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International Journal of Surgery... Aug 2018The role of surgical resection for patients with recurrent or metastatic gastrointestinal stromal tumors is still controversial. This meta-analysis aims to investigate... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The role of surgical resection for patients with recurrent or metastatic gastrointestinal stromal tumors is still controversial. This meta-analysis aims to investigate the clinical outcomes of surgery combined with tyrosine kinase inhibitors among patients with recurrent or metastatic gastrointestinal stromal tumors.
METHODS
We systematically searched PubMed, EMBASE, the Cochrane Library and Wanfangdata without language restriction. Random effect models were used to estimate pooled hazard ratio and the corresponding 95% confidence intervals. Subgroup analyses, sensitivity analysis and trim and fill analysis were also performed.
RESULTS
A total of 1416 patient from 9 studies were finally enrolled in this meta-analysis. The summary results showed that surgery combined with tyrosine kinase inhibitors showed a tendency of a longer overall survival compared with tyrosine kinase inhibitors treatment alone (HR by random-effects model 0.68, 95% CI 0.54-0.85, I = 44.7%) and improved progress-free survival (HR by random-effects model 0.50,95% CI, 0.33-0.76, I = 17.9%). The trim and fill analysis and sensitive analysis indicated the relatively robust result.
CONCLUSION
Surgery combined with tyrosine kinase inhibitors therapy is associated with a better overall survival and progression free survival for patients with recurrent or metastatic gastrointestinal stromal tumors as compared with TKIs treatment alone.
Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Combined Modality Therapy; Disease-Free Survival; Female; Gastrointestinal Neoplasms; Gastrointestinal Stromal Tumors; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Protein Kinase Inhibitors; Treatment Outcome
PubMed: 29920339
DOI: 10.1016/j.ijsu.2018.06.016 -
Health Technology Assessment... Jul 2005To assess the clinical and cost-effectiveness of imatinib in the treatment of unresectable and/or metastatic, KIT-positive, gastrointestinal stromal tumours (GISTs),... (Review)
Review
OBJECTIVES
To assess the clinical and cost-effectiveness of imatinib in the treatment of unresectable and/or metastatic, KIT-positive, gastrointestinal stromal tumours (GISTs), relative to current standard treatments.
DATA SOURCES
Electronic databases.
REVIEW METHODS
As there were no randomised trials that have directly compared imatinib with the current standard treatment in patients with advanced GIST, this review included non-randomised controlled studies, cohort studies, and case series that reported effectiveness results of treatment with imatinib and/or other interventions in patients with advanced GIST. The effectiveness assessment was based on the comparison of results from imatinib trials and results from studies of historical control patients. Economic evaluation was mainly based on an assessment and modification (when judged necessary) of a model submitted by Novartis.
RESULTS
Evidence from published uncontrolled trials involving 187 patients, and from abstracts reporting similar uncontrolled trials involving 1700 patients, indicates that approximately 50% of imatinib-treated individuals with advanced GIST experience a dramatic clinical response in terms of at least a 50% reduction in tumour mass. At present, although useful data are accumulating, it is not possible to predict which patients may respond in this way. Fifteen studies where possible GIST patients had been treated with therapies other than imatinib or best supportive care were also identified. All imatinib-treated patients experienced adverse effects, although they were relatively mild. Overall, imatinib was reported to be well tolerated. The most common serious events included unspecified haemorrhage and neutropenia. Skin rash, oedema and periorbital oedema were the common adverse events observed. Patients on the highest dose regimen (1000 mg per day in one trial) may experience dose-limiting drug toxicity. A structured assessment was carried out of the Novartis economic evaluation of imatinib for unresectable and/or metastatic GIST. The model was clearly presented and well written, its structure and input data were transparent, and the level of simplification was reasonable in terms of the objectives and data availability. However, the original Novartis model overestimated the cost-effectiveness of imatinib because of disproportion of survival and time-to-treatment failure in the imatinib arm, and the use of a possibly biased survival curve for patients in the control arm. The original Novartis model was modified to correct these two important shortcomings, which made it less sensitive to the choice of the survival curve for the control patients. According to the modified Novartis model, the estimated cost per quality-adjusted life-year (QALY) was 85,224 UK pounds (range 51,515--98,889 UK pounds) after 2 years, 41,219 UK pounds (27,331--44,236 UK pounds) after 5 years and 29,789 UK pounds (21,404--33,976 UK pounds) after 10 years. The results from a new Birmingham model were also within the range of estimates from the modified Novartis model.
