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Suppression of Insulin Secretion in the Treatment of Obesity: A Systematic Review and Meta-Analysis.Obesity (Silver Spring, Md.) Nov 2020This proof-of-concept study aimed to evaluate the efficacy and safety of suppression of insulin secretion in the treatment of obesity. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
This proof-of-concept study aimed to evaluate the efficacy and safety of suppression of insulin secretion in the treatment of obesity.
METHODS
A search of PubMed, Embase, and Cochrane databases was performed to identify randomized controlled trials (up to January 1, 2020) that used drugs that directly suppress insulin secretion (diazoxide or octreotide) in the treatment of obesity. The extracted data were analyzed using random-effects meta-analysis.
RESULTS
A total of seven randomized controlled trials were included, with four using diazoxide and three using octreotide to suppress insulin secretion. Suppression of insulin secretion significantly reduced fasting insulin level (mean difference: -3.94 mIU/L; 95% CI: -7.40 to -0.47) but slightly increased fasting blood glucose level (mean difference: 0.48 mmol/L; 95% CI: 0.24 to 0.72). Following the suppression of insulin secretion, significant reductions in body weight (mean difference: -3.19 kg; 95% CI: -5.71 to -0.66), BMI (mean difference: -1.65 kg/m ; 95% CI: -2.41 to -0.90), and fat mass (mean difference: -5.92 kg; 95% CI: -8.28 to -3.56) were observed compared with placebo in the pooled data. No significant difference in fat-free mass was observed (mean difference: 0.56 kg; 95% CI: -0.40 to 1.52).
CONCLUSIONS
Results suggest that suppression of insulin secretion may lead to reduced body weight and fat mass with slightly increased blood glucose in individuals with obesity.
Topics: Adult; Animals; Blood Glucose; Body Weight; Female; Humans; Insulin; Insulin Secretion; Male; Mice; Obesity; Proof of Concept Study; Randomized Controlled Trials as Topic; Rats
PubMed: 33150747
DOI: 10.1002/oby.22955 -
Pancreatology : Official Journal of the... Dec 2020Postoperative pancreatic fistula/POPF is the most feared complication in pancreatic surgery. Although several systematic reviews investigated the impact of somatostatin... (Meta-Analysis)
Meta-Analysis
Do somatostatin-analogues have the same impact on postoperative morbidity and pancreatic fistula in patients after pancreaticoduodenectomy and distal pancreatectomy? - A systematic review with meta-analysis of randomized-controlled trials.
OBJECTIVE
Postoperative pancreatic fistula/POPF is the most feared complication in pancreatic surgery. Although several systematic reviews investigated the impact of somatostatin analogues on POPF, no stratification was performed regarding type of pancreatic resection (pancreaticoduodenectomy/PD; distal pancreatectomy/DP) and different somatostatin analogues.
METHODS
This study was planed according to the Preferred-Reporting-Items-for-Systematic -Review-and-Meta-Analysis/PRISMA-guidelines. After screening databases for randomized controlled trials/RCT, studies were stratified into pancreatic resection techniques and data were pooled in meta-analyses containing subgroups of octreotide, somatostatin, lanreotide, pasireotide and vapreotide.
RESULTS
The meta-analysis of studies with a mixed cohort of patients after pancreatic resection revealed a protective effect of somatostatin analogues for morbidity (RR: 0.71, p < .00001) but not for mortality (RR: 1.07, = 0.78) or intra-abdominal abscesses (RR: 1.00, p = 1.00). Moreover, no effect was visible for mortality (RR: 1.57, p = .15), morbidity (RR: 0.87, p = .15) and intra-abdominal abscesses (RR: 0.92, p = .48) after PD. The meta-analysis of patients after PD revealed no impact of somatostatin analogues on POPF (RR: 0.87, p = .19) and clinically relevant POPF (RR: 0.69, p = .30). However, treatment with somatostatin analogues in the mixed cohort showed less POPF (RR: 0.60, p < .00001) and clinically relevant POPF (RR: 0.47, p = .02), which was also the case after DP (RR: 0.41, p = .03).
CONCLUSION
Somatostatin analogues did not affect POPF and clinically relevant POPF after PD, but seemed to be associated with less POPF after DP. As no sufficiently powered RCT could be identified by the systematic review, further RCTs are urgently needed to investigate the effect of somatostatin analogues after DP.
STUDY REGISTRATION
CRD42018099808.
