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BMJ (Clinical Research Ed.) Jan 2015To evaluate potential linear and non-linear dose-response relations between blood glucose and risk of pancreatic cancer. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To evaluate potential linear and non-linear dose-response relations between blood glucose and risk of pancreatic cancer.
DESIGN
Systematic review and dose-response meta-analysis of prospective observational studies.
DATA SOURCES
Search of PubMed, Scopus, and related reviews before 30 November 2013 without language restriction.
ELIGIBILITY CRITERIA
Prospective studies evaluating the association between blood glucose concentration and pancreatic cancer. Retrospective and cross sectional studies excluded to avoid reverse causality.
DATA EXTRACTION AND SYNTHESIS
Two reviewers independently extracted relevant information and assessed study quality with the Newcastle-Ottawa scale. Random effects dose-response meta-analysis was conducted to assess potential linear and non-linear dose-response relations.
RESULTS
Nine studies were included for analysis, with a total of 2408 patients with pancreatic cancer. There was a strong linear dose-response association between fasting blood glucose concentration and the rate of pancreatic cancer across the range of prediabetes and diabetes. No non-linear association was detected. The pooled rate ratio of pancreatic cancer per 0.56 mmol/L (10 mg/dL) increase in fasting blood glucose was 1.14 (95% confidence interval 1.06 to 1.22; P<0.001) without significant heterogeneity. Sensitivity analysis excluding blood glucose categories in the range of diabetes showed similar results (pooled rate ratio per 0.56 mmol/L increase in fasting blood glucose was 1.15, 95% confidence interval 1.05 to 1.27; P=0.003), strengthening the association between prediabetes and pancreatic cancer.
CONCLUSIONS
Every 0.56 mmol/L increase in fasting blood glucose is associated with a 14% increase in the rate of pancreatic cancer. As prediabetes can be improved or even reversed through lifestyle changes, early detection of prediabetes coupled with lifestyle changes could represent a viable strategy to curb the increasing incidence of pancreatic cancer.
Topics: Biometry; Blood Glucose; Early Diagnosis; Health Behavior; Humans; Hyperglycemia; Observational Studies as Topic; Pancreatic Neoplasms; Prediabetic State; Risk Factors; Statistics as Topic
PubMed: 25556126
DOI: 10.1136/bmj.g7371 -
The Cochrane Database of Systematic... Nov 2021Several available therapies for neuroendocrine tumours (NETs) have demonstrated efficacy in randomised controlled trials. However, translation of these results into... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Several available therapies for neuroendocrine tumours (NETs) have demonstrated efficacy in randomised controlled trials. However, translation of these results into improved care faces several challenges, as a direct comparison of the most pertinent therapies is incomplete.
OBJECTIVES
To evaluate the safety and efficacy of therapies for NETs, to guide clinical decision-making, and to provide estimates of relative efficiency of the different treatment options (including placebo) and rank the treatments according to their efficiency based on a network meta-analysis.
SEARCH METHODS
We identified studies through systematic searches of the following bibliographic databases: the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library; MEDLINE (Ovid); and Embase from January 1947 to December 2020. In addition, we checked trial registries for ongoing or unpublished eligible trials and manually searched for abstracts from scientific and clinical meetings.
SELECTION CRITERIA
We evaluated randomised controlled trials (RCTs) comparing two or more therapies in people with NETs (primarily gastrointestinal and pancreatic).
DATA COLLECTION AND ANALYSIS
Two review authors independently selected studies and extracted data to a pre-designed data extraction form. Multi-arm studies were included in the network meta-analysis using the R-package netmeta. We separately analysed two different outcomes (disease control and progression-free survival) and two types of NET (gastrointestinal and pancreatic NET) in four network meta-analyses. A frequentist approach was used to compare the efficacy of therapies.
