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Digestive Surgery 2015The use of somatostatin analogues (SAs) following pancreaticoduodenectomy (PD) is controversial. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The use of somatostatin analogues (SAs) following pancreaticoduodenectomy (PD) is controversial.
METHOD
Literature databases were searched systematically for relevant articles. A meta-analysis of all randomized controlled trials (RCTs) evaluating prophylactic SAs in PD was performed.
RESULTS
Fifteen RCTs involving 1,352 patients were included. There was a towards reduced incidences of pancreatic fistulas (p = 0.26), clinically significant pancreatic fistulas (p = 0.08), and bleeding (p = 0.05) in prophylactic SAs group. In subgroup analyses, prophylactic somatostatin significantly reduced the incidence of pancreatic fistulas(p = 0.02), with a nonsignificant trend toward reduced incidence of clinically significantly pancreatic fistulas (p = 0.06).Pasireotide significantly reduced the incidence of clinically significantly pancreatic fistulas (p = 0.03). Octreotide had no influence on the incidence of pancreatic fistulas.
CONCLUSION
The current best evidence suggests prophylactic treatment with somatostatin or pasireotide has a potential role in reducing the incidence of pancreatic fistulas, while octreotide had no influence on the incidence of pancreatic fistulas.High-quality RCTs assessing the role of somatostatin and pasireotide are required for further verification.
Topics: Gastrointestinal Agents; Humans; Models, Statistical; Octreotide; Pancreatic Fistula; Pancreaticoduodenectomy; Postoperative Complications; Postoperative Hemorrhage; Somatostatin; Treatment Outcome
PubMed: 25872003
DOI: 10.1159/000381032 -
World Journal of Gastroenterology Feb 2015To review literature on efficacy and safety of octreotide-long-acting repeatable (LAR) used at doses higher than the Food and Drug Administration (FDA)-approved 30 mg/mo... (Review)
Review
AIM
To review literature on efficacy and safety of octreotide-long-acting repeatable (LAR) used at doses higher than the Food and Drug Administration (FDA)-approved 30 mg/mo for treatment of neuroendocrine tumors (NETs).
METHODS
We searched PubMed and Cochrane Library from 1998-2012, 5 conferences (American Society of Clinical Oncology, Endocrine Society, European Neuroendocrine Tumor Society, European Society for Medical Oncology, North American Neuroendocrine Tumor Society) from 2000-2013 using MeSH and keyterms including neuroendocrine tumors, carcinoid tumor, carcinoma, neuroendocrine, and octreotide. Bibliographies of accepted articles were also searched. Two reviewers reviewed titles, abstracts, and full-length articles. Studies that reported data on efficacy and safety of ≥ 30 mg/mo octreotide-LAR for NETs in human subjects, published in any language were included in the review.
RESULTS
The search identified 1086 publications, of which 238 underwent full-text review (20 were translated into English); 17 were included in the review. Studies varied in designs, subjects, octreotide-LAR regimens, and definition of outcomes. Eleven studies reported use of higher doses to control symptoms and tumor progression, although symptom severity and formal quality-of-life analysis were not quantitatively measured. Ten studies reported efficacy, describing 260 subjects with doses ranging from 40 mg/mo or 30 mg/3 wk up to 120 mg/mo. Eight studies reported expert clinical opinion that supported dose escalation of octreotide-LAR up to 60 mg/mo for symptom control and suggested increased doses may be effective at preventing tumor progression. Eight studies reported safety; there was no evidence of increased toxicity associated with doses of octreotide-LAR > 30 mg/mo.
CONCLUSION
As reported in this review, octreotide-LAR at doses > 30 mg/mo is being prescribed for symptom and tumor control in NET patients. Furthermore, expert clinical opinion provided support for escalation of somatostatin analogs for refractory hormonal symptoms.
Topics: Antineoplastic Agents, Hormonal; Gastrointestinal Neoplasms; Humans; Neuroendocrine Tumors; Octreotide; Treatment Outcome
PubMed: 25684964
DOI: 10.3748/wjg.v21.i6.1945 -
International Journal of Surgery... 2013A best evidence topic was written according to a structured protocol. The question addressed was whether the prophylactic administration of somatostatin or somatostatin... (Review)
Review
A best evidence topic was written according to a structured protocol. The question addressed was whether the prophylactic administration of somatostatin or somatostatin analogues in patients undergoing pancreaticoduodenectomy (Whipple's procedure) is beneficial in terms of improved surgical outcomes, reduced morbidity or reduced mortality. A total of 118 papers were found using the reported searches of which 5 represented the best evidence (1 meta-analysis, 1 systematic review and 3 randomized control trials). The authors, date, journal, study type, population, main outcome measures and results were tabulated. There is evidence that the perioperative administration of somatostatin or somatostatin analogues reduces biochemical incidence of pancreatic fistula but, it is still unclear if there is a beneficial effect in the incidence of clinically significant pancreatic fistula. Further adequately powered trials with low risk of bias are necessary. From the available data, somatostatin or somatostatin analogues have no effect on mortality post Whipple's. Interestingly, there are only limited data available on the cost-benefit and financial constraints imposed by this treatment, an issue that has only been addressed in a few studies.
