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International Journal of Surgery... Jun 2024The aim was to explore the optimal neoadjuvant therapy strategy for resectable, borderline resectable, and locally advanced pancreatic cancer, in order to provide a... (Meta-Analysis)
Meta-Analysis Comparative Study
Comparing upfront surgery with neoadjuvant treatments in patients with resectable, borderline resectable or locally advanced pancreatic cancer: a systematic review and network meta-analysis of randomized clinical trials.
BACKGROUND
The aim was to explore the optimal neoadjuvant therapy strategy for resectable, borderline resectable, and locally advanced pancreatic cancer, in order to provide a theoretical basis for the development of new neoadjuvant treatment protocols for clinical use.
PATIENTS AND METHODS
The authors reviewed literature titles and abstracts comparing three treatment strategies (neoadjuvant chemoradiotherapy, neoadjuvant chemotherapy, and upfront surgery) in PubMed, Embase, The Cochrane Library, Web of Science from 2009 to 2023 to estimate relative odds ratios for resection rate and hazard ratios (HRs) for overall survival (OS) in all include trials.
RESULTS
A total of nine studies involving 889 patients were included in the analysis. The treatment methods included upfront surgery, neoadjuvant chemotherapy, and neoadjuvant chemoradiotherapy followed by surgery. The network meta-analysis results demonstrated that neoadjuvant chemoradiotherapy followed by surgery was an effective approach in improving OS for resectable and borderline resectable pancreatic cancer (RPC) patients compared to upfront surgery (HR: 0.79, 95% CI: 0.64-0.98) and neoadjuvant chemotherapy (HR: 0.79, 95% CI: 0.64-0.98). Additionally, neoadjuvant chemoradiotherapy significantly increased the margin negative resection (R0) rate and pathological negative lymph node (pN0) rate in patients with resectable and borderline RPC. However, it is worth noting that neoadjuvant chemoradiotherapy increased the risk of grade 3 or higher treatment-related adverse events, including in patients with locally advanced pancreatic cancer.
CONCLUSIONS
The current evidence suggests that neoadjuvant chemoradiotherapy followed by surgery is the optimal choice for treating patients with resectable and borderline RPC. Future research should focus on optimizing neoadjuvant chemoradiotherapy regimens to effectively improve OS while reducing the occurrence of adverse events.
Topics: Humans; Pancreatic Neoplasms; Neoadjuvant Therapy; Network Meta-Analysis; Randomized Controlled Trials as Topic; Pancreatectomy
PubMed: 38935819
DOI: 10.1097/JS9.0000000000001313 -
PloS One 2024The association between red meat, fish, and processed meat consumption and the risk of developing gastrointestinal (GI) cancers remains inconclusive despite several... (Meta-Analysis)
Meta-Analysis
The association between major gastrointestinal cancers and red and processed meat and fish consumption: A systematic review and meta-analysis of the observational studies.
BACKGROUND
The association between red meat, fish, and processed meat consumption and the risk of developing gastrointestinal (GI) cancers remains inconclusive despite several investigations. Therefore, we conducted a systematic review and meta-analysis of observational studies to update the existing scientific evidence.
METHODS
We searched PubMed, Web of Science, and Scopus databases until May 20, 2023. We analyzed observational studies that examined the associations between red and processed meat and fish consumption and GI cancers. We assessed between-study heterogeneity using the χ2 and τ2 tests, as well as I2 statistics. We explored the likelihood of publication bias using Begg's and Egger's tests and trim-and-fill analysis. We reported the overall effect sizes as odds ratios (ORs) with a 95% confidence interval (CI) using a random-effects model.
RESULTS
Of the 21,004 studies identified, 95 studies involving 5,794,219 participants were included in the meta-analysis. The consumption of high levels of red meat, as compared to low levels, was found to significantly increase the risk of developing esophageal, pancreatic, liver, colon, rectal, and colorectal cancers. Similarly, the consumption of high levels of processed meat, as compared to low levels, significantly increased the risk of pancreatic, colon, rectal, and colorectal cancers. In contrast, the consumption of high levels of fish, as compared to low levels, significantly reduced the risk of colon, rectal, and colorectal cancers.
CONCLUSIONS
This meta-analysis provides updated evidence on the association between red meat, processed meat, and fish consumption and the risk of developing five major types of GI cancers.
