Postoperative Outcomes of Enucleation and Standard Resections in Patients with a Pancreatic Neuroendocrine Tumor

Anneke P J Jilesen, Casper H J van Eijck, Olivier R C Busch, Thomas M van Gulik, Dirk J Gouma, Els J M Nieveen van Dijkum, Anneke P J Jilesen, Casper H J van Eijck, Olivier R C Busch, Thomas M van Gulik, Dirk J Gouma, Els J M Nieveen van Dijkum

Abstract

Background: Either enucleation or more extended resection is performed to treat patients with pancreatic neuroendocrine tumor (pNET). Aim was to analyze the postoperative complications for each operation separately. Furthermore, independent risk factors for complications and incidence of pancreatic insufficiency were analyzed.

Methods: Retrospective all resected patients from two academic hospitals in The Netherlands between 1992 and 2013 were included. Postoperative complications were scored by both ISGPS and Clavien-Dindo criteria. Based on tumor location, operations were compared. Independent risk factors for overall complications were identified. During long-term follow-up, pancreatic insufficiency and recurrent disease were analyzed.

Results: Tumor enucleation was performed in 60/205 patients (29%), pancreatoduodenectomy in 65/205 (31%), distal pancreatectomy in 72/205 (35%) and central pancreatectomy in 8/205 (4%) patients. Overall complications after tumor enucleation of the pancreatic head and pancreatoduodenectomy were comparable, 24/35 (69%) versus 52/65 (80%). The same was found after tumor enucleation and resection of the pancreatic tail (36 vs.58%). Number of re-interventions and readmissions were comparable between all operations. After pancreatoduodenectomy, 33/65 patients had lymph node metastasis and in patients with tumor size ≤2 cm, 55% had lymph node metastasis. Tumor in the head and BMI ≥25 kg/m(2) were independent risk factors for complications after enucleation. During follow-up, incidence of exocrine and endocrine insufficiency was significant higher after pancreatoduodenectomy (resp. 55 and 19%) compared to the tumor enucleation and distal pancreatectomy (resp. 5 and 7% vs. 8 and 13%). After tumor enucleation 19% developed recurrent disease.

Conclusion: Since the complication rate, need for re-interventions and readmissions were comparable for all resections, tumor enucleation may be regarded as high risk. Appropriate operation should be based on tumor size, location, and functional status of the pNET.

Figures

Fig. 1
Fig. 1
In-hospital stay in patients with complications for each operation separately. • outlier patients
Fig. 2
Fig. 2
Distribution between pathology, operation, and tumor type after surgical resection in patients with pancreatic neuroendocrine tumor

