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Veterinary Pathology Mar 2024One of the most relevant prognostic indices for tumors is cellular proliferation, which is most commonly measured by the mitotic activity in routine tumor sections. The...
One of the most relevant prognostic indices for tumors is cellular proliferation, which is most commonly measured by the mitotic activity in routine tumor sections. The goal of this systematic review was to analyze the methods and prognostic relevance of histologically measuring mitotic activity that have been reported for canine tumors in the literature. A total of 137 articles that correlated the mitotic activity in canine tumors with patient outcome were identified through a systematic (PubMed and Scopus) and nonsystematic (Google Scholar) literature search and eligibility screening process. Mitotic activity methods encompassed the mitotic count (MC, number of mitotic figures per tumor area) in 126 studies, presumably the MC (method not specified) in 6 studies, and the mitotic index (MI, number of mitotic figures per number of tumor cells) in 5 studies. A particularly high risk of bias was identified based on the available details of the MC methods and statistical analyses, which often did not quantify the prognostic discriminative ability of the MC and only reported values. A significant association of the MC with survival was found in 72 of 109 (66%) studies. However, survival was evaluated by at least 3 studies in only 7 tumor types/groups, of which a prognostic relevance is apparent for mast cell tumors of the skin, cutaneous melanoma, and soft tissue tumor of the skin and subcutis. None of the studies using the MI found a prognostic relevance. This review highlights the need for more studies with standardized methods and appropriate analysis of the discriminative ability to prove the prognostic value of the MC and MI in various tumor types. Future studies are needed to evaluate the influence of the performance of individual pathologists on the appropriateness of prognostic thresholds and investigate methods to improve interobserver reproducibility.
PubMed: 38533804
DOI: 10.1177/03009858241239565 -
Veterinary Pathology Mar 2024Increased proliferation is a driver of tumorigenesis, and quantification of mitotic activity is a standard task for prognostication. This systematic review is an...
Increased proliferation is a driver of tumorigenesis, and quantification of mitotic activity is a standard task for prognostication. This systematic review is an analysis of all available references on mitotic activity in feline tumors to provide an overview of the assessment methods and prognostic value. A systematic literature search in PubMed and Scopus and a nonsystematic search in Google Scholar were conducted. All articles on feline tumors that correlated mitotic activity with patient outcome were identified. Data analysis revealed that of the 42 eligible articles, mitotic count (MC, mitotic figures/tumor area) was evaluated in 39 studies, and mitotic index (MI, mitotic figures/tumor cells) in 3 studies. The risk of bias was considered high for most studies (26/42, 62%) based on small study populations, insufficient details of the MC/MI methods, and lack of statistical measures for diagnostic accuracy or effect on outcome. The MC/MI methods varied between studies. A significant association of MC with survival was determined in 20 of 28 (71%) studies (10 studies evaluated other outcome metrics or provided individual patient data), while 1 study found an inverse effect. Three tumor types had at least 4 studies, and a prognostic association with survival was found in 5 of 6 studies on mast cell tumors, 5 of 5 on mammary tumors, and 3 of 4 on soft-tissue sarcomas. MI was shown to correlate with survival for mammary tumors by 2 research groups; however, comparisons to MC were not conducted. Further studies with standardized mitotic activity methods and appropriate statistical analysis for discriminant ability of patient outcome are needed to infer the prognostic value of MC and MI.
PubMed: 38533803
DOI: 10.1177/03009858241239566 -
Journal of Clinical Medicine Apr 2023Chorangiocarcinoma is a very rare and misdiagnosed placental neoplasm. The unique morphologic features of the lesion distinguish it from other trophoblastic tumors and... (Review)
Review
Chorangiocarcinoma is a very rare and misdiagnosed placental neoplasm. The unique morphologic features of the lesion distinguish it from other trophoblastic tumors and vascular abnormalities. We present a systematic review of the literature to provide clarity on chorangiocarcinoma entity and biology. A literature search was carried out in December 2022 using the keywords "Placental chorangiocarcinoma", "Chorangioma", "Placenta", and "Throphoblast proliferation". Articles published from 1988 to 2022 were obtained from Scopus, Google Scholar, and PUBMED. In our review, we examined maternal age, gestational age at the time of delivery, parity, type of pregnancy, placental weight, ultrasound features of the placenta, macroscopic examination and tumor size, microscopic examination, immunostaining, maternal beta-human chorionic gonadotropin, fetal and maternal outcome. Eight manuscripts were detected. They are all case reports. The macroscopic characteristics of the lesions were represented by the presence of a grey-yellow-white color well-demarcated round nodule. Microscopically, all the authors described typical aspects of malignancy as a high rate of mitosis, nuclear atypia and necrotic areas. In some cases, the presence of AE1/AE3 cytoplasmic positivity, p63 nuclear staining, and beta-human chorionic gonadotropin (BHCG) were reported. A good fetal outcome was reported in all cases of newborns with normal birth weight, except one with fetal growth restriction. Maternal outcome was good in all cases except one with maternal lung metastasis three months after delivery. The clinical course has probably underestimated the real incidence of the pathology. Only greater knowledge of its histology and its clinical course will allow us to evaluate the real prevalence of the disease.