Topics: Anastomosis, Surgical; Humans; Morbidity; Pancreas; Pancreatectomy; Pancreatic Fistula; Pancreaticoduodenectomy; Postoperative Complications; Postoperative Period; Somatostatin
PubMed: 33121847
DOI: 10.1016/j.pan.2020.10.043 -
Neuroendocrinology 2021This study described a Chinese case of X-linked acrogigantism (X-LAG) and summarized the characteristics and treatment of all reported cases.
INTRODUCTION
This study described a Chinese case of X-linked acrogigantism (X-LAG) and summarized the characteristics and treatment of all reported cases.
METHODS
Clinical materials and biological samples from a 5-year and 2-month-old female due to "growth acceleration for 4 years" were collected. Array comparative genomic hybrid (aCGH) and further verification were performed. All X-LAG cases from the PubMed and Web of Science databases were collected and summarized with available data.
RESULTS
The patient presented accelerating growth since 1 year, and her height reached 134.6 cm (+5.24 standard deviation score [SDS]) when she was 5-year and 2-month old. She also had coarsening facial features, snoring, and acral enlargement. Growth hormone (GH) was not suppressed by the glucose-GH inhibition test, and insulin-like growth factor 1 (IGF-1) and prolactin (PRL) levels were elevated. Pituitary MRI revealed a pituitary enlargement with a maximum diameter of 22.3 mm. Octreotide imaging indicated the presence of a pituitary adenoma. The tumor shrank slightly after 3 courses of somatostatin analog but without clinical or biochemical remissions, of which the GH nadir value was 9.4 ng/mL, and IGF-1 was elevated to 749 ng/mL. Therefore, she underwent transsphenoidal surgery. Immunohistochemistry showed GH-positive and PRL-positive cells in the pituitary adenoma. Xq26.3 microduplication of the patient's germline DNA was identified by aCGH. Of all 35 reported cases, females accounted for 71.43%. There were 93.10% and 53.83% patients with hyperprolactinemia and hyperinsulinemia, respectively. Pathology showed that 75.00% of cases were adenomas. Ninety percent of cases had germline variants. The clinical and biochemical remission rates were 78.26% and 82.61%, respectively. However, the rate of complication occurrence during therapy reached 80%.
CONCLUSION
It is important to recognize the possibility of X-LAG when a child under 2-year old presents overgrowth. Early diagnosis and treatment are of great importance for better treatment efficacy and clinical outcome.
Topics: Acromegaly; Child, Preschool; China; Female; Genetic Diseases, X-Linked; Humans
PubMed: 33049741
DOI: 10.1159/000512240 -
Journal of Cancer Research and Clinical... Jun 2020To evaluate the efficacy of Lu-DOTA0-Tyr3-octreotate (Lu-DOTATATE) radionuclide therapy in patients with inoperable or metastatic neuroendocrine tumours (NETs),... (Meta-Analysis)
Meta-Analysis
PURPOSE
To evaluate the efficacy of Lu-DOTA0-Tyr3-octreotate (Lu-DOTATATE) radionuclide therapy in patients with inoperable or metastatic neuroendocrine tumours (NETs), (PROSPERO ID CRD42019130755).
METHODS
All published clinical studies of NETs treated with Lu-DOTATATE were identified based on systematic searches in the PubMed, EMBASE, Cochrane Library, Web of Science and ClinicalTrials.gov databases up to January 2019. Among these studies, only the reports evaluated with the "Response Evaluation Criteria in Solid Tumours (RECIST)" or "Southwest Oncology Group (SWOG)" criteria or both were included. We analysed the disease response rate (DRR) and disease control rate (DCR) of each group to evaluate the efficacy of Lu-DOTATATE.
RESULTS
Fifteen studies were selected from 715 references. The pooled effect in the RECIST group (13 studies) was 27.58% (95% confidence interval (CI) 21.03-35.27%) for the DRR and 79.14% (95% CI 75.83-82.1%) for the DCR. In the SWOG criteria group (7 studies), the pooled effect was 20.59% (95% CI 10.89-35.51%) for the DRR and 78.28% (95% CI 74.39-81.72%) for the DCR. Therefore, the RECIST and SWOG groups showed similar DRRs and DCRs afterLu-DOTATATE treatment, indicating that Lu-DOTATATE treatment has excellent efficacy with a control rate of approximately 78-79%. Moreover, adverse effects of Lu-DOTATATE were minimal, including fatigue, nausea, vomiting and hormonal disorders.
