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Chest Oct 2015Visceral pleural invasion (VPI) is considered an aggressive and invasive factor in non-small cell lung cancer (NSCLC). Recent studies found that depending on tumor size,... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Visceral pleural invasion (VPI) is considered an aggressive and invasive factor in non-small cell lung cancer (NSCLC). Recent studies found that depending on tumor size, VPI influences T stage, but there is no consensus on whether VPI is important in node-negative NSCLC. In addition, its role in stage IB NSCLC is still uncertain. In this meta-analysis, we assessed the role of VPI in node-negative NSCLC according to various tumor sizes and especially in stage IB disease.
METHODS
A systematic literature search of four databases (EBSCO, PubMed, Ovid, and Springer) was performed to find relevant articles. The primary end point was 5-year overall survival. Pooled ORs were calculated using control as a reference group, and significance was determined by the Z-test.
RESULTS
Thirteen relevant studies in 27,171 patients were included in this study. The number of patients with VPI was 5,821 (21%). VPI was a significant adverse prognostic factor in patients with tumor size ≤ 3 cm (OR, 0.71; 95% CI, 0.64-0.79; P < .001), > 3 but ≤ 5 cm (OR, 0.69; 95% CI, 0.56-0.86; P < .001), and > 5 but ≤ 7 cm (OR, 0.70; 95% CI, 0.54-0.91; P = .007). A further comparison was made with stage IB NSCLC. Tumor size ≤ 3 cm with VPI was associated with a better survival than tumor size > 3 but ≤ 5 cm regardless of VPI (OR, 1.31; 95% CI, 1.19-1.45; P < .001). Exploratory analysis found no survival benefit between tumor size ≤ 3 cm with VPI and tumor size > 3 but ≤ 5 cm without VPI (OR, 1.16; 95% CI, 0.95-1.43; P = .15); however, the prognosis for tumor size > 3 but ≤ 5 cm with VPI was not as good as that for tumor size ≤ 3 cm with VPI.
CONCLUSIONS
VPI together with tumor size has a synergistic effect on survival in node-negative NSCLC. Patients with stage IB NSCLC and larger tumor size with VPI might be considered for adjuvant chemotherapy after surgical resection and need careful preoperative evaluation and postoperative follow-up. Further randomized clinical trials to determine the impact of adjuvant chemotherapy in patients with stage IB NSCLC with VPI are warranted.
Topics: Carcinoma, Non-Small-Cell Lung; Disease-Free Survival; Humans; Lymph Nodes; Neoplasm Invasiveness; Neoplasm Staging; Pleura
PubMed: 25675151
DOI: 10.1378/chest.14-2765 -
Respiration; International Review of... 2017The role of combinations of tumor markers such as carcinoembryonic antigen (CEA), carbohydrate antigens (CA) 125, 15-3, and 19-9, and CYFRA 21-1 (a fragment of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The role of combinations of tumor markers such as carcinoembryonic antigen (CEA), carbohydrate antigens (CA) 125, 15-3, and 19-9, and CYFRA 21-1 (a fragment of cytokeratin 19) in diagnosing malignant pleural effusion (MPE) has not been clearly established.
OBJECTIVES
This meta-analysis was performed to establish the overall diagnostic accuracies of combinations of these pleural fluid tumor markers for MPE.
METHODS
The PubMed, Ovid, Embase, Web of Science, and Cochrane bibliographic databases were searched. Sensitivity, specificity, and other measures of the accuracy of combinations of pleural CEA, CA 125, CA 15-3, CA 19-9, and CYFRA 21-1 in the diagnosis of MPE were pooled after a systematic review of English-language studies.
RESULTS
Twenty studies met the inclusion criteria. For pleural fluid tumor marker combinations including more than 3 studies, the summary estimates of the sensitivity/specificity for diagnosing MPE were as follows: CEA + CA 125, 0.65/0.98; CEA + CA 15-3, 0.64/0.98; CEA + CA 19-9, 0.58/0.98; CEA + CYFRA 21-1, 0.82/0.92; and CA 15-3 + CYFRA 21-1, 0.88/0.94.
CONCLUSIONS
In patients with undiagnosed pleural effusion, the combinations of positive pleural CEA + CA 15-3 and CEA + CA 19-9 are highly suspicious for pleural malignancy, but the sensitivity of these tests is poor. Therefore, their routine role in the diagnostic algorithm of these patients is questionable, and management decisions should depend on positive cytological or biopsy results from the pleura.
