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Archives of Razi Institute Feb 2023Sepsis is a systemic inflammatory consequence resulting from microbial infection, assessed as a worldwide healthcare issue. Sepsis can result in multiorgan dysfunction,...
Sepsis is a systemic inflammatory consequence resulting from microbial infection, assessed as a worldwide healthcare issue. Sepsis can result in multiorgan dysfunction, including cardiac, renal, hepatic, and cerebral dysfunction. Cardiotoxicity can occur in humans and rodents during sepsis, leading to increased mortality. The current study aims to explore the possible cardioprotective effects of octreotide during sepsis-induced cardiotoxicity. This study was done with a total of forty male albino Swiss mice, aged 8-12 weeks and weighing 25-30 gm. These animals had free access to food and water. After two weeks of adaptation, mice were divided into four groups (n=10): 1) Normal group: healthy mice; 2) CLP group: mice underwent CLP operation; 3) Vehicle group: mice received DMSO. 4) Octreotide group: mice received octreotide (10 mg/kg) subcutaneously in 2 divided doses for 5 consecutive days. All groups underwent CLP operation on the 4th day, then sacrificed on the 5th day then blood, and tissue sampling was done. The Octreotide group demonstrated a significant (<0.05) decrease in the myocardial levels of cardiac troponin-I as compared to the CLP group. Furthermore, the octreotide group demonstrated a significant (<0.05) decrease in the serum level of inflammatory cytokines (TNF-α, IL-6, & IL-1β) as compared to the CLP group. Additionally, the octreotide group showed a significant (<0.05) elevation in the myocardial activity of SOD and a reduction in MDA level compared to the CLP group. Histologically, all mice in the CLP group showed a significant (<0.05) cardiac tissue injury, while the octreotide groups showed a significant (<0.05) reduced level of cardiac tissue injury. The results of the present study revealed that octreotide attenuates sepsis-induced cardiotoxicity through different protective effects; they include the anti-inflammatory effect through their ability to decrease serum levels of inflammatory cytokines (TNF-α, IL-1β, and IL-6). Also, the anti-oxidant effect through their ability to decrease myocardial levels of MDA and increase the myocardial activity of SOD. Additionally, the direct cardiac protective effect through the lower level of cardiac troponin- I and the reduction of histopathological changes during sepsis-induced cardiotoxicity.
Topics: Animals; Male; Mice; Cardiotoxicity; Cytokines; Interleukin-6; Octreotide; Sepsis; Superoxide Dismutase; Tumor Necrosis Factor-alpha
PubMed: 37312717
DOI: 10.22092/ARI.2022.358339.2201 -
Gut Dec 2001Pancreaticoduodenectomy (Whipple's procedure) represents a considerable surgical challenge. Postoperative complications are common and typically related to leakage of... (Review)
Review
Pancreaticoduodenectomy (Whipple's procedure) represents a considerable surgical challenge. Postoperative complications are common and typically related to leakage of pancreatic exocrine secretions following anastomosis failure. Pancreatic proteases and lipase leaking from the organ remnant attack the surrounding tissue, potentially leading to severe inflammation, tissue necrosis, and fistula formation. In addition, the soft consistency of the normal pancreas can lead to difficulties in manipulating the organ and reduce the integrity of sutures. Pancreatic fistula is the most serious postoperative complication and especially common following resectional surgery for malignant disease. Through prophylactic inhibition of digestive secretions, it should be possible to reduce postoperative morbidity after pancreatic surgery. One such inhibitor is somatostatin-14, an endogenous peptide hormone with pronounced effects on secretion of pancreatic enzymes and hormones, gastrointestinal secretions, and pancreatic blood flow, all of which may decrease the risk of postoperative complications. A limited number of randomised controlled trials have investigated prophylactic administration of somatostatin-14 and the synthetic somatostatin analogue octreotide in reducing complications following pancreatic surgery. While the majority of studies with octreotide demonstrated a significant reduction in the overall complication rate, the benefits appeared less marked in relation to events specifically related to pancreatic secretion. However, preliminary results from a limited number of trials with somatostatin-14, administered as a continuous intravenous infusion, suggest that prophylactic pharmacotherapy produces a significant decrease in fistula formation and secretion related events after pancreaticoduodenectomy. Due to these promising data, further investigation of the role of somatostatin-14 prophylaxis in pancreatic surgery is warranted in large well controlled trials.
