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The Cochrane Database of Systematic... Sep 2019Hepatorenal syndrome is defined as renal failure in people with cirrhosis in the absence of other causes. In addition to supportive treatment such as albumin to restore...
BACKGROUND
Hepatorenal syndrome is defined as renal failure in people with cirrhosis in the absence of other causes. In addition to supportive treatment such as albumin to restore fluid balance, the other potential treatments include systemic vasoconstrictor drugs (such as vasopressin analogues or noradrenaline), renal vasodilator drugs (such as dopamine), transjugular intrahepatic portosystemic shunt (TIPS), and liver support with molecular adsorbent recirculating system (MARS). There is uncertainty over the best treatment regimen for hepatorenal syndrome.
OBJECTIVES
To compare the benefits and harms of different treatments for hepatorenal syndrome in people with decompensated liver cirrhosis.
SEARCH METHODS
We searched CENTRAL, MEDLINE, Embase, Science Citation Index Expanded, World Health Organization International Clinical Trials Registry Platform, and trial registers until December 2018 to identify randomised clinical trials on hepatorenal syndrome in people with cirrhosis.
SELECTION CRITERIA
We included only randomised clinical trials (irrespective of language, blinding, or publication status) in adults with cirrhosis and hepatorenal syndrome. We excluded randomised clinical trials in which participants had previously undergone liver transplantation.
DATA COLLECTION AND ANALYSIS
Two authors independently identified eligible trials and collected data. The outcomes for this review included mortality, serious adverse events, any adverse events, resolution of hepatorenal syndrome, liver transplantation, and other decompensation events. We performed a network meta-analysis with OpenBUGS using Bayesian methods and calculated the odds ratio (OR), rate ratio, hazard ratio (HR), and mean difference (MD) with 95% credible intervals (CrI) based on an available-case analysis, according to National Institute of Health and Care Excellence Decision Support Unit guidance.
MAIN RESULTS
We included a total of 25 trials (1263 participants; 12 interventions) in the review. Twenty-three trials (1185 participants) were included in one or more outcomes. All the trials were at high risk of bias, and all the evidence was of low or very low certainty. The trials included participants with liver cirrhosis of varied aetiologies as well as a mixture of type I hepatorenal syndrome only, type II hepatorenal syndrome only, or people with both type I and type II hepatorenal syndrome. Participant age ranged from 42 to 60 years, and the proportion of females ranged from 5.8% to 61.5% in the trials that reported this information. The follow-up in the trials ranged from one week to six months. Overall, 59% of participants died during this period and about 35% of participants recovered from hepatorenal syndrome. The most common interventions compared were albumin plus terlipressin, albumin plus noradrenaline, and albumin alone.There was no evidence of a difference in mortality (22 trials; 1153 participants) at maximal follow-up between the different interventions. None of the trials reported health-related quality of life. There was no evidence of differences in the proportion of people with serious adverse events (three trials; 428 participants), number of participants with serious adverse events per participant (two trials; 166 participants), proportion of participants with any adverse events (four trials; 402 participants), the proportion of people who underwent liver transplantation at maximal follow-up (four trials; 342 participants), or other features of decompensation at maximal follow-up (one trial; 466 participants). Five trials (293 participants) reported number of any adverse events, and five trials (219 participants) reported treatment costs. Albumin plus noradrenaline had fewer numbers of adverse events per participant (rate ratio 0.51, 95% CrI 0.28 to 0.87). Eighteen trials (1047 participants) reported recovery from hepatorenal syndrome (as per definition of hepatorenal syndrome). In terms of recovery from hepatorenal syndrome, in the direct comparisons, albumin plus midodrine plus octreotide and albumin plus octreotide had lower recovery from hepatorenal syndrome than albumin plus terlipressin (HR 0.04; 95% CrI 0.00 to 0.25 and HR 0.26, 95% CrI 0.07 to 0.80 respectively). There was no evidence of differences between the groups in any of the other direct comparisons. In the network meta-analysis, albumin and albumin plus midodrine plus octreotide had lower recovery from hepatorenal syndrome compared with albumin plus terlipressin.
FUNDING
two trials were funded by pharmaceutical companies; five trials were funded by parties who had no vested interest in the results of the trial; and 18 trials did not report the source of funding.
AUTHORS' CONCLUSIONS
Based on very low-certainty evidence, there is no evidence of benefit or harm of any of the interventions for hepatorenal syndrome with regards to the following outcomes: all-cause mortality, serious adverse events (proportion), number of serious adverse events per participant, any adverse events (proportion), liver transplantation, or other decompensation events. Low-certainty evidence suggests that albumin plus noradrenaline had fewer 'any adverse events per participant' than albumin plus terlipressin. Low- or very low-certainty evidence also found that albumin plus midodrine plus octreotide and albumin alone had lower recovery from hepatorenal syndrome compared with albumin plus terlipressin.Future randomised clinical trials should be adequately powered; employ blinding, avoid post-randomisation dropouts or planned cross-overs (or perform an intention-to-treat analysis); and report clinically important outcomes such as mortality, health-related quality of life, adverse events, and recovery from hepatorenal syndrome. Albumin plus noradrenaline and albumin plus terlipressin appear to be the interventions that should be compared in future trials.
