Abstract
Background
Surgical resection is advocated for all stages of pancreatic neuroendocrine tumors (PNETs); whether small PNETs can be managed by observation alone is controversial.
Methods
The prognoses of patients with non-functional PNET managed by surgical resection or observation alone were retrospectively analyzed. In patients who had undergone resection, correlation of pathologically assessed tumor extension and grade with tumor size were evaluated.
Results
Nineteen patients with PNET of median tumor diameters of 12 mm (range 6–38 mm) were followed up by observation for 19–162 months. Increase of tumor size >20 % occurred in three patients, resulting in 5-year progression-free survival of 83 %, but no distant metastases occurred. Surgical resection was performed in 71 patients. Tumor size correlated with the incidence of lymph node or hepatic metastases, portal vein invasion, and Ki-67 index. None of the 18 patients with a tumor size ≤15 mm developed lymph node or distant metastases, and all these patients survived without recurrence for 5–283 months. The smallest tumor size with lymph node metastases was 19 mm. The 5-year recurrence-free survivals of patients with a tumor size ≤15 mm (100 %) was significantly better than patients with tumor sizes 16–20 mm (86 %), 21–30 mm (71 %), 31–50 mm (83 %), and >50 mm (48 %).
Conclusion
Because PNETs ≤15 mm in size have little risk of metastases or recurrence, careful observation with serial image studies is acceptable. Once the tumor size exceeds 15 mm, the risk of metastases and recurrence increases significantly.
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References
Fitzgerald TL, Hickner ZJ, Schmitz M, Kort EJ. Changing incidence of pancreatic neoplasms: a 16-year review of statewide tumor registry. Pancreas. 2008;37:134–38.
Kuo EJ, Salem RR. Population-level analysis of pancreatic neuroendocrine tumors 2 cm or less in dize. Ann Surg Oncol. 2013;20:2815–21.
Ferrone CR, Tang LH, Tomlinson J, et al. Determining prognosis in patients with pancreatic endocrine neoplasms: can the WHO classification system be simplified? J Clin Oncol. 2007;25:5609–15.
Nomura N, Fujii T, Kanazumi N, et al. Nonfunctioning neuroendocrine pancreatic tumors: our experience and management. J Hepatobiliary Pancreat Surg. 2009;16:639–47.
Haynes AB, Deshpande V, Ingkakul T, et al. Implications of incidentally discovered, nonfunctioning pancreatic endocrine tumors: short-term and long-term patient outcomes. Arch Surg. 2011;146:534–8.
Hamilton NA, Liu TC, Cavatiao A, et al. Ki-67 predicts disease recurrence and poor prognosis in pancreatic neuroendocrine neoplasms. Surgery. 2012;152:107–13.
Tsutsumi K, Ohtsuka T, Mori Y, et al. Analysis of lymph node metastasis in pancreatic neuroendocrine tumors (PNETs) based on the tumor size and hormonal production. J Gastroenterol. 2012;47:678–85.
Krampitz GW, Norton JA, Poultsides GA, Visser BC, Sun L, Jensen RT. Lymph nodes and survival in pancreatic neuroendocrine tumors. Arch Surg. 2012;147:820–7.
Kim MJ, Choi DW, Choi SH, et al. Surgical strategies for non-functioning pancreatic neuroendocrine tumours. Br J Surg. 2012;99:1562–8.
Norton JA, Kivlen M, Li M, Schneider D, Chuter T, Jensen RT. Morbidity and mortality of aggressive resection in patients with advanced neuroendocrine tumors. Arch Surg. 2003;138:859–66.
Schurr PG, Strate T, Rese K, et al. Aggressive surgery improves long-term survival in neuroendocrine pancreatic tumors: an institutional experience. Ann Surg. 2007;245:273–81.
Kleine M, Schrem H, Vondran FW, Krech T, Klempnauer J, Bektas H. Extended surgery for advanced pancreatic endocrine tumours. Br J Surg. 2012;99:88–94.
Cusati D, Zhang L, Harmsen WS, et al. Metastatic nonfunctioning pancreatic neuroendocrine carcinoma to liver: surgical treatment and outcomes. J Am Coll Surg. 2012;215:117–24; discussion 124–5.
