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Annals of Surgical Oncology Jul 2023Pancreatic cancer often presents as locally advanced (LAPC) or borderline resectable (BRPC). Neoadjuvant systemic therapy is recommended as initial treatment. It is... (Meta-Analysis)
Meta-Analysis Review
FOLFIRINOX or Gemcitabine-based Chemotherapy for Borderline Resectable and Locally Advanced Pancreatic Cancer: A Multi-institutional, Patient-Level, Meta-analysis and Systematic Review.
BACKGROUND
Pancreatic cancer often presents as locally advanced (LAPC) or borderline resectable (BRPC). Neoadjuvant systemic therapy is recommended as initial treatment. It is currently unclear what chemotherapy should be preferred for patients with BRPC or LAPC.
METHODS
We performed a systematic review and multi-institutional meta-analysis of patient-level data regarding the use of initial systemic therapy for BRPC and LAPC. Outcomes were reported separately for tumor entity and by chemotherapy regimen including FOLFIRINOX (FIO) or gemcitabine-based.
RESULTS
A total of 23 studies comprising 2930 patients were analyzed for overall survival (OS) calculated from the beginning of systemic treatment. OS for patients with BRPC was 22.0 months with FIO, 16.9 months with gemcitabine/nab-paclitaxel (Gem/nab), 21.6 months with gemcitabine/cisplatin or oxaliplatin or docetaxel or capecitabine (GemX), and 10 months with gemcitabine monotherapy (Gem-mono) (p < 0.0001). In patients with LAPC, OS also was higher with FIO (17.1 months) compared with Gem/nab (12.5 months), GemX (12.3 months), and Gem-mono (9.4 months; p < 0.0001). This difference was driven by the patients who did not undergo surgery, where FIO was superior to other regimens. The resection rates for patients with BRPC were 0.55 for gemcitabine-based chemotherapy and 0.53 with FIO. In patients with LAPC, resection rates were 0.19 with Gemcitabine and 0.28 with FIO. In resected patients, OS for patients with BRPC was 32.9 months with FIO and not different compared to Gem/nab, (28.6 months, p = 0.285), GemX (38.8 months, p = 0.1), or Gem-mono (23.1 months, p = 0.083). A similar trend was observed in resected patients converted from LAPC.
CONCLUSIONS
In patients with BRPC or LAPC, primary treatment with FOLFIRINOX compared with Gemcitabine-based chemotherapy appears to provide a survival benefit for patients that are ultimately unresectable. For patients that undergo surgical resection, outcomes are similar between GEM+ and FOLFIRINOX when delivered in the neoadjuvant setting.
Topics: Humans; Gemcitabine; Antineoplastic Combined Chemotherapy Protocols; Oxaliplatin; Pancreatic Neoplasms; Fluorouracil; Leucovorin; Neoadjuvant Therapy; Paclitaxel; Multicenter Studies as Topic
PubMed: 37020094
DOI: 10.1245/s10434-023-13353-2 -
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 -
Cellular Oncology (Dordrecht) Feb 2023As a malignant tumor, pancreatic cancer has an extremely low overall 5-year survival rate. Pancreatic adenosquamous carcinoma (PASC), a rare pancreatic malignancy, owns... (Review)
Review
BACKGROUND
As a malignant tumor, pancreatic cancer has an extremely low overall 5-year survival rate. Pancreatic adenosquamous carcinoma (PASC), a rare pancreatic malignancy, owns clinical presentation similar to pancreatic ductal adenocarcinoma (PDAC), which is the most prevalent pancreatic cancer subtype. PASC is generally defined as a pancreatic tumor consisting mainly of adenocarcinoma tissue and squamous carcinoma tissue. Compared with PDAC, PASC has a higher metastatic potential and worse prognosis, and lacks of effective treatment options to date. However, the pathogenesis and treatment of PASC are not yet clear and are accompanied with difficulties.
