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Abdominal Radiology (New York) Sep 2022Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of cancer-related death with a 5-year survival rate of 10%. Quantitative CT perfusion (CTP) can... (Review)
Review
Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of cancer-related death with a 5-year survival rate of 10%. Quantitative CT perfusion (CTP) can provide additional diagnostic information compared to the limited accuracy of the current standard, contrast-enhanced CT (CECT). This systematic review evaluates CTP for diagnosis, grading, and treatment assessment of PDAC. The secondary goal is to provide an overview of scan protocols and perfusion models used for CTP in PDAC. The search strategy combined synonyms for 'CTP' and 'PDAC.' Pubmed, Embase, and Web of Science were systematically searched from January 2000 to December 2020 for studies using CTP to evaluate PDAC. The risk of bias was assessed using QUADAS-2. 607 abstracts were screened, of which 29 were selected for full-text eligibility. 21 studies were included in the final analysis with a total of 760 patients. All studies comparing PDAC with non-tumorous parenchyma found significant CTP-based differences in blood flow (BF) and blood volume (BV). Two studies found significant differences between pathological grades. Two other studies showed that BF could predict neoadjuvant treatment response. A wide variety in kinetic models and acquisition protocol was found among included studies. Quantitative CTP shows a potential benefit in PDAC diagnosis and can serve as a tool for pathological grading and treatment assessment; however, clinical evidence is still limited. To improve clinical use, standardized acquisition and reconstruction parameters are necessary for interchangeability of the perfusion parameters.
Topics: Carcinoma, Pancreatic Ductal; Humans; Pancreatic Neoplasms; Perfusion Imaging; Tomography, X-Ray Computed
PubMed: 34223961
DOI: 10.1007/s00261-021-03190-w -
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 -
Cancer Reports (Hoboken, N.J.) Oct 2021While adjuvant chemotherapy benefits patients with pancreatic ductal adenocarcinoma (PDAC), the importance of the time to initiation of adjuvant therapy remains unclear. (Meta-Analysis)
Meta-Analysis
BACKGROUND
While adjuvant chemotherapy benefits patients with pancreatic ductal adenocarcinoma (PDAC), the importance of the time to initiation of adjuvant therapy remains unclear.
AIM
This study seeks to better understand whether the timing of postoperative chemotherapy initiation affects long-term outcomes in PDAC.
METHODS AND RESULTS
A systematic literature search was performed in Medline, Embase, and Cochrane Library in March 2020. Studies focused on the association between the timing of adjuvant therapy on long-term outcomes in resected PDAC patients were included. The impact of early and delayed therapy as defined by the respective studies was evaluated using forest plot analysis. Overall survival (OS) and disease-free survival (DFS) served as primary endpoints. Out of 3099 published articles, 10 retrospective studies met inclusion criteria. Combined, these studies included clinical data of 13 344 patients. The cut off used to define "early" and "delayed" treatment groups varied in the included studies ranging from 3 to 12 weeks. Due to this heterogeneity, a sub-group analysis of three time cut offs was performed: 3 to 5 weeks, 6 to 8 weeks, and 9 to 12 weeks. There was a significant decrease in OS and DFS when adjuvant therapy was delayed by 3 to 5 weeks after surgery (OS, pooled hazard ratio [HR] = 1.86, 95% confidence interval [CI] = 1.25-2.78; DFS, pooled HR = 1.62, 95% CI = 1.12-2.34). However, due to small sample size and limited studies in this subgroup analysis, the results may be indeterminate. There was no significant decrease in OS with delayed initiation of adjuvant therapy by 6 to 8 weeks and 9 to 12 weeks. Similarly, delay in adjuvant therapy beyond 3-5 weeks.
CONCLUSIONS
There was no conclusive evidence suggesting improved survival in patients starting treatment at various time cut offs. Studies investigating the extreme ends of the time-to-treatment spectrum may prove more informative.