Topics: Antigens, Neoplasm; Biomarkers, Tumor; CA-125 Antigen; CA-19-9 Antigen; Carcinoembryonic Antigen; Humans; Keratin-19; Mucin-1; Pleural Effusion, Malignant; Sensitivity and Specificity
PubMed: 28427079
DOI: 10.1159/000468545 -
Annals of Surgical Oncology May 2015Due to the increased adoption of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC), patients with malignant peritoneal mesothelioma (MPM)... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Due to the increased adoption of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC), patients with malignant peritoneal mesothelioma (MPM) have seen improved outcomes. We aimed to evaluate and synthesize the recent published literature.
METHODS
The review was conducted according to the recommendation of the Meta-Analysis of Observational Studies in Epidemiology group with prespecified inclusion and exclusion criteria. The DEALE method was used to combine mortality rates, and imputation techniques were used to calculate standard errors. Meta-regression techniques were used to synthesize data. Publication bias was assessed using funnel plots.
RESULTS
Of 6,528 citations collected, 20 articles reporting on 1,047 patients were included in the analysis. The median age was 51 years (interquartile range 49-55), with 59 % (54-67) female. The median peritoneal carcinomatosis index score was 19 (16-23). Complete cytoreduction (CC0, 1) was performed in 67 % (46-93 %) of patients. Pooled estimates of survival yielded a 1-, 3- and 5-year survival of 84, 59, and 42 %, respectively. Patients receiving early postoperative intraperitoneal chemotherapy [EPIC] (44 %) and those receiving cisplatin intraperitoneal chemotherapy alone (48 %) or in combination (44 %) had an improved 5-year survival.
CONCLUSIONS
While CRS + HIPEC has led to an improved survival for patients with MPM compared to historic data, heterogeneity of studies precludes generalizable inferences. EPIC chemotherapy and cisplatin chemoperfusion may infer survival benefit.
Topics: Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Chemotherapy, Cancer, Regional Perfusion; Combined Modality Therapy; Cytoreduction Surgical Procedures; Female; Humans; Hyperthermia, Induced; Lung Neoplasms; Male; Mesothelioma; Mesothelioma, Malignant; Neoplasm Staging; Peritoneal Neoplasms; Prognosis
PubMed: 25124472
DOI: 10.1245/s10434-014-3978-x -
Epidemiologia E Prevenzione 2021to perform a meta-analysis of cohort studies on lung cancer mortality in occupational sectors exposed to asbestos, particularly in the construction sector, and to use... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
to perform a meta-analysis of cohort studies on lung cancer mortality in occupational sectors exposed to asbestos, particularly in the construction sector, and to use data from Italian cohorts exposed to asbestos to estimate the number of lung cancer cases attributable to asbestos in Italy.
METHODS
systematic literature review and estimation of lung cancer deaths and cases attributable to asbestos in Italian cohorts and from the Italian National Register of Malignant Mesothelioma (ReNaM).
SETTING AND PARTICIPANTS
the literature search was conducted in Medline and Embase (Ovid), including papers published from 1999 to May 2019. The following sectors were considered most exposed to asbestos: asbestos-cement, rolling-stock, shipyards, dockyards, glass workers, insulators, asphalt roll production workers, industrial ovens, miners. Moreover, the construction sector was included.
MAIN OUTCOME MEASURES
the standardized mortality ratio (SMR) was estimated from the meta-analysis of the literature review. The ratio lung cancer to mesothelioma attributable cases was estimated by occupational sector from the Italian cohorts. For the construction sector, the ratio lung cancer to mesothelioma cases was estimated within the exposed workers estimated by CAREX (1990-1993). The ratios were applied to the mesothelioma cases registered at the ReNaM for the 2010-2015 period, to obtain a national estimate of lung cancer cases attributable to occupational exposure to asbestos.
RESULTS
the meta-analytical SMR for lung cancer in men varied between 1.05 (asphalt roll) and 2.36 (insulation). The mean risk for all sectors was 1.37 in men and 1.60 in women. It increased in cohorts with latency higher than 20 years. Significant risks were observed in asbestos-cement (both genders), construction, and mining sectors. There was a mean of 1.1, 2.7, and 2.8 lung cancer deaths per mesothelioma death in the cement-asbestos, harbour, and construction sectors, respectively. The impact in terms of lung cancer cases estimated at the national level was equal to 3,814 cases between 2010 and 2015.
