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International Journal of Surgery... Dec 2023Pancreatic cancer frequently involves the surrounding major arteries, preventing surgeons from making a radical excision. Neoadjuvant therapy (NAT) can lessen the size... (Meta-Analysis)
Meta-Analysis
Perioperative and long-term survival outcomes of pancreatectomy with arterial resection in borderline resectable or locally advanced pancreatic cancer following neoadjuvant therapy: a systematic review and meta-analysis.
BACKGROUND
Pancreatic cancer frequently involves the surrounding major arteries, preventing surgeons from making a radical excision. Neoadjuvant therapy (NAT) can lessen the size of local tumors and eliminate potential micrommetastases. However, systematic and evidence-based recommendations for the treatment of arterial resection (AR) after NAT in pancreatic cancer are scarce.
METHOD
A computerized search of the Medline, Embase, Cochrane Library databases, and Clinicaltrials was performed to identify studies reporting the outcomes of patients who underwent pancreatectomy with AR and NAT for pancreatic cancer. Studies that reported perioperative and/or long-term results after pancreatectomy with AR and NAT were eligible for inclusion. The quality of the evidence was assessed with Newcastle-Ottawa Quality Assessment Form of bias tool. Data were pooled and analyzed by Stata 14.0 software.
RESULT
Nine studies with an overall sample size of 215 met our eligibility criteria and were included in the meta-analysis. All studies were retrospective studies, and the methodological quality was moderate. The pooled morbidity and mortality rates were 51% (95% CI: 41-61%; I²= 0.0%) and 2% (95% CI: 0-0.08; I²=33.3%), respectively. Meta-analysis showed that the overall R0 resection rate was 79% (CI: 70-86%, I²=15.5%). Comparative data on R0 rates of patients who underwent pancreatectomy with and without NAT showed a significant difference in favor of the former group with moderate statistical heterogeneity (Relative risk=1.21; 95% CI: 0.776-1.915; I²=48.0%). The median 1-, 2-, 3-, and 5-year survival rates of patients who had AR were 92.3% (range: 72.7-100%), 64.8% (range: 25-78.8%), 51.6% (range: 16.7-63.6%), and 14% (range: 0-41.1%), respectively. Data on median progression-free survival ranged from 5.25 to 36.3 months, and the median overall survival ranged from 17 to 44.9 months.
CONCLUSIONS
Pancreatectomy with major AR following NAT has the potential to enhance the survival rate of patients with unresectable pancreatic cancer involving the arteries by achieving R0 resection, despite a significant risk of postoperative complications. However, to validate the feasibility and effectiveness of this procedure, prospective controlled studies are necessary to address limitations arising from small sample sizes and potential biases inherent in retrospective studies.
Topics: Humans; Pancreatectomy; Neoadjuvant Therapy; Prospective Studies; Retrospective Studies; Pancreatic Neoplasms; Arteries; Neoplasms, Second Primary
PubMed: 38259002
DOI: 10.1097/JS9.0000000000000742 -
Indian Journal of Cancer 2022Patients with ductal adenocarcinoma of the body and tail of the pancreas usually remain asymptomatic until late in the course of the disease, and the survival of such... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Patients with ductal adenocarcinoma of the body and tail of the pancreas usually remain asymptomatic until late in the course of the disease, and the survival of such patients depends on multiple factors, which may affect the therapeutic approach and patient survival. Hence, the aim of this study was to investigate such risk factors by pooling various available studies.
METHODS
A systematic review was conducted according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines between January 1, 2007, and December 31, 2016, using the following databases: Medline, Scopus, the Cochrane Library, and Google Scholar. Studies were selected according to the predesigned eligibility criteria, and information was extracted for demographics, clinical features, and survival outcomes. Data were pooled using fixed- or random-effects models.
RESULTS
Sixteen studies were included (5,660 patients) with a median age of 64.8 years and a median survival of 28.5 (range 13-38) months. Identified significant factors for overall survival were higher age (hazard ratio [HR] = 1.211), men (HR = 1.182), presence of lymph node metastasis (HR = 1.964), multivisceral resection (HR = 1.947), N stage (1 versus 0; HR = 1.601), surgical margin (R0 versus No R0; HR = 0.519) and tumor size (>3 cm; HR = 1.890).
CONCLUSION
The pooled results of this study revealed several risk factors for overall survival in patients with left-sided pancreatic cancer.