Topics: Gastrointestinal Agents; Humans; Octreotide; Pancreas; Pancreatic Neoplasms; Pancreaticoduodenectomy; Postoperative Complications; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 23800512
DOI: 10.1016/j.ijsu.2013.06.013 -
Journal of Pain and Symptom Management Jan 2014Death rattle, or respiratory tract secretion in the dying patient, is a common and potentially distressing symptom in dying patients. Health care professionals often... (Review)
Review
CONTEXT
Death rattle, or respiratory tract secretion in the dying patient, is a common and potentially distressing symptom in dying patients. Health care professionals often struggle with this symptom because of the uncertainty about management.
OBJECTIVES
To give an overview of the current evidence on the prevalence of death rattle in dying patients, its impact on patients, relatives, and professional caregivers, and the effectiveness of interventions.
METHODS
We systematically searched the databases PubMed, Embase, CINAHL, PsychINFO, and Web of Science. English-language articles containing original data on the prevalence or impact of death rattle or on the effects of interventions were included.
RESULTS
We identified 39 articles, of which 29 reported on the prevalence of death rattle, eight on its impact, and 11 on the effectiveness of interventions. There is a wide variation in reported prevalence rates (12%-92%; weighted mean, 35%). Death rattle leads to distress in both relatives and professional caregivers, but its impact on patients is unclear. Different medication regimens have been studied, that is, scopolamine, glycopyrronium, hyoscine butylbromide, atropine, and/or octreotide. Only one study used a placebo group. There is no evidence that the use of any antimuscarinic drug is superior to no treatment.
CONCLUSION
Death rattle is a rather common symptom in dying patients, but it is doubtful if patients suffer from this symptom. Current literature does not support the standard use of antimuscarinic drugs in the treatment of death rattle.
Topics: Humans; Muscarinic Antagonists; Prevalence; Respiratory Mucosa; Respiratory Sounds; Terminal Care
PubMed: 23790419
DOI: 10.1016/j.jpainsymman.2013.03.011 -
The Cochrane Database of Systematic... Apr 2013Pancreatic resections are associated with high morbidity (30% to 60%) and mortality (5%). Synthetic analogues of somatostatin are advocated by some surgeons to reduce... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Pancreatic resections are associated with high morbidity (30% to 60%) and mortality (5%). Synthetic analogues of somatostatin are advocated by some surgeons to reduce complications following pancreatic surgery; however, their use is controversial.
OBJECTIVES
To determine whether prophylactic somatostatin analogues should be used routinely in pancreatic surgery.
SEARCH METHODS
We searched the Cochrane Upper Gastrointestinal and Pancreatic Diseases Group Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2013, Issue 1), MEDLINE, EMBASE and Science Citation Index Expanded to February 2013.
SELECTION CRITERIA
We included randomised controlled trials comparing prophylactic somatostatin or one of its analogues versus no drug or placebo during pancreatic surgery (irrespective of language or publication status).
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed trials for inclusion and independently extracted data. We analysed data with both the fixed-effect and random-effects models using Review Manager (RevMan). We calculated the risk ratio (RR), mean difference (MD) or standardised mean difference (SMD) with 95% confidence intervals (CI) based on an intention-to-treat or available case analysis. When it was not possible to perform either of the above, we performed a per protocol analysis.
MAIN RESULTS
We identified 21 trials (19 trials of high risk of bias) involving 2348 people. There was no significant difference in the perioperative mortality (RR 0.80; 95% CI 0.56 to 1.16; n = 2210) or the number of people with drug-related adverse effects between the two groups (RR 2.09; 95% CI 0.83 to 5.24; n = 1199). Quality of life was not reported in any of the trials. The overall number of participants with postoperative complications was significantly lower in the somatostatin analogue group (RR 0.70; 95% CI 0.61 to 0.80; n = 1903) but there was no significant difference in the re-operation rate (RR 1.26; 95% CI 0.58 to 2.70; n = 687) or hospital stay (MD -1.29 days; 95% CI -2.60 to 0.03; n = 1314) between the groups. The incidence of pancreatic fistula was lower in the somatostatin analogue group (RR 0.66; 95% CI 0.55 to 0.79; n = 2206). The proportion of these fistulas that were clinically significant was not mentioned in most trials. On inclusion of trials that clearly distinguished clinically significant fistulas, there was no significant difference between the two groups (RR 0.69; 95% CI 0.38 to 1.28; n = 292).
