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Translational Research : the Journal of... Jun 2022Extensive research is focused on the role of liquid biopsy in pancreatic cancer since reliable diagnostic and follow-up biomarkers represent an unmet need for this... (Meta-Analysis)
Meta-Analysis Review
Extensive research is focused on the role of liquid biopsy in pancreatic cancer since reliable diagnostic and follow-up biomarkers represent an unmet need for this highly lethal malignancy. We performed a systematic review and meta-analysis on the prognostic value of exosomal biomarkers in pancreatic ductal adenocarcinoma (PDAC). MEDLINE, Embase, Scopus, Web of Science, and CENTRAL were systematically searched on the 18th of January, 2021 for studies reporting on the differences in overall (OS) and progression-free survival (PFS) in PDAC patients with positive vs negative exosomal biomarkers isolated from blood. The random-effects model estimated pooled multivariate-adjusted (AHR) and univariate hazard ratios (UHRs) with 95% confidence intervals (CIs). Eleven studies comprising 634 patients were eligible for meta-analysis. Detection of positive exosomal biomarkers indicated increased risk of mortality (UHR = 2.81, CI:1.31-6,00, I = 88.7%, P < 0.001), and progression (UHR = 3.33, CI: 2.33-4.77, I = 0, P = 0.879) across various disease stages. Positive exosomal biomarkers identified preoperatively revealed a higher risk of mortality in resectable stages (UHR = 5.55, CI: 3.24-9.49, I = 0, P = 0.898). The risk of mortality in unresectable stages was not significantly increased with positive exosomal biomarkers (UHR = 2.51, CI: 0.55-11.43, I = 90.3%, P < 0.001). Detectable exosomal micro ribonucleic acids were associated with a decreased OS (UHR = 4.08, CI: 2.16-7.69, I = 46.9%, P = 0.152) across various stages. Our results reflect the potential of exosomal biomarkers for prognosis evaluation in PDAC. The associated heterogeneity reflects the variability of study methods and need for their uniformization before transition to clinical use.
Topics: Biomarkers, Tumor; Carcinoma, Pancreatic Ductal; Exosomes; Humans; Pancreatic Neoplasms; Prognosis
PubMed: 35066189
DOI: 10.1016/j.trsl.2022.01.001 -
Oncology 2020The present study evaluated the potential benefit of adding cetuximab to neoadjuvant, adjuvant, or palliative standard therapy for pancreatic cancer. (Meta-Analysis)
Meta-Analysis
INTRODUCTION
The present study evaluated the potential benefit of adding cetuximab to neoadjuvant, adjuvant, or palliative standard therapy for pancreatic cancer.
METHODS
A systematic literature search was performed in MEDLINE, Web of Science, and Cochrane Central Register of Controlled Trials (CENTRAL). Only randomised controlled trials (RCTs) investigating the effect of adding cetuximab to standard chemotherapy in pancreatic cancer were included. Evaluated outcomes were overall survival, progression-free survival, objective response, and toxicity. For overall survival and progression-free survival, hazard ratios (HR) with 95% confidence intervals (CI) were chosen as effect measure. For objective response, odds ratios (OR) with 95% CI were used. Analysis was based on a random effects model.
RESULTS
After screening 568 publications, a total of 4 RCTs with 924 patients were included. In all trials, patients were adequately randomised with balanced intervention and control groups. There was no significant difference in overall survival (HR 1.04; 95% CI: 0.90-1.19; p = 0.60), progression-free survival (HR 1.06; 95% CI: 0.93-1.22; p = 0.36), or objective response (OR 0.99; 95% CI: 0.66 -1.49; p = 0.96) when adding cetuximab to a standard therapy. Toxicity was the same or higher in each of the included trials. According to GRADE, the certainty of the evidence is high. Therefore, adding cetuximab to pancreatic cancer therapy has no clinically relevant benefit.
CONCLUSION
In the presence of no survival benefit, increased toxicity, and higher costs, a decreased cost-benefit ratio compared to the standard care must be suggested. Conducting further RCTs in unselected pancreatic cancer populations is unlikely to change this conclusion.