Topics: Chemotherapy, Adjuvant; Humans; Pancreatic Neoplasms; Prognosis; Survival Rate; Time-to-Treatment
PubMed: 34245139
DOI: 10.1002/cnr2.1390 -
Cureus Aug 2023Pancreatic ductal adenocarcinoma (PDAC) is a significant challenge due to its silent progression and well-advanced, unresectable, complicated presentation. Detecting... (Review)
Review
Pancreatic ductal adenocarcinoma (PDAC) is a significant challenge due to its silent progression and well-advanced, unresectable, complicated presentation. Detecting this disease early on is crucial, and researchers have been investigating various potential biological markers, such as carbohydrate antigen 19-9 (CA 19-9), hoping to find indicators that can aid in its early detection. The primary focus of this review is on the diagnostic usefulness of CA 19-9 in detecting pancreatic cancer (PC) in the beginning stage and its usefulness in predicting progression. The database search of articles from PubMed, PMC, the Cochrane Library, and Google Scholar identified 227 articles published from 2013 to 2023. The keyword mix used in the search technique included terms like "CA 19-9," "pancreatic cancer," "diagnosis," and "early detection." This study provides evidence of CA 19-9's ability in detecting PDAC in the pre-diagnostic stage. But since the outcomes were inconsistent among the included trials, further analysis is required to develop standardized diagnostic criteria and methodologies. Furthermore, because of the variability of the study, it is not easy to make firm conclusions on CA 19-9's sensitivity as well as specificity in the first stage of pancreatic neoplasm. This in-depth overview of the available literature provides new insights into using CA 19-9 as a biological marker for detecting undiagnosed PC before progressing into the advanced stage, and was proven beneficial. However, this has to be shown in broader research with adequate sample size. Although it shows promise as a diagnostic tool, further study is required to confirm these findings.
PubMed: 37671217
DOI: 10.7759/cureus.44382 -
Cancers Apr 2019The tumor microenvironment plays an important role in the initiation and progression of pancreatic adenocarcinoma (PDAC). In this systematic review, we provide an... (Review)
Review
The tumor microenvironment plays an important role in the initiation and progression of pancreatic adenocarcinoma (PDAC). In this systematic review, we provide an overview of clinical trials with stroma-targeting agents. We systematically searched MEDLINE/PubMed and the EMBASE database, using the PRISMA guidelines, for eligible clinical trials. In total, 2330 records were screened, from which we have included 106 articles. A meta-analysis could be performed on 51 articles which describe the targeting of the vascular endothelial growth factor (VEGF) pathway, and three articles which describe the targeting of hyaluronic acid. Anti-VEGF therapies did not show an increase in median overall survival (OS) with combined hazard ratios (HRs) of 1.01 (95% confidence interval (CI) 0.90-1.13). Treatment with hyaluronidase PEGPH20 showed promising results, but, thus far, only in combination with gemcitabine and nab-paclitaxel in selected patients with hyaluronic acid (HA) tumors: An increase in median progression free survival (PFS) of 2.9 months, as well as a HR of 0.51 (95% CI 0.26-1.00). In conclusion, we found that anti-angiogenic therapies did not show an increased benefit in median OS or PFS in contrast to promising results with anti-hyaluronic acid treatment in combination with gemcitabine and nab-paclitaxel. The PEGPH20 clinical trials used patient selection to determine eligibility based on tumor biology, which underlines the importance to personalize treatment for pancreatic cancer patients.
PubMed: 31035512
DOI: 10.3390/cancers11050588 -
Cancers Apr 2021Major vascular invasion represents one of the most frequent reasons to consider pancreatic adenocarcinomas unresectable, although in the last decades, demolitive... (Review)
Review
BACKGROUND
Major vascular invasion represents one of the most frequent reasons to consider pancreatic adenocarcinomas unresectable, although in the last decades, demolitive surgeries such as distal pancreatectomy with celiac axis resection (DP-CAR) have become a therapeutical option.
METHODS
A meta-analysis of studies comparing DP-CAR and standard DP in patients with pancreatic adenocarcinoma was conducted. Moreover, a systematic review of studies analyzing oncological, postoperative and survival outcomes of DP-CAR was conducted.
