Functional techniques are playing a pivotal role in the imaging of cancer today. Our aim was to compare, on a head-to-head basis, 3 functional imaging techniques in patients with histologically verified neuroendocrine tumors: somatostatin receptor scintigraphy (SRS) with ¹¹¹In-diethylenetriaminepentaacetic acid-octreotide, scintigraphy with ¹²³I-metaiodobenzylguanidine (MIBG), and ¹⁸F-FDG PET. Methods: Ninety-six prospectively enrolled patients with neuroendocrine tumors underwent SRS, ¹²³I-MIBG scintigraphy, and ¹⁸F-FDG PET on average within 40 d. The functional images were fused with low-dose CT scans for anatomic localization, and the imaging results were compared with the proliferation index as determined by Ki67. Results: The overall sensitivity of SRS, ¹²³I-MIBG scintigraphy, and ¹⁸F-FDG PET was 89%, 52%, and 58%, respectively. Of the 11 SRS-negative patients, 7 were ¹⁸F-FDG PET-positive, of which 3 were also ¹²³I-MIBG scintigraphy–positive, giving a combined overall sensitivity of 96%. SRS also exceeded ¹²³I-MIBG scintigraphy and ¹⁸F-FDG PET based on the number of lesions detected (393, 185, and 225, respectively) and tumor subtypes. ¹²³I-MIBG scintigraphy was superior to ¹⁸F-FDG PET for ileal neuroendocrine tumors, and ¹⁸F-FDG PET was superior to ¹²³I-MIBG scintigraphy for pancreaticoduodenal neuroendocrine tumors. The sensitivity of ¹⁸F-FDG PET (92%) exceeded that of both SRS (69%) and ¹²³I-MIBG scintigraphy (46%) for tumors with a proliferation index above 15%. Conclusion: The overall sensitivity of ¹²³I-MIBG scintigraphy and ¹⁸F-FDG PET was low compared with SRS. However, for tumors with a high proliferation rate, ¹⁸F-FDG PET had the highest sensitivity. The results indicate that, although SRS should still be the routine method, ¹⁸F-FDG PET provides complementary diagnostic information and is of value for neuroendocrine tumor patients with negative SRS findings or a high proliferation index.

Glucagon is believed to be a pancreas-specific hormone, and hyperglucagonemia has been shown to contribute significantly to the hyperglycemic state of patients with diabetes. This hyperglucagonemia has been thought to arise from α-cell insensitivity to suppressive effects of glucose and insulin combined with reduced insulin secretion. We hypothesized that postabsorptive hyperglucagonemia represents a gut-dependent phenomenon and subjected 10 totally pancreatectomized patients and 10 healthy control subjects to a 75-g oral glucose tolerance test and a corresponding isoglycemic intravenous glucose infusion. We applied novel analytical methods of plasma glucagon (sandwich ELISA and mass spectrometry–based proteomics) and show that 29–amino acid glucagon circulates in patients without a pancreas and that glucose stimulation of the gastrointestinal tract elicits significant hyperglucagonemia in these patients. These findings emphasize the existence of extrapancreatic glucagon (perhaps originating from the gut) in man and suggest that it may play a role in diabetes secondary to total pancreatectomy.

Aim: Limited therapeutic options have highlighted the demand for new treatment modalities for patients with advanced neuroendocrine tumors (NET). Promising results of initial studies have warranted the implementation of peptide receptor radionuclide therapy (PRRT) in clinical practice. However, this treatment option still needs clinical evaluation. Methods: In this study, we evaluated the PRRT treatment response of 69 Danish patients with NET mainly originating from the gastroenteropancreatic system. Fifty-six patients (81%) were referred for PRRT to the Department of Nuclear Medicine, University Hospital Basel, Switzerland, between 2004 and 2008 due to progression assessed by the referring physicians. However, when retrospectively evaluated, only 42 of the 69 patients (61%) had progression according to RECIST (Response Evaluation Criteria in Solid Tumors). Most patients were treated with 90Y-DOTATOC. Results: Based on RECIST, a complete response was observed in 5 patients (7.4%), a partial response in 11 patients (16.2%) and stable disease in 42 patients (61.8%). Progressive disease after completed therapy was observed in 10 patients (14.7%). The median progression-free survival was 29 months (95% CI: 22–36 months). Pancreatic NET seemed to respond better to PRRT than small intestinal carcinoid tumors (p = 0.03). The overall frequency of serious adverse events was low. Conclusion: Implementation of PRRT in clinical routine has provided a valuable new therapeutic option for the treatment of advanced NET. We suggest that PRRT may advance from second- or third-line to first- or second-line therapy in inoperable/unresectable NET patients.