Topics: Antineoplastic Agents, Immunological; Cetuximab; Humans; Pancreatic Neoplasms; Prognosis; Treatment Outcome
PubMed: 31578019
DOI: 10.1159/000502844 -
Exocrine Pancreatic Insufficiency Following Acute Pancreatitis: Systematic Review and Meta-Analysis.Digestive Diseases and Sciences Jul 2019The epidemiology of exocrine pancreatic insufficiency (EPI) after acute pancreatitis (AP) is uncertain. We sought to determine the prevalence, progression, etiology and... (Meta-Analysis)
Meta-Analysis
BACKGROUND/OBJECTIVES
The epidemiology of exocrine pancreatic insufficiency (EPI) after acute pancreatitis (AP) is uncertain. We sought to determine the prevalence, progression, etiology and pancreatic enzyme replacement therapy (PERT) requirements for EPI during follow-up of AP by systematic review and meta-analysis.
METHODS
Scopus, Medline and Embase were searched for prospective observational studies or randomized clinical trials (RCTs) of PERT reporting EPI during the first admission (between the start of oral refeeding and before discharge) or follow-up (≥ 1 month of discharge) for AP in adults. EPI was diagnosed by direct and/or indirect laboratory exocrine pancreatic function tests.
RESULTS
Quantitative data were analyzed from 370 patients studied during admission (10 studies) and 1795 patients during follow-up (39 studies). The pooled prevalence of EPI during admission was 62% (95% confidence interval: 39-82%), decreasing significantly during follow-up to 35% (27-43%; risk difference: - 0.34, - 0.53 to - 0.14). There was a two-fold increase in the prevalence of EPI with severe compared with mild AP, and it was higher in patients with pancreatic necrosis and those with an alcohol etiology. The prevalence decreased during recovery, but persisted in a third of patients. There was no statistically significant difference between EPI and new-onset pre-diabetes/diabetes (risk difference: 0.8, 0.7-1.1, P = 0.33) in studies reporting both. Sensitivity analysis showed fecal elastase-1 assay detected significantly fewer patients with EPI than other tests.
CONCLUSIONS
The prevalence of EPI during admission and follow-up is substantial in patients with a first attack of AP. Unanswered questions remain about the way this is managed, and further RCTs are indicated.
Topics: Adult; Aged; Aged, 80 and over; Enzyme Replacement Therapy; Exocrine Pancreatic Insufficiency; Female; Humans; Male; Middle Aged; Observational Studies as Topic; Pancreatitis; Prevalence; Randomized Controlled Trials as Topic; Risk Factors; Treatment Outcome
PubMed: 31161524
DOI: 10.1007/s10620-019-05568-9 -
International Journal of Medical... Jan 2022Acute pancreatitis (AP) is a common clinical pancreatic disease. Patients with different severity levels have different clinical outcomes. With the advantages of... (Review)
Review
INTRODUCTION
Acute pancreatitis (AP) is a common clinical pancreatic disease. Patients with different severity levels have different clinical outcomes. With the advantages of algorithms, machine learning (ML) has gradually emerged in the field of disease prediction, assisting doctors in decision-making.
METHODS
A systematic review was conducted using the PubMed, Web of Science, Scopus, and Embase databases, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Publication time was limited from inception to 29 May 2021. Studies that have used ML to establish predictive tools for AP were eligible for inclusion. Quality assessment of the included studies was conducted in accordance with the IJMEDI checklist.
RESULTS
In this systematic review, 24 of 2,913 articles, with a total of 8,327 patients and 47 models, were included. The studies could be divided into five categories: 10 studies (42%) reported severity prediction; 10 studies (42%), complication prediction; 3 studies (13%), mortality prediction; 2 studies (8%), recurrence prediction; and 2 studies (8%), surgery timing prediction. ML showed great accuracy in several prediction tasks. However, most of the included studies were retrospective in nature, conducted at a single centre, based on database data, and lacked external validation. According to the IJMEDI checklist and our scoring criteria, two studies were considered to be of high quality. Most studies had an obvious bias in the quality of data preparation, validation, and deployment dimensions.
CONCLUSION
In the prediction tasks for AP, ML has shown great potential in assisting decision-making. However, the existing studies still have some deficiencies in the process of model construction. Future studies need to optimize the deficiencies and further evaluate the comparability of the ML systems and model performance, so as to consequently develop high-quality ML-based models that can be used in clinical practice.
