Diagnostic features and management options for duodenal neuroendocrine neoplasms: a retrospective, multi-centre study.

Duodenal neuroendocrine neoplasms (dNENs) are rare neoplasms but their incidence is on the rise. They are classified into 5 sub-types but there remains much heterogeneity in behaviour in particular of non-functioning dNENs. To retrospectively analyse outcomes for all types of dNENs, and highlight prognostic factors associated with worse outcome. 102 (57 m/45f.) patients were identified with mean age at diagnosis 62 (range 32-87) years. The majority were non-functioning tumours 87/102 and median size was 10 mm (range 0.9-130 mm). 83 patients had Stage I or II disease, of which 17 underwent endoscopic resection with R1 rate of 45% and complication rate 12%. 36 patients were kept under endoscopic surveillance. There were 11 deaths of which 4 were disease related. Age and Ki67 > 20% were associated with worse OS in all dNENs. In non-functioning dNENs Ki67 > 3% was a predictor of lymph nodes metastases with OR 18.2 (2.54-13) (p < 0.005) in univariate analyses and liver metastases with OR 6.79 (1.56-29.5) (p < 0.05) in the multivariate analysis. Lesions 11-20 mm in size had OR 11.1 (1.16-106) compared to lesions < 11 mm for the prediction of lymph node metastases in the multivariate analysis (p < 0.05). ROC analysis of size of non-functioning dNENs to predict LN metastases found < 15 mm had an AUROC of 0.9 (0.81-0.99) with a sensitivity of 85% and specificity of 88%. dNENs are increasing in incidence, however low grade and smaller lesions have an indolent course and the role of endoscopic resection and active surveillance needs to be reviewed.

Increasing oxygen prescribing during the COVID-19 pandemic.

Valid oxygen prescriptions for hospital inpatients have been a long-standing problem and have been described extensively in BMJ Open Quality with numerous quality improvement projects (QIPs) with the aim of improving compliance with oxygen prescribing.The British Thoracic Society recommends that all inpatients should have oxygen target saturation set on admission: this is motivated by risks of both undertreatment and overtreatment with oxygen. The discrepancy between the recommendation and the reality produced a number of interventions studied in QIPs over the past years, all aiming at bringing the local ward teams closer to the target. This has become even more important during the COVID-19 pandemic, where non-standard oxygen saturation targets and oxygen scarcity led hospital systems to rethink their internal guidelines on the subject.We propose three novel interventions to improve compliance: a remote, personally directed email communication to a ward pharmacist, a similar communication to ward nurses, and a remote, personally directed WhatsApp communication to junior ward doctors. We undertake a QIP which compares novel interventions developed in-house with the most successful interventions from oxygen prescribing initiatives that have previously been published by BMJ Open Quality The main outcome measure was the proportion of patients with valid oxygen prescription on a ward.The series of novel interventions in three plan, do study, act cycles led to improvement in the outcome measure from 0% at baseline to 70% at the end of the QIP. The successful interventions from previous QIPs were ran in parallel on a similar ward and achieved improvement from 17.9% at baseline to 55.6% at the end of the QIP.This QIP demonstrates adapted interventions performed in context of social distancing aimed at members of multidisciplinary team which achieve superiority in increasing proportion of patients with a valid oxygen prescription, when compared with previously described methods from BMJ Open Quality.

Is local excision sufficient in selected grade 1 or 2 type III gastric neuroendocrine neoplasms?

PURPOSE: Type III gastric neuroendocrine neoplasms (g-NENs) have historically been regarded as aggressive tumours, hence current guidelines advocate radical surgery with lymph node dissection. Data on the roles of endoscopic or less extensive surgical resections are more limited. The aim of our study is to evaluate the clinicopathological features and long-term outcomes of patients undergoing endoscopic or limited surgical resection for localised grade 1 or 2 type III g-NENs when compared to radical surgery. METHODS: Retrospective analysis of all patients diagnosed with a localised grade 1 or 2 type III g-NENs across six tertiary NEN centers between 2006 and 2019. RESULTS: Forty-five patients were diagnosed with a potentially resectable grade 1 or 2 type III g-NEN of whom 36 underwent either endoscopic or surgical resection. No statistically significant differences were found between the three resection groups in terms of patient age, tumour location, grade or size. Only tumour size was found to be significantly associated with poor clinical outcome (p = 0.012) and ROC curve analysis identified tumour size >10 mm as a negative predictor (AUC:0.8030, p = 0.0021). Tumours >10 mm were also more likely to be associated with lymph node metastases on imaging and histology (p = 0.039 and p = 0.026 respectively). CONCLUSIONS: Localised grade 1 or 2 type III g-NENs had a good prognosis in this series. Tumour size >10 mm was the most significant prognostic factor affecting patient outcome. Endoscopic resection or limited surgical resection is feasible and safe in small type III g-NENs which demonstrate favourable grade 1/2, well differentiated histology.

