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Pancreatology : Official Journal of the... Nov 2022Pancreatic cancer has a dismal prognosis. So far, imaging has been proven incapable of establishing an early enough diagnosis. Thus, biomarkers are urgently needed for... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND AIMS
Pancreatic cancer has a dismal prognosis. So far, imaging has been proven incapable of establishing an early enough diagnosis. Thus, biomarkers are urgently needed for early detection and improved survival. Our aim was to evaluate the pooled diagnostic performance of DNA alterations in pancreatic juice.
METHODS
A systematic literature search was performed in EMBASE, MEDLINE Ovid, Cochrane CENTRAL and Web of Science for studies concerning the diagnostic performance of DNA alterations in pancreatic juice to differentiate patients with high-grade dysplasia or pancreatic cancer from controls. Study quality was assessed using QUADAS-2. The pooled prevalence, sensitivity, specificity and diagnostic odds ratio were calculated.
RESULTS
Studies mostly concerned cell-free DNA mutations (32 studies: 939 cases, 1678 controls) and methylation patterns (14 studies: 579 cases, 467 controls). KRAS, TP53, CDKN2A, GNAS and SMAD4 mutations were evaluated most. Of these, TP53 had the highest diagnostic performance with a pooled sensitivity of 42% (95% CI: 31-54%), specificity of 98% (95%-CI: 92%-100%) and diagnostic odds ratio of 36 (95% CI: 9-133). Of DNA methylation patterns, hypermethylation of CDKN2A, NPTX2 and ppENK were studied most. Hypermethylation of NPTX2 performed best with a sensitivity of 39-70% and specificity of 94-100% for distinguishing pancreatic cancer from controls.
CONCLUSIONS
This meta-analysis shows that, in pancreatic juice, the presence of distinct DNA mutations (TP53, SMAD4 or CDKN2A) and NPTX2 hypermethylation have a high specificity (close to 100%) for the presence of high-grade dysplasia or pancreatic cancer. However, the sensitivity of these DNA alterations is poor to moderate, yet may increase if they are combined in a panel.
Topics: Humans; Biomarkers, Tumor; Carcinoma, Pancreatic Ductal; Early Detection of Cancer; Mutation; Pancreatic Juice; Pancreatic Neoplasms
PubMed: 35864067
DOI: 10.1016/j.pan.2022.06.260 -
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 -
BMC Pediatrics Oct 2023Shwachman-Diamond syndrome (SDS) is an autosomal recessive disease which results in inherited bone marrow failure (IBMF) and is characterized by exocrine pancreatic...
BACKGROUND
Shwachman-Diamond syndrome (SDS) is an autosomal recessive disease which results in inherited bone marrow failure (IBMF) and is characterized by exocrine pancreatic dysfunction and diverse clinical phenotypes. In the present study, we reviewed the internationally published reports on SDS patients, in order to summarize the clinical features, epidemiology, and treatment of SDS.
METHODS
We searched the WangFang and China National Knowledge Infrastructure databases with the keywords "Shwachman-Diamond syndrome," "SDS," "SBDS gene" and "inherited bone marrow failure" for relevant articles published from January 2002 to October 2022. In addition, studies published from January 2002 to October 2022 were searched from the Web of Science, PubMed, and MEDLINE databases, using "Shwachman-diamond syndrome" as the keyword. Finally, one child with SDS treated in Tongji Hospital was also included.
RESULTS
The clinical features of 156 patients with SDS were summarized. The three major clinical features of SDS were found to be peripheral blood cytopenia (96.8%), exocrine pancreatic dysfunction (83.3%), and failure to thrive (83.3%). The detection rate of SDS mutations was 94.6% (125/132). Mutations in SBDS, DNAJC21, SRP54, ELF6, and ELF1 have been reported. The male-to-female ratio was approximately 1.3/1. The median age of onset was 0.16 years, but the diagnostic age lagged by a median age of 1.3 years.
CONCLUSIONS
Pancreatic exocrine insufficiency and growth failure were common initial symptoms. SDS onset occurred early in childhood, and individual differences were obvious. Comprehensive collection and analysis of case-related data can help clinicians understand the clinical characteristics of SDS, which may improve early diagnosis and promote effective clinical intervention.