Topics: Male; Humans; Infant; Child, Preschool; Prognosis; Pancreatic Neoplasms; Margins of Excision; Lymphatic Metastasis
PubMed: 36412310
DOI: 10.4103/ijc.IJC_1150_20 -
Cureus Jun 2021Over the years, the world has witnessed many advances in diagnosing and treating multiple types of cancers. These breakthroughs have revolutionized the understanding of... (Review)
Review
Over the years, the world has witnessed many advances in diagnosing and treating multiple types of cancers. These breakthroughs have revolutionized the understanding of the molecular drive behind these neoplasms, leading to tangible therapeutic evolution and promising prognostic implications. However, pancreatic cancer remains a highly lethal disease. With recent discoveries, modern medicine has been able to delineate histopathologic subtypes of pancreatic cancer in hopes of improved diagnosis and treatment to improve survival. A once vague entity, clear cell adenocarcinoma of the pancreas, in particular, has been better characterized on a histopathological and molecular level over the past two decades. With novel technological support, this disease has become less inconspicuous, and more researchers have reported its occurrence. Its diagnosis relies heavily on a mix of histological and immunohistochemical clues such as a clear cell cytoplasm and positivity for cytokeratins and other markers. However, new molecular markers, such as hepatocyte nuclear factor 1 beta, have been associated with this entity and may aid in further diagnostic and therapeutic strategies. This review article aims to portray how the identification and description of clear cell adenocarcinoma of the pancreas have evolved over the past few decades and how this may impact future treatment strategies.
PubMed: 34150416
DOI: 10.7759/cureus.15668 -
Updates in Surgery Jun 2021The treatment of periampullary and pancreatic head neoplasms is evolving. While minimally invasive Pancreaticoduodenectomy (PD) has gained worldwide interest, there has... (Meta-Analysis)
Meta-Analysis
The treatment of periampullary and pancreatic head neoplasms is evolving. While minimally invasive Pancreaticoduodenectomy (PD) has gained worldwide interest, there has been a debate on its related outcomes. The purpose of this paper was to provide an updated evidence comparing short-term surgical and oncologic outcomes within Open Pancreaticoduodenectomy (OpenPD), Laparoscopic Pancreaticoduodenectomy (LapPD), and Robotic Pancreaticoduodenectomy (RobPD). MEDLINE, Web of Science, PubMed, Cochrane Central Library, and ClinicalTrials.gov were referred for systematic search. A Bayesian network meta-analysis was executed. Forty-one articles (56,440 patients) were included; 48,382 (85.7%) underwent OpenPD, 5570 (9.8%) LapPD, and 2488 (4.5%) RobPD. Compared to OpenPD, LapPD and RobPD had similar postoperative mortality [Risk Ratio (RR) = 1.26; 95%CrI 0.91-1.61 and RR = 0.78; 95%CrI 0.54-1.12)], clinically relevant (grade B/C) postoperative pancreatic fistula (POPF) (RR = 1.12; 95%CrI 0.82-1.43 and RR = 0.87; 95%CrI 0.64-1.14, respectively), and severe (Clavien-Dindo ≥ 3) postoperative complications (RR = 1.03; 95%CrI 0.80-1.46 and RR = 0.93; 95%CrI 0.65-1.14, respectively). Compared to OpenPD, both LapPD and RobPD had significantly reduced hospital length-of-stay, estimated blood loss, infectious, pulmonary, overall complications, postoperative bleeding, and hospital readmission. No differences were found in the number of retrieved lymph nodes and R0. OpenPD, LapPD, and RobPD seem to be comparable across clinically relevant POPF, severe complications, postoperative mortality, retrieved lymphnodes, and R0. LapPD and RobPD appears to be safer in terms of infectious, pulmonary, and overall complications with reduced hospital readmission We advocate surgeons to choose their preferred surgical approach according to their expertise, however, the adoption of minimally invasive techniques may possibly improve patients' outcomes.
Topics: Bayes Theorem; Humans; Laparoscopy; Network Meta-Analysis; Pancreatic Neoplasms; Pancreaticoduodenectomy; Postoperative Complications; Robotic Surgical Procedures
PubMed: 33315230
DOI: 10.1007/s13304-020-00916-1 -
HPB : the Official Journal of the... Aug 2016Pancreatic ductal adenocarcinoma (PDAC) continues to be associated with a poor prognosis. This systematic review aimed to summarize the literature regarding potential... (Review)
Review
BACKGROUND
Pancreatic ductal adenocarcinoma (PDAC) continues to be associated with a poor prognosis. This systematic review aimed to summarize the literature regarding potential prognostic biomarkers to facilitate validation studies and clinical application.
METHODS
A systematic review was performed (2004-2014) according to PRISMA guidelines. Studies were ranked using REMARK criteria and the following outcomes were examined: overall/disease free survival, nodal involvement, tumour characteristics, metastasis, recurrence and resectability.
RESULTS
256 biomarkers were identified in 158 studies. 171 biomarkers were assessed with respect to overall survival: urokinase-type plasminogen activator receptor, atypical protein kinase C and HSP27 ranked the highest. 33 biomarkers were assessed for disease free survival: CD24 and S100A4 were the highest ranking. 17 biomarkers were identified for lymph node involvement: Smad4/Dpc4 and FOXC1 ranked highest. 13 biomarkers were examined for tumour grade: mesothelin and EGFR were the highest ranking biomarkers. 10 biomarkers were identified for metastasis: p16 and sCD40L were the highest ranking. 4 biomarkers were assessed resectability: sCD40L, s100a2, Ca 19-9, CEA.