CONCLUSIONS
For patients with inoperable or metastatic NETs, Lu-DOTATATE is an effective treatment with minimal side effects.
Topics: Humans; Neoplasm Metastasis; Neuroendocrine Tumors; Octreotide; Organometallic Compounds; Radiopharmaceuticals
PubMed: 32281025
DOI: 10.1007/s00432-020-03181-2 -
United European Gastroenterology Journal Mar 2020Type-1 gastric neuroendocrine tumors represent a recurring disease and long-acting somatostatin analogs can inhibit both gastrin release and endocrine cell... (Meta-Analysis)
Meta-Analysis
Response and relapse rates after treatment with long-acting somatostatin analogs in multifocal or recurrent type-1 gastric carcinoids: A systematic review and meta-analysis.
BACKGROUND
Type-1 gastric neuroendocrine tumors represent a recurring disease and long-acting somatostatin analogs can inhibit both gastrin release and endocrine cell proliferation. The efficacy and timing of this treatment are still unclear. We performed a systematic review of the literature to clarify the role of somatostatin analog treatment in type-1 gastric neuroendocrine tumors.
METHODS
A computerized literature search was performed using relevant keywords to identify all the pertinent articles published in the last 15 years.
RESULTS
Eight studies were included in this systematic review on somatostatin analogs in type-1 gastric neuroendocrine tumors. A complete response rate ranged from 25-100%. When only the six prospective studies were considered, no significant heterogeneity was observed, and the pooled cumulative complete response rate was 84.5% (confidence interval 73.8-92.8). Three studies evaluated the type-1 gastric neuroendocrine tumor recurrence, with a cumulative relapse rate of 30.2% (confidence interval 13.1-50.6) after 34 months.
CONCLUSION
Somatostatin analogs, namely lanreotide and octreotide, have an excellent response rate, with a good safety profile in selected type-1 gastric neuroendocrine tumors, which cannot be safely managed by endoscopic follow-up or resection due to multiple or frequently recurring disease. After therapy discontinuation, the cumulative relapse rate observed after a median 34-month follow-up was relatively high (30.2%).
Topics: Carcinoid Tumor; Disease-Free Survival; Drug Administration Schedule; Follow-Up Studies; Humans; Intestinal Neoplasms; Neoplasm Recurrence, Local; Neuroendocrine Tumors; Octreotide; Pancreatic Neoplasms; Peptides, Cyclic; Prospective Studies; Somatostatin; Stomach; Stomach Neoplasms
PubMed: 32213066
DOI: 10.1177/2050640619890465 -
Medicine Mar 2020Somatostatin analog therapies showed great potential for patients suffering advanced neuroendocrine tumors (NETs). This study was aimed to evaluate the therapeutic... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Somatostatin analog therapies showed great potential for patients suffering advanced neuroendocrine tumors (NETs). This study was aimed to evaluate the therapeutic efficacy of Lu-DOTATATE/DOTATOC (Lu-octreotate/octreotide) peptide receptor radionuclide therapy (PRRT) in advanced or inoperable NETs patients.
METHODS
Pubmed, Web of Science, Embase and Cochrane Library were searched from 1950 to April 2019. Eligible studies should include randomized or nonrandomized controlled trials (RCTs)-based investigations of Lu-octreotate/octreotide PRRT for NETs. All these studies were assessed with Response Evaluation Criteria in Solid Tumors (RECIST), RECIST 1.1, Southwest Oncology Group (SWOG) criteria or World Health Organization (WHO) criteria. Disease response rates (DRRs) and disease control rates (DCRs) were calculated according to each response criteria group. DRRs were defined as the percentages of patients with complete response (CR) + partial response (PR), while DCRs represented the percentages of patients with CR+ PR+ stable disease (SD). The pooled proportions were calculated with either a fixed-effects model or a random-effects model depending on the test for heterogeneity.