Topics: Female; Humans; Infant; Male; Bone Marrow Diseases; Exocrine Pancreatic Insufficiency; Mutation; Phenotype; Shwachman-Diamond Syndrome; Signal Recognition Particle
PubMed: 37803383
DOI: 10.1186/s12887-023-04324-3 -
Medical Oncology (Northwood, London,... May 2017Neoadjuvant treatment in non-metastatic pancreatic cancer (PaC) has the theoretical advantages of downstaging the tumor, sterilizing any present systemic undetectable... (Meta-Analysis)
Meta-Analysis Review
Neoadjuvant treatment in non-metastatic pancreatic cancer (PaC) has the theoretical advantages of downstaging the tumor, sterilizing any present systemic undetectable disease, selecting patients for surgery and administering therapy to each patient. The aim of this systematic review is to analyze the state of the art on neoadjuvant protocols for non-metastatic PaC. A literature search over the last 10 years was conducted, and papers had to be focused on resectable, borderline resectable (BLR) or locally advanced (LA) histo- or cytologically proven PaC; to be prospective studies or prospectively collected databases; to report percentage of protocol achievement and survival data at least in an intention-to-treat (ITT) analysis. Twelve studies were eligible for systematic review. Studies included a total of 624 patients: 248 resectable, 268 BLR, 71 LA and 37 non-specified. All studies were included for meta-analysis. ITT overall survival (OS) was 16.7 months (95% CI 15.16-18.26 months); for resected patients OS was 22.78 months (95% CI 20.42-25.16), and for eventually non-resected patients it was 9.89 months (95% CI 8.84-10.96). Neoadjuvant approaches for resectable, BLR and LA PaC are spreading. Outcomes tend to be better outside an RCT context, but strong evidences are lacking. Actually such treatments should be performed only in a randomized clinical trial setting.
Topics: Evidence-Based Medicine; Humans; Neoadjuvant Therapy; Pancreatectomy; Pancreatic Neoplasms
PubMed: 28391577
DOI: 10.1007/s12032-017-0951-0 -
Annals of the Royal College of Surgeons... Jul 2012The terms 'enhanced recovery after surgery', 'enhanced recovery programme' (ERP) and 'fast track surgery' refer to multimodal strategies aiming to streamline... (Review)
Review
INTRODUCTION
The terms 'enhanced recovery after surgery', 'enhanced recovery programme' (ERP) and 'fast track surgery' refer to multimodal strategies aiming to streamline peri-operative care pathways, to maximise effectiveness and minimise costs. While the results of ERP in colorectal surgery are well reported, there have been no reviews examining if these concepts could be applied safely to hepatopancreatobiliary (HPB) surgery. The aim of this systematic review was to appraise the current evidence for ERP in HPB surgery.
METHODS
A MEDLINE ® literature search was undertaken using the keywords 'enhanced recovery', 'fast-track', 'peri-operative', 'surgery', 'pancreas' and 'liver' and their derivatives such as 'pancreatic' or 'hepatic'. The primary endpoint was length of post-operative hospital stay. Secondary endpoints were morbidity, mortality and readmission rate.
RESULTS
Ten articles were retrieved describing an ERP. ERP protocols varied slightly between studies. A reduction in length of stay was a consistent finding following the incorporation of ERP when compared with historical controls. This was not at the expense of increased rates of readmission, morbidity or mortality in any study.
CONCLUSIONS
The introduction of an ERP in HPB surgery appears safe and feasible. Currently, many of the principles of the multimodal pathway are derived from the colorectal ERP and distinct differences exist, which may impede its implementation in HPB surgery.
Topics: Bile Duct Diseases; Bile Ducts; Clinical Protocols; Convalescence; Humans; Length of Stay; Liver; Liver Diseases; Pancreas; Pancreatic Diseases; Perioperative Care
PubMed: 22943226
DOI: 10.1308/003588412X13171221592410 -
Injury Sep 2021Blunt abdominal trauma is the major cause of abdominal injury in children. No clear guidelines exist for the initial management of blunt pancreatic trauma in children.... (Meta-Analysis)
Meta-Analysis
AIM
Blunt abdominal trauma is the major cause of abdominal injury in children. No clear guidelines exist for the initial management of blunt pancreatic trauma in children. The aim of this study was to perform a systematic review and meta-analysis of initially non-operative versus initially operative treatment in children with blunt pancreatic injury.
