-
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 -
Human Reproduction Update 2016ICSI is currently the most commonly used assisted reproductive technology, accounting for 70-80% of the cycles performed. This extensive use, even excessive, is partly... (Review)
Review
BACKGROUND
ICSI is currently the most commonly used assisted reproductive technology, accounting for 70-80% of the cycles performed. This extensive use, even excessive, is partly due to the high level of standardization reached by the procedure. There are, however, some aspects that deserve attention and can still be ameliorated. The aim of this systematic review was to evaluate the results of available publications dealing with the management of specific situations during ICSI in order to support embryologists in trying to offer the best laboratory individualized treatment.
METHODS
This systematic review is based on material obtained by searching PUBMED between January 1996 and March 2015. We included peer-reviewed, English-language journal articles that have evaluated ICSI outcomes in the case of (i) immature oocytes, (ii) oocyte degeneration, (iii) timing of the various phases, (iv) polar body position during injection, (v) zona-free oocytes, (vi) fertilization deficiency, (vii) round-headed sperm, (viii) immotile sperm and (ix) semen samples with high DNA fragmentation.
RESULTS
More than 1770 articles were obtained, from which only 90 were specifically related to the issues developed for female gametes and 55 for the issues developed for male gametes. The studies selected for this review were organized in order to provide a guide to overcome roadblocks. According to these studies, the injection of rescue metaphase I oocytes should be discouraged due to poor clinical outcomes and a high aneuploidy rates; laser-assisted ICSI represents an efficient method to solve the high oocyte degeneration rate; the optimal ICSI timing and the best polar body position during the injection have not been clarified; injected zona-free oocytes, if handled carefully, can develop up to blastocyst stage and implant; efficient options can be offered to patients who suffered fertilization failure in previous conventional ICSI cycles. Most controversial and inconclusive are data on the best method to select a viable spermatozoa when only immotile spermatozoa are available for ICSI and, to date, there is no reliable approach to completely filter out spermatozoa with fragmented DNA from an ejaculate. However, most of the studies do not report essential clinical outcomes, such as live birth, miscarriage and fetal abnormality rate, which are essential to establish the safety of a procedure.
CONCLUSIONS
This review provides the current knowledge on some controversial technical aspects of the ICSI procedures in order to improve its efficacy in specific contexts. Notwithstanding that embryologists might benefit from the approaches presented herein in order to improve ICSI outcomes, this area of expertise still demands a greater number of well-designed studies, especially in order to solve open issues about the safety of these procedures.
Topics: Asthenozoospermia; DNA Fragmentation; Female; Fertilization; Humans; Male; Metaphase; Microinjections; Oocytes; Pregnancy; Sperm Injections, Intracytoplasmic; Spermatozoa
PubMed: 26586241
DOI: 10.1093/humupd/dmv050 -
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 -
European Journal of Surgical Oncology :... Jul 2017The identification of small (<2 cm) gastrointestinal stromal tumors (GISTs) is increasingly recognized. The malignancy potential is not absent. However, data on risk is... (Review)
Review
INTRODUCTION
The identification of small (<2 cm) gastrointestinal stromal tumors (GISTs) is increasingly recognized. The malignancy potential is not absent. However, data on risk is scarce. The aim was to review the existing data on perceived risk of small GISTs in population-based studies.
METHODS
A combined review of small GISTs (<2 cm) in a population-based dataset compared with a systematic review of available population-based studies.
RESULTS
About one in every four (27%) patient has a small GIST, of which 79% were incidental in presentation, and all had a low-risk mitoses index (<5/hpf). The small GISTs had C-KIT mutations in exon 11 or 9 (66%), none had mutation in PDGFRA, and 33% were non-KIT/PDGFRA. The rate of small GISTs increased for each advancing age group. None of the small GISTs had a recurrence nor were there any GIST-specific deaths during follow-up. A "small GIST" rate at one-fourth of all GISTs reported was corroborated in other population-based studies from Norway, Iceland and Korea. Common to studies reporting mitosis index were an almost universal finding of very low-risk in small GISTs, with very few recurrences and an excellent long-term survival reported to 95-100% in several series.
