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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 -
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 -
Endocrine Practice : Official Journal... Feb 2021Adrenocorticotropic hormone-producing pancreatic neuroendocrine neoplasm (ACTHoma) is an exceedingly rare type of pancreatic neuroendocrine neoplasm (pNEN) that often... (Review)
Review
OBJECTIVE
Adrenocorticotropic hormone-producing pancreatic neuroendocrine neoplasm (ACTHoma) is an exceedingly rare type of pancreatic neuroendocrine neoplasm (pNEN) that often causes ectopic adrenocorticotropic hormone syndrome. These neoplasms have been found to be very aggressive and challenging to treat. The current systematic review aimed to analyze the clinical features, immunohistochemical characteristics, diagnosis, therapy, and prognosis of ACTHoma.
METHODS
A systematic review of the English- and Chinese-language literature was performed. PubMed, EMBASE, and Wanfang databases were searched to identify articles about ACTHoma in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines.
RESULTS
A total of 210 studies encompassing 336 patients diagnosed with ACTHoma were selected for the systematic review, including 16 Chinese patients.
CONCLUSION
ACTHoma was more common in women (66.4%), and the mean age was 44.7 years. Tumors were generally large, and the mean tumor size was 4.43 cm. The incidence of clinical manifestations was: hypokalemia, 69.3%; diabetes, 63.2%; weakness, 60.1%, hypertension, 56.4%; moon face 41.1%; and edema, 37.4%. These tumors are more commonly found in the tail of pancreas, and the most frequent site of metastasis was the liver. The pNENs or other functioning pNENs could evolve into ACTHoma. ACTHoma is a very rare disease, and the mean follow-up time was 28.3 months.
Topics: ACTH Syndrome, Ectopic; Adrenocorticotropic Hormone; Adult; Female; Humans; Neuroendocrine Tumors; Pancreatic Neoplasms; Prognosis
PubMed: 33616046
DOI: 10.1016/j.eprac.2020.10.012 -
World Journal of Gastroenterology Mar 2016To construct a global "metabolic phenotype" of pancreatic ductal adenocarcinoma (PDAC) reflecting tumour-related metabolic enzyme expression. (Review)
Review
AIM
To construct a global "metabolic phenotype" of pancreatic ductal adenocarcinoma (PDAC) reflecting tumour-related metabolic enzyme expression.
METHODS
A systematic review of the literature was performed using OvidSP and PubMed databases using keywords "pancreatic cancer" and individual glycolytic and mitochondrial oxidative phosphorylation (MOP) enzymes. Both human and animal studies investigating the oncological effect of enzyme expression changes and inhibitors in both an in vitro and in vivo setting were included in the review. Data reporting changes in enzyme expression and the effects on PDAC cells, such as survival and metastatic potential, were extracted to construct a metabolic phenotype.
RESULTS
Seven hundred and ten papers were initially retrieved, and were screened to meet the review inclusion criteria. 107 unique articles were identified as reporting data involving glycolytic enzymes, and 28 articles involving MOP enzymes in PDAC. Data extraction followed a pre-defined protocol. There is consistent over-expression of glycolytic enzymes and lactate dehydrogenase in keeping with the Warburg effect to facilitate rapid adenosine-triphosphate production from glycolysis. Certain isoforms of these enzymes were over-expressed specifically in PDAC. Altering expression levels of HK, PGI, FBA, enolase, PK-M2 and LDA-A with metabolic inhibitors have shown a favourable effect on PDAC, thus identifying these as potential therapeutic targets. However, the Warburg effect on MOP enzymes is less clear, with different expression levels at different points in the Krebs cycle resulting in a fundamental change of metabolite levels, suggesting that other essential anabolic pathways are being stimulated.
CONCLUSION
Further characterisation of the PDAC metabolic phenotype is necessary as currently there are few clinical studies and no successful clinical trials targeting metabolic enzymes.
Topics: Animals; Carcinoma, Pancreatic Ductal; Energy Metabolism; Gene Expression Regulation, Enzymologic; Gene Expression Regulation, Neoplastic; Glucose; Humans; Pancreatic Neoplasms; Phenotype
PubMed: 27022229
DOI: 10.3748/wjg.v22.i12.3471 -
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 -
Journal of Gastrointestinal Surgery :... Nov 2020Excess adiposity is considered causally related to pancreatic cancer. While most knowledge on the topic comes from studies on general and visceral adiposity, the role of...
BACKGROUND
Excess adiposity is considered causally related to pancreatic cancer. While most knowledge on the topic comes from studies on general and visceral adiposity, the role of intra-pancreatic fat deposition in pancreatic carcinogenesis just begins to be elucidated. The aim was to conduct a comprehensive systematic review of clinical studies on intra-pancreatic fat deposition in individuals with pancreatic cancer or pre-malignant lesions.
METHODS
A literature search was conducted independently by two reviewers using three electronic databases. Studies were included if they reported on intra-pancreatic fat deposition determined based on modern radiology or histology. Summary estimates were presented as pooled prevalence or relative risk and 95% confidence interval.
RESULTS
A total of 13 studies (encompassing 2178 individuals) were included. The pooled prevalence of intra-pancreatic fat deposition in individuals with pancreatic cancer or pre-malignant lesions was 52% (95% confidence interval, 38-66%). The presence of pancreatic cancer or pre-malignant lesions was associated with a significantly increased risk of intra-pancreatic fat deposition (relative risk 2.78 (95% confidence interval, 1.56-4.94, p < 0.001).