CONCLUSIONS
Evidence from uncontrolled studies indicates that the treatment with imatinib brings about clinically significant shrinkage of tumour mass in about half of patients with unresectable and/or metastatic, KIT-positive GIST. Results of modelling based on data from uncontrolled studies suggest that imatinib treatment improves survival in patients with unresectable and/or metastatic GIST. The economic evaluation modelling suggests that the cost per QALY gained ranges from 51,515 to 98,889 UK pounds after 2 years, from 27,331 to 44,236 UK pounds after 5 years, and from 21,404 to 33,976 UK pounds after 10 years. Further research is needed into quality of life within trials involving patients with advanced malignancy, and long-term follow-up of adverse events is needed. Subgroup analysis of which, if any, patient types have a better or worse response to imatinib is also required. Analysis of individual patient data may be a good way of exploring these issues. There are many uncertainties surrounding imatinib prescription, such as the length of time patients should be on imatinib, the dose, drug resistance and the optimum time-point in the disease course at which to give the drug. Secondary research such as an update of this systematic review and a reassessment of the model is highly recommended when ongoing trials reach completion.
Topics: Adult; Aged; Antineoplastic Agents; Benzamides; Controlled Clinical Trials as Topic; Cost-Benefit Analysis; Female; Gastrointestinal Stromal Tumors; Humans; Imatinib Mesylate; Male; Middle Aged; Neoplasm Metastasis; Piperazines; Pyrimidines; State Medicine; United Kingdom
PubMed: 15985189
DOI: 10.3310/hta9250 -
Archives of Dermatological Research Apr 2018Multipotent mesenchymal stem/stromal cells (MSCs) have strong tropism towards cancer cells, thus being tested as tools for the targeted delivery of therapeutic... (Meta-Analysis)
Meta-Analysis Review
Subcutaneous injection of multipotent mesenchymal stromal cells admixed with melanoma cells in mice favors tumor incidence and growth: a systematic review and meta-analysis.
Multipotent mesenchymal stem/stromal cells (MSCs) have strong tropism towards cancer cells, thus being tested as tools for the targeted delivery of therapeutic substances for the treatment of melanoma. However, different experimental approaches for melanoma induction and MSC treatment can have a direct impact on the outcomes. Systematic search was carried out in three databases (PubMed, Scopus, and Web of Science) to include all studies, where stem cells were used as intervention for animal models for melanoma. Selected articles were classified according to SYRCLE's risk of bias tool for animals' studies. Experimental variables and published data for tumor incidence and growth were extracted from the eligible articles and standardized using Hedge's G for random effects meta-analysis and meta-regression. From 627 entries, 11 articles were eligible for meta-analysis. All studies tested the effects of a single injection of mesenchymal stem/stromal cells (MSCs) (from bone marrow or adipose tissue) admixed with B16 mouse melanoma cells (B16-F0 or B16-F10) or with human melanoma cells (A375 or M4Beu) in mice. Mean SYRCLE score was 3.09 out of 10. Results from random effects meta-analysis indicate that MSCs favored both tumor incidence and tumor growth (p = 0.001) in melanoma. Our results show that MSCs are protumorigenic in co-injection mice models for melanoma, increasing both tumor incidence and growth.
