Introduction Neuroendocrine tumors (NETs) frequently metastasize to the liver. Surgical debulking offers symptomatic relief and improved survival. However, the frequent presence of multifocal, bilobar disease and high recurrence rates introduce doubt regarding their optimal management. Parenchyma-sparing debulking (PSD) procedures (ablation, enucleation, wedge resections) may offer similar survival improvements as resection, while minimizing morbidity and preserving functional liver tissue. Methods Clinicopathologic variables from 228 patients with small bowel (SBNETs) or pancreatic NETs (PNETs) managed surgically at one institution were collected. Liver-directed surgery (LDS) was carried out when significant debulking was deemed feasible. Survival was assessed using the Kaplan-Meier method. Results 108 PNET and SBNET patients underwent LDS with primarily PSD procedures. Nearly two-thirds of patients achieved 70% cytoreduction and 84% had concurrent resection of their primary. The median number of lesions treated was 6 (range 1–36). There were no 30-day operative mortalities. The 30-day major complication rate was 13.0%. Patients that achieved 70% cytoreduction enjoyed improved progression free (median 3.2 years) and overall survival (median not reached). Conclusion PSD procedures are safe and can achieve significant cytoreduction, which is associated with improved survival. Lowering the debulking target threshold to 70% may benefit NET patients by increasing eligibility for cytoreduction.

Neuroendocrine tumors are a heterogeneous group of neoplasms that are best worked up and managed using a variety of clinical and imaging studies. They are often diagnosed after they have already metastasized, though this does not necessarily preclude an attempt at curative surgical treatment or surgical debulking. Tumor burden assessment often requires use of multiple imaging modalities including computed tomography, magnetic resonance imaging and ultrasound. Somatostatin receptor-based imaging is also of great utility in looking for primaries and determining the extent of metastatic disease. This paper will review the most common imaging modalities used in the diagnosis and treatment of neuroendocrine tumors.

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.

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.

Medullary thyroid cancer (MTC) is an aggressive form of thyroid cancer, which occurs in both heritable and sporadic forms. Discovery that mutations in the RET protooncogene predispose to familial cases of this disease has allowed for presymptomatic identification of gene carriers and prophylactic surgery to improve the prognosis of these patients. A significant number of patients with the sporadic type of MTC and even with familial disease, still present with nodal or distant metastases, making surgical cure difficult. Over the past several decades, many different types of therapy for metastatic disease have been attempted, with limited success. Improved understanding of the molecular defects and pathways involved in both familial and sporadic MTC has resulted in new hope for these patients with the development of drugs targeting the specific alterations responsible. This new era of targeted therapy with kinase inhibitors represents a significant step forward from previous trials of chemotherapy, radiotherapy, and hormonal therapy. Although much progress has been made, additional agents and strategies are needed to achieve durable, long-term responses in patients with metastatic MTC. This article reviews the history and results of medical management for metastatic MTC from the early 1970s up until the present day.