Topics: Acute Disease; Algorithms; Humans; Machine Learning; Pancreatitis; Retrospective Studies
PubMed: 34785488
DOI: 10.1016/j.ijmedinf.2021.104641 -
International Journal of Surgery... Oct 2015This study to evaluate the utility of drain fluid amylase as a predictor of PF in patients undergoing pancreatic surgery based on the International Study Group of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND OBJECTIVES
This study to evaluate the utility of drain fluid amylase as a predictor of PF in patients undergoing pancreatic surgery based on the International Study Group of Pancreatic Fistula definitions of pancreatic fistula.
METHODS
A comprehensive search was carried out using Pubmed (Medline), Embase, Web of science and Cochrane database for clinical trials, which studied DFA as a diagnostic marker for pancreatic fistula after pancreatic surgery. Sensitivity, specificity and the diagnostic odds ratios with 95% confidence interval were calculated for each study. Summary receiver-operating curves were conducted and the area under the curve was evaluated.
RESULTS
A total of 10 studies were included. The pooled sensitivity and specificity of drain fluid amylase Day 1 for the diagnosis of postoperative pancreatic fistula were 81% and 87%, respectively (area under the curve was 0.897, diagnostic odds ratios was 16.83 and 95%CI was 12.66-22.36), the pooled sensitivity and specificity of drain fluid amylase Day 3 for the diagnosis of postoperative pancreatic fistula were 56% and 79%, respectively (area under the curve was 0.668, diagnostic odds ratios was 3.26 and 95%CI was 1.83-5.82) CONCLUSIONS: The drain fluid amylase Day 1, instead of drain fluid amylase Day 3, may be a useful criterion for the early identification of postoperative pancreatic fistula, and a value of drain fluid amylase Day 1 over than 1300 U/L was a risk factor of pancreatic fistula. And the diagnostic accuracy and the proposed cut-off levels of drain fluid amylase Day 1 in predicting the postoperative pancreatic fistula will have to be validated by multicenter prospective studies.
Topics: Amylases; Drainage; Humans; Odds Ratio; Pancreatectomy; Pancreatic Fistula; Pancreaticoduodenectomy; Risk Factors; Sensitivity and Specificity
PubMed: 26211439
DOI: 10.1016/j.ijsu.2015.07.007 -
Frontiers in Immunology 2023This review aims to determine the incidence and risk of pancreatic adverse events (AEs) associated with immune checkpoint inhibitors (ICIs) therapy for solid tumors. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
This review aims to determine the incidence and risk of pancreatic adverse events (AEs) associated with immune checkpoint inhibitors (ICIs) therapy for solid tumors.
METHODS
We conducted a comprehensive systematic literature search in PubMed, Embase, and Cochrane Library up to March 15, 2023, to identify all randomized controlled trials comparing ICIs with standard treatment in solid tumors. We included studies that reported immune-related pancreatitis or elevation of serum amylase or lipase levels. Following protocol registration in PROSPERO, we conducted a systematic review and meta-analysis.
RESULTS
59 unique randomized controlled trials with at least one ICI-containing arm (41 757 patients) were retrieved. The incidences for all-grade pancreatitis, amylase elevation and lipase elevation were 0.93% (95% CI 0.77-1.13), 2.57% (95% CI 1.83-3.60) and 2.78% (95% CI 1.83-4.19), respectively. The incidences for grade ≥3 pancreatitis, amylase elevation and lipase elevation were 0.68% (95% CI 0.54-0.85), 1.17% (95% CI 0.83-1.64) and 1.71% (95% CI 1.18-2.49), respectively. The use of ICIs was associated with an increased risk of all-grade pancreatic immune-related AEs (irAEs) including pancreatitis (OR=2.04, 95% CI 1.42-2.94, P =0.0001), amylase elevation (OR=1.91, 95% CI 1.47-2.49, P < 0.0001) and lipase elevation (OR=1.77, 95% CI 1.37-2.29, P < 0.0001). In addition to these, the analysis found that PD-1 inhibitors had a significant higher risk of pancreatic AEs compared with PD-L1 inhibitors and the patients undergoing dual ICI therapy were at a significantly higher risk of pancreatic AEs than the patients receiving single ICI therapy.
