Perioperative Management of a Rare Pancreatic Insulinoma Resection: Anaesthetic Challenge!

Insulinoma is a rare, mostly benign and solitary neuroendocrine tumour of the β-cells of islets of langerhans of pancreas. Clinically it presents with a classical ‘Whipple Triad’ encompassing symptomatic hypoglycemia, fasting hypoglycemia (<50 mg/dl) and immediate relief of symptoms after glucose administration. Definitive treatment is laparoscopic or open surgical excision of the tumour. We report and discuss the distinctive anaesthetic considerations and implications during perioperative period. A comprehensive approach including preoperative optimization of blood glucose levels with various drugs and dietary modifications, scrupulous hemodynamic and blood sugar monitoring with prompt initiation of dextrose infusion during surgical handling of tumour and meticulous management of rebound hyperglycemia with insulin infusion in postoperative period remains the essence for better outcome in these subset of patients.

Prognostic stratification for patients with neuroendocrine tumours receiving 177Lu-Dotatate

177Lu-Dotatate is increasingly used in patients with advanced neuroendocrine tumour (NET). However, few prognostic markers are available to stratify progression-free survival (PFS) of patients received 177Lu-Dotatate. Clinicopathological data, including baseline circulating biomarkers of patients with advanced NET received 177Lu-Dotatate that were routinely collected were retrospectively analysed. Continuous variables were normalized by dividing them by their upper normal limits. The whole dataset was randomly divided into a training set and a validation set. Univariate and multivariate logistic regression analysis were used to identify independent markers and develop a scoring model to predict treatment failure at 1-year. In total, 195 patients were included. Elevated baseline chromogranin A (CgA), normal creatinine and previous chemotherapy were three risk factors independently associated with 1-year treatment failure. By combining these risk factors, a scoring model was developed which could accurately predict 1-year treatment failure both in the training set (area under curve, AUC, 0.813; 95% confidence interval, 95%CI, 0.731-0.895; P<0.001) and the validation set (ACU, 0.816; 95%CI, 0.644-0.968; P<0.001). After selecting a score of 29.7 as the cutoff value of the scoring model, patients could be stratified into two groups, low-risk and high-risk with significantly different 1-year treatment failure rate, PFS and overall survival (OS; P<0.001) both in training set and validation set. In conclusion, baseline CgA, creatinine level, and previous chemotherapy were independently associated with 1-year treatment failure of patients with advanced NET who received 177Lu-Dotatate and the scoring model and prognostic stratification based on these markers could accurately predict 1-year treatment failure, PFS and OS.

P-O02 Management Experiences of Post-gastrectomy Severe Alkaline Reflux Oesophagitis

Background Alkaline reflux oeosphagitis is a recognized complication of procedures that compromise the lower oesophageal sphincter (LES), including gastrectomy. Incidence of reflux is dependent on the reconstructive procedure with Roux-en-Y esophagojejunostomy commonly accepted as the optimal method. The authors report their experience of 6 patients who underwent remedial intervention for severe alkaline reflux esophagitis following gastric surgery. Methods A retrospective review of 6 patients who had underwent a previous gastric procedure and developed symptoms of gastroesophageal reflux disease, over a 6-year period (2014-2020). Reflux symptoms were diagnosed by clinical history, radiology, endoscopy and esophageal manometry prior to proceeding to surgical reflux control. Post-operative outcomes following anti-reflux surgery were assessed by means of serial outpatient assessments and endoscopy. Results Six patients were included in this report, 4 males and 2 females with an average age of 73 years (range 58-91). Primary diagnoses encompassed; 4 gastric adenocarcinomas, 1 gastric neuroendocrine tumour and 1 patient with debilitating gastric antral vascular ectasia (GAVE) syndrome. Four patients underwent total gastrectomy and 2 subtotal gastrectomy with Roux-en-Y reconstruction. Onset of post-operative reflux symptoms ranged from 2-weeks to 3-years. Failing medical management, all patients underwent jejunojejunal anastomosis and Roux limb length revision with surgical jejunostomy. At follow up 5 patients had some degree of symptom resolution; 3 complete resolution, 2 initial resolution and 1 with unresolved symptoms. Conclusions Severe alkaline reflux oesophagitis is a recognized complication of gastric procedures compromising the LES. The authors report our experience of managing this complication following gastrectomy with jejunojejunal anastomosis and Roux limb length revision, with a majority of patients having improvement in if not complete resolution of reflux symptoms.