References

    1. Jensen RT, Cadiot G, Brandi ML, et al. ENETS consensus guidelines for the management of patients with digestive neuroendocrine neoplasms: functional pancreatic endocrine tumor syndromes. Neuroendocrinology. 2012;95:98–119. doi: 10.1159/000335591.
    1. Falconi M, Bartsch DK, Eriksson B, et al. ENETS consensus guidelines for the management of patients with digestive neuroendocrine neoplasms of the digestive system: well-differentiated pancreatic non-functioning tumors. Neuroendocrinology. 2012;95:120–134. doi: 10.1159/000335587.
    1. Siegel R, Naishadham D, Jemal A. Cancer statistics 2012. CA Cancer J Clin. 2012;62:10–29. doi: 10.3322/caac.20138.
    1. Wente MN, Bassi C, Dervenis C, et al. Delayed gastric emptying (DGE) after pancreatic surgery: a suggested definition by the International Study Group of Pancreatic Surgery (ISGPS) Surgery. 2007;142:761–768. doi: 10.1016/j.surg.2007.05.005.
    1. Bassi C, Dervenis C, Butturini G. Postoperative pancreatic fistula: an international study group (ISGPF) definition. Surgery. 2005;138:8–13. doi: 10.1016/j.surg.2005.05.001.
    1. Welsch T, Eisele H, Zschäbitz S, et al. Critical appraisal of the International Study Group of Pancreatic Surgery (ISGPS) consensus definition of postoperative hemorrhage after pancreatoduodenectomy. Langenbecks Arch Surg. 2011;396:783–791. doi: 10.1007/s00423-011-0811-x.
    1. Clavien PA, Barkun J, de Oliveira ML, et al. The Clavien–Dindo classification of surgical complications: five-year experience. Ann Surg. 2009;250:187–196. doi: 10.1097/SLA.0b013e3181b13ca2.
    1. Fendrich V, Merz MK, Waldmann J, et al. Neuroendocrine pancreatic tumors are risk factors for pancreatic fistula after pancreatic surgery. Dig Surg. 2011;28:263–269. doi: 10.1159/000328667.
    1. Bramhall SR, Stamp GW, Dunn J, et al. Expression of collagenase (MMP2), stromelysin (MMP3) and tissue inhibitor of the metalloproteinases (TIMP1) in pancreatic and ampullary disease. Br J Cancer. 1996;73:972–978. doi: 10.1038/bjc.1996.190.
    1. Kim WS, Choi DW, Choi SH, et al. Clinical validation of the ISGPF classification and the risk factors of pancreatic fistula formation following duct-to-mucosa pancreaticojejunostomy by one surgeon at a single center. J Gastrointest Surg. 2011;15:2187–2192. doi: 10.1007/s11605-011-1726-0.
    1. Yang Y-M, Tian X-D, Zhuang Y, et al. Risk factors of pancreatic leakage after pancreaticoduodenectomy. World J Gastroenterol. 2005;11:2456–2461. doi: 10.3748/wjg.v11.i16.2456.
    1. Okabayashi T, Kobayashi M, Nishimori I, et al. Risk factors, predictors and prevention of pancreatic fistula formation after pancreatoduodenectomy. J Hepatobiliary Pancreat Surg. 2007;14:557–563. doi: 10.1007/s00534-007-1242-5.
    1. Pratt WB, Callery MP, Vollmer CM. Risk prediction for development of pancreatic fistula using the ISGPF classification scheme. World J Surg. 2008;32:419–428. doi: 10.1007/s00268-007-9388-5.
    1. Fendrich F, Waldmann J, Bartsch D, Langer P. Surgical management of pancreatic endocrine tumors. Nat Rev Clin Oncol. 2009;6:419–428. doi: 10.1038/nrclinonc.2009.82.
    1. Inchauste SM, Lanier BJ, Libutti SK, et al. Rate of clinically significant postoperative pancreatic fistula in pancreatic neuroendocrine tumors. World J Surg. 2012;36:1517–1526. doi: 10.1007/s00268-012-1598-9.
    1. Crippa S, Zerbi A, Boninsegna L, et al. Surgical management of insulinomas. Arch Surg. 2012;147:261–266. doi: 10.1001/archsurg.2011.1843.
    1. Pitt SC, Pitt HA, Baker MS, et al. Small pancreatic and periampullary neuroendocrine tumors: resect or enucleate? J Gastrointest Surg. 2009;13:1692–1698. doi: 10.1007/s11605-009-0946-z.
    1. Hackert T, Hinz U, Fritz S, et al. Enucleation in pancreatic surgery: indications, technique, and outcome compared to standard pancreatic resections. Langenbeck’s Arch Surg. 2011;396:1197–1203. doi: 10.1007/s00423-011-0801-z.
    1. Gouma DJ, van Dijkum EJMN, Obertop H. Pancreatic cancer: matters for debate. The standard diagnostic work-up and surgical treatment of pancreatic head tumours. Eur J Surg Oncol. 2000;25:113–123. doi: 10.1053/ejso.1998.0612.
