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Clinics (Sao Paulo, Brazil) 2022The increase in the incidence of pancreatic and biliary cancers has attracted the search for methods of early detection of diseases and biomarkers. The authors propose... (Review)
Review
INTRODUCTION
The increase in the incidence of pancreatic and biliary cancers has attracted the search for methods of early detection of diseases and biomarkers. The authors propose to analyze new findings on the association between microbiota and Pancreatic Ductal Adenocarcinoma (PDAC) or Cholangiocarcinoma (CCA).
METHODS
This systematic review was carried out according to the items of Preferred Reports for Systematic Reviews and Protocol Meta-Analysis (PRISMA-P). This study was registered by the Prospective Register of Systematic Reviews (PROSPERO), identification code CRD42020192748 before the review was carried out. Articles were selected from the PUBMED, EMBASE, and Cochrane databases.
RESULTS
Most studies (86.67%) used 16s rRNA as a sequencing method. The main comorbidities found were diabetes mellitus, systemic arterial hypertension, and dyslipidemia. Many studies were limited by the small number of participants, but the biases were mostly low. There was very little concordance about the composition of the microbiome of different sites, for both case and control groups when compared to other studies' results. Bile sample analysis was the one with a greater agreement between studies, as three out of four studies found Escherichia in cases of CCA.
CONCLUSION
There was great disagreement in the characterization of both the microbiota of cases and control groups. Studies are still scarce, making it difficult to adequately assess the data in this regard. It was not possible to specify any marker or to associate any genus of microbiota bacteria with PDAC or CCA.
Topics: Carcinoma, Pancreatic Ductal; Humans; Microbiota; Pancreatic Neoplasms; RNA, Ribosomal, 16S; Syndrome
PubMed: 36122499
DOI: 10.1016/j.clinsp.2022.100101 -
Cureus Jun 2021Over the years, the world has witnessed many advances in diagnosing and treating multiple types of cancers. These breakthroughs have revolutionized the understanding of... (Review)
Review
Over the years, the world has witnessed many advances in diagnosing and treating multiple types of cancers. These breakthroughs have revolutionized the understanding of the molecular drive behind these neoplasms, leading to tangible therapeutic evolution and promising prognostic implications. However, pancreatic cancer remains a highly lethal disease. With recent discoveries, modern medicine has been able to delineate histopathologic subtypes of pancreatic cancer in hopes of improved diagnosis and treatment to improve survival. A once vague entity, clear cell adenocarcinoma of the pancreas, in particular, has been better characterized on a histopathological and molecular level over the past two decades. With novel technological support, this disease has become less inconspicuous, and more researchers have reported its occurrence. Its diagnosis relies heavily on a mix of histological and immunohistochemical clues such as a clear cell cytoplasm and positivity for cytokeratins and other markers. However, new molecular markers, such as hepatocyte nuclear factor 1 beta, have been associated with this entity and may aid in further diagnostic and therapeutic strategies. This review article aims to portray how the identification and description of clear cell adenocarcinoma of the pancreas have evolved over the past few decades and how this may impact future treatment strategies.
PubMed: 34150416
DOI: 10.7759/cureus.15668 -
HPB : the Official Journal of the... Aug 2022Surgery for patients with pancreatic cancer carries a high risk of major post-operative complications and only marginally improves overall survival. This review aims to... (Review)
Review
BACKGROUND
Surgery for patients with pancreatic cancer carries a high risk of major post-operative complications and only marginally improves overall survival. This review aims to assess the impact of surgical resection on health-related quality of life (HRQOL) of pancreatic cancer patients.
METHODS
A systematic review of the literature was performed according to the PRISMA guidelines. All studies assessing QOL using validated questionnaires in pancreatic cancer patients undergoing surgical resection were included.
RESULTS
Twenty-two studies were assessed. Patients reported a decrease in physical, social and global scales within the first 3 months after surgery. These values showed improvement and were comparable to baseline values by 6 months. Recovery in emotional functioning towards baseline figures was demonstrated in the first 3 months post-operatively. Symptom scales including pain, fatigue and diarrhoea deteriorated after surgery, but reverted to baseline after 3-6 months.
CONCLUSIONS
Surgical resection for pancreatic cancer has short-term negative impact on QOL. In the longer term, this will improve and eventually recover to baseline values after 6 months. Knowledge on the impact of surgery on QOL of pancreatic cancer patients is necessary to facilitate decision-making and tailoring of surgical techniques to the individual patient.
Topics: Humans; Pancreatic Neoplasms; Prospective Studies; Quality of Life; Surveys and Questionnaires
PubMed: 35304039
DOI: 10.1016/j.hpb.2022.02.013 -
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 -
HPB : the Official Journal of the... Aug 2016Pancreatic ductal adenocarcinoma (PDAC) continues to be associated with a poor prognosis. This systematic review aimed to summarize the literature regarding potential... (Review)
Review
BACKGROUND
Pancreatic ductal adenocarcinoma (PDAC) continues to be associated with a poor prognosis. This systematic review aimed to summarize the literature regarding potential prognostic biomarkers to facilitate validation studies and clinical application.
