The Impact of Combined Chemotherapy and Intra-Tumoural Injection of Phosphorus-32 Microparticles on Vascularity in Locally Advanced Pancreatic Carcinoma.

BACKGROUND: Poor intra-tumoural vascularity contributes to a lack of response to chemotherapy in pancreatic cancers. Preliminary data suggest that the addition of endoscopic ultrasound (EUS)-guided intra-tumoural injection of phosphorus-32 (32P) microparticles to standard chemotherapy is potentially beneficial in locally advanced pancreatic cancer (LAPC). We aimed to assess changes in pancreatic tumour vascularity following 32P implantation, using contrast-enhanced EUS (CE-EUS). METHODS: This was a prospective single-centre trial from January 2022 to 2024 of patients with unresectable, non-metastatic LAPC undergoing standard FOLFIRINOX chemotherapy and 32P implantation. We performed CE-EUS pre-implantation after two chemotherapy cycles and 4 and 12 weeks after implantation. Time-intensity curves were analysed for 90 s after IV contrast bolus to ascertain peak intensity and intensity gain. RESULTS: A total of 20 patients underwent 32P implantation, with 15 completing 12-week follow-up. The technical success of 32P implantation was 100%. The median primary tumour size reduced from 32 mm (IQR 27.5-38.75) pre-implantation to 24 mm (IQR 16-26) 12 weeks post-implantation (p < 0.001). Five patients (25%) had tumour downstaging, and four underwent resections. The baseline (pre-implantation, post-chemotherapy) median intensity gain of contrast enhancement within the tumour was 32.15 (IQR 18.08-54.35). This increased to 46.85 (IQR 35.05-76.6; p = 0.007) and 66.3 (IQR 54.7-76.3; p = 0.001) at 4 weeks and 12 weeks post-implantation, respectively. Over a median follow-up of 11.2 months (IQR 7.8-12.8), 15/20 (75%) of patients remained alive, with 3/20 (15%) demonstrating local disease progression. Overall survival was not significantly different between patients with or without an increased intensity of 10 a.u. or more at 12 weeks post-implantation. CONCLUSION: This is the first clinical study to demonstrate treatment-induced increased vascularity within pancreatic primary tumours, which followed 32P implantation and FOLFIRINOX chemotherapy. Larger comparative trials are warranted.

Once in a Bile - the Incidence of Bile Reflux Post-Bariatric Surgery.

PURPOSE: Excellent metabolic improvement following one anastomosis gastric bypass (OAGB) remains compromised by the risk of esophageal bile reflux and theoretical carcinogenic potential. No 'gold standard' investigation exists for esophageal bile reflux, with diverse methods employed in the few studies evaluating it post-obesity surgery. As such, data on the incidence and severity of esophageal bile reflux is limited, with comparative studies lacking. This study aims to use specifically tailored biliary scintigraphy and upper gastrointestinal endoscopy protocols to evaluate esophageal bile reflux after OAGB, sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB). METHODS: Fifty-eight participants underwent OAGB (20), SG (15) or RYGB (23) between November 2018 and July 2020. Pre-operative reflux symptom assessment and gastroscopy were performed and repeated post-operatively at 6 months along with biliary scintigraphy. RESULTS: Gastric reflux of bile was identified by biliary scintigraphy in 14 OAGB (70%), one RYGB (5%) and four SG participants (31%), with a mean of 2.9% (SD 1.5) reflux (% of total radioactivity). One participant (OAGB) demonstrated esophageal bile reflux. De novo macro- or microscopic gastroesophagitis occurred in 11 OAGB (58%), 8 SG (57%) and 7 RYGB (30%) participants. Thirteen participants had worsened reflux symptoms post-operatively (OAGB, 4; SG, 7; RYGB, 2). Scintigraphic esophageal bile reflux bore no statistical association with de novo gastroesophagitis or reflux symptoms. CONCLUSION: Despite high incidence of gastric bile reflux post-OAGB, esophageal bile reflux is rare. With scarce literature of tumour development post-OAGB, frequent low-volume gastric bile reflux likely bears little clinical consequence; however, longer-term studies are needed. CLINICAL TRIAL REGISTRY: Australian New Zealand Clinical Trials Registry number ACTRN12618000806268.

