-
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 -
Defining oligometastatic pancreatic cancer: a systematic review and critical synthesis of consensus.ESMO Open Dec 2023Small retrospective series suggest that local consolidative treatment (LCT) may improve survival in oligometastatic pancreatic ductal adenocarcinoma (PDAC). However, no...
BACKGROUND
Small retrospective series suggest that local consolidative treatment (LCT) may improve survival in oligometastatic pancreatic ductal adenocarcinoma (PDAC). However, no uniform definition of oligometastatic disease (OMD) in PDAC exists; this impedes meaningful conclusions.
PATIENTS AND METHODS
A systematic literature search using PubMed, Web of Science, and Cochrane CENTRAL registries for studies and protocols reporting on definitions and/or LCT of OMD in PDAC was performed. The primary endpoint was the definition of OMD. Levels of agreement were categorized as consensus (≥75% agreement between studies), fair agreement (50%-74%), and absent/poor agreement (<50%).
RESULTS
After screening of 5374 abstracts, the full text of 218 studies was assessed, of which 76 were included in the qualitative synthesis. The majority of studies were retrospective (n = 66, 87%), two were prospective studies and eight were study protocols. Studies investigated mostly liver (n = 38, 51%) and lung metastases (n = 15, 20%). Across studies, less than one-half (n = 32, 42%) reported a definition of OMD, while 44 (58%) did not. Involvement was limited to a single organ (consensus). Additional criteria for defining OMD were the number of lesions (consensus), metastatic site (poor agreement), metastatic size (poor agreement), treatment possibilities (poor agreement), and biomarker response (poor agreement). Liver OMD could involve three or fewer lesions (consensus) and synchronous disease (fair agreement), while lung metastases could involve two or fewer lesions and metachronous disease (consensus). The large majority of studies were at a high risk of bias or did not include any control groups.
CONCLUSION
Definitions of OMD were not used or varied widely between studies hampering across-study comparability and highlighting an unmet need for a consensus. The present study is part of a multistep process that aims to develop an interdisciplinary consensus on OMD in pancreatic cancer.
Topics: Humans; Retrospective Studies; Prospective Studies; Consensus; Lung Neoplasms; Pancreatic Neoplasms
PubMed: 37988953
DOI: 10.1016/j.esmoop.2023.102067 -
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 -
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 -
Langenbeck's Archives of Surgery Aug 2023Most studies on minimally invasive pancreatoduodenectomy (MIPD) combine patients with pancreatic and periampullary cancers even though there is substantial heterogeneity... (Meta-Analysis)
Meta-Analysis Review
The clinical implication of minimally invasive versus open pancreatoduodenectomy for non-pancreatic periampullary cancer: a systematic review and individual patient data meta-analysis.
BACKGROUND
Most studies on minimally invasive pancreatoduodenectomy (MIPD) combine patients with pancreatic and periampullary cancers even though there is substantial heterogeneity between these tumors. Therefore, this study aimed to evaluate the role of MIPD compared to open pancreatoduodenectomy (OPD) in patients with non-pancreatic periampullary cancer (NPPC).
METHODS
A systematic review of Pubmed, Embase, and Cochrane databases was performed by two independent reviewers to identify studies comparing MIPD and OPD for NPPC (ampullary, distal cholangio, and duodenal adenocarcinoma) (01/2015-12/2021). Individual patient data were required from all identified studies. Primary outcomes were (90-day) mortality, and major morbidity (Clavien-Dindo 3a-5). Secondary outcomes were postoperative pancreatic fistula (POPF), delayed gastric emptying (DGE), postpancreatectomy hemorrhage (PPH), blood-loss, length of hospital stay (LOS), and overall survival (OS).
RESULTS
Overall, 16 studies with 1949 patients were included, combining 928 patients with ampullary, 526 with distal cholangio, and 461 with duodenal cancer. In total, 902 (46.3%) patients underwent MIPD, and 1047 (53.7%) patients underwent OPD. The rates of 90-day mortality, major morbidity, POPF, DGE, PPH, blood-loss, and length of hospital stay did not differ between MIPD and OPD. Operation time was 67 min longer in the MIPD group (P = 0.009). A decrease in DFS for ampullary (HR 2.27, P = 0.019) and distal cholangio (HR 1.84, P = 0.025) cancer, as well as a decrease in OS for distal cholangio (HR 1.71, P = 0.045) and duodenal cancer (HR 4.59, P < 0.001) was found in the MIPD group.
CONCLUSIONS
This individual patient data meta-analysis of MIPD versus OPD in patients with NPPC suggests that MIPD is not inferior in terms of short-term morbidity and mortality. Several major limitations in long-term data highlight a research gap that should be studied in prospective maintained international registries or randomized studies for ampullary, distal cholangio, and duodenum cancer separately.