RESULTS
A total of 22 studies (1758 patients) were included in this meta-analysis: 8 studies with 478 patients met RECIST criteria, 10 studies with 1127 patients met RECIST 1.1 criteria, 5 studies with 459 patients met SWOG criteria, and 1 study with 40 patients met WHO criteria, and among these articles 1 study met both RECIST and RECIST 1.1 criteria and 1 met both RECIST 1.1 and SWOG criteria. The pooled DRRs were 33.0% (95% CI: 25.0%-42.0%, I = 65%), 35.0% (95% CI: 26.0%-45.0%, I = 91%) and 25.0% (95% CI: 14.0%-36.0%, I = 84%) according to RECIST, RECIST 1.1 and SWOG criteria, respectively. The pooled DCRs were 79.0% (95% CI: 75.0%-83.0%, I = 97%), 83.0% (95% CI: 78.0%-88.0%, I = 0) and 82.0% (95% CI: 75.0%-89.0%, I = 91%), respectively.
CONCLUSION
In advanced NETs patients, DRRs and DCRs were significantly elevated after initial treatment with Lu-DOTATATE PRRT, which shows that this treatment would be beneficial and promising for advanced or inoperable NETs patients.
Topics: Humans; Neuroendocrine Tumors; Octreotide; Radiopharmaceuticals; Response Evaluation Criteria in Solid Tumors
PubMed: 32150065
DOI: 10.1097/MD.0000000000019304 -
Endocrine Practice : Official Journal... Apr 2020Comprehensive evidence comparing different medications for acromegaly is scarce. The aim of this study was to perform a network meta-analysis based on evidence from...
Comprehensive evidence comparing different medications for acromegaly is scarce. The aim of this study was to perform a network meta-analysis based on evidence from both randomized trials and observational studies of medical treatments for acromegaly. Electronic databases were searched for both observational studies and randomized trials that enrolled acromegaly patients treated with medications of interest. Simulated trials were generated by a machine learning algorithm and then synthesized with Bayesian random-effects network meta-analyses. The main outcome was the rate of insulin-like growth factor 1 (IGF-1) control after medical treatment. We included 90 studies (100 arms, 4,523 patients) before matching. After matching, 28 simulated trials were generated. Balance of matched arms was checked by spatial distance and correlation matrix. Cotreatment with somatostatin receptor ligands and pegvisomant was the most effective treatment compared with other treatments. In unselected patients, pegvisomant was better than octreotide long-acting release (logOR, 0.85; 95% credible interval [CrI], 0.05 to 1.65) or lanreotide (logOR, 1.09, 95% CrI, 0.05 to 2.14), and the mean absolute IGF-1 control rate ranged from 40 to 60%. In partially responsive patients, cotreatment with somatostatin receptor ligands and pegvisomant was similar to pegvisomant monotherapy, ranking as the most two effective treatments, and the mean absolute IGF-1 control rate was over 60%. Our analysis suggested that the combination of data from observational studies and randomized trials in network meta-analysis was feasible. The findings of this network meta-analysis provided robust evidence supporting the current guidelines in treatment strategy for acromegaly. = credible interval; = dopamine agonist; = growth hormone; = insulin-like growth factor 1; = intention-to-treat; = lanreotide; = lanreotide autogel; = octreotide; = octreotide long acting repeatable; = odds ratio; = pegvisomant; = per-protocol; = somatostatin receptor ligand.
Topics: Acromegaly; Bayes Theorem; Human Growth Hormone; Humans; Insulin-Like Growth Factor I; Network Meta-Analysis; Observational Studies as Topic; Octreotide; Peptides, Cyclic; Randomized Controlled Trials as Topic
PubMed: 32045295
DOI: 10.4158/EP-2019-0528 -
Annals of Translational Medicine Dec 2019We aimed to compare the efficacy of different drugs facilitating endoscopy in patients with acute variceal bleeding.
BACKGROUND
We aimed to compare the efficacy of different drugs facilitating endoscopy in patients with acute variceal bleeding.
METHODS
Databases were searched to identify randomized controlled trials which compared the efficacy of vasoactive drugs (vasopressin, terlipressin, octreotide, somatostatin) with placebo or each other. The primary outcomes were 6-week and 5-day mortality. Secondary outcomes were 5-day rebleeding, control of initial bleeding and adverse events. Pairwise and network meta-analysis were performed.
RESULTS
We identified 14 RCTs involved 2,187 patients. Four drugs had comparable clinical efficacy in all involving outcomes, except for adverse events. However, we do exhibit a superiority when vasopressin (OR, 4.40; 95% CI: 1.04-19.57), terlipressin (OR, 4.58; 95% CI: 1.63-13.63), octreotide (OR, 5.79; 95% CI: 2.41-16.71) and somatostatin (OR, 5.15; 95% CI: 1.40-27.39) were compared to placebo respectively as for initial hemostasis. In addition, only octreotide was more effective than placebo in decreasing 5-day rebleeding (OR, 0.44; 95% CI: 0.22-0.90). Meanwhile, octreotide was shown to have the highest probability ranking the best to improve initial hemostasis (mean rank =1.8) and carries a lowest risk of adverse events (9.1%) and serious adverse events (0.0%) compared to other drugs.