MAIN RESULTS
We identified 55 studies in 90 records in the qualitative analysis, reporting 39 primary RCTs and 16 subgroup analyses. We included 22 RCTs, with 4299 participants, that reported disease control and/or progression-free survival in the network meta-analysis. Precision-of-treatment estimates and estimated heterogeneity were limited, although the risk of bias was predominantly low. The network meta-analysis of progression-free survival found nine therapies for pancreatic NETs: everolimus (hazard ratio [HR], 0.36 [95% CI, 0.28 to 0.46]), interferon plus somatostatin analogue (HR, 0.34 [95% CI, 0.14 to 0.80]), everolimus plus somatostatin analogue (HR, 0.38 [95% CI, 0.26 to 0.57]), bevacizumab plus somatostatin analogue (HR, 0.36 [95% CI, 0.15 to 0.89]), interferon (HR, 0.41 [95% CI, 0.18 to 0.94]), sunitinib (HR, 0.42 [95% CI, 0.26 to 0.67]), everolimus plus bevacizumab plus somatostatin analogue (HR, 0.48 [95% CI, 0.28 to 0.83]), surufatinib (HR, 0.49 [95% CI, 0.32 to 0.76]), and somatostatin analogue (HR, 0.51 [95% CI, 0.34 to 0.77]); and six therapies for gastrointestinal NETs: 177-Lu-DOTATATE plus somatostatin analogue (HR, 0.07 [95% CI, 0.02 to 0.26]), everolimus plus somatostatin analogue (HR, 0.12 [95%CI, 0.03 to 0.54]), bevacizumab plus somatostatin analogue (HR, 0.18 [95% CI, 0.04 to 0.94]), interferon plus somatostatin analogue (HR, 0.23 [95% CI, 0.06 to 0.93]), surufatinib (HR, 0.33 [95%CI, 0.12 to 0.88]), and somatostatin analogue (HR, 0.34 [95% CI, 0.16 to 0.76]), with higher efficacy than placebo. Besides everolimus for pancreatic NETs, the results suggested an overall superiority of combination therapies, including somatostatin analogues. The results indicate that NET therapies have a broad range of risk for adverse events and effects on quality of life, but these were reported inconsistently. Evidence from this network meta-analysis (and underlying RCTs) does not support any particular therapy (or combinations of therapies) with respect to patient-centred outcomes (e.g. overall survival and quality of life).
AUTHORS' CONCLUSIONS
The findings from this study suggest that a range of efficient therapies with different safety profiles is available for people with NETs.
Topics: Humans; Indoles; Network Meta-Analysis; Pancreatic Neoplasms; Positron-Emission Tomography; Pyrimidines; Radionuclide Imaging; Sulfonamides
PubMed: 34822169
DOI: 10.1002/14651858.CD013700.pub2 -
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 -
International Journal of Surgery... Dec 2023Diagnosing pancreatic lesions, including chronic pancreatitis, autoimmune pancreatitis, and pancreatic cancer, poses a challenge and, as a result, is time-consuming. To... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Diagnosing pancreatic lesions, including chronic pancreatitis, autoimmune pancreatitis, and pancreatic cancer, poses a challenge and, as a result, is time-consuming. To tackle this issue, artificial intelligence (AI) has been increasingly utilized over the years. AI can analyze large data sets with heightened accuracy, reduce interobserver variability, and can standardize the interpretation of radiologic and histopathologic lesions. Therefore, this study aims to review the use of AI in the detection and differentiation of pancreatic space-occupying lesions and to compare AI-assisted endoscopic ultrasound (EUS) with conventional EUS in terms of their detection capabilities.
METHODS
Literature searches were conducted through PubMed/Medline, SCOPUS, and Embase to identify studies eligible for inclusion. Original articles, including observational studies, randomized control trials, systematic reviews, meta-analyses, and case series specifically focused on AI-assisted EUS in adults, were included. Data were extracted and pooled, and a meta-analysis was conducted using Meta-xl. For results exhibiting significant heterogeneity, a random-effects model was employed; otherwise, a fixed-effects model was utilized.
RESULTS
A total of 21 studies were included in the review with four studies pooled for a meta-analysis. A pooled accuracy of 93.6% (CI 90.4-96.8%) was found using the random-effects model on four studies that showed significant heterogeneity ( P <0.05) in the Cochrane's Q test. Further, a pooled sensitivity of 93.9% (CI 92.4-95.3%) was found using a fixed-effects model on seven studies that showed no significant heterogeneity in the Cochrane's Q test. When it came to pooled specificity, a fixed-effects model was utilized in six studies that showed no significant heterogeneity in the Cochrane's Q test and determined as 93.1% (CI 90.7-95.4%). The pooled positive predictive value which was done using the random-effects model on six studies that showed significant heterogeneity was 91.6% (CI 87.3-95.8%). The pooled negative predictive value which was done using the random-effects model on six studies that showed significant heterogeneity was 93.6% (CI 90.4-96.8%).
CONCLUSION
AI-assisted EUS shows a high degree of accuracy in the detection and differentiation of pancreatic space-occupying lesions over conventional EUS. Its application may promote prompt and accurate diagnosis of pancreatic pathologies.
