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European Journal of Nuclear Medicine... Jul 2024The need for an interval between the administration of long-acting Somatostatin Receptor Analogues (SSA) and the [Ga]Ga-DOTA-TATE PET has been questioned based on recent...
PURPOSE
The need for an interval between the administration of long-acting Somatostatin Receptor Analogues (SSA) and the [Ga]Ga-DOTA-TATE PET has been questioned based on recent literature in the new EANM guidelines. Here an earlier studies showed that SSA injection immediately before SSTR PET had minimal effect on normal organ and tumor uptake (1). However, data are scarce and there are (small) differences between [Ga]Ga-DOTA-TATE and [Ga]Ga-DOTA-TOC binding affinity, and it remains unknown whether these findings can be directly translated to scans with [Ga]Ga-DOTA-TOC as well. The purpose of this study was to assess the effect of SSA use on the biodistribution in a subsequent [Ga]Ga-DOTA-TOC PET/CT and compare this intra-individually across several cycles of SSA treatments.
METHODS
Retrospectively, 35 patients with NENs were included. [Ga]Ga-DOTA-TOC PET at staging and after the 1st and 2nd cycle of SSA were included. SUVmean and SUVmax of blood, visceral organs, primary tumor and two metastases were determined. Also, the interval between SSA therapy and the PET scan was registered.
RESULTS
Treatment with SSA resulted in a significantly higher bloodpool activity and lower visceral tracer uptake. This effect was maintained after a 2nd cycle of SSA therapy. Furthermore, there was an inverse relationship between bloodpool tracer availability and visceral tracer binding and a positive correlation between bloodpool tracer availability and primary tumor tracer uptake. With an interval of up to 5 days, there was a significantly higher bloodpool activity than at longer intervals.
CONCLUSION
Absolute comparison of the SUV on [Ga]Ga-DOTA-TOC PET should be done with caution as the altered biodistribution of the tracer after SSA treatment should be taken into account. We recommend not to perform a scan within the first 5 days after the injection of lanreotide.
Topics: Humans; Middle Aged; Tissue Distribution; Female; Male; Neuroendocrine Tumors; Positron Emission Tomography Computed Tomography; Aged; Octreotide; Somatostatin; Organometallic Compounds; Adult; Retrospective Studies; Radiopharmaceuticals; Aged, 80 and over
PubMed: 38403723
DOI: 10.1007/s00259-024-06659-0 -
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 -
Physica Medica : PM : An International... Mar 2024Physiologically based pharmacokinetic (PBPK) models offer the ability to simulate and predict the biodistribution of radiopharmaceuticals and have the potential to...
UNLABELLED
Physiologically based pharmacokinetic (PBPK) models offer the ability to simulate and predict the biodistribution of radiopharmaceuticals and have the potential to enable individualised treatment planning in molecular radiotherapy. The objective of this study was to develop and implement a whole-body compartmental PBPK model for peptide receptor radionuclide therapy (PRRT) with [Lu]Lu-DOTA-TATE in SimBiology to allow for more complex analyses. The correctness of the model implementation was ensured by comparing its outputs, such as the time-integrated activity (TIA), with those of a PBPK model implemented in SAAM II software.
METHODS
A combined PBPK model for [Ga]Ga-DOTA-TATE and [Lu]Lu-DOTA-TATE was developed and implemented in both SAAM II and SimBiology. A retrospective analysis of 12 patients with metastatic neuroendocrine tumours (NETs) was conducted. First, time-activity curves (TACs) and TIAs from the two software were calculated and compared for identical parameter values. Second, pharmacokinetic parameters were fitted to activity concentrations, analysed and compared.
RESULTS
The PBPK model implemented in SimBiology produced TIA results comparable to those generated by the model implemented in SAAM II, with a relative deviation of less than 0.5% when using the same input parameters. The relative deviation of the fitted TIAs was less than 5% when model parameter values were fitted to the measured activity concentrations.
CONCLUSION
The proposed PBPK model implemented in SimBiology can be used for dosimetry in radioligand therapy and TIA prediction. Its outputs are similar to those generated by the PBPK model implemented in SAAM II, confirming the correctness of the model implementation in SimBiology.