Topics: Adult; Bayes Theorem; Female; Hepatorenal Syndrome; Humans; Liver Cirrhosis; Liver Transplantation; Male; Middle Aged; Network Meta-Analysis; Quality of Life; Randomized Controlled Trials as Topic; Vasoconstrictor Agents
PubMed: 31513287
DOI: 10.1002/14651858.CD013103.pub2 -
World Journal of Hepatology Feb 2016To describe the pathophysiology, clinical presentation, natural history, and therapy of portal hypertensive gastropathy (PHG) based on a systematic literature review.
AIM
To describe the pathophysiology, clinical presentation, natural history, and therapy of portal hypertensive gastropathy (PHG) based on a systematic literature review.
METHODS
Computerized search of the literature was performed via PubMed using the following medical subject headings or keywords: "portal" and "gastropathy"; or "portal" and "hypertensive"; or "congestive" and "gastropathy"; or "congestive" and "gastroenteropathy". The following criteria were applied for study inclusion: Publication in peer-reviewed journals, and publication since 1980. Articles were independently evaluated by each author and selected for inclusion by consensus after discussion based on the following criteria: Well-designed, prospective trials; recent studies; large study populations; and study emphasis on PHG.
RESULTS
PHG is diagnosed by characteristic endoscopic findings of small polygonal areas of variable erythema surrounded by a pale, reticular border in a mosaic pattern in the gastric fundus/body in a patient with cirrhotic or non-cirrhotic portal hypertension. Histologic findings include capillary and venule dilatation, congestion, and tortuosity, without vascular fibrin thrombi or inflammatory cells in gastric submucosa. PHG is differentiated from gastric antral vascular ectasia by a different endoscopic appearance. The etiology of PHG is inadequately understood. Portal hypertension is necessary but insufficient to develop PHG because many patients have portal hypertension without PHG. PHG increases in frequency with more severe portal hypertension, advanced liver disease, longer liver disease duration, presence of esophageal varices, and endoscopic variceal obliteration. PHG pathogenesis is related to a hyperdynamic circulation, induced by portal hypertension, characterized by increased intrahepatic resistance to flow, increased splanchnic flow, increased total gastric flow, and most likely decreased gastric mucosal flow. Gastric mucosa in PHG shows increased susceptibility to gastrotoxic chemicals and poor wound healing. Nitrous oxide, free radicals, tumor necrosis factor-alpha, and glucagon may contribute to PHG development. Acute and chronic gastrointestinal bleeding are the only clinical complications. Bleeding is typically mild-to-moderate. Endoscopic therapy is rarely useful because the bleeding is typically diffuse. Acute bleeding is primarily treated with octreotide, often with concomitant proton pump inhibitor therapy, or secondarily treated with vasopressin or terlipressin. Nonselective β-adrenergic receptor antagonists, particularly propranolol, are used to prevent bleeding after an acute episode or for chronic bleeding. Iron deficiency anemia from chronic bleeding may require iron replacement therapy. Transjugular-intrahepatic-portosystemic-shunt and liver transplantation are highly successful ultimate therapies because they reduce the underlying portal hypertension.
CONCLUSION
PHG is important to recognize in patients with cirrhotic or non-cirrhotic portal hypertension because it can cause acute or chronic GI bleeding that often requires pharmacologic therapy.
PubMed: 26855694
DOI: 10.4254/wjh.v8.i4.231 -
World Journal of Surgical Oncology May 2015Tumor-induced osteomalacia (TIO) is a rare disorder, which is commonly found in craniofacial locations and in the extremities. To the best of our knowledge, only 16... (Review)
Review
BACKGROUND
Tumor-induced osteomalacia (TIO) is a rare disorder, which is commonly found in craniofacial locations and in the extremities. To the best of our knowledge, only 16 cases have been described in the spine, and this is the first report to describe a case of patient with TIO in the thoracic spine combined with a mesenchymal hamartoma which had confused the therapeutic strategies to date.