CONCLUSION
Our study provides an overview of the incidence and risk of ICI-associated pancreatitis and pancreatic enzyme elevations in the treatment of solid tumors. Our findings may help raise awareness among clinicians of the potential for ICI-associated pancreatic AEs in clinical practice.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO, identifier 345350.
Topics: Humans; Immune Checkpoint Inhibitors; Pancreatitis; Neoplasms; Amylases; Lipase
PubMed: 37359551
DOI: 10.3389/fimmu.2023.1166299 -
United European Gastroenterology Journal May 2020Although pancreatic tuberculosis (TB) is traditionally considered to be a rare clinical entity, in recent times, an increase in the number of reports of pancreatic TB...
INTRODUCTION
Although pancreatic tuberculosis (TB) is traditionally considered to be a rare clinical entity, in recent times, an increase in the number of reports of pancreatic TB has been noted. We conducted a systematic review in order to summarise currently available data on pancreatic TB.
METHODS
A comprehensive literature search of Medline, Scopus and ISI Web of Science databases was conducted in order to identify papers reporting cases of pancreatic TB. The eligibility criteria for inclusion in the review required that the studies reported patient(s) affected by pancreatic TB and that individual data on age, sex, clinical presentation and outcome were available.
RESULTS
In total, 116 studies reporting data on 166 patients were included in the analysis. The majority of patients were males (62.1%) diagnosed at a mean age of 41.61 ± 13.95 years. Most cases were diagnosed in Asia (50.0%), followed by North America (22.9%), Europe (20.5%), Africa (4.2%) and South America (2.4%). Human immunodeficiency virus (HIV) infection was diagnosed in 25.3% of those affected. Pancreatic TB most frequently presented itself in the form of a pancreatic mass (79.5%) localised mainly in the head (59.0%) and less frequently in the body (18.2%) and tail (13.4%). Extrapancreatic TB involvement most frequently affected the peripancreatic lymph nodes (47.3%). More than half of patients (55.2%) were subjected to laparotomy, while 21.08% underwent endoscopic ultrasound fine-needle aspiration biopsy. The presence of TB was identified most frequently through histological analysis (59.6%), followed by culture (28.9%), staining (27.7%) and, in a smaller number, by polymerase chain reaction (9.6%) and cytology (6.6%). Almost all patients received anti-tubercular pharmacological therapy (98.2%), while 24.1% underwent surgery. Despite treatment, 8.7% of patients died.
CONCLUSION
Increased awareness of pancreatic TB is needed, not only in endemic areas but especially in relation to HIV infection and other clinical conditions associated with immunoincompetence.
Topics: Antitubercular Agents; Endemic Diseases; Global Burden of Disease; HIV Infections; Humans; Lymph Node Excision; Lymph Nodes; Mycobacterium tuberculosis; Pancreas; Pancreatectomy; Pancreatitis; Tuberculosis, Endocrine; Tuberculosis, Lymph Node
PubMed: 32213022
DOI: 10.1177/2050640620902353 -
Cancer Medicine Jun 2017There is a strong rationale and many theoretical advantages for neoadjuvant therapy in pancreatic cancer (PC). However, study results have varied significantly. In this... (Meta-Analysis)
Meta-Analysis Review
There is a strong rationale and many theoretical advantages for neoadjuvant therapy in pancreatic cancer (PC). However, study results have varied significantly. In this study, a systematic review and meta-analysis of prospective studies were performed in order to evaluate safety and effectiveness of neoadjuvant therapy in PC. Thirty-nine studies were selected (n = 1458 patients), with 14 studies focusing on patients with resectable disease (group 1), and 19 studies focusing on patients with borderline resectable and locally advanced disease (group 2). Neoadjuvant chemotherapy was administered in 97.4% of the studies, in which 76.9% was given radiotherapy and 74.4% administered with chemoradiation. The complete and partial response rate was 3.8% and 20.9%. The incidence of grade 3/4 toxicity was 11.3%. The overall resection rate after neoadjuvant therapy was 57.7% (group 1: 73.0%, group 2: 40.2%). The R0 resection rate was 84.2% (group 1: 88.2%, group 2: 79.4%). The overall survival for all patients was 16.79 months (resected 24.24, unresected 9.81; group 1: 17.76, group 2: 16.20). Our results demonstrate that neoadjuvant therapy has not been proven to be beneficial and should be considered with caution in patients with resectable PC. Patients with borderline resectable or locally advanced disease may benefit from neoadjuvant therapy, but further research is needed.
