Structural basis for activation of somatostatin receptor 5 by cyclic neuropeptide agonists.

Somatostatin receptor 5 (SSTR5) is an important G protein-coupled receptor and drug target for neuroendocrine tumors and pituitary disorders. This study presents two high-resolution cryogenicelectron microscope structures of the SSTR5-Gi complexes bound to the cyclic neuropeptide agonists, cortistatin-17 (CST17) and octreotide, with resolutions of 2.7 Å and 2.9 Å, respectively. The structures reveal that binding of these peptides causes rearrangement of a "hydrophobic lock", consisting of residues from transmembrane helices TM3 and TM6. This rearrangement triggers outward movement of TM6, enabling Gαi protein engagement and receptor activation. In addition to hydrophobic interactions, CST17 forms conserved polar contacts similar to somatostatin-14 binding to SSTR2, while further structural and functional analysis shows that extracellular loops differently recognize CST17 and octreotide. These insights elucidate agonist selectivity and activation mechanisms of SSTR5, providing valuable guidance for structure-based drug development targeting this therapeutically relevant receptor.

18F-AlF-NOTA-octreotide PET/CT in the localization of tumor-induced osteomalacia: case series and literature review.

Introduction: This study explores tumor-induced osteomalacia (TIO) through a case series and literature review, assessing the diagnostic potential of 18F-AlF-NOTA-octreotide (18F-OC) positron emission tomography/computed tomography (PET/CT). Methods: We analyzed TIO patients who underwent 18F-OC PET/CT. Parameters such as tumor dimension, the maximum standardized uptake value (SUVmax), the mean standardized uptake value (SUVmean) and metabolic tumor volume (MTV) were meticulously assessed. Clinical features and imaging characteristics pertinent to TIO were reviewed. Results: 6 patients with clinical suspicion of TIO exhibited hypophosphatemia (0.25 to 0.64 mmol/L), elevated alkaline phosphatase (ALP) levels (142 to 506 U/L), and increased parathyroid hormone (PTH) levels (92.9 to 281.7 pg/mL). Of these patients, two underwent FGF-23 testing, with results of 3185.00 pg/ml and 17.56 pg/ml, respectively. Conventional imaging modalities depicted widespread osteoporosis, with several cases demonstrating fractures indicative of osteomalacic and associated pathological fractures. Subsequent 18F-OC PET/CT facilitated the accurate localization of causative tumors, with histopathological examination confirming the diagnosis of phosphaturic mesenchymal tumor (PMT). The interval from initial clinical presentation to definitive TIO diagnosis spanned approximately 2.5 years (range: 1 - 4 years), with tumors varying in size (maximum diameter: 7.8 to 40.0 mm), SUVmax (5.47 to 25.69), SUVmean (3.43 to 7.26), and MTV (1.27 to 18.59 cm3). Conclusion: The implementation of whole-body 18F-OC PET/CT imaging emerges as a critical tool in the identification of occult tumors causing TIO. Future investigations incorporating a broader cohort are imperative to further delineate the diagnostic and therapeutic implications of 18F-OC PET/CT in managing TIO.

In transfusion-dependent, angiodysplasia-related anemia, adding octreotide to usual care reduced transfusions at 1 y.

SOURCE CITATION: Goltstein LC, Grooteman KV, Bernts LH, et al. Standard of care versus octreotide in angiodysplasia-related bleeding (the OCEAN study): a multicenter randomized controlled trial. Gastroenterology. 2024;166:690-703. 38158089.

Diagnostic performance and clinical impact of 18F-AlF-NOTA-octreotide in a large cohort of patients with neuroendocrine neoplasms: A prospective single-center study.