    1. Tran KTC, Smeenk HG, van Eijck CHJ, et al. Pylorus preserving pancreaticoduodenectomy versus standard Whipple procedure. Ann Surg. 2004;240:738–745. doi: 10.1097/01.sla.0000143248.71964.29.
    1. Eshuis WJ, Tol JAMG, Nio CY, et al. Leakage of the gastroenteric anastomosis after pancreatoduodenectomy. Surgery. 2014;156:75–82. doi: 10.1016/j.surg.2014.03.044.
    1. Warshaw AL. Distal pancreatectomy with preservation of the spleen. J Hepatobiliary Pancreat Sci. 2010;17:808–812. doi: 10.1007/s00534-009-0226-z.
    1. Crippa S, Bassi C, Warshaw AL, et al. Middle pancreatectomy: indications, short- and long-term operative outcomes. Ann Surg. 2007;246:69–76. doi: 10.1097/01.sla.0000262790.51512.57.
    1. Warshaw AL, Rattner DW, Fernández-del Castillo CZK. Middle segment pancreatectomy. Arch Surg. 2014;133:327–331.
    1. Kam BLR, Teunissen JJM, Krenning EP, et al. Lutetium-labelled peptides for therapy of neuroendocrine tumours. Eur J Nucl Med Mol Imaging. 2012;39(Suppl 1):S103–S112. doi: 10.1007/s00259-011-2039-y.
    1. Koti RS, Gurusamy KS, Fusai G, Davidson BR. Meta-analysis of randomized controlled trials on the effectiveness of somatostatin analogues for pancreatic surgery: a Cochrane review. HPB. 2010;12:155–165. doi: 10.1111/j.1477-2574.2010.00157.x.
    1. Berger AC, Howard TJ, Kennedy EP, et al. Does type of pancreaticojejunostomy after pancreaticoduodenectomy decrease rate of pancreatic fistula? A randomized, prospective, dual-institution trial. J Am Coll Surg. 2009;208:738–749. doi: 10.1016/j.jamcollsurg.2008.12.031.
    1. El Nakeeb A, Salah T, Sultan A, et al. Pancreatic anastomotic leakage after pancreaticoduodenectomy. risk factors, clinical predictors, and management (single center experience) World J Surg. 2013;37:1405–1418. doi: 10.1007/s00268-013-1998-5.
    1. Visser A, Ubbink DT, van Wijngaarden KS, et al. Quality of care and analysis of surgical complications. Dig Surg. 2012;29:391–399. doi: 10.1159/000344007.
    1. Bosman F, Carneiro F, Hruban R, Theise N. WHO classification of tumours of the digestive system. 4. Lyon: IARC WHO Classification of Tumours; 2010. p. 417.
    1. Van der Gaag N, Verhaar A, Haverkort E, et al. Chylous ascites after pancreaticoduodenectomy: introduction of a grading system. J Am Coll Surg. 2008;207:751–757. doi: 10.1016/j.jamcollsurg.2008.07.007.
    1. Tablan OC, Anderson LJ, Besser R, et al. Guidelines for preventing health-care-associated pneumonia. MMWR Recomm Rep. 2004;53(RR-3):1–36.
    1. Mangram AJ, Horan TC, Pearson ML, et al. Guideline for prevention of surgical site infection, 1999. Am J Infect Control. 1999;27:97–134. doi: 10.1016/S0196-6553(99)70088-X.
    1. Centers for Disease Control and Prevention (CDC) CDC/NHSN surveillance definitions for specific types of infections. Atlanta: CDC; 2014. pp. 1–24.
    1. Stephenson TJ, Cross SS, Chetty R. Standards and datasets for reporting cancers Dataset for neuroendocrine tumours of the gastrointestinal tract including pancreas (3rd edition) R Coll Pathol. 2013;6:1–40.
    1. Van der Heijden G, Donders R, Stijnen T, Moons K. Imputation of missing values is superior to complete case analysis and the missing-indicator method in multivariable diagnostic research: a clinical example. J Clin Epidemiol. 2006;59:1102–1109. doi: 10.1016/j.jclinepi.2006.01.015.
    1. Cherif R, Gaujoux S, Couvelard A, et al. Parenchyma-sparing resections for pancreatic neuroendocrine tumors. J Gastrointest Surg. 2012;16:2045–2055. doi: 10.1007/s11605-012-2002-7.
    1. Falconi M, Zerbi A, Crippa S, et al. Parenchyma-preserving resections for small nonfunctioning pancreatic endocrine tumors. Ann Surg Oncol. 2010;17:1621–1627. doi: 10.1245/s10434-010-0949-8.
    1. Stauffer J, Rosales-Velderrain A, Goldberg R, et al. Comparison of open with laparoscopic distal pancreatectomy: a single institution’s transition over a 7-year period. HPB. 2013;15:149–155. doi: 10.1111/j.1477-2574.2012.00603.x.
    1. Drymousis P, Raptis D, Spalding D, et al. Laparoscopic versus open pancreas resection for pancreatic neuroendocrine tumours: a systematic review and meta-analysis. HPB. 2014;16:397–406. doi: 10.1111/hpb.12162.
