-
Journal of Indian Association of... 2024Idiopathic chylopericardium (CP) in the pediatric population is a rare entity with very few reported cases and is characterized by the accumulation of chyle in the...
Idiopathic chylopericardium (CP) in the pediatric population is a rare entity with very few reported cases and is characterized by the accumulation of chyle in the pericardial cavity. There are no guidelines for the management of this rare entity. The present study reports a case of idiopathic CP in an infant and our experience of managing it by pericardial window creation using VATS and a multidisciplinary approach providing the optimum care for the child.
PubMed: 38912020
DOI: 10.4103/jiaps.jiaps_20_24 -
Frontiers in Endocrinology 2024This study explores tumor-induced osteomalacia (TIO) through a case series and literature review, assessing the diagnostic potential of F-AlF-NOTA-octreotide (F-OC)... (Review)
Review
INTRODUCTION
This study explores tumor-induced osteomalacia (TIO) through a case series and literature review, assessing the diagnostic potential of F-AlF-NOTA-octreotide (F-OC) positron emission tomography/computed tomography (PET/CT).
METHODS
We analyzed TIO patients who underwent F-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 F-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 cm).
CONCLUSION
The implementation of whole-body F-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 F-OC PET/CT in managing TIO.
Topics: Humans; Fibroblast Growth Factor-23; Fluorine Radioisotopes; Heterocyclic Compounds; Heterocyclic Compounds, 1-Ring; Neoplasms, Connective Tissue; Octreotide; Osteomalacia; Paraneoplastic Syndromes; Positron Emission Tomography Computed Tomography; Radiopharmaceuticals
PubMed: 38887276
DOI: 10.3389/fendo.2024.1400751 -
The Oncologist Jun 2024Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are rare neoplasms with an increasing annual incidence and prevalence. Many are metastatic at presentation or...
BACKGROUND
Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are rare neoplasms with an increasing annual incidence and prevalence. Many are metastatic at presentation or recur following surgical resection and require systemic therapy, for which somatostatin analogs such as octreotide or lanreotide comprise typical first-line therapies. Nonetheless, treatment options remain limited. Epigenetic processes such as histone modifications have been implicated in malignant transformation and progression. In this study, we evaluated the anti-proliferative effects of a histone deacetylase (HDAC) inhibitor, entinostat, which was computationally predicted to show anti-cancer activity, as confirmed in in vitro and in vivo models of GEP-NETs.
METHODS
This was a phase II study to evaluate the efficacy and safety of entinostat in patients with relapsed or refractory abdominal NETs. The primary objective was to estimate the objective response rate to entinostat. Additionally, with each patient as his/her own control we estimated the rates of tumor growth prior to enrollment on study and while receiving entinostat. Patients received 5 mg entinostat weekly until disease progression or intolerable toxicity. The dose could be changed to 10 mg biweekly for patients who did not experience grade ≥ 2 treatment-related adverse events (AEs) in cycle 1, but was primarily administered at the starting 5 mg weekly dose.
RESULTS
The study enrolled only 5 patients due to early termination by the drug sponsor. The first patient that enrolled had advanced disease and died within days of enrollment before follow-up imaging due to a grade 5 AE unrelated to study treatment and was considered non-evaluable. Best RECIST response for the remaining 4 patients was stable disease (SD) with time on study of 154+, 243, 574, and 741 days. With each patient as his/her own control, rates of tumor growth on entinostat were markedly reduced with rates 20%, 33%, 54%, and 68% of the rates prior to enrollment on study. Toxicities possibly or definitely related to entinostat included grade 2/3 neutrophil count decrease [2/4 (50%)/ 2/4 (50%)], grade 3 hypophosphatemia [1/4, (25%)], grade 1/2 fatigue [1/4 (25%)/ 2/4 (50%)], and other self-limiting grade 1/2 AEs.
CONCLUSION
In the treatment of relapsed or refractory abdominal NETs, entinostat 5 mg weekly led to prolonged SD and reduced the rate of tumor growth by 32% to 80% with an acceptable safety profile (ClinicalTrials.gov Identifier: NCT03211988).
PubMed: 38886159
DOI: 10.1093/oncolo/oyae118 -
Theranostics 2024Somatostatin receptor imaging with F-AlF-NOTA-octreotide (F-AlF-OC) has shown promising performance in neuroendocrine neoplasms (NENs). In this study, we aim to...
