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Journal of Nuclear Medicine : Official... Sep 2017Ga-DOTATOC, a somatostatin receptor-targeted ligand, has been used clinically in Europe over the past decade for imaging neuroendocrine tumors (NETs). It appears to be... (Meta-Analysis)
Meta-Analysis Review
Ga-DOTATOC, a somatostatin receptor-targeted ligand, has been used clinically in Europe over the past decade for imaging neuroendocrine tumors (NETs). It appears to be quite sensitive and effective for clinical management decision making. This metaanalysis summarizes the efficacy of Ga-DOTATOC for several distinct indications and is intended to support approval of this agent by the U.S. Food and Drug Administration. The major electronic medical databases were searched for relevant papers over the period from January 2001 to November 2015. Papers were selected for review in 3 categories: clinical trials that reported sensitivity and specificity, comparison studies with In-octreotide, and change of management studies. All the eligible papers underwent Quality Assessment of Diagnostic Accuracy Studies (QUADAS) assessment, which was useful in the final selection of papers for review. The initial search yielded 468 papers. After detailed evaluation, 17 papers were finally selected. Five types of studies emerged: workup of patients with symptoms and biomarker findings suggestive of NET, but with negative conventional imaging (3 papers, yield was only 13%); sensitivity (12 papers; sensitivity, 92%) and specificity (7 papers; specificity, 82%); identification of site of unknown primary in patients with metastatic NET (4 papers, yield was 44%); impact on subsequent NET patient management (4 papers, change in management in 51%); and comparison with In-octreotide (2 papers, sensitivity of DOTATOC on a per-lesion basis was 100%, for In-octreotide it was 78.2%; specificity was not available). Safety was not explicitly addressed in any study, but there were no reports of adverse events. Ga-DOTATOC is useful for evaluating the presence and extent in disease for staging and restaging and for assisting in treatment decision making for patients with NET. It is also effective in locating the site of an unknown primary in NET patients who present with metastatic NET, but no known primary tumor. It also appears to be more accurate than In-octreotide. Although Ga-DOTATOC would seem to be useful in evaluating patients with suggestive symptoms and biomarker findings, it does not perform well in this setting and has low yield. Overall, it appears to be an excellent imaging agent to assess patients with known NET and frequently leads to a change in management.
Topics: Diagnostic Imaging; Humans; Neuroendocrine Tumors; Octreotide; Organometallic Compounds; Sensitivity and Specificity
PubMed: 28280220
DOI: 10.2967/jnumed.117.191197 -
International Journal of Molecular... Feb 2024Carcinoid heart disease (CHD) is a frequent and life-threatening complication in patients with carcinoid tumors. Its clinical management is challenging is some cases...
Carcinoid heart disease (CHD) is a frequent and life-threatening complication in patients with carcinoid tumors. Its clinical management is challenging is some cases since serotonin-induced valve fibrosis leads to heart failure. Telotristat is an inhibitor of tryptophan-hydroxylase (TPH), a key enzyme in serotonin production. Telotristat use in patients with carcinoid syndrome and uncontrollable diarrhea under somatostatin analogs is approved, but its specific role in patients with CHD is still not clear. IN this context, we aimed to explore the effect of telotristat in heart fibrosis using a mouse model of serotonin-secreting metastasized neuroendocrine neoplasm (NEN). To this aim, four treatment groups (n = 10/group) were evaluated: control, monthly octreotide, telotristat alone, and telotristat combined with octreotide. Plasma serotonin and NT-proBNP levels were determined. Heart fibrosis was histologically evaluated after 6 weeks of treatment or when an individual mouse's condition was close to being terminal. Heart fibrosis was observed in all groups. Non-significant reductions in primary tumor growth were observed in all of the treated groups. Feces volume was increased in all groups. A non-significant decrease in feces volume was observed in the octreotide or telotristat-treated groups, while it was significantly reduced with the combined treatment at the end of the study compared with octreotide (52 g reduction; < 0.01) and the control (44.5 g reduction; = 0.05). Additionally, plasma NT-proBNP decreased in a non-significant, but clinically relevant, manner in the octreotide (28.2% reduction), telotristat (45.9% reduction), and the octreotide + telotristat (54.1% reduction) treatment groups. No significant changes were observed in plasma serotonin levels. A similar non-significant decrease in heart valve fibrosis was observed in the three treated groups. In conclusion, Telotristat alone and especially in combination with octreotide decreases NT-proBNP levels in a mouse model of serotonin-secreting metastasized NEN, when compared with the control and octreotide, but its effect on heart valve fibrosis (alone and in combination) was not superior to octreotide in monotherapy.
