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Peptide Receptor Radionuclide Therapy for Neuroendocrine Tumours
Published in Michael Ljungberg, Handbook of Nuclear Medicine and Molecular Imaging for Physicists, 2022
Anna Sundlöv, Katarina Sjögreen Gleisner
The somatostatin receptor (SSTR) is a transmembrane, G-protein-coupled receptor that is expressed by neuroendocrine cells present in most tissues and organs throughout the body. NETs, being tumours made up of neuroendocrine cells, have an especially high receptor density. There are five subtypes of the SSTR, and different tissues express different combinations of receptor subtypes. The natural ligand, somatostatin, is a hormone secreted by the hypothalamus, whose function is to inhibit the hormonal secretion from neuroendocrine cells [2]. The same effect can be achieved through injection of a synthetic analogue of somatostatin (SSA), which has been used since the 1980s to treat acromegaly (hypersecretion of growth hormone) and NETs.
Endocrine Therapies
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
In the brain, somatostatin is produced by several populations of cells such as the neuroendocrine neurons of the ventro medial nucleus of the hypothalamus. These project into the area known as the median eminence, from where somatostatin is released from neurosecretory nerve endings in the neuron axons into the hypothalamo-hypophysial system. It is then carried to the anterior pituitary gland where it interacts with somatostatin receptors to cause a number of effects including inhibition of release of Growth Hormone (thus opposing the effects of Growth Hormone–Releasing Hormone (GHRH)), thyroid-stimulating hormone (TSH), and prolactin (PRL). Somatostatin receptors are expressed at many different sites in the brain including the hippocampus and brainstem nucleus of the solitary tract which explains the wide-reaching influence of this hormone system. Furthermore, the somatostatin neurons in the periventricular nucleus mediate negative feedback effects for the release of Growth Hormone.
Postoperative complications
Published in Tom Cecil, John Bunni, Akash Mehta, A Practical Guide to Peritoneal Malignancy, 2019
Splenectomy is frequently performed during CRS, especially for PMP. In the largest single-centre experience in Basingstoke, no instances of overwhelming post-splenectomy sepsis have been reported, probably due to the development and implementation of post-splenectomy prophylaxis protocols and early administration of antibiotics in patients who develop infective complications. Post-splenectomy pancreatitis occurs in approximately 5% of patients and can usually be treated adequately with conservative management. Similarly, most pancreatic leaks (defined as a left upper quadrant fluid collection after the third postoperative day with an amylase content 3 times the serum amylase level) are managed conservatively with total parenteral nutrition (TPN) and prolonged drainage. Repeat imaging and further percutaneous drainage is often required. Occasionally, a somatostatin analogue and antibiotics are administered. Occasionally an endoscopically placed pancreatic duct stent (via ERCP) is required and advice and help should be sought for patients with persistent pancreatic fistulas.
Octreotide and Octreotide-derived delivery systems
Published in Journal of Drug Targeting, 2023
Mingliang Fan, Yue Huang, Xinlin Zhu, Jiayu Zheng, Mingwei Du
The tetradecapeptide somatostatin is secreted by hypothalamus or delta cells in gastrointestinal tract and interacts with somatostatin receptors (SSTRs), which is a group of GPCRs (G-protein-coupled receptors) with five human receptor subtypes (SSTR 1-5). Somatostatin can inhibit the release of a series of hormones or neuropeptides in many organs, including growth hormone, insulin, glucagon, among others, thus taking important roles in many physiological functions. However, its clinical applications are remarkably restricted by poor circulation time (about 3 min) in the blood. Hence a variety of somatostatin analogs with longer circulation time have been developed for clinical use since 1970s [1]. Among them, Octreotide (SMS 201-995) is the most widely developed representative of somatostatin analog and stands the test of clinical application [2]. As a therapeutic agent and targeting ligand, Octreotide (OCT) has also been involved in the construction of many novel pharmaceutical systems for tumour targeted treatment. Given OCT-derived radionuclide therapy and radionuclide imaging were well reviewed by previous publication [3], we herein focus on the preclinical studies of some novel pharmaceutical delivery systems related to OCT, including microsphere, conjugate, liposome, polymeric nanoparticle, hydrogel and inorganic nanoparticle.
Metastatic neuroendocrine carcinoma presenting with left lateral rectus enlargement and orbital cellulitis
Published in Baylor University Medical Center Proceedings, 2021
Kevin Garrett Tayon, Vishal Kaila, Deepak Sobti, Ivan Vrcek
The patient underwent transconjunctival left orbitotomy with incisional biopsy and debulking of the lateral rectus lesion. Histopathologic analysis showed well-differentiated NET with uniform cells and regular nuclei with expression of neuroendocrine markers including chromogranin A and synaptophysin. Immunostaining revealed expression of CDX2 and villin, found in small intestine primary tumors (Figure 2). The Ki-67 proliferative index was low. Subsequent staging computed tomography (CT) revealed a 10 mm enhancing nodule in the small bowel mesentery. A 68Ga-DOTATATE scan revealed the focus of activity within the lateral aspect of the left orbit, the distal ileum, and an ileocolic mesenteric lymph node. Somatostatin receptor scintigraphy demonstrated no somatostatin-receptor positivity. At 2-month follow-up, the patient’s headache, diplopia, and afferent pupillary defect had resolved. Given the low volume of residual disease, further surgical debulking and systemic therapies were deferred.
Partial splenic embolization is superior to intravenous somatostatin for decreasing portal pressure in cirrhotic patients: a dynamic self-controlled cohort study
Published in Scandinavian Journal of Gastroenterology, 2020
Jiangtao Liu, Xuyang Sun, Suvranu Ganguli, Eric Paul Wehrenberg-Klee, Irun Bhan, Yiming Zhao, Li Zhao, Ke Meng, Rui Sun, Haotian Yu, Gang Sun
A total of 18 subjects were included in the study. Demographic and clinical information is shown in Table 1. All subjects completed the entire procedure, with a 100% technical success rate. No adverse events were recorded during the administration of somatostatin aside from mild self-resolving abdominal pain in one patient. 10 patients (10/18) developed fever with oral temperature 38.1–38.7 °C sustained for 1–4 days post-PSE. 13 patients (13/18) had left upper abdominal pain with a numeric rating scale (NRS-11) of 2–5 points post-PSE and no intervention was required. The mean time of hospitalization post-PSE was 6.8 ± 1.6 days and no subjects had serious adverse events during hospitalization. Consecutive endoscopic follow-up after discharge for risk evaluation of esophageal and/or gastric varices was advised. During the 6-month follow-up endoscopic study of patients with a history of variceal bleeding and a 1-year routine endoscopic monitor of patients without a history of variceal bleeding, there was no evidence of varices progression and no clinical variceal bleeding attack was recorded. The ‘Red sign’ of 4 patients, out of 16 (25%)with this sign on endoscopy, disappeared at follow-up endoscopy.