Role Of Octreotide Research Articles

Role of Octreotide and Somatostatin in the Treatment of Intestinal Fistulae

Intestinal fistulae usually arise as a complication of abdominal surgery. Its treatment is complex and intestinal fistula-related morbidity and mortality is high. Fistula closure rates under conservative medical treatment vary between 24 and 72%. Octreotide and somatostatin reduce gastrointestinal, biliary and pancreatic secretion and increase intestinal water and electrolyte absorption. In recent years, octreotide and somatostatin have been associated with conservative medical treatment for patients with intestinal fistulae. Four placebo-controlled studies have been published within the past 6 years. The interpretation of their results is difficult because patient collectives were small and heterogeneous. In one study, somatostatin decreased fistula-related complications when compared to placebo, and in another study, octreotide decreased the healing time of intestinal fistulae and the time patients required total parenteral nutrition when compared to placebo. In contrast, the fistula closure rate, hospitalization time and mortality were not influenced by the use of octreotide or somatostatin in conservative medical treatment. In conclusion, octreotide and somatostatin actually cannot be recommended in the treatment of intestinal fistulae in settings outside of controlled trials.

Small Bowel Dysmotility.

The most important initial step in treating patients with intestinal dysmotility is to exclude reversible causes, in particular mechanical obstruction. The presence or absence of bacterial overgrowth should be determined by small bowel aspirate or breath test, although an empiric trial with antibiotics is an appropriate alternative. Physicians should use agents effective against gram-negative organisms, such as broad-spectrum penicillins or tetracycline, particularly those that provide coverage of anaerobes, such as metronidazole. Nutritional support, by enteral or parenteral means, is currently the most important aspect of management of patients with severe intestinal dysmotility. A low-fat diet, supplemented by liquid formulas, can be tried first. The presence of gastroparesis should be determined; if severe, jejunal feeding should be attempted. Because of the costs and risks associated with total parenteral nutrition (TPN), every attempt should be made to use the native intestine for feeding. A trial of several days of naso-jejunal feeding can help select those patients who can obtain sufficient nutrition by enteral routes and is recommended prior to committing a patient to TPN therapy. Even while on TPN, some oral intake should be encouraged. Prokinetic agents currently in use are less effective in the small bowel than they are in the stomach. They should always be tried initially, though, particularly because improvement of concomitant gastric dysmotility can alleviate symptoms. Although certain manometric patterns can select those patients who respond better to therapy, manometry should not be used to direct therapy in individual patients. For the moment, cisapride is the drug of choice. Erythromycin, particularly when given intravenously and in small, sub-antibiotic doses, can also be tried. The role of octreotide is not clear, but when given at small doses, and when combined with erythromycin, it may be useful in selected patients. Ablative surgery may be useful in a few, highly selected patients. One of the most beneficial surgical procedures is a venting jejunostomy. The use of this simple intervention can substantially reduce the number of hospital admissions and emergency room visits in selected patients with intermittent obstructive symptoms.

Blood digestion-induced splanchnic hyperemia and portal blood flow in portal hypertensive rats and the role of octreotide.