Topics: Humans; Octreotide; Carcinoid Heart Disease; Serotonin; Neuroendocrine Tumors; Fibrosis; Phenylalanine; Pyrimidines
PubMed: 38396713
DOI: 10.3390/ijms25042036 -
BMC Gastroenterology May 2021Efficacy of pancreatic enzyme inhibitors in acute pancreatitis (AP) is unclear in China.
BACKGROUND
Efficacy of pancreatic enzyme inhibitors in acute pancreatitis (AP) is unclear in China.
AIMS
We aimed to present the current status of AP and evaluate the efficacy of pancreatic enzyme inhibitors in a larger population in China.
METHOD
A retrospective, cross-sectional, real-world, multicenter analysis of a large dataset of patients presenting with AP from four hospitals of China over a two-year period was performed. Data were collected from the existing clinical records and the patients were grouped into medication group (somatostatin or octreotide or somatostatin and octreotide) and no medication group. Pair wise propensity score matching was performed for comparing somatostatin, octreotide and somatostatin/octreotide. The end points were incidence of disease complications, organ failure, hospitalization duration, and recovery time taken (hours) for serum amylase/serum lipase to normalcy.
RESULTS
A total of 3900 patients were recruited and 2775 patients were included for analysis. A total of 1100, 661, 676 and 338 patients received either somatostatin or octreotide or somatostatin and octreotide or no medication, respectively. The incidence of complications (7.6% vs 13.6%), organ failure (4.5% vs 7.4%), and the instances of entering ICU (9.3% vs 13.3%) were higher in unmedicated group. Complications at discharge (2.91 times), organ failure (2.53 times), and hospitalization stay were higher in octreotide-treated patients compared with somatostatin-treated patients. In comparison to the octreotide group, the serum amylase/lipase recovery time was shorter in the somatostatin group.
CONCLUSION
This real-world study suggested that the use of pancreatic enzyme inhibitors was positively associated with greater clinical efficacy in AP patients and somatostatin might be more effective than octreotide in real-world settings in China.
Topics: Acute Disease; China; Cross-Sectional Studies; Humans; Octreotide; Pancreatitis; Retrospective Studies
PubMed: 33964868
DOI: 10.1186/s12876-021-01799-1 -
Endocrine Journal Sep 2017Octreotide, a long-acting somatostatin analog, has been used for treating hypoglycemia caused by congenital hyperinsulinism (CHI). However, octreotide has not been... (Clinical Trial)
Clinical Trial Observational Study
Efficacy and safety of octreotide for the treatment of congenital hyperinsulinism: a prospective, open-label clinical trial and an observational study in Japan using a nationwide registry.
Octreotide, a long-acting somatostatin analog, has been used for treating hypoglycemia caused by congenital hyperinsulinism (CHI). However, octreotide has not been evaluated in clinical trials and has not been approved in any developed country. We aimed to test the efficacy and safety of octreotide for diazoxide-unresponsive CHI through a combination of a single-arm, open-label clinical trial (SCORCH study) and an observational study to collect data on the clinical course of patients treated off-label in Japan (SCORCH registry). In the SCORCH study, 5 patients were stabilized (blood glucose > 45 mg/dL) by hypertonic glucose infusion, and treated by continuous subcutaneous octreotide infusion at a dose of 5-25 μg/kg/day. Continuous blood glucose monitoring was performed between -24 and +48 hours. In 3 patients, a clinically meaningful rise in blood glucose was achieved and therapy was continued. The glucose infusion was gradually decreased and stopped after 5, 11, and 174 days, respectively. In one case, remission of CHI was reached after 606 days and octreotide was discontinued. The SCORCH registry included 19 diazoxide-unresponsive patients treated by subcutaneous octreotide, by continuous infusion or multiple daily injections. Of the 17 patients treated with hypertonic glucose infusion, the infusion rate was reduced after 4 weeks to less than 50% in 11 patients (64.7%) and stopped in 9 (52.9%). During the combined observation period of 695.4 patient-months in both studies, no severe adverse events related to octreotide were observed. In conclusion, subcutaneous octreotide injection was effective and well tolerated in the majority of patients with diazoxide-unresponsive CHI.
Topics: Blood Glucose; Congenital Hyperinsulinism; Female; Humans; Infant; Infant, Newborn; Japan; Male; Octreotide; Prospective Studies; Registries; Remission Induction; Somatostatin; Treatment Outcome
PubMed: 28701683
DOI: 10.1507/endocrj.EJ17-0024 -
Frontiers in Endocrinology 2022The process of GPCR dimerization can have profound effects on GPCR activation, signaling, and intracellular trafficking. Somatostatin receptors (SSTs) are class A GPCRs...