AUTHORS' CONCLUSIONS
Somatostatin analogues may reduce perioperative complications but do not reduce perioperative mortality. Further adequately powered trials with low risk of bias are necessary. Based on the current available evidence, somatostatin and its analogues are recommended for routine use in people undergoing pancreatic resection.
Topics: Gastrointestinal Agents; Humans; Length of Stay; Octreotide; Pancreas; Pancreatectomy; Pancreatic Diseases; Pancreatic Fistula; Pancreaticoduodenectomy; Postoperative Complications; Publication Bias; Randomized Controlled Trials as Topic; Reoperation; Sepsis; Somatostatin
PubMed: 23633353
DOI: 10.1002/14651858.CD008370.pub3 -
The Oncologist 2012For decades, somatostatin analogs (including octreotide and lanreotide) have been indicated for relief of the symptoms of flushing, diarrhea, and wheezing associated... (Review)
Review
BACKGROUND
For decades, somatostatin analogs (including octreotide and lanreotide) have been indicated for relief of the symptoms of flushing, diarrhea, and wheezing associated with secretory neuroendocrine tumors (NETs). Recently, it has been suggested that somatostatin analogs may provide direct and indirect antitumor effects in secretory and nonsecretory NETs in addition to symptom control in secretory NETs.
METHODS
A systematic review of MEDLINE was conducted to identify studies that investigated the antitumor effects of octreotide or lanreotide for patients with NETs. Additional studies not published in the peer-reviewed literature were identified by searching online abstracts. Results. In all, 17 octreotide trials and 11 lanreotide trials that included antitumor effects were identified. Partial response rates were between 0% and 31%, and stable disease rates were between 15% and 89%. Octreotide was the only somatostatin analog for which results of a phase III, randomized, placebo-controlled clinical trial that investigated antitumor effects were published. After 6 months of treatment in this randomized phase III trial, stable disease was observed in 67% of patients (hazard ratio for time to disease progression: 0.34; 95% confidence interval: 0.20-0.59; p = .000072).
CONCLUSIONS
In addition to symptom control for NETs, the data support an antitumor effect of somatostatin analogs and suggest that they may slow tumor growth. Long-acting repeatable octreotide has been shown to have an antitumor effect in a randomized phase III trial in midgut NETs, whereas results are pending in a corresponding controlled trial with lanreotide for patients with intestinal and pancreatic primary NETs.
Topics: Antineoplastic Agents, Hormonal; Clinical Trials, Phase III as Topic; Diarrhea; Flushing; Humans; Neuroendocrine Tumors; Octreotide; Peptides, Cyclic; Randomized Controlled Trials as Topic; Somatostatin
PubMed: 22628056
DOI: 10.1634/theoncologist.2011-0458 -
Medical Science Monitor : International... Aug 2011The role of somatostatin analogues in advanced hepatocellular carcinoma (HCC) remains controversial. The aim of this study was to examine the effect of octreotide on the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The role of somatostatin analogues in advanced hepatocellular carcinoma (HCC) remains controversial. The aim of this study was to examine the effect of octreotide on the survival of patients with advanced HCC.
MATERIAL/METHODS
Electronic databases including Medline, Embase, Cochrane controlled trials register, Web of Science and PubMed (updated to Dec 2010) and manual bibliographical searches were conducted. A meta-analysis of all randomized controlled trials (RCTs) comparing octreotide versus placebo or no treatment was performed.
RESULTS
Eleven RCTs including 802 patients were assessed and 9 were included in the meta-analysis. Meta-analysis showed that the 6-mo and 12-mo survival rates in the octreotide group were significantly higher than those of the control group (6-mo: RR 1.41, 95%CI 1.12-1.77, P=0.003; 12-mo: RR 2.66, 95%CI 1.30-5.44, P=0.008). When including the studies using no treatment as control, with high quality, being performed in China, including >50 patients and with follow-up >2 years, the sensitivity analyses tended to confirm the primary meta-analysis. Whereas, when including the studies using placebo as control or being performed in western countries, the difference was not significant.
CONCLUSIONS
This meta-analysis demonstrates that octreotide could improve the survival of patients with advanced HCC, but possibly not in western countries. The role of detecting SSTR expression in the administration of octreotide in advanced HCC needs further investigation.