CONCLUSION
The present paper systematically summarizes the possible pathogenesis, diagnosis methods, and further suggests potential new treatment directions through reviewing research results of PASC, including the clinical manifestations, pathological manifestation, the original hypothesis of squamous carcinoma and the potential regulatory mechanism. In short, the present paper provides a systematic review of the research progress and new ideas for the development mechanism and treatment of PASC.
Topics: Humans; Carcinoma, Adenosquamous; Pancreatic Neoplasms; Carcinoma, Pancreatic Ductal; Carcinoma, Squamous Cell; Adenocarcinoma
PubMed: 36316580
DOI: 10.1007/s13402-022-00732-2 -
Expert Opinion on Drug Safety Jun 2024The existing evidence from pre- and post-marketing studies is conflicting on the risk of pancreatic events for anti-diabetic medications. (Meta-Analysis)
Meta-Analysis
Risk of pancreatitis and pancreatic carcinoma for anti-diabetic medications: findings from real-world safety data analysis and systematic review and meta-analysis of randomized controlled trials.
BACKGROUND
The existing evidence from pre- and post-marketing studies is conflicting on the risk of pancreatic events for anti-diabetic medications.
RESEARCH DESIGN AND METHODS
A retrospective case/non-case study was conducted by using spontaneous reports on pancreatic events for anti-diabetic medications from the FDA Adverse Event Reporting System (FAERS) and VigiBase. Proportional Reporting Ratio (PRR), Reporting Odds Ratio (ROR), and Information Component (IC) were calculated by a disproportionality analysis. Furthermore, PubMed, Google Scholar, Scopus, and ClinicalTrials.gov were systematically searched for randomized controlled trials (RCTs) on anti-diabetic drugs with pancreatic outcomes.
RESULTS
The FAERS data analysis found strong signals on incretin mimetics causing pancreatic events, with sitagliptin having the highest risk [PRR = 24.2, lower bound (LB) ROR = 24.4, IC = 4.4 for pancreatitis, and PRR = 15.4, LB ROR = 14.9, IC = 3.8 for pancreatic carcinoma]. Empagliflozin was the most pancreatitis-risk sodium-glucose co-transporter-2 inhibitor [PRR = 4.0, LB ROR = 3.5, IC = 1.8]. VigiBase reiterated these findings and identified some new signals for novel anti-diabetics. Meta-analysis revealed that the incidence of pancreatitis and pancreatic carcinoma with anti-diabetic medications was insignificant. However, compared to the placebo/active comparator, gliptins had a higher risk of acute pancreatitis (OR 1.44; 95% CI 1.03, 2.01; = 0.03).
CONCLUSION
Evidence from the post-marketing safety data analysis identified a strong association between incretin mimetics and pancreatic events. Fewer events in RCTs may justify insignificant meta-analysis results.
Topics: Humans; Pancreatic Neoplasms; Pancreatitis; Randomized Controlled Trials as Topic; Hypoglycemic Agents; Adverse Drug Reaction Reporting Systems; Retrospective Studies; Risk; Sodium-Glucose Transporter 2 Inhibitors
PubMed: 37986140
DOI: 10.1080/14740338.2023.2284992 -
Surgical Oncology Sep 2022Surgical resection is feasible in a small proportion of patients with oligometastatic renal cell carcinoma (mRCC) involving the liver or pancreas. The aim of this study... (Review)
Review
Surgical resection is feasible in a small proportion of patients with oligometastatic renal cell carcinoma (mRCC) involving the liver or pancreas. The aim of this study was to evaluate the effect of liver and pancreatic resection or ablation for mRCC on survival and to identify factors associated with improved outcomes. A systematic search of the Medline and EMBASE databases was performed to identify studies reporting outcomes following hepatic or pancreatic resection or ablation for mRCC. The study was conducted according to PRISMA guidelines. A total of 35 studies reporting pancreatic resection outcomes and 14 studies reporting hepatic resection for mRCC were identified. There were no randomised controlled trials. Median overall survival (OS) following liver resection ranged from 16 to 142 months and 5-year OS from 14.7 to 62%. Following pancreatic resection, median OS ranged from 6 to 106 months and 5-year OS from 26 to 88%. Metachronous presentation and a longer DFI from resection of the primary tumour were associated with better survival outcomes. Mortality following liver and pancreatic resection was 2.7% and 4.2%, whilst significant morbidity (Clavien-Dindo Grade 3a or above) was reported in 20.9% and 25.4% of cases respectively. Liver or pancreatic resection or ablation for oligometastatic RCC may benefit a very select group of patients and they should be discussed within a hepatopancreatobiliary multidisciplinary tumour board meeting. Further studies are required to further define patients most likely to benefit, including potential utilization of molecular precision oncology strategies.
