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Frontiers in Pharmacology 2022Malignant ascites (MA) is a common complication of terminal cancer, which seriously affects the life quality and prognosis of patients. Both hyperthermic...
Malignant ascites (MA) is a common complication of terminal cancer, which seriously affects the life quality and prognosis of patients. Both hyperthermic intraperitoneal chemotherapy (HIPEC) and traditional Chinese medicine (TCM) preparations have achieved significant efficacy in the treatment of MA. The treatment strategy of TCM combined with HIPEC has been gradually promoted and applied in China. The purpose of this systematic review and meta-analysis was to assess the efficacy of TCM combined with HIPEC in the treatment of MA. Randomized controlled trials (RCTs) of TCM combined with HIPEC for MA were searched from seven electronic databases. Two researchers used the Cochrane Collaboration's tool to assess the risk of bias. Excel 2019 was used to establish a database for information extraction, RevMan 5.4 software was used to analyze the included test data, and STATA v16.0 was used to conduct Egger's test to further detect publication bias. A total of 19 studies involving 1,504 patients were included in this meta-analysis. The results showed that compared with the single use of HIPEC, TCM combined with HIPEC could significantly improve the clinical efficacy (RR = 1.51, 95% CI [1.40, 1.63], < 0.00001) and karnofsky performance status (KPS) score (MD = 8.16, 95% CI [6.46, 9.85], < 0.00001), reduce the ascites volume (MD = -156.98, 95% CI [-213.71, -100.25], < 0.00001). However, there was no statistical significance in reducing abdominal circumference between TCM combined with HIPEC and HIPEC alone (MD = -1.8, 95% CI [-4.57, -0.97], = 0.2). This study found that TCM combined with HIPEC had a beneficial therapeutic effect on MA. However, more standard, double-blind, multicenter RCTs are needed to further confirm the efficacy of TCM combined with HIPEC in the treatment of MA. https://www.crd.york.ac.uk/, identifier CRD42022319993.
PubMed: 36105234
DOI: 10.3389/fphar.2022.938472 -
Cureus Jul 2022Ascites is the most common complication of liver cirrhosis. Midodrine is a vasoconstrictor that improves splanchnic and systemic hemodynamics, reduces ascites, and... (Review)
Review
Ascites is the most common complication of liver cirrhosis. Midodrine is a vasoconstrictor that improves splanchnic and systemic hemodynamics, reduces ascites, and improves clinical outcomes. Here, we aimed to examine the role of midodrine in cirrhosis-related ascites. Scopus, Embase, PubMed, and PubMed Central databases were searched for relevant randomized controlled trials comparing midodrine with other interventions in patients with cirrhotic ascites on November 25, 2020, using appropriate keywords like "midodrine", "ascitic cirrhosis", "peritoneal paracentesis" and suitable Boolean operators. Odds ratio (OR) and mean difference (MD) were used to analyze pool data as appropriate with a 95% confident interval (CI). A total of 14 studies were included in our analysis including 1199 patients. The addition of midodrine resulted in statistically significant improvement in mean arterial pressure (MAP) (MD, 3.95 mmHg; 95% CI, 1.53-6.36) and MELD (Model for End-Stage Liver Disease) score (MD, -1.27; 95% CI, -2.49 to -0.04) compared to standard medical treatment (SMT). There was also a significant improvement in plasma renin activity and plasma aldosterone concentration. However, there was no significant improvement in mortality or serum creatinine compared to SMT. In addition, there was no statistically significant improvement in MAP, plasma renin activity, plasma aldosterone concentration, MELD score, overall mortality, and paracentesis-induced circulatory dysfunction comparing midodrine with albumin. Midodrine alone leads to significant improvement in various clinical parameters in patients with cirrhotic ascites compared to standard medical care. At the same time, it was found to be non-inferior to albumin. Therefore, further well-designed studies need to be carried out on midodrine in addition to albumin for optimal clinical benefits among patients with ascites due to cirrhosis.
PubMed: 36060403
DOI: 10.7759/cureus.27483 -
World Journal of Hepatology Jun 2022Spontaneous bacterial empyema (SBE) occurs when a hepatic hydrothorax becomes infected and runs a course similar to spontaneous bacterial peritonitis (SBP). It remains...