CONCLUSIONS
to provide an overall assessment of the impact of the occupational asbestos exposure, it is important to consider lung cancer cases, in addition to malignant mesotheliomas. This study was able to estimate the impact of asbestos on lung cancer in Italy 25 years after the ban of this occupational carcinogen, with the largest contribution in terms of attributable cases coming from the construction sector. It is urgent to implement adequate information and prevention strategies, health surveillance of workers, and the appropriate legal framework for insurance purposes.
Topics: Asbestos; Female; Humans; Italy; Lung Neoplasms; Male; Mesothelioma; Occupational Diseases; Occupational Exposure; Pleural Neoplasms
PubMed: 34841838
DOI: 10.19191/EP21.5.P353.102 -
Frontiers in Oncology 2022Cellular immunotherapy has become a new and promising treatment for patients with liver tumor. However, as most immune cells are delivered by intravenous injection, the...
BACKGROUND
Cellular immunotherapy has become a new and promising treatment for patients with liver tumor. However, as most immune cells are delivered by intravenous injection, the effect is limited and is likely to produce systemic toxicity. Here, the objective was to investigate the efficacy and safety of cellular immunotherapy by local infusion, which seems to be a promising approach and has not been well-studied.
METHODS
The PubMed, Web of Science, Embase, and Cochrane Library databases were searched to obtain literature. The overall response rate (ORR), overall survival (OS) rates, and adverse events were investigated to evaluate the effectiveness and safety of locoregional therapy. The methodological quality of the articles was assessed using the methodological index for non-randomized studies (MINORS) score. The meta-analysis was performed using Stata 15.0.
RESULTS
The eligible 17 studies involved a total of 318 patients. The random-effects model demonstrated that the ORR of local cell infusion therapy was 48% (95% confidence interval [CI]: 26%-70%). The pooled OS rate was 94% (95% CI: 83%-100%) at 6 months, 87% (95% CI: 74%-96%) at 12 months, and 42% (95% CI: 16%-70%) at 24 months. Subgroup analyses suggested that minimally invasive treatment and absence of metastasis were significantly associated with better ORR. Fourteen studies reported a variety of adverse events related to cell therapy by local perfusion. The most common complications after regional infusion of immune cells were myelosuppression (66%), fever (50%), gastrointestinal toxicity (22%), hepatic dysfunction (15%), and pleural effusion and/or ascites (14%).
CONCLUSIONS
Immune cell therapy through local perfusion is effective for patients with liver cancer, with manageable toxicity. It demonstrates better prognosis when combined with minimally invasive therapy. Considering the potential limitations, more randomized controlled trials are needed to provide solid evidence for our findings.
PubMed: 35296019
DOI: 10.3389/fonc.2022.772509 -
Critical Reviews in Oncology/hematology Sep 2020Volatile organic compounds (VOCs) have shown potential as non-invasive breath biomarkers for lung cancer, but their unclear biological origin currently limits clinical... (Review)
Review
Volatile organic compounds (VOCs) have shown potential as non-invasive breath biomarkers for lung cancer, but their unclear biological origin currently limits clinical applications. This systematic review explores headspace analysis of VOCs in patient-derived body fluids and lung cancer cell lines to pinpoint lung cancer-specific VOCs and uncover their biological origin. A search was performed in the databases MEDLINE and Web of Science. Twenty-two articles were included in this systematic review. Since there is no standardised approach to analyse VOCs, a plethora of techniques and matrices/cell lines were explored, which is reflected in the various VOCs identified. However, comparing VOCs in the headspace of urine, blood and pleural effusions from patients and lung cancer cell lines showed some overlapping VOCs, indicating their potential use in lung cancer diagnosis. This review demonstrates that VOCs are promising biomarkers for lung cancer. However, due to lack of inter-matrix consensus, standardised prospective trials will have to be conducted to validate clinically relevant biomarkers.
Topics: Biomarkers; Biomarkers, Tumor; Breath Tests; Humans; Lung Neoplasms; Prospective Studies; Volatile Organic Compounds
PubMed: 32771940
DOI: 10.1016/j.critrevonc.2020.103037 -
Journal of Visceral Surgery Dec 2018Patients with esophageal carcinoma and concomitant liver cirrhosis carry a high operative risk and may be denied esophagectomy. We performed a systematic review of the... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Patients with esophageal carcinoma and concomitant liver cirrhosis carry a high operative risk and may be denied esophagectomy. We performed a systematic review of the literature and meta-analysis to investigate postoperative outcomes in these patients.