Effects of Standard vs Energy-Dense Formulae on Gastric Retention, Energy Delivery, and Glycemia in Critically Ill Patients.

BACKGROUND: Energy-dense formulae are often provided to critically ill patients with enteral feed intolerance with the aim of increasing energy delivery, yet the effect on gastric emptying is unknown. The rate of gastric emptying of a standard compared with an energy-dense formula was quantified in critically ill patients. METHODS: Mechanically ventilated adults were randomized to receive radiolabeled intragastric infusions of 200 mL standard (1 kcal/mL) or 100 mL energy-dense (2 kcal/mL) enteral formulae on consecutive days in this noninferiority, blinded, crossover trial. The primary outcome was scintigraphic measurement of gastric retention (percentage at 120 minutes). Other measures included area under the curve (AUC) for gastric retention and intestinal energy delivery (calculated from gastric retention of formulae over time), blood glucose (peak and AUC), and intestinal glucose absorption (using 3-O-methyl-D-gluco-pyranose [3-OMG] concentrations). Comparisons were undertaken using paired mixed-effects models. Data presented are mean ± SE. RESULTS: Eighteen patients were studied (male/female, 14:4; age, 55.2 ± 5.3 years). Gastric retention at 120 minutes was greater with the energy-dense formula (standard, 17.0 ± 5.9 vs energy-dense, 32.5 ± 7.1; difference, 12.7% [90% confidence interval, 0.8%-30.1%]). Energy delivery (AUC120 , 13,038 ± 1119 vs 9763 ± 1346 kcal/120 minutes; P = 0.057), glucose control (peak glucose, 10.1 ± 0.3 vs 9.7 ± 0.3 mmol/L, P = 0.362; and glucose AUC120 8.7 ± 0.3 vs 8.5 ± 0.3 mmol/L.120 minutes, P = 0.661), and absorption (3-OMG AUC120 , 38.5 ± 4.0 vs 35.7 ± 4.0 mmol/L.120 minutes; P = .508) were not improved with the energy-dense formula. CONCLUSION: In critical illness, administration of an energy-dense formula does not reduce gastric retention, increase energy delivery to the small intestine, or improve glucose absorption or glucose control; instead, there is a signal for delayed gastric emptying.

HIDA and Seek: Challenges of Scintigraphy to Diagnose Bile Reflux Post-Bariatric Surgery.

INTRODUCTION: Oesophageal bile reflux after bariatric surgery may trigger development of Barrett's oesophagus. Gastro-oesophageal reflux of bile is captured by hepatobiliary iminodiacetic acid (HIDA) scintigraphy; however, anatomical and physiological changes after bariatric surgery warrant protocol modifications to optimise bile reflux detection. METHODS: HIDA scintigraphy occurred 6 months after either sleeve gastrectomy, Roux-en-Y gastric bypass or one-anastomosis gastric bypass. Standard HIDA scanning involves (i) 6-h fast and 24-h abstinence from opioids; (ii) IV administration of 99mTc di-isopropyl iminodiacetic acid; and (iii) dual anterior/posterior 60-min dynamic scanning of the duodenum, stomach and oesophagus. Three challenges were identified, and modifications were implemented, namely, (1) anatomical localisation of refluxed bile on planar scintigraphy was improved by adding a SPECT/CT for 3D imaging; (2) impaired cholecystokinin-controlled gallbladder emptying, following bypassed duodenum, was addressed by ingestion of a 'fatty meal'; and (3) intestinal hypomotility after gastric bypass was counteracted by longer scan duration (75-90 min) to allow bile to pass beyond the gastro-jejunal anastomosis. RESULTS: HIDA scan was undertaken in 18 patients, 13 of whom underwent the modified protocol. The tailored protocol ameliorated issues identified with the standard HIDA scan protocol; thus, accurate anatomical localisation was achieved in all patients, no delayed gallbladder emptying was observed, and bile was observed beyond the gastro-jejunal anastomosis in all gastric bypass patients. The modified technique was well tolerated by patients. CONCLUSION: A tailored HIDA scan protocol with addition of a SPECT-CT scan, ingestion of a fatty meal and prolonged scanning duration results in enhanced bile reflux detection in post-bariatric surgical patients.