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Critical Reviews in Toxicology Nov 2022Existing literature suggests an association between chronic cadmium (Cd) exposure and the induction of DNA damage and genotoxicity. However, observations from individual... (Meta-Analysis)
Meta-Analysis Review
Existing literature suggests an association between chronic cadmium (Cd) exposure and the induction of DNA damage and genotoxicity. However, observations from individual studies are inconsistent and conflicting. Therefore current systematic review aimed to pool evidence from existing literature to synthesize quantitative and qualitative corroboration on the association between markers of genotoxicity and occupational Cd exposed population. Studies that evaluated markers of DNA damage among occupationally Cd-exposed and unexposed workers were selected after a systematic literature search. The DNA damage markers included were chromosomal aberrations (chromosomal, chromatid, sister chromatid exchange), Micronucleus (MN) frequency in mono and binucleated cells (MN with condensed chromatin, lobed nucleus, nuclear buds, mitotic index, nucleoplasmatic bridges, pyknosis, and karyorrhexis), comet assay (tail intensity, tail length, tail moment, and olive tail moment), and oxidative DNA damage (8-hydroxy-deoxyguanosine). Mean differences or standardized mean differences were pooled using a random-effects model. The Cochran- test and statistic were used to monitor heterogeneity among included studies. Twenty-nine studies with 3080 occupationally Cd-exposed and 1807 unexposed workers were included in the review. Cd among the exposed group was higher in blood [4.77 μg/L (-4.94-14.48)] and urine samples [standardized mean difference 0.47 (0.10-0.85)] than in the exposed group. The Cd exposure is positively associated with higher levels of DNA damage characterized by increased frequency of MN [7.35 (-0.32-15.02)], sister chromatid exchange [20.30 (4.34-36.26)], chromosomal aberrations, and oxidative DNA damage (comet assay and 8OHdG [0.41 (0.20-0.63)]) compared to the unexposed. However, with considerable between-study heterogeneity. Chronic Cd exposure is associated with augmented DNA damage. However, more extensive longitudinal studies with adequate sample sizes are necessary to assist the current observations and promote comprehension of the Cd's role in inducing DNA damage. CRD42022348874.
Topics: Humans; Cadmium; Micronucleus Tests; Occupational Exposure; DNA Damage; Chromosome Aberrations
PubMed: 36802997
DOI: 10.1080/10408444.2023.2173557 -
EJIFCC Nov 2019Breast cancer is the most common malignancy in women worldwide. In this systematic review 28 studies were taken into account, in order to evaluate the role of DNA... (Review)
Review
Breast cancer is the most common malignancy in women worldwide. In this systematic review 28 studies were taken into account, in order to evaluate the role of DNA content and cell cycle phases, measured by flow cytometry in breast cancer. Presence of aneuploidy and S-phase fraction have been extensively studied as a prognostication tool. With the current dawn of the age of intraoperative flow cytometry the present systematic review provide an insight of the current role of flow cytometry in breast cancer and future horizons.
PubMed: 31814815
DOI: No ID Found -
Mutation Research Mar 2004The potential role of genotoxicity in human leukemias associated with benzene (BZ) exposures was investigated by a systematic review of over 1400 genotoxicity test... (Review)
Review
The potential role of genotoxicity in human leukemias associated with benzene (BZ) exposures was investigated by a systematic review of over 1400 genotoxicity test results for BZ and its metabolites. Studies of rodents exposed to radiolabeled BZ found a low level of radiolabel in isolated DNA with no preferential binding in target tissues of neoplasia. Adducts were not identified by 32P-postlabeling (equivalent to a covalent binding index <0.002) under the dosage conditions producing neoplasia in the rodent bioassays, and this method would have detected adducts at 1/10,000th the levels reported in the DNA-binding studies. Adducts were detected by 32P-postlabeling in vitro and following high acute BZ doses in vivo, but levels were about 100-fold less than those found by DNA binding. These findings suggest that DNA-adduct formation may not be a significant mechanism for BZ-induced neoplasia in rodents. The evaluation of other genotoxicity test results revealed that BZ and its metabolites did not produce reverse mutations in Salmonella typhimurium but were clastogenic and aneugenic, producing micronuclei, chromosomal aberrations, sister chromatid exchanges and DNA strand breaks. Rodent and human data were compared, and BZ genotoxicity results in both were similar for the available tests. Also, the biotransformation of BZ was qualitatively similar in rodents, humans and non-human primates, further indicating that rodent and human genotoxicity data were compatible. The genotoxicity test results for BZ and its metabolites were the most similar to those of topoisomerase II inhibitors and provided less support for proposed mechanisms involving DNA reactivity, mitotic spindle poisoning or oxidative DNA damage as genotoxic mechanisms; all of which have been demonstrated experimentally for BZ or its metabolites. Studies of the chromosomal translocations found in BZ-exposed persons and secondary human leukemias produced by topoisomerase II inhibitors provide some additional support for this mechanism being potentially operative in BZ-induced leukemia.