BACKGROUND
Spontaneous bacterial empyema (SBE) occurs when a hepatic hydrothorax becomes infected and runs a course similar to spontaneous bacterial peritonitis (SBP). It remains underdiagnosed as patients with cirrhosis do not routinely undergo diagnostic thoracentesis. Current understanding is limited by small cohorts, while studies reporting its association with ascites/SBP are conflicting.
AIM
To explore the incidence of SBE, to determine its association with ascites, and to summarize what is known regarding treatment and outcomes for patients with SBE.
METHODS
Major databases were searched until June 2021. Outcomes include the incidence of SBE in pleural effusions, SBP in peritoneal fluid, and SBE in patients without ascites within our cohort of patients with cirrhosis. We performed a meta-analysis using a random-effects model with pooled proportions and 95% confidence intervals (CI). We assessed heterogeneity using and classic fail-safe to determine bias.
RESULTS
Eight studies with 8899 cirrhosis patients were included. The median age ranged between 41.2 to 69.7 years. The majority of the patients were Child-Pugh B and C. Mean MELD score was 18.6 ± 8.09. A total of 1334 patients had pleural effusions and the pooled incidence of SBE was 15.6% (CI 12.6-19; 50). Amongst patients diagnosed with SBE, the most common locations included right (202), left (64), and bilateral (8). Amongst our cohort, a total of 2636 patients had ascites with a pooled incidence of SBP of 22.2% (CI 9.9-42.7; 97.8). The pooled incidence of SBE in patients with cirrhosis but without concomitant ascites was 9.5% (CI 3.6-22.8; 82.5).
CONCLUSION
SBE frequently occurs with concurrent ascites/SBP; our results suggest high incidence rates of SBE even in the absence of ascites. The pleura can be an unrecognized nidus and our findings support the use of diagnostic thoracentesis in patients with decompensated cirrhosis after exclusion of other causes of pleural effusion. Thoracentesis should be considered particularly in patients without ascites and when there is a high suspicion of infection. The need for diagnostic thoracentesis will continue to be important as rates of multi-drug resistant bacterial infections increase and antibiotic susceptibility information is required for adequate treatment.
PubMed: 35978675
DOI: 10.4254/wjh.v14.i6.1258 -
Cureus Jun 2022The presence of ascites is a common clinical presentation in gynecologic oncology patients. Hemorrhagic ascites (HA) due to endometriosis is a rare presentation that can... (Review)
Review
The presence of ascites is a common clinical presentation in gynecologic oncology patients. Hemorrhagic ascites (HA) due to endometriosis is a rare presentation that can be easily misdiagnosed as ovarian malignancies. The present study aims to update the currently available knowledge on the characteristics of patients presenting with HA due to endometriosis. A systematic search was conducted for articles published from January 2000 to July 2020 using the Medline, Scopus, and Google Scholar databases along with the references of the full-text articles retrieved. Papers describing cases of women over 18 years with or without previous history of endometriosis were assessed. Only cases with histologically proven hemorrhagic ascites of endometriosis origin were included. Twenty-nine studies (27 case reports and two case series) comprising 32 patients were evaluated. The mean patients' age was 32 years, while six of the patients had a previous history of endometriosis. The mean amount of drained ascitic fluid was 4,200 mL, whereas three patients underwent thoracentesis due to pleural effusions. The treatment options included not only medical but also surgical therapies. Fertility preservation was achieved in 27 patients, while two of them achieved pregnancy with in vitro fertilization (IVF) techniques. Endometriosis-related hemorrhagic ascites is a relatively rare expression of the disease. Endometriosis-related hemorrhagic ascites should be considered in the differential diagnosis (DD) of women with ascites and clinical suspicion of endometriosis. The available literature is limited to case reports and case series and thus indicates further research in the field to decode the pathophysiology of the disease and decide on the optimal treatment.
PubMed: 35911338
DOI: 10.7759/cureus.26222 -
Translational Gastroenterology and... 2022Radiofrequency ablation (RFA) has been used to treat various abdominal tumors including pancreatic tumors. Multiple approaches such as laparoscopic, open, and...