Purpose: Somatostatin receptor imaging with 18F-AlF-NOTA-octreotide (18F-AlF-OC) has shown promising performance in neuroendocrine neoplasms (NENs). In this study, we aim to investigate the diagnostic performance and clinical impact of 18F-AlF-OC in a large prospective cohort of patients with NEN. Methods: Between January 2023 and November 2023, a total of 219 patients with confirmed or suspected NEN were enrolled prospectively and underwent 18F-AlF-OC PET/CT at 2 h post-injection. The primary endpoint was the diagnostic performance, including sensitivity, specificity, and accuracy. An additional primary endpoint was the impact of 18F-AlF-OC on clinical management. The reference standard was based on the results of histopathology or radiological follow-up. Results: 205 patients were included in the final analysis. The patient-level sensitivity, specificity, and accuracy of 18F-AlF-OC PET/CT compared with contrast-enhanced CT/MRI were 90.5% vs. 81.8%, 93.1% vs. 71.1%, and 91.2% vs. 79.4%, respectively. 26 patients had tiny gastrointestinal NENs (smaller than 1 cm in diameter). The patient-based sensitivity of 18F-AlF-OC PET/CT and contrast-enhanced CT/MRI were 61.5% (16/26) and 37.5% (9/24), respectively. The smallest diameter of gastrointestinal NEN detected by 18F-AlF-OC PET/CT was 0.6 cm in the rectum, 0.3 cm in the stomach, and 0.5 cm in the duodenum. 18F-AlF-OC PET/CT results led to changes in clinical management in 19.5% of patients (40/205), owing mainly to new or unexpected findings compared to contrast-enhanced CT/MRI. Conclusion: 18F-AlF-OC PET/CT demonstrated great diagnostic performance in patients with NEN, particularly for detecting tiny gastrointestinal NEN. Furthermore, 18F-AlF-OC PET/CT impacted the therapeutic management in 19.5% of patients. Our results further validate the role of 18F-AlF-OC as a somatostatin receptor imaging tracer in clinical practice.

Dosimetric Considerations for 177 Lu-DOTATATE Therapy in a Patient With Chronic Renal Failure Under Hemodialysis.

ABSTRACT: This case report explores the use of 177 Lu-DOTATATE in a hemodialysis patient. For the first time, this study assesses the average dose received by the bone marrow, the primary organ at risk, using an original double estimation method through independently acquired imaging and biological samples counting data. Despite elevated doses, the absorbed doses to the bone marrow (0.662-0.740 Gy) were within safe limits. Radiation protection measurements for staff were also compliant. This work supports that effective early dialysis and systematic personalized dosimetry are crucial for hemodialysis patients undergoing 177 Lu-PRRT due to their variability (residual excretion, treatment history, etc).

Safety and Efficacy of 177 Lu-DOTATATE in Children and Young Adult Population : A Single-Center Experience.

PURPOSE: This single-center retrospective study explores the safety and efficacy of 177 Lu-DOTATATE in children and young adult population with metastatic/inoperable neuroendocrine tumors (NETs). PATIENTS AND METHODS: This study is a retrospective analysis of all children and young adult patients (≤29 years) with advanced inoperable/metastatic epithelial or nonepithelial NETs who were administered a median of 4 cycles of 177 Lu-DOTATATE therapy and low-dose oral capecitabine as a radiosensitizer every 8-12 weeks, except 2 patients who received CAPTEM chemotherapy. The radiological response was assessed using RECIST 1.1 on interim and end-of-treatment 68 Ga-DOTANOC PET/CT. The primary endpoint was objective response rate, whereas disease control rate, toxicity profile, progression-free survival, and overall survival were secondary endpoints. RESULTS: Nineteen biopsy-proven NET patients (median age, 22 ± 10 years) with 8 of them adolescents (10-18 years) and the remaining young adults (19-29 years) were included. Fourteen patients had gastroenteropancreatic neuroendocrine tumor (pancreas being most common primary site), whereas the rest had non-gastroenteropancreatic neuroendocrine tumor. A total of 65 cycles of 177 Lu-DOTATATE (range, 1-6 cycles) were administered with a median cumulative activity of 600 mCi (range, 100-1000 mCi). The objective response rate and disease control rate were 41% and 94%, respectively. Grade 1 and 2 adverse events were observed in 14 (74%) and 5 (26%) of 19 patients, respectively. In a total of 8 events (42%), 4 events each of disease progression and death occurred during a median follow-up of 80.1 months with an estimated 5-year progression-free survival and overall survival of 54% (95% confidence interval, 30-78) and 63% (95% confidence interval, 39-87), respectively. CONCLUSIONS: 177 Lu-DOTATATE appears safe and effective in children and young adults with metastatic/inoperable NETs. Large prospective trials are required to validate these results.