CASE DESCRIPTION
We report the case of a 60-year-old patient with hypophosphatemia and presented with limb weakness. Treating with phosphate did not correct the hypophosphatemia and an (111)In pentetreotide scintigraphy (octreotide scan) revealed an increased uptake at the right forearm. The tumor was resected totally, and the histopathology revealed a mesenchymal hamartoma, but we noticed that hypophosphatemia was not corrected after the tumor resection. Then a whole-body magnetic resonance imaging (WB-MRI) was performed and the results revealed tumorous tissues at the right T1 vertebral pedicle. The tumor was removed with an en bloc method, and the pathology showed phosphaturic mesenchymal tumor. Follow-up at 1 year after surgery revealed no recurrence, and the serum phosphorus level of the patient was normal.
CONCLUSIONS
Tumor-induced osteomalacia is exceedingly rare with only 16 cases in spine published in the literature. It is difficult to find and leads to years of suffering debilitating complications. In this regard, the WB-MRI is a better method to locate the real tumor. Treating with phosphate can only relieve symptoms, and a complete surgical removal remains the gold standard treatment.
Topics: Humans; Hypophosphatemia; Indium Radioisotopes; Magnetic Resonance Imaging; Male; Mesenchymoma; Middle Aged; Octreotide; Osteomalacia; Positron-Emission Tomography; Spinal Neoplasms
PubMed: 25951872
DOI: 10.1186/s12957-015-0589-3 -
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 -
Endocrine Mar 2023A systematic literature review was conducted to assess the use of home injections (self/partner/healthcare provider [HCP]-administered) of somatostatin analogs (SSAs) as...
PURPOSE
A systematic literature review was conducted to assess the use of home injections (self/partner/healthcare provider [HCP]-administered) of somatostatin analogs (SSAs) as an alternative to healthcare-setting injections in patients with acromegaly and neuroendocrine tumors (NETs).
METHODS
MEDLINE/Embase/the Cochrane Library (2001-September 2021), key congresses (2019-2021), and bibliographies of relevant systematic reviews were searched. Eligible studies reported on efficacy/effectiveness, safety, adherence, patient-reported outcomes (PROs), and economic outcomes in populations receiving home injections of SSAs.
RESULTS
Overall, 12 studies were included, all reporting on SSAs (lanreotide Autogel/Depot or octreotide long-acting release) in acromegaly or NETs. Across four studies, home injection was associated with similar disease control in patients with acromegaly/NETs compared with healthcare-setting administration. High rates of treatment adherence were shown in two studies of patients with acromegaly receiving lanreotide injections at home. Two studies reported non-serious adverse events; incidence of adverse reactions was similar in both the home and healthcare administration settings. Preference for injection setting varied between studies and indications; nonetheless, higher satisfaction/convenience (>75% patients) was reported for home injections. Self- or partner-injection was associated with economic savings compared with administration in the healthcare setting across five studies.
CONCLUSION
Efficacy/effectiveness, adherence, and safety outcomes of SSAs in the home injection setting were similar to those in the healthcare setting, with high reported satisfaction and convenience. Self/partner injection also resulted in cost savings. These findings provide a basis to understand outcomes related to home injection and encourage healthcare providers to discuss optimal treatment choices with their patients.
Topics: Humans; Somatostatin; Acromegaly; Peptides, Cyclic; Octreotide; Injections, Subcutaneous; Neuroendocrine Tumors
PubMed: 36369434
DOI: 10.1007/s12020-022-03227-0 -
Quantitative Imaging in Medicine and... Oct 2023The imaging of somatostatin receptors (SSTRs) plays a significant role in imaging neuroendocrine tumors (NETs). However, there has been no clear definition on whether it...
BACKGROUND
The imaging of somatostatin receptors (SSTRs) plays a significant role in imaging neuroendocrine tumors (NETs). However, there has been no clear definition on whether it is necessary to withdraw somatostatin analogs (SSAs) before SSTRs imaging. We aimed to assess whether nonradioactive SSAs affect the uptake of radiolabeled SSAs on imaging for NETs patients.
METHODS
The databases of PubMed, Embase, and Web of Science (WoS) were searched until March 12, 2022 to identify eligible studies. Maximum standardized uptake values (SUVmax) in tumor and normal tissues were extracted, pooled, and compared before and after SSAs treatment. The change of tumor-to-background/liver ratio was also described. The quality of each study was assessed using the revised Quality Assessment of Diagnostic Accuracy Studies-2 tool.
RESULTS
A total of 9 articles involving 285 patients were included and 5 studies using Gallium-68-labeled [1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid]-D-Phe-Tyr-Thr-octreotide (Ga-DOTATATE) were used for pooled evaluation. We found a significantly decreased SUVmax in the liver (9.56±2.47 7.62±2.12, P=0.001) and spleen (25.74±7.14 20.39±6.07, P=0.006) after SSAs treatment whereas no significant differences were observed in the uptake of thyroid, adrenal, and pituitary gland. For either primary tumor sites or metastases, the SUVmax did not change significantly before and after SSAs treatment. The tumor-to-liver/background ratio increased following SSAs therapy. High heterogeneity was observed across the studies, mainly due to inherent diversity of study design, sample size, and scanning technique.