Topics: Animals; Cell Line, Tumor; Cell Proliferation; Cell- and Tissue-Based Therapy; Cocarcinogenesis; Coculture Techniques; Humans; Melanoma, Experimental; Mesenchymal Stem Cells; Mice; Mice, Inbred C57BL
PubMed: 29396596
DOI: 10.1007/s00403-018-1819-7 -
Cells Jun 2023Tumor endothelial cells (TECs) are key stromal components of the tumor microenvironment, and are essential for tumor angiogenesis, growth and metastasis. Accumulating... (Review)
Review
Tumor endothelial cells (TECs) are key stromal components of the tumor microenvironment, and are essential for tumor angiogenesis, growth and metastasis. Accumulating evidence has shown that small single-stranded non-coding microRNAs (miRNAs) act as powerful endogenous regulators of TEC function and blood vessel formation. This systematic review provides an up-to-date overview of these endothelial miRNAs. Their expression is mainly regulated by hypoxia, pro-angiogenic factors, gap junctions and extracellular vesicles, as well as long non-coding RNAs and circular RNAs. In preclinical studies, they have been shown to modulate diverse fundamental angiogenesis-related signaling pathways and proteins, including the vascular endothelial growth factor (VEGF)/VEGF receptor (VEGFR) pathway; the rat sarcoma virus (Ras)/rapidly accelerated fibrosarcoma (Raf)/mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) pathway; the phosphoinositide 3-kinase (PI3K)/AKT pathway; and the transforming growth factor (TGF)-β/TGF-β receptor (TGFBR) pathway, as well as krüppel-like factors (KLFs), suppressor of cytokine signaling (SOCS) and metalloproteinases (MMPs). Accordingly, endothelial miRNAs represent promising targets for future anti-angiogenic cancer therapy. To achieve this, it will be necessary to further unravel the regulatory and functional networks of endothelial miRNAs and to develop safe and efficient TEC-specific miRNA delivery technologies.
Topics: Humans; MicroRNAs; Endothelial Cells; Vascular Endothelial Growth Factor A; Phosphatidylinositol 3-Kinases; Neoplasms; Mitogen-Activated Protein Kinase Kinases; Receptors, Vascular Endothelial Growth Factor; Tumor Microenvironment
PubMed: 37443725
DOI: 10.3390/cells12131692 -
World Journal of Surgical Oncology Jul 2014In past decades, laparoscopic surgery has been introduced for the treatment of gastrointestinal stromal tumors (GISTs). Recently, additional studies comparing... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
In past decades, laparoscopic surgery has been introduced for the treatment of gastrointestinal stromal tumors (GISTs). Recently, additional studies comparing laparoscopic versus open surgery for gastric GISTs have been published, and an updated meta-analysis of this subject is necessary.
METHODS
A systematic search was conducted in PubMed, Embase, Cochrane Library, and Web of Science. Comparative studies of laparoscopic and open surgery for gastric GISTs published before June 2014 were identified from databases. The Newcastle-Ottawa Quality Assessment Scale was used to perform quality assessment and original data were extracted. The statistical software STATA (version 12.0) was used for the meta-analysis.
RESULTS
Finally, 22 studies, including a total of 1,166 cases, meet the inclusion criteria for meta-analysis. The operation time was similar between laparoscopic and open surgery. Compared to open surgery, laparoscopic resection was associated withless blood loss (WMD = -58.91 ml; 95% CI, -84.60 to -33.22 ml; P <0.01); earlier time to flatus (WMD = -1.31 d; 95% CI, -1.56 to -1.06, P <0.01) and oral diet (WMD = -1.75 d; 95% CI, -2.12 to -1.39; P <0.01); shorter hospital stay (WMD = -3.68 d; 95% CI, -4.47 to -2.88; P <0.01); and decreased overall complications (relative risk = 0.57; 95% CI, 0.37 to 0.89; P = 0.01). For long-term outcomes, there were no significant differences between two surgical procedures on recurrence.
CONCLUSION
Laparoscopic surgery for gastric GISTs is acceptable for selective patients with better short-term outcomes compared with open surgery. The long-term survival situation of patients mainly depends on the nature of tumor itself, and laparoscopic surgery was not associated with worse oncological outcomes.