Topics: Humans; Gastrointestinal Neoplasms; Red Meat; Animals; Observational Studies as Topic; Fishes; Meat Products; Risk Factors; Meat; Seafood; Diet
PubMed: 38924054
DOI: 10.1371/journal.pone.0305994 -
Techniques in Coloproctology Jun 2024Anastomotic leakage (AL) represents a major complication after rectal low anterior resection (LAR). Transanal drainage tube (TDT) placement offers a potential strategy... (Meta-Analysis)
Meta-Analysis
Updated evidence of the effectiveness and safety of transanal drainage tube for the prevention of anastomotic leakage after rectal low anterior resection: a systematic review and meta-analysis.
BACKGROUNDS
Anastomotic leakage (AL) represents a major complication after rectal low anterior resection (LAR). Transanal drainage tube (TDT) placement offers a potential strategy for AL prevention; however, its efficacy and safety remain contentious.
METHODS
A systematic review and meta-analysis were used to evaluate the influence of TDT subsequent to LAR as part of the revision of the surgical site infection prevention guidelines of the Japanese Society of Surgical Infectious Diseases (PROSPERO registration; CRD42023476655). We searched each database, and included randomized controlled trials (RCTs) and observational studies (OBSs) comparing TDT and non-TDT outcomes. The main outcome was AL. Data were independently extracted by three authors and random-effects models were implemented.
RESULTS
A total of three RCTs and 18 OBSs were included. RCTs reported no significant difference in AL rate between the TDT and non-TDT groups [relative risk (RR): 0.69, 95% confidence interval (CI) 0.42-1.15]. OBSs reported that TDT reduced AL risk [odds ratio (OR): 0.45, 95% CI 0.31-0.64]. In the subgroup excluding diverting stoma (DS), TDT significantly lowered the AL rate in RCTs (RR: 0.57, 95% CI 0.33-0.99) and OBSs (OR: 0.41, 95% CI 0.27-0.62). Reoperation rates were significantly lower in the TDT without DS groups in both RCTs (RR: 0.26, 95% CI 0.07-0.94) and OBSs (OR: 0.40, 95% CI 0.24-0.66). TDT groups exhibited a higher anastomotic bleeding rate only in RCTs (RR: 4.28, 95% CI 2.14-8.54), while shorter hospital stays were observed in RCTs [standard mean difference (SMD): -0.44, 95% CI -0.65 to -0.23] and OBSs (SMD: -0.54, 95% CI -0.97 to -0.11) compared with the non-TDT group.
CONCLUSIONS
A universal TDT placement cannot be recommended for all rectal LAR patients. Some patients may benefit from TDT, such as patients without DS creation. Further investigation is necessary to identify the specific beneficiaries.
Topics: Humans; Anastomotic Leak; Drainage; Proctectomy; Randomized Controlled Trials as Topic; Rectum; Anal Canal; Rectal Neoplasms; Treatment Outcome; Female; Male; Observational Studies as Topic; Middle Aged
PubMed: 38916755
DOI: 10.1007/s10151-024-02942-2 -
Clinical Epigenetics Jun 2024Gastrointestinal malignancies encompass a diverse group of cancers that pose significant challenges to global health. The major histocompatibility complex (MHC) plays a... (Review)
Review
BACKGROUND
Gastrointestinal malignancies encompass a diverse group of cancers that pose significant challenges to global health. The major histocompatibility complex (MHC) plays a pivotal role in immune surveillance, orchestrating the recognition and elimination of tumor cells by the immune system. However, the intricate regulation of MHC gene expression is susceptible to dynamic epigenetic modification, which can influence functionality and pathological outcomes.
MAIN BODY
By understanding the epigenetic alterations that drive MHC downregulation, insights are gained into the molecular mechanisms underlying immune escape, tumor progression, and immunotherapy resistance. This systematic review examines the current literature on epigenetic mechanisms that contribute to MHC deregulation in esophageal, gastric, pancreatic, hepatic and colorectal malignancies. Potential clinical implications are discussed of targeting aberrant epigenetic modifications to restore MHC expression and 0 the effectiveness of immunotherapeutic interventions.
CONCLUSION
The integration of epigenetic-targeted therapies with immunotherapies holds great potential for improving clinical outcomes in patients with gastrointestinal malignancies and represents a compelling avenue for future research and therapeutic development.
Topics: Humans; Gastrointestinal Neoplasms; Epigenesis, Genetic; Major Histocompatibility Complex; Gene Expression Regulation, Neoplastic; Immunotherapy; DNA Methylation; Tumor Escape
PubMed: 38915093
DOI: 10.1186/s13148-024-01698-8 -
European Radiology Jun 2024Recent studies have shown the potential of fibroblast activating protein inhibitor (FAPI) PET imaging for pancreatic cancer assessment.