The process of GPCR dimerization can have profound effects on GPCR activation, signaling, and intracellular trafficking. Somatostatin receptors (SSTs) are class A GPCRs abundantly expressed in pituitary tumors where they represent the main pharmacological targets of somatostatin analogs (SSAs), thanks to their antisecretory and antiproliferative actions. The cytoskeletal protein filamin A (FLNA) directly interacts with both somatostatin receptor type 2 (SST) and 5 (SST) and regulates their expression and signaling in pituitary tumoral cells. So far, the existence and physiological relevance of SSTs homo- and hetero-dimerization in the pituitary have not been explored. Moreover, whether octreotide or pasireotide may play modulatory effects and whether FLNA may participate to this level of receptor organization have remained elusive. Here, we used a proximity ligation assay (PLA)-based approach for the visualization and quantification of SST/SST dimerization in rat GH3 as well as in human melanoma cells either expressing (A7) or lacking (M2) FLNA. First, we observed the formation of endogenous SST homo-dimers in GH3, A7, and M2 cells. Using the PLA approach combined with epitope tagging, we detected homo-dimers of human SST in GH3, A7, and M2 cells transiently co-expressing HA- and SNAP-tagged SST. SST and SST can also form endogenous hetero-dimers in these cells. Interestingly, FLNA absence reduced the basal number of hetero-dimers (-36.8 ± 6.3% reduction of PLA events in M2, P < 0.05 . A7), and octreotide but not pasireotide promoted hetero-dimerization in both A7 and M2 (+20.0 ± 11.8% and +44.1 ± 16.3% increase of PLA events in A7 and M2, respectively, P < 0.05 . basal). Finally, immunofluorescence data showed that SST and SST recruitment at the plasma membrane and internalization are similarly induced by octreotide and pasireotide in GH3 and A7 cells. On the contrary, in M2 cells, octreotide failed to internalize both receptors whereas pasireotide promoted robust receptor internalization at shorter times than in A7 cells. In conclusion, we demonstrated that in GH3 cells SST and SST can form both homo- and hetero-dimers and that FLNA plays a role in the formation of SST/SST hetero-dimers. Moreover, we showed that FLNA regulates SST and SST intracellular trafficking induced by octreotide and pasireotide.
Topics: Animals; Dimerization; Filamins; Humans; Octreotide; Pituitary Neoplasms; Rats; Somatostatin
PubMed: 35992099
DOI: 10.3389/fendo.2022.892668 -
The Quarterly Journal of Nuclear... Dec 2008Meta-iodobenzylguanidine (MIBG) is a structural analogue of the neurotransmitter norepinephrine (NE) and is taken up by cells rich in sympathetic neurons by an active... (Review)
Review
Meta-iodobenzylguanidine (MIBG) is a structural analogue of the neurotransmitter norepinephrine (NE) and is taken up by cells rich in sympathetic neurons by an active uptake process mediated by the NE transporter, which is referred to as uptake-1. It is a valuable agent in the diagnosis of myocardial abnormalities as well as that of several neuroendocrine tumors such as neuroblastoma, pheochromocytoma and carcinoid tumors. MIBG labeled with (131)I also is used extensively in the therapy of several neuroendocrine tumors. Over the years, a substantial amount of work has been undertaken to improve its clinical utility. Currently, radio-iodinated MIBG used in the clinic is prepared by an exchange radio-iodination method and, thus, is of low specific activity. For possible better targeting and to ward off pharmacological effects, its preparation at a no-carrier-added level both by solution-phase and solid-phase synthesis has been developed. For potential use in the treatment of micrometastatic diseases, synthesis of an analogue labeled with the a emitter (211)At was devised. Development of analogues labeled with positron emitting radionuclides such as (124)I, (18)F, and (76)Br has been reported. Further, efforts have been put in to improve its pharmacokinetic properties by structural modifications. Various aspects of these developments are reviewed herein.
Topics: 3-Iodobenzylguanidine; Animals; Guanidine; Humans; Iodine Radioisotopes; Octreotide; Positron-Emission Tomography
PubMed: 19088690
DOI: No ID Found -
Acta Gastro-enterologica Belgica 2010This paper reviews the research that has been conducted into the use of Sandostatin to control the debilitating symptoms of diarrhea in a number of different etiologies.... (Review)
Review
This paper reviews the research that has been conducted into the use of Sandostatin to control the debilitating symptoms of diarrhea in a number of different etiologies. These are cancer-related diarrheas, including diarrhea related to chemotherapy, radiotherapy, neuroendocrine tumor carcinoid syndrome, vasoactive intestinal peptide-secreting tumors and also non-cancer related diarrhea, including short bowel syndrome, ileo- and jejunostomy, dumping syndrome, graft versus host disease and AIDS-related diarrhea. There is an increasing recognition of the need to balance the cost of care with patient outcome. It is becoming clear that although the cost of a therapeutic regimen with Sandostatin is substantially greater than the current non-specific therapy, the overall cost is potentially greater without the use of Sandostatin for patients with refractory diarrhea due to the inevitable need for further treatment and/or hospitalization with intravenous fluid supplementation. Initial trials and reports from preclinical testing and clinical practice have shown promising results and, although in the majority of cases they strengthen the view taken in the published consensus guidelines for the use of Sandostatin for refractory diarrhea, further, larger scale, comparative clinical trials are required for any evidence-based definition of dosage and efficacy as a treatment or prophylactic agent to combat and control diarrhea.
