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Gastroenterology Apr 2024
PubMed: 38679395
DOI: 10.1053/j.gastro.2024.04.023 -
Pharmaceuticals (Basel, Switzerland) Apr 2024Nanodiamonds (NDs) are emerging as a novel nanoparticle class with growing interest in medical applications. The surface coating of NDs can be modified by attaching...
Nanodiamonds (NDs) are emerging as a novel nanoparticle class with growing interest in medical applications. The surface coating of NDs can be modified by attaching binding ligands or imaging probes, turning them into multi-modal targeting agents. In this investigation, we assessed the targeting efficacy of octreotide-functionalized Ga-radiolabelled NDs for cancer imaging and compared it with the tumor uptake using [Ga]Ga-DOTA-TOC. In vivo studies in mice bearing AR42J tumors demonstrated the highest accumulation of the radiolabeled functionalized NDs in the liver and spleen, with relatively low tumor uptake compared to [Ga]Ga-DOTA-TOC. Our findings suggest that, within the scope of this study, functionalization did not enhance the tumor-targeting capabilities of NDs.
PubMed: 38675474
DOI: 10.3390/ph17040514 -
Annals of Surgery Apr 2024Pharmacological prevention of postoperative pancreatic fistula (POPF) after pancreatectomy is open to debate. The present study compares clinically significant POPF...
OBJECTIVE
Pharmacological prevention of postoperative pancreatic fistula (POPF) after pancreatectomy is open to debate. The present study compares clinically significant POPF rates in patients randomized between somatostatin versus octreotide as prophylactic treatment.
PATIENTS AND METHODS
Multicentric randomized controlled open study in patient's candidate for pancreaticoduodenectomy (PD) or distal pancreatectomy (DP) comparing somatostatin continuous intravenous infusion for 7 days versus octreotid 100 μg, every 8 hours subcutaneous injection for 7 days, stratified by procedure (PD vs. DP) and size of the main pancreatic duct (>4 mm) on grade B/C POPF rates at 90 days based on an intention-to-treat analysis.
RESULTS
Of 763 eligible patients, 651 were randomized: 327 in the octreotide arm and 324 in the somatostatin arm, with comparable the stratification criteria - type of surgery and main pancreatic duct dilatation. Most patients had PD (n=480; 73.8%), on soft/normal pancreas (n=367; 63.2%) with a non-dilated main pancreatic duct (n=472; 72.5%), most often for pancreatic adenocarcinoma (n=311; 47.8%). Almost all patients had abdominal drainage (n=621; 96.1%) and 121 (19.5%) left the hospital with the drain in place (median length of stay=16 d). A total of 153 patients (23.5%) developed a grade B/C POPF with no difference between both groups: 24.1%: somatostatin arm and 22.9%: octreotide arm (Chi-2 test, P=0.73, ITT analysis). Absence of statistically significant difference persisted after adjustment for stratification variables and in per-protocol analysis.
CONCLUSIONS
Continuous intravenous somatostatin is not statistically different from subcutaneous octreotide in the prevention of grade B/C POPF after pancreatectomy.
PubMed: 38662619
DOI: 10.1097/SLA.0000000000006313 -
Asian Cardiovascular & Thoracic Annals May 2024A single centre experience with chylothorax in post cardiac surgical patients. (Comparative Study)
Comparative Study
OBJECTIVE
A single centre experience with chylothorax in post cardiac surgical patients.
METHODS
Retrospective review.
RESULTS
Chylothorax developed in 55 out of 873 operated patients (6.3%). Median age of the chylothorax cohort was 95 days (range 1-995). Neonates constituted 36% and 49% were infants. Group-1(35 patients-treated during the years 2011-2015) included those who were managed with low fat diet initially with other standard measures including steroid, octreotide, pleurodesis, lymphangiogram or thoracic duct ligation whenever required.Group-2 (20 patients, treated between year 2016-2018) were managed with nil per oral, total parenteral nutrition, extended use of milrinone and no use of chest tube suction with other above standard measures when required.Group-1 and group-2 were comparable in terms of their age and weight ( > 0.05).We observed lower volume of chest drainage, shorter intubation time, length of intensive care stay and hospital stay in group-2 compared to group-1 though they were statistically not significant ( > 0.05). Occurrence of massive chylothorax (>20 ml/kg/day) in group-1 was significantly higher [18 patients (51%) in group-1 vs 4 patients in group-2 (20%) (Chi-square 5.25, = 0.02)]. In hospital mortality in group-1 was higher compared to group-2 (5/35 = 14.5% vs 1/20 = 5%), however, it was statistically not significant [risk ratio 2.86; 95% CI 0.36, 22.77; = 0.59)]. Acute kidney injury was observed in about 25% of patients who had chylothorax. A higher mortality was observed in patients with chylothorax who had acute kidney injury [5/14 (35%)] compared to those who did not have acute kidney injury [1/41 (2.4%)] (Chi-square 11.89, = 0.001)].