BACKGROUND
Radiofrequency ablation (RFA) has been used to treat various abdominal tumors including pancreatic tumors. Multiple approaches such as laparoscopic, open, and percutaneous have been used for pancreatic tissue ablation. More recently, endoscopic ultrasound (EUS)-guided RFA has emerged as a new technique for pancreatic tissue ablation. The role of EUS-RFA in management of pancreatic lesions is still not well-established. In this study, our aim is to assess efficacy and safety of EUS-RFA for management of pancreatic lesions.
METHODS
MEDLINE, Scopus, and Cochrane Library databases were searched to identify studies reporting EUS-RFA of pancreatic lesions with outcomes of interest. Studies with <5 patients were excluded. Clinical success was defined as symptom resolution, decrease in tumor size, and/or evidence of necrosis on radiologic imaging. Efficacy was assessed by the pooled clinical response rate whereas safety was assessed by the pooled adverse events rate. Heterogeneity was assessed using I. Pooled estimates and the 95% CI were calculated using random-effect model.
RESULTS
Ten studies (5 retrospective and 5 prospective) involving 115 patients with 125 pancreatic lesions were included. 152 EUS-RFA procedures were performed. The lesions comprised of 37.6% non-functional neuroendocrine tumors (NFNETs), 15.4% were insulinomas, 26.5% were pancreatic cystic neoplasms (PCNs), and 19.7% were pancreatic adenocarcinomas. The majority were present in the pancreatic head (40.2%), 38.3% in the body, 11.2% in the tail, and 10.3% in the uncinate process. Pooled overall clinical response rate was 88.9% (95% CI: 82.4-93.7, I=38.1%). Pooled overall adverse events rate was 6.7% (95% CI: 3.4-11.7, I=34.0%). The most common complication was acute pancreatitis (3.3%) followed by pancreatic duct stenosis, peripancreatic fluid collection, and ascites (2.8%) each. Only one case of perforation was reported with pooled rate of (2.1%).
DISCUSSION
This study demonstrates that EUS-RFA is an effective treatment modality for pancreatic lesions, especially functional neuroendocrine tumors such as insulinomas.
PubMed: 35892058
DOI: 10.21037/tgh-20-84 -
Gastroenterology Oct 2022Magnetic resonance elastography (MRE) is an accurate biomarker of liver fibrosis; however, limited data characterize its association with clinical outcomes. We conducted... (Meta-Analysis)
Meta-Analysis
Liver Stiffness on Magnetic Resonance Elastography and the MEFIB Index and Liver-Related Outcomes in Nonalcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis of Individual Participants.
BACKGROUND & AIMS
Magnetic resonance elastography (MRE) is an accurate biomarker of liver fibrosis; however, limited data characterize its association with clinical outcomes. We conducted an individual participant data pooled meta-analysis on patients with nonalcoholic fatty liver disease to evaluate the association between liver stiffness on MRE and liver-related outcomes.
METHODS
A systematic search identified 6 cohorts of adults with nonalcoholic fatty liver disease who underwent a baseline MRE and were followed for hepatic decompensation, hepatocellular carcinoma, and death. Cox and logistic regression were used to assess the association between liver stiffness on MRE and liver-related outcomes, including a composite primary outcome defined as varices needing treatment, ascites, and hepatic encephalopathy.
RESULTS
This individual participant data pooled meta-analysis included 2018 patients (53% women) with a mean (± standard deviation) age of 57.8 (±14) years and MRE at baseline of 4.15 (±2.19) kPa, respectively. Among 1707 patients with available longitudinal data with a median (interquartile range) of 3 (4.2) years of follow-up, the hazard ratio for the primary outcome for MRE of 5 to 8 kPa was 11.0 (95% confidence interval [CI]: 7.03-17.1, P < .001) and for ≥ 8 kPa was 15.9 (95% CI: 9.32-27.2, P < .001), compared with those with MRE <5 kPa. The MEFIB index (defined as positive when MRE ≥3.3 kPa and Fibrosis-4 ≥1.6) had a robust association with the primary outcome with a hazard ratio of 20.6 (95% CI: 10.4-40.8, P < .001) and a negative MEFIB had a high negative predictive value for the primary outcome, 99.1% at 5 years. The 3-year risk of incident hepatocellular carcinoma was 0.35% for MRE <5 kPa, 5.25% for 5 to 8 kPa, and 5.66% for MRE ≥8 kPa, respectively.