Topics: Adult; Humans; Artificial Intelligence; Sensitivity and Specificity; Pancreas; Endosonography; Pancreatic Neoplasms
PubMed: 37800594
DOI: 10.1097/JS9.0000000000000717 -
Chemotherapy regimens for advanced pancreatic cancer: a systematic review and network meta-analysis.BMC Cancer Jun 2014Advanced pancreatic cancer confers poor prognosis and treatment advancement has been slow. Recent randomized clinical trials (RCTs) have demonstrated survival benefits... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Advanced pancreatic cancer confers poor prognosis and treatment advancement has been slow. Recent randomized clinical trials (RCTs) have demonstrated survival benefits for combination therapy compared to gemcitabine alone. However, the comparative benefits and harms of available combination chemotherapy treatments are not clear. We therefore conducted a systematic review and Bayesian network meta-analysis to assess the comparative safety and efficacy of chemotherapy regimens for the treatment of advanced pancreatic cancer.
METHODS
MEDLINE, PubMed, EMBASE, Cochrane Central Registry of Clinical trials and abstracts from major scientific meetings were searched for RCTs published from 2002 to 2013. Key outcomes were overall survival (OS), progression free survival (PFS), and safety including grade 3-4 febrile neutropenia, neutropenia, vomiting, diarrhea, fatigue and sensory neuropathy. Bayesian network meta-analyses were conducted to calculate survival and safety outcomes using gemcitabine (GEM) as the reference comparator. Effect estimates and 95% credible intervals were calculated for each comparison. Mean ranks and the probability of being best were obtained for each treatment analyzed in the network meta-analysis.
RESULTS
The search identified 23 studies involving 19 different treatment regimens and 9,989 patients. FOLFIRINOX, GEM/cisplatin/epirubicin/5FU (PEFG), GEM/NAB-paclitaxel (NAB-P), GEM/erlotinib+/-bevacizumab, GEM/capecitabine, and GEM/oxaliplatin were associated with statistically significant improvements in OS and PFS relative to gemcitabine alone and several other treatments. They were amongst the top ranked for survival outcomes amongst other treatments included. No significant differences were found for other combination chemotherapy treatments. Effect estimates from indirect comparisons matched closely to estimates derived from pairwise comparisons. Overall, combination therapies had greater risk for evaluated grade 3-4 toxicities over gemcitabine alone.
CONCLUSIONS
In the absence of head-to-head comparisons, we performed a mixed-treatment analysis to achieve high-quality information on the effectiveness and safety of each treatment. This study suggests that some combination therapies may offer greater benefits in the treatment of advanced pancreatic cancer than others. To more fully elucidate the comparative benefits and harms of different combination chemotherapy regimens, rigorously conducted comparative studies, or network meta-analysis of patient-level data are required.
Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Bayes Theorem; Databases as Topic; Humans; Pancreatic Neoplasms; Randomized Controlled Trials as Topic; Survival Analysis; Treatment Outcome
PubMed: 24972449
DOI: 10.1186/1471-2407-14-471 -
HPB : the Official Journal of the... Nov 2022Gastroenteropancreatic neuroendocrine tumors are often diagnosed when metastatic. The liver is the main site of metastases. Unfortunately, optimal management of... (Review)
Review
BACKGROUND
Gastroenteropancreatic neuroendocrine tumors are often diagnosed when metastatic. The liver is the main site of metastases. Unfortunately, optimal management of neuroendocrine liver metastases remains a topic of debate. The aim of this study was to make a systematic review of the current literature about the results of the different treatments of neuroendocrine liver metastases.
METHODS
A systematic review was conducted for English language publications from 1995 to 2021. Outcomes were analyzed according to survival, disease-free survival, and in the case of systemic therapies, progression-free survival.
RESULTS
5509 patients were analyzed in the review. 67% of patients underwent surgery achieving 5 years overall survival despite only 30% percent without a recurrence. 60% of patients that had received a transplant reached 5 years survival with a low disease-free survival rate (20%). Five-year survival rate was 36.2% for patients undergoing loco-regional therapies.
CONCLUSION
Surgical resection is the best treatment when metastases are resectable, with the highest rate of survival, although liver transplantation shows good results for patients not eligible for surgery. Loco-regional therapies may be useful when surgical resection is contraindicated, or selectively used as a bridge to surgery or transplantation. Systemic therapies are indicated in patients for whom curative treatment cannot be obtained.
