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Pancreatology : Official Journal of the... Nov 2023Mucinous pancreatic cysts harbor the potential to progress to highly lethal pancreatic ductal adenocarcinoma (PDAC). Since these precursor cysts require cancer... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Mucinous pancreatic cysts harbor the potential to progress to highly lethal pancreatic ductal adenocarcinoma (PDAC). Since these precursor cysts require cancer surveillance or surgical resection, they need to be reliably distinguished from harmless pancreatic cysts. Current clinical and radiographic assessment is imperfect and the value of cyst fluid analysis for differential diagnosis is unclear. Therefore, we set out to investigate the value of cyst fluid biomarkers in distinguishing pancreatic cysts.
METHODS
We performed a systematic review of the current literature to identify articles that evaluated the diagnostic performance of clinically relevant and promising candidate cyst fluid biomarkers, with a particular emphasis on DNA-based biomarkers. Meta-analysis was performed for biomarkers targeted at identifying cyst type and presence of high-grade dysplasia or PDAC.
RESULTS
Data from a total of 42 studies was analyzed. Mutations in KRAS and/or GNAS allowed identification of mucinous cysts with a sensitivity of 79% and specificity of 98%. This exceeded the performance of the traditional biomarker carcinoembryonic antigen (CEA; sensitivity 58%, specificity 87%). Mutations in VHL were specific for serous cystadenomas (SCAs; sensitivity 56%, specificity 99%) and help to exclude mucinous cysts. Mutations in CDKN2A, PIK3CA, SMAD4, and TP53 each had high specificities of 97%, 97%, 98%, and 95%, respectively, to identify high-grade dysplasia or PDAC in mucinous cysts.
CONCLUSIONS
Cyst fluid analysis can be a valuable tool in the characterization of pancreatic cysts, with relevant clinical implications. Our results support the use of DNA-based cyst fluid biomarkers in the multidisciplinary diagnostic work-up of pancreatic cysts.
Topics: Humans; Cyst Fluid; Pancreatic Neoplasms; Carcinoembryonic Antigen; Carcinoma, Pancreatic Ductal; Pancreatic Cyst; DNA; Biomarkers, Tumor
PubMed: 37230894
DOI: 10.1016/j.pan.2023.05.005 -
Nutrition and Cancer 2022Although several epidemiological studies have investigated associations between poultry and fish consumption and pancreatic cancer (PC) risk, these findings have been... (Meta-Analysis)
Meta-Analysis
Although several epidemiological studies have investigated associations between poultry and fish consumption and pancreatic cancer (PC) risk, these findings have been inconsistent. The present study aimed to perform a meta-analysis to comprehensively evaluate these associations. We retrieved Eligible cohort studies and case-control studies published before February 2020 from the Medline, EMBASE, and Cochrane Library and applied a random or fixed effects model to calculate the pooled relative risk (RR) and the corresponding 95% confidence intervals (CI). Publication bias was detected using funnel plots, Begg's test, and Egger's test, and the study quality was evaluated using the Newcastle-Ottawa scale. We included 25 studies in the analyses. The pooled RR of PC for the highest vs. lowest poultry intake category was 1.14 (95% CI: 1.02-1.26) in cohort studies. There was no appreciable link between fish intake and PC risk (RR: 1.00, 95% CI: 0.93-1.07). Our results suggest that large amount of poultry intake may increase PC risk, while fish intake is unlikely to be linked to PC risk. These links require further investigation, particularly between poultry and PC.
