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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 -
European Journal of Nuclear Medicine... May 2024Accurate dosimetry is critical for ensuring the safety and efficacy of radiopharmaceutical therapies. In current clinical dosimetry practice, MIRD formalisms are widely...
PURPOSE
Accurate dosimetry is critical for ensuring the safety and efficacy of radiopharmaceutical therapies. In current clinical dosimetry practice, MIRD formalisms are widely employed. However, with the rapid advancement of deep learning (DL) algorithms, there has been an increasing interest in leveraging the calculation speed and automation capabilities for different tasks. We aimed to develop a hybrid transformer-based deep learning (DL) model that incorporates a multiple voxel S-value (MSV) approach for voxel-level dosimetry in [Lu]Lu-DOTATATE therapy. The goal was to enhance the performance of the model to achieve accuracy levels closely aligned with Monte Carlo (MC) simulations, considered as the standard of reference. We extended our analysis to include MIRD formalisms (SSV and MSV), thereby conducting a comprehensive dosimetry study.
METHODS
We used a dataset consisting of 22 patients undergoing up to 4 cycles of [Lu]Lu-DOTATATE therapy. MC simulations were used to generate reference absorbed dose maps. In addition, MIRD formalism approaches, namely, single S-value (SSV) and MSV techniques, were performed. A UNEt TRansformer (UNETR) DL architecture was trained using five-fold cross-validation to generate MC-based dose maps. Co-registered CT images were fed into the network as input, whereas the difference between MC and MSV (MC-MSV) was set as output. DL results are then integrated to MSV to revive the MC dose maps. Finally, the dose maps generated by MSV, SSV, and DL were quantitatively compared to the MC reference at both voxel level and organ level (organs at risk and lesions).
RESULTS
The DL approach showed slightly better performance (voxel relative absolute error (RAE) = 5.28 ± 1.32) compared to MSV (voxel RAE = 5.54 ± 1.4) and outperformed SSV (voxel RAE = 7.8 ± 3.02). Gamma analysis pass rates were 99.0 ± 1.2%, 98.8 ± 1.3%, and 98.7 ± 1.52% for DL, MSV, and SSV approaches, respectively. The computational time for MC was the highest (~2 days for a single-bed SPECT study) compared to MSV, SSV, and DL, whereas the DL-based approach outperformed the other approaches in terms of time efficiency (3 s for a single-bed SPECT). Organ-wise analysis showed absolute percent errors of 1.44 ± 3.05%, 1.18 ± 2.65%, and 1.15 ± 2.5% for SSV, MSV, and DL approaches, respectively, in lesion-absorbed doses.
CONCLUSION
A hybrid transformer-based deep learning model was developed for fast and accurate dose map generation, outperforming the MIRD approaches, specifically in heterogenous regions. The model achieved accuracy close to MC gold standard and has potential for clinical implementation for use on large-scale datasets.
Topics: Humans; Octreotide; Organometallic Compounds; Single Photon Emission Computed Tomography Computed Tomography; Radiometry; Radiopharmaceuticals; Precision Medicine; Deep Learning; Male; Female; Monte Carlo Method; Image Processing, Computer-Assisted; Neuroendocrine Tumors
PubMed: 38267686
DOI: 10.1007/s00259-024-06618-9 -
Pharmaceutics Dec 2023To meet unmet medical needs, middle-to-large molecules, including peptides and oligonucleotides, have emerged as new therapeutic modalities. Owing to their... (Review)
Review
To meet unmet medical needs, middle-to-large molecules, including peptides and oligonucleotides, have emerged as new therapeutic modalities. Owing to their middle-to-large molecular sizes, middle-to-large molecules are not suitable for oral absorption, but there are high expectations around orally bioavailable macromolecular drugs, since oral administration is the most convenient dosing route. Therefore, extensive efforts have been made to create bioavailable middle-to-large molecules or develop absorption enhancement technology, from which some successes have recently been reported. For example, Rybelsus tablets and Mycapssa capsules, both of which contain absorption enhancers, were approved as oral medications for type 2 diabetes and acromegaly, respectively. The oral administration of Rybelsus and Mycapssa exposes their pharmacologically active peptides with molecular weights greater than 1000, namely, semaglutide and octreotide, respectively, into systemic circulation. Although these two medications represent major achievements in the development of orally absorbable peptide formulations, the oral bioavailability of peptides after taking Rybelsus and Mycapssa is still only around 1%. In this article, we review the approaches and recent advances of orally bioavailable middle-to-large molecules and discuss challenges for improving their oral absorption.
PubMed: 38258058
DOI: 10.3390/pharmaceutics16010047 -
Medicina (Kaunas, Lithuania) Dec 2023Primary adrenal tumors (AT) are a heterogeneous group of neoplasms due to their functional heterogeneity, which results in the diverse clinical presentation of these...