Topics: Humans; Tissue Distribution; Retrospective Studies; Octreotide; Heterocyclic Compounds, 1-Ring; Radiopharmaceuticals
PubMed: 38367588
DOI: 10.1016/j.ejmp.2024.103299 -
Frontiers in Oncology 2023Primary gallbladder gastrinoma is an exceptionally uncommon tumor and is a rare form of neuroendocrine neoplasm. Until now, no cases of primary gallbladder gastrinoma...
BACKGROUND
Primary gallbladder gastrinoma is an exceptionally uncommon tumor and is a rare form of neuroendocrine neoplasm. Until now, no cases of primary gallbladder gastrinoma and rare cases of primary gastrinoma from the biliary system have been reported.
CASE PRESENTATION
We report a case of a 50-year-old woman with watery diarrhea who intermittently received proton pump inhibitors (PPIs) as treatment. A serum gastrin level of 711 pg/ml was recorded after the withdrawal of PPI over 1 week. Enhanced computed tomography (CT) imaging and octreotide imaging uncovered a solitary tumor at the hepatic hilar region. During the laparoscopic surgery, it was determined that the tumor had its origin in the wall of the gallbladder neck, prompting the implementation of a laparoscopic cholecystectomy. Histological analysis revealed a primary neuroendocrine tumor from the neck of the gallbladder. The patient's symptoms disappeared after the surgery with a follow-up of 6 months.
CONCLUSIONS
This case confirmed that primary gallbladder gastrinoma represents a distinct nosological entity. Immunohistochemical analysis plays a pivotal role in the diagnostic process. Given the limited understanding of primary gallbladder gastrinoma, our objective is to offer novel insights into this rare disease by delivering distinctive information and highlighting the therapeutic significance of surgical intervention.
PubMed: 38357423
DOI: 10.3389/fonc.2023.1279766 -
World Journal of Clinical Cases Feb 2024While primary intestinal lymphangiectasia (PIL) is considered a rare condition, there have been several reported cases in adults. Nevertheless, the absence of clear...
BACKGROUND
While primary intestinal lymphangiectasia (PIL) is considered a rare condition, there have been several reported cases in adults. Nevertheless, the absence of clear guidance from diagnosis to treatment and prognosis poses challenges for both physicians and patients.
AIM
To enhance understanding by investigating clinical presentation, diagnosis, treatment, complications, and prognoses in adult PIL cases.
METHODS
We enrolled adult patients diagnosed with PIL between March 2016 and September 2021. The primary outcome involved examining the diagnosis and treatment process of these patients. The secondary outcomes included identifying complications (infections, thromboembolism) and assessing prognoses (frequency of hospitalization and mortality) during the follow-up period.
RESULTS
Among the 12 included patients, peripheral edema (100%) and diarrhea (75%) were the main presenting complaints. Laboratory tests showed that all the patients exhibited symptoms of hypoalbuminemia and hypogammaglobulinemia. Radiologically, the predominant findings were edema of the small intestine (67%) and ascites (58%). The typical endoscopic finding with a snowflake appearance was observed in 75% of patients. Among the 12 patients, two responded positively to octreotide and sirolimus, and eight who could undergo maintenance therapy discontinued subsequently. Complications due to PIL led to infection in half of the patients, thromboembolism in three patients, and one death.
CONCLUSION
PIL can be diagnosed in adults across various age groups, with different severity and treatment responses among patients, leading to diverse complications and prognoses. Consequently, tailored treatments will be necessary. We anticipate that our findings will contribute to the management of PIL, an etiology of protein-losing enteropathy.
PubMed: 38322684
DOI: 10.12998/wjcc.v12.i4.746 -
Frontiers in Endocrinology 2023Peptide receptor radionuclide therapy (PRRT) is a treatment option for well-differentiated, somatostatin receptor positive, unresectable or/and metastatic neuroendocrine...
INTRODUCTION
Peptide receptor radionuclide therapy (PRRT) is a treatment option for well-differentiated, somatostatin receptor positive, unresectable or/and metastatic neuroendocrine tumors (NETs). Although high disease control rates seen with PRRT a significant number NET patients have a short progression-free interval, and currently, there is a deficiency of effective biomarkers to pre-identify these patients. This study is aimed at determining the prognostic significance of biomarkers on survival of patients with NETs in initial PRRT treatment.