Topics: Animals; Case-Control Studies; Cohort Studies; Humans; Pancreatic Neoplasms; Poultry; Risk; Risk Factors
PubMed: 33432844
DOI: 10.1080/01635581.2020.1869276 -
Cancer Research Communications Oct 2022Pancreatic ductal adenocarcinoma (PDAC) has a 5-year survival rate below 5%. Carbohydrate antigen 19-9 (CA19-9) is the most commonly used blood-based biomarker for PDAC... (Meta-Analysis)
Meta-Analysis
UNLABELLED
Pancreatic ductal adenocarcinoma (PDAC) has a 5-year survival rate below 5%. Carbohydrate antigen 19-9 (CA19-9) is the most commonly used blood-based biomarker for PDAC in current clinical practice, despite having been shown repeatedly to be inaccurate and have poor diagnostic performance. This review aims to assess the reported diagnostic accuracy of all blood-based biomarkers investigated to date in PDAC, by directly comparing individual biomarkers and multi-biomarker panels, both containing CA19-9 and not (novel). A systematic review was conducted in accordance with PRISMA standards in July 2020. Individualized search strategies for three academic databases identified 5,885 studies between the years 1973 and 2020. After two rounds of screening, 250 studies were included. Data were extracted and assessed for bias. A multivariate three-level meta-analysis with subgroup moderators was run in R using AUC values as effect size. On the basis of this model, the pooled AUC value for all multi-biomarker panels (AUC = 0.898; 95% confidence interval (CI): 0.88-0.91) was significantly higher than all single biomarkers (AUC = 0.803; 95% CI: 0.78-0.83; < 0.0001). The pooled AUC value for CA19-9 alone was significantly lower compared with the multi-biomarker panels containing CA19-9 ( < 0.0001). For the novel biomarkers, the pooled AUC for single biomarkers was also significantly lower compared with multi-biomarker panels ( < 0.0001). Novel biomarkers that have been repeatedly examined across the literature, such as TIMP-1, CEA, and CA125, are highlighted as promising. These results suggest that CA19-9 may be best used as an addition to a panel of biomarkers rather than alone, and that multi-biomarker panels generate the most robust results in blood-based PDAC diagnosis.
SIGNIFICANCE
In a systematic review and three-level multivariate meta-analysis, it is shown for the first time that blood-based multi-biomarker panels for the diagnosis of PDAC exhibit superior performance in comparison with single biomarkers. CA19-9 is demonstrated to have limited utility alone, and to perform poorly in patient control cohorts of both healthy and benign individuals. Multi-biomarker panels containing CA19-9 produce the best diagnostic performance overall.
Topics: Humans; CA-19-9 Antigen; Biomarkers, Tumor; Case-Control Studies; Pancreatic Neoplasms; Carcinoma, Pancreatic Ductal
PubMed: 36969742
DOI: 10.1158/2767-9764.CRC-22-0190 -
Clinical Gastroenterology and... Mar 2016Obesity is associated with an increased risk for pancreatic cancer, but it is unclear whether it affects mortality. We performed a systematic review and meta-analysis to... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND & AIMS
Obesity is associated with an increased risk for pancreatic cancer, but it is unclear whether it affects mortality. We performed a systematic review and meta-analysis to assess the association between premorbid obesity and mortality from pancreatic cancer.
METHODS
We performed a systematic search through January 2015 and identified studies of the association between premorbid obesity (at least 1 year prior to pancreatic cancer diagnosis) and pancreatic cancer-related mortality. We estimated summary adjusted hazard ratio (aHR) with 95% confidence interval (CI), comparing data from obese (body mass index [BMI] ≥30 kg/m(2)) and overweight subjects (BMI, 25.0-29.9 kg/m(2)) with those from individuals with a normal BMI (controls) by using random-effects model.
RESULTS
We identified 13 studies (including 3 studies that pooled multiple cohorts); 5 studies included only patients with pancreatic cancer, whereas 8 studies evaluated pancreatic cancer-related mortality in cancer-free individuals at inception. In the meta-analysis, we observed increase in pancreatic cancer-related mortality among overweight (aHR, 1.06; 95% CI, 1.02-1.11; I(2) = 0) and obese individuals (aHR, 1.31; 95% CI, 1.20-1.42; I(2) = 43%), compared with controls; the association remained when we analyzed data from only subjects with pancreatic cancer. Each 1 kg/m(2) increase in BMI was associated with 10% increase in mortality (aHR, 1.10; 95% CI, 1.05-1.15) with minimal heterogeneity (I(2) = 0). In the subgroup analysis, obesity was associated with increased mortality in Western populations (11 studies; aHR, 1.32; 95% CI, 1.22-1.42) but not in Asia-Pacific populations (2 studies; aHR, 0.98; 95% CI, 0.76-1.27).
CONCLUSIONS
In a systematic review and meta-analysis, we associated increasing level of obesity with increased mortality in patients with pancreatic cancer in Western but not Asia-Pacific populations. Strategies to reduce obesity-induced metabolic abnormalities might be developed to treat patients with pancreatic cancer.