CONCLUSION
Liver stiffness assessed by MRE is associated with liver-related events, and the combination of MRE and Fibrosis-4 has excellent negative predictive value for hepatic decompensation. These data have important implications for clinical practice.
Topics: Adult; Aged; Biomarkers; Carcinoma, Hepatocellular; Elasticity Imaging Techniques; Female; Fibrosis; Humans; Liver; Liver Cirrhosis; Liver Neoplasms; Magnetic Resonance Imaging; Male; Middle Aged; Non-alcoholic Fatty Liver Disease
PubMed: 35788349
DOI: 10.1053/j.gastro.2022.06.073 -
Journal of Gynecologic Oncology Jul 2022Advances in ovarian cancer cytoreductive surgery have enabled more extensive procedures to achieve maximal cytoreduction but with a consequent increase in postoperative... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Advances in ovarian cancer cytoreductive surgery have enabled more extensive procedures to achieve maximal cytoreduction but with a consequent increase in postoperative morbidity and mortality. The aim of this study was to evaluate factors for postoperative morbidity after extensive cytoreductive surgery for primary epithelial ovarian cancer (EOC), particularly those which may be modifiable.
METHODS
Electronic databases were searched. Meta-analysis was conducted using random-effects models.
RESULTS
Fifteen relevant studies, involving 15,325 ovarian cancer patients, were included in this review. Severe 30-day postoperative complications occurred in 2,357 (15.4%) patients. The postoperative mortality rate was 1.92%. Meta-analysis demonstrated that patient with following risk factors; age (p<0.001), Eastern Cooperative Oncology Group score >0 (p=0.001), albumin level <3.5 g/dL (p<0.001), presence of ascites on CT scan (p=0.013), stage IV disease (p<0.001) and extensive surgical procedure (p<0.001) has a significantly increase risk of developing postoperative complications. Surgical procedures including peritonectomy (p=0.012), splenectomy (p<0.001) and colon surgery (p<0.001) were significant predictors for postoperative complications. Moreover, we found that patients who received neoadjuvant chemotherapy followed by interval debulking surgery (NACT-IDS) had a lower risk of developing severe complications compared to those who underwent primary debulking surgery (PDS) (p<0.001).
CONCLUSION
Our study demonstrated that patient performance status and hypoalbuminemia were the only significant adjustable preoperative risk factors associated with postoperative complications. Patients who underwent NACT-IDS had a lower risk of developing severe complications compared to PDS.
TRIAL REGISTRATION
International Prospective Register of Systematic Reviews (PROSPERO) Identifier: CRD42021282770.
Topics: Carcinoma, Ovarian Epithelial; Chemotherapy, Adjuvant; Cytoreduction Surgical Procedures; Female; Humans; Morbidity; Neoadjuvant Therapy; Neoplasm Staging; Ovarian Neoplasms; Postoperative Complications; Retrospective Studies
PubMed: 35712967
DOI: 10.3802/jgo.2022.33.e53 -
Journal of Hepatology Oct 2022Whether non-selective β-blockers can prevent decompensation of cirrhosis warrants clarification. Carvedilol might be particularly effective since its intrinsic... (Meta-Analysis)
Meta-Analysis
BACKGROUND & AIMS
Whether non-selective β-blockers can prevent decompensation of cirrhosis warrants clarification. Carvedilol might be particularly effective since its intrinsic vasodilatory activity may ameliorate hepatic vascular resistance, a major mechanism of portal hypertension in early cirrhosis. We assessed whether carvedilol may prevent decompensation and improve survival in patients with compensated cirrhosis and clinically significant portal hypertension (CSPH).
METHODS
By systematic review we identified randomized-controlled trials (RCTs) comparing carvedilol vs. control therapy (no-active treatment or endoscopic variceal ligation [EVL]) in patients with cirrhosis and CSPH without previous bleeding. We performed a competing-risk time-to-event meta-analysis using individual patient data (IPD) obtained from principal investigators of RCTs. Only compensated patients were included. Primary outcomes were prevention of decompensation (liver transplantation and death were competing events) and death (liver transplantation was a competing event). Models were adjusted using propensity scores for baseline covariates with the inverse probability of treatment weighting (IPTW) approach.