CONCLUSION
This review has identified and ranked specific biomarkers that should be a primary focus of ongoing validation and clinical translational work in PDAC.
Topics: Biomarkers, Tumor; Carcinoma, Pancreatic Ductal; Disease Progression; Disease-Free Survival; Humans; Lymphatic Metastasis; Neoplasm Grading; Neoplasm Recurrence, Local; Pancreatectomy; Pancreatic Neoplasms; Predictive Value of Tests; Risk Factors; Time Factors; Treatment Outcome
PubMed: 27485059
DOI: 10.1016/j.hpb.2016.05.004 -
ESMO Open Apr 2023Germline BRCA1 and BRCA2 mutations (gBRCAm) can inform pancreatic cancer (PC) risk and treatment but most of the available information is derived from white patients.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Germline BRCA1 and BRCA2 mutations (gBRCAm) can inform pancreatic cancer (PC) risk and treatment but most of the available information is derived from white patients. The ethnic and geographic variability of gBRCAm prevalence and of germline BRCA (gBRCA) testing uptake in PC globally is largely unknown.
MATERIALS AND METHODS
We carried out a systematic review and prevalence meta-analysis of gBRCA testing and gBRCAm prevalence in PC patients stratified by ethnicity. The main outcome was the distribution of gBRCA testing uptake across diverse populations worldwide. Secondary outcomes included: geographic distribution of gBRCA testing uptake, temporal analysis of gBRCA testing uptake in ethnic groups, and pooled proportion of gBRCAm stratified by ethnicity. The study is listed under PROSPERO registration number #CRD42022311769.
RESULTS
A total of 51 studies with 16 621 patients were included. Twelve of the studies (23.5%) enrolled white patients only, 10 Asians only (19.6%), and 29 (56.9%) included mixed populations. The pooled prevalence of white, Asian, African American, and Hispanic patients tested per study was 88.7%, 34.8%, 3.6%, and 5.2%, respectively. The majority of included studies were from high-income countries (HICs) (64; 91.2%). Temporal analysis showed a significant increase only in white and Asians patients tested from 2000 to present (P < 0.001). The pooled prevalence of gBRCAm was: 3.3% in white, 1.7% in Asian, and negligible (<0.3%) in African American and Hispanic patients.
CONCLUSIONS
Data on gBRCA testing and gBRCAm in PC derive mostly from white patients and from HICs. This limits the interpretation of gBRCAm for treating PC across diverse populations and implies substantial global and racial disparities in access to BRCA testing in PC.
Topics: Humans; BRCA2 Protein; Genetic Testing; Pancreatic Neoplasms; Mutation
PubMed: 36822114
DOI: 10.1016/j.esmoop.2023.100881 -
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 -
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 -
Hormones & Cancer Aug 2012Recent epidemiological studies suggest that treatment with insulin may promote cancer growth. The present systematic review and meta-analysis of published observational... (Meta-Analysis)
Meta-Analysis Review
Recent epidemiological studies suggest that treatment with insulin may promote cancer growth. The present systematic review and meta-analysis of published observational studies was conducted to assess the risk of cancer during treatment with insulin. A search of online database through January 2011 was performed and examined the reference lists of pertinent articles, limited to observational studies in humans. Pooled relative risks (RRs) and 95% confidence intervals (CIs) were calculated with a random-effects model. Fifteen studies (five case-control and ten cohort studies) were included, with 562,043 participants and 14,085 cases of cancer. Insulin treatment was associated with an increased risk of overall cancer [summary RR (95% CI)=1.39 (1.14, 1.70)]. Summary RR (9% CI) for case-control studies was 1.83 (0.99, 3.38), whereas RR for cohort studies was 1.28 (1.03, 1.59). These results were consistent between studies conducted in the USA and in Europe. For studies that included combined type 1 and 2 diabetes, the summary estimate was stronger than studies including only type 2 diabetes mellitus. The association between insulin treatment and cancer was stronger for pancreatic cancer [summary RR (95% CI)=4.78 (3.12, 7.32)] than for colorectal cancer [1.50 (1.08, 2.08)]. Insulin treatment was not associated with breast, prostate, and hepatocelluar cancer, and their effect estimates were not statistically significant. Our findings support an association between insulin use and increased risk of overall, pancreatic, and colorectal cancer.
Topics: Adult; Aged; Aged, 80 and over; Case-Control Studies; Cell Growth Processes; Cohort Studies; Diabetes Mellitus, Type 2; Female; Humans; Insulin; Male; Middle Aged; Neoplasms; Risk Factors; Young Adult
PubMed: 22528451
DOI: 10.1007/s12672-012-0112-z -
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