RESULTS
Twenty-four articles were selected for the systematic review, whereas eleven were selected for the meta-analysis, for a total of 1077 patients. Survival outcomes between the two groups were similar in terms of 1 year overall survival (OS) (odds ratio (OR) 0.67, 95% confidence interval (CI) 0.34 to 1.31, = 0.24). Patients who received DP-CAR were more likely to have T4 tumors (OR 28.45, 95% CI 10.46 to 77.37, < 0.00001) and positive margins (R+) (OR 2.28, 95% CI 1.24 to 4.17, = 0.008). Overall complications (OR, 1.72, 95% CI, 1.15 to 2.58, = 0.008) were more frequent in the DP-CAR group, whereas rates of pancreatic fistula (OR 1.16, 95% CI 0.81 to 1.65, = 0.41) were similar.
CONCLUSIONS
DP-CAR was not associated with higher mortality compared to standard DP; however, overall morbidity was higher. Celiac axis involvement should no longer be considered a strict contraindication to surgery in patients with locally advanced pancreatic adenocarcinoma. Considering the different baseline tumor characteristics, DP-CAR may need to be compared with palliative therapies instead of standard DP.
PubMed: 33921838
DOI: 10.3390/cancers13081967 -
International Journal of Surgery... Nov 2023Hepatocellular carcinoma (HCC) is the third-most lethal malignant tumor worldwide. The rapid development of immunotherapy utilizing immune checkpoint inhibitors for... (Meta-Analysis)
Meta-Analysis
Clinico-characteristics of patients which correlated with preferable treatment outcomes in immunotherapy for advanced hepatocellular carcinoma: a systematic review and meta-analysis.
BACKGROUND AND AIMS
Hepatocellular carcinoma (HCC) is the third-most lethal malignant tumor worldwide. The rapid development of immunotherapy utilizing immune checkpoint inhibitors for advanced HCC patients has been witnessed in recent years, along with numerous randomized clinical trials demonstrating the survival benefits for these individuals. This systematic review and meta-analysis aimed to identify specific clinico-pathological characteristics of advanced HCC patients that may lead to preferable responses to immunotherapy in terms of overall survival (OS), progression-free survival (PFS), and objective response rate (ORR).
METHODS
The included clinical trials were retrieved from PubMed, Embase, the Cochrane library, and the Web of Science databases published in English between 1 January 2002 and 20 October 2022. A systematic review and meta-analysis for first-line and second-line phase II/III studies were conducted on immunotherapy for patients with advanced HCC by using OS as the primary outcome measure, and PFS and ORR as the secondary outcome measures to obtain clinico-pathological characteristics of patients which might be preferable responses to programmed death-1 (PD-1) and programmed cell death-Ligand 1 (PD-L1) inhibitors. Toxicity and specific treatment-related adverse events (TRAEs) were also determined.
RESULTS
After screening 1392 relevant studies, 12 studies were included in this systematic review and meta-analysis to include 5948 patients. Based on the analysis of interaction, the difference in OS after first-line immunotherapy between the subgroups of viral hepatitis [hazard ratio (HR)=0.73 vs 0.87, P for interaction=0.02] and macrovascular invasion and/or extrahepatic spread (HR=0.73 vs 0.89, P for interaction=0.02) were significant. The difference in PFS between the subgroups of viral hepatitis was highly significant (pooled HR=0.55 vs 0.81, P for interaction=0.007). After second-line immunotherapy, the difference in ORR between the subgroups of Barcelona Clinic Liver Cancer was significant (pooled ES=0.12 vs 0.23, P for interaction=0.04). Compared with PD-L1 inhibitors, PD-1 inhibitors may have a higher probability to cause TRAEs. Diarrhea, increased aspartate aminotransferase, and hypertension were the top three TRAEs.
CONCLUSIONS
This systematic review and meta-analysis represents the first pilot study aimed at identifying crucial clinico-pathological characteristics of patients with advanced HCC that may predict favorable treatment outcomes in terms of OS, PFS, and ORR to immunotherapy. Findings suggest that patients with viral hepatitis positivity (especially hepatitis B virus) and macrovascular invasion and/or extrahepatic spread may benefit more in OS when treated with PD-1/PD-L1 immune checkpoint inhibitors.
