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Indian Journal of Cancer 2023Postoperative pancreatic fistula (POPF) is the most feared complication following pancreatic resection. Octreotide, a synthetic somatostatin analog, has been widely used... (Review)
Review
Postoperative pancreatic fistula (POPF) is the most feared complication following pancreatic resection. Octreotide, a synthetic somatostatin analog, has been widely used by pancreatic surgeons worldwide after pancreatic resections, often as per surgeon's discretion, to prevent POPF especially in cases at high risk of developing POPF. We herein analyze the data available till date of the subject. A PubMed search with keywords "somatostatin OR octreotide OR somatostatin analogues AND postoperative pancreatic fistula" was made. Further filters were applied in the search "Clinical Trial, Meta-Analysis, Randomized Controlled Trial, Systematic Review, from 1990 - 2021," and the 68 results thus obtained were analyzed and included in this narrative review. There is considerable heterogeneity among the studies assessing the role of octreotide in the prevention of POPF making data comparison difficult, and hence results remain inconclusive. Most of the earlier studies used different definitions of POPF and other complications; included patients with varied pancreatic pathologies such as cancer, chronic pancreatitis, and benign lesions; surgical techniques such as pancreaticoduodenectomy, distal pancreatectomy, and other procedures; use of somatostatin and its analogs such as octreotide, lanreotide, pasireotide, and vapreotide; varied surgeon and institutional volume; and so on. Besides, pancreatic surgery is per se a complex surgical procedure and has its own inherent biases related to patient and the pancreas itself affecting the overall outcome. Data indicate favorable role of newer somatostatin analogs, and further studies are urgently needed. The question about the efficacy of prophylactic octreotide to reduce POPF after pancreaticoduodenectomy remains open to debate.
Topics: Humans; Octreotide; Pancreas; Pancreatectomy; Pancreatic Fistula; Pancreaticoduodenectomy; Postoperative Complications; Randomized Controlled Trials as Topic; Risk Factors; Somatostatin; Treatment Outcome
PubMed: 37530235
DOI: 10.4103/ijc.IJC_280_21 -
British Journal of Clinical Pharmacology Feb 1999Somatostatin analogues (e.g. vapreotide) are used for treatment of acromegaly, endocrine tumours and variceal bleeding. The pharmacodynamic effects of vapreotide have,... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
The effects of vapreotide, a somatostatin analogue, on gastric acidity, gallbladder emptying and hormone release after 1 week of continuous subcutaneous infusion in normal subjects.
AIMS
Somatostatin analogues (e.g. vapreotide) are used for treatment of acromegaly, endocrine tumours and variceal bleeding. The pharmacodynamic effects of vapreotide have, however, not been documented in the gastrointestinal tract. The aim of this study was to investigate the effects of continuous vapreotide administration on gastric acidity, gallbladder contraction and hormone release.
METHODS
Ten healthy males participated in this randomised, placebo-controlled, double-blind, crossover trial. A constant vapreotide (or placebo) infusion (1.5 mg day(-1) s.c.) was given for 7 days with a portable pump. Intragastric pH was monitored on days 2 and 7. Gallbladder volume was sonographically assessed and the maximal ejection fraction was calculated. In addition basal and postprandial plasma levels of gastrin and cholecystokinin (CCK) were measured.
RESULTS
After an initial increase in the median 24 h intragastric pH to a value of 2.6 on day 2, vapreotide's effect on pH decreased: (day 7: median pH=1.9; respective placebo values were 1.7 and 1.5). On the same days with vapreotide treatment, gallbladder contraction and plasma levels of CCK were reduced; maximal ejection fractions after meal stimulation were 18% and 20% (respective placebo values were 57% and 62%). Plasma gastrin levels were not changed with vapreotide treatment.
CONCLUSIONS
The short lasting effect of vapreotide on intragastric acidity suggests a down-regulation of somatostatin receptors during treatment. The lack of effect on gastrin indicates that the effects on gastric pH are not mediated by gastrin. Constant vapreotide infusion (but not placebo) reduced gallbladder contraction suggesting a long-lasting effect on biliary function.