68 Ga-DOTATOC Pictorial Essay of Various Recurrent Meningiomas Rejected for Treatment With 177 Lu-DOTATATE : Is There a Place for Another Theranostic Examination?

ABSTRACT: We report the cases of 4 patients treated for recurrent meningiomas of various grades. Pretreatment 68 Ga-DOTATOC PET/CT was performed prior to screening for vectorized internal radiotherapy with 177 Lu-DOTATATE or prior external radiotherapy to aid contouring. None of these patients had sufficient uptake to be eligible for 177 Lu-DOTATATE or reliable contouring. Most recurrences were grades II and III, suggesting a loss of physiological somatostatin receptor overexpression in these tumors. Therefore, the benefit of treatment with 177 Lu-DOTATATE in the current indication is questionable. In the absence of a validated systemic treatment, and considering a few case reports, treatment with 177 Lu-PSMA could be investigated as an additional vectorized internal radiotherapy option.

False-Negative 68 Ga-FAPI PET/CT in Pediatric Thyroid Medullary Carcinoma Seen With 68 Ga-DOTATOC PET/CT and 18 F-FDG PET/CT.

ABSTRACT: In adults, 68 Ga-FAP inhibitor ( 68 Ga-FAPI) PET/CT outperforms 68 Ga-radiolabeled somatostatin analog peptides ( 68 Ga PET/CT) and 18 F-FDG PET/CT in detecting thyroid lesions. This is the case of a 13-year-old boy newly diagnosed with medullary thyroid cancer with high calcitonin level. 68 Ga PET/CT revealed the presence of only a primary thyroid lesion. Proven to be superior in detecting metastasis, 68 Ga-FAPI PET/CT was performed. The results came out negative for primary and potential metastatic lesions. This case sheds shed light on false-negatives reported in 68 Ga-FAPI PET/CT scans in pediatric patients, emphasizing the need for alternate radiotracers when a negative study is met.

Expression of somatostatin receptors in hemangioblastomas associated with von Hippel-Lindau disease as a novel diagnostic, therapeutic, and follow-up opportunity: A case report and literature review.

Hemangioblastomas associated with von Hippel-Lindau (VHL) disease are frequently multiple and recur during prolonged follow-up. Currently, no systemic treatment is available for these tumors. Recent studies have shown the expression of somatostatin receptors in these types of hemangioblastomas. Notably, increased somatostatin receptor expression in a tumor, as determined by peptide-receptor radionuclide imaging, is a predictive factor of response to treatment with somatostatin analogs and peptide-receptor radionuclide therapy. The aim of this study was to describe the case of a patient with increased expression of somatostatin receptors in a suprasellar hemangioblastoma associated with VHL disease and conduct a literature review on somatostatin receptor expression in patients with VHL-associated hemangioblastomas. We describe herein the case of a 51-year-old man with VHL disease who had a suprasellar hemangioblastoma detected on magnetic resonance imaging. Peptide-receptor radionuclide imaging using gallium-68-DOTATOC (68Ga-DOTATOC) identified increased expression of somatostatin receptors in the suprasellar hemangioblastoma, along with multiple pancreatic neuroendocrine tumors and bilateral pheochromocytomas. The patient was treated for 1 year with lanreotide, a somatostatin analog. A repeat 68Ga-DOTATOC 1 year after starting lanreotide revealed decreased radiotracer uptake by the hemangioblastoma, consistent with a metabolic response. The presence of somatostatin receptors in hemangioblastomas associated with VHL disease is a novel finding. The decreased expression of these receptors after treatment with a somatostatin analog, as described in the present case, positions the somatostatin receptor as a new target for novel diagnostic, therapeutic, and follow-up opportunities in patients with VHL disease.