SUMMARY
In a heterogenous cohort of post-cardiac surgical patients who developed chylothorax, our suggested new regime (nil per oral, parenteral nutrition, extended use of milrinone and no suction applied to the chest drains) contributed to reduce the frequency of massive chylothorax occurrence significantly.
Topics: Humans; Chylothorax; Retrospective Studies; Infant; Male; Female; Treatment Outcome; Cardiac Surgical Procedures; Infant, Newborn; Parenteral Nutrition, Total; Chest Tubes; Drainage; Milrinone; Time Factors; Child, Preschool; Risk Factors; Administration, Oral; Heart Defects, Congenital; Child
PubMed: 38659299
DOI: 10.1177/02184923241249198 -
PET Clinics Jul 2024Peptide receptor radionuclide therapy (PRRT) has become mainstream therapy of metastatic neuroendocrine tumors not controlled by somatostatin analog therapy. Currently,... (Review)
Review
Peptide receptor radionuclide therapy (PRRT) has become mainstream therapy of metastatic neuroendocrine tumors not controlled by somatostatin analog therapy. Currently, beta particle-emitting radiopharmaceuticals are the mainstay of PRRT. Alpha particle-emitting radiopharmaceuticals have a theoretic advantage over beta emitters in terms of improved therapeutic efficacy due to higher cancer cell death and lower nontarget tissue radiation-induced adverse events due to shorter path length of alpha particles. We discuss the available evidence for and the role of alpha particle PRRT.
Topics: Humans; Neuroendocrine Tumors; Radiopharmaceuticals; Alpha Particles; Receptors, Peptide; Octreotide; Radioisotopes
PubMed: 38658229
DOI: 10.1016/j.cpet.2024.03.005 -
Qatar Medical Journal 2024The somatostatin analog, pasireotide, is used for the treatment of acromegaly after the failure of surgery and/or first-line medical treatment.
BACKGROUND
The somatostatin analog, pasireotide, is used for the treatment of acromegaly after the failure of surgery and/or first-line medical treatment.
CASE PRESENTATION
A 48-year-old male reported that during a workup for obesity in his home country, hyperprolactinemia was diagnosed and a 3.5 × 3.5 cm pituitary macroadenoma was identified on pituitary MRI. He received cabergoline for 6 months; then he was lost to follow-up. He presented at our Endocrine clinic 2 years later for treatment of obesity (BMI 49.5 kg/m). Biochemical workup revealed that in addition to hyperprolactinemia (7,237 [normal: 85-323 mIU/L), he had acromegaly, evident by elevated insulin-like growth factor 1 (IGF-1) level (450 [normal: 88-210 µg/L]), and a positive growth hormone suppression test, secondary hypothyroidism, and secondary hypogonadism. Pituitary MRI showed that the adenoma encased parts of the left and right internal carotid arteries and encroached on the optic chiasm. Surgical excision was therefore not feasible. He was treated with cabergoline and later, long-acting release (LAR) octreotide. Prolactin levels were reduced with cabergoline, but IGF-1 levels did not respond to octreotide, and it was discontinued. The patient abandoned radiotherapy after two sessions. He was started on LAR pasireotide 40 mg every 4 weeks and continued on cabergoline 0.5 mg per week. His biochemical response was dramatic, with a near normalization of IGF-1 levels in 3 months. After 6 months from starting pasireotide, we increased cabergoline dose from 0.5 mg/week to 3 mg/week. Three months later, IGF-1 level was normalized. The patient developed type 2 diabetes as a side effect of pasireotide; however, this was well-controlled with medications.