PROTOCOL REGISTRATION
PROSPERO (CRD42021277495) on the 25th of October 2021.
Topics: Humans; Pancreaticoduodenectomy; Duodenal Neoplasms; Prospective Studies; Pancreas; Postoperative Complications; Laparoscopy; Pancreatic Neoplasms; Retrospective Studies
PubMed: 37581763
DOI: 10.1007/s00423-023-03047-4 -
The International Journal of Behavioral... May 2023Studies of the associations between soft drinks and the risk of cancer showed inconsistent results. No previous published systematic reviews and meta-analysis has... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Studies of the associations between soft drinks and the risk of cancer showed inconsistent results. No previous published systematic reviews and meta-analysis has investigated a dose-response association between exposure dose and cancer risk or assessed the certainty of currently available evidence. Therefore, we aim to demonstrate the associations and assessed the certainty of the evidence to show our confidence in the associations.
METHODS
We searched Embase, PubMed, Web of Science, and the Cochrane Library from inception to Jun 2022, to include relevant prospective cohort studies. We used a restricted cubic spline model to conduct a dose-response meta-analysis and calculated the absolute effect estimates to present the results. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to assess the certainty of the evidence.
RESULTS
Forty-two articles including on 37 cohorts enrolled 4,518,547 participants were included. With low certainty evidence, increased consumption of sugar-sweetened beverages (SSBs) per 250 mL/day was significantly associated with a 17% greater risk of breast cancer, a 10% greater risk of colorectal cancer, a 30% greater risk of biliary tract cancer, and a 10% greater risk of prostate cancer; increased consumption of artificially sweetened beverages (ASBs)re per 250 mL/day was significantly associated with a 16% greater risk of leukemia; increased consumption of 100% fruit juice per 250 mL/day was significantly associated with a 31% greater risk of overall cancer, 22% greater risk of melanoma, 2% greater risk of squamous cell carcinoma, and 29% greater risk of thyroid cancer. The associations with other specific cancer were no significant. We found linear dose-response associations between consumption of SSBs and the risk of breast and kidney cancer, and between consumption of ASBs and 100% fruit juices and the risk of pancreatic cancer.
CONCLUSIONS
An increment in consumption of SSBs of 250 mL/day was positively associated with increased risk of breast, colorectal, and biliary tract cancer. Fruit juices consumption was also positively associated with the risk of overall cancer, thyroid cancer, and melanoma. The magnitude of absolute effects, however, was small and mainly based on low or very low certainty of evidence. The association of ASBs consumption with specific cancer risk was uncertain.
TRIAL REGISTRATION
PROSPERO: CRD42020152223.
Topics: Humans; Male; Beverages; Biliary Tract Neoplasms; Carbonated Beverages; Fruit and Vegetable Juices; Melanoma; Prospective Studies; Sweetening Agents
PubMed: 37189146
DOI: 10.1186/s12966-023-01459-5 -
Daru : Journal of Faculty of Pharmacy,... Dec 2022Association between vitamins C (VC)/ E (VE) and cancer survival is inconsistent. This systematic review is aimed to summarize trials for effects of VC/VE on cancer... (Review)
Review
PURPOSE
Association between vitamins C (VC)/ E (VE) and cancer survival is inconsistent. This systematic review is aimed to summarize trials for effects of VC/VE on cancer survival.
METHODS
Relevant English trials were retrieved from PubMed, Cochrane Library, Embase, Web of Science, Scopus databases, and Clinicaltrials.gov through 21/June/2022. Inclusion criteria were all trials which assessed sole/combinations intake of VC/VE on survival rate, mortality, or remission of any cancer. Exclusion criteria were observational and animal studies.
RESULTS
We reached 30 trials conducted on 38,936 patients with various cancers. Due to severe methodological heterogeneity, meta-analysis was impossible. High dose VC + chemotherapy or radiation was safe with an overall survival (OS) 182 days - 21.5 months. Sole oral or intravenous high dose VC was safe with non-significant change in OS (2.9-8.2 months). VE plus chemotherapy was safe, resulted in stabling diseases for 5 years in 70- 86.7% of patients and OS 109 months. It was found 60% and 16% non-significant reductions in adjusted hazard ratio (HR) deaths or recurrence by 200 mg/d tocotrienol + tamoxifen in breast cancer, respectively. Sole intake of 200-3200 mg/d tocotrienol before resectable pancreatic cancer was safe and significantly increased cancer cells' apoptosis. Combination VC and VE was non-significantly reduced 7% in rate of neoplastic gastric polyp.
CONCLUSION
Although our study is supported improvement of survival and progression rates of cancers by VC/VE, more high quality trials with large sample sizes are required to confirm.
PROSPERO REGISTRATION NUMBER
CRD42020152795.
