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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 -
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 -
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 -
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 -
Frontiers in Oncology 2023In recent years, there has been rapid development in systemic therapeutic agents for advanced hepatocellular carcinoma. However, most treatment modalities lack...
BACKGROUND
In recent years, there has been rapid development in systemic therapeutic agents for advanced hepatocellular carcinoma. However, most treatment modalities lack head-to-head comparisons, and the distinctions in their efficacy and safety have yet to be elucidated. Consequently, the accurate selection of a treatment regimen poses a significant challenge for clinicians.
METHODS
This study incorporated twenty-three randomized controlled trials, encompassing fifteen first-line and eight second-line treatments, and involving a total of 14,703 patients with advanced hepatocellular carcinoma. Results: In the context of first-line treatment, it was observed that the combination of a PD-1 inhibitor with bevacizumab (1/15) significantly extended overall survival in patients with advanced HCC. Furthermore, PD-1 inhibitors combined with TKIs (1/15) and PD-1 inhibitors combined with bevacizumab (2/15) exhibited enhanced efficacy in reducing the risk of progression-free survival events. In second-line therapy, the network meta-analysis revealed that all investigational agents prolonged progression-free survival in patients with advanced hepatocellular carcinoma when compared to placebo. Cabozantinib ranked first (1/7) in this regard. However, this translated into an overall survival benefit only for cabozantinib, regorafenib, ramucirumab, and pembrolizumab, with regorafenib achieving the highest ranking (1/7).
CONCLUSION
In the treatment of advanced HCC, the immune checkpoint inhibitor combined with bevacizumab regimen and the immune checkpoint inhibitor combined with TKI regimen stand out as the two most effective first-line treatment options. It is noteworthy that, for patients with absolute contraindications to VEGF inhibitors, dual immunotherapy is the preferred choice. For second-line treatment, regorafenib and cabozantinib are identified as the two most effective options.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero, identifier CRD42023440173.
PubMed: 38125936
DOI: 10.3389/fonc.2023.1274754 -
Frontiers in Public Health 2023The benefits of vitamin E (VE) for multiple health outcomes have been well evaluated in many recent studies.
BACKGROUND
The benefits of vitamin E (VE) for multiple health outcomes have been well evaluated in many recent studies.
OBJECTIVE
The purpose of this umbrella review was to conduct a systematic evaluation of the possible associations between VE intake and various health outcomes.
METHODS
We systematically searched various databases, such as PubMed, Embase, and the Web of Science, to identify related meta-analyses of observational studies and randomized trials. We estimated the effect size of each association by using the random or fixed effects models and the 95% confidence intervals. We used standard approaches to evaluate the quality of the articles (AMSTAR) and classified the evidence into different levels of quality (GRADE).
RESULTS
A total of 1,974 review articles were searched, and 27 articles with 28 health outcomes were yielded according to our exclusion criteria. The intake of VE was inversely associated with the risk of breast cancer, lung cancer, esophageal cancer, gastric cancer, pancreatic cancer, kidney cancer, bladder cancer, cervical neoplasms, cardiovascular disease, Parkinson's disease, depression, age-related cataracts, metabolic syndrome, and fracture. Overall, most of the quality of the evidence was low or very low. Three outcomes (stroke, age-related cataracts, obesity) were identified as having a "moderate" level of quality. The AMSTAR scores for all health outcomes ranged from 5 to 10.
CONCLUSION
Our study revealed that VE intake is beneficially related to multiple health outcomes. However, future studies on recommended doses and recommended populations of VE are also needed.
SYSTEMATIC REVIEW REGISTRATION
http://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42022339571.
PubMed: 37522003
DOI: 10.3389/fpubh.2023.1035674 -
Journal of Science and Medicine in Sport Nov 2023This systematic review aimed to analyze the effects of different exercise protocols on physical fitness (cardiorespiratory fitness, muscle strength, and body... (Review)
Review
OBJECTIVES
This systematic review aimed to analyze the effects of different exercise protocols on physical fitness (cardiorespiratory fitness, muscle strength, and body composition), quality of life, cancer-related fatigue, and sleep quality in patients with different types of cancer undergoing neoadjuvant treatment.