Topics: Humans; Neuroendocrine Tumors; Liver Neoplasms; Intestinal Neoplasms; Pancreatic Neoplasms; Liver Transplantation
PubMed: 35794053
DOI: 10.1016/j.hpb.2022.06.009 -
Frontiers in Endocrinology 2021Pancreatic neuroendocrine tumors (PanNETs) are a heterogeneous group of neoplasms with increasing incidence and unpredictable behavior. Whole-exome sequencing recently... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Pancreatic neuroendocrine tumors (PanNETs) are a heterogeneous group of neoplasms with increasing incidence and unpredictable behavior. Whole-exome sequencing recently has shown very frequent somatic mutations in the alpha-thalassemia/mental retardation X-linked (ATRX) and death domain-associated protein (DAXX) genes in PanNETs. And the prognostic significance of altered ATRX/DAXX genes in PanNETs patients have been revealed in several reports. However, many of these include small sample size and hold controversial opinions. To increase statistical power, we performed a systematic review and meta-analysis to determine a pooled conclusion. We examined the impact of altered ATRX/DAXX genes mainly on overall survival (OS), disease-free survival (DFS) and relapse-free survival (RFS) in PanNETs.
METHODS
Eligible studies were identified and quality was assessed using multiple search strategies (last search May 2021). Data were collected from studies about prognostic significance of altered ATRX/DAXX in PanNETs. Studies were pooled, and combined hazard ratios (HRs) with 95% confidence intervals (CIs) were used to estimate strength of the associations.
RESULTS
Fourteen studies involving 2313 patients treated for PanNETs were included. After evaluating for publication bias, disease-free survival and relapse-free survival was significantly shortened in patients with altered ATRX/DAXX gene, with combined HR 5.05 (95% confidence interval (CI): 1.58-16.20, = 0.01) and 3.21 (95% confidence interval (CI): 1.44-7.16, < 0.01) respectively. However, the combined data showed there were no difference between patients with altered ATRX/DAXX gene or not in overall survival, with a combined HR 0.71 (95% confidence interval (CI): 0.44-1.15, = 0.23). We also performed a subgroup analysis with metastatic patients in overall survival, showing a combined HR 0.22 (95% confidence interval (CI): 0.11-0.48, = 0.96). The small number of studies and paucity of multivariate analyses are the limitations of our study.
CONCLUSIONS
This is the first rigorous pooled analysis assessing ATRX/DAXX mutation as prognostic biomarkers in PanNETs. Patients with altered ATRX/DAXX gene would have poor DFS according to the combined data. And altered ATRX/DAXX genes in metastatic patients showed a trend towards improved overall survival, although the difference did not reach statistical significance.
Topics: Co-Repressor Proteins; Humans; Molecular Chaperones; Neuroendocrine Tumors; Pancreatic Neoplasms; Prognosis; X-linked Nuclear Protein
PubMed: 34220718
DOI: 10.3389/fendo.2021.691557 -
European Journal of Gastroenterology &... Dec 2023The effect of gallstones and cholecystectomy on the development of pancreatic cancer has recently prompted many population-based studies. However, the results are... (Meta-Analysis)
Meta-Analysis
The effect of gallstones and cholecystectomy on the development of pancreatic cancer has recently prompted many population-based studies. However, the results are controversial. We conducted an updated systematic review and meta-analysis to explore the causality among gallstones, cholecystectomy and pancreatic cancer. Cohort studies published in the PubMed, Web of Science, Embase, and Cochrane Library databases up to May 2023 were retrieved. Pooled relative risks (RRs) and 95% confidence intervals (CIs) were analyzed using a random-effects model. We screened 1391 articles and included 16 studies. Gallstones were not associated with an increased risk of pancreatic cancer ( P = 0.082), with only the Asian population ( P = 0.011) showing an increased risk in the subgroup analysis. A markedly higher risk of pancreatic cancer was observed among patients with cholecystectomy (RR = 1.23; 95% CI, 1.07-1.41; P = 0.004; I 2 = 74.4%). The association remained significant in the Asian population ( P = 0.004), in the subgroup analyses stratified by sex, lag period, and time interval since cholecystectomy, and when the models were adjusted for diabetes, smoking, and BMI. Interestingly, cholecystectomy due to gallstones (RR = 1.30; 95% CI, 1.14-1.48; P < 0.001; I 2 = 30.8%), rather than for unspecified reasons ( P = 0.116), markedly increased the risk of pancreatic cancer. In conclusion, cholecystectomy due to gallstones, rather than gallstone formation, conferred an increased risk for pancreatic cancer. There was a higher risk for the Asian population for both gallstones and cholecystectomy.
