Background Tumor grade is an important predictor of survival in gastroenteropancreatic (GEP) neuroendocrine tumors (NETs), as determined by Ki-67 expression and mitotic rate. NETs generally grow indolently, but some cells may acquire traits facilitating metastasis. It is unclear how frequently metastases differ in grade from their primary tumors, and whether increasing grade in metastases affects prognosis. Methods Ki-67 immunohistochemistry was performed on resected GEPNET specimens and cases with results for both primary tumors and concurrent metastases were identified. Grade was determined using a modified WHO classification (Ki-67:G1= 0–2%; G2 >2–20%; G3 >20%). Results Ki-67 was performed on both the primary tumor and metastases in 103 patients. Tumor grade was higher in metastases from 25 (24%) patients, 24 increased from G1 to G2, and 1 from G2 to G3; 68 (66%) patients had no change in grade (42 G1 and 26 G2) and 10 (10%) decreased from G2 to G1. No clinicopathologic factors were predictive of higher grade in metastases. The 5-year PFS was 55 % for patients with stable grade vs. 8% with increased grade, while 5-year OS was 92% and 54%, respectively. The 5-year OS of patients who had stable grade with G1 and G2 primaries was 92% and 64%, respectively. Conclusions Nearly one-third of patients had metastases with a different grade than their primary, and when grade increased, both PFS and OS significantly decreased. Determining the grade in both the primary tumor and a metastasis is important for estimating prognosis and to help inform decisions regarding additional therapies.

Background: Cytoreductive surgery for neuroendocrine tumor liver metastases improves survival and symptomatic control. However, the feasibility of adequate cytoreduction in patients with many liver metastases remains uncertain. We compared patient outcomes based on the number of lesions treated to better define the efficacy of cytoreductive surgery for numerous neuroendocrine tumor liver metastases. Methods: Patients undergoing hepatic cytoreductive surgery for gastroenteropancreatic neuroendocrine tumors were identified in our institutional surgical neuroendocrine tumor database. Imaging studies were reviewed to determine the liver tumor burden and percent cytoreduced. Overall survival and progressionfree survival were compared, using the number of lesions treated, percent tumor debulked, and additional clinicopathologic characteristics. Results: A total of 188 hepatic cytoreductive procedures were identified and stratified into groups according to the number of metastases treated: 1–5, 6–10, and >10. Median overall survival and progressionfree survival were 89.4 and 22.5 months, respectively, and did not differ significantly between groups. Greater than 70% cytoreduction was associated with significantly better overall survival than <70% cytoreduction (134 months versus 38 months). Conclusion: In patients with gastroenteropancreatic neuroendocrine tumors and liver metastases, >70% cytoreduction led to improved overall survival and progression-free survival and was achieved reliably in patients undergoing debulking of > 10 lesions. These data support an aggressive approach to patients with numerous neuroendocrine tumor liver metastases to achieve >70% cytoreduction.

Objectives Many patients with small bowel neuroendocrine tumors (SBNETs) have multifocal tumors (MFTs), but the frequency of MFTs has varied widely across SBNET studies. It is also unclear whether patients with MFTs have more advanced disease or worse clinical course than those with unifocal SBNETs (UFTs). We set out to determine the frequency of multifocal and unifocal SBNETs, compare clinicopathologic factors, somatostatin receptor (SSTR2) expression, and survival. Methods Clinicopathologic variables from 179 patients with surgically managed SBNETs were collected. Statistical comparisons were made using Welch’s t-test, Wilcoxon test and Fisher’s exact test. Survival was assessed using the Kaplan-Meier method. SSTR2 expression was analyzed by qPC, and Ki-67 expression by immunohistochemistry. Results MFTs were found in 45% of patients with SBNETs. Clinicopathologic factors such as grade, TNM stage, presence of distant metastases, mean SSTR2 expression, success of imaging modalities, preoperative and postoperative hormone levels were not significantly different between multifocal and unifocal groups. Progression-free and overall survival were also not significantly affected by multifocality. Conclusions Clinicopathologic features and survival of patients with MFTs and UFTs are remarkably similar. Although the etiology of MFTs is unclear, patients with MFTs do not have a more aggressive clinical course than patients with unifocal SBNETs.

Background Patients with gastroenteropancreatic neuroendocrine tumors often present with metastases. Identification of the primary tumor is important for operative management, and therefore we sought to determine our success at identifying primary tumors with diagnostic testing and operative exploration. Methods A clinical neuroendocrine tumor database was reviewed to identify patients presenting with metastases and primary tumor in situ. Results of radiologic, endoscopic, and operative procedures were evaluated to determine which correctly identified the primary tumor. Results There were 197 patients presenting with metastases and unresected primaries, 134 who had an operation and 63 managed nonoperatively. Primaries were identified preoperatively in 168 (84%), at operative exploration in 7, and were not found in 22 patients. Computed tomography found 150/197 primary tumors, somatostatin-receptor scintigraphy 88/155, and endoscopy 43/107. The sensitivity of computed tomography surpassed scintigraphy (76% vs 57%, P < .01). The primary was removed in 130/134 (97%) patients, and hepatic debulking was performed in 67%. Median survival for operative patients with small bowel and pancreatic tumors was 145 and 71 months, respectively. Conclusion Imaging and endoscopy identified the primary tumor in most patients, and the majority of the others were found at exploration. Preoperative testing facilitated operative planning, allowing for resection of the primary and hepatic debulking in most patients.

SBNETs are frequently multifocal and most commonly located within 100 cm of the ICV. SBNETs are less prevalent proximally in the small bowel, which may result from anatomic differences in enterochromaffin cell density, hormonal factors, or environmental exposures in the distal SB.