111 In-diethylenetriaminepentaacetic acid (DTPA)-octreotide scintigraphy is currently the nuclear medicine imaging modality of choice for identifying neuroendocrine tumors. However, there are cohorts of patients in whom scintigraphy findings are negative or equivocal. We evaluated the role of 68 Ga-DOTATATE PET in a selected group of patients with negative or weakly positive findings on 111 In-DTPA-octreotide scintigraphy to determine whether 68 Ga-DOTATATE PET is able to detect additional disease and, if so, whether patient management is altered. Methods: Fifty-one patients with a histologically confirmed diagnosis of neuroendocrine tumors were included. Of the 51 patients, 35 who were negative and 16 equivocal for uptake on 111 In-DTPA-octreotide scintigraphy underwent 68 Ga-DOTATATE PET. Findings were compared using a region-by-region analysis. All findings were verified with CT or MRI. After 68 Ga-DOTATATE PET, all cases were reviewed to determine whether the 68 Ga-DOTATATE PET findings resulted in any alteration in management, in terms of suitability for peptide receptor therapy, somatostatin analogs, and surgery. Results: Of the 51 patients, 47 had evidence of disease on cross-sectional imaging or biochemically. 68 Ga-DOTATATE PET was positive in 41 of these 47 patients (87.2%). No falsepositive lesions were identified. 68 Ga-DOTATATE PET detected 168 of the 226 lesions (74.3%) that were identified with crosssectional imaging. 68 Ga-DOTATATE PET identified significantly more lesions than 111 In-DTPA-octreotide scintigraphy (P , 0.001). There was no correlation between 68 Ga-DOTATATE uptake and histologic grade of neuroendocrine tumors. 68 Ga-DOTATATE imaging changed management in 36 patients (70.6%), who were subsequently deemed suitable for peptide receptor-targeted therapy. Conclusion: In patients with negative or equivocal 111 In-DTPA-octreotide findings, 68 Ga-DOTATATE PET identifies additional lesions and may alter management in most cases.

Background Tranexamic acid reduces surgical bleeding and reduces death due to bleeding in patients with trauma. Meta-analyses of small trials show that tranexamic acid might decrease deaths from gastrointestinal bleeding. We aimed to assess the effects of tranexamic acid in patients with gastrointestinal bleeding. Methods We did an international, multicentre, randomised, placebo-controlled trial in 164 hospitals in 15 countries. Patients were enrolled if the responsible clinician was uncertain whether to use tranexamic acid, were aged above the minimum age considered an adult in their country (either aged 16 years and older or aged 18 years and older), and had significant (defined as at risk of bleeding to death) upper or lower gastrointestinal bleeding. Patients were randomly assigned by selection of a numbered treatment pack from a box containing eight packs that were identical apart from the pack number. Patients received either a loading dose of 1 g tranexamic acid, which was added to 100 mL infusion bag of 0•9% sodium chloride and infused by slow intravenous injection over 10 min, followed by a maintenance dose of 3 g tranexamic acid added to 1 L of any isotonic intravenous solution and infused at 125 mg/h for 24 h, or placebo (sodium chloride 0•9%). Patients, caregivers, and those assessing outcomes were masked to allocation. The primary outcome was death due to bleeding within 5 days of randomisation; analysis excluded patients who received neither dose of the allocated treatment and those for whom outcome data on death were unavailable. This trial was registered with Current Controlled Trials, ISRCTN11225767, and ClinicalTrials.gov, NCT01658124.

Background The diagnosis of neuroendocrine neoplasms (NENs) is often delayed. This first UK population-based epidemiological study of NENs compares outcomes with non-NENs to identify any inequalities. Methods Age-standardised incidence rate (ASR), 1-year overall survival, hazard ratios and standardised mortality rates (SMRs) were calculated for all malignant NENs diagnosed 2013–2015 from UK national Public Health records. Comparison with non-NENs assessed 1-year overall survival (1YS) and association between diagnosis at stage IV and morphology. Results A total of 15,222 NENs were identified, with an ASR (2013–2015 combined) of 8.6 per 100,000 (95% CI 8.5–8.7); 4.6 per 100 000 (95% CI, 4.5–4.7) for gastro-entero-pancreatic (GEP) NENs. The 1YS was 75% (95% CI, 73.9–75.4) varying significantly by sex. Site and morphology were prognostic. NENs (predominantly small cell carcinomas) in the oesophagus, bladder, prostate, and female reproductive organs had a poorer outcome and were three times more likely to be diagnosed at stage IV than non-NENs. Conclusion Advanced stage at diagnosis with significantly poorer outcomes of some NENs compared with non-NENs at the same anatomical site, highlight the need for improved access to specialist services and targeted service improvement.

Purpose To assess the impact of baseline liver tumour burden, alkaline phosphatase (ALP) elevation, and target lesion size on treatment outcomes with 177 Lu-Dotatate. Methods In the phase 3 NETTER-1 trial, patients with advanced, progressive midgut neuroendocrine tumours (NET) were randomised to 177Lu-Dotatate (every 8 weeks, four cycles) plus octreotide long-acting release (LAR) or to octreotide LAR 60 mg. Primary endpoint was progression-free survival (PFS). Analyses of PFS by baseline factors, including liver tumour burden, ALP elevation, and target lesion size, were performed using Kaplan-Meier estimates; hazard ratios (HRs) with corresponding 95% CIs were estimated using Cox regression. Results Significantly prolonged median PFS occurred with 177 Lu-Dotatate versus octreotide LAR 60 mg in patients with low (< 25%), moderate (25-50%), and high (> 50%) liver tumour burden (HR 0.187, 0.216, 0.145), and normal or elevated ALP (HR 0.153, 0.177), and in the presence or absence of a large target lesion (diameter > 30 mm; HR, 0.213, 0.063). Within the 177 Lu-Dotatate arm, no significant difference in PFS was observed amongst patients with low/moderate/high liver tumour burden (P = 0.7225) or with normal/elevated baseline ALP (P = 0.3532), but absence of a large target lesion was associated with improved PFS (P = 0.0222). Grade 3 and 4 liver function abnormalities were rare and did not appear to be associated with high baseline liver tumour burden. Conclusions 177 Lu-Dotatate demonstrated significant prolongation in PFS versus high-dose octreotide LAR in patients with advanced, progressive midgut NET, regardless of baseline liver tumour burden, elevated ALP, or the presence of a large target lesion. Clinicaltrials.gov: NCT01578239, EudraCT: 2011-005049-11 This article is part of the Topical Collection on Endocrinology.