Topics: Humans; Gallstones; Cholecystectomy; Cohort Studies; Risk; Pancreatic Neoplasms
PubMed: 37823406
DOI: 10.1097/MEG.0000000000002652 -
International Journal of Environmental... Jan 2023Pancreatic cancer (PC) represents the 6th cause of cancer death. Although the aetiology of PC is not completely understood, numerous risk factors have been identified in... (Meta-Analysis)
Meta-Analysis Review
Pancreatic cancer (PC) represents the 6th cause of cancer death. Although the aetiology of PC is not completely understood, numerous risk factors have been identified in association with this cancer, among them diet. However, little is known about the association between the Mediterranean Diet (MedDiet) and the risk of PC. For this reason, we conducted a systematic review with meta-analysis according to the PRISMA guidelines, searching on three databases (PubMed/MEDLINE, Scopus, and EMBASE). The protocol was registered in PROSPERO. Both fixed and random effect models were performed. The Effect size was reported as a hazard ratio (HR) with a 95% Confidence Interval (CI). A total of eight articles were included. The methodological quality of the included meta-analyses was high. Our results show that a higher adherence to the MedDiet is associated with a lower risk of PC [HR:0.82 (0.76-0.88) < 0.001, based on 1,301,320 subjects]. The results were also confirmed in sensitivity and subgroups analyses (avoidance of potential overlapping effects, type of tools used to assess dietary intake and the diagnosis of PC, prevalence and incidence of PC risk, country where the studies took place, sex, and cancer site). Promoting a higher adherence to the MedDiet could be an effective approach to reduce the risk of PC.
Topics: Humans; Diet, Mediterranean; Risk Factors; Pancreatic Neoplasms; Incidence
PubMed: 36767770
DOI: 10.3390/ijerph20032403 -
HPB : the Official Journal of the... Jun 2023Minimally Invasive Pancreatic Enucleation, either laparoscopic or robot-assisted, is rarely performed. The aim of this study was to offer the current available evidence... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Minimally Invasive Pancreatic Enucleation, either laparoscopic or robot-assisted, is rarely performed. The aim of this study was to offer the current available evidence about the outcomes of minimally invasive pancreatic enucleations and explore the possible advantage of this approach over traditional surgery.
METHODS
PubMed (MEDLINE), Cochrane Library and Embase (ELSEVIER) medical databases were searched for articles published from January 1990 to March 2022. Studies which included more than 10 cases of minimally-invasive pancreatic enucleation were included. Data on the outcomes were synthetized and meta-analyzed when appropriate.
RESULTS
Twenty studies published between 2009 and 2022 with a total of 552 patients were included in the systematic review: three hundred fifty-one patients (63.5%) had a laparoscopic intervention, two hundred and one (36.5%) robot-assisted with a cumulative incidence of conversion rate of 5%. Minimally-invasive surgery was performed in 63% of cases on the body/tail of the Pancreas and in 37% of the cases on the head/uncinate process of the Pancreas. The cumulative post-operative 30 days - mortality rate was 0.2% and the major postoperative morbidity (Clavien-Dindo III-IV-V) 35%. Clinically relevant pancreatic fistula was observed in 17% of the patients. Compared with the standardized open approach (n: 366 patients), mean length of hospital stay was significantly reduced in patients undergoing minimally invasive pancreatic enucleation (2.45 days, p = 0.003) with a favorable trend for post-operative major morbidity (Clavien-Dindo III-IV) (- 24% RR, p: 0.13). Operative time, blood loss and clinically relevant pancreatic fistula rate were comparable between the two groups. One hundred and fourteen robot-assisted enucleations entered in a subgroup analysis with comparable results to open surgery.
CONCLUSION
Minimally-Invasive approach for pancreatic enucleation is safe, feasible and offers short-term clinical outcomes comparable with open surgery. The potential benefit of robotic surgery will need to be verified in further studies.
Topics: Humans; Pancreatectomy; Pancreatic Neoplasms; Pancreatic Fistula; Laparoscopy; Minimally Invasive Surgical Procedures; Pancreas; Postoperative Complications
PubMed: 36958987
DOI: 10.1016/j.hpb.2023.02.014