Topics: Gastrectomy; Gastrointestinal Stromal Tumors; Humans; Laparoscopy; Length of Stay; Postoperative Complications; Stomach Neoplasms; Treatment Outcome
PubMed: 25022283
DOI: 10.1186/1477-7819-12-206 -
Obesity Surgery Nov 2020The number of bariatric procedures has increased notably, with incidental findings such as gastrointestinal stromal tumors (GISTs) being observed in 2%. The number of... (Review)
Review
The number of bariatric procedures has increased notably, with incidental findings such as gastrointestinal stromal tumors (GISTs) being observed in 2%. The number of studies dealing with incidental findings during bariatric surgery (BS), especially GISTs, is scarce. This review aims to summarize the evidence about GIST diagnosis during BS, and to establish recommendations for the management and follow-up of these patients. A systematic literature search from January 2000 to March 2020 was performed. Retrospective cohort studies, case series, case reports, reviews, and conference abstracts were considered eligible. The present systematic review focused on a descriptive analysis of the data included in the articles selected. The calculated incidence was 0.65%. A change in operative plan was observed in 5% of the cases. In 98% of the cases, GISTs were gastric, with a mean size of 10.3 mm. The mitotic index was < 5 in 99%. Accordingly, all patients were classified as having a very low or low risk of recurrence. R0 resection was achieved in 100% of cases. The incidence of GISTs in patients with MO submitted to BS is considerably higher than in the general population. The diagnosis is related to the depth of preoperative work, the exhaustiveness of the intraoperative examination, and the meticulousness of the histopathological analysis. Although GISTs have a low risk of recurrence and it was previously unnecessary to modify the surgical technique, we recommend that bariatric surgeons are aware of the diagnosis and management of incidental GISTs.
Topics: Bariatric Surgery; Gastrointestinal Stromal Tumors; Humans; Neoplasm Recurrence, Local; Obesity, Morbid; Retrospective Studies
PubMed: 32710370
DOI: 10.1007/s11695-020-04853-1 -
American Journal of Surgery Sep 2017The contemporary surgery has reported the safety of laparoscopic surgery (LAP) for patients with gastrointestinal stromal tumors (GISTs). However, its use is still... (Comparative Study)
Comparative Study Meta-Analysis Review
PURPOSES
The contemporary surgery has reported the safety of laparoscopic surgery (LAP) for patients with gastrointestinal stromal tumors (GISTs). However, its use is still debated due to suspicion of the oncologic equivalence to open surgery (OPEN). We conducted a systematic review and meta-analysis of updated original articles to investigate the short- and long-term clinical outcomes of LAP compared with OPEN for GISTs.
METHODS
A systematic search was performed in PubMed, Embase, Web of Science, Cochrane Library and CNKI. Comparative studies of laparoscopic and open surgery for GISTs were published before November 2016. The Newcastle-Ottawa scale was utilized to conduct quality assessment. The Review Manager (RevMan) software version 5.0 was used for meta-analysis.
RESULTS
Twenty-four studies involving 2140 patients were included for the meta-analysis. The meta-analysis results showed that, compared with OPEN, LAP indicated potentially favorable outcomes in terms of operative time (WMD, -30.71; 95% CI, -58.48 to -2.95; P = 0.03); intraoperative blood loss (WMD, -60.90; 95% CI, -91.53 to -30.28; P < 0.0001); time to flatus (WMD, -1.10; 95% CI, -1.41 to -0.79; P < 0.00001); time to oral intake (WMD, -1.25; 95% CI, -1.64 to -0.86; P < 0.00001); length of hospital stay (WMD, -3.42; 95% CI, -4.37 to -2.46; P < 0.00001); overall complications (OR, 0.38; 95% CI, 0.27 to 0.54; P < 0.00001); and recurrence (OR, 0.45; 95% CI, 0.30 to 0.66; P < 0.0001).
CONCLUSIONS
Laparoscopic surgery is safe and feasible for the treatment of GISTs including less operative time and intraoperative blood loss, earlier postoperative recovery, shorter hospital stay, and lower rate of overall complications and recurrence.
Topics: Gastrointestinal Neoplasms; Gastrointestinal Stromal Tumors; Humans; Laparoscopy; Treatment Outcome
PubMed: 28412996
DOI: 10.1016/j.amjsurg.2017.03.042 -
Advanced Drug Delivery Reviews 2020Recent advances have identified a growing array of roles played by lymphatics in the tumor microenvironment, from providing a route of metastasis to immune modulation....
Recent advances have identified a growing array of roles played by lymphatics in the tumor microenvironment, from providing a route of metastasis to immune modulation. The tumor microenvironment represents an exceptionally complex, dynamic niche comprised of a diverse mixture of cancer cells and normal host cells termed the stroma. This review discusses our current understanding of stromal elements and how they regulate lymphatic growth and functional properties in the tumor context.