Topics: Carcinoma, Renal Cell; Humans; Kidney Neoplasms; Liver; Liver Neoplasms; Pancreas; Pancreatic Neoplasms; Precision Medicine
PubMed: 35940030
DOI: 10.1016/j.suronc.2022.101819 -
International Journal of Surgery... Nov 2019Previous studies have indicated that there may be a difference in tumor biology between intraductal papillary mucinous carcinoma (IPMC) and pancreatic ductal... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Previous studies have indicated that there may be a difference in tumor biology between intraductal papillary mucinous carcinoma (IPMC) and pancreatic ductal adenocarcinoma (PDAC). However, the data are still controversial. The aim of this systematic review and meta-analysis was to summarize and compare the outcome of IPMC and PDAC after surgical resection.
METHODS
Studies comparing IPMC and PDAC were identified using Medline and Embase search engines. Primary outcomes of interest were survival and recurrence. Secondary outcomes were clinicopathological characteristics. Meta-analysis of data was conducted using a random-effects model.
RESULTS
A total of 14 studies were included. Pooled analysis revealed an improved 5-year overall survival (OS) for IPMC compared to PDAC (OR 0.23, 95% CI 0.09-0.56). Both colloid and tubular IPMC showed improved 5-year OS compared to PDAC (OR 0.12, 95% CI 0.05-0.25 and OR 0.38, 95% CI 0.26-0.54, respectively). Median survival time ranged from 21 to 58 months in the IPMC group compared to 12-23 months in the PDAC group. No meta-analysis could be performed on recurrence or on time-to-event data. Descriptive data showed no survival difference for higher TNM stages. IPMC was more often found at a TNM-stage of 1 (OR 4.40, 95% CI 2.71-7.15) and had lower rates of lymph node spread (OR 0.43, 95% CI 0.32-0.57).
CONCLUSION
Available data suggest that IPMC has a more indolent course with a better 5-year OS compared to PDAC. The histopathological features are less aggressive in IPMC. The reason may be earlier detection. However, for IPMC with higher TNM stages the survival seems to be similar to that of PDAC.
Topics: Adenocarcinoma, Mucinous; Adenocarcinoma, Papillary; Aged; Breast Neoplasms; Carcinoma, Ductal, Breast; Carcinoma, Pancreatic Ductal; Female; Humans; Middle Aged; Neoplasm Staging; Pancreatic Neoplasms; Survival Rate
PubMed: 31546033
DOI: 10.1016/j.ijsu.2019.09.014 -
Nutrition Reviews Nov 2017Pancreatic cancer has the highest case fatality rate of all major cancers. (Meta-Analysis)
Meta-Analysis Review
CONTEXT
Pancreatic cancer has the highest case fatality rate of all major cancers.
OBJECTIVE
A systematic review using PRISMA guidelines was conducted to summarize the associations between dietary patterns and risk of pancreatic cancer.
DATA SOURCES
PubMed and Web of Science databases were searched for case-control and cohort studies published up to June 15, 2016.
STUDY SELECTION
Eligible studies included a dietary pattern as exposure and pancreatic cancer incidence or mortality as outcome and reported odds ratios, hazard ratios, or relative risks, along with corresponding 95%CIs.