Primary adrenal tumors (AT) are a heterogeneous group of neoplasms due to their functional heterogeneity, which results in the diverse clinical presentation of these tumors. The purpose of this study was to examine cross-sectional imaging characteristics using multi-detector computed tomography (MDCT) to provide insight into the lesion characterization and functional status of these tumors. The radionuclide imaging using Technetium-99m radiolabeled hydrazinonicotinylacid-d-phenylalanyl-tyrosine3-octreotide (Tc-HYNIC-TOC), was also used in the diagnostic evaluation of these tumors. : This cross-sectional study included 50 patients with confirmed diagnoses of AT (21 hormone-secreting and 29 non-functional) at the University Clinical Center, Kragujevac, Serbia, during the 2019-2022 year period. The morphological and dynamic characteristics using MDCT were performed, using qualitative, semi-quantitative, and quantitative analysis. Absolute washout (APW) and relative washout (RPW) values were also calculated. A semi-quantitative analysis of all visual findings with Tc-HYNIC-TOC was performed to compare the tumor to non-tumor tracer uptake. : A statistically significant difference was found in the MDCT values in the native phase ( < 0.05), the venous phase ( < 0.05), and the delayed phase ( < 0.001) to detect the existence of adrenal tumors. Most of these functional adrenocortical lesions (n = 44) can be differentiated using the delayed phase ( < 0.05), absolute percentage washout (APW) ( < 0.05), and relative percentage washout (RPW) ( < 0.001). Furthermore, Tc-HYNIC-TOC could have a high diagnostic yield to detect adrenal tumor existence ( < 0.001). There is a positive correlation between radionuclide imaging scan and APW to detect all AT ( < 0.01) and adrenocortical adenomas as well ( < 0.01). The results can be very helpful in a diagnostic algorithm to quickly and precisely diagnose the expansive processes of the adrenal glands, as well as to learn about the advantages and limitations of the mentioned imaging modalities.
Topics: Humans; Adrenocortical Adenoma; Cross-Sectional Studies; Adrenal Gland Neoplasms; Adenoma; Tomography, X-Ray Computed
PubMed: 38256333
DOI: 10.3390/medicina60010072 -
International Journal of Molecular... Jan 2024Drugs based on peptides and proteins (PPs) have been widely used in medicine, beginning with insulin therapy in patients with diabetes mellitus over a century ago.... (Review)
Review
Drugs based on peptides and proteins (PPs) have been widely used in medicine, beginning with insulin therapy in patients with diabetes mellitus over a century ago. Although the oral route of drug administration is the preferred one by the vast majority of patients and improves compliance, medications of this kind due to their specific chemical structure are typically delivered parenterally, which ensures optimal bioavailability. In order to overcome issues connected with oral absorption of PPs such as their instability depending on digestive enzymes and pH changes in the gastrointestinal (GI) system on the one hand, but also their limited permeability across physiological barriers (mucus and epithelium) on the other hand, scientists have been strenuously searching for novel delivery methods enabling peptide and protein drugs (PPDs) to be administered enterally. These include utilization of different nanoparticles, transport channels, substances enhancing permeation, chemical modifications, hydrogels, microneedles, microemulsion, proteolytic enzyme inhibitors, and cell-penetrating peptides, all of which are extensively discussed in this review. Furthermore, this article highlights oral PP therapeutics both previously used in therapy and currently available on the medical market.
Topics: Humans; Gastrointestinal Agents; Insulin; Cell-Penetrating Peptides; Biological Availability; Hydrogels
PubMed: 38255888
DOI: 10.3390/ijms25020815 -
Iranian Journal of Basic Medical... 2024Long-term consumption of pump inhibitors causes osteoporosis. Some possible mechanisms are gastrin over-secretion and hypochlorhydria. Octreotide is a somatostatin...
OBJECTIVES
Long-term consumption of pump inhibitors causes osteoporosis. Some possible mechanisms are gastrin over-secretion and hypochlorhydria. Octreotide is a somatostatin analog that inhibits the secretion of many hormones such as gastrin. This study aimed to assess the effects of pantoprazole on the bone when used with octreotide in an animal model.
MATERIALS AND METHODS
Forty-eight male Wistar rats were randomly assigned into 4 groups: A) pantoprazole 3 mg/Kg/day orally; B) Sandostatin LAR 1 mg/month intramuscular injection; C) Pantoprazole and Sandostatin LAR; and D) Control group. After 90 days of the experiment, bone densitometry was done and serum and urine samples were collected for analysis.
RESULTS
The results indicated a significant decrease in the global, spine, femur, and tibia bone mineral density (BMD) and bone mineral content (BMC) in the pantoprazole group compared to the control group (<0.05). There was a significant increase in the levels of PTH, gastrin, and alkaline phosphatase (ALP) in the pantoprazole group compared to the control group (<0.05). There was no significant difference in the serum levels of gastrin, PTH, ALP, and also BMD in the rats that received sandostatin+ pantoprazole or sandostatin alone, compared to the control group.
CONCLUSION
This study showed that the pantoprazole-induced bone loss, through elevation of serum gastrin and PTH, was preventable by concomitant use of a long-acting somatostatin analog.