CONCLUSIONS
The case suggests that pasireotide can provide marked biochemical improvement in acromegaly after the failure of both cabergoline monotherapy and cabergoline plus octreotide. This further confirms a potentially efficacious treatment regimen in treatment-resistant acromegaly with hyperprolactinemia.
PubMed: 38654814
DOI: 10.5339/qmj.2024.17 -
Annals of Surgical Oncology Jul 2024Radio-guided surgery (RGS) holds promise for improving surgical outcomes in neuroendocrine tumors (NETs). Previous studies showed low specificity (SP) using γ-probes to...
BACKGROUND
Radio-guided surgery (RGS) holds promise for improving surgical outcomes in neuroendocrine tumors (NETs). Previous studies showed low specificity (SP) using γ-probes to detect radiation emitted by radio-labeled somatostatin analogs.
OBJECTIVE
We aimed to assess the sensitivity (SE) and SP of the intraoperative RGS approach using a β-probe with a per-lesion analysis, while assessing safety and feasibility as secondary objectives.
METHODS
This prospective, single-arm, single-center, phase II trial (NCT05448157) enrolled 20 patients diagnosed with small intestine NETs (SI-NETs) with positive lesions detected at Ga-DOTA-TOC positron emission tomography/computed tomography (PET/CT). Patients received an intravenous injection of 1.1 MBq/Kg of 68Ga-DOTA-TOC 10 min prior to surgery. In vivo measurements were conducted using a β-probe. Receiver operating characteristic (ROC) analysis was performed, with the tumor-to-background ratio (TBR) as the independent variable and pathology result (cancer vs. non-cancer) as the dependent variable. The area under the curve (AUC), optimal TBR, and absorbed dose for the surgery staff were reported.
RESULTS
The intraoperative RGS approach was feasible in all cases without adverse effects. Of 134 specimens, the AUC was 0.928, with a TBR cut-off of 1.35 yielding 89.3% SE and 86.4% SP. The median absorbed dose for the surgery staff was 30 µSv (range 12-41 µSv).
CONCLUSION
This study reports optimal accuracy in detecting lesions of SI-NETs using the intraoperative RGS approach with a novel β-probe. The method was found to be safe, feasible, and easily reproducible in daily clinical practice, with minimal radiation exposure for the staff. RGS might potentially improve radical resection rates in SI-NETs.
CLINICAL TRIALS REGISTRATION
Ga-DOTATOC Radio-Guided Surgery with β-Probe in GEP-NET (RGS GEP-NET) [NCT0544815; https://classic.
CLINICALTRIALS
gov/ct2/show/NCT05448157 ].
Topics: Humans; Neuroendocrine Tumors; Female; Male; Prospective Studies; Middle Aged; Intestinal Neoplasms; Radiopharmaceuticals; Positron Emission Tomography Computed Tomography; Aged; Intestine, Small; Octreotide; Adult; Surgery, Computer-Assisted; Organometallic Compounds; Somatostatin; Follow-Up Studies; Prognosis; Beta Particles; Feasibility Studies
PubMed: 38652200
DOI: 10.1245/s10434-024-15277-x -
Biomacromolecules May 2024Autosomal dominant polycystic kidney disease (ADPKD) is a complex disorder characterized by uncontrolled renal cyst growth, leading to kidney function decline. The...
Autosomal dominant polycystic kidney disease (ADPKD) is a complex disorder characterized by uncontrolled renal cyst growth, leading to kidney function decline. The multifaceted nature of ADPKD suggests that single-pathway interventions using individual small molecule drugs may not be optimally effective. As such, a strategy encompassing combination therapy that addresses multiple ADPKD-associated signaling pathways could offer synergistic therapeutic results. However, severe off-targeting side effects of small molecule drugs pose a major hurdle to their clinical transition. To address this, we identified four drug candidates from ADPKD clinical trials, bardoxolone methyl (Bar), octreotide (Oct), salsalate (Sal), and pravastatin (Pra), and incorporated them into peptide amphiphile micelles containing the RGD peptide (GRGDSP), which binds to the basolateral surface of renal tubules via integrin receptors on the extracellular matrix. We hypothesized that encapsulating drug combinations into RGD micelles would enable targeting to the basolateral side of renal tubules, which is the site of disease, via renal secretion, leading to superior therapeutic benefits compared to free drugs. To test this, we first evaluated the synergistic effect of drug combinations using the 20% inhibitory concentration for each drug (IC) on renal proximal tubule cells derived from mice. Next, we synthesized and characterized the RGD micelles encapsulated with drug combinations and measured their therapeutic effects via a 3D PKD growth model. Upon both IV and IP injections , RGD micelles showed a significantly higher accumulation in the kidneys compared to NT micelles, and the renal access of RGD micelles was significantly reduced after the inhibition of renal secretion. Specifically, both Bar+Oct and Bar+Sal in the RGD micelle treatment showed enhanced therapeutic efficacy in ADPKD mice () with a significantly lower KW/BW ratio and cyst index as compared to PBS and free drug-treated controls, while other combinations did not show a significant difference. Hence, we demonstrate that renal targeting through basolateral targeting micelles enhances the therapeutic potential of combination therapy in genetic kidney disease.