Topics: Antineoplastic Agents, Hormonal; Carcinoma, Hepatocellular; Databases, Factual; Humans; Liver Neoplasms; Octreotide; Randomized Controlled Trials as Topic; Sensitivity and Specificity; Somatostatin; Survival Rate
PubMed: 21804474
DOI: 10.12659/msm.881892 -
The Cochrane Database of Systematic... Jul 2010Ovarian cancer is the sixth most common cancer among women and is usually diagnosed at an advanced stage. Bowel obstruction is a common feature of advanced or recurrent... (Review)
Review
BACKGROUND
Ovarian cancer is the sixth most common cancer among women and is usually diagnosed at an advanced stage. Bowel obstruction is a common feature of advanced or recurrent ovarian cancer. Patients with bowel obstruction are generally in poor physical condition with a limited life expectancy. Therefore, maintaining their QoL with effective symptom control is the main purpose of the management of bowel obstruction.
OBJECTIVES
To compare the effectiveness and safety of palliative surgery (surgery performed to control the cancer, reduce symptoms and improve quality of life for those whose cancer is not able to be entirely removed) and medical management for bowel obstruction in women with ovarian cancer.
SEARCH STRATEGY
We searched the Cochrane Gynaecological Cancer Group Trials Register, The Cochrane Central Register of Controlled trials (CENTRAL), Issue 1 2009, MEDLINE and EMBASE up to February 2009. We also searched registers of clinical trials, abstracts of scientific meetings, reference lists of included studies and contacted experts in the field.
SELECTION CRITERIA
Studies that compared palliative surgery and medical interventions, in adult women diagnosed with ovarian cancer who had either full or partial obstruction of the bowel. Randomised controlled trials (RCTs) and non-RCTs that used multivariable statistical adjustment for baseline case mix were eligible.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed whether potentially relevant studies met the inclusion criteria, abstracted data and assessed risk of bias. One non-randomised study was identified so no meta-analyses were performed.
MAIN RESULTS
The search strategy identified 183 unique references of which 22 were identified as being potentially eligible on the basis of title and abstract. Only one study met our inclusion criteria and was included in the review. It analysed retrospective data for 47 women who received either palliative surgery (n = 27) or medical management with Octreotide (n = 20) and reported overall survival and perioperative mortality and morbidity. Women with poor performance status were excluded from surgery. Although six (22%) women who received surgery had serious complications of the operation and three (11%) died of complications, multivariable analysis found that women who received surgery had significantly (p < 0.001) better survival than women who received Octreotide, after adjustment for important prognostic factors. However, the magnitude of this effect was not reported. Quality of life (QoL) was not reported and adverse events were incompletely documented.
AUTHORS' CONCLUSIONS
We found only low quality evidence comparing palliative surgery and medical management for bowel obstruction in ovarian cancer. Therefore we are unable to reach definite conclusions about the relative benefits and harms of the two forms of treatment, or to identify sub-groups of women who are likely to benefit from one treatment or the other. However, there is weak evidence in support of surgical management to prolong survival.
Topics: Adult; Antiemetics; Antineoplastic Agents, Hormonal; Female; Humans; Intestinal Obstruction; Octreotide; Ovarian Neoplasms; Palliative Care
PubMed: 20614464
DOI: 10.1002/14651858.CD007792.pub2 -
Journal of Pain and Symptom Management Apr 2010A systematic review of antiemetics for emesis in cancer unrelated to chemotherapy and radiation is an important step in establishing treatment recommendations and... (Meta-Analysis)
Meta-Analysis Review
CONTEXT
A systematic review of antiemetics for emesis in cancer unrelated to chemotherapy and radiation is an important step in establishing treatment recommendations and guiding future research. Therefore, a systematic review based on the question "What is the evidence that supports antiemetic choices in advanced cancer?" guided this review.
OBJECTIVES
To determine the level of evidence for antiemtrics in the management of nausea and vomiting in advanced cancer unrelated to chemotherapy and radiation, and to discover gaps in the evidence, which would provide important areas for future research.
METHODS
Three databases and independent searches using different MeSH terms were performed. Related links were searched and hand searches of related articles were made. Eligible studies included randomized controlled trials (RCTs), prospective single-drug studies, studies that used guidelines based on the etiology of emesis, cohort studies, retrospective studies, and case series or single-patient reports. Studies that involved treatment of chemotherapy, radiation, or postoperation-related emesis were excluded. Studies that involved the treatment of emesis related to bowel obstruction were included. The strength of evidence was graded as follows: 1) RCTs, A; 2) single-drug prospective studies, B1; 3) studies based on multiple drug choices for etiology of emesis, B2; and 4) cohort, case series, retrospective, and single-patient reports, E. Level of evidence was determined by the Oxford Centre for Evidence-Based Medicine Levels of Evidence (May 2001) (A, B, C, D).