METHODS
A systematic review was performed (2004-2014) according to PRISMA guidelines. Studies were ranked using REMARK criteria and the following outcomes were examined: overall/disease free survival, nodal involvement, tumour characteristics, metastasis, recurrence and resectability.
RESULTS
256 biomarkers were identified in 158 studies. 171 biomarkers were assessed with respect to overall survival: urokinase-type plasminogen activator receptor, atypical protein kinase C and HSP27 ranked the highest. 33 biomarkers were assessed for disease free survival: CD24 and S100A4 were the highest ranking. 17 biomarkers were identified for lymph node involvement: Smad4/Dpc4 and FOXC1 ranked highest. 13 biomarkers were examined for tumour grade: mesothelin and EGFR were the highest ranking biomarkers. 10 biomarkers were identified for metastasis: p16 and sCD40L were the highest ranking. 4 biomarkers were assessed resectability: sCD40L, s100a2, Ca 19-9, CEA.
CONCLUSION
This review has identified and ranked specific biomarkers that should be a primary focus of ongoing validation and clinical translational work in PDAC.
Topics: Biomarkers, Tumor; Carcinoma, Pancreatic Ductal; Disease Progression; Disease-Free Survival; Humans; Lymphatic Metastasis; Neoplasm Grading; Neoplasm Recurrence, Local; Pancreatectomy; Pancreatic Neoplasms; Predictive Value of Tests; Risk Factors; Time Factors; Treatment Outcome
PubMed: 27485059
DOI: 10.1016/j.hpb.2016.05.004 -
Surgery Nov 2022This systematic review and meta-analysis aimed to give an overview on the postoperative outcome after a minimally invasive (ie, laparoscopic and robot-assisted) central... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
This systematic review and meta-analysis aimed to give an overview on the postoperative outcome after a minimally invasive (ie, laparoscopic and robot-assisted) central pancreatectomy and open central pancreatectomy with a specific emphasis on the postoperative pancreatic fistula. For benign and low-grade malignant lesions in the pancreatic neck and body, central pancreatectomy may be an alternative to distal pancreatectomy. Exocrine and endocrine insufficiency occur less often after central pancreatectomy, but the rate of postoperative pancreatic fistula is higher.
METHODS
An electronic search was performed for studies on elective minimally invasive central pancreatectomy and open central pancreatectomy, which reported on major morbidity and postoperative pancreatic fistula in PubMed, Cochrane Register, Embase, and Google Scholar until June 1, 2021. A review protocol was developed a priori and registered in PROSPERO as CRD42021259738. A meta-regression was performed by using a random effects model.
RESULTS
Overall, 41 studies were included involving 1,004 patients, consisting of 158 laparoscopic minimally invasive central pancreatectomies, 80 robot-assisted minimally invasive central pancreatectomies, and 766 open central pancreatectomies. The overall rate of postoperative pancreatic fistula was 14%, major morbidity 14%, and 30-day mortality 1%. The rates of postoperative pancreatic fistula (17% vs 24%, P = .194), major morbidity (17% vs 14%, P = .672), and new-onset diabetes (3% vs 6%, P = .353) did not differ significantly between minimally invasive central pancreatectomy and open central pancreatectomy, respectively. Minimally invasive central pancreatectomy was associated with significantly fewer blood transfusions, less exocrine pancreatic insufficiency, and fewer readmissions compared with open central pancreatectomy. A meta-regression was performed with a random effects model between minimally invasive central pancreatectomy and open central pancreatectomy and showed no significant difference for postoperative pancreatic fistula (random effects model 0.16 [0.10; 0.24] with P = .789), major morbidity (random effects model 0.20 [0.15; 0.25] with P = .410), and new-onset diabetes mellitus (random effects model 0.04 [0.02; 0.07] with P = .651).
CONCLUSION
In selected patients and in experienced hands, minimally invasive central pancreatectomy is a safe alternative to open central pancreatectomy for benign and low-grade malignant lesions of the neck and body. Ideally, further research should confirm this with the main focus on postoperative pancreatic fistula and endocrine and exocrine insufficiency.
Topics: Humans; Laparoscopy; Pancreas; Pancreatectomy; Pancreatic Fistula; Pancreatic Neoplasms; Postoperative Complications; Retrospective Studies; Treatment Outcome
PubMed: 35987787
DOI: 10.1016/j.surg.2022.06.024 -
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 -
Diagnostics (Basel, Switzerland) Aug 2022There is a pressing demand for the development of cancer-specific diagnostic imaging tools, particularly for staging of pancreatic-, gastric- or cholangiocarcinoma, as... (Review)
Review
INTRODUCTION
There is a pressing demand for the development of cancer-specific diagnostic imaging tools, particularly for staging of pancreatic-, gastric- or cholangiocarcinoma, as current diagnostic imaging techniques, including CT, MRI and PET using FDG, are not fully adequate. The novel PET-tracer "FAPI" has the potential to visualize even small tumour deposits employing the tumour-specific expression of fibroblast-activating protein (FAP) in malignant cells.