Topics: Clinical Trials as Topic; Gastrointestinal Agents; Humans; Multicenter Studies as Topic; Octreotide; Pancreaticoduodenectomy; Postoperative Complications; Somatostatin
PubMed: 11878792
DOI: 10.1136/gut.49.suppl_4.iv29 -
International Journal of Obesity (2005) Nov 2023After Roux-en-Y gastric bypass (RYGB) a subset of patients never obtain excess BMI loss (EBMIL) > 50% and are categorized as having primary weight loss (WL) failure....
BACKGROUND/OBJECTIVES
After Roux-en-Y gastric bypass (RYGB) a subset of patients never obtain excess BMI loss (EBMIL) > 50% and are categorized as having primary weight loss (WL) failure. We hypothesized that postprandial concentrations of glucagon-like peptide 1 (GLP-1) and peptide YY (PYY) would be lower in patients with primary WL failure compared with patients with successfully maintained WL. Furthermore, that inhibition of gut hormone secretions would increase ad libitum food intake less in patients with primary WL failure.
SUBJECTS/METHODS
Twenty women with primary WL failure (LowEBMIL < 50%) were individually matched to twenty women with successful WL (HighEBMIL > 60%) on age, preoperative BMI and time from RYGB. On separate days performed in a random order, patient-blinded subcutaneous injections of octreotide or saline (placebo) were followed by a fixed breakfast and an ad libitum lunch with blood sampling for appetite regulating hormones and Visual-Analogue-Scale (VAS)-scoring of hunger/satiety. Furthermore, participants underwent gene variant analysis for GLP-1, PYY and their receptors, indirect calorimetry, dual-energy X-ray absorptiometry (DXA)-scans, 4-days at-home food registration and 14-days step counting.
RESULTS
On placebo days, postprandial GLP-1, PYY and cholecystokinin (CCK) concentrations were similar between groups after breakfast. Fasting ghrelin was lower in LowEBMIL, but the postprandial suppression was similar. LowEBMIL had lower satiety VAS-scores and less suppression of hunger VAS-scores. Gene variants did not differ between groups. Octreotide diminished GLP-1, PYY, CCK and ghrelin concentrations in both groups. Octreotide did not affect ad libitum food intake in LowEBMIL (-1% [-13, 12], mean [95%CI]), while food intake increased in HighEBMIL (+23% [2,44]).
CONCLUSIONS
Primary WL failure after RYGB was not characterized by impaired secretions of appetite regulating gut hormones. Interestingly, inhibition of gut hormone secretions with octreotide only increased food intake in patients with successful WL post-RYGB. Thus, an impaired central anorectic response to gut hormones may contribute to primary WL failure after RYGB.
Topics: Humans; Female; Gastric Bypass; Ghrelin; Octreotide; Gastrointestinal Hormones; Peptide YY; Glucagon-Like Peptide 1; Cholecystokinin; Eating; Weight Loss
PubMed: 37653071
DOI: 10.1038/s41366-023-01372-8 -
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 -
Canadian Journal of Surgery. Journal... Apr 2015Discordant practice patterns may be a consequence of evidence-practice gaps or deficiencies in knowledge translation. We examined the current strategies used by...
BACKGROUND
Discordant practice patterns may be a consequence of evidence-practice gaps or deficiencies in knowledge translation. We examined the current strategies used by hepato-pancreatico-biliary (HPB) surgeons in Canada for the perioperative management of pancreaticoduodenectomy (PD).
METHODS
We generated a web-based survey that focused on the perioperative measures surrounding PD. The survey was distributed to all members of the Canadian Hepato-Pancreatico-Biliary Association.
RESULTS
The survey was distributed to 74 surgeons and received a response rate of 50%. Many similarities in surgical techniques were reported; for example, most surgeons (86.5%) reconstruct the pancreas with pancreaticojejunostomy rather than pancreaticogastrostomy. In contrast, variable techniques regarding the use of peritoneal drainage tubes, anastomotic stents, octreotide and other intraoperative modalities were reported. Most surgeons (75.7%) reported that their patients frequently required preoperative biliary drainage, yet there was minimal agreement with the designated criteria. There was variability in postoperative care, including the use of epidural analgesia and timing of postoperative oral nutrition.
CONCLUSION
We identified heterogeneity among Canadian HPB surgeons, suggesting a number of evidence-practice gaps within specific domains of pancreatic resections. Focused research in these areas may facilitate technical agreement and improve patient outcomes following PD.