DATA EXTRACTION
Important characteristics of each study, along with the dietary assessment instrument, the component foods or nutrients included in each dietary pattern or the scoring algorithm of a priori dietary patterns, were presented. For each dietary pattern identified, the estimate of association and the 95%CI comparing the highest versus the lowest category from the model with the most covariate adjustment were reported.
RESULTS
A total of 16 studies were identified. Among the 8 studies that examined data-driven dietary patterns, significant positive associations were found between pancreatic cancer risk and the Animal Products, Starch Rich, and Western dietary patterns, with effect estimates ranging from 1.69 to 2.40. Significant inverse relationships were found between risk of pancreatic cancer and dietary patterns designated as Fruits and Vegetables, Vitamins and Fiber, and Prudent, with effect estimates ranging from 0.51 to 0.55. Eight studies of a priori dietary patterns consistently suggested that improved dietary quality was associated with reduced risk of pancreatic cancer.
CONCLUSIONS
Better diet quality is associated with reduced risk of pancreatic cancer. The associations between dietary patterns and pancreatic cancer were stronger in case-control studies than in cohort studies and were stronger among men than among women.
Topics: Diet; Diet, Western; Dietary Fiber; Female; Fruit; Humans; Incidence; Male; Meat; Pancreatic Neoplasms; Risk; Starch; Vegetables; Vitamins
PubMed: 29025004
DOI: 10.1093/nutrit/nux038 -
Medicine Aug 2017The identification of pancreatic carcinoma (PC) patients with poor prognosis is a priority in clinical oncology because of their high 5-year mortality. However, the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The identification of pancreatic carcinoma (PC) patients with poor prognosis is a priority in clinical oncology because of their high 5-year mortality. However, the prognostic value of pretreatment F-fluorodeoxyglucose (F-FDG)- positron emission tomography (PET)/computed tomography (CT) parameters in PC patients is controversial and no consensus exists as to its predictive capability. This meta-analysis was performed to comprehensively explore the prognostic significance of F-FDG-PET/CT parameters in patients with pancreatic carcinoma.
METHODS
Extensive literature searches of the PubMed, Embase, Web of Science, and Cochrane Library databases were conducted to identify literature published until March 5, 2017. Comparative analyses of the pooled hazard ratios (HRs) for event-free survival (EFS) and overall survival (OS) were performed to assess their correlations with pretreatment maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG). Either the fixed- or the random-effects model was adopted, depending on the heterogeneity observed across studies. Subgroup and sensitivity analyses were performed to assess the robustness of the results.
RESULTS
Sixteen studies including 1146 patients were identified. The pooled HRs for the probability of EFS were 1.90 (95% confidential interval (CI): 1.48-2.45) for SUVmax, 1.76 (95% CI: 1.20-2.58) for MTV, and 1.81 (95% CI: 1.27-2.58) for TLG. The pooled HRs for the probability of OS were 1.21 (95% CI: 1.12-1.31) for SUVmax, 1.56 (95% CI: 1.13-2.16) for MTV, and 1.70 (95% CI: 1.25-2.30) for TLG. A slight publication bias was detected using Begg test. After adjustment using the trim and fill procedure, the corrected HRs were not significantly different. The results of the subgroup analyses by SUVmax, MTV, and TLG showed that these factors may have similar prognostic significance.
CONCLUSION
F-FDG-PET/CT parameters, such as SUVmax, MTV, and TLG, may be significant prognostic factors in patients with pancreatic carcinoma. F-FDG-PET/CT imaging could be a promising tool to provide prognostic information for these patients.
