The NANETS Consensus Guidelines for the Diagnosis and Management of Gastrointestinal Neuroendocrine Tumors (NETs)

Abstract

Neuroendocrine tumors (NETs) of the distal colon and rectum are also known as hindgut carcinoids based on their common embryologic derivation. Their annual incidence in the United States is rising, primarily as a result of increased incidental detection. Symptoms of rectal NETs include hematochezia, pain, and change in bowel habits. Most rectal NETs are small, submucosal in location, and associated with a very low malignant potential. Tumors larger than 2 cm or those invading the muscularis propria are associated with a significantly higher risk of metastatic spread. Colonic NETs proximal to the rectum are rarer and tend to behave more aggressively. The incidence of rectal NETs in African Americans and Asians is substantially higher than in Caucasians. Colorectal NETs are generally not associated with a hormonal syndrome such as flushing or diarrhea. A multidisciplinary approach is recommended in diagnosing and managing hindgut NETs.

A 92-gene cancer classifier predicts the site of origin for neuroendocrine tumors

“…Clinical situations that may cause diagnostic subtyping challenges include: multiple possible primary tumors (in the context of Multiple Endocrine Neoplasia syndromes), widespread metastatic disease, lack of tumor-expressing site-specific serological markers and small biopsies with insufficient clinical data. The site of origin for neuroendocrine carcinoma has become increasingly important for grading/staging purposes, 1,2 for new clinical management guidelines, [3][4][5][6][7] and for primary site-specific targeted therapy. [8][9][10] When a primary site cannot be identified, tumors generally are treated according to the presumed aggressiveness of the tumor, as determined by a combination of the tumor grade [11][12][13][14] and available clinical and radiographic information about tumor metabolism.…”

Hindgut Neuroendocrine Neoplasia

“…Tumors between 1 and 2 cms have been traditionally treated by local excision, however recent evidence suggest that tumor size greater than 1 cm along with lympho-vascular invasion and involvement of the muscularis propria is associated with tumor metastases and recurrence. [13,14] Consideration for rectal resection with TME should therefore be given for tumors between 1-2 cms, particularly if other adverse features [15] For left colon WDNET, as these tumors are rare, there is little evidence to identify patients that are LN negative and therefore could be excised endoscopically. Again if the tumor can be removed by polypectomy or EMR with negative margins and is less than 1 cm this would seem a reasonable treatment option.…”

“…If the margins are positive, the tumor is greater than 1 cm or there are high risk features such as intermediate grade NET or LVI, a standard left hemi-colectomy should be performed according to oncologic principles. [15] Patients with hingut WDNET rarely present distant metastatic disease with series reporting the incidence ranging between 5 and 10 %. (Table 2) The size of the tumor is the greatest factor associated with metastatic disease.…”

“…The most common site of metastatic disease is the liver with other sites including the lung and retroperitoneal lymph nodes. [15] Surgical resection can be considered for sites of respectable disease however recurrence rates are high. [15] The mainstay of systemic treatment is somatostatin analogues such as octreotide both for limiting progression of disease and in the management of the symptoms of carcinoid syndrome.…”

Erratum: Calculation of the Ki67 index in pancreatic neuroendocrine tumors: a comparative analysis of four counting methodologies

“…8 Some members of the European Neuroendocrine Tumor Society consider the 'eye-balling' method of counting adequate, and other sources such as North American Neuroendocrine Tumor Society have also endorsed 'eye-balling' in their guidelines. 9,10 However, recent studies have questioned the accuracy and reproducibility of this method, especially for tumors with equivocal 'gray zone' grades. 11,12 In this study, we investigated the reproducibility, applicability, and practicality of the four most widely used methods for Ki67 index calculation.…”