RESULTS
Ninety-three articles were found. Fourteen were RCTs, most of them of low quality, based either on lack of blinding, lack of description of the method of randomization, concealment, and/or attrition. Metoclopramide had modest evidence (B) based on RCTs and prospective cohort studies. Octreotide, dexamethasone, and hyoscine butylbromide are effective in reducing symptoms of bowel obstruction, based on prospective studies and/or one RCT. There was no evidence that either multiple antiemetics or antiemetic choices based on the etiology of emesis were any better than a single antiemetic. There is poor evidence for dose response, intraclass or interclass drug switch, or antiemetic combinations in those individuals failing to respond to the initial antiemetic.
CONCLUSION
There are discrepancies between antiemetic studies and published antiemetic guidelines, which are largely based on expert opinion. Antiemetic recommendations have moderate to weak evidence at best. Prospective randomized trials of single antiemetics are needed to properly establish evidence-based guidelines.
Topics: Comorbidity; Drug Therapy; Humans; Nausea; Neoplasms; Practice Patterns, Physicians'; Prevalence; Radiation Injuries; Vomiting
PubMed: 20413062
DOI: 10.1016/j.jpainsymman.2009.08.010 -
The Cochrane Database of Systematic... Mar 2010Emergency sclerotherapy is still widely used as a first line therapy for variceal bleeding in patients with cirrhosis, particularly when banding ligation is not... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Emergency sclerotherapy is still widely used as a first line therapy for variceal bleeding in patients with cirrhosis, particularly when banding ligation is not available or feasible. However, pharmacological treatment may stop bleeding in the majority of these patients.
OBJECTIVES
To assess the benefits and harms of emergency sclerotherapy versus vasoactive drugs for variceal bleeding in cirrhosis.
SEARCH STRATEGY
Search of trials was based on The Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, and Science Citation Index Expanded through January 2010.
SELECTION CRITERIA
Randomised clinical trials comparing sclerotherapy with vasoactive drugs (vasopressin (with or without nitroglycerin), terlipressin, somatostatin, or octreotide) for acute variceal bleeding in cirrhotic patients.
DATA COLLECTION AND ANALYSIS
Outcome measures were failure to control bleeding, five-day treatment failure, rebleeding, mortality, number of blood transfusions, and adverse events. Data were analysed by a random-effects model according to the vasoactive treatment. Sensitivity analyses included combined analysis of all the trials irrespective of the vasoactive drug, type of publication, and risk of bias.
MAIN RESULTS
Seventeen trials including 1817 patients were identified. Vasoactive drugs were vasopressin (one trial), terlipressin (one trial), somatostatin (five trials), and octreotide (ten trials). No significant differences were found comparing sclerotherapy with each vasoactive drug for any outcome. Combining all the trials irrespective of the vasoactive drug, the risk differences (95% confidence intervals) were failure to control bleeding -0.02 (-0.06 to 0.02), five-day failure rate -0.05 (-0.10 to 0.01), rebleeding 0.01 (-0.03 to 0.05), mortality (17 randomised trials, 1817 patients) -0.02 (-0.06 to 0.02), and transfused blood units (8 randomised trials, 849 patients) (weighted mean difference) -0.24 (-0.54 to 0.07). Adverse events 0.08 (0.03 to 0.14) and serious adverse events 0.05 (0.02 to 0.08) were significantly more frequent with sclerotherapy.
AUTHORS' CONCLUSIONS
We found no convincing evidence to support the use of emergency sclerotherapy for variceal bleeding in cirrhosis as the first, single treatment when compared with vasoactive drugs. Vasoactive drugs may be safe and effective whenever endoscopic therapy is not promptly available and seems to be associated with less adverse events than emergency sclerotherapy. Other meta-analyses and guidelines advocate that combined vasoactive drugs and endoscopic therapy is superior to either intervention alone.
Topics: Emergencies; Esophageal and Gastric Varices; Gastrointestinal Hemorrhage; Hemostatics; Humans; Liver Cirrhosis; Lypressin; Octreotide; Sclerotherapy; Somatostatin; Terlipressin; Treatment Outcome; Vasoconstrictor Agents; Vasopressins
PubMed: 20238318
DOI: 10.1002/14651858.CD002233.pub2