserves normoinsulinemia and normoglycemia. American Journal of Physiology-Endocrinology And Metabolism. 2000;279(1):E68-E73.
Kendall DM, Sutherland DE, Najarian JS, et al. Effects of hemipancreatectomy on insulin secretion and glucose tolerance in healthy humans. New England Journal of Medicine. 1990;322(13):898-903.
King J, Kazanjian K, Matsumoto J, et al. Distal pancreatectomy: incidence of postoperative diabetes. Journal of Gastrointestinal Surgery. 2008;12(9):1548-1553.
Büchler MW, Friess H, Bittner R, et al. Duodenum-preserving pancreatic head resection: long-term results. Journal of Gastrointestinal Surgery. 1997;1(1):13-19.
Büchler MW, Friess H, Müller MW, et al. Randomized trial of duodenum-preserving pancreatic head resection versus pylorus-preserving Whipple in chronic pancreatitis. The American journal of surgery. 1995;169(1):65-70.
Mezza T, Sorice GP, Conte C, et al. β-Cell glucose sensitivity is linked to insulin/glucagon bihormonal cells in nondiabetic humans. The Journal of Clinical Endocrinology & Metabolism. 2016;101(2):470-475.
American Diabetes Association. 2. Classification and diagnosis of diabetes. Diabetes care. 2017; 40(Supplement 1):S11-S24.
Hardt PD, Brendel MD, Kloer HU, et al. Is pancreatic diabetes (type 3c diabetes) underdiagnosed and misdiagnosed? Diabetes Care. 2008;31(Suppl 2):S165-169.
Schrader H, Menge BA, Breuer TG, et al. Impaired glucose-induced glucagon suppression after partial pancreatectomy. J Clin Endocrinol Metab. 2009;94(8):2857-2863.
Lee BW, Kang HW, Heo JS, et al. Insulin secretory defect plays a major role in the development of diabetes in patients with distal pancreatectomy. Metab Clin Exp. 2006;55(1):135-141.
Muscogiuri G, Mezza T, Prioletta A, et al. Removal of duodenum elicits GLP-1 secretion. Diabetes Care. 2013;36(6):1641-1646.
Kang JS, Jang JY, Kang MJ, et al. Endocrine function impairment after distal pancreatectomy: incidence and related factors. World J Surg. 2016;40(2):440-446.
Kwon JH, Kim SC, Shim IK, et al. Factors affecting the development of diabetes mellitus after pancreatic resection. Pancreas. 2015;44(8):1296-1303
Shirakawa S, Matsumoto I, Toyama H, et al. Pancreatic volumetric assessment as a predictor of new-onset diabetes following distal pancreatectomy. J Gastrointest Surg. 2012;16(12):2212-2219.
Jones AG, Hattersley AT. The clinical utility of C-peptide measurement in the care of patients with diabetes. Diabet Med. 2013;30(7):803-817.
Leighton E, Sainsbury CA, Jones GC. A practical review of C-peptide testing in diabetes. Diabetes Ther. 2017;8(3):475-487.
Muller MW, Friess H, Kleeff J, et al. Is there still a role for total pancreatectomy? Ann Surg. 2007;246(6):966–974 discussion 74-5.
Heidt DG, Burant C, Simeone DM. Total pancreatectomy: indications, operative technique, and postoperative sequelae. J Gastrointest Surg. 2007;11(2):209–216.
Maker AV, Sheikh R, Bhagia V. Perioperative management of endocrine insufficiency after total pancreatectomy for neoplasia. Langenbeck's archives of surgery. 2017;402(6):873-883.
Blanchet MC, Andreelli F, Scoazec JY, et al. Total pancreatectomy for mucinous pancreatic tumor. Ann Chir. 2002;127(6):439–448.
Sauvanet A. Intraductal papillary mucinous neoplasms of the pancreas: indication, extent, and results of surgery. Surg Oncol Clin N Am. 2008; 17(3):587–606 ix.