Background: The World Health Organization (WHO) and the American Joint Cancer Committee (AJCC) modified the grading of pancreatic neuroendocrine neoplasms from a three-tier (WHO-AJCC 2010) to a four-tier system by introducing the novel category of NET G3 (WHO-AJCC 2017). Objectives: This study aims at validating the WHO-AJCC 2017 and identifying the most effective grading system. Method: A total of 2,102 patients were enrolled; entry criteria were: (i) patient underwent surgery; (ii) at least 2 years of follow-up; (iii) observation time up to 2015. Data from 34 variables were collected; grading was assessed and compared for efficacy by statistical means including Kaplan-Meier method, Cox regression analysis, Harrell’s C statistics, and Royston’s explained variation in univariable and multivariable analyses. Results: In descriptive analysis, the two grading systems demonstrated statistically significant differences for the major category sex but not for age groups. In Cox regression analysis, both grading systems showed statistically significant differences between grades for OS and EFS; however, no statistically significant difference was observed between the two G3 classes of WHO-AJCC 2017. In multivariable analysis for the two models fitted to compare efficacy, the two grading systems performed equally well with substantially similar optimal discrimination and well-explained variation for both OS and EFS. The WHO-AJCC 2017 grading system retained statistically significant difference between the two G3 classes for OS but not for EFS. Conclusions: The WHO-AJCC 2017 grading system is at least equally performing as the WHO-AJCC 2010 but allows the successful identification of the most aggressive PanNET subgroup. Grading is confirmed as probably the most powerful tool for predicting patient survival.

The aim of this study was to validate previously described diagnostic and prognostic microRNA expression profiles in tissue samples from patients with pancreatic cancer and other periampullary cancers. Expression of 46 selected microRNAs was studied in formalin-fixed paraffin-embedded tissue from patients with resected pancreatic ductal adenocarcinoma (n = 165), ampullary cancer (n=59), duodenal cancer (n = 6), distal common bile duct cancer (n = 21), and gastric cancer (n = 20); chronic pancreatitis (n = 39); and normal pancreas (n = 35). The microRNAs were analyzed by PCR using the Fluidigm platform. Twenty-two microRNAs were significantly differently expressed in patients with pancreatic cancer when compared to healthy controls and chronic pancreatitis patients; 17 miRNAs were upregulated (miR-21-5p, −23a-3p, −31-5p, −34c-5p, −93-3p, −135b-3p, −155-5p, −186-5p, −196b-5p, −203, −205-5p, −210, −222-3p, −451, −492, −614, and miR-622) and 5 were downregulated (miR-122-5p, −130b-3p, −216b, −217, and miR-375). MicroRNAs were grouped into diagnostic indices of varying complexity. Ten microRNAs associated with prognosis were identified (let-7 g, miR-29a-5p, −34a-5p, −125a-3p, −146a-5p, −187, −205-5p, −212-3p, −222-5p, and miR-450b-5p). Prognostic indices based on differences in expression of 2 different microRNAs were constructed for pancreatic and ampullary cancer combined and separately (30, 5, and 21 indices). The study confirms that pancreatic cancer tissue has a microRNA expression profile that is different from that of other periampullary cancers, chronic pancreatitis, and normal pancreas. We identified prognostic microRNAs and microRNA indices that were associated with shorter overall survival in patients with radically resected pancreatic cancer.