METHODS
We performed a systematic review to select studies investigating the use of FAPI PET for staging pancreatic-, gastric- and cholangiocarcinoma (PROSPERO CRD42022329512). Patient-wise and lesion-wise comparisons were performed for primary tumour (T), lymph nodes (N), organ metastases (M) and peritoneal carcinomatosis (PC). Maximum standardized uptake values (SUVmax) and tumour-to-background ratios (TBR) were compared between PET using FAPI versus FDG (if reported).
RESULTS
Ten articles met the inclusion criteria. In all studies, FAPI PET showed superiority over FDG-PET/CT/MRI for the detection of T, N, M and PC, both in the patient-wise and in lesion-wise comparisons (when performed). Additionally, higher SUVmax and TBRmax values were reported for use of FAPI compared to FDG.
CONCLUSIONS
The positive results of this review warrant prospective clinical studies to investigate the accuracy and clinical value of FAPI PET for diagnosing and staging patients with pancreatic-, gastric- and cholangiocarcinoma.
PubMed: 36010308
DOI: 10.3390/diagnostics12081958 -
Translational Research : the Journal of... Jun 2022Extensive research is focused on the role of liquid biopsy in pancreatic cancer since reliable diagnostic and follow-up biomarkers represent an unmet need for this... (Meta-Analysis)
Meta-Analysis Review
Extensive research is focused on the role of liquid biopsy in pancreatic cancer since reliable diagnostic and follow-up biomarkers represent an unmet need for this highly lethal malignancy. We performed a systematic review and meta-analysis on the prognostic value of exosomal biomarkers in pancreatic ductal adenocarcinoma (PDAC). MEDLINE, Embase, Scopus, Web of Science, and CENTRAL were systematically searched on the 18th of January, 2021 for studies reporting on the differences in overall (OS) and progression-free survival (PFS) in PDAC patients with positive vs negative exosomal biomarkers isolated from blood. The random-effects model estimated pooled multivariate-adjusted (AHR) and univariate hazard ratios (UHRs) with 95% confidence intervals (CIs). Eleven studies comprising 634 patients were eligible for meta-analysis. Detection of positive exosomal biomarkers indicated increased risk of mortality (UHR = 2.81, CI:1.31-6,00, I = 88.7%, P < 0.001), and progression (UHR = 3.33, CI: 2.33-4.77, I = 0, P = 0.879) across various disease stages. Positive exosomal biomarkers identified preoperatively revealed a higher risk of mortality in resectable stages (UHR = 5.55, CI: 3.24-9.49, I = 0, P = 0.898). The risk of mortality in unresectable stages was not significantly increased with positive exosomal biomarkers (UHR = 2.51, CI: 0.55-11.43, I = 90.3%, P < 0.001). Detectable exosomal micro ribonucleic acids were associated with a decreased OS (UHR = 4.08, CI: 2.16-7.69, I = 46.9%, P = 0.152) across various stages. Our results reflect the potential of exosomal biomarkers for prognosis evaluation in PDAC. The associated heterogeneity reflects the variability of study methods and need for their uniformization before transition to clinical use.
Topics: Biomarkers, Tumor; Carcinoma, Pancreatic Ductal; Exosomes; Humans; Pancreatic Neoplasms; Prognosis
PubMed: 35066189
DOI: 10.1016/j.trsl.2022.01.001 -
Toxics Feb 2023N-nitroso compounds (NOCs) are a class of chemical carcinogens found in various environmental sources such as food, drinking water, cigarette smoke, the work... (Review)
Review
N-nitroso compounds (NOCs) are a class of chemical carcinogens found in various environmental sources such as food, drinking water, cigarette smoke, the work environment, and the indoor air population. We conducted a systematic review and meta-analysis to investigate the links between nitrate, nitrite, and NOCs in food and water and the risk of gastrointestinal (GI) cancers, including esophageal cancer (EC), gastric cancer (GC), colorectal cancer (CRC), and pancreatic cancer (PC). A systematic search of the literature in Scopus, PubMed, Google Scholar, Web of Science, ScienceDirect, and Embase was performed for studies on the association between NOCs in drinking water and food sources and GI cancers. Forest plots of relative risk (RR) were constructed for all the cancer sites and the intake sources. The random-effects model was used to assess the heterogeneity between studies. Forty articles were included after removing duplicate and irrelevant articles. The meta-analysis indicated that the intake of high dose vs. low dose of these compounds was significantly associated with the overall GI cancer risk and nitrite (RR = 1.18, 95% CI = 1.07-1.29), and N-nitrosodimethylamine (NDMA) (RR = 1.32, 95% CI = 1.06-1.65). We found that dietary nitrite intake increased GC (RR = 1.33, 95% CI = 1.02-1.73), and EC (RR = 1.38, 95% CI = 1.01-1.89). Additionally, dietary NDMA intake increased the risk of CRC (RR = 1.36, 95% CI = 1.18-1.58). This meta-analysis provides some evidence that the intake of dietary and water nitrate, nitrite, and NOCs may be associated with GI cancers. In particular, dietary nitrite is linked to GC and EC risks and dietary NDMA intake is associated with CRC.
PubMed: 36851064
DOI: 10.3390/toxics11020190