METHODS
Studies including children (<18 years) with blunt pancreatic injuries published in any language after year 1990 were included. Total of 849 studies were identified by searching PubMed, Scopus, CINAHL and Cochrane Database. After review, 42 studies met inclusion criteria and were included in this systematic review. There were 1754 patients, of whom 1095 were initially managed non-operatively (NOM), and 659 operatively (OM). Primary outcome was non-operative management success rate, and secondary outcomes were mortality, complications (including specifically pseudocysts and pancreatic fistulas), percent of patients and days on total parenteral nutrition (TPN), length of hospital stay and readmissions.
RESULTS
There was no difference in mortality between NOM and OM groups. The incidence of pseudocysts was significantly higher in NOM group compared to OM (P<0.001), especially for AAST grade III or higher (P<0.00001). Overall incidence of pancreatic fistulas was significantly lower for NOM group (p = 0.02) but no difference was observed for AAST grades III or higher (p = 0.49). There was no difference in the length of hospital stay (P = 0.31). Duration of total parenteral nutrition was not different for all AAST grades (P = 0.35), but was significantly shorter for OM group for AAST grades III and higher (p = 0.0001). There was no overall difference in readmissions (P = 0.94). Overall success rate of initial non-operative treatment was 87%.
CONCLUSIONS
Most patients with pancreatic trauma can initially be treated non-operatively, while early surgical treatment may benefit patients with lesions of the main pancreatic duct. ERCP offers both highly accurate diagnosis and potential treatment of ductal injuries.
Topics: Abdominal Injuries; Child; Humans; Injury Severity Score; Pancreas; Pancreatic Diseases; Retrospective Studies; Treatment Outcome; Wounds, Nonpenetrating
PubMed: 32089286
DOI: 10.1016/j.injury.2020.02.035 -
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 -
Journal of Gastrointestinal Surgery :... Sep 2021Exocrine pancreatic insufficiency (EPI) occurs when pancreatic enzyme activity in the intestinal lumen is insufficient for normal digestion to occur. The true incidence...
BACKGROUND
Exocrine pancreatic insufficiency (EPI) occurs when pancreatic enzyme activity in the intestinal lumen is insufficient for normal digestion to occur. The true incidence and diagnosis of EPI after pancreatectomy has not been fully understood and optimized. The aim of this study was to present incidence and diagnostic criteria for EPI after pancreatectomy for cancer and provide a guide for management and optimal therapy in pancreatectomy patients with cancer.
METHODS
A comprehensive review of the literature with publication dates from 2014 to 2019 was performed. A comprehensive diagnostic and treatment algorithm was then created based on literature review and current treatment options.
RESULTS
In total, 30 studies were included, 19 combined both pancreaticoduodenectomy (PD) and distal pancreatectomy (DP), 9 for central pancreatectomy, and 2 others. EPI was defined subjectively without definitive testing using any of the established diagnostic studies in the majority of studies 23 (76%). Preoperative EPI was calculated to be 11.52%. Most studies assessed exocrine function at least 6 months postoperatively with four studies extending the follow-up period beyond 12 months. EPI diagnosed postoperatively at 1 month (40.27%), 3 months (30.94%), 6 months (36.06%), and 12 months (34.69%). After PD, the median prevalence of postoperative EPI was 43.14%, CP, the median prevalence was 4.85%, DP, median prevalence of postoperative EPI of 11.94%.
CONCLUSION
EPI is a frequent outcome that is often misdiagnosed or under-reported by the patient post-pancreatectomy. Given the increasing overall survival in pancreatectomy patients for cancer, surgeon awareness and assessment is critical to improving patients' overall quality of life.
