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 111 In-diethylenetriaminepentaacetic acidoctreotide, scintigraphy with 123 I-metaiodobenzylguanidine (MIBG), and 18 F-FDG PET. Methods: Ninety-six prospectively enrolled patients with neuroendocrine tumors underwent SRS, 123 I-MIBG scintigraphy, and 18 F-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, 123 I-MIBG scintigraphy, and 18 F-FDG PET was 89%, 52%, and 58%, respectively. Of the 11 SRS-negative patients, 7 were 18 F-FDG PET-positive, of which 3 were also 123 I-MIBG scintigraphypositive, giving a combined overall sensitivity of 96%. SRS also exceeded 123 I-MIBG scintigraphy and 18 F-FDG PET based on the number of lesions detected (393, 185, and 225, respectively) and tumor subtypes. 123 I-MIBG scintigraphy was superior to 18 F-FDG PET for ileal neuroendocrine tumors, and 18 F-FDG PET was superior to 123 I-MIBG scintigraphy for pancreaticoduodenal neuroendocrine tumors. The sensitivity of 18 F-FDG PET (92%) exceeded that of both SRS (69%) and 123 I-MIBG scintigraphy (46%) for tumors with a proliferation index above 15%. Conclusion: The overall sensitivity of 123 I-MIBG scintigraphy and 18 F-FDG PET was low compared with SRS. However, for tumors with a high proliferation rate, 18 F-FDG PET had the highest sensitivity. The results indicate that, although SRS should still be the routine method, 18 F-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 a-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.Patients with diabetes are characterized not only by compromised insulin secretion and action but also by elevated plasma concentrations of the 29-amino acid peptide hormone glucagon, which hitherto has been considered a pancreas-derived hormone in humans (produced in and secreted from a-cells in the islet of Langerhans) (1). In patients with diabetes, plasma concentrations of glucagon are elevated in the fasting state and fail to decrease appropriately or even increase in response to an oral glucose tolerance test (OGTT) and show exaggerated increases in response to ingestion of a mixed meal (1,2). The elevated glucagon concentrations increase the hepatic glucose production and thereby contribute significantly to the fasting and postprandial hyperglycemia characterizing patients with diabetes. The etiology behind diabetic hyperglucagonemia is still controversial. Whereas oral intake of glucose elicits a hyperglucagonemic response, intravenous glucose administration causes suppression of plasma glucagon levels (3,4). A "lighter version" of this phenomenon has also been observed in healthy individuals after ingestion of larger oral glucose loads (4). Together, these findings led us to speculate that postprandial hyperglucagonemia could be gut derived and independent of the endocrine pancreas.The notion of extrapancreatic glucagon secretion in man has been debated for years, and several studies looking at glucagon responses after total pancreatectomy in animals (5-10) and man (11-24) have been published. Overall, these investigations have reported very conflicting

Background. Knowledge of the clinical efficacy in recurrent neuroendocrine carcinomas is sparse. Treatment with temozolomide alone or in combination with capecitabine and bevacizumab has recently shown promising results. Patients and Methods. Analysis of consecutive patients with neuroendocrine carcinomas (Ki-67 proliferation index >20%) and performance status 0–2 treated with temozolomide 200 mg/sqm orally days 1–5 every 28 days after at least one previous platin-containing chemotherapy regimen. Results. Twenty-eight eligible patients received a median of 3 courses. Sixteen patients were evaluable for response: Six achieved stable disease and ten progressed. The median survival for the 28 patients was 3.5 months. Survival in patients with tumors of pancreatic origin (n = 7) was 7.0 months versus 2.9 months in non-pancreatic origin (n = 21). Patients in PS 0-1 (n = 22) had a median survival of 4.5 months versus 1.1 months in patients in PS 2 (n = 6). Ki-67 index ≥50% was associated with a significantly shorter median survival than Ki-67 index <50% (2.7 months versus 10.9 months). The treatment was well tolerated. Conclusion. Temozolomide monotherapy has limited effect in treatment of recurrent neuroendocrine carcinomas. Second line treatment with temozolomide in combination with other compounds should be further investigated in patients in good performance with Ki-67 index <50%.

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.

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EUS-guided microbiopsy procedure was technically feasible, with a high diagnostic yield. Further prospective studies are needed to confirm these promising results.

Major gastrointestinal surgery is associated with immune suppression and a high risk of postoperative complications. The aim of this open, randomized controlled trial was to examine the effect of supplementary per oral immunonutrition (IN) seven days before surgery for pancreatic cancer (PC) on postoperative complications and length of hospital stay (LOS). Secondary outcomes were the changes in functional capability and body weight (BW). Consecutive patients referred for surgery for diagnosed or plausible PC were included. The patients in the intervention group received supplementary IN (Oral Impact®, Nestlé) to reach a goal of 1.5 g protein/kg BW. The control group continued their habitual diet. Complications and LOS were independently assessed by the surgical staff. Secondary outcomes were measured 10, 20, and 30 days postoperatively. Thirty-five patients were included, of whom 19 (54%) were allocated to the intervention group. The doses of IN ranged from 250 to 1000 ml per day and the median compliance was 100 (0-100%). Based on the principle of intention-to-treat, no significant differences were found between the groups. We conclude that the lack of effect could be due to the limited dosage of IN, and/or because only 40% of the patients were at nutritional risk.