We aimed to investigate whether the presence of blood within the intestinal lumen after variceal bleeding would lead to reactive intestinal hyperemia, which in turn could result in the worsening of portal hemodynamics, and thus bleeding recurrence. Two models of portal hypertensive Wistar rats were used: 32 CCl4-cirrhotics with a low index of portal-systemic shunting and 32 that had been previously subjected to portal vein stenosis, with a high index of portal-systemic shunting; 32 Wistar rats served as controls. The rats were divided into four groups, each comprising 8 cirrhotics, 8 portal vein stenosis rats, and 8 controls. Intestinal microcirculation and portal blood flow were assessed by laser-Doppler and transit-time ultrasonic flow probes, respectively, before and 60 min after the injection of 2 ml of blood (groups 1 and 2) or an equal volume of NaCl 0.9% (placebo; groups 3 and 4) into the intestinal lumen. Octreotide (0.2 microg/100 g body weight [BW]) (groups 1 and 3) or NaCl 0.9% (groups 2 and 4) was then given subcutaneously, and 30 min later the final measurements were performed. The presence of blood within the intestinal lumen resulted in an increase in intestinal microcirculation in rats in all groups, while portal blood flow was increased in portal vein stenosis rats and controls, and decreased in cirrhotics. The presence of NaCl 0.9% had no effect. Octreotide, but not NaCl 0.9%, led to a decrease in both intestinal microcirculation and portal blood flow. The findings of this study suggest that intestinal hyperemia induced by digestion of blood in the enteric lumen increases or decreases portal blood flow, the result being strongly related to the portal hypertension model used. Since the main difference between the models was the extent of portal-systemic shunting, this may suggest a relationship between portal blood flow and portal-systemic shunting. This relationship could explain why variceal bleeding stops in some patients but recurs in others.

Long-term follow-up of two patients with metastatic neuroendocrine tumours treated with octreotide

Two patients are described with metastatic neuroendocrine tumours of the pancreas head and region of Vater. After surgery, administration of the long-acting somatostatin analogue octreotide was started. In the first patient we found an IgG-lambda paraproteinaemia and a parathyroid hormone-related protein (PTHrP) driven hypercalcaemia. By increasing the dose of octreotide the paraproteinaemia disappeared. In the second patient with a metastasized somatostatin producing neuroendocrine tumour, octreotide showed a long-term stabilizing effect on symptoms and progression of disease. The role of octreotide in the induction of changes in biological behaviour of malignant neuroendocrine cells is discussed.

Acromegaly

Subcellular mechanisms support the notion of an intrinsic pituitary defect in acromegaly, with elevated growth hormone (GH) and insulin-like growth factor-1 (IGF-1) levels that affect the cardiovascular and respiratory system, as well as neoplastic cell proliferative activity. Surgery, even with external-beam irradiation adjuvant therapy, is only successful in less than 60% of patients, and there are side effects. Normalization of GH levels may improve survival rates. Octreotide has revolutionized patient management, normalizing GH and IGF-1 levels in up to 60%, ameliorating soft-tissue abnormalities and reducing tumor size in up to 50%, and attenuating GH levels in more than 90% of patients. Issues concerning the role of octreotide, as well as clarifying precise outcome measures, still need to be resolved.

Effect of octreotide on neuroenolase levels in patients with small cell lung cancer.

The somatostatin analog octreotide has an antiproliferative effect on small cell lung cancer lines in vitro and in experimental xenograft transplantation systems in vivo. Thus it is worth investigating octreotide activity in the clinical setting. We studied the effect of octreotide (200 micrograms three times a day subcutaneously for seven days) on serum levels of the tumor marker neuroenolase in 13 patients with small cell lung cancer. A decrease in neuroenolase levels was observed at day 7 during octreotide treatment, with a mean +/- SD of 32.6 +/- 42.0 ng/ml compared to basal values of 44.4 +/- 57.7 ng/ml and to washout values of 50.3 +/- 65.7 ng/ml (P < 0.03). Our results indicate that octreotide is effective in reducing neuroenolase levels in small cell lung cancer patients. These data suggest a possible role for octreotide in the treatment of this kind of tumor.

Somatostatin in gastroenterology More studies needed

EDITOR, - We noted with concern the enthusiasm with which A Shulkes and J S Wilson endorse the use of somatostatin and its analogue octreotide in gastroenterology.1 In particular, we have reservations concerning the reported role of octreotide in the management of enterocutaneous fistula since, despite a successful pilot study,2 more studies seem warranted to clarify the timing and the cost-benefit of such treatment. Indeed, more recent studies of patients with such fistulas have failed …

The role of octreotide in palliative care

Octreotide, an analogue of somatostatin with a more favorable pharmacokinetic profile, is a new drug that may offer some advantages in the palliative care setting. It has been used with favorable results in the management of some gastrointestinal disorders, such as gastrointestinal hemorrhage, diarrhea, short-bowel syndrome, fistula, and intestinal occlusion in the palliative care setting. These favorable results occurred without important side effects, underlining the potential role of this drug. The cost-benefit ratio of this expensive drug must be considered, however.