Topics: Animals; Benzene; Biological Assay; DNA Damage; Female; Humans; Male; Mutagenicity Tests; Mutagens; Topoisomerase II Inhibitors
PubMed: 15164977
DOI: 10.1016/s1383-5742(03)00053-x -
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 -
Breast (Edinburgh, Scotland) Aug 2008We have performed a systematic review and meta-analysis of proliferation markers (Ki-67, mitotic index (MI), proliferating cell nuclear antigen (PCNA) and thymidine or... (Meta-Analysis)
Meta-Analysis Review
We have performed a systematic review and meta-analysis of proliferation markers (Ki-67, mitotic index (MI), proliferating cell nuclear antigen (PCNA) and thymidine or bromodeoxyuridine labelling index (LI)) with respect to survival in early breast cancer. Eighty-five studies involving 32,825 patients were analysed. Ki-67 (43 studies, 15,790 patients), MI (20 studies, 7021 patients), and LI (11 studies, 7337 patients) were associated with significantly shorter overall and disease free survival, using results from univariate and multivariate analyses from the individual studies. PCNA (11 studies, 2677 patients) was associated with shorter overall survival by multivariate analysis only, because of lack of data. There was some evidence for publication bias, but all markers remained significant after allowing for this. Ki-67, MI, PCNA and LI are associated with worse survival outcomes in early breast cancer. However, whether these proliferation markers provide additional prognostic information to commonly used prognostic indices remains unclear.
Topics: Breast Neoplasms; Disease-Free Survival; Female; Humans; Ki-67 Antigen; Mitotic Index; Predictive Value of Tests; Proliferating Cell Nuclear Antigen; Survival Rate
PubMed: 18455396
DOI: 10.1016/j.breast.2008.02.002 -
Surgery Jul 2014Cystic pancreatic neuroendocrine neoplasms (PNENs) are rare neoplasms, and presently, it is uncertain whether their behavior is similar or distinct from their solid... (Comparative Study)
Comparative Study Meta-Analysis Review
INTRODUCTION
Cystic pancreatic neuroendocrine neoplasms (PNENs) are rare neoplasms, and presently, it is uncertain whether their behavior is similar or distinct from their solid counterparts. This study aimed to review systematically the present literature to compare the clinicopathologic characteristics of cystic PNENs versus their solid counterparts to determine whether cystic PNENs are likely to be a distinct entity from solid PNENs.
METHODS
Comparative studies of solid versus cystic PNENs studies were reviewed. Cystic and solid PNENs were compared on the basis of several clinicopathologic characteristics.
RESULTS
Seven nonrandomized case control studies compared 152 cystic versus 915 solid PNENs. Pooled analysis demonstrated that the likelihood of PNENs to be located in the head/uncinate of the pancreas was lower for cystic than solid neoplasms (27.7% vs 45.5%, odds ratio [OR] 0.452, 95% confidence interval [95% CI] 0.304-0.673, P < .001). Cystic PNENs were less likely to be functional (14% vs 24.4%, OR 0.405, 95% CI 0.221-0.742, P = .003) and were more likely to be benign/uncertain rather than malignant compared with solid PNENs (90.3% vs 65.9%, OR 3.151, 95% CI 1.297-7.652, P = .011). Cystic PNENs were more likely to have a mitotic count <2 per 10 hpf and a Ki67 index <2% (93.3% vs 72.7%, OR 4.897, 95% CI 2.139-11.209, P < .001 and 82.4% vs 54.1%, OR 4.079, 95% CI 2.177-7.641, P < .001), respectively. Cystic neoplasms were also less likely to have regional lymph node metastases than solid neoplasms (11.2% vs 28.9%, OR 0.387, 95% CI 0.219-0.685, P = .001).In this meta-analysis, there was no difference in the 5-year overall survival and 5-year disease-free survival between cystic vs solid PNENs (92.0% vs 86.8%, P .214) and (98.1% vs 83.9%, P = .185).