Topics: Administration, Cutaneous; Adult; Antineoplastic Agents; Cholecystokinin; Cross-Over Studies; Double-Blind Method; Drug Administration Schedule; Gallbladder Emptying; Gastric Acid; Gastrins; Humans; Hydrogen-Ion Concentration; Infusion Pumps; Male; Placebos; Somatostatin; Time Factors
PubMed: 10190655
DOI: 10.1046/j.1365-2125.1999.00878.x -
Neuroimmunomodulation 2013Vapreotide, a synthetic analog of somatostatin, has analgesic activity most likely mediated through the blockade of neurokinin-1 receptor (NK1R), the substance P...
OBJECTIVES
Vapreotide, a synthetic analog of somatostatin, has analgesic activity most likely mediated through the blockade of neurokinin-1 receptor (NK1R), the substance P (SP)-preferring receptor. The ability of vapreotide to interfere with other biological effects of SP has yet to be investigated.
METHODS
We studied the ability of vapreotide to antagonize NK1R in three different cell types: immortalized U373MG human astrocytoma cells, human monocyte-derived macrophages (MDM) and a human embryonic kidney cell line, HEK293. Both U373MG and MDM express endogenous NK1R while HEK293 cells, which normally do not express NK1R, are stably transformed to express human NK1R (HEK293-NK1R).
RESULTS
Vapreotide attenuates SP-triggered intracellular calcium increases and nuclear factor-κB activation in a dose-dependent manner. Vapreotide also inhibits SP-induced interleukin-8 and monocyte chemotactic protein-1 production in HEK293-NK1R and U373MG cell lines. Vapreotide inhibits HIV-1 infection of human MDM in vitro, an effect that is reversible by SP pretreatment.
CONCLUSIONS
Our findings indicate that vapreotide has NK1R antagonist activity and may have a potential application as a therapeutic intervention in HIV-1 infection.
Topics: Analgesics; Aprepitant; Calcium; Cell Line; Chemokine CCL2; Cytokines; Dose-Response Relationship, Drug; Drug Interactions; Gene Expression Regulation; Humans; Macrophages; Morpholines; NF-kappa B; Neurokinin-1 Receptor Antagonists; Receptors, Neurokinin-1; Receptors, Somatostatin; Signal Transduction; Somatostatin; Substance P; Transfection; gag Gene Products, Human Immunodeficiency Virus
PubMed: 23921645
DOI: 10.1159/000350468 -
Postgraduate Medical Journal Jul 1996The long-acting analogues of somatostatin have an established place in the medical treatment of patients with neuroendocrine tumours. They act through binding with... (Review)
Review
The long-acting analogues of somatostatin have an established place in the medical treatment of patients with neuroendocrine tumours. They act through binding with specific, high-affinity membrane receptors. Somatostatin analogue therapy is an effective and safe treatment for most growth hormone and thyrothropin-secreting pituitary adenomas. The potential therapeutic consequences of the presence of somatostatin receptors on clinically 'nonfunctioning' pituitary tumours are still uncertain. Somatostatin analogues are not useful in the treatment of patients with prolactinomas, or adrenocorticotropin (ACTH)-secreting adenomas. However, the somatostatin analogue octreotide suppressed pathological ACTH release in some patients with Nelson's syndrome and ACTH and cortisol secretion in several patients with Cushing's syndrome caused by ectopic ACTH secretion. Somatostatin analogues are effective in the sympatomatic treatment of most (metastatic) pancreatic islet cell tumours and most (metastatic) carcinoids. In some of these patients, they also induce tumour stabilisation or reduction. In some patients with (metastatic) medullary thyroid carcinomas, continuous treatment with very high doses of octreotide can be of temporary relief. The clinical effectiveness of somatostatin analogues in patients with small cell lung cancer is currently under investigation. Long-term therapy with somatostatin analogues of catecholamine-secreting (malignant) paragangliomas and phaeochromocytomas has not shown clinical benefits.