Topics: Analgesia, Epidural; Canada; Gastrointestinal Agents; Health Care Surveys; Humans; Octreotide; Pancreaticoduodenectomy; Perioperative Care; Stents
PubMed: 25799248
DOI: 10.1503/cjs.011714 -
European Journal of Nuclear Medicine... Oct 2011
Topics: Female; Humans; Lutetium; Male; Neuroendocrine Tumors; Octreotide; Organometallic Compounds; Radioisotopes; Radiotherapy
PubMed: 21755369
DOI: 10.1007/s00259-011-1878-x -
The Oncologist Sep 2018Rate of progression-free survival at a particular point in time, i.e., a landmark analysis, is a difficult endpoint for a heterogenous malignancy such as neuroendocrine...
LESSONS LEARNED
Rate of progression-free survival at a particular point in time, i.e., a landmark analysis, is a difficult endpoint for a heterogenous malignancy such as neuroendocrine cancer.Landmark analyses can also be complicated by evolution in the standard of care during the conduct of a clinical trial.Improvements in biomarker development would be useful in developing future clinical trials in NET to better tailor individualized therapies and assess for possible efficacy endpoints.
BACKGROUND
Neuroendocrine tumors (NETs) are rare malignancies of the gastrointestinal (GI) tract that are highly vascularized and overexpress vascular-endothelial growth factor (VEGF). Sunitinib has demonstrated efficacy in the pancreatic subset of NET. This study explored the activity of another oral VEGF inhibitor, AMG 706 or motesanib, a multikinase inhibitor that targets receptor tyrosine kinases, including VEGFR1, VEGFR2, VEGFR3, KIT, RET, and PDGFR (IC50s = 2, 3, 6, 8, 59, and 84 nM, respectively).
METHODS
This was a single-arm, first-line, phase II study run through the Eastern Cooperative Oncology Group. Patients with low-grade NET (as defined by central confirmation of Ki-67 of 0%-2%) were administered a flat dose of 125 mg per day orally combined with octreotide long acting-repeatable (LAR) for patients who had been on a stable dose. The primary objective was to determine the 4-month progression-free survival (PFS).
RESULTS
Forty-four patients were evaluated per protocol. The 4-month PFS was 78.5%. The partial response rate was 13.6% (6/44), stable disease was 54.5% (24/44), 9.1% (4/44) had progressive disease, and 10/44 were not evaluable for response. Common toxicities included fatigue, hypertension, nausea, and headache, and most were grade 1-2. Median PFS was 8.7 months, and overall survival was 27.5 months.
CONCLUSION
Motesanib (AMG 706) demonstrated a 4-month PFS that met the per-protocol definition of efficacy. Fatigue and hypertension were the most common toxicities, and few grade 3-4 toxicities were encountered. The progression-free survival of 8.7 months in all NETs merits further study.
Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents, Hormonal; Humans; Indoles; Middle Aged; Neuroendocrine Tumors; Niacinamide; Octreotide; Treatment Outcome
PubMed: 29853660
DOI: 10.1634/theoncologist.2018-0294 -
Medicine Jul 2017The use of octreotide prophylaxis in the prevention of complications after pancreatic resection remains controversial. The aim of this systematic review and... (Meta-Analysis)
Meta-Analysis Review
Efficacy of the prophylactic use of octreotide for the prevention of complications after pancreatic resection: An updated systematic review and meta-analysis of randomized controlled trials.
BACKGROUND
The use of octreotide prophylaxis in the prevention of complications after pancreatic resection remains controversial. The aim of this systematic review and meta-analysis was to evaluate the efficacy of octreotide prophylactic treatment to prevent complications after pancreatic resection.
METHODS
Five databases (PubMed, Medline, SinoMed, Embase, and Cochrane Library) were searched for eligible studies from 1980 to November 2016 with the limitation of human subjects and randomized controlled trials (RCTs). Data were extracted independently and were analyzed using RevMan statistical software version 5.3 (Cochrane Collaboration, http://tech.cochrane.org/revman/download). Weighted mean differences (WMDs), risk ratios (RRs), and 95% confidence intervals (CIs) were calculated. Cochrane Collaboration risk of bias tool was used to assess the risk of bias.
RESULTS
Twelve RCTs comprising 1902 patients were identified as eligible. The methodological quality of the trials ranged from low to moderate. A pooled analysis of effectiveness based on the data from each study revealed that octreotide could significantly reduce the rate of pancreatic fistula (PF) after pancreatic resection (RR = 0.75, 95% CI = 0.57-0.98, P = .04). The same findings were discovered in multicenter and European subgroups with a subgroup analysis; no obvious differences were noted in American, Asian, and single-center subgroup analyses. An equal effect was observed between the use or non-use of octreotide groups regarding mortality (RR = 1.24, 95% CI = 0.77-2.02, P = .38). Octreotide had no advantages in regards to mortality improvement. The total numbers of complications associated with the use or non-use of octreotide were similar (RR = 0.77, 95% CI = 0.58-1.03, P = .08). Among the high-risk group, octreotide was more effective in reducing complications (RR = 0.61, 95% CI = 0.46-0.82, P = .0009). Compared with the patients who did not receive prophylactic treatment, the patients who underwent pancreatic resection benefited from octreotide because it had better efficacy in preventing fluid collection and postoperative pancreatitis.