CONCLUSION
These findings suggest that cystic PNENs tend to be biologically less aggressive compared with their solid counterparts; more data, however, with respect to molecular analysis are required to establish whether cystic and solid PNENs were distinct pathologic entities.
Topics: Biomarkers, Tumor; Humans; Lymphatic Metastasis; Models, Statistical; Neuroendocrine Tumors; Pancreatic Neoplasms; Prognosis; Survival Analysis
PubMed: 24878455
DOI: 10.1016/j.surg.2014.03.026 -
Pediatric Surgery International Sep 2021Gastrointestinal stromal tumor (GIST) is a rare cancer of mesenchymal origin mostly seen in adult and elderly populations. Therefore, the prognostic and therapeutic... (Review)
Review
Gastrointestinal stromal tumor (GIST) is a rare cancer of mesenchymal origin mostly seen in adult and elderly populations. Therefore, the prognostic and therapeutic features of pediatric GIST are not clearly defined. Clinical knowledge has been largely extrapolated from case series and adult studies. In this systematic review, we aimed to analyze the health outcome metrics of pediatric GIST. Medline and Embase databases were searched using relevant key terms. The original search retrieved 1,892 titles; 27 studies with 184 patients (68% female) were included for final review. The primary tumors were located in the stomach (165/184, 90%), small bowel (12/184, 7%), and elsewhere (7/184, 4%). Individual patient data were available in 125 cases with a median follow-up of 6.7 years. All patients underwent surgical resection, which varied from wide local excision to total gastrectomy. There were 12 deaths (10%), 65 (52%) patients were alive with no evidence of disease, and 31 cases (25%) were alive with disease. Tumor size > 5 cm, high mitotic index, and spindle morphology were predictive of mortality. Pediatric GIST has a more favorable prognosis and different characteristics versus adult tumors. There is a crucial need for international consensus and specific pediatric guidelines for the treatment of this rare tumor.
Topics: Adult; Aged; Child; Female; Gastrointestinal Stromal Tumors; Humans; Intestine, Small; Male; Prognosis; Retrospective Studies; Treatment Outcome
PubMed: 34081161
DOI: 10.1007/s00383-021-04931-0 -
Asian Journal of Surgery Jan 2020The purpose of this study is to assess the clinical outcomes and prognostic factors for survival of patients with duodenal gastrointestinal stromal tumors (GIST) who... (Meta-Analysis)
Meta-Analysis Review
The purpose of this study is to assess the clinical outcomes and prognostic factors for survival of patients with duodenal gastrointestinal stromal tumors (GIST) who underwent pancreaticoduodenectomy (PD) or local resection (LR). PubMed database was searched for relevant studies. A meta-analysis was performed with Review Manager 5.3 software. Twenty-seven observational studies involving 1103 patients were included in the review. The overall morbidity and 30-day mortality was 27% and 0.5% respectively. The median (range) 5-year overall survival (OS) and disease-free survival (DFS) rates were 87% (60-100%) and 71% (44-100%) respectively. In meta-analyses, factors associated with shorter DFS included male sex, mitotic index >5/50 high-power fields, high risk, tumor size >5 cm, and the PD procedure. Factors associated with shorter OS included mitotic index >5/50 high-power fields and tumor size >5 cm. Patients in PD group had a higher incidence of mitotic index >5/50 HPF, a higher incidence of high-risk classification, a higher incidence of tumors in the second portion of the duodenum, a larger tumor size, a longer duration of operation, more intraoperative blood loss, a greater blood transfusion requirement, a higher morbidity rate, a longer hospital stay, and an increased recurrence rate than those in LR group. In conclusion, the current literature review demonstrates that the postoperative prognosis of duodenal GIST is promising and mainly affected by tumor factors. The choice of the surgical approach should depend on the anatomical location and tumor size.