RESULTS
Among 125 full-text studies evaluated, 4 RCTs were eligible. The 4 provided IPD and were included, comprising 352 patients with compensated cirrhosis, 181 treated with carvedilol and 171 controls (79 received EVL and 92 placebo). Baseline characteristics were similar between groups. Standardized differences were <10% by IPTW. The risk of developing decompensation of cirrhosis was lower with carvedilol than in controls (subdistribution hazard ratio [SHR] 0.506; 95% CI 0.289-0.887; p = 0.017; I = 0.0%, Q-statistic-p = 0.880), mainly due to a reduced risk of ascites (SHR 0.491; 95% CI 0.247-0.974; p = 0.042; I = 0.0%, Q-statistic-p = 0.384). The risk of death was also lower with carvedilol (SHR 0.417; 95% CI 0.194-0.896; p = 0.025; I = 0.0%, Q-statistic-p = 0.989).
CONCLUSIONS
Long-term carvedilol therapy reduced decompensation of cirrhosis and significantly improved survival in compensated patients with CSPH. This suggests that screening patients with compensated cirrhosis for CSPH to enable the prompt initiation of carvedilol could improve outcomes.
PROSPERO REGISTRATION NUMBER
CRD42019144786.
LAY SUMMARY
The transition from compensated cirrhosis to decompensated cirrhosis is associated with markedly reduced life expectancy. Therefore, preventing decompensation in patients with compensated cirrhosis would be associated with greatly improved patient outcomes. There has been controversy regarding the use of non-selective β-blockers (portal pressure-lowering medications) in patients with cirrhosis and elevated portal blood pressure (portal hypertension). Herein, using a competing-risk meta-analysis to optimize sample size and properly investigate cirrhosis as a multistate disease and outcomes as time-dependent events, we show that carvedilol (a non-selective β-blocker) is associated with a reduced risk of decompensating events and improved survival in patients with cirrhosis and portal hypertension.
Topics: Adrenergic beta-Antagonists; Ascites; Carvedilol; Esophageal and Gastric Varices; Humans; Hypertension, Portal; Liver Cirrhosis; Portal Pressure; Randomized Controlled Trials as Topic
PubMed: 35661713
DOI: 10.1016/j.jhep.2022.05.021 -
World Journal of Hepatology Apr 2022Natriuretic peptides are involved in the cascade of pathophysiological events occurring in liver cirrhosis, counterbalancing vasoconstriction and anti-natriuretic...
BACKGROUND
Natriuretic peptides are involved in the cascade of pathophysiological events occurring in liver cirrhosis, counterbalancing vasoconstriction and anti-natriuretic factors. The effects of natriuretic peptides as treatment of cirrhotic ascites have been investigated only in small studies, and definitive results are lacking.
AIM
To examine the effects and safety of natriuretic peptides in cirrhosis patients with ascites.
METHODS
We searched MEDLINE, Web of Science, Scopus, Cochrane Library and Embase for all available studies applying intravenous administration of any natriuretic peptide to patients suffering from cirrhotic ascites. Inclusion was not limited by treatment duration or dose, or by follow-up duration. Both randomised controlled trials and non-randomised studies were eligible for inclusion. The primary outcome was change in renal sodium excretion. Secondary outcomes included safety measures and changes in renal water excretion, plasma aldosterone concentration, and plasma renin activity.
RESULTS
Twenty-two studies were included. Atrial natriuretic peptide (ANP) was the only intensively studied treatment. Sodium excretion increased in response to continuous ANP infusion and was more pronounced when infusion rates of > 30 ng/kg/min were administered compared with ≤ 30 ng/kg/min ( < 0.01). Moreover, natriuresis was significantly higher in study subgroups with mild/moderate ascites compared with moderate/severe and refractory ascites ( < 0.01). ANP infusions increased renal water excretion, although without reaching a statistically significant dose-response gradient. Plasma aldosterone concentration and plasma renin activity were significantly lower at baseline in study subgroups achieving a negative sodium balance in response to an ANP administration compared with treatment non-responders ( < 0.01). Blood pressure decreases occurred less frequently when ANP doses ≤ 30 ng/kg/min were applied. The quality of evidence for a natriuretic response to ANP was low, mainly due to small sample sizes and considerable between-study heterogeneity. Data were sparse for the other natriuretic peptides; B-type natriuretic peptide and urodilatin.