Safety and efficacy of peptide receptor radionuclide therapy in neuroendocrine tumors: A single center experience.

Peptide receptor radionucleotide therapy (PRRT) with 177Lu-dotatate is widely used for the treatment of patients with neuroendocrine tumors (NETs). We analyzed data from 104 patients with NETs treated with 177Lu -dotatate at a US academic center between December 2017 and October 2020 to better understand patterns of long-term efficacy, safety, and toxicity in the real-world setting. 177Lu-dotatate (200 mCi) was administered every eight weeks for four doses. The most common sites of primary disease were small intestine NETs (n = 49, 47%), pancreatic NETs (n = 32, 31%), and lung NETs (n = 7, 7%). Twenty-seven percent had Ki-67 <3%, 49% had Ki-67 between 3-20%, and 13.5% had Ki-67 >20%. The cohort had been pretreated with a median of two prior lines of treatment. Forty percent had received prior liver-directed treatment. Seventy-four percent of patients completed all four doses of treatment. The objective response rate was 18%. The median time-to-treatment failure/death was significantly longer for small-bowel NETs when compared to pancreatic NETs (37.3 months vs. 13.2 months, p = 0.001). In a multivariate model, Ki-67, primary site, and liver tumor burden ≥50% were found to independently predict time-to-treatment failure/death. Around 40% of patients experienced adverse events of ≥grade 3 severity. Treatment-related adverse events leading to discontinuation of therapy happened in 10% of patients. Preexisting mesenteric/peritoneal disease was present in 33 patients; seven of these patients developed bowel-related toxicities including two grade 5 events. We also report two cases of delayed-onset minimal change nephrotic syndrome, which occurred 14 and 27 months after the last dose of PRRT. Lastly, we describe six patients who developed rapid tumor progression in the liver leading to terminal liver failure within 7.3 months from the start of PRRT, and identify potential risk factors associated with this occurrence, which will need further study.

Nanotechnology-Based Strategy for Enhancing Therapeutic Efficacy in Pancreatic Cancer: Receptor-Targeted Drug Delivery by Somatostatin Analog.

A novel nanotechnology-based drug delivery system (DDS) targeted at pancreatic cancer cells was developed, characterized, and tested. The system consisted of liposomes as carriers, an anticancer drug (paclitaxel) as a chemotherapeutic agent, and a modified synthetic somatostatin analog, 5-pentacarbonyl-octreotide, a ligand for somatostatin receptor 2 (SSTR2), as a targeting moiety for pancreatic cancer. The cellular internalization, cytotoxicity, and antitumor activity of the DDS were tested in vitro using human pancreatic ductal adenocarcinoma (PDAC) cells with different expressions of the targeted SSTR2 receptors, and in vivo on immunodeficient mice bearing human PDAC xenografts. The targeted drug delivery system containing paclitaxel exhibited significantly enhanced cytotoxicity compared to non-targeted DDS, and this efficacy was directly related to the levels of SSTR2 expression. It was found that octreotide-targeted DDS proved exceptionally effective in suppressing the growth of PDAC tumors. This study underscores the potential of octreotide-targeted liposomal delivery systems to enhance the therapeutic outcomes for PDAC compared with non-targeted liposomal DDS and Paclitaxel-Cremophor® EL, suggesting a promising avenue for future cancer therapy innovations.

PRRT with Lu-177 DOTATATE in Treatment-Refractory Progressive Meningioma: Initial Experience from a Tertiary-Care Neuro-Oncology Center.