Emerging indications for octreotide therapy, Part 1

Possible new indications for the use of octreotide are discussed. In October 1988, octreotide received FDA-approved labeling for use in the management of carcinoid syndrome and vipomas. Since that time, research results and clinical experience have accumulated that suggest a potentially much broader therapeutic role for octreotide. Reports continue to be published on the use of octreotide for treating pituitary tumors, gastroenteropancreatic tumors, diabetes mellitus, AIDS-associated diarrhea, autonomic neuropathy, pancreatitis, pancreatic pseudocysts and ascites, complications of pancreatic surgery and transplantation, ileostomy-associated diarrhea, enterocutaneous fistulas, pancreatic fistulas, dumping syndrome, short bowel syndrome, and gastrointestinal bleeding. Other emerging indications for the use of octreotide include psoriasis, hypercalcemia, cancer-related pain, polycystic ovary syndrome, and certain cancers. In children, octreotide has been studied for use in treating hyperinsulinemic hypoglycemia of infancy. Along with the common adverse effects of octreotide, such as pain at the injection site and nausea, less frequent effects, such as cholelithiasis, gallbladder hypercontractility, and gastritis have now been described. Much of what has been learned is based on small uncontrolled studies and case reports, since the rarity of many of the conditions for which octreotide has shown promise has tended to preclude larger studies. As clinical experience with octreotide accumulates and better-designed trials are completed where possible, a broader therapeutic role for octreotide is likely to be recognized.

Potential role for octreotide in Cushing??s syndrome

Potential role for octreotide in Cushing??s syndrome

Perioperative Use of Octreotide in Gastrointestinal Surgery

The evolution of gastrointestinal endocrinology has led to the design and application of analogs of gut peptides to treat disease. Octreotide, a long-acting analog of the inhibitory peptide somatostatin, has proven useful in the management of disorders such as carcinoid syndrome and secretory diarrhea due to VIPoma. More recent experience suggests a role for this peptide in the management of certain complications of gastrointestinal surgery. Prophylactic use of octreotide appears warranted in the prevention of carcinoid crisis in selected patients with carcinoid syndrome undergoing invasive procedures, and in the prevention of complications in selected patients undergoing pancreatic surgery. Evidence from placebo-controlled trials supports a role for octreotide in the management of dumping symptoms in severely affected patients, at least in the short term. Octreotide appears to serve a useful adjunctive role in controlling output from postoperative gastrointestinal fistulae and may hasten closure, particularly in pancreatic fistulae. Selected patients with ileostomy diarrhea and short bowel syndrome benefit from octreotide treatment, but the long-term value of the peptide in controlling stool output is less clear. Rare patients with other forms of postoperative secretory diarrhea have been successfully treated with octreotide. Finally, animal and early human experience suggests that octreotide may have a role as an adjunctive treatment of partial small bowel obstruction. In most of these conditions, the available data is sparse and further controlled trials are warranted.

The role of octreotide (Sandostatin ®) in non-growth hormone-, non-thyroid-stimulating hormone-, and non-prolactin-secreting adenomas

Octreotide may act on non-growth hormone-, non-thyroid-stimulating hormone, and non-prolactin-secreting adenomas. Its efficacy was reported in some corticotropin-secreting adenomas from Nelson's syndrome and from Cushing's disease. In gonadotropin-secreting adenomas, octreotide was shown to be effective in two of eight cases. In nonfunctioning adenomas, visual improvement was observed with octreotide in 14 of 23 cases in a French multicenter study. Among the 33 patients whose tumor volume was checked, shrinkage occurred in seven, but an increase in tumor volume was observed in another seven patients. Mechanism(s) and prediction of efficacy of octreotide remain to be documented.

