Insulinoma Guidelines

Updated: Oct 03, 2017
  • Author: Zonera Ashraf Ali, MBBS; Chief Editor: Neetu Radhakrishnan, MD  more...
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Guidelines

Guidelines Summary

Guidelines contributor:  Evan S Ong, MD, MS Assistant Professor of Surgery, Section of Surgical Oncology, University of Arizona College of Medicine

The following organizations have issued clinical guidelines for the management of gastroenteropancreatic neuroendocrine tumors (GEP-NETs):

  • National Comprehensive Cancer Network (NCCN)
  • North American Neuroendocrine Tumor Society (NANETS)
  • European Neuroendocrine Tumor Society (ENETS)
  • European Society for Medical Oncology (ESM0)
  • UK and Ireland Neuroendocrine Tumour Society (UKI NETS)

Grading and Staging

Grading schemes for neuroendocrine tumors (NETs) use mitotic count; the level of the nuclear protein Ki-67, which is associated with cellular proliferation; and assessment of necrosis. The World Health Organization (WHO) and the European Neuroendocrine Tumor Society (ENETS)  both incorporate mitotic count and Ki-67 proliferation for the classification of gastroenteropancreatic NETs (GEP-NETs). [46, 47, 48]

Tumors fall into one of the following three grades:

  • G1: well differentiated, low grade
  • G2: well differentiated, intermediate grade
  • G3: poorly differentiated, high grade

The National Comprehensive Cancer Network (NCCN) recommends that tumor differentiation, mitotic rate, and Ki-67 rate be included in the pathology report and that the specific classification and grading scheme be noted to avoid confusion. Clinicians are advised to view histologic grade as a general guide and use clinical judgment to make treatment decisions, particularly in cases of discordance between differentiation and Ki-67 proliferation results. [49]

NCCN guidelines recommend staging according to the 7th edition of the American Joint Committee on Cancer's AJCC Cancer Staging Manual. [50]

For staging of GEP-NETs, the European Society for Medical Oncology (ESMO) guidelines, updated in 2012, utilize the tumor-node-metastasis (TNM) classification created by the ENETS and the 2010 WHO grading system. [51]

In 2012, the UK and Ireland Neuroendocrine Tumour Society (UKI NETS) released updated guidelines for the management of GEP-NETs. Recommendations for grading and staging are as follows [52] :

  • For grading: WHO 2010 grading system
  • For staging: 7 th edition of the AJCC Cancer Staging Manual
  • Also stage NETs of the stomach, pancreas and appendix with the ENETS site-specific T-staging system
  • The TNM classification used should be specified
  • Underlying features of the T-stage classification (eg, tumor size, extent of invasion) should be documented to allow for translation between different classification systems

In 2013, the North American Neuroendocrine Tumor Society (NANETS) concluded that while the criteria differ among the various classification systems, the underlying data are similar and pathology reports should include notation of the systems and parameters used to assign the grade and stage. [53]

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Treatment

Treatment for locoregional disease

National Comprehensive Cancer Network (NCCN) guidelines recommend resection as the primary treatment for most localized pancreatic neuroendocrine tumors (NETs). Exceptions include patients with life-limiting comorbidities or high surgical risk. In addition, observation may be appropriate for incidentally discovered tumors <1 cm, depending on the site. [49]

Prior to surgery, NCCN recommends that symptoms of hormonal excess be treated with octreotide or lanreotide; however, such treatment is contraindicated in patients with insulinoma because of the potential for fatal complications. Specific recommendations vary by tumor subtype.Cholecystectomy is recommended during surgical resection if treatment with octreotide or lanreotide is planned, due to the increased rate of biliary problems associated with long-term use of these agents. [49]

Additional NCCN recommendations for insulinoma treatment include the following [49] :

  • Stabilize glucose levels with diet and/or diazoxide; everolimus may be considered
  • Primary treatment is enucleation; consider laparoscopic resection for solitary tumors
  • Deeper or invasive tumors or those with proximity to the main pancreatic duct require pancreatoduodenectomy if located in the head and laparoscopic distal pancreatectomy if in a distal location, with preservation of the spleen for smaller tumors
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