Topics: Body Mass Index; Global Health; Humans; Obesity; Pancreatic Neoplasms
PubMed: 26460214
DOI: 10.1016/j.cgh.2015.09.036 -
Surgical Oncology Dec 2023Pancreatic ductal adenocarcinoma (PDAC) is a challenging disease, with surgery being the only possible cure. However, despite surgery, the majority of patients... (Meta-Analysis)
Meta-Analysis Review
Prognostic utility of preoperative and postoperative KRAS-mutated circulating tumor DNA (ctDNA) in resected pancreatic ductal adenocarcinoma: A systematic review and meta-analysis.
BACKGROUND
Pancreatic ductal adenocarcinoma (PDAC) is a challenging disease, with surgery being the only possible cure. However, despite surgery, the majority of patients experience recurrence. Recent evidence suggests that perioperative KRAS-mutated circulating tumor DNA (ctDNA) may have prognostic value. Therefore, we conducted a systematic review and meta-analysis to explore the prognostic significance of preoperative and postoperative KRAS-mutated ctDNA testing in resected PDAC.
METHODS
We searched PubMed/MEDLINE, Embase, and Cochrane Central Register of Controlled Trials databases for studies that reported the effect of preoperative and postoperative KRAS-mutated ctDNA on overall survival (OS) and/or relapse-free survival (RFS) in resected PDAC. We used a random-effects model to determine the pooled OS and RFS hazard ratios (HR) and their corresponding 95 % confidence intervals (CI).
RESULTS
We identified 15 studies (868 patients) eligible for analysis. In the preoperative setting, positive ctDNA correlated with worse RFS in 8 studies (HR, 2.067; 95 % CI, 1.346-3.174, P < 0.001) and worse OS in 10 studies (HR, 2.170; 95 % CI, 1.451-3.245, P < 0.001) compared to negative ctDNA. In the postoperative setting, positive ctDNA correlated with worse RFS across 9 studies (HR, 3.32; 95 % CI, 2.19-5.03, P < 0.001) and worse OS in 6 studies (HR, 6.62; 95 % CI, 2.18-20.16, P < 0.001) compared to negative ctDNA.
CONCLUSION
Our meta-analysis supports the utility of preoperative and postoperative KRAS-mutated ctDNA testing as a prognostic marker for resected PDAC. Further controlled studies are warranted to confirm these results and to investigate the potential therapeutic implications of positive KRAS-mutated ctDNA.
Topics: Humans; Prognosis; Circulating Tumor DNA; Proto-Oncogene Proteins p21(ras); Mutation; Carcinoma, Pancreatic Ductal; Pancreatic Neoplasms; Biomarkers, Tumor
PubMed: 37852124
DOI: 10.1016/j.suronc.2023.102007 -
Public Health Nutrition Dec 2021The meta-analysis was conducted to test the link between pancreatic cancer (PC) risk and dietary inflammatory index (DII®) score. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
The meta-analysis was conducted to test the link between pancreatic cancer (PC) risk and dietary inflammatory index (DII®) score.
DESIGN
Systematic review and meta-analysis.
SETTING
We searched PubMed, Embase, Web of Science and the Cochrane Library up to 22 November 2020 to identify the relevant studies. Studies that reported the risk estimates and the corresponding 95 % CI for the DII category and PC risk were included. The effect sizes were pooled using the random-effects model. Dose-response analysis was conducted where possible.
PARTICIPANTS
Two prospective cohort studies of 634 705 participants (3152 incident cases), and four case-control studies of 2737 cases and 4861 controls.
RESULTS
Overall, the pooled risk ratio (RR) indicated that individuals in the highest category compared with the lowest category had an increased PC risk (RR = 1·45; 95 % CI 1·11, 1·90; P = 0·006). Meanwhile, significant heterogeneity was also revealed. The dose-response meta-analysis indicated that a 1-unit increase in the DII score was associated with the PC risk (RR = 1·08; 95 % CI 1·002, 1·166; P = 0·045; I2 = 94·1 %, P < 0·001). Nonlinear result showed an increased risk of moving from fewer to more inflammatory borders with increasing DII score (Pnonlinearity = 0·003; I2 = 76·5 %, P < 0·001). Subgroup analyses found that significant positive association between PC risk and DII score appeared to be in case-control studies (RR = 1·70; 95 % CI 1·16, 2·50; P = 0·007) and studies with ≤ 31 DII components (RR = 1·76; 95 % CI 1·14, 2·72; P = 0·011).