Pancreatic ascites and effusion. Risk factors for failure of conservative therapy and the role of octreotide.

The possible risk factors for failure of medical therapy were examined in 23 patients with pancreatic ascites or effusion. The ascites or effusion resolved completely in 10 patients after a mean (+/- SEM) of 30 +/- 2 days of conventional medical treatment. In five patients in whom conventional medical therapy failed, the addition of an octreotide (SMS 201-995) analogue to the medical therapy led to a resolution of the ascites (three patients) or effusion (two patients). Six patients underwent surgery after failed medical therapy, one patient died while receiving conservative therapy, and one patient refused hospital treatment. Serum sodium and albumin levels were significantly lower, and the ratio of total fluid protein to total serum protein was significantly higher in the group that failed to heal in response to conventional medical therapy. Nine of 11 patients with mild to moderately severe chronic pancreatitis healed in response to conservative therapy. Only one of 10 patients with advanced pancreatitis healed in response to conventional medical therapy. Our results suggest that a selective surgical approach is warranted to treat pancreatic ascites and effusion. In patients with mild or moderately severe pancreatitis, medical therapy is recommended. Patients with advanced pancreatic disease should be selected for early surgery. Octreotide may be useful in the patient in whom surgery may be associated with a prohibitive morbidity or mortality.

Octreotide inhibits insulin-like growth factor-I hepatic gene expression in the hypophysectomized rat: evidence for a direct and indirect mechanism of action.

Somatostatin and somatostatin analogs are known to interact with the GH-insulin-like growth factor (IGF)-I axis by inhibiting GH secretion and consequently hepatic IGF-I production. Indirect evidence suggests that octreotide, a somatostatin analog, reduces serum IGF-I levels relatively more than expected from GH reduction, implying a GH-independent pathway of action. To study the role of octreotide in the regulation of IGF-I production, independently of endogenous GH, we used the hypophysectomized (hypox) rat to measure hepatic IGF-I expression and also employed cultured rat hepatocytes to examine whether octreotide has any direct effect on the production of IGF-I. Forty male hypox Sprague-Dawley rats were randomized into 4 groups to receive daily injections for 3 days of either saline, human GH (hGH) (100 g), octreotide (100 g twice), or both hGH (100 g) and octreotide (100 g twice). GH stimulated serum IGF-I levels to 104 +/- 10 micrograms/liter as compared to saline (26 +/- 2 micrograms/liter). Octreotide alone had no effect, but combining octreotide and hGH significantly reduced the hGH-induced rise in the IGF-I levels (52 +/- 6 micrograms/liter). The relative expression of hepatic IGF-I in the rats treated with hGH increased by 4-fold compared to that in the saline-treated rats. Octreotide administered simultaneously with hGH potently blocked the hGH-induced IGF-I expression to control levels. In cultured hepatocytes, IGF-I mRNA levels maximally stimulated by combining bGH and glucagon were significantly inhibited in the presence of octreotide at low concentrations (0.3 and 3 ng/ml) by 25% and 45%, respectively. In contrast, high concentrations of octreotide (30 and 300 ng/ml) had no significant effect on IGF-I mRNA abundance. We conclude that: 1) octreotide inhibits IGF-I serum levels and hepatic gene expression in the hypox rat; and 2) octreotide can inhibit partially the direct effects of GH and glucagon on hepatic IGF-I production.