METHODS
Studies reporting outcomes after esophagectomy in patients with liver cirrhosis were searched in Medline, Embase, Cochrane Library, ISI Web of Science, and Scopus until June 2017, matching the terms "liver cirrhosis", "esophageal neoplasm" and/or "esophageal surgery". Extracted data included study characteristics, demographic and clinical patient characteristics, type of surgical procedure, and postoperative outcomes. A systematic review and Bayesian meta-analysis were performed.
RESULTS
Five observational, retrospective and single-arm studies with a total of 157 patients were included. The main cause of death was liver failure followed by pneumonia/sepsis and anastomotic leak. Ascites and pleural effusion were the most frequent postoperative complications (pooled rates 36% and 34%, respectively). The pooled morbidity rate was 74% (95% HPD=46-81%) while the pooled mortality was 18% (95% HPD=17-27%). Study heterogeneity (τ2) was low, ranging from 0.046 to 0.080. An incidental diagnosis of liver cirrhosis was reported in 15.6% of patients in one series. Five-year survival was similar between cirrhotic and non-cirrhotic patients but was statistically significantly higher in patients with MELD score<10.
CONCLUSIONS
Sound scientific evidence with regard to efficacy and outcomes of esophagectomy in patients with concomitant liver cirrhosis is lacking. There is a need to properly select these frail patients to reduce postoperative morbidity and mortality rates.
Topics: Bayes Theorem; Carcinoma; Cause of Death; Esophageal Neoplasms; Esophagectomy; Humans; Liver Cirrhosis; Monte Carlo Method; Observational Studies as Topic; Postoperative Complications; Retrospective Studies; Treatment Outcome
PubMed: 29653854
DOI: 10.1016/j.jviscsurg.2018.03.014 -
Lung Cancer (Amsterdam, Netherlands) Nov 2014Malignant pleural mesothelioma is an almost universally fatal malignancy primarily related to asbestos exposure. Based on the differences in immunologic markers and gene... (Meta-Analysis)
Meta-Analysis Review
RATIONALE
Malignant pleural mesothelioma is an almost universally fatal malignancy primarily related to asbestos exposure. Based on the differences in immunologic markers and gene expression between histologic subtypes of mesothelioma, and our clinical impression that response rates vary by histology, we decided to examine the reported response rates of mesothelioma subtypes.
OBJECTIVES
Our objective was to compare the response rates of sarcomatoid mesotheliomas to the overall response rates in published clinical trials.
METHODS
We searched PubMed for "mesothelioma" with the clinical trials filter selected. We included articles published between January 1, 2000 and March 20, 2014 in which subjects received first or second line systemic therapy for malignant pleural mesothelioma. Studies investigating multi-modality therapy including surgery were excluded. Response rates [including 95% confidence intervals (95% CI)] were estimated for the entire patient cohort and then separately for subjects with sarcomatoid tumors.
MEASUREMENTS AND MAIN RESULTS
We reviewed 544 publications of which 41 trials met our inclusion criteria. Eleven of these trials did not include patients with sarcomatoid mesothelioma (27% of eligible studies). The remaining 30 publications included 1475 subjects, 1011 with epithelioid tumors (68.5%), 203 with biphasic tumors (13.8%), 137 with sarcomatoid tumors (9.3%) and 124 with unknown subtypes (8.4%). In total, there were 323 responses (21.9%, complete and partial responses, 95% CI: 16.3, 28.8) to systemic therapy across all histological subtypes. In patients with sarcomatoid tumors (n=137) 19 responses were observed. This accounted for 5.9% of all responses and yields a 13.9% (95% CI: 8.6, 21.6) response rate for patients with sarcomatoid tumors. Multiple biases likely affected this systematic review.
CONCLUSION
Response rates for different histological subtypes of malignant pleural mesothelioma are infrequently reported. Partial and complete responses to systemic therapies appear to be less common among patients with sarcomatoid tumors.
Topics: Clinical Trials as Topic; Combined Modality Therapy; Humans; Lung Neoplasms; Mesothelioma; Mesothelioma, Malignant; Pleural Neoplasms; Treatment Outcome
PubMed: 25217189
DOI: 10.1016/j.lungcan.2014.08.017 -
Scientific Reports Feb 2022To clarify the predominance of Th1 or Th2 immune responses in malignant and tuberculous pleural effusion (MPE and TPE, respectively), we performed a meta-analysis of...