Neuroendocrine tumors. Version 2. 2414. NCCN Clinical Practice Guidelines in Oncology. http://www.nccn.org/professionals/physician_gls/pdf/neuroendocrine.pdf. Accessed 11 Jan 2014.
Lee LC, Grant CS, Salomao DR, et al. Small, nonfunctioning, asymptomatic pancreatic neuroendocrine tumors (PNETs): role for nonoperative management. Surgery. 2012;152:965–74.
Gaujoux S, Partelli S, Maire F, et al. Observational study of natural history of small sporadic non-functioning pancreatic neuroendocrine tumors. J Clin Endocrinol Metab. 2013;98:4784–9.
Therasse P, Arbuck SG, Eisenhauer EA, et al. New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst. 2000;92:205–16.
Bosman FT, Cameiro F, Hruban RH, Theise N, editors. WHO classification of tumours. No. 3. WHO classification of tumours of the digestive system, 4th ed. Lyon: IARC; 2010.
Rindi G, Kloppel G, Alhman H, et al. TNM staging of foregut (neuro)endocrine tumors: a consensus proposal including a grading system. Virchows Archiv. 2006;449:395–401.
Bassi C, Dervenis C, Butturini G, et al. Postoperative pancreatic fistula: an international study group (ISGPF) definition. Surgery. 2005;138:8–13.
Casadei R, Ricci C, Pezzilli R, et al. Are there prognostic factors related to recurrence in pancreatic endocrine tumors? Pancreatology. 2010;10:33–8.
Boninsegna L, Panzuto F, Partelli S, et al. Malignant pancreatic neuroendocrine tumour: lymph node ratio and Ki67 are predictors of recurrence after curative resections. Eur J Cancer. 2012;48:1608–15.
Strosberg JR, Cheema A, Weber JM, et al. Relapse-free survival in patients with nonmetastatic, surgically resected pancreatic neuroendocrine tumors: an analysis of the AJCC and ENETS staging classifications. Ann Surg. 2012;256:321–5.
Ellison TA, Wolfgang CL, Shi C, et al. A single institution’s 26-year experience with nonfunctional pancreatic neuroendocrine tumors: a validation of current staging systems and a new prognostic nomogram. Ann Surg. 2014;259:204–12.
Marion Audibert A-M, Barel C, Gouysse G, et al. Low microvessel density is an unfavorable histoprognostic factor in pancreatic endocrine tumors. Gastroenterology. 2003;125:1094–104.
Takahashi Y, Akishima Fukasawa Y, Kobayashi N, et al. Prognostic value of tumor architecture, tumor-associated vascular characteristics, and expression of angiogenic molecules in pancreatic endocrine tumors. Clin Cancer Res. 2007;13:187–96.
Parekh JR, Wang SC, Bergsland EK, et al. Lymph node sampling rates and predictors of nodal metastasis in pancreatic neuroendocrine tumor resections: the UCSF experience with 149 patients. Pancreas. 2012;41:840–4.
Norton JA, Fraker DL, Alexander HR, Jensen RT. Value of surgery in patients with negative imaging and sporadic Zollinger-Ellison syndrome. Ann Surg. 2012;256:509–517.
King J, Kazanjian K, Matsumoto J, et al. Distal pancreatectomy: incidence of postoperative diabetes. J Gastrointest Surg. 2008;12:1548–53.
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;16:2212–9.
Bernstein J, Ustun B, Alomari A, et al. Performance of endoscopic ultrasound-guided fine needle aspiration in diagnosing pancreatic neuroendocrine tumors. CytoJournal. 2013;10:10.
Katanuma A, Maguchi H, Yane K, et al. Factors predictive of adverse events associated with endoscopic ultrasound-guided fine needle aspiration of pancreatic solid lesions. Dig Dis Sci. 2013;58:2093–99.
Acknowledgment
This work was supported by a Grant-in-Aid for Young Scientists (B) [#23791518] from the Ministry of Education, Culture, Sports, Science and Technology of Japan.
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Kishi, Y., Shimada, K., Nara, S. et al. Basing Treatment Strategy for Non-functional Pancreatic Neuroendocrine Tumors on Tumor Size. Ann Surg Oncol 21, 2882–2888 (2014). https://doi.org/10.1245/s10434-014-3701-y
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DOI: https://doi.org/10.1245/s10434-014-3701-y