METHODOLOGY
We retrospectively analyzed 51 patients with NETs treated with PRRT at the Department for nuclear medicine, University Clinical Center Kragujevac, Serbia, with a five-year follow-up. Eligible patients with confirmed inoperable NETs, were retrospectively evaluated hematological, blood-based inflammatory markers, biochemical markers and clinical characteristics on disease progression. In accordance with the progression og the disease, the patients were divided into two groups: progression group (n=18) and a non-progression group (n=33). Clinical data were compared between the two groups.
RESULTS
A total of 51 patients (Md=60, age 25-75 years) were treated with PRRT, of whom 29 (56.86%) demonstrated stable disease, 4 (7.84%) demonstrated a partial response, and 14 (27.46%) demonstrated progressive disease and death was recorded in 4 (7.84%) patients. The mean PFS was a 36.22 months (95% CI 30.14-42.29) and the mean OS was 44.68 months (95% CI 37.40-51.97). Univariate logistic regression analysis displayed that age (p<0.05), functional tumors (p<0.05), absolute neutrophil count (p<0.05), neutrophil-lymphocyte ratio-NLR (p<0.05), C-reactive protein-CRP (p<0.05), CRP/Albumin (p<0.05), alanine aminotransferase-ALT (p<0.05), were risk factors for disease progression. Multivariate logistic regression analysis exhibited that functional tumors (p<0.001), age (p<0.05), CRP (p<0.05), and ALT (p<0.05), were independent risk factors for the disease progression in patients with NETs. Tumor functionality was the most powerful prognostic factor. The median PFS (11.86 ± 1.41 vs. 43.38 ± 3.16 months; p=0.001) and OS (21.81 ± 2.70 vs 53.86 ± 3.70, p=0.001) were significantly shorter in patients with functional than non-functional NETs respectively.
CONCLUSION
The study's results suggest that tumor functionality, and certain biomarkers may serve as prognostic survival indicators for patients with NETs undergoing PRRT. The findings can potentially help to identify patients who are at higher risk of disease progression and tailor treatment strategies accordingly.
Topics: Humans; Adult; Middle Aged; Aged; Octreotide; Retrospective Studies; Serbia; Neuroendocrine Tumors; Radioisotopes; Disease Progression; Biomarkers; Receptors, Peptide
PubMed: 38317712
DOI: 10.3389/fendo.2023.1270421 -
Annals of Palliative Medicine Jan 2024Efficacy of the combination of octreotide and other drugs for the management of malignant bowel obstruction (MBO) has been well described. However, long-lasting stages...
BACKGROUND
Efficacy of the combination of octreotide and other drugs for the management of malignant bowel obstruction (MBO) has been well described. However, long-lasting stages with lack of stool emission are a challenging clinical condition of MBO that have never described.
CASE DESCRIPTION
We describe two cases in which the addition of octreotide to supportive care measures, even given late after more than 3 weeks of no stool emission, resulted to be still effective in recovering the bowel transit. In the first case, a patient admitted to home palliative care had a nasogastric tube and reported to not have stool emission and passing gas for 25 days. Two days after starting the combination of octreotide and other drugs, the patient evacuated and the nasogastric tube was removed, without reporting nausea or episodes of vomiting. In the second case, a patient admitted to an acute palliative care unit, the patient had no stool emission for more than 3 weeks. A nasogastric tube was placed and comprehensive palliative care treatment was provided. Two days after starting a combination of octreotide and other drugs, the nasogastric tube was removed, without reporting vomiting. In both cases, bowel transit recovered and patients were able to initiate oral nutrition.
CONCLUSIONS
The combination of octreotide with other drugs described for standard treatment for the management of MBO, should be attempted even in patients with very long periods of lack of feces emission.
Topics: Humans; Octreotide; Gastrointestinal Agents; Intestinal Obstruction; Vomiting; Nausea; Palliative Care
PubMed: 38316401
DOI: 10.21037/apm-23-311 -
Thyroid Research Feb 2024Coexistence of TSH-secreting pituitary adenoma (TSHoma) and Graves' disease (GD) is rare and complicates the management decision.
BACKGROUND
Coexistence of TSH-secreting pituitary adenoma (TSHoma) and Graves' disease (GD) is rare and complicates the management decision.