Somatostatin receptor imaging with F-AlF-NOTA-octreotide (F-AlF-OC) has shown promising performance in neuroendocrine neoplasms (NENs). In this study, we aim to investigate the diagnostic performance and clinical impact of F-AlF-OC in a large prospective cohort of patients with NEN. Between January 2023 and November 2023, a total of 219 patients with confirmed or suspected NEN were enrolled prospectively and underwent F-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 F-AlF-OC on clinical management. The reference standard was based on the results of histopathology or radiological follow-up. 205 patients were included in the final analysis. The patient-level sensitivity, specificity, and accuracy of F-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 F-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 F-AlF-OC PET/CT was 0.6 cm in the rectum, 0.3 cm in the stomach, and 0.5 cm in the duodenum. F-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. F-AlF-OC PET/CT demonstrated great diagnostic performance in patients with NEN, particularly for detecting tiny gastrointestinal NEN. Furthermore, F-AlF-OC PET/CT impacted the therapeutic management in 19.5% of patients. Our results further validate the role of F-AlF-OC as a somatostatin receptor imaging tracer in clinical practice.
Topics: Humans; Neuroendocrine Tumors; Male; Female; Middle Aged; Prospective Studies; Positron Emission Tomography Computed Tomography; Octreotide; Aged; Adult; Sensitivity and Specificity; Radiopharmaceuticals; Heterocyclic Compounds, 1-Ring; Receptors, Somatostatin; Fluorine Radioisotopes; Magnetic Resonance Imaging; Aged, 80 and over; Heterocyclic Compounds
PubMed: 38855183
DOI: 10.7150/thno.96762 -
Heliyon May 2024Patients with high-risk neuroblastoma (NB) have a 5-year event-free survival of less than 50 %, and novel and improved treatment options are needed. Radiolabeled...
BACKGROUND
Patients with high-risk neuroblastoma (NB) have a 5-year event-free survival of less than 50 %, and novel and improved treatment options are needed. Radiolabeled somatostatin analogs (SSTAs) could be a treatment option. The aims of this work were to compare the biodistribution and the therapeutic effects of Lu-octreotate and Lu-octreotide in mice bearing the human CLB-BAR NB cell line, and to evaluate their regulatory effects on apoptosis-related genes.
METHODS
The biodistribution of Lu-octreotide in mice bearing CLB-BAR tumors was studied at 1, 24, and 168 h after administration, and the absorbed dose was estimated to tumor and normal tissues. Further, animals were administered different amounts of Lu-octreotate or Lu-octreotide. Tumor volume was measured over time and compared to a control group given saline. RNA was extracted from tumors, and the expression of 84 selected genes involved in apoptosis was quantified with qPCR.
RESULTS
The activity concentration was generally lower in most tissues for Lu-octreotide compared to Lu-octreotate. Mean absorbed dose per administered activity to tumor after injection of 1.5 MBq and 15 MBq was 0.74 and 0.03 Gy/MBq for Lu-octreotide and 2.9 and 0.45 Gy/MBq for Lu-octreotate, respectively. Lu-octreotide treatment resulted in statistically significant differences compared to controls. Fractionated administration led to a higher survival fraction than after a single administration. The pro-apoptotic genes , , and were regulated after administration with Lu-octreotate. Treatment with Lu-octreotide yielded regulation of the pro-apoptotic genes and , and of the anti-apoptotic gene as well as the apoptosis-related gene .
CONCLUSION
Lu-octreotide gave somewhat better anti-tumor effects than Lu-octreotate. The similar effect observed in the treated groups with Lu-octreotate suggests saturation of the somatostatin receptors. Pronounced anti-tumor effects following fractionated administration merited receptor saturation as an explanation. The gene expression analyses suggest apoptosis activation through the extrinsic pathway for both radiopharmaceuticals.
PubMed: 38826727
DOI: 10.1016/j.heliyon.2024.e31409 -
Journal of Hand Surgery Global Online May 2024Chylous joint effusion is a rare condition characterized by the presence of a milky, viscous synovial fluid with abnormal lipid concentrations. The thorax is the most...
Chylous joint effusion is a rare condition characterized by the presence of a milky, viscous synovial fluid with abnormal lipid concentrations. The thorax is the most common site of involvement. Only a handful of cases have been reported in the field of orthopedic surgery and even fewer have been reported involving uncommon locations such as the knee. Treatment of chylous joint effusion may require surgical intervention along with the use of somatostatin or octreotide and a low-fat diet. We present herein a case of post-traumatic chylous effusion in the wrist treated with surgical incision and drainage, octreotide, and a low-fat diet. There have been few reports of chylous effusion in the knee; however, to our knowledge, this is the first report of post-traumatic chylous effusion in the wrist.