PURPOSE: Refractory and/or recurrent meningiomas have poor outcomes, and the treatment options are limited. Peptide receptor radionuclide therapy (PRRT) has been used in this setting with promising results. We have documented our experience of using intravenous (IV) and intra-arterial (IA) approaches of Lu-177 DOTATATE PRRT. METHODS: Eight patients with relapsed/refractory high-grade meningioma received PRRT with Lu-177 DOTATATE by IV and an IA route. At least 2 cycles were administered. Time to progression was calculated from the first PRRT session to progression. The response was assessed on MRI using RANO criteria, and visual analysis of uptake was done on Ga-68 DOTANOC PET/CT. Post-therapy dosimetry calculations for estimating the absorbed dose were performed. RESULTS: Median time to progression was 8.9 months. One patient showed disease progression, whereas seven patients showed stable disease at 4 weeks following 2 cycles of PRRT. Dosimetric analysis showed higher dose and retention time by IA approach. No significant peri-procedural or PRRT associated toxicity was seen. CONCLUSION: PRRT is a safe and effective therapeutic option for relapsed/refractory meningioma. The IA approach yields better dose delivery and should be routinely practised.

Alpha-emitter Peptide Receptor Radionuclide Therapy in Neuroendocrine Tumors.

Peptide receptor radionuclide therapy (PRRT) has become mainstream therapy of metastatic neuroendocrine tumors not controlled by somatostatin analog therapy. Currently, beta particle-emitting radiopharmaceuticals are the mainstay of PRRT. Alpha particle-emitting radiopharmaceuticals have a theoretic advantage over beta emitters in terms of improved therapeutic efficacy due to higher cancer cell death and lower nontarget tissue radiation-induced adverse events due to shorter path length of alpha particles. We discuss the available evidence for and the role of alpha particle PRRT.

Absorbed Dose-Response Relationship in Patients with Gastroenteropancreatic Neuroendocrine Tumors Treated with [177Lu]Lu-DOTATATE: One Step Closer to Personalized Medicine.

[177Lu]Lu-DOTATATE has been approved for progressive and inoperable gastroenteropancreatic neuroendocrine tumors (GEP-NETs) that overexpress somatostatin receptors. The absorbed doses by limiting organs and tumors can be quantified by serial postinfusion scintigraphy measurements of the γ-emissions from 177Lu. The objective of this work was to explore how postinfusion [177Lu]Lu-DOTATATE dosimetry could influence clinical management by predicting treatment efficacy (tumor shrinkage and survival) and toxicity. Methods: Patients with GEP-NETs treated with [177Lu]Lu-DOTATATE between 2016 and 2022 and who underwent dosimetry were included. Absorbed doses were calculated for healthy organs (liver, kidneys, bone marrow, and spleen) and tumors using PLANET Dose and the local energy deposition method based on serial posttreatment SPECT/CT. Up to 5 lesions per site were selected and measured on images collected at baseline and 3 mo after treatment end (measurement masked to the somatostatin receptor imaging uptake). For toxicity assessment, laboratory parameters were regularly monitored. Clinical data, including time to death or progression, were collected from the patients' health records. Correlations between absorbed doses by organs and toxicity and between absorbed doses by lesions and tumor volume variation were studied using regression models. Results: In total, 35 dosimetric studies were performed in patients with mostly grade 2 (77%) tumors and metastases in liver (89%), lymph nodes (77%), and bone (34%), and 146 lesions were analyzed: 1-9 lesions per patient, mostly liver metastases (65%) and lymph nodes (25%). The median total absorbed dose by tumors was 94.4 Gy. The absorbed doses by tumors significantly decreased between cycles. The absorbed dose by tumors was significantly associated with tumor volume variation (P < 0.001) 3 mo after treatment end, and it was a significant prognostic factor for survival. Toxicity analysis showed a correlation between the decrease of hematologic parameters such as lymphocytes or platelet concentrations and the absorbed doses by the spleen or bone marrow. The mean absorbed dose by the kidneys was not correlated with nephrotoxicity during the studied period. Conclusion: In patients treated with [177Lu]Lu-DOTATATE for GEP-NETs, tumor and healthy organ dosimetry can predict survival and toxicities, thus influencing clinical management.