Topics: Antineoplastic Agents; Apudoma; Hormone Antagonists; Humans; Neuroendocrine Tumors; Octreotide; Peptides, Cyclic; Pituitary Neoplasms; Receptors, Somatostatin; Somatostatin
PubMed: 8935599
DOI: 10.1136/pgmj.72.849.403 -
The New England Journal of Medicine Jan 2001In patients with cirrhosis, pharmacologic or endoscopic treatment may control variceal bleeding. However, the effects of early administration of a somatostatin analogue... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
BACKGROUND
In patients with cirrhosis, pharmacologic or endoscopic treatment may control variceal bleeding. However, the effects of early administration of a somatostatin analogue followed by endoscopic treatment are unknown.
METHODS
We studied the effects of treatment with vapreotide, a somatostatin analogue, begun before endoscopic treatment in 227 patients with cirrhosis who were hospitalized for acute upper gastrointestinal bleeding. The patients were randomly assigned to receive vapreotide (a 50-microg intravenous bolus followed by an infusion at a rate of 50 microg per hour for five days) or placebo within a mean (+/-SD) of 2.3+/-1.5 hours after admission. All the patients received endoscopic treatment a mean of 2.6+/-3.3 hours after the infusion was begun. After the exclusion of 31 patients whose bleeding was not caused by portal hypertension, there were 98 patients in each group.
RESULTS
At the time of endoscopy, active bleeding was evident in 28 of 91 patients in the vapreotide group (31 percent), as compared with 43 of 93 patients in the placebo group (46 percent) (P=0.03). During the five-day infusion, the primary objective--survival and control of bleeding--was achieved in 65 of 98 patients in the vapreotide group (66 percent) as compared with 49 of 98 patients in the placebo group (50 percent) (P=0.02). The patients in the vapreotide group received significantly fewer blood transfusions (2.0+/-2.2 vs. 2.8+/-2.8 units, P=0.04). Overall mortality rates at 42 days were not significantly different in the two groups.
CONCLUSIONS
In patients with cirrhosis and variceal bleeding, the combination of vapreotide and endoscopic treatment is more effective than endoscopic treatment alone as a method of controlling acute bleeding. However, the use of combination therapy does not affect mortality rates at 42 days.
Topics: Blood Transfusion; Combined Modality Therapy; Endoscopy; Esophageal and Gastric Varices; Female; Gastrointestinal Hemorrhage; Humans; Hypertension, Portal; Liver Cirrhosis; Male; Middle Aged; Multivariate Analysis; Sclerotherapy; Secondary Prevention; Somatostatin
PubMed: 11136956
DOI: 10.1056/NEJM200101043440104 -
Annals of Oncology : Official Journal... May 2002Somatostatin (SST) analogues represent a novel approach for the treatment of certain cancers. The objective of this article is to summarise the current knowledge on SST... (Review)
Review
BACKGROUND
Somatostatin (SST) analogues represent a novel approach for the treatment of certain cancers. The objective of this article is to summarise the current knowledge on SST analogues in the treatment of cancer patients.
METHODS
Computerised (Medline) and manual searches were performed to identify publications on clinical trials published in the English-speaking literature between 1966 and 2000. Information abstracted included patients' pre-treatment status, histology, SST receptor (SSTR) evaluation, type of SST analogue, application schedule and dose, duration of treatment, side-effects, response criteria applied (i.e. WHO response criteria, biochemical criteria or symptomatic investigations) and survival.
RESULTS
Our search disclosed 22 case reports, five phase 1 and 47 phase II trials, and eight randomised clinical trials using SST analogues (octreotide, lanreotide and vapreotide) as antineoplastic agents. With regard to the phase II trials, conflicting results have been demonstrated in almost all tumour entities investigated. The few randomised studies published so far have shown an impact on survival in patients with hepatocellular cancer, while the effect attributed to treatment in patients with gastrointestinal adenocarcinomas might well have been due to an exceptionally short survival in the control group. There appears to be evidence that SST analogues are able to enhance the therapeutic effects of hormonal intervention in patients with breast cancer, prostate cancer and probably pancreatic cancer. Interpretation of the findings, however, is complicated by the fact that patients were heavily pre-treated in some studies and response criteria have not been uniformly applied. In addition, most studies have not been designed to distinguish between receptor-mediated (direct) and indirect effects of SST analogues in tumour patients.
