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Frontiers in Endocrinology 2023Reprogramming of cellular metabolism is now a hallmark of tumorigenesis. In recent years, research on pancreatic neuroendocrine tumors (pNETs) has focused on genetic and... (Review)
Review
INTRODUCTION
Reprogramming of cellular metabolism is now a hallmark of tumorigenesis. In recent years, research on pancreatic neuroendocrine tumors (pNETs) has focused on genetic and epigenetic modifications and related signaling pathways, but few studies have been devoted to characterizing the metabolic profile of these tumors. In this review, we thoroughly investigate the metabolic pathways in pNETs by analyzing the transcriptomic and metabolomic data available in the literature.
METHODOLOGY
We retrieved and downloaded gene expression profiles from all publicly available gene set enrichments (GSE43797, GSE73338, and GSE117851) to compare the differences in expressed genes based on both the stage and MEN1 mutational status. In addition, we conducted a systematic review of metabolomic data in NETs.
RESULTS
By combining transcriptomic and metabolomic approaches, we have identified a distinctive metabolism in pNETs compared with controls without pNETs. Our analysis showed dysregulations in the one-carbon, glutathione, and polyamine metabolisms, fatty acid biosynthesis, and branched-chain amino acid catabolism, which supply the tricarboxylic acid cycle. These targets are implicated in pNET cell proliferation and metastasis and could also have a prognostic impact. When analyzing the profiles of patients with or without metastasis, or with or without MEN1 mutation, we observed only a few differences due to the scarcity of published clinical data in the existing research. Consequently, further studies are now necessary to validate our data and investigate these potential targets as biomarkers or therapeutic solutions, with a specific focus on pNETs.
Topics: Humans; Pancreatic Neoplasms; Neuroendocrine Tumors; Prognosis; Epigenesis, Genetic; Neuroectodermal Tumors, Primitive
PubMed: 37908747
DOI: 10.3389/fendo.2023.1248575 -
BMC Cancer Aug 2023The association between gastrointestinal cancer and types of meat consumption, including red meat, processed meat, or a combination of both, remains disputable.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The association between gastrointestinal cancer and types of meat consumption, including red meat, processed meat, or a combination of both, remains disputable. Therefore, we performed a systematic review and meta-analysis of prospective cohort studies to estimate the association between meat consumption and gastrointestinal cancer risk.
METHODS
PubMed, EmBase, and the Cochrane library databases were searched systematically for eligible studies that investigated the relation between meat consumption and the risk of developing gastrointestinal cancers, including esophageal cancer (EC), gastric cancer (GC), colorectal cancer (CRC), colon cancer (CC), rectal cancer (RC), pancreatic cancer (PC), and hepatocellular carcinoma (HCC) throughout February, 2023. The pooled relative risk (RR) with 95% confidence interval (CI) was assigned as an effect estimate and calculated using a random-effects model with inverse variance weighting.
RESULTS
Forty cohorts comprising 3,780,590 individuals were selected for the final quantitative analysis. The summary results indicated that a higher red meat consumption was associated with an increased risk of CRC (RR: 1.09; 95% CI: 1.02-1.16; P = 0.007) and CC (RR: 1.13; 95% CI: 1.03-1.25; P = 0.011). Moreover, a higher processed meat consumption was associated with an increased risk of CRC (RR: 1.19; 95% CI: 1.13-1.26; P < 0.001), CC (RR: 1.24; 95% CI: 1.13-1.26; P < 0.001), and RC (RR: 1.24; 95% CI: 1.08-1.42; P = 0.002). Furthermore, a higher total consumption of red and processed meat was associated with an increased risk of CRC (RR: 1.13; 95% CI: 1.06-1.20; P < 0.001), CC (RR: 1.17; 95% CI: 1.04-1.33; P = 0.012), and RC (RR: 1.20; 95% CI: 1.04-1.39; P = 0.016). Finally, the strength of higher consumption of total red and processed meat with the risk of GC, and higher consumption of red meat with the risk of RC in subgroup of high adjusted level was lower than subgroup of moderate adjusted level, while the strength of higher consumption of processed meat with the risk of RC and HCC in subgroup of follow-up ≥ 10.0 years was higher than subgroup of follow-up < 10.0 years.
CONCLUSIONS
This study found that meat consumption was associated with an increased risk of CRC, CC, and RC, and dietary intervention could be considered an effective strategy in preventing CRC.