Radio-Guided Surgery with a New-Generation ß-Probe for Radiolabeled Somatostatin Analog, in Patients with Small Intestinal Neuroendocrine Tumors.

BACKGROUND: Radio-guided surgery (RGS) holds promise for improving surgical outcomes in neuroendocrine tumors (NETs). Previous studies showed low specificity (SP) using γ-probes to detect radiation emitted by radio-labeled somatostatin analogs. OBJECTIVE: We aimed to assess the sensitivity (SE) and SP of the intraoperative RGS approach using a ß-probe with a per-lesion analysis, while assessing safety and feasibility as secondary objectives. METHODS: This prospective, single-arm, single-center, phase II trial (NCT05448157) enrolled 20 patients diagnosed with small intestine NETs (SI-NETs) with positive lesions detected at 68Ga-DOTA-TOC positron emission tomography/computed tomography (PET/CT). Patients received an intravenous injection of 1.1 MBq/Kg of 68Ga-DOTA-TOC 10 min prior to surgery. In vivo measurements were conducted using a ß-probe. Receiver operating characteristic (ROC) analysis was performed, with the tumor-to-background ratio (TBR) as the independent variable and pathology result (cancer vs. non-cancer) as the dependent variable. The area under the curve (AUC), optimal TBR, and absorbed dose for the surgery staff were reported. RESULTS: The intraoperative RGS approach was feasible in all cases without adverse effects. Of 134 specimens, the AUC was 0.928, with a TBR cut-off of 1.35 yielding 89.3% SE and 86.4% SP. The median absorbed dose for the surgery staff was 30 µSv (range 12-41 µSv). CONCLUSION: This study reports optimal accuracy in detecting lesions of SI-NETs using the intraoperative RGS approach with a novel ß-probe. The method was found to be safe, feasible, and easily reproducible in daily clinical practice, with minimal radiation exposure for the staff. RGS might potentially improve radical resection rates in SI-NETs. CLINICAL TRIALS REGISTRATION: 68Ga-DOTATOC Radio-Guided Surgery with ß-Probe in GEP-NET (RGS GEP-NET) [NCT0544815; https://classic. CLINICALTRIALS: gov/ct2/show/NCT05448157 ].

Functional imaging in neuroendocrine tumors: assessment of molecular heterogeneity using [68Ga]Ga-DOTA-TOC and [18F]FDG PET/CT.

OBJECTIVE: The aim of the study was evaluate the diagnostic performance of [68Ga]Ga-DOTA-TOC and [18F]FDG PET/CT in patients with histologically proven neuroendocrine tumors (NETs), as well as the correlation of the visualized findings with the tumor grade. MATERIAL AND METHODS: We included 50 patients with NETs who underwent both [68Ga]Ga-DOTA-TOC and [18F]FDG PET/TC. The pooled sensitivity of both scans was compared, as well as [68Ga]Ga-DOTA-TOC and [18F]FDG for each tumor grade (grade 1/G1, grade 2/G2 and grade 3/G3). Also, the sensitivity of [68Ga]Ga-DOTA-TOC and [18F]FDG as a function of the continuous variable Ki-67 was investigated. Finally, the number of lesions detected by both PET radiopharmaceuticals for each tumor grade was compared. RESULTS: The pooled sensitivity of both PET/CT (96%) was higher than [68Ga]Ga-DOTA-TOC (84%) and [18F]FDG (44%) separately, with statistically significant differences. The sensitivity of [68Ga]Ga-DOTA-TOC was higher than [18F]FDG in both G1 (p = 0.004) and G2 (p < 0.001). In G3 the performance of both scans detected disease in 100% of this subgroup. The sensitivity of [68Ga]Ga-DOTA-TOC and [18F]FDG PET/CT correlated significantly with the Ki-67 proliferative index. In G2 patients the number of lesions detected with [68Ga]Ga-DOTA-TOC was higher than [18F]FDG. CONCLUSIONS: The performance of both PET/CT, particularly in G2 and G3, demonstrates the molecular heterogeneity of metastatic NETs and contributes to the selection of a more appropriate treatment, particularly in those high-grade patients who may benefit from radionuclide therapy (PRRT).