Topics: Animals; Micelles; Mice; Drug Delivery Systems; Humans; Polycystic Kidney, Autosomal Dominant; Oligopeptides; Polycystic Kidney Diseases
PubMed: 38652072
DOI: 10.1021/acs.biomac.3c01397 -
Expert Opinion on Investigational Drugs May 2024Disease control is essential to decrease morbidity burden and mortality in acromegaly patients. In the last decades, the availability of new drugs increased the rate of... (Review)
Review
INTRODUCTION
Disease control is essential to decrease morbidity burden and mortality in acromegaly patients. In the last decades, the availability of new drugs increased the rate of disease control. However, up to 55% of patients remain uncontrolled despite available treatment strategies in real-world data. The reasons for this finding may include poor adherence, inadequate tolerability, therapeutic inertia, and high costs. Since acromegaly is a chronic disease and medical therapy is usually life-long, patient's adherence to treatment is fundamental in both achieving and maintaining disease control. Less invasive routes of administration could improve adherence and concur to increase disease control rate.
AREAS COVERED
The aim of current review is to provide a detailed update about investigational drugs for acromegaly treatment currently under investigation as paltusotine, ONO-5788, AP102, GT-02037, ISIS 766720, CAM2024, Lanreotide PRF, DP1038, MTD201, solid dose injection of octreotide.
EXPERT OPINION
Medical therapy of acromegaly is an evolving field. Current studies are addressing patient's need for both new molecules and less invasive routes of administration for already existing drugs. It cannot be ruled out that drugs currently used for other diseases such as cancer could be considered in the future for the treatment of acromegaly.
Topics: Humans; Acromegaly; Drug Development; Drugs, Investigational; Medication Adherence
PubMed: 38651260
DOI: 10.1080/13543784.2024.2343056 -
Radiologie (Heidelberg, Germany) Jul 2024Well-differentiated neuroendocrine tumors (NET) are rare malignancies that are clinically very heterogeneous. Accordingly, their treatment is also complex and dependent... (Review)
Review
BACKGROUND
Well-differentiated neuroendocrine tumors (NET) are rare malignancies that are clinically very heterogeneous. Accordingly, their treatment is also complex and dependent on various factors. With currently available systemic therapies, the prognosis is often favorable.
OBJECTIVES
This article aims to provide an overview of current treatment strategies for NET, addressing the most important NET locations.
METHODS
The current European guidelines and further relevant literature on the treatment of NET were reviewed for this purpose.
RESULTS
The therapeutic spectrum for NET is extremely broad: For NET of the stomach/duodenum, appendix, and rectum, endoscopic or surgical resection is often sufficient, and metastatic tumors are rare. NET of the pancreas, small intestine and lung should also undergo potentially curative resection in the early stages. In the metastatic stage, locoregional treatments such as surgery and liver tumor embolization play a role. Major advances have been made in drug therapy, with somatostatin analogs (octreotide and lanreotide), an mTOR inhibitor (everolimus), and a tyrosine kinase inhibitor (sunitinib) being widely used. Peptide receptor radionuclide therapy (PRRT) is also an invaluable option. In some cases, classic chemotherapy is indicated.
CONCLUSIONS
Many effective therapies are now available for NET. It is important to select the right therapy at the right time for each patient through interdisciplinary management.
Topics: Humans; Neuroendocrine Tumors; Antineoplastic Agents; Practice Guidelines as Topic
PubMed: 38649498
DOI: 10.1007/s00117-024-01303-2