Topics: Antineoplastic Agents; Ascorbic Acid; Neoplasms; Tamoxifen; Tocotrienols; Vitamins
PubMed: 36136247
DOI: 10.1007/s40199-022-00451-x -
International Journal of Environmental... May 2021Imaging methods and the most appropriate criteria to be used for detecting and evaluating response to oncological treatments depend on the pathology and anatomical site... (Review)
Review
BACKGROUND
Imaging methods and the most appropriate criteria to be used for detecting and evaluating response to oncological treatments depend on the pathology and anatomical site to be treated and on the treatment to be performed. This document provides a general overview of the main imaging and histopathological findings of electroporation-based treatments (Electrochemotherapy-ECT and Irreversible electroporation-IRE) compared to thermal approach, such as radiofrequency ablation (RFA), in deep-seated cancers with a particular attention to pancreatic and liver cancer.
METHODS
Numerous electronic datasets were examined: PubMed, Scopus, Web of Science and Google Scholar. The research covered the years from January 1990 to April 2021. All titles and abstracts were analyzed. The inclusion criteria were the following: studies that report imaging or histopathological findings after ablative thermal and not thermal loco-regional treatments (ECT, IRE, RFA) in deep-seated cancers including pancreatic and liver cancer and articles published in the English language. Exclusion criteria were unavailability of full text and congress abstracts or posters and different topic respect to inclusion criteria.
RESULTS
558 potentially relevant references through electronic searches were identified. A total of 38 articles met the inclusion criteria: 20 studies report imaging findings after RFA or ECT or IRE in pancreatic and liver cancer; 17 studies report histopathological findings after RFA or ECT or IRE; 1 study reports both imaging and histopathological findings after RFA or ECT or IRE.
CONCLUSIONS
Imaging features are related to the type of therapy administrated, to the timing of re-assessment post therapy and to the imaging technique being used to observe the effects. Histological findings after both ECT and IRE show that the treated area becomes necrotic and encapsulated in fibrous tissue, suggesting that the size of the treated lesion cannot be measured as an endpoint to detect response. Moreover, histology frequently reported signs of apoptosis and reduced vital tissue, implying that imaging criteria, which take into account the viability and not the size of the lesion, are more appropriate to evaluate response to treatment.
Topics: Electroporation; Humans; Liver Neoplasms; Pancreas; Radiofrequency Ablation
PubMed: 34073865
DOI: 10.3390/ijerph18115592 -
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 -
Histopathology Sep 2022Intraductal tubulopapillary neoplasm (ITPN) of the pancreas is a recently recognized pancreatic tumor entity. Here we aimed to determine the most important features with... (Review)
Review
AIMS
Intraductal tubulopapillary neoplasm (ITPN) of the pancreas is a recently recognized pancreatic tumor entity. Here we aimed to determine the most important features with a systematic review coupled with an integrated statistical approach.
METHODS AND RESULTS
PubMed, SCOPUS, and Embase were searched for studies reporting data on pancreatic ITPN. The clinicopathological, immunohistochemical, and molecular data were summarized. Then a comprehensive survival analysis and a comparative analysis of the molecular alterations of ITPN with those of pancreatic ductal adenocarcinoma (PDAC) and intraductal papillary mucinous neoplasm (IPMN) from reference cohorts (including the International Cancer Genome Consortium- ICGC dataset and The Cancer Genome Atlas, TCGA program) were conducted. The core findings of 128 patients were as follows: (i) Clinicopathological parameters: pancreatic head is the most common site; presence of an associated adenocarcinoma was reported in 60% of cases, but with rare nodal metastasis. (ii) Immunohistochemistry: MUC1 (>90%) and MUC6 (70%) were the most frequently expressed mucins. ITPN lacked the intestinal marker MUC2; unlike IPMN, it did not express MUC5AC. (iii) Molecular landscape: Compared with PDAC/IPMN, the classic pancreatic drivers KRAS, TP53, CDKN2A, SMAD4, GNAS, and RNF43 were less altered in ITPN (P < 0.001), whereas MCL amplifications, FGFR2 fusions, and PI3KCA mutations were commonly altered (P < 0.001). (iv) Survival analysis: ITPN with a "pure" branch duct involvement showed the lowest risk of recurrence.
CONCLUSION
ITPN is a distinct pancreatic neoplasm with specific clinicopathological and molecular characteristics. Its recognition is fundamental for its clinical/prognostic implications and for the enrichment of potential targets for precision oncology.
Topics: Carcinoma, Pancreatic Ductal; Carcinoma, Papillary; Humans; Pancreas; Pancreatic Intraductal Neoplasms; Pancreatic Neoplasms; Precision Medicine
PubMed: 35583805
DOI: 10.1111/his.14698