BACKGROUND
Recent studies have shown the potential of fibroblast activating protein inhibitor (FAPI) PET imaging for pancreatic cancer assessment.
PURPOSE
This article is dedicated to comparing the diagnostic efficacy of FAPI PET and [F]fluorodeoxyglucose (FDG) PET in the evaluation of primary tumors, lymph nodes, and distant metastases in pancreatic cancer.
METHODS
In this review, we conducted a systematic search of studies published in PubMed and Web of Science databases up to September 18, 2023. All included studies used radionuclide labeled FAPI and FDG as PET diagnostic tracers to evaluate their applicability in patients with pancreatic cancer.
RESULTS
The FAPI PET imaging group showed significantly higher sensitivity in the detection of primary lesions (1.000, [95% CI: 0.999-1.000]), lymph node metastases (0.624 [95% CI: 0.391-0.834]) and distant metastatic (0.965 [95% CI: 0.804-1.000]) in pancreatic cancer compared to the FDG PET imaging group (0.889 [95% CI: 0.788-0.966], 0.373 [95% CI: 0.163-0.606] and 0.889 [95% CI: 0.689-0.999], respectively). Furthermore, the maximum standardized uptake value (SUVmax) in FAPI PET imaging is significantly higher than that in FDG imaging for primary lesions (mean difference (MD) = 7.51, 95% CI: 5.34-9.67).
CONCLUSION
Compared with [F]FDG PET/CT, FAPI PET imaging showed higher sensitivity, SUVmax. This method can be effectively utilized for the evaluation of pancreatic cancer.
CLINICAL RELEVANCE STATEMENT
Fibroblast activating protein inhibitor PET may be a better alternative to [F]FDG in evaluating primary pancreatic cancer, lymph node metastases, and distant metastases.
KEY POINTS
Fibroblast activating protein inhibitor (FAPI) PET is compared with FDG PET for evaluating pancreatic cancer. Multiple radiolabeled FAPI variants have shown promising results in the diagnosis of pancreatic cancer. FAPI PET imaging effectively helps clinicians diagnose and stage pancreatic cancer.
PubMed: 38907099
DOI: 10.1007/s00330-024-10843-z -
Frontiers in Endocrinology 2024Well-differentiated pancreatic neuroendocrine tumors (PNETs) can be non-functional or functional, e.g. insulinoma and glucagonoma. The majority of PNETs are sporadic,... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Well-differentiated pancreatic neuroendocrine tumors (PNETs) can be non-functional or functional, e.g. insulinoma and glucagonoma. The majority of PNETs are sporadic, but PNETs also occur in hereditary syndromes, primarily multiple endocrine neoplasia type 1 (MEN1). The Knudson hypothesis stated a second, somatic hit in as the cause of PNETs of MEN1 syndrome. In the recent years, reports on genetic somatic events in both sporadic and hereditary PNETs have emerged, providing a basis for a more detailed molecular understanding of the pathophysiology. In this systematic review and meta-analysis, we made a collation and statistical analysis of aggregated frequent genetic alterations and potential driver events in human grade G1/G2 PNETs.
METHODS
A systematic search was performed in concordance with the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) reporting guidelines of 2020. A search in Pubmed for published studies using whole exome, whole genome, or targeted gene panel (+400 genes) sequencing of human G1/G2 PNETs was conducted at the 25 of September 2023. Fourteen datasets from published studies were included with data on 221 patients and 225 G1/G2 PNETs, which were divided into sporadic tumors, and hereditary tumors with pre-disposing germline variants, and tumors with unknown germline status. Further, non-functioning and functioning PNETs were distinguished into two groups for pathway evaluation. The collated genetical analyses were conducted using the 'maftools' R-package.
RESULTS
Sporadic PNETs accounted 72.0% (162/225), hereditary PNETs 13.3% (30/225), unknown germline status 14.7% (33/225). The most frequently altered gene was , with somatic variants and copy number variations in overall 42% (95/225); hereditary PNETs (germline variations in , , , , , , and/or ) 57% (16/30); sporadic PNETs 36% (58/162); unknown germline status 64% (21/33). The point mutations/indels were distributed throughout . Overall, (16%, 37/225) and -variants (12%, 27/225) were also abundant with missense mutations clustered in mutational hotspots associated with histone binding, and translocase activity, respectively. mutations occurred more frequently in PNETs with mutations, p<0.05. While functioning PNETs shared few variated genes, non-functioning PNETs had more recurrent variations in genes associated with the Phosphoinositide 3-kinase, Wnt, NOTCH, and Receptor Tyrosine Kinase-Ras signaling onco-pathways.