PubMed: 38234669
DOI: 10.22038/IJBMS.2023.71245.15571 -
Trials Jan 2024The current standard of care (SoC) for the initial treatment of unresectable or metastatic well-differentiated gastroenteropancreatic neuroendocrine tumours (GEP-NET)... (Randomized Controlled Trial)
Randomized Controlled Trial
Methodology of the SORENTO clinical trial: a prospective, randomised, active-controlled phase 3 trial assessing the efficacy and safety of high exposure octreotide subcutaneous depot (CAM2029) in patients with GEP-NET.
BACKGROUND
The current standard of care (SoC) for the initial treatment of unresectable or metastatic well-differentiated gastroenteropancreatic neuroendocrine tumours (GEP-NET) requires initiation of first-generation somatostatin receptor ligand (SRL) therapy, octreotide and lanreotide, which provide safe and efficacious tumour/symptom control in most patients. However, disease progression can occur with SoC SRL treatment and the optimal dose response of SRL remains unknown. Octreotide subcutaneous depot (CAM2029) is a novel, long-acting, high-exposure formulation that has shown greater bioavailability and improved administration than octreotide long-acting release (LAR) with a well-tolerated safety profile. Retrospective data have highlighted a potential benefit of high-exposure SRL for improved disease control in patients who did not adequately respond to the current SoC SRL treatment. This trial will investigate the efficacy and tolerability of CAM2029 compared to the current SoC, including octreotide LAR and lanreotide autogel (ATG).
METHODS
SORENTO is a prospective, multicentre, randomised, active-controlled, open-label phase 3 trial aiming to demonstrate superiority of treatment with 20 mg octreotide subcutaneous depot (CAM2029) every 2 weeks (Q2W) compared to treatment with the Investigator's choice of SRL therapy at standard doses for tumour control (octreotide LAR 30 mg or lanreotide ATG 120 mg every 4 weeks [Q4W]) as assessed by progression-free survival (PFS) in approximately 300 patients with unresectable/metastatic and well-differentiated GEP-NET. Upon confirmation of disease progression (determined by a Blinded Independent Review Committee [BIRC] and defined as per RECIST 1.1), patients may enter an open-label extension treatment period with once weekly dosing, to investigate the effects of higher frequency dosing. Overall survival follow-up will end a maximum of 2 years after primary analysis. The primary endpoint will be analysed after 194 confirmed PFS events.
DISCUSSION
This is the first trial investigating the efficacy of CAM2029 versus SoC SRL therapy using a head-to-head, superiority trial design. It is expected to be the first trial to investigate the efficacy of increased dosing frequency of a high-exposure SRL. A BIRC will limit bias and measurement variability and ensure high-quality efficacy data. Additionally, inclusion of patients with well-differentiated Grade 3 NET may elucidate treatment strategies for this rarely investigated patient population.
TRIAL REGISTRATION
ClinicalTrials.gov NCT05050942. Registered on 21st September 2021.
Topics: Humans; Octreotide; Retrospective Studies; Prospective Studies; Neuroendocrine Tumors; Disease Progression
PubMed: 38229199
DOI: 10.1186/s13063-023-07834-8 -
BMC Endocrine Disorders Jan 2024ABCC8 variants can cause hyperinsulinemia by activating or deactivating gene expression. This study used targeted exon sequencing to investigate genetic variants of...
BACKGROUND
ABCC8 variants can cause hyperinsulinemia by activating or deactivating gene expression. This study used targeted exon sequencing to investigate genetic variants of ABCC8 and the associated phenotypic features in Chinese patients with hyperinsulinemic hypoglycemia (HH).
METHODS
We enrolled eight Chinese children with HH and analyzed their clinical characteristics, laboratory results, and genetic variations.
RESULTS
The age at presentation among the patients ranged from neonates to 0.6 years old, and the age at diagnosis ranged from 1 month to 5 years, with an average of 1.3 ± 0.7 years. Among these patients, three presented with seizures, and five with hypoglycemia. One patient (Patient 7) also had microcephaly. All eight patients exhibited ABCC8 abnormalities, including six missense mutations (c. 2521 C > G, c. 3784G > A, c. 4478G > A, c. 4532T > C, c. 2669T > C, and c. 331G > A), two deletion-insertion mutations (c. 3126_3129delinsTC and c. 3124_3126delins13), and one splicing mutation (c. 1332 + 2T > C). Two of these mutations (c. 3126_3129delinsTC and c. 4532T > C) are novel. Six variations were paternal, two were maternal, and one was de novo. Three patients responded to diazoxide and one patient responded to octreotide treatment. All there patients had diazoxide withdrawal with age. Two patients (patients 3 and 7) were unresponsive to both diazoxide and octreotide and had mental retardation.
CONCLUSIONS
Gene analysis can aid in the classification, treatment, and prognosis of children with HH. In this study, the identification of seven known and two novel variants in the ABCC8 gene further enriched the variation spectrum of the gene.
Topics: Infant, Newborn; Child; Humans; Congenital Hyperinsulinism; Diazoxide; Octreotide; Mutation; China; Sulfonylurea Receptors
PubMed: 38212772
DOI: 10.1186/s12902-023-01527-8