METHODS
We present a case of the co-existence of TSHoma and GD. In addition, we systematically searched articles describing TSHoma and GD in the same patient published until 20th March 2023, using Pubmed, Scopus and Embase.
CASE PRESENTATION
A 46-year-old man presented with symptoms of thyrotoxicosis. His thyroid function tests showed serum TSH 3.35 (reference range 0.3-4.2) mIU/L, FT3 19.7 (3.7-6.4) pmol/L, and FT4 68.9 (11-23.3) pmol/L. The serum TSH receptor antibody was 11.5 mIU/L (positive at ≥ 1.75 mIU/L). Pituitary magnetic resonance imaging showed macroadenoma compressing the optic chiasm. The patient underwent trans-sphenoidal resection of pituitary adenoma. Postoperatively, he remained on maintenance carbimazole and octreotide.
RESULTS
Fourteen articles comprising 15 patients were identified from the systemic search. A total of 16 patients (including the current case) were included in the systematic review. The mean (± SD) age at diagnosis was 41 ± 13.6 years. The majority were females (75%). The median (IQR) TSH was 1.95 (0.12-5.5) mIU/L, the median (IQR) free T3 was 11.7 (7.6-19.7) pmol/L and the median (IQR) free T4 level was 47.6 (33.3-64.4) pmol/L. Ten (76.9%) patients had positive TSH receptor antibody levels. 84.6% had pituitary macroadenoma. Pituitary surgery was performed in 12 (75%) patients. At the last follow-up, 4 (25%) patients had complete resolution of symptoms after pituitary surgery, 3 (18.7%) were on maintenance treatment with thionamides for GD, 1 (6.25%) on beta-blockers and 1 (6.25%) on somatostatin analog.
CONCLUSION
TSHoma and GD can co-exist, and it is essential to identify this rare association as it can significantly impact treatment strategies.
PubMed: 38311752
DOI: 10.1186/s13044-023-00184-2 -
JCEM Case Reports Feb 2024The 1p36 deletion syndrome involves a phenotypic presentation that includes central nervous system, cardiac, and craniofacial anomalies. We report the case of a...
The 1p36 deletion syndrome involves a phenotypic presentation that includes central nervous system, cardiac, and craniofacial anomalies. We report the case of a 21-year-old female patient with 1p36 deletion syndrome who was found to have noninsulinoma pancreatogenous hypoglycemia syndrome (NIPHS) after hospitalization for persistent falls. On admission, vital signs were normal and physical examination revealed a thin, nonverbal patient. During hospitalization and prolonged fasting (14-18 hours), she persistently developed hypoglycemia (serum glucose nadir 57 mg/dL [3.2 mmol/L] [70-100 mg/dL; 3.9-5.6 mmol/L]). Subjective symptoms of hypoglycemia were not confirmed due to patient's cognitive impairment. Hypoglycemic events continued despite feeding and dextrose-containing fluids. Further workup included a critical sample that revealed a serum glucose 59 mg/dL (3.3 mmol/L), insulin 20.6 μIU/mL (123.6 pmol/L [5-15 μIU/mL; 30.0-90 pmol/L]), proinsulin 33 pmol/L (3.6-22 pmol/L), C-peptide 1.74 ng/mL (0.58 nmol/L [0.8-3.85 ng/mL; 0.27-1.28 nmol/L]) and beta-hydroxybutyrate < 1.04 mg/dL (< 0.10 mmol/L; [< 4.2 mg/dL; < 0.4 mmol/L]). Insulin antibodies were negative. After confirmed insulin-mediated hypoglycemia, imaging studies followed. Pancreatic protocol abdominal computed tomography (CT), Ga-68 DOTATATE PET/CT scan, and endoscopic ultrasound found no pancreatic mass. Selective arterial calcium stimulation test showed a two-fold increase in insulin levels in 3/3 catheterized pancreatic territories. The patient started octreotide injections with resolution of hypoglycemia and was discharged on monthly lanreotide injections. To our knowledge, this is the first case reported of noninsulinoma pancreatogenous hypoglycemia in a patient with 1p36 deletion syndrome.
PubMed: 38304011
DOI: 10.1210/jcemcr/luae003