    1. Gallagher TK, McErlean S, O’Farrell A, et al. Incidence and risk factors of delirium in patients post pancreaticoduodenectomy. HPB. 2014;16:864–869. doi: 10.1111/hpb.12266.
    1. Merdrignac A, Sulpice L, Rayar M, et al. Pancreatic head cancer in patients with chronic pancreatitis. Hepatobiliary Pancreat Dis Int. 2014;13:192–197. doi: 10.1016/S1499-3872(14)60030-8.
    1. Fischer L, Bergmann F, Schimmack S, et al. (2014) Outcome of surgery for pancreatic neuroendocrine neoplasms. Br J Surg 1405–1412
    1. McPhee JT, Hill JS, Whalen GF, et al. Perioperative mortality for pancreatectomy: a national perspective. Ann Surg. 2007;246:246–253. doi: 10.1097/01.sla.0000259993.17350.3a.
    1. Samra JS, Bachmann RA, Choi J, et al. One hundred and seventy-eight consecutive pancreatoduodenectomies without mortality: role of the multidisciplinary approach. Hepatobiliary Pancreat Dis Int. 2011;10:415–421. doi: 10.1016/S1499-3872(11)60070-2.
    1. Butturini G, Marcucci S, Molinari E, et al. Complications after pancreaticoduodenectomy: the problem of current definitions. J Hepatobiliary Pancreat Surg. 2006;13:207–211. doi: 10.1007/s00534-005-1035-7.
    1. De Wilde RF, Besselink MGH, van der Tweel I, et al. Impact of nationwide centralization of pancreaticoduodenectomy on hospital mortality. Br J Surg. 2012;99:404–410. doi: 10.1002/bjs.8664.
    1. Falconi M, Mantovani W, Crippa S, et al. Pancreatic insufficiency after different resections for benign tumours. Br J Surg. 2008;95:85–91. doi: 10.1002/bjs.5652.
    1. Cauley CE, Pitt HA, Ziegler KM, et al. Pancreatic enucleation: improved outcomes compared to resection. J Gastrointest Surg. 2012;16:1347–1353. doi: 10.1007/s11605-012-1893-7.
    1. Buchler MW, Friess H, Wagner M, et al. Pancreatic fistula after pancreatic head resection. Br J Surg. 2000;87:883–889. doi: 10.1046/j.1365-2168.2000.01465.x.
    1. Kazanjian KK, Hines OJ, Eibl G, Reber HA. Management of pancreatic fistulas after pancreaticoduodenectomy. Arch Surg. 2013;140:849–855. doi: 10.1001/archsurg.140.9.849.
    1. Brient C, Regenet N, Sulpice L, et al. Risk factors for postoperative pancreatic fistulization subsequent to enucleation. J Gastrointest Surg. 2012;16:1883–1887. doi: 10.1007/s11605-012-1971-x.
    1. Heeger K, Falconi M, Partelli S, et al. Increased rate of clinically relevant pancreatic fistula after deep enucleation of small pancreatic tumors. Langenbeck’s Arch Surg. 2014;399:315–321. doi: 10.1007/s00423-014-1171-0.
    1. Iannitti D, Coburn N, Somberg J, et al. Use of the round ligament of the liver to decrease pancreatic fistulas: a novel technique. J Am Coll Surg. 2006;203:857–864. doi: 10.1016/j.jamcollsurg.2006.08.021.
    1. Hackert T, Lozanovski VJ, Werner J, et al. Teres hepatis ligament flap plasty to prevent pancreatic fistula after tumor enucleation. J Am Coll Surg. 2013;217:e29–e34. doi: 10.1016/j.jamcollsurg.2013.06.014.
    1. Shimura T, Suehiro T, Suzuki H, et al. Preoperative endoscopic pancreatic stenting for prophylaxis of pancreatic duct disruption during extirpation of a pancreatic head tumor. Am J Surg. 2007;194:553–555. doi: 10.1016/j.amjsurg.2006.11.043.
    1. Abe N, Sugiyama M, Suzuki Y, et al. Preoperative endoscopic pancreatic stenting for prophylaxis of pancreatic fistula development after distal pancreatectomy. Am J Surg. 2006;191:198–200. doi: 10.1016/j.amjsurg.2005.07.036.
    1. Zhou Y, Zhou Q, Li Z, Chen R. Internal pancreatic duct stent does not decrease pancreatic fistula rate after pancreatic resection: a meta-analysis. Am J Surg. 2013;205:718–725. doi: 10.1016/j.amjsurg.2012.07.039.
    1. De Rooij T, Jilesen AP, Boerma D, et al. A nationwide comparison of laparoscopic and open distal pancreatectomy for benign and malignant disease. J Am Coll Surg. 2015;220:263–270. doi: 10.1016/j.jamcollsurg.2014.11.010.
    1. Verbeke C, Menon K. Redefining resection margin status in pancreatic cancer. HPB. 2009;11:282–289. doi: 10.1111/j.1477-2574.2009.00055.x.

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