Topics: Cancer-Associated Fibroblasts; Endothelial Cells; Extracellular Matrix; Humans; Lymphatic System; Lymphatic Vessels; Models, Biological; Neoplasms; Neovascularization, Pathologic; Receptor Cross-Talk; Tumor Microenvironment
PubMed: 32783989
DOI: 10.1016/j.addr.2020.08.001 -
Tumour Biology : the Journal of the... Aug 2015Esophageal cancer (EC) is an aggressive malignant solid tumor with rapid progression and unfavorable prognosis. The 5-year survival rate for EC patients was estimated to... (Review)
Review
Esophageal cancer (EC) is an aggressive malignant solid tumor with rapid progression and unfavorable prognosis. The 5-year survival rate for EC patients was estimated to be less than 10 %. Therefore, there is an urgent need to improve diagnostic tool and effective treatment therapies for EC patients. In our paper, the general structure and function of chemokines and their receptors as well as their role in cancer progression were shortly presented. Moreover, the aim of our paper was to summarize and refer the current findings concerning the role of selected chemokines and their receptors as candidates for tumor markers of EC. Some clinical investigations have proved the involvement of these proteins in proliferation, migration, invasiveness and metastasis of tumor cells. Increasing evidence from previous studies suggested that C-X-C motif chemokine 12 (CXCL12), also known as stromal cell-derived factor 1 (SDF-1) and its receptor CXCR4 may provide novel diagnostic and prognostic strategies to reduce the burden of EC. Moreover, therapy targeting the CXCL12/CXCR4 axis may open a new direction for treatment of EC patients. However, given their nonspecific nature, the diagnostic value of chemokines and their receptors may be limited. Therefore, future larger investigations, especially in the blood of EC patients, still need to be continued to further clarify the significance of these proteins as potential candidates for tumor markers in diagnosis and prognosis of EC patients.
Topics: Adenocarcinoma; Carcinoma, Squamous Cell; Cell Movement; Cell Proliferation; Chemokine CXCL12; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Humans; Molecular Targeted Therapy; Neoplasm Invasiveness; Neoplasm Metastasis; Prognosis; Receptors, CXCR4; Signal Transduction
PubMed: 26130416
DOI: 10.1007/s13277-015-3705-7 -
Journal of Gastroenterology and... Oct 2022Gastric IgG4-related disease (IgG4-RD) can mimic malignancy, submucosal tumors (SMT), and ulcers, leading to over-triage and unnecessary medical interventions such as... (Review)
Review
BACKGROUND AND AIM
Gastric IgG4-related disease (IgG4-RD) can mimic malignancy, submucosal tumors (SMT), and ulcers, leading to over-triage and unnecessary medical interventions such as gastrectomy. The variability in the clinicopathological presentation of IgG4-related disease is not yet well defined, posing a diagnostic challenge.
METHODS
Following the PRISMA Extension for Scoping Reviews, we searched MEDLINE and EMBASE for all peer-reviewed articles using keywords including "gastritis," "stomach," "gastrointestinal stromal tumor," and "IgG4-RD" from their inception to December 28, 2021.
RESULTS
Thirty-nine articles, including 2 observational studies and 42 cases, were included in the systematic review. While bottom-heavy lymphoplasmacytic mucosal infiltration is a characteristic finding of gastric IgG4-RD, it was only present in less than half of the patients in the observational studies. Patients with gastric IgG4-RD were more likely to be diagnosed with gastrointestinal stromal tumor (GIST), gastric cancer, or peptic ulcer disease and their clinical course involved resection (51.3%) or even gastrectomy. Diagnosis of gastric IgG4-RD was most frequently made by post-operative pathological analysis.
CONCLUSION
This systematic review summarizes the current understanding of the characteristics of gastric IgG4-RD. Increased awareness of gastric IgG4-RD as a differential diagnosis of gastric SMT or ulcers among clinicians is crucial in order to reduce unnecessary high-risk, invasive interventions.
Topics: Gastrointestinal Stromal Tumors; Humans; Immunoglobulin G; Immunoglobulin G4-Related Disease; Stomach Neoplasms; Ulcer
PubMed: 35949057
DOI: 10.1111/jgh.15980