Topics: Humans; Carcinoma, Hepatocellular; Prospective Studies; Liver Neoplasms; Gastrointestinal Neoplasms; Stomach Neoplasms; Meat; Colonic Neoplasms
PubMed: 37612616
DOI: 10.1186/s12885-023-11218-1 -
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 -
Nutrients Nov 2023Bioelectrical Impedance Analysis (BIA) is a reliable, non-invasive, objective, and cost-effective body composition assessment method, with high reproducibility. This... (Review)
Review
Bioelectrical Impedance Analysis (BIA) is a reliable, non-invasive, objective, and cost-effective body composition assessment method, with high reproducibility. This scoping review aims to evaluate the current scientific and clinical evidence on BIA for body composition assessment in oncology patients, under active treatment. Literature search was conducted through MEDLINE, CINAHL, Scopus and Web of Science databases, following PRISMA-ScR Guidelines. Inclusion criteria comprised studies reporting the use of BIA for body composition evaluation in adults with cancer diagnosis. Studies including non-cancer pathology or only assessing nutritional status were excluded. This scoping review comprised a total of 36 studies: 25 were original studies including 18 prospective studies, six cross-sectional studies and one retrospective study and 11 were systematic reviews. Population size for the included original articles ranged from 18 to 1217 participants, comprising a total of 3015 patients with cancer with a mean baseline Body Mass Index (BMI) ranging from 20.3 to 30.0 kg/m and mean age ranging between 47 and 70 years. Review articles included a total of 273 studies, with a total of 78,350 participants. The current review considered studies reporting patients with head and neck cancer (HNC) ( = 8), breast cancer (BC) ( = 4), esophageal cancer (EC) ( = 2), liver cancer ( = 2), pancreatic cancer (PC) ( = 3), gastric cancer (GC) ( = 3), colorectal cancer (CRC) ( = 8), lung cancer (LC) ( = 1), skin cancer (SK) ( = 1) and multiple cancer types ( = 6). BIA is a suitable and valid method for the assessment of body composition in oncology. BIA-derived measures have shown good potential and relevant clinical value in preoperative risk evaluation, in the reduction of postoperative complications and hospital stay and as an important prognostic indicator in persons with cancer. Future research on the diagnostic value and clinical applications of BIA and BIA-derived phase angle (PhA) should be conducted in order to predict its impact on patient survival and other clinical outcomes.
Topics: Adult; Humans; Middle Aged; Aged; Electric Impedance; Reproducibility of Results; Prospective Studies; Retrospective Studies; Cross-Sectional Studies; Body Composition; Head and Neck Neoplasms
PubMed: 38004186
DOI: 10.3390/nu15224792 -
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 -
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 -
Journal of Gastrointestinal Surgery :... Nov 2023Pancreatic benign, cystic, and neuroendocrine neoplasms are increasingly detected and recommended for surgical treatment. In multiorgan resection pancreatoduodenectomy... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Pancreatic benign, cystic, and neuroendocrine neoplasms are increasingly detected and recommended for surgical treatment. In multiorgan resection pancreatoduodenectomy or parenchyma-sparing, local extirpation is a challenge for decision-making regarding surgery-related early and late postoperative morbidity.
METHODS
PubMed, Embase, and Cochrane Libraries were searched for studies reporting early surgery-related complications following pancreatoduodenectomy (PD) and duodenum-preserving total (DPPHRt) or partial (DPPHRp) pancreatic head resection for benign tumors. Thirty-four cohort studies comprising data from 1099 patients were analyzed. In total, 654 patients underwent DPPHR and 445 patients PD for benign tumors. This review and meta-analysis does not need ethical approval.
RESULTS
Comparing DPPHRt and PD, the need for blood transfusion (OR 0.20, 95% CI 0.10-0.41, p<0.01), re-intervention for serious surgery-related complications (OR 0.48, 95% CI 0.31-0.73, p<0.001), and re-operation for severe complications (OR 0.50, 95% CI 0.26-0.95, p=0.04) were significantly less frequent following DPPHRt. Pancreatic fistula B+C (19.0 to 15.3%, p=0.99) and biliary fistula (6.3 to 4.3%; p=0.33) were in the same range following PD and DPPHRt. In-hospital mortality after DPPHRt was one of 350 patients (0.28%) and after PD eight of 445 patients (1.79%) (OR 0.32, 95% CI 0.10-1.09, p=0.07). Following DPPHRp, there was no mortality among the 192 patients.
CONCLUSION
DPPHR for benign pancreatic tumors is associated with significantly fewer surgery-related, serious, and severe postoperative complications and lower in-hospital mortality compared to PD. Tailored use of DPPHRt or DPPHRp contributes to a reduction of surgery-related complications. DPPHR has the potential to replace PD for benign tumors and premalignant cystic and neuroendocrine neoplasms of the pancreatic head.