CONCLUSIONS
Balanced with curative effect and tolerability, octreotide may be the preferred vasoactive drug facilitating endoscopy.
PubMed: 32042733
DOI: 10.21037/atm.2019.12.26 -
Pancreatology : Official Journal of the... Mar 2020Post-operative pancreatic fistula (POPF) is a common complication of pancreatic resection. Somatostatin analogues (SA) have been used as prophylaxis to reduce its... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Post-operative pancreatic fistula (POPF) is a common complication of pancreatic resection. Somatostatin analogues (SA) have been used as prophylaxis to reduce its incidence. The aim of this study is to appraise the current literature on the effects of SA prophylaxis on the prevention of POPF following pancreatic resection.
METHODS
The review of the literature was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Data from studies that reported the effects of SA prophylaxis on POPF following pancreatic resection were extracted, to determine the effect of SA on POPF morbidity and mortality.
RESULTS
A total of 15 studies, involving 2221 patients, were included. Meta-analysis revealed significant reductions in overall POPF (Odds ratio: 0.65 (95% CI 0.53-0.81, p < 0.01)), clinically significant POPF (Odds ratio: 0.53 (95% CI 0.34-0.83, p < 0.01)) and overall morbidity (OR: 0.69 (95% CI: 0.50-0.95, p = 0.02)) following SA prophylaxis. There is no evidence that SA prophylaxis reduces mortality (OR: 1.10 (95%CI: 0.68-1.79, p = 0.68)).
CONCLUSION
SA prophylaxis following pancreatic resection reduces the incidence of POPF. However, mortality is unaffected.
Topics: Humans; Incidence; Pancreas; Pancreatic Fistula; Postoperative Complications; Risk Assessment; Somatostatin
PubMed: 31980352
DOI: 10.1016/j.pan.2019.12.015 -
Nuclear Medicine Communications Dec 2019Advanced pancreatic neuroendocrine tumors (pNETs) present a therapeutic challenge with targeted therapies like Everolimus and Lu-DOTATATE peptide receptor radionuclide... (Comparative Study)
Comparative Study Meta-Analysis Review
OBJECTIVE
Advanced pancreatic neuroendocrine tumors (pNETs) present a therapeutic challenge with targeted therapies like Everolimus and Lu-DOTATATE peptide receptor radionuclide therapy (PRRT) showing beneficial effects in various cohort studies and randomized trials. Currently there is a paucity of trials with head-to-head comparison between PRRT and Everolimus in advanced pNETs. This systematic review was conducted to compare the therapeutic efficacy and safety profile of Lu-DOTATATE and Everolimus in advanced pNETs.
METHODS
The review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Searches in Pubmed, Scopus and Embase using relevant keywords selected articles up to June 2019. Data on efficacy and safety were extracted from the individual articles. Random effects model was used for meta-analysis.
RESULTS
Fifteen articles consisting of 697 patients reported on Lu-DOTATATE and 12 articles consisting of 946 patients reported on Everolimus. Overall, treatment with Lu-DOTATATE had better objective response rate (47% vs. 12%, P < 0.001) and disease control rate (81% vs. 73%, P < 0.001) and longer progression-free survival (25.7 months vs. 14.7 months, P < 0.001) than with Everolimus. Lu-DOTATATE also had a better safety profile than Everolimus with fewer patients showing grade 3/4 hematological toxicity (5% vs. 11%, P = 0.02) and nephrotoxicity (1% vs. 2.5%, P = 0.34). Treatment-related adverse events caused discontinuation of therapy more frequently for Everolimus than for Lu-DOTATATE (59 out of 371 patients vs. 0 out of 128 patients).
CONCLUSION
From this meta-analysis, Lu-DOTATATE showed better therapeutic efficacy and safety profile compared to Everolimus in advanced pNETs.
Topics: Coordination Complexes; Everolimus; Humans; Neuroendocrine Tumors; Octreotide; Pancreatic Neoplasms; Receptors, Peptide
PubMed: 31658219
DOI: 10.1097/MNM.0000000000001103