PubMed: 37176506
DOI: 10.3390/jcm12093065 -
Frontiers in Oncology 2022Digital pathology with whole-slide imaging (WSI) has many potential clinical and non-clinical applications. In the past two decades, despite significant advances in WSI...
OBJECTIVE
Digital pathology with whole-slide imaging (WSI) has many potential clinical and non-clinical applications. In the past two decades, despite significant advances in WSI technology adoption remains slow for primary diagnosis. The aim of this study was to identify common pitfalls of WSI reported in validation studies and offer measures to overcome these challenges.
METHODS
A systematic search was conducted in the electronic databases Pubmed-MEDLINE and Embase. Inclusion criteria were all validation studies designed to evaluate the feasibility of WSI for diagnostic clinical use in pathology. Technical and diagnostic problems encountered with WSI in these studies were recorded.
RESULTS
A total of 45 studies were identified in which technical issues were reported in 15 (33%), diagnostic issues in 8 (18%), and 22 (49%) reported both. Key technical problems encompassed slide scan failure, prolonged time for pathologists to review cases, and a need for higher image resolution. Diagnostic challenges encountered were concerned with grading dysplasia, reliable assessment of mitoses, identification of microorganisms, and clearly defining the invasive front of tumors.
CONCLUSION
Despite technical advances with WSI technology, some critical concerns remain that need to be addressed to ensure trustworthy clinical diagnostic use. More focus on the quality of the pre-scanning phase and training of pathologists could help reduce the negative impact of WSI technical difficulties. WSI also seems to exacerbate specific diagnostic tasks that are already challenging among pathologists even when examining glass slides with conventional light microscopy.
PubMed: 35785212
DOI: 10.3389/fonc.2022.918580 -
Frontiers in Oncology 2022The indications for sentinel lymph node biopsy (SLNB) for thin melanoma are still unclear. This meta-analysis aims to determine the positive rate of SLNB in thin...
BACKGROUND
The indications for sentinel lymph node biopsy (SLNB) for thin melanoma are still unclear. This meta-analysis aims to determine the positive rate of SLNB in thin melanoma and to summarize the predictive value of different high-risk features for positive results of SLNB.
METHODS
Four databases were searched for literature on SLNB performed in patients with thin melanoma published between January 2000 and December 2020. The overall positive rate and positive rate of each high-risk feature were calculated and obtained with 95% confidence intervals (CIs). Both unadjusted odds ratios (ORs) and adjusted ORs (AORs) of high-risk features were analyzed. Pooled effects were estimated using random-effects model meta-analyses.
RESULTS
Sixty-six studies reporting 38,844 patients with thin melanoma who underwent SLNB met the inclusion criteria. The pooled positive rate of SLNB was 5.1% [95% confidence interval (CI) 4.9%-5.3%]. Features significantly predicted a positive result of SLNB were thickness≥0.8 mm [AOR 1.94 (95%CI 1.28-2.95); positive rate 7.0% (95%CI 6.0-8.0%)]; ulceration [AOR 3.09 (95%CI 1.75-5.44); positive rate 4.2% (95%CI 1.8-7.2%)]; mitosis rate >0/mm2 [AOR 1.63 (95%CI 1.13-2.36); positive rate 7.7% (95%CI 6.3-9.1%)]; microsatellites [OR 3.8 (95%CI 1.38-10.47); positive rate 16.6% (95%CI 2.4-36.6%)]; and vertical growth phase [OR 2.76 (95%CI 1.72-4.43); positive rate 8.1% (95%CI 6.3-10.1%)].