CONCLUSION
Individuals with pancreatic cancer or pre-malignant lesions are characterized by increased intra-pancreatic fat deposition. There are sound grounds for conceptually viewing intra-pancreatic fat deposition as a combination of fat accumulation in the pancreas (due to expansion of excess visceral fat) and fatty replacement of the pancreas (due to changes in cellular identity within the pancreas). Guidelines on reporting intra-pancreatic fat deposition need to be developed with a view to informing a comprehensive and standardized characterization of this clinical entity in future studies.
Topics: Adiposity; Carcinogenesis; Humans; Intra-Abdominal Fat; Pancreas; Pancreatic Neoplasms
PubMed: 31749093
DOI: 10.1007/s11605-019-04417-4 -
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 -
Annals of Oncology : Official Journal... May 2017Periodontal disease (PD), now our commonest infectious disorder leads to tooth loss, and has been linked to various systemic diseases, including various types of cancer.... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Periodontal disease (PD), now our commonest infectious disorder leads to tooth loss, and has been linked to various systemic diseases, including various types of cancer. The aim of this study is to provide a systematic review and a meta-analysis of the relationship between PD, edentulism, and pancreatic cancer (PC).
PATIENTS AND METHODS
From an initial review of 327 references we selected eight studies concerning periodontitis or edentulism with sufficient quantitative information to allow us to examine the risk of PC. We used relative risks (RRs), hazard ratios, or odds ratios to measure the association between periodontitis, edentulism, and PC. We employed random effects models to obtain summary risks, and we also provide measures of study differences and possible biases.
RESULTS
The summary RR for periodontitis and PC was 1.74 [95% confidence interval (CI) 1.41-2.15] and 1.54 for edentulism (95% CI 1.16-2.05). There was no evidence of heterogeneity for either variable, and no evidence of publication bias. The studies included reports from three continents, suggesting that the association is generalizable. Most of the studies were adjusted for variables thought to be associated with PC, such as gender, smoking, BMI, diabetes, and alcohol.
CONCLUSIONS
Using meta-analysis, both periodontitis and edentulism appear to be associated with PC, even after adjusting for common risk factors. As yet, the mechanisms linking oral disease and PC are uncertain, but could be related to changes in the oral microbiome-an area of current research.
Topics: Animals; Causality; Humans; Pancreatic Neoplasms; Periodontal Diseases; Proportional Hazards Models; Risk Factors; Tooth Loss
PubMed: 28453689
DOI: 10.1093/annonc/mdx019 -
World Journal of Surgical Oncology Oct 2017Recent years have seen standardization of the anatomic definitions of pancreatic adenocarcinoma, and increasing utilization of neoadjuvant therapy (NAT). The aim of the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Recent years have seen standardization of the anatomic definitions of pancreatic adenocarcinoma, and increasing utilization of neoadjuvant therapy (NAT). The aim of the current review was to summarize the evidence for NAT in pancreatic adenocarcinoma since 2009, when consensus criteria for resectable (R), borderline resectable (BR), and locally advanced (LA) disease were endorsed.
METHODS
PubMed search was undertaken along with extensive backward search of the references of published articles to identify studies utilizing NAT for pancreatic adenocarcinoma. Abstracts from ASCO-GI 2014 and 2015 were also searched.
RESULTS
A total of 96 studies including 5520 patients were included in the final quantitative synthesis. Pooled estimates revealed 36% grade ≥ 3 toxicities, 5% biliary complications, 21% hospitalization rate and low mortality (0%, range 0-16%) during NAT. The majority of patients (59%) had stable disease. On an intention-to-treat basis, R0-resection rates varied from 63% among R patients to 23% among LA patients. R0 rates were > 80% among all patients who were resected after NAT. Among R and BR patients who underwent resection after NAT, median OS was 30 and 27.4 months, respectively.
CONCLUSIONS
The current study summarizes the recent literature for NAT in pancreatic adenocarcinoma and demonstrates improving outcomes after NAT compared to those historically associated with a surgery-first approach for pancreatic adenocarcinoma.
Topics: Adenocarcinoma; Biliary Tract Diseases; Combined Modality Therapy; Hospitalization; Humans; Neoadjuvant Therapy; Pancreatectomy; Pancreatic Neoplasms; Prognosis; Retrospective Studies; Treatment Outcome
PubMed: 29017581
DOI: 10.1186/s12957-017-1240-2 -
International Journal of Environmental... Nov 2021The burden of pancreatic cancer varies greatly across countries, with the number of deaths, incident cases, and disability-adjusted life years more than doubling in... (Meta-Analysis)
Meta-Analysis Review
The burden of pancreatic cancer varies greatly across countries, with the number of deaths, incident cases, and disability-adjusted life years more than doubling in recent years, and with high-income countries having the highest incidence and mortality rates. We conducted this systematic review with meta-analysis with the goal of summarizing the current evidence on dietary fiber intake and its role in reducing the risk of pancreatic cancer, given the importance of identifying risk factors. This systematic review followed the guidelines of the Cochrane Collaboration and the Meta-analysis of Observational Studies in Epidemiology and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020. The structured literature search was conducted on PubMed/Medline and Scopus, combining free text words and medical subject headings. Our review contained 18 records at the end of the process. Our results show that dietary fiber intake reduces the risk of pancreatic cancer. When the analysis was differentiated according to the type of fiber considered, sub-grouped by gender (reduction of around 60% among women), and when case-control studies were conducted, the strength of the association increased. Clinicians and policymakers should improve interventions to raise the population's awareness regarding the consumption of high-fiber diets, both in practice and in terms of public health policy.
Topics: Case-Control Studies; Dietary Fiber; Female; Humans; Incidence; Observational Studies as Topic; Pancreatic Neoplasms; Risk Factors
PubMed: 34770068
DOI: 10.3390/ijerph182111556