CONCLUSIONS
According to the results obtained so far, there can be no doubt about the wide therapeutic index and the high efficacy of SST analogues in the symptomatic management of neuroendocrine tumours. Apart from these indications, the data do not justify recommendation of SST analogues as antineoplastic agents outside of clinical trials, as the optimal dose and schedule of application for antineoplastic activity has not been defined for currently used agents. Carefully designed clinical trials including investigation of SSTR status before treatment, evaluation of an indirect mechanism of SST analogues, and assessment of optimal combination of hormone therapy and chemotherapy with SST analogues are clearly needed in the near future.
Topics: Antineoplastic Combined Chemotherapy Protocols; Female; Humans; Male; Neoplasms; Octreotide; Peptides, Cyclic; Randomized Controlled Trials as Topic; Sensitivity and Specificity; Somatostatin; Survival Analysis; Treatment Outcome
PubMed: 12075733
DOI: 10.1093/annonc/mdf142 -
The Journal of Biological Chemistry Sep 2013Somatostatin (SST) 14 and SST 28 activate somatostatin 2A receptors (SSTR2A) on enteric neurons to control gut functions. SST analogs are treatments of neuroendocrine...
Somatostatin (SST) 14 and SST 28 activate somatostatin 2A receptors (SSTR2A) on enteric neurons to control gut functions. SST analogs are treatments of neuroendocrine and bleeding disorders, cancer, and diarrhea, with gastrointestinal side effects of constipation, abdominal pain, and nausea. How endogenous agonists and drugs differentially regulate neuronal SSTR2A is unexplored. We evaluated SSTR2A trafficking in murine myenteric neurons and neuroendocrine AtT-20 cells by microscopy and determined whether agonist degradation by endosomal endothelin-converting enzyme 1 (ECE-1) controls SSTR2A trafficking and association with β-arrestins, key regulators of receptors. SST-14, SST-28, and peptide analogs (octreotide, lanreotide, and vapreotide) stimulated clathrin- and dynamin-mediated internalization of SSTR2A, which colocalized with ECE-1 in endosomes and the Golgi. After incubation with SST-14, SSTR2A recycled to the plasma membrane, which required active ECE-1 and an intact Golgi. SSTR2A activated by SST-28, octreotide, lanreotide, or vapreotide was retained within the Golgi and did not recycle. Although ECE-1 rapidly degraded SST-14, SST-28 was resistant to degradation, and ECE-1 did not degrade SST analogs. SST-14 and SST-28 induced transient interactions between SSTR2A and β-arrestins that were stabilized by an ECE-1 inhibitor. Octreotide induced sustained SSTR2A/β-arrestin interactions that were not regulated by ECE-1. Thus, when activated by SST-14, SSTR2A internalizes and recycles via the Golgi, which requires ECE-1 degradation of SST-14 and receptor dissociation from β-arrestins. After activation by ECE-1-resistant SST-28 and analogs, SSTR2A remains in endosomes because of sustained β-arrestin interactions. Therapeutic SST analogs are ECE-1-resistant and retain SSTR2A in endosomes, which may explain their long-lasting actions.
Topics: Animals; Arrestins; Aspartic Acid Endopeptidases; Cell Line, Tumor; Endosomes; Endothelin-Converting Enzymes; Enteric Nervous System; Female; Gastrointestinal Agents; Golgi Apparatus; Male; Metalloendopeptidases; Mice; Neurons; Octreotide; Protein Transport; Proteolysis; Rats; Rats, Sprague-Dawley; Receptors, Somatostatin; Somatostatin; Somatostatin-28; beta-Arrestins
PubMed: 23913690
DOI: 10.1074/jbc.M113.496414