CONCLUSION
Intravenous ANP infusions increase sodium excretion in patients with cirrhotic ascites. Continuous infusion rates > 30 ng/kg/min are the most effective. However, safety increases with infusion rates ≤ 30 ng/kg/min.
PubMed: 35646272
DOI: 10.4254/wjh.v14.i4.827 -
PloS One 2022Changes in endothelial function are implicated in the spread of tuberculosis (TB). Studies suggest a role for the vascular endothelial growth factor (VEGF) in TB-related... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Changes in endothelial function are implicated in the spread of tuberculosis (TB). Studies suggest a role for the vascular endothelial growth factor (VEGF) in TB-related endothelial function changes. However, the findings of studies investigating the VGEF profile in TB are not consistent, and no formal systematic review and meta-analysis exists summarizing these studies.
METHODS
We did a meta-analysis of studies assessing VEGF levels in patients with TB. A systematic search on June 25, 2021, was conducted for eligible studies that made VEGF measurements in an unstimulated sample, e.g., a blood fraction (plasma or serum), cerebrospinal fluid (CSF), pleural effusion (PE), or bronchoalveolar lavage fluid, and ascites or pericardial fluid for patients with TB and controls without TB. Also, studies that made simultaneous measurements of VEGF in blood and PE or CSF in the same patients with TB were included. Longitudinal studies that provided these data at baseline or compared pre-post anti-tuberculosis treatment (ATT) levels of VEGF were included. The primary outcome was the standardized mean difference (SMD) of VEGF levels between the comparison groups.
RESULTS
52 studies were included in the meta-analysis. There were 1787 patients with TB and 3352 control subjects of eight categories: 107 patients with transudative pleural effusion, 228 patients with congestive heart failure (CHF)/chronic renal failure (CRF), 261 patients with empyema and parapneumonic effusion (PPE), 241 patients with cirrhosis, 694 healthy controls (with latent TB infection or uninfected individuals), 20 patients with inactive tuberculous meningitis (TBM), 123 patients with non-TBM, and 1678 patients with malignancy. The main findings are as follows: (1) serum levels of VEGF are higher in patients with active TB compared with healthy controls without other respiratory diseases, including those with latent TB infection or uninfected individuals; (2) both serum and pleural levels of VEGF are increased in patients with TPE compared with patients with transudative, CHF/CRF, or cirrhotic pleural effusion; (3) ascitic/pericardial fluid, serum, and pleural levels of VEGF are decreased in patients with TB compared with patients with malignancy; (4) pleural levels of VEGF are lower in patients with TPE compared with those with empyema and PPE, whereas serum levels of VEGF are not different between these patients; (5) both CSF and serum levels of VEGF are increased in patients with active TBM compared with controls, including patients with inactive TBM or non-TBM subjects; (6) post-ATT levels of VEGF are increased compared with pre-ATT levels of VEGF; and (7) the mean age and male percentage of the TB group explained large and total amount of heterogeneity for the meta-analysis of blood and pleural VEGF levels compared with healthy controls and patients with PPE, respectively, whereas these moderators did not show any significant interaction with the effect size for other analyses.
DISCUSSION
The important limitation of the study is that we could not address the high heterogeneity among studies. There might be unmeasured factors behind this heterogeneity that need to be explored in future research. Meta-analysis findings align with the hypothesis that TB may be associated with abnormal vascular function, and both local and systemic levels of VEGF can be used to trace this abnormality.
Topics: Exudates and Transudates; Humans; Latent Tuberculosis; Male; Pleural Effusion; Tuberculosis, Meningeal; Tuberculosis, Pleural; Vascular Endothelial Growth Factor A
PubMed: 35613134
DOI: 10.1371/journal.pone.0268543