Role of octreotide in the prevention of postoperative complications following pancreatic resection

Though morbidity and mortality rates following pancreatic resection have improved in recent years, they are still around 35% and 5%, respectively. Typical complications, such as pancreatic fistula, abscess, and subsequent sepsis, are chiefly associated with exocrine pancreatic secretion. In order to clarify whether the perioperative inhibition of exocrine pancreatic secretion prevents complications, we assessed the efficacy of octreotide, a long-acting somatostatin analogue.We conducted a randomized, double-blind, placebo-controlled, multicenter trial in 246 patients undergoing major elective pancreatic surgery. Patients were stratified into a high-risk stratum (limited to patients with pancreatic and periampullary tumors) or low-risk stratum (patients with chronic pancreatitis). Patients received octreotide (3 X 100 μg) or placebo subcutaneously for 7 days perioperatively. Eleven complications were defined: death, leakage of anastomosis, pancreatic fistula, abscess, fluid collection, shock, sepsis, bleeding, pulmonary insufficiency, renal insufficiency, and postoperative pancreatitis.Two hundred patients underwent pancreatic head resection, 31 patients underwent left resection, and 15 patients had other procedures. The overall mortality rate within 90 days was 4.5%, with 3.2% in the octreotide group and 5.8% in the placebo group. The complication rate was 32% in the patients receiving octreotide (40 of 125 patients) and 55% in patients receiving placebo (67 of 121 patients) (p < 0.005). In the patients in the high-risk stratum, complications were observed in 26 of the 68 (38%) patients treated with octreotide and in 46 of 71 (65%) patients given placebo (p < 0.01). Whereas in patients in the low-risk stratum, the complication rate was 25% (14 of 57 patients) in those treated with octreotide and 42% (21 of 50 patients) in patients given placebo (p = NS).The perioperative application of octreotide reduces the occurrence of typical postoperative complications after pancreatic resection, particularly in patients with tumors.

ROLE OF OCTREOTIDE ON OUTCOME OF PATIENTS WITH ACUTE PANCREATITIS

BACKGROUND: acute pancreatitis is a multisystem disease carrying broad spectrum of clinicalpresentation and complications. The objective of this study was to determine the positive role ofoctreotide in the out come of patients suffering from acute pancreatitis.OBJECTIVE: The objective of this study was to assess the role of octreotide in patients having acutepancreatitis.PATIENTS AND METHODS: This is a descriptive, comparative, prospective study. The study wasconducted in the department of surgery Saidu Group of Teaching hospital Saidu Sharif Swat fromJanuary 2011 to June 2014. Total of seventy consecutive patients having acute pancreatitis wasrandomized in a prospective trail for the treatment, at tertiary care hospital in Malakand division SwatKPK Pakistan. The data of patients were recorded on a purposely prepared proforma for this study. Thediagnosis of patients was established on basis of biochemical (serum amylase, WCC, C-reactive protein)and radiological (USG, CT- scan) investigations. The patients were divided into two groups, A and B.Group A, had received octreotide along with fluids, omeprazole, analgesic. Group B received fluids,omeprazole, analgesic without octreotide. Ages of the Group A and B were matched (±5 years). Datawas analyzed using SPSS version 16 employing chi-square test (X" test). A p-value below 0.05 wasconsidered statistically significant.RESULTS: In this prospective, comparative study two groups, each of 35 consecutive patients wereselected. The mean age in Group A was 37 ±12.41 years and in Group B 40±10.32 years (p DO.364).There were 12 males and 23 females in group A, while 14 males and 21 females in group B. Both thegroups were comparable. All the patients in octreotide group A and non-octreotide group B weresurvived. No major complications were noted in either group. As far as mean hospital stay was 7 ±2.10days in group A, while it was 9±3.14 days in group B (p&lt;0.032). All the P- values for the criteria ofstudy were calculated. P-values were significant when we consider pain control and hospital stay intwo groups.CONCLUSION: In our study we found that octreotide was more effective in the final outcome ofpatients with acute pancreatitis. There is clear cut beneficial effect of octreotide on hospital stay andreduced need of analgesics in patients having acute pancreatitis.KEYWORDS: Acute Pancreatitis, Octreotide, Hospital Stay, pain control.