Topics: Digestive System Surgical Procedures; Gastrointestinal Neoplasms; Gastrointestinal Stromal Tumors; Humans; Pancreaticoduodenectomy; Prognosis; Treatment Outcome
PubMed: 30853211
DOI: 10.1016/j.asjsur.2019.02.006 -
Journal of Clinical Pathology Jul 2016Gastroenteropancreatic neuroendocrine tumours (GEP NETs) are classified according to tumour mitotic count or Ki-67 labelling index (LI). (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Gastroenteropancreatic neuroendocrine tumours (GEP NETs) are classified according to tumour mitotic count or Ki-67 labelling index (LI).
AIMS
To systematically review articles reporting the prognosis of patients by Ki-67 LI and thereby improve the ability of clinicians to prognosticate for their patients.
METHOD
265 abstracts were identified relating Ki-67 and survival. After exclusion criteria were applied, 22 articles remained. Articles were excluded if they described non-human specimens, were non-English language, published prior to 2000, reported non-GEP NETs, reported subgroups selected by treatment modality or included <20 cases. Random-effects meta-analysis was used to combine studies to estimate survival proportions.
RESULTS
Authors used varied methods in which to present 5-year survival, with often limited survival information. This reduced the number of studies that could be included in the meta-analysis. 5-year survival for patients with grade 1 and 2 GEP NETs were estimated to be 89% (95% CI 85% to 92%, m=12 studies, n=977 participants) and 70% (95% CI 62% to 79%, m=9, n=726), respectively. Using an alternative grade 1/2 boundary of 5%, 5-year survival rates for Ki-67≤5% and 5-20% were estimated as 89% (95% CI 84% to 94%, m=7, n=654) and 51% (95% CI 44% to 59%, m=4, n=183), respectively. For Ki-67>20%, 5-year survival was estimated to be 25% (95% CI 12% to 38%, m=10, n=208).
CONCLUSIONS
Standardisation of grade boundaries has allowed us to combine data from multiple studies and amass a body of evidence linking Ki-67 and survival.
Topics: Biomarkers, Tumor; Disease-Free Survival; Humans; Ki-67 Antigen; Mitotic Index; Neuroendocrine Tumors; Prognosis; Survival Rate
PubMed: 26680267
DOI: 10.1136/jclinpath-2015-203340 -
Annals of Surgical Oncology Dec 2016Most patients with melanoma have a thin (≤1.00 mm) lesion. There is uncertainty as to which patients with thin melanoma should undergo sentinel lymph node (SN)... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Most patients with melanoma have a thin (≤1.00 mm) lesion. There is uncertainty as to which patients with thin melanoma should undergo sentinel lymph node (SN) biopsy. We sought to quantify the proportion of SN metastases in patients with thin melanoma and to determine the pooled effect of high-risk features of the primary lesion on SN positivity.
METHODS
Published literature between 1980 and 2015 was searched and critically appraised. Primary outcome was the proportion of SN metastases in patients with thin cutaneous melanoma. Secondary outcomes included the effect of high-risk pathological features of the primary lesion on the proportion of SN metastases. Summary measures were estimated by Mantel-Haenszel method using random effects meta-analyses.
RESULTS
Sixty studies (10,928 patients) met the criteria for inclusion. Pooled SN positivity was 4.5 % [95 % confidence interval (CI) 3.8-5.2 %]. Predictors of a positive SN were: thickness ≥0.75 mm [adjusted odds ratio (AOR) 1.90 (95 % CI 1.08-3.34); with a likelihood of SN metastases of 8.8 % (95 % CI 6.4-11.2 %)]; Clark level IV/V [AOR 2.24 (95 % CI 1.23-4.08); with a likelihood of 7.3 % (95 % CI 6.2-8.4 %)]; ≥1 mitoses/mm [AOR 6.64 (95 % CI 2.77-15.88); pooled likelihood 8.8 % (95 % CI 6.2-11.4 %)]; and the presence of microsatellites [unadjusted OR 6.94 (95 % CI 2.13-22.60); likelihood 26.6 % (95 % CI 4.3-48.9 %)].
CONCLUSIONS
The pooled proportion of SN metastases in thin melanoma is 4.5 %. Thickness ≥0.75 mm, Clark level IV/V, mitoses, and microsatellites significantly increased the odds of SN positivity and should prompt strong consideration of SN biopsy.
Topics: Humans; Lymph Nodes; Lymphatic Metastasis; Melanoma; Mitotic Index; Patient Selection; Risk Factors; Sentinel Lymph Node Biopsy; Skin Neoplasms; Tumor Burden
PubMed: 26932710
DOI: 10.1245/s10434-016-5137-z