CONCLUSIONS
The overall positive rate of SLNB in thin melanoma was 5.1%. The strongest predictor for SLN positivity identified was microsatellites on unadjusted analysis and ulceration on adjusted analysis. Breslow thickness ≥0.8 mm and mitosis rate >0/mm both predict SLN positivity in adjusted analysis and increase the positive rate to 7.0% and 7.7%. We suggest patients with thin melanoma with the above high-risk features should be considered for giving an SLNB.
PubMed: 35155254
DOI: 10.3389/fonc.2022.817510 -
Cells Jun 2021Telomeres are aging biomarkers, as they shorten while cells undergo mitosis. The aim of this study was to evaluate whether psychiatric disorders marked by psychological...
Telomeres are aging biomarkers, as they shorten while cells undergo mitosis. The aim of this study was to evaluate whether psychiatric disorders marked by psychological distress lead to alterations to telomere length (TL), corroborating the hypothesis that mental disorders might have a deeper impact on our physiology and aging than it was previously thought. A systematic search of the literature using MeSH descriptors of psychological distress ("Traumatic Stress Disorder" or "Anxiety Disorder" or "depression") and telomere length ("cellular senescence", "oxidative stress" and "telomere") was conducted on PubMed, Cochrane Library and ScienceDirect databases. A total of 56 studies (113,699 patients) measured the TL from individuals diagnosed with anxiety, depression and posttraumatic disorders and compared them with those from healthy subjects. Overall, TL negatively associates with distress-related mental disorders. The possible underlying molecular mechanisms that underly psychiatric diseases to telomere shortening include oxidative stress, inflammation and mitochondrial dysfunction linking. It is still unclear whether psychological distress is either a cause or a consequence of telomere shortening.
Topics: Humans; Mental Disorders; Mitochondria; Oxidative Stress; Telomere; Telomere Shortening
PubMed: 34200513
DOI: 10.3390/cells10061423 -
Frontiers in Oncology 2020Aurora kinase A (AURKA) is a cell cycle regulatory serine/threonine kinase that promotes cell cycle progression. It plays an important role in regulating the transition...
Aurora kinase A (AURKA) is a cell cycle regulatory serine/threonine kinase that promotes cell cycle progression. It plays an important role in regulating the transition from G2 to M phase during mitosis. The association between the AURKA rs2273535 T>A polymorphism and cancer risk has been investigated, but the results remain inconsistent. To get a more accurate conclusion, we conducted a comprehensive meta-analysis of 36 case-control studies, involving 22,884 cancer cases and 30,497 healthy controls. Crude odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to determine the association of interest. Pooled analysis indicated that the AURKA rs2273535 T>A polymorphism increased the overall risk of cancer (homozygous: OR = 1.17, 95% CI = 1.04-1.33; recessive: OR = 1.15, 95% CI = 1.05-1.25; allele: OR = 1.07, 95% CI = 1.02-1.13). Stratification analysis by cancer type further showed that this polymorphism was associated with an increased breast cancer risk. This meta-analysis indicated that the AURKA rs2273535 T>A polymorphism was associated with an overall increased cancer risk, especially breast cancer. Further validation experiments are needed to strengthen our conclusion.
PubMed: 32733797
DOI: 10.3389/fonc.2020.01040 -
Cancer Cell International 2020One of the most prominent features of tumor cells is uncontrolled cell proliferation caused by an abnormal cell cycle, and the abnormal expression of cell cycle-related... (Review)
Review
One of the most prominent features of tumor cells is uncontrolled cell proliferation caused by an abnormal cell cycle, and the abnormal expression of cell cycle-related proteins gives tumor cells their invasive, metastatic, drug-resistance, and anti-apoptotic abilities. Recently, an increasing number of cell cycle-associated proteins have become the candidate biomarkers for early diagnosis of malignant tumors and potential targets for cancer therapies. As an important cell cycle regulatory protein, Cell Division Cycle 25C (CDC25C) participates in regulating G2/M progression and in mediating DNA damage repair. CDC25C is a cyclin of the specific phosphatase family that activates the cyclin B1/CDK1 complex in cells for entering mitosis and regulates G2/M progression and plays an important role in checkpoint protein regulation in case of DNA damage, which can ensure accurate DNA information transmission to the daughter cells. The regulation of CDC25C in the cell cycle is affected by multiple signaling pathways, such as cyclin B1/CDK1, PLK1/Aurora A, ATR/CHK1, ATM/CHK2, CHK2/ERK, Wee1/Myt1, p53/Pin1, and ASK1/JNK-/38. Recently, it has evident that changes in the expression of CDC25C are closely related to tumorigenesis and tumor development and can be used as a potential target for cancer treatment. This review summarizes the role of CDC25C phosphatase in regulating cell cycle. Based on the role of CDC25 family proteins in the development of tumors, it will become a hot target for a new generation of cancer treatments.