Topics: Disease-Free Survival; Fluorodeoxyglucose F18; Humans; Pancreatic Neoplasms; Positron Emission Tomography Computed Tomography; Prognosis; Proportional Hazards Models; Radiopharmaceuticals; Retrospective Studies; Tumor Burden
PubMed: 28816978
DOI: 10.1097/MD.0000000000007813 -
International Journal of Surgery... Dec 2023Diagnosing pancreatic lesions, including chronic pancreatitis, autoimmune pancreatitis, and pancreatic cancer, poses a challenge and, as a result, is time-consuming. To... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Diagnosing pancreatic lesions, including chronic pancreatitis, autoimmune pancreatitis, and pancreatic cancer, poses a challenge and, as a result, is time-consuming. To tackle this issue, artificial intelligence (AI) has been increasingly utilized over the years. AI can analyze large data sets with heightened accuracy, reduce interobserver variability, and can standardize the interpretation of radiologic and histopathologic lesions. Therefore, this study aims to review the use of AI in the detection and differentiation of pancreatic space-occupying lesions and to compare AI-assisted endoscopic ultrasound (EUS) with conventional EUS in terms of their detection capabilities.
METHODS
Literature searches were conducted through PubMed/Medline, SCOPUS, and Embase to identify studies eligible for inclusion. Original articles, including observational studies, randomized control trials, systematic reviews, meta-analyses, and case series specifically focused on AI-assisted EUS in adults, were included. Data were extracted and pooled, and a meta-analysis was conducted using Meta-xl. For results exhibiting significant heterogeneity, a random-effects model was employed; otherwise, a fixed-effects model was utilized.
RESULTS
A total of 21 studies were included in the review with four studies pooled for a meta-analysis. A pooled accuracy of 93.6% (CI 90.4-96.8%) was found using the random-effects model on four studies that showed significant heterogeneity ( P <0.05) in the Cochrane's Q test. Further, a pooled sensitivity of 93.9% (CI 92.4-95.3%) was found using a fixed-effects model on seven studies that showed no significant heterogeneity in the Cochrane's Q test. When it came to pooled specificity, a fixed-effects model was utilized in six studies that showed no significant heterogeneity in the Cochrane's Q test and determined as 93.1% (CI 90.7-95.4%). The pooled positive predictive value which was done using the random-effects model on six studies that showed significant heterogeneity was 91.6% (CI 87.3-95.8%). The pooled negative predictive value which was done using the random-effects model on six studies that showed significant heterogeneity was 93.6% (CI 90.4-96.8%).
CONCLUSION
AI-assisted EUS shows a high degree of accuracy in the detection and differentiation of pancreatic space-occupying lesions over conventional EUS. Its application may promote prompt and accurate diagnosis of pancreatic pathologies.
Topics: Adult; Humans; Artificial Intelligence; Sensitivity and Specificity; Pancreas; Endosonography; Pancreatic Neoplasms
PubMed: 37800594
DOI: 10.1097/JS9.0000000000000717 -
Pancreas Feb 2020The role of total pancreatectomy (TP) to treat pancreatic carcinoma is still debated. The aims of this study were to systematically review the previous literature and to...
The role of total pancreatectomy (TP) to treat pancreatic carcinoma is still debated. The aims of this study were to systematically review the previous literature and to summarize the indications and results of TP for pancreatic carcinoma. A systematic search was performed to identify all studies published up to November 2018 analyzing the survival of patients undergoing TP for pancreatic carcinoma. Clinical effectiveness was synthetized through a narrative review with full tabulation of results. Six studies published between 2009 and 2016 were retrieved, including 316 patients. The major indication was positive pancreatic margin at frozen section during partial pancreatectomy. The overall morbidity ranged from 36% to 69%, and mortality from 0% to 27%. Overall survival ranged from 52.7% to 67% at 1 year, from 20% to 42% at 3 years of follow-up, whereas the 5-year estimated overall survival ranged from 4.5% to 21.9%. Total pancreatectomy has an important role in the armamentarium of pancreatic surgeons. Postoperative morbidity and mortality are not negligible, but a trend for better postoperative outcomes in recent years is noticed. Mortality related to difficult glycemic control is rare. Long-term survival is comparable with survival after partial pancreatectomy for carcinoma.
Topics: Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Combined Modality Therapy; Outcome Assessment, Health Care; Pancreatectomy; Pancreatic Neoplasms; Postoperative Complications; Survival Analysis; Survival Rate; Time Factors
PubMed: 32011524
DOI: 10.1097/MPA.0000000000001474