Topics: Humans; Carcinoma, Hepatocellular; B7-H1 Antigen; Immune Checkpoint Inhibitors; Pilot Projects; Programmed Cell Death 1 Receptor; Liver Neoplasms; Treatment Outcome; Immunotherapy; Hepatitis, Viral, Human; Lung Neoplasms
PubMed: 37598406
DOI: 10.1097/JS9.0000000000000652 -
HPB : the Official Journal of the... Nov 2013Ampullary adenocarcinoma is considered to have a better prognosis than either pancreatic or bile duct adenocarcinoma. Pancreaticoduodenectomy is associated with... (Review)
Review
BACKGROUND
Ampullary adenocarcinoma is considered to have a better prognosis than either pancreatic or bile duct adenocarcinoma. Pancreaticoduodenectomy is associated with significant mortality and morbidity. Some recent publications have advocated the use of endoscopic papillectomy for the treatment of early ampullary adenocarcinoma. This article reviews investigations and surgical treatment options of ampullary tumours.
METHODS
A systematic review of English-language articles was carried out using an electronic search of the Ovid MEDLINE (from 1996 onwards), PubMed and Cochrane Database of Systematic Reviews databases to identify studies related to the investigation and management of ampullary tumours.
RESULTS
Distinguishing between ampullary adenoma and adenocarcinoma is challenging given the inaccuracy of endoscopic biopsy, for which high false negative rates of 25-50% have been reported. Endoscopic ultrasound is the most accurate method for local staging of ampullary lesions, but distinguishing between T1 and T2 adenocarcinomas is difficult. Lymph node metastasis occurs early in the disease process; it is lowest for T1 tumours, but the risk is still high at 8-45%. Case reports of successful endoscopic resection and transduodenal ampullectomy of T1 adenocarcinomas have been published, but their duration of follow-up is limited.
CONCLUSIONS
Optimal staging should be used to distinguish between ampullary adenoma and adenocarcinoma. Pancreaticoduodenectomy remains the treatment of choice for all ampullary adenocarcinomas.
Topics: Adenocarcinoma; Ampulla of Vater; Biopsy; Cholangiopancreatography, Endoscopic Retrograde; Common Bile Duct Neoplasms; Endosonography; Humans; Image-Guided Biopsy
PubMed: 23458317
DOI: 10.1111/hpb.12038 -
PloS One 2020The real impact of specific sites of metastasis on prognosis of metastatic pancreatic cancer (MPC) is unknown. To evaluate the association of specific metastatic sites... (Meta-Analysis)
Meta-Analysis
The real impact of specific sites of metastasis on prognosis of metastatic pancreatic cancer (MPC) is unknown. To evaluate the association of specific metastatic sites and survival outcomes in MPC a systematic literature review was performed including prospective randomized trials of systemic treatments in metastatic pancreatic cancer indexed in PubMed, Embase and Web of Science. Data regarding systemic treatment regimens, progression free survival and overall survival were extracted. The outcomes were compared using a random effects model. The index I2 and the graphs of funnel plot were used for the interpretation of the data. Of 1,052 abstracts, 7 randomized trials were considered eligible with a combined sample size of 2,975 MPC patients. Combining the studies with meta-analysis, we could see that patients with liver metastasis had a HR for death of 1.53 with 95% CI of 1.15 to 2.02 (p-value 0.003) and HR for risk of progression of 1.96 with 95% CI of 1.28 to 2.99 (p-value 0.002), without significant heterogeneity. Having two or more sites of metastasis comparing to one site did not have impact on overall survival; RR of 1.05 with 95% CI 0.91 to 1.23 (p-value 0.493). In conclusion, liver metastasis confers worse outcomes among patients with MPC. Apparently, multiple metastatic sites do not present worse prognosis when compared with only one organ involved, therefore, demonstrating the severity of this disease. Prospective studies evaluating other treatments are necessary to address the impact of local treatments in liver metastasis in MPC.
Topics: Adenocarcinoma; Humans; Liver Neoplasms; Pancreatic Neoplasms; Prognosis; Prospective Studies; Randomized Controlled Trials as Topic; Survival Rate
PubMed: 32130264
DOI: 10.1371/journal.pone.0230060 -
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