PubMed: 32518522
DOI: 10.1186/s12935-020-01304-w -
Asian Journal of Andrology 2020Peripheral nerve damage, such as that found after surgery or trauma, is a substantial clinical challenge. Much research continues in attempts to improve outcomes after...
Peripheral nerve damage, such as that found after surgery or trauma, is a substantial clinical challenge. Much research continues in attempts to improve outcomes after peripheral nerve damage and to promote nerve repair after injury. In recent years, low-intensity pulsed ultrasound (LIPUS) has been studied as a potential method of stimulating peripheral nerve regeneration. In this review, the physiology of peripheral nerve regeneration is reviewed, and the experiments employing LIPUS to improve peripheral nerve regeneration are discussed. Application of LIPUS following nerve surgery may promote nerve regeneration and improve functional outcomes through a variety of proposed mechanisms. These include an increase of neurotrophic factors, Schwann cell (SC) activation, cellular signaling activations, and induction of mitosis. We searched PubMed for articles related to these topics in both in vitro and in vivo animal research models. We found numerous studies, suggesting that LIPUS following nerve surgery promotes nerve regeneration and improves functional outcomes. Based on these findings, LIPUS could be a novel and valuable treatment for nerve injury-induced erectile dysfunction.
Topics: Animals; Cell Proliferation; Cell Survival; Erectile Dysfunction; Humans; Male; Mitosis; Nerve Growth Factors; Nerve Regeneration; Penis; Peripheral Nerve Injuries; Pudendal Nerve; Schwann Cells; Signal Transduction; Ultrasonic Therapy; Ultrasonic Waves
PubMed: 31535626
DOI: 10.4103/aja.aja_95_19 -
BMC Surgery Aug 2019By comparing the long-term prognostic outcomes after pancreaticoduodenectomy (PD) and limited resection (LR), this study aimed to investigate the optimal surgical... (Comparative Study)
Comparative Study Meta-Analysis
BACKGROUND
By comparing the long-term prognostic outcomes after pancreaticoduodenectomy (PD) and limited resection (LR), this study aimed to investigate the optimal surgical modality for duodenal gastrointestinal stromal tumors (GISTs).
METHODS
Two authors independently searched PubMed, Web of Science, Embase, and the Cochrane Library for published articles comparing the long-term prognostic and clinicopathological factors of duodenal GIST patients undergoing PD versus LR. Relevant information was extracted and analyzed.
RESULTS
After screening, 10 items comprising 623 cases were eventually included. This meta-analysis explicitly indicated that PD treatment was associated with worse long-term prognosis (hazard ratio = 1.93; 95% confidence interval [CI], 1.39-2.69; p < 0.001; I = 0) and more complications (odds ratio [OR] = 2.90; 95% CI, 1.90-4.42; p < 0.001; I = 10%) than LR treatment. Nevertheless, for duodenal GISTs, PD was related to the following clinicopathological features: invasion of the second part of the duodenum (OR = 3.39; 95% CI, 1.69-6.79; p < 0.001; I = 50%), high-degree tumor mitosis (> 5/50 high-power fields; OR = 2.24; 95% CI, 1.42-3.52; p < 0.001; I = 0), and high-risk classification (OR = 3.17; 95% CI; 2.13-4.71; p < 0.001; I = 0).
CONCLUSIONS
Since PD is associated with worse long-term prognosis and more complications, its safety and efficacy should be ascertained. Our findings recommend the use of LR to obtain negative incision margins when conditions permit it.
Topics: Duodenal Neoplasms; Duodenum; Gastrointestinal Stromal Tumors; Humans; Margins of Excision; Middle Aged; Pancreaticoduodenectomy; Prognosis
PubMed: 31455328
DOI: 10.1186/s12893-019-0587-4