Topics: Diarrhea; Gastrointestinal Agents; Humans; Octreotide
PubMed: 20458847
DOI: No ID Found -
Revista de Gastroenterologia de Mexico... 2022Fifty percent of small bowel bleeding is caused by angioectasia and the rebleeding rate due to small bowel angioectasia (SBA) is 80%. Its endoscopic treatment is...
INTRODUCTION
Fifty percent of small bowel bleeding is caused by angioectasia and the rebleeding rate due to small bowel angioectasia (SBA) is 80%. Its endoscopic treatment is difficult. Beneficial effects of octreotide on gastrointestinal angioectasia have been described, but no studies have reported its efficacy in SBA.
AIM
Our aim was to investigate the effectiveness of octreotide in the prevention of rebleeding due to SBA.
MATERIAL AND METHODS
Sixteen patients with bleeding caused by SBA were assigned to treatment with octreotide 100 μg/24 h SC, for at least 6 months, and compared with a non-treatment group of 36 patients. The primary outcome was the rebleeding rate, and the secondary outcomes were the number of hospital readmissions, bleeding-related death, and adverse effects.
RESULTS
Octreotide was administered for 10.5 ± 8.4 months. Follow-up was 12.9 ± 17.3 months and 15.3 ± 17.7 months, in the treatment and non-treatment groups, respectively (p = 0.09). At the end of follow-up, 4 (25%) treatment group patients and 26 (72.2%) non-treatment group patients presented with rebleeding (p = 0.002). In the treatment group and non-treatment group, the cumulative probability of remaining rebleeding-free at one year was 79% vs 44.2%, and 79% vs 34.6% at 2 years, respectively (p = 0.05). Through the multiple logistic regression analysis, treatment was the protective variable. Six patients presented with adverse events. One of those patients (6.25%) had a major adverse event.
CONCLUSIONS
Our results suggest that treatment with octreotide could be efficacious in the prevention of rebleeding due to SBA.
Topics: Humans; Octreotide; Intestine, Small; Gastrointestinal Hemorrhage; Dilatation, Pathologic
PubMed: 35691890
DOI: 10.1016/j.rgmxen.2022.05.016 -
Supportive Care in Cancer : Official... Jul 2022Neuroendocrine tumors (NETs) negatively impact patients' quality of life. Octreotide long-acting release (LAR) and lanreotide depot are somatostatin analogs (SSAs)...
PURPOSE
Neuroendocrine tumors (NETs) negatively impact patients' quality of life. Octreotide long-acting release (LAR) and lanreotide depot are somatostatin analogs (SSAs) approved to treat NETs. The study objective was to explore SSA treatment experiences and preferences of patients with NETs.
METHODS
Qualitative interviews were conducted in US adults (≥ 21 years) with NETs who had ≥ 6 months' treatment with each SSA and transitioned from octreotide LAR to lanreotide depot within the previous year. Participants were asked open-ended questions about their experiences with octreotide LAR and lanreotide depot, treatment preferences, and SSA treatment attributes.
RESULTS
Twenty participants (mean age: 58 years; 90% female; 85% white) completed interviews. The most common reasons for treatment transition were doctor recommendation (70%), treatment not working as expected (55%), and injection type preference (45%). Participants reported 34 unique favorable attributes of SSA treatment and 82 unique unfavorable attributes. Symptom control was the most frequently reported favorable attribute (associated with octreotide LAR by 60% of participants and lanreotide depot by 65%). Painful injection (65%) was most frequently cited unfavorable attribute for octreotide LAR and injection experience dependent on administrator (35%) for lanreotide depot. The three SSA treatment attributes rated as most important were side effects, symptom control, and ability to stabilize tumor.
CONCLUSION
Our qualitative data provide valuable insight into the treatment attributes that patients with NETs consider important when making SSA treatment decisions. Factors related to injection administration, side effects, and symptom control are important to patients and should be included in patient-provider communications in clinical contexts.
Topics: Female; Humans; Male; Middle Aged; Neuroendocrine Tumors; Octreotide; Quality of Life; Somatostatin
PubMed: 35476113
DOI: 10.1007/s00520-022-07054-x -
Journal of Pain and Symptom Management Jul 2010
Review
Topics: Ascites; Gastrointestinal Agents; Humans; Intestinal Obstruction; Octreotide; Pain
PubMed: 21634046
DOI: 10.1016/j.jpainsymman.2010.05.002