Topics: Exocrine Pancreatic Insufficiency; Humans; Pancreatectomy; Pancreatic Neoplasms; Postoperative Complications; Quality of Life
PubMed: 33483914
DOI: 10.1007/s11605-020-04883-1 -
Asian Pacific Journal of Cancer... 2014This study aimed to summarize published epidemiological evidence for the relationship between pancreatitis and subsequent risk of pancreatic cancer (PC). We searched... (Review)
Review
This study aimed to summarize published epidemiological evidence for the relationship between pancreatitis and subsequent risk of pancreatic cancer (PC). We searched Medline and Embase for epidemiological studies published by February 5th, 2014 examining the risk of PC in pancreatitis patients using highly inclusive algorithms. Information about first author, year of publication, country of study, recruitment period, type of pancreatitis, study design, sample size, source of controls and attained age of subjects were extracted by two researchers and Stata 11.0 was used to perform the statistical analyses and examine publication bias. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated with the random effects model. A total of 17 articles documenting 3 cohort and 14 case-control studies containing 14,667 PC cases and 17,587 pancreatitis cases were included in this study. The pooled OR between pancreatitis and PC risk was 7.05 (95%CI: 6.42-7.75). However, the pooled ORs of case-control and cohort studies were 4.62 (95%CI: 4.08-5.22) and 16.3 (95%CI: 14.3-18.6) respectively. The risk of PC was the highest in patients with chronic pancreatitis (pooled OR=10.35; 95%CI: 9.13-11.75), followed by unspecified type of pancreatitis (pooled OR=6.41; 95%CI: 4.93-8.34), both acute and chronic pancreatitis (pooled OR=6.13; 95%CI: 5.00-7.52), and acute pancreatitis (pooled OR=2.12; 95%CI: 1.59-2.83). The pooled OR of PC in pancreatitis cases diagnosed within 1 year was the highest (pooled OR=23.3; 95%CI: 14.0-38.9); and the risk in subjects diagnosed with pancreatitis for no less than 2, 5 and 10 years were 3.03 (95%CI: 2.41-3.81), 2.82 (95%CI: 2.12-3.76) and 2.25 (95%CI: 1.59-3.19) respectively. Pancreatitis, especially chronic pancreatitis, was associated with a significantly increased risk of PC; and the risk decreased with increasing duration since diagnosis of pancreatitis.
Topics: China; Epidemiologic Studies; Humans; Pancreatic Neoplasms; Pancreatitis; Prognosis; Risk Factors
PubMed: 24998582
DOI: 10.7314/apjcp.2014.15.12.5029 -
Medicine Jul 2022Clinically relevant postoperative pancreatic fistula (CR-POPF) is a common and troublesome complication after pancreatoduodenectomy (PD). We conducted a systematic... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Clinically relevant postoperative pancreatic fistula (CR-POPF) is a common and troublesome complication after pancreatoduodenectomy (PD). We conducted a systematic review and meta-analysis to identify the risk factors of CR-POPF after PD.
METHODS
We searched PubMed, EMBASE, and Cochrane Library databases for studies related to risk factors of CR-POPF after PD. Odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were extracted from the included studies, then a meta-analysis was conducted. If necessary, sensitivity analysis would be performed by changing the effect model or excluding 1 study at a time. Publication bias was assessed by funnel plot and Begg test and Egger test.
RESULTS
A total of 27 studies with 24,740 patients were included, and CR-POPF occurred in 3843 patients (incidence = 17%, 95% CI: 16%-19%). Male (OR = 1.56, 95% CI: 1.42-1.70), body mass index >25 kg/m2 (OR = 1.98, 95% CI: 1.23-3.18), pancreatic duct diameter <3 mm (OR = 1.87, 95% CI: 1.66-2.12), soft pancreatic texture (OR = 3.49, 95% CI: 2.61-4.67), and blood transfusion (OR = 3.10, 95% CI: 2.01-4.77) can significantly increase the risk of CR-POPF. Pancreatic adenocarcinoma (OR = 0.54, 95% CI: 0.47-0.61), vascular resection (OR = 0.57, 95% CI: 0.39-0.83), and preoperative chemoradiotherapy (OR = 0.68, 95% CI: 0.57-0.81) can significantly decrease the factor of CR-POPF. Diabetes mellitus was not statistically associated with CR-POPF (OR = 0.66, 95% CI: 0.40-1.08). However, the analysis of body mass index, pancreatic texture, and diabetes mellitus had a high heterogeneity, then sensitivity analysis was performed, and the result after sensitivity analysis showed diabetes mellitus can significantly decrease the risk of CR-POPF. There was no significant publication bias in this meta-analysis.
CONCLUSIONS
The current review assessed the effects of different factors on CR-POPF. This can provide a basis for the prevention and management of CR-POPF. Effective interventions targeting the above risk factors should be investigated in future studies for decreasing the occurrence of CR-POPF.
Topics: Adenocarcinoma; Humans; Male; Pancreatic Fistula; Pancreatic Neoplasms; Pancreaticoduodenectomy; Postoperative Complications; Retrospective Studies; Risk Factors
PubMed: 35776984
DOI: 10.1097/MD.0000000000029757