Yamaguchi K, Konomi H, Kobayashi K, et al. Total pancreatectomy for intraductal papillary-mucinous tumor of the pancreas: reappraisal of total pancreatectomy. Hepato-Gastroenterology. 2005;52(65):1585–1590.
Zerbi A, Ortolano E, Balzano G, et al. Pancreatic metastasis from renal cell carcinoma: which patients benefit from surgical resection? Ann Surg Oncol. 2008;15(4):1161–1168.
Del Chiaro M, Zerbi A, Capurso G, et al. Familial pancreatic cancer in Italy. Risk assessment, screening programs and clinical approach: a position paper from the Italian Registry. Dig Liver Dis. 2010;42(9):597–605.
Billings BJ, Christein JD, HarmsenWS, et al. Quality-of-life after total pancreatectomy: is it really that bad on long-term follow-up? J Gastrointest Surg. 2005;9(8):1059–1066
Dresler CM, Fortner JG, McDermott K, et al. Metabolic consequences of (regional) total pancreatectomy. Ann Surg. 1991;214(2):131–140.
Casadei R, Ricci C, Monari F, et al. Clinical outcome of patients who underwent total pancreatectomy. Pancreas. 2010;39(4):546–547.
Parsaik AK, Murad MH, Sathananthan A, et al. Metabolic and target organ outcomes after total pancreatectomy: Mayo Clinic experience and meta-analysis of the literature. Clin Endocrinol. 2010;73(6):723–731.
Jaleel A, Halvatsiotis P, Williamson B, et al. Identification of Amadori-modified plasma proteins in type 2 diabetes and the effect of short-term intensive insulin treatment. Diabetes Care. 2005;28(3):645–65.
Munoz M, Pronovost P, Dintzis J, et al.. Implementing and evaluating a multicomponent inpatient diabetes management program: putting research into practice. The Joint Commission Journal on Quality and Patient Safety. 2012;38(5):195-AP4.
Christopher DS, Rita RK, Frederick L (2011). Johns Hopkins Poc-It Center Diabetes Guide 2012 (1st edition). Montgomery; Jones & Bartlett Learning
Bolli GB, Andreoli AM, Lucidi P. Optimizing the replacement of basal insulin in type 1 diabetes mellitus: no longer an elusive goal in the post-NPH era. Diabetes Technol Ther. 2011;13(Suppl 1):S43–S52.
Schmeltz LR, DeSantis AJ, Thiyagarajan V, et al. Reduction of surgical mortality and morbidity in diabetic patients undergoing cardiac surgery with a combined intravenous and subcutaneous insulin glucose management strategy. Diabetes Care. 2007;30(4):823–828.
Walsh J, Roberts R, Bailey T. Guidelines for insulin dosing in continuous subcutaneous insulin infusion using new formulas from a retrospective study of individuals with optimal glucose levels. J Diabetes Sci Technol. 2010;4(5):1174–1181
Okabayashi T, Nishimori I, Yamashita K, et al. Continuous postoperative blood glucose monitoring and control by artificial pancreas in patients having pancreatic resection: a prospective randomized clinical trial. Arch Surg. 2009;144(10):933–937.
Pickup J, Keen H. Continuous subcutaneous insulin infusion at 25 years: evidence base for the expanding use of insulin pump therapy in type 1 diabetes. Diabetes Care. 2002;25(3):593–98
Bertuzzi F, Secchi A, Di Carlo V. Islet transplantation in type 1 diabetic patients. Transplant Proc. 2004;36(3):603–604.
Hering BJ, Clarke WR, Bridges ND, et al. Phase 3 trial of transplantation of human islets in type 1 diabetes complicated by severe hypoglycemia. Diabetes Care. 2016; 39(7):1230–1240.
Shapiro AM, Ricordi C, Hering BJ, et al. International trial of the Edmonton protocol for islet transplantation. N Engl J Med. 2006; 355(13):1318–1330.