DISCUSSION
The somatic genetic alterations in G1/G2 PNETs are diverse, but with distinct differences between sporadic vs. hereditary, and functional vs. non-functional PNETs. Increased understanding of the genetic alterations may lead to identification of more drivers and driver hotspots in the tumorigenesis in well-differentiated PNETs, potentially giving a basis for the identification of new drug targets. (Funded by Novo Nordisk Foundation, grant number NNF19OC0057915).
Topics: Humans; Pancreatic Neoplasms; Neuroendocrine Tumors; Sequence Analysis, DNA; Mutation
PubMed: 38868744
DOI: 10.3389/fendo.2024.1351624 -
Journal of the ASEAN Federation of... 2024Insulinoma is one of the causes of recurrent hypoglycemia, one of the chief complaints for emergency department admission. The gold standard in diagnosing insulinoma is... (Review)
Review
BACKGROUND
Insulinoma is one of the causes of recurrent hypoglycemia, one of the chief complaints for emergency department admission. The gold standard in diagnosing insulinoma is a 72-hour fasting test which is inconvenient and inefficient as it requires hospitalization. Research has found that measurement of insulin and C-peptide during OGTT may help diagnose insulinoma. We aimed to assess the diagnostic value of OGTT in diagnosing insulinoma.
METHODOLOGY
The literature search was conducted on 19 August 2022 using several databases (MEDLINE, Scopus, Embase, and ScienceDirect). All studies that measured OGTT as diagnostic tools in diagnosing insulinoma and 72-hour fasting test as reference standard were included. The quality assessment of the selected studies was based on the Centre of Evidence-Based Medicine University of Oxford and the Quality Assessment of Diagnostic Accuracy-2 tool (QUADAS-2). Analysis of the included studies was performed qualitatively. This study was registered on PROSPERO (CRD42022360205).
RESULTS
A total of two case-control studies (106 patients) were included, which were at risk of bias and low concern of applicability. Both studies demonstrated that the combination of insulin and C-peptide levels measured during OGTT had high specificity, sensitivity, positive predictive value, and negative predictive value in diagnosing insulinoma compared to the reference standard. A logistic regression model of 8.305 - (0.441 × insulin 2-h/0-h) - (1.679 × C-peptide 1-h/0-h) >0.351 has the highest diagnostic value in one study (AUC 0.97, Sensitivity 86.5%, Specificity 95.2%, PPV 94.1, NPV 88.9).
CONCLUSION
The measurement of 0-h and 2-h insulin and C-peptide levels during 2-h OGTT was found in two small case-control studies with a total of 106 patients to have good sensitivity and specificity. However, due to these limitations, future research is still needed to validate the potential use of OGTT for the diagnosis of insulinoma.
Topics: Humans; C-Peptide; Insulinoma; Glucose Tolerance Test; Pancreatic Neoplasms; Insulin; Sensitivity and Specificity; Insulin Secretion
PubMed: 38863915
DOI: 10.15605/jafes.039.01.16 -
Cirugia Y Cirujanos 2024The effect of a pre-operative biliary stent on complications after pancreaticoduodenectomy (PD) remains controversial. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The effect of a pre-operative biliary stent on complications after pancreaticoduodenectomy (PD) remains controversial.
MATERIALS AND METHOD
We conducted a meta-analysis according to the preferred reporting items for systematic reviews and meta-analyses guidelines, and PubMed, Web of Science Knowledge, and Ovid's databases were searched by the end of February 2023. 35 retrospective studies and 2 randomized controlled trials with a total of 12641 patients were included.
RESULTS
The overall complication rate of the pre-operative biliary drainage (PBD) group was significantly higher than the no-PBD group (odds ratio [OR] 1.46, 95% confidence interval [CI] 1.22-1.74; p < 0.0001), the incidence of post-operative delayed gastric emptying was increased in patients with PBD compared those with early surgery (OR 1.21, 95% CI: 1.02-1.43; p = 0.03), and there was a significant increase in post-operative wound infections in patients receiving PBD with an OR of 2.2 (95% CI: 1.76-2.76; p < 0.00001).
CONCLUSIONS
PBD has no beneficial effect on post-operative outcomes. The increase in post-operative overall complications and wound infections urges the exact indications for PBD and against routine pre-operative biliary decompression, especially for patients with total bilirubin < 250 umol/L waiting for PD.