CONCLUSION
The prophylactic use of octreotide is suitable for preventing postoperative complications, especially PF and fluid collection as well as postoperative pancreatitis. However, no obvious differences were noted regarding mortality. In view of the clinical heterogeneity and varying definitions of PF, whether these conclusions are broadly applicable should be further determined in future studies.
Topics: Gastrointestinal Agents; Humans; Octreotide; Pancreatectomy; Postoperative Complications; Randomized Controlled Trials as Topic
PubMed: 28723761
DOI: 10.1097/MD.0000000000007500 -
Gut 1994Acute pancreatitis is caused by the activation of digestive enzymes in the pancreas and a possible treatment, therefore, is the inhibition of enzyme secretion. This... (Comparative Study)
Comparative Study Review
Acute pancreatitis is caused by the activation of digestive enzymes in the pancreas and a possible treatment, therefore, is the inhibition of enzyme secretion. This approach is somewhat controversial, however, as it is not clear whether pancreatic secretion continues to occur during the course of acute pancreatitis. Animal studies show an appreciable reduction of secretion in the inflamed pancreas, but studies in humans are not conclusive. The use of somatostatin or its analogue, octreotide, has been investigated in several clinical studies. A meta analysis of six individual studies in which somatostatin was given for acute pancreatitis showed that somatostatin significantly reduces mortality. A trial in patients with moderate to severe acute pancreatitis showed a lower rate (although not statistically significant) of complications in patients treated with 3 x 200 and 3 x 500 micrograms/day octreotide, compared with controls and patients receiving a lower dose of octreotide. A further study showed a significant reduction in patient controlled analgesics in patients treated with octreotide compared with controls. Pain is the important clinical symptom of chronic pancreatitis, possibly resulting from an increased intraductal pressure during secretion. The effect on pain of the inhibition of pancreatic secretion by octreotide has been investigated in two studies. One showed no significant reduction in pain after treatment with octreotide for three days. In the other, in which octreotide was used for three weeks, significantly less pain and analgesic use was recorded during octreotide treatment than during placebo. The most common complication of chronic pancreatitis is the formation of pseudocysts. There is some evidence that octreotide may be useful in their treatment.
Topics: Acute Disease; Chronic Disease; Female; Humans; Male; Middle Aged; Octreotide; Pancreatitis; Somatostatin
PubMed: 7911442
DOI: 10.1136/gut.35.3_suppl.s15 -
Drugs in R&D Sep 2018Octreotide is a somatostatin analogue and has been used off-label for a variety of conditions. There are no specific guidelines for the use of octreotide in neonates and...
BACKGROUND AND OBJECTIVE
Octreotide is a somatostatin analogue and has been used off-label for a variety of conditions. There are no specific guidelines for the use of octreotide in neonates and its safety and efficacy have not been systematically evaluated. The objective of this study is to present our experience of using octreotide therapy in neonates.
METHODS
This is a retrospective study of neonates who received octreotide therapy during their hospital stay over a 15 years period (2003-2017) in a tertiary neonatal centre. The demographic details and indications of octreotide therapy including time of initiation, route, dose, duration and adverse effects of therapy were noted. The clinical course following octreotide administration was also analysed.
RESULTS
Eleven neonates received octreotide therapy during the study period, of which nine had chylothorax and two had chylous ascites. Resolution of the chylous effusion with octreotide therapy was achieved in 4 out of 11 (36.3%) of the cases. The median duration of octreotide therapy in cases with successful resolution was 17.5 days. With the exception of minor side effects such as hyperglycaemia, none of the patients had any significant side effects that required discontinuation of therapy.
CONCLUSION
Octreotide was used safely as an adjunctive therapy for the treatment of chylothorax and chylous ascites in neonates. However, larger prospective controlled trials are required to establish the optimal dose, time of initiation, duration and efficacy of octreotide therapy in neonates.
Topics: Chylothorax; Chylous Ascites; Combined Modality Therapy; Female; Humans; Infant, Newborn; Male; Octreotide; Retrospective Studies
PubMed: 29948779
DOI: 10.1007/s40268-018-0237-9