Topics: Humans; Pancreatectomy; Pancreas; Pancreaticoduodenectomy; Pancreatic Neoplasms; Duodenum; Neuroendocrine Tumors; Pancreatic Cyst
PubMed: 37670106
DOI: 10.1007/s11605-023-05789-4 -
Metabolites Jul 2023Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers, with five-year survival rates around 10%. The only curative option remains complete surgical... (Review)
Review
Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers, with five-year survival rates around 10%. The only curative option remains complete surgical resection, but due to the delay in diagnosis, less than 20% of patients are eligible for surgery. Therefore, discovering diagnostic biomarkers for early detection is crucial for improving clinical outcomes. Metabolomics has become a powerful technology for biomarker discovery, and several metabolomic-based panels have been proposed for PDAC diagnosis, but these advances have not yet been translated into the clinic. Therefore, this review focused on summarizing metabolites identified for the early diagnosis of PDAC in the last five years. Bibliographic searches were performed in the PubMed, Scopus and WOS databases, using the terms "Biomarkers, Tumor", "Pancreatic Neoplasms", "Early Diagnosis", "Metabolomics" and "Lipidome" (January 2018-March 2023), and resulted in the selection of fourteen original studies that compared PDAC patients with subjects with other pancreatic diseases. These investigations showed amino acid and lipid metabolic pathways as the most commonly altered, reflecting their potential for biomarker research. Furthermore, other relevant metabolites such as glucose and lactate were detected in the pancreas tissue and body fluids from PDAC patients. Our results suggest that the use of metabolomics remains a robust approach to improve the early diagnosis of PDAC. However, these studies showed heterogeneity with respect to the metabolomics techniques used and further studies will be needed to validate the clinical utility of these biomarkers.
PubMed: 37512579
DOI: 10.3390/metabo13070872 -
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 -
Journal of Cachexia, Sarcopenia and... Dec 2023Sarcopenia has been considered an adverse prognostic factor in cancer patients. Intramuscular adipose tissue content, as a new marker of sarcopenia, can effectively... (Meta-Analysis)
Meta-Analysis Review
Sarcopenia has been considered an adverse prognostic factor in cancer patients. Intramuscular adipose tissue content, as a new marker of sarcopenia, can effectively reflect skeletal muscle quality. The aim of this study was performed to evaluate the association between high intramuscular adipose tissue content (IMAC) and survival outcomes and postoperative complications in cancer patients. Specific databases, including the Web of Science, Embase and Web of Science, were systematically searched to identify relevant articles evaluating the prognostic value of IMAC in cancer patients. Hazard ratios (HRs) or odds ratios (ORs) with 95% confidence intervals (CIs) were utilized for comprehensive analysis. All data analyses were performed using STATA 12.0 software. A total of 25 studies from 24 articles including 5663 patients were enrolled in the study. Meta-analysis showed that high IMAC was associated with unfavourable overall survival (OS) (HR: 2.21, 95% CI: 1.70-2.86, P < 0.001), relapse-free survival (RFS) (HR: 1.51, 95% CI: 1.30-1.75, P < 0.001) and disease-specific survival (DSS) (HR: 1.64, 95% CI: 1.19-2.28, P = 0.003). Subgroup analysis revealed that high IMAC remained an adverse prognostic factor when stratified by different country, treatment methods, cancer type or analysis type. High IMAC had better predictive value for gallbladder carcinoma (GBC) (HR: 3.50, 95% CI: 1.98-6.17, P < 0.001), hepatocellular carcinoma (HCC) (HR: 1.84, 95% CI: 1.45-2.33, P < 0.001), pancreatic cancer (PC) (HR: 2.11, 95% CI: 1.67-2.66, P < 0.001) and colorectal cancer (CRC) (HR: 2.54, 95% CI: 1.27-5.10, P = 0.009). High IMAC was also identified as a significant risk factor for postoperative complications (OR: 2.05, 95% CI: 1.22-3.46, P = 0.007). High IMAC was associated with an adverse prognosis and an increased risk of postoperative complications in cancer patients. IMAC may be a good indicator of sarcopenia.
Topics: Humans; Carcinoma, Hepatocellular; Sarcopenia; Liver Neoplasms; Retrospective Studies; Prognosis; Adipose Tissue; Postoperative Complications
PubMed: 37990969
DOI: 10.1002/jcsm.13371