To clarify the predominance of Th1 or Th2 immune responses in malignant and tuberculous pleural effusion (MPE and TPE, respectively), we performed a meta-analysis of previously published results of the levels of Th1/Th2 cytokines associated with these two types of pleural effusion to evaluate the use of Th1/Th2 cytokine profiles in distinguishing TPE from MPE. We searched the PubMed and EMBASE databases for studies indexed from 2000 to March 2021. We included studies that (a) diagnosed TPE and MPE based on culture or pleural tissue biopsy and that (b) compared levels of Th1/Th2 cytokines between TPE and MPE. Pooled data based on a random-effects model or fixed-effects model and standardized mean differences (SMDs) across studies were used to compare TPE and MPE. We also performed Egger's test to assess publication bias. Of 917 identified studies, a total of 42 studies were selected for the meta-analysis. Compared with MPE subjects, TPE subjects had a significantly higher level of TNF-α [2.22, (1.60-2.84)], an elevated level of IFN-γ [3.30, (2.57-4.40)] in pleural effusion, a situation where the Th1 immune response dominated. Conversely, the levels of interleukin-4 (IL-4) and IL-10 (Th2 cytokines) were higher in the MPE subjects than in the TPE subjects, showing statistically nonsignificant tiny effects [-0.15, (-0.94 to 0.63) and -0.04, (-0.21 to 0.12), respectively]. We confirmed that TPE, a situation in which the Th1 cytokines are predominant. The slight preponderance of Th2 cytokines in MPE, which is not convincing enough to prove.
Topics: Cytokines; Diagnosis, Differential; Humans; Pleural Effusion, Malignant; Th1 Cells; Th2 Cells; Tuberculosis, Pleural
PubMed: 35177742
DOI: 10.1038/s41598-022-06685-8 -
Pathology, Research and Practice May 2024Malignant pleural mesothelioma (MPM) poses diagnostic challenges due to its resemblance to benign pleural pathologies and different histological subtypes. Several... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Malignant pleural mesothelioma (MPM) poses diagnostic challenges due to its resemblance to benign pleural pathologies and different histological subtypes. Several immunohistochemistry markers have been employed to aid in accurate diagnosis.
METHODS
The present systematic review and meta-analysis aimed to assess the diagnostic performance of various immunohistochemistry markers in malignant pleural mesothelioma diagnosis and its histological subtypes. Following the PRISMA guidelines, we systematically searched the literature for articles on using different immunohistochemical markers in MPM and its histological subtypes. EMBASE, LILACS, MEDLINE, and Virtual Health Library were searched for studies published up to August 2023. We used the QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies) criteria to assess the quality of the included articles. Meta-analyses were performed to determine prevalence using a random-effects model.
RESULTS
103 studies met the inclusion criteria, comprising a diverse range of immunohistochemistry markers. EMA and desmin-loss exhibited high sensitivity (96% and 92%, respectively) in distinguishing malignant pleural mesothelioma from benign pleural pathologies. Specificity was notably high for both BAP1-loss and survivin expression at 100%. Subtype-specific analyses demonstrated that EMA and HEG1 were sensitive markers for epithelioid mesothelioma, while GLUT1 showed high sensitivity for sarcomatoid mesothelioma. In cases comparing epithelioid mesothelioma and lung adenocarcinoma, CAM5.2 and calretinin displayed high sensitivity, while WT1 and BAP1-loss demonstrated exceptional specificity for malignant epithelioid mesothelioma. In the case of sarcomatoid mesothelioma and sarcomatoid lung carcinoma, GATA3 exhibited the most heightened sensitivity, while GATA3 and D2-40 displayed the best specificity for sarcomatoid malignant mesothelioma diagnosis.
CONCLUSION
Immunohistochemistry markers are essential in accurately diagnosing malignant pleural mesothelioma and its histological subtypes. This systematic review and meta-analysis provide a comprehensive insight into the diagnostic performance of these markers, facilitating their potential clinical utility in the discrimination of malignant pleural mesothelioma from other pleural pathologies and the differentiation of malignant pleural mesothelioma subtypes.
Topics: Humans; Mesothelioma, Malignant; Biomarkers, Tumor; Immunohistochemistry; Pleural Neoplasms; Lung Neoplasms; Diagnosis, Differential
PubMed: 38603842
DOI: 10.1016/j.prp.2024.155276