Predictors of antiproliferative effect of lanreotide autogel in advanced gastroenteropancreatic neuroendocrine neoplasms.

PURPOSE: The antiproliferative properties of lanreotide autogel (LAN) in gastroenteropancreatic neuroendocrine neoplasms (GEP NENs) were demonstrated in the CLARINET study. However, there is limited literature regarding factors that affect progression-free survival (PFS) in patients with GEP NENs treated with LAN. METHODS: We identified a total of 191 treatment-naive patients with advanced GEP NENs and positive SSTR uptake on imaging (Octreoscan or 68Gallium DOTATATE Positron Emission Tomography [68GaPET]) who received first-line LAN monotherapy, albeit at various starting doses (60, 90 or 120 mg/month). A group of 102 patients who initiated treatment at the standard dose of 120 mg/month were included in the study and further evaluated by univariate and multivariate analyses to identify predictors of PFS. RESULTS: The location of tumour primary was in the small bowel in 63 (62%), pancreas in 31 (30%) and colon/rectum in 8 patients (8%). The tumours were well-differentiated, and the majority were grade 1 (52%), or 2 (38%). About 60% of cases had progressive disease at the time of treatment initiation. Most patients with available pretreatment nuclear medicine imaging (Octreoscan or 68Ga PET) had a Krenning score of 3 (44%) or 4 (50%). The median PFS for the entire cohort was 19 months (95% CI 12, 26 months). The univariate analysis demonstrated that grade 2 tumours, progressive disease at baseline and metastatic liver disease were associated with a significantly shorter PFS, while other evaluated variables did not affect PFS at a statistically significant level. However, at multivariate analysis only the tumour grade remained statistically significant. CONCLUSIONS: The current study showed that, of many evaluated variables, only the tumour grade was predictive of PFS duration and this should be considered during patient selection for treatment.

Orbital metastases from neuroendocrine neoplasms: clinical implications and outcomes.

PURPOSE: Neuroendocrine neoplasms (NENs) may rarely metastasise to the orbit. Published data on epidemiology, incidence and preferred treatment is limited. We present the largest cohort of symptomatic and asymptomatic NEN patients with orbital metastases and data on epidemiological parameters, symptoms as well as diagnostic/treatment modalities used. METHODS: We identified patients from our internal NEN database of patients who had also undergone Gallium68-DOTATATE PET (Ga68-DOTA). The diagnosis of orbital metastatic NEN was made on somatostatin receptor imaging and confirmed on a dedicated MRI of orbits. RESULTS: We identified 27 patients of 994 patients evaluated with Ga68-DOTATATE PET imaging during their surveillance monitoring in our department; 15 female, average age at NEN diagnosis 53 years and orbital metastatic NEN diagnosis 59 years. The majority of NEN primaries originated from small bowel (18/27, 66.4%) or pancreas 4/27 (4/27, 14.8%). Hepatic with or without concomitant skeletal metastases were present in 23/27 (85%) of patients. Ocular symptoms and/or signs were evident in 11/27 (41%) of patients. 5/11 symptomatic patients underwent external beam radiotherapy (EBRT) resulting in complete symptoms resolution. The 5-year survival was estimated at 84.1%. CONCLUSIONS: Orbital metastases of NEN have a relatively low prevalence, more commonly associated with small bowel primary. Extraocular muscles are primarily affected, irrespectively of liver disease burden. Survival does not seem to be affected. EBRT is an efficacious treatment modality for both symptom relief and tumour growth control. Administration of peptide receptor radionuclide therapy may occasionally induce temporary ocular symptoms, which resolve following treatment with a short course of steroids.