PubMed: 38817763
DOI: 10.1016/j.jhsg.2024.02.008 -
Cureus Apr 2024Gallstone disease is extremely common and frequently and safely treated by cholecystectomy. Chyle leak is a rare but significant side effect of many abdominal surgeries...
Gallstone disease is extremely common and frequently and safely treated by cholecystectomy. Chyle leak is a rare but significant side effect of many abdominal surgeries with rarely reported post-cholecystectomy. In this case, we report a 78-year-old lady with multiple comorbidities and symptomatic gallstones who underwent open cholecystectomy complicated by bile and chyle leak, which was successfully managed with endoscopic retrograde cholangiopancreatography (ERCP) and stenting for bile leak and conservative management for the chyle leak, which included drainage, low-fat diet, and octreotide.
PubMed: 38817462
DOI: 10.7759/cureus.59338 -
TouchREVIEWS in Endocrinology Apr 2024Injectable somatostatin receptor ligands (iSRL) are the most frequently utilized medical therapy in patients with acromegaly; however, satisfaction rates are suboptimal.... (Review)
Review
Injectable somatostatin receptor ligands (iSRL) are the most frequently utilized medical therapy in patients with acromegaly; however, satisfaction rates are suboptimal. Injections can result in local erythema, discomfort and subcutaneous nodule formation, encompassed with the inconvenience of attending either primary or secondary care medical facilities for injections every 4 weeks. Some patients also note breakthrough of acromegaly-related symptoms towards the end of the injection cycle. To improve acceptance and ultimately improve wellbeing of these individuals, two oral SRLs, oral octreotide capsules (OOC) and paltusotine, have been developed. The OOC combines an enteric coating to allow delivery to the small intestines and a transient permeability enhancer to enable oral bioavailability. Comparable octreotide levels are obtained with twice-daily OOC and subcutaneous octreotide 100 µg. Phase III studies show OOC to maintain equivalent biochemical control in at least 60% of patients previously receiving a stable dose of iSRL. In longer-term studies, the response to OOC was durable up to 3 years. Paltusotine is a novel potent orally available non-peptidyl somatostatin receptor subtype-2 ligand. Studies in healthy volunteers show dose-dependent suppression of growth hormone-releasing hormone-induced growth hormone secretion and suppression of insulin-like growth factor-I (IGF-I) with repeat doses. In the recent phase II study, patients with acromegaly who were partial responders (IGF-I 1.0 - 2.5 x upper limit of normal) to monotherapy with iSRL when switched to once-daily paltusotine maintained control of IGF-I within 20% of baseline or lower in 87% after 13 weeks. Adverse events with both OOC and paltusotine were reflective of those recognized with iSRL and occurred at a similar frequency. OOC and paltusotine are well-received additions to the therapeutic armamentarium in medical therapy for the management of acromegaly; however, further data on efficacy, tumour control and shrinkage are required to allow positioning of this medication within the management algorithm for acromegaly.
PubMed: 38812672
DOI: 10.17925/EE.2023.20.1.3 -
TouchREVIEWS in Endocrinology Apr 2024The primary goal of acromegaly treatment is to normalize biochemical parameters as it significantly reduces the risks of complications and comorbidities associated with... (Review)
Review
The primary goal of acromegaly treatment is to normalize biochemical parameters as it significantly reduces the risks of complications and comorbidities associated with the disease. First-line medical treatment is commonly represented by injectable somatostatin analogues (SRLs) after surgery. In June 2020, with the integration of Transient Permeation Enhancer® technology, oral octreotide capsules (OOCs) received regulatory approval from the US Food and Drug Administration for long-term maintenance treatment in patients with acromegaly who have responded to and tolerated treatment with octreotide or lanreotide. We reviewed the clinical pharmacological data on the development and clinical use of OOCs. The pharmacokinetic and pharmacodynamic data on OOCs showed a dose-dependent increase in octreotide levels and remarkable suppression of growth hormone secretion. The efficacy and safety of OOCs were investigated in four clinical trials conducted on patients with complete or partially controlled acromegaly. The trials resulted in the maintenance of biochemical control after switching from injectable SRLs to OOCs, with a comparable side-effect profile. Moreover, the acromegaly symptoms improved in patients on OOC. The data showed a patient preference to continue in the OOC arm for the extension phase of the trials. From the clinical pharmacological perspective, oral formulation of octreotide has the advantage of efficacy and safety with respect to injectable octreotide.
PubMed: 38812667
DOI: 10.17925/EE.2024.20.1.9