Topics: Humans; Drainage; Pancreaticoduodenectomy; Preoperative Care; Postoperative Complications; Stents; Surgical Wound Infection; Randomized Controlled Trials as Topic; Gastric Emptying; Ampulla of Vater; Pancreatic Neoplasms; Common Bile Duct Neoplasms
PubMed: 38862121
DOI: 10.24875/CIRU.23000318 -
Scientific Reports Jun 2024The effectiveness of psychological interventions (PI) for malignant diseases is controversial. We aimed to investigate the effect of PI on survival and quality of life... (Meta-Analysis)
Meta-Analysis
The effectiveness of psychological interventions (PI) for malignant diseases is controversial. We aimed to investigate the effect of PI on survival and quality of life (QoL) in patients with cancer. We performed a systematic search of MEDLINE, Cochrane, and Embase databases to identify randomized controlled trials comparing PI to standard care (PROSPERO registration number CRD42021282327). Outcomes were overall survival (OS), recurrence-free survival (RFS), and different domains of QoL. Subgroup analysis was performed based on the provider-, type-, environment-, duration of intervention; cancer stage, and type. Pooled hazard ratios (HR) and standardized mean difference (SMD) with 95% confidence intervals (CI) were calculated using a random-effects model. The OS and RFS did not differ significantly between the two groups (OS:HR = 0.97; CI 0.87-1.08; RFS:HR = 0.99; CI 0.84-1.16). However, there was significant improvement in the intervention group in all the analyzed domains of QoL; in the global (SMD = 0.65; CI 0.35-0.94), emotional (SMD = 0.64; CI 0.33-0.95), social (SMD = 0.32; CI 0.13-0.51) and physical (SMD = 0.33; CI 0.05-0.60) domains. The effect of PI on QoL was generally positive immediately, 12 and 24 weeks after intervention, but the effect decreased over time and was no longer found significant at 48 weeks. The results were better in the breast cancer group and early stages of cancer. PIs do not prolong survival, but they significantly improve the QoL of cancer patients. PI should be added as standard of care 3-4 times a year, at least for patients with early-stage cancer.
Topics: Humans; Quality of Life; Randomized Controlled Trials as Topic; Neoplasms; Psychosocial Intervention; Neoplasm Staging; Female
PubMed: 38853187
DOI: 10.1038/s41598-024-63431-y -
Frontiers in Immunology 2024A single immune checkpoint inhibitor (ICI) regimen has limited value in treating advanced bile tract cancer (BTC); therefore, ICI combination therapy is often applied.... (Meta-Analysis)
Meta-Analysis
Clinical outcomes of immune checkpoint inhibitor combined with other targeted or immunological therapy regimens for the treatment of advanced bile tract cancer: a systematic review and meta-analysis.
BACKGROUND AND AIMS
A single immune checkpoint inhibitor (ICI) regimen has limited value in treating advanced bile tract cancer (BTC); therefore, ICI combination therapy is often applied. This meta-analysis aimed to evaluate the effectiveness and safety of ICI combination therapy for advanced BTC.
METHODS
The study protocol was registered on PROSPERO (CRD42023452422). Data on the median progression-free survival (PFS), median overall survival (OS), objective response rate (ORR), disease control rate (DCR), and grade ≥3 adverse events (AEs) reported in relevant studies were pooled and analyzed to determine the efficacy and safety of ICI combination therapy.
RESULTS
In total, 15 studies with 665 patients were included in this meta-analysis. The overall ORR and DCR were 34.6% and 77.6%, respectively. The overall median PFS and OS were 6.06 months [95% confidence interval (CI): 4.91-7.21] and 12.11 months (95% CI: 10.66-13.55), respectively. Patients receiving ICI combination therapy in addition to other therapies had a considerably prolonged median PFS and OS (z=9.69, <0.001 and z=16.17, <0.001). Patients treated as first-line treatment had a substantially longer median PFS and OS compared to patients treated as non-first-line treatment (z=11.19, <0.001 and z=49.17, <0.001). The overall pooled grade ≥3 AEs rate was 38.2% (95% CI: 0.268-0.497) and was not influenced by whether ICI therapy was combined with other treatments or not or the treatment line.
CONCLUSION
Advanced BTC patients may benefit from ICI combination treatment without additional AEs. However, concurrent chemotherapy or radiotherapy is still needed to achieve better outcomes.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/, identifier CRD42023452422.
Topics: Humans; Immune Checkpoint Inhibitors; Antineoplastic Combined Chemotherapy Protocols; Treatment Outcome; Biliary Tract Neoplasms; Immunotherapy
PubMed: 38840927
DOI: 10.3389/fimmu.2024.1378760