CONCLUSION
These findings suggested dietary habits with high inflammatory features (high DII score) might increase PC risk.
Topics: Diet; Humans; Inflammation; Pancreatic Neoplasms; Prospective Studies; Risk Factors
PubMed: 33843543
DOI: 10.1017/S1368980021001579 -
Pancreatology : Official Journal of the... 2016A systematic review and meta-analysis from literature has been performed to assess the impact of targeted therapy in advanced pancreatic cancer. (Meta-Analysis)
Meta-Analysis Review
AIM
A systematic review and meta-analysis from literature has been performed to assess the impact of targeted therapy in advanced pancreatic cancer.
METHODS
By searching different literature databases and major cancer meetings proceedings, data from all randomized clinical trials designed to investigate molecular targeted agents in the treatment of advanced pancreatic cancer were collected. The time-frame between January 2007 and March 2015 was selected. Data on predefined end-points, including overall survival, progression-free survival in terms of Hazard Ratio and response-rate were extracted and analyzed by a random effects model. Pooled data analysis was performed according to the DerSimonian and Laird test. The occurrence of publication bias was investigated through Begg's test by visual inspection of funnel plots.
RESULTS
Twenty-seven randomized clinical trials for a total of 8205 patients were selected and included in the final analysis. A significant benefit was demonstrated for anti-EGFR agents on overall survival (HR = 0.880; 95% confidence interval (CI) 0.797-0.972; p = 0.011). In the pooled analysis no benefit on overall survival (OS: pooled HR = 0.957; 95%CI 0.900-1.017; p = 0.153), or progression-free survival (PFS: pooled HR = 0.908; 95%CI 0.817-1.010; p = 0.075) for targeted-based therapies as compared to conventional treatments could be demonstrated. No advantage was reported in response-rate (OR for RR = 1.210; 95%CI 0.990-1.478; p = 0.063). Begg's funnel plot showed no evidence of publication bias.
CONCLUSION
The use of molecular targeted agents does not translate into clinical benefit. Therefore, our work highlights the need to identify predictive factors for patient selection and rationally designed clinical trials.
Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Genetic Predisposition to Disease; Humans; Pancreatic Neoplasms; Signal Transduction
PubMed: 26852170
DOI: 10.1016/j.pan.2016.01.003 -
Pancreatology : Official Journal of the... 2015Potential benefits of local extirpation of benign pancreatic head tumors are tissue conservation of pancreas, stomach, duodenum and common bile duct (CBD) and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Potential benefits of local extirpation of benign pancreatic head tumors are tissue conservation of pancreas, stomach, duodenum and common bile duct (CBD) and maintenance of pancreatic functions.
METHODS
Medline/PubMed, Embase and Cochrane Library databases were searched to identify studies applying duodenum-preserving total or partial pancreatic-head resection (DPPHRt/p) and reporting short- and long-term outcomes. Twenty-four studies, including 416 patients who underwent DPPHRt/p, were identified for systematic analysis. The meta-analysis was based on 10 prospective controlled and 4 retrospective controlled cohort studies, comparing 293 DPPHRt/p resections with 372 pancreato-duodenectomies (PD).
RESULTS, SYSTEMATIC ANALYSIS
Of 416 patients, 75.7% underwent total and 24.3% partial head resection, while 47.1% included segmentectomy of duodenum and CBD. The most common pathology was cystic neoplasm (65.8%) and endocrine tumors (13.4%). The frequencies of severe postoperative complications of 8.8%, pancreatic fistula of 19.2%, re-operation of 1.7% and hospital mortality of 0.48%, indicate a low level of early post-operative complications.
META-ANALYSIS
DPPHRt/p significantly preserved the level of exocrine (IV = -0.67, 95% CI -0.98 to -0.35, p = 0.0001) and endocrine (IV = 18.20, fixed, 95% CI -0.92 to 25.48, p = 0.0001) pancreatic functions compared to PD when the pre- and postoperative functional status in both groups are analyzed. There were no significant differences between DPPHRt/p and PD in frequency of pancreatic fistula, delayed gastric emptying or hospital mortality.