Prevalence of metastases outside the liver and abdominal lymph nodes on 68Ga-DOTATOC-PET/CT in patients with small intestinal and pancreatic neuroendocrine tumours.

Metastases outside the liver and abdominal/retroperitoneal lymph nodes are nowadays detected frequently in patients with neuroendocrine tumours (NETs), owing to the high sensitivity of positron emission tomography (PET) with Gallium-68-DOTA-somatostatin analogues (68Ga-SSA) and concomitant diagnostic computed tomography (CT). Our aim was to determine the prevalence of extra-abdominal metastases on 68Ga-DOTATOC-PET/CT in a cohort of patients with small intestinal (Si-NET) and pancreatic NET (Pan-NET), as well as that of pancreatic metastasis in patients with Si-NET. Among 2090 patients examined by 68Ga-DOTATOC-PET/CT at two tertiary referral centres, a total of 1177 patients with a history of Si- or Pan-NET, were identified. The most recent 68Ga-DOTATOC-PET/CT report for each patient was reviewed, and the location and number of metastases of interest were recorded. Lesions outside the liver and abdominal nodes were found in 26% of patients (n = 310/1177), of whom 21.5% (255/1177) were diagnosed with Si-NET and 4.5% (55/1177) Pan-NET. Bone metastases were found in 18.4% (215/1177), metastases to Virchow's lymph node in 7.1% (83/1177), and lung/pleura in 4.8% (56/1177). In the subset of 255 Si-NET patients, 5.4% (41/255) manifested lesions in the pancreas, 1.5% in the breast (18/255), 1.3% in the heart (15/255) and 1% in the orbita (12/255). In Si-NET patients, the Ki-67 proliferation index was higher in those with ≥2 metastatic sites of interest, than with 1 metastatic site, (p <0.001). Overall, extra-abdominal or pancreatic metastases were more often found in patients with Si-NET (34%) than in those with Pan-NET (13%) (p <0.001). Bone metastases were 2.6 times more frequent in patients with Si-NET compared to Pan-NET patients (p <0.001). Lesions to the breast and orbita were encountered in almost only Si-NET patients. In conclusion, lesions outside the liver and abdominal nodes were detected in as many as 26% of the patients, with different prevalence and metastatic patterns in patients with Si-NET compared to Pan-NET. The impact of such metastases on overall survival and clinical decision-making needs further evaluation.

Refractory Hypoglycemia Due to Sulfonylurea Contamination of Illicit Opioid Medications.

Illicit drug supply adulteration can heighten the risk for adverse health outcomes. Sulfonylurea medications are widely used in the treatment of diabetes mellitus (DM). Unintentional or intentional overdose of sulfonylureas can cause refractory hypoglycemia. This case report describes a 62-year-old male patient who presented to the emergency department (ED) after being found on the ground with signs of mild trauma. He was noted to be persistently hypoglycemic despite boluses of intravenous dextrose, a dextrose infusion, and oral nutrition. The patient did report purchase and oral ingestion of pills sold as oxycodone and that the pill shape and color were different from his usual supply. The patient was empirically treated with octreotide resulting in normalization of his serum glucose. Testing demonstrated a serum glipizide concentration six times the reporting range. This case represents unintentional sulfonylurea exposure in the setting of non-prescribed oxycodone use, resulting in hypoglycemia refractory to intravenous dextrose and oral nutrition. Octreotide is an additional potential treatment for this condition. As in this case, ingestion of street drugs may present a potential source of sulfonylurea exposure. Opioid contamination with sulfonylureas has not been widely reported in the literature and knowledge about this potential exposure is important for the prompt recognition and treatment of these patients by emergency physicians.