DESIGN
Systematic review.
METHOD
A comprehensive search of existing literature was carried out using four electronic databases: PubMed, Scopus, Web of Science, and Cochrane Library (published until October 19, 2022). All databases were searched for randomized controlled trials, quasi-experimental investigations, and pre-post investigations assessing the effects of exercise in cancer patients during neoadjuvant treatment. Excluded articles included multicomponent interventions, such as exercise plus diet or behavioral therapy, and investigations performed during adjuvant treatment or survivorship. The methodological quality of each study was assessed using the Physiotherapy Evidence Database (PEDro) scale.
RESULTS
Twenty-seven trials involving 999 cancer patients were included in this review. The interventions were conducted in cancer patients undergoing neoadjuvant treatment for rectal (n = 11), breast (n = 5), pancreatic (n = 4), esophageal (n = 3), gastro-esophageal (n = 2), and prostate (n = 1) cancers, and leukemia (n = 1). Among the investigations included, 14 utilized combined exercise protocols, 11 utilized aerobic exercise, and two utilized both aerobic and resistance training separately. Exercise interventions appeared to improve cardiorespiratory fitness, muscle strength, body composition, and quality of life, although many investigations lacked a between-group analysis.
CONCLUSION
Despite limited evidence, exercise interventions applied during neoadjuvant treatment demonstrate promising potential in enhancing cardiorespiratory fitness, muscle strength, body composition, and overall quality of life. However, a scarcity of evidence remains on the effects of exercise on cancer-related fatigue and sleep quality. Further research with high-quality randomized controlled trials is warranted.
Topics: Humans; Male; Exercise; Exercise Therapy; Fatigue; Neoadjuvant Therapy; Neoplasms; Quality of Life; Female
PubMed: 37696693
DOI: 10.1016/j.jsams.2023.08.178 -
BMC Cancer Aug 2023Patients with advanced pancreatic cancer have a poor prognosis and high burden of cancer-related symptoms. It is necessary to assess the trade-off of clinical benefits...
BACKGROUND
Patients with advanced pancreatic cancer have a poor prognosis and high burden of cancer-related symptoms. It is necessary to assess the trade-off of clinical benefits and possible harms of treatments with anticancer drugs (TAD). This systematic review aims to compare the effectiveness of TAD versus supportive care or no treatment, considering all patient-important outcomes.
METHODS
We searched PubMed, Embase, Cochrane Library, and Epistemonikos. Two reviewers performed selection, data extraction and risk of bias assessment. We assessed certainty of the evidence using the GRADE approach.
RESULTS
We included 14 randomised controlled trials. Chemotherapy may result in a slight increase in overall survival (MD: 2.97 months (95%CI 1.23, 4.70)) and fewer hospital days (MD: -6.7 (-8.3, -5.1)), however, the evidence is very uncertain about its effect on symptoms, quality of life, functional status, and adverse events. Targeted/biological therapy may result in little to no difference in overall survival and a slight increment in progression-free survival (HR: 0.83 (95%CI 0.63, 1.10)), but probably results in more adverse events (RR: 5.54 (95%CI 1.24, 23.97)). The evidence is very uncertain about the effect of immunotherapy in overall survival and functional status.
CONCLUSIONS
The evidence is very uncertain about whether the benefits of using treatment with anticancer drugs outweigh their risks for patients with advanced pancreatic cancer. This uncertainty is further highlighted when considering immunotherapy or a second line of chemotherapy and thus, best supportive care would be an appropriate alternative. Future studies should assess their impact on all patient-important outcomes to inform patients in setting their goals of care.
Topics: Humans; Quality of Life; Antineoplastic Agents; Pancreatic Neoplasms; Immunotherapy
PubMed: 37573294
DOI: 10.1186/s12885-023-11207-4 -
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 -
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