Haematotoxicity during peptide receptor radionuclide therapy: Baseline parameters differences and effect on patient’s therapy course

Background Mainly severe (CTCAE grade 3–4) haematotoxicity during peptide receptor radionuclide therapy (PRRT) is reported in literature due to major clinical impact, however moderate (CTCAE grade 2) haematotoxicity is common and could affect therapy management. The aim of this study was to evaluate the haematotoxicity course during PRRT and to compare baseline parameters between haematotoxicity grades. Methods In this retrospective study, 100 patients with a neuroendocrine tumour treated with PRRT were included. Patients were treated with an aimed number of four cycles with 7.4 GBq [177Lu]Lu-DOTA-TATE administered every 10 weeks. Haematological assessment was performed at baseline and frequently up to 10 weeks after the fourth cycle. The lowest haematological value was graded according to CTCAE v5.0, and patients were classified using the highest observed grade. Differences in baseline parameters, including [68Ga]Ga-DOTA-TATE positive tumour volume, were evaluated between CTCAE grades. Results Four cycles were completed by 86/100 of patients, 4/100 patients discontinued due to haematotoxicity, and 10/100 patients due to progressive disease. The treatment course was adjusted due to haematotoxicity in 24/100 patients, including postponed next cycle (n = 17), reduced administered activity (n = 13), and both adjustments (n = 10). The most observed haematotoxicity grade was grade 0–1 in 54/100 patients, grade 2 in 38/100 and grade 3–4 in 8/100. Significant differences in baseline leucocyte, neutrophil and platelet counts were observed between grade 0–1 and grade 2. However, the correlation between baseline and lowest observed values was poor to moderate. No differences between haematotoxicity grades and baseline parameters or somatostatin receptor positive tumour volume was observed. Conclusions The incidence of severe haematotoxicity was low with extensive screening and monitoring. The vast majority of patients (96/100) was not restricted in treatment continuation by haematotoxicity; therefore, our selection criteria appeared appropriate for safe PRRT treatment. Baseline parameters showed limited correlation with the degree of decline in haematological values.

Orbital metastasis from neuroendocrine tumour: Case report and literature review

Orbital metastases from neuroendocrine tumour are rare entities. An incidental finding of orbital metastasis originating from neuroendocrine tumour is presented in the context of a comprehensive review of all case reports and series published to date. Demographics, clinical features, diagnostic work-up, treatment and prognostic data from the published literature are discussed. Ninety-five patients with orbital metastases from neuroendocrine tumours have been reported so far. Average age at presentation is 63.8 years (range 25–86), with no significant gender predominance. Gastrointestinal tract is the most common site of primary neuroendocrine tumours (62–85%). Typical presentation includes proptosis (80–85%) and diplopia (27–62%) in patients with known primary neuroendocrine tumour elsewhere. Histological subtype and presence of metastases seem to be important prognostic factors. Incidental finding of neuroendocrine tumour mestastases in asymptomatic patients with unknown primary disease is uncommon. In such cases, orbital biopsy and structural and functional imaging are essential to establish a diagnosis and stage the disease.

Immunohistochemical Evaluation of Adaptor Protein FAM159B Expression in Normal and Neoplastic Human Tissues

FAM159B is a so-called adaptor protein. These proteins are essential components in numerous cell signalling pathways. However, little is known regarding FAM159B expression in normal and neoplastic human tissues. The commercially available rabbit polyclonal anti-human FAM159B antibody HPA011778 was initially characterised for its specificity using Western blot analyses and immunocytochemistry and then applied to a large series of formalin-fixed, paraffin-embedded normal and neoplastic human tissue samples. Confirmation of FAM159B’s predicted size and antibody specificity was achieved in BON-1 cells, a neuroendocrine tumour cell line endogenously expressing FAM159B, using targeted siRNA. Immunocytochemical experiments additionally revealed cytoplasmic expression of the adaptor protein. Immunohistochemical staining detected FAM159B expression in neuronal and neuroendocrine tissues such as the cortex, the trigeminal ganglia, dorsal root and intestinal ganglia, the pancreatic islets and the neuroendocrine cells of the bronchopulmonary and gastrointestinal tract, but also in the syncytiotrophoblasts of the placenta. FAM159B was also expressed in many of the 28 tumour entities investigated, with high levels in medullary and anaplastic thyroid carcinomas, parathyroid adenomas, lung and ovarian carcinomas, lymphomas and neuroendocrine tumours of different origins. The antibody HPA011778 can act as a useful tool for basic research and identifying FAM159B expression in tissue samples.