CONCLUSION
DPPHRt/p for benign neoplasms and neuro-endocrine tumors of the pancreatic head is associated with a low level of early-postoperative complications and a better conservation of exocrine and endocrine functions.
Topics: Common Bile Duct; Duodenum; Humans; Pancreas; Pancreatic Function Tests; Pancreatic Neoplasms
PubMed: 25732271
DOI: 10.1016/j.pan.2015.01.009 -
Clinics (Sao Paulo, Brazil) 2022The increase in the incidence of pancreatic and biliary cancers has attracted the search for methods of early detection of diseases and biomarkers. The authors propose... (Review)
Review
INTRODUCTION
The increase in the incidence of pancreatic and biliary cancers has attracted the search for methods of early detection of diseases and biomarkers. The authors propose to analyze new findings on the association between microbiota and Pancreatic Ductal Adenocarcinoma (PDAC) or Cholangiocarcinoma (CCA).
METHODS
This systematic review was carried out according to the items of Preferred Reports for Systematic Reviews and Protocol Meta-Analysis (PRISMA-P). This study was registered by the Prospective Register of Systematic Reviews (PROSPERO), identification code CRD42020192748 before the review was carried out. Articles were selected from the PUBMED, EMBASE, and Cochrane databases.
RESULTS
Most studies (86.67%) used 16s rRNA as a sequencing method. The main comorbidities found were diabetes mellitus, systemic arterial hypertension, and dyslipidemia. Many studies were limited by the small number of participants, but the biases were mostly low. There was very little concordance about the composition of the microbiome of different sites, for both case and control groups when compared to other studies' results. Bile sample analysis was the one with a greater agreement between studies, as three out of four studies found Escherichia in cases of CCA.
CONCLUSION
There was great disagreement in the characterization of both the microbiota of cases and control groups. Studies are still scarce, making it difficult to adequately assess the data in this regard. It was not possible to specify any marker or to associate any genus of microbiota bacteria with PDAC or CCA.
Topics: Carcinoma, Pancreatic Ductal; Humans; Microbiota; Pancreatic Neoplasms; RNA, Ribosomal, 16S; Syndrome
PubMed: 36122499
DOI: 10.1016/j.clinsp.2022.100101 -
European Journal of Clinical... Dec 2022Pancreatic cancer is considered one of the most deadly malignancies, primarily because of its diagnostic challenges. We performed a systematic review and diagnostic... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Pancreatic cancer is considered one of the most deadly malignancies, primarily because of its diagnostic challenges. We performed a systematic review and diagnostic meta-analysis to evaluate the diagnostic value of noncoding salivary RNAs in pancreatic cancer diagnosis.
METHODS
Our investigation involved pertinent studies published in PubMed, Scopus, Web of Science, LIVIVO, Ovid and also the Google Scholar search engine. Specificity and sensitivity were calculated, as were positive and negative likelihood ratios (PLR and NLR), and the diagnostic odds ratio (DOR). The summary receiver-operating characteristics and area under the curve were plotted and assessed.
RESULTS
This meta-analysis and systematic review involved and examined five studies that contained 145 study units with a total of 2731 subjects (1465 pancreatic cancer patients versus 1266 noncancer controls). The pooled specificity, sensitivity, NLR, PLR and DOR were 0.783 (95% CI: 0.759-0.805), 0.829 (95% CI: 0.809-0.848), 0.309 (95% CI: 0.279-0.343), 3.386 (95% CI: 2.956-3.879) and 18.403 (95% CI: 14.753-22.954), respectively, with the area under the curve (AUC) equal to 0.882. Subgroup analyses were conducted based on the saliva type (unstimulated and stimulated), mean age of patients, sample size, type of control, serum carbohydrate antigen 19-9 (CA19-9) level and type of salivary noncoding RNA (microRNA (miRNA) and long noncoding RNA (lncRNA)).
CONCLUSIONS
The results of our systematic review and meta-analysis suggest that noncoding RNA biomarkers in the stimulated saliva could be a promising approach for accurate pancreatic cancer diagnosis in the early stages.
Topics: Humans; Pancreatic Neoplasms; ROC Curve; MicroRNAs; Area Under Curve
PubMed: 35906804
DOI: 10.1111/eci.13848