CONCLUSIONS
Based on current evidence, long-acting SSAs therapy before imaging has no effect on the uptake of radiolabeled SSAs at tumor primary sites and metastatic lesions, but results in a significant reduction of uptake in the liver and spleen. These findings may implicate the unnecessary discontinuation of SSAs before radiolabeled SSAs imaging.
PubMed: 37869289
DOI: 10.21037/qims-23-477 -
Clinical Nuclear Medicine Jun 2023The interactions between the administration of cold somatostatin analogs (cSAs) and their radiolabeled counterpart remain unclear, and discontinuation before imaging is...
PURPOSE
The interactions between the administration of cold somatostatin analogs (cSAs) and their radiolabeled counterpart remain unclear, and discontinuation before imaging is still advised as a precaution. The aim of this systematic review is to evaluate the consequences of cSA administration on tumoral and surrounding healthy organs' uptake at somatostatin receptor (SSTR) imaging with SPECT or PET.
METHODS
After registration of the study on Prospero (CRD42022360260), an electronic search of PubMed and Scopus databases was performed. Inclusion criteria were as follows: human patients referred for SSTR imaging for oncological purposes; at least 1 examination performed either before cSA administration or after a long-enough withdrawal of cSA treatment; at least 1 examination was performed under cSA treatment. Included articles were independently appraised by 2 authors using the standardized protocol provided by the Quality Assessment of Diagnostic Accuracy Studies. Discrepancies were solved by consensus.
RESULTS
A total of 12 articles were included, 4 using 111In-pentetreotide and 8 using 68Ga-DOTA peptides. Administration of cSAs consistently resulted in decreased spleen and liver uptake (from 6.9% to 80% for spleen, 10% to 60% for liver) and increased tumor-to-background or tumor-to-healthy organ ratios. After cSA treatment, tumor uptake alone was unchanged or moderately decreased. Similar results were noted whether patient was octreotide-naive.
CONCLUSION
Impairment in SSTR imaging quality after cSA administration has not been demonstrated. On the contrary, the administration of cSAs seems to improve the contrast between tumoral lesions and the surroundings.
Topics: Humans; Receptors, Somatostatin; Somatostatin; Octreotide; Tomography, Emission-Computed, Single-Photon; Neoplasms; Neuroendocrine Tumors
PubMed: 37133509
DOI: 10.1097/RLU.0000000000004670 -
Medicine Nov 2018Acute variceal bleeding (AVB) is life-threatening. We aimed to systematically review the current evidence regarding the efficacy and safety of terlipressin for AVB in... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND AIM
Acute variceal bleeding (AVB) is life-threatening. We aimed to systematically review the current evidence regarding the efficacy and safety of terlipressin for AVB in liver cirrhosis.
METHODS
We searched the PubMed, EMBASE, and Cochrane Library databases. The reference list was also hand-searched. Using a random-effect model, we combined the data obtained according to the different time points when the events developed. Odds ratio (OR) and weighted mean difference (WMD) were calculated. Quality of evidence was evaluated by the GRADE methodology.
RESULTS
Thirty randomized controlled trials with 3344 patients were included. Compared with no vasoactive drug, terlipressin significantly improved the control of bleeding within 48 hours (OR = 2.94, P = .0008) and decreased the in-hospital mortality (OR = 0.31, P = .008). Compared with somatostatin, terlipressin had a significantly higher risk of complications (OR = 2.44, P = .04). Compared with octreotide, terlipressin had a significantly inferior control of bleeding within 24 hours (OR = 0.37, P = .007). Compared with vasopressin, terlipressin had a significantly lower risk of complications (OR = 0.15, P = .02). Compared with terlipressin combined with endoscopic variceal ligation, terlipressin alone had significantly higher 5-day treatment failure (OR = 14.46, P = .01) and transfusion requirements within 49 to 120 hours (WMD = 1.20, P = .002). No outcome was significantly different between terlipressin and sclerotherapy. Compared with balloon tamponade, terlipressin significantly decreased the 30-day rebleeding (OR = 0.05, P = .001) and transfusion requirements (WMD = -2.70, P = .02). Quality of evidence was very low to moderate.
CONCLUSION
Our findings were in accordance with the current recommendations regarding terlipressin for the treatment of AVB in cirrhosis. However, due to low quality of evidence, further studies are recommended.
Topics: Esophageal and Gastric Varices; Gastrointestinal Hemorrhage; Humans; Liver Cirrhosis; Randomized Controlled Trials as Topic; Sclerotherapy; Terlipressin; Vasoconstrictor Agents
PubMed: 30508958
DOI: 10.1097/MD.0000000000013437