Topics: Antineoplastic Agents; Humans; Morbidity; Neoadjuvant Therapy; Pancreatic Neoplasms; Prospective Studies; Treatment Outcome
PubMed: 28544758
DOI: 10.1002/cam4.1071 -
HPB : the Official Journal of the... Feb 2023Acute pancreatitis (AP) has variable clinical courses. This systematic review and meta-analysis aimed to determine the safety, efficacy, and impact of epidural... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Acute pancreatitis (AP) has variable clinical courses. This systematic review and meta-analysis aimed to determine the safety, efficacy, and impact of epidural anaesthesia (EA) use in AP.
METHODS
The PubMed, EMBASE, SCOPUS and Cochrane library databases were systematically searched between 1980 and 2022 using the PRISMA guidelines, to identify observational and comparative studies reporting on EA in AP. The meta-analysis was performed in R Foundation for Statistical Computing using the meta R Package for Meta-Analysis.
RESULTS
A total of 9 studies with 2006 patients of which 726 (36%) patients had EA were included. All studies demonstrated high safety and feasibility of EA in AP with no reported major local or neurological complications. One randomised controlled trial demonstrated an improvement in pain severity using a 0-10 visual analogue scale (VAS) at the outset (1.6 in EA vs 3.5 in non-EA, P = 0.02) and on day 10 (0.2 in EA vs 2.33 in non-EA, P = 0.034). There was also improvement in pancreatic perfusion with EA measured with computerised tomography 13 (43%) in EA vs 2 (7%) in non-EA, P = 0.003. The need for ventilatory support and overall mortality was lower in EA patients 40 (19%) vs 285 (24%) P = 0.025 (OR: 0.49, 95% CI: 0.28-0.84) and 16 (7%) vs 214 (20%), P = 0.050 (OR: 0.39, 95% CI: 0.15-1.00), respectively.
CONCLUSION
EA is infrequently used for pain management in AP and yet the available evidence suggests that it is safe and effective in reducing pain severity, improving pancreatic perfusion, and decreasing mortality.
Topics: Humans; Pancreatitis; Acute Disease; Anesthesia, Epidural; Pancreas; Analgesia, Epidural; Randomized Controlled Trials as Topic
PubMed: 36593161
DOI: 10.1016/j.hpb.2022.12.004 -
Cancer Epidemiology Dec 2014Smokeless tobacco is a possible risk factor for developing pancreatic adenocarcinoma. This systematic review addressed the question: Is there an association between... (Review)
Review
BACKGROUND
Smokeless tobacco is a possible risk factor for developing pancreatic adenocarcinoma. This systematic review addressed the question: Is there an association between smokeless tobacco use and pancreatic adenocarcinoma diagnosis?
METHODS
Five electronic databases, grey literature, and citations of relevant articles were searched to identify studies. Six researchers double-reviewed records for inclusion in the review. The information extracted from these studies was selected using criteria outlined in the Newcastle-Ottawa Quality Assessment Scale for observational studies. A qualitative synthesis of included studies was performed.
RESULTS
The search of electronic databases resulted in a total of 1747 citations. Eleven studies met the inclusion criteria for this review, including three cohort studies, seven case control studies and one study that pooled data from multiple case-control studies. Studies were heterogeneous in their assessment of exposure intensity and ascertainment of outcomes. Quality of the studies varied. Existing investigations of the association of interest appear to exhibit several types of biases including selection bias, information bias and bias in the analysis.
CONCLUSION
The association between smokeless tobacco use and pancreatic adenocarcinoma is inconclusive. More definitive conclusions regarding this relationship await the results of more methodologically rigorous epidemiologic studies.
Topics: Adenocarcinoma; Cohort Studies; Humans; Pancreatic Neoplasms; Risk Factors; Tobacco, Smokeless
PubMed: 25262376
DOI: 10.1016/j.canep.2014.08.010