DISCUSSION
One in every four GIST diagnosed is a small GIST (<2 cm). Small GISTs are increasingly found with advanced age and have an overall excellent prognosis. Defining true risk-features for proper surveillance and treatment strategy is needed in order to avoid over- and under-treatment.
Topics: Age Factors; Aged; Cell Transformation, Neoplastic; Gastrointestinal Neoplasms; Gastrointestinal Stromal Tumors; Humans; Middle Aged; Mitotic Index; Neoplasm Recurrence, Local; Norway; Proto-Oncogene Proteins c-kit; Receptor, Platelet-Derived Growth Factor alpha; Survival Rate; Tumor Burden
PubMed: 28222971
DOI: 10.1016/j.ejso.2017.01.240 -
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 -
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 -
Oncotarget Aug 2017Polo-like kinases 1 (PLK1), a key regulator of mitosis, plays an essential role in maintaining genomic stability. Up-regulation of PLK1 was found in tumorigenesis and... (Review)
Review
Polo-like kinases 1 (PLK1), a key regulator of mitosis, plays an essential role in maintaining genomic stability. Up-regulation of PLK1 was found in tumorigenesis and tumor progression of diverse cancers. However, the clinicopathological and prognostic implications of PLK1 in breast cancer (BC) have yet to be unveiled. Therefore, using PubMed, Web of Science, Embase, and Chinese databases, we conducted a meta-analysis to define the potential clinical value of PLK1 in BC. Eleven eligible articles with 2481 patients enrolled were included in the present meta-analysis, of which eight studies reported on the relationship between PLK1 expression and clinicopathological features, and nine studies provided survival data in BC patients. Furthermore, the results revealed that high PLK1 levels were significantly associated with larger tumor size (OR=1.703, 95%CIs: 1.315-2.205, <0.001), higher pathological grading (OR=6.028, 95%CIs: 2.639-13.772, <0.001), and lymph node metastasis (OR= 1.524, 95%CIs: 1.192-1.950, =0.001). Moreover, PLK1 was found to be a valuable factor for distinguishing lobular BC from ductal BC with the pooled OR=0.215(95%CIs: 0.083-0.557, =0.002). Analysis of included data showed that high PLK1 expression significantly indicated worse overall survival for BC patients (HR= 3.438, 95%CIs: 2.293-5.154, <0.001), as well as worse cancer specific survival and disease-free survival (HR=2.414, 95%CIs: 1.633-3.567, <0.001 and HR= 2.261, 95%CIs: 1.796-2.951, <0.001, respectively). This quantitative meta-analysis suggests that high PLK1 expression is a credible indicator for the progression of BC and confirms a higher risk of a worse survival rate in patients with BC.
PubMed: 28915707
DOI: 10.18632/oncotarget.17301 -
Annals of Surgical Oncology May 2019This systematic review and meta-analysis aimed to investigate local recurrence (LR) rates among the three grades (benign, borderline, and malignant) of phyllodes tumors... (Meta-Analysis)
Meta-Analysis
BACKGROUND
This systematic review and meta-analysis aimed to investigate local recurrence (LR) rates among the three grades (benign, borderline, and malignant) of phyllodes tumors (PTs). The study also assessed various risk factors for LR.
METHODS
Electronic articles published between 1 January 1995 and 31 May 2018, were searched and critically appraised. The authors independently reviewed the abstracts and extracted data for LR rates and LR risk factors.
RESULTS
The review incorporated 54 studies with 9234 individual cases. The pooled LR rates were 8% for benign, 13% for borderline, and 18% for malignant PTs. The risk of LR was significantly increased by borderline versus benign PTs (odds ratio [OR] 2.00; 95% confidence interval [CI] 1.68-2.38) and malignant versus borderline PTs (OR 1.28; 95% CI 1.05-1.55). The significant risk factors for LR were mitoses, tumor border (infiltrating vs. pushing), stromal cellularity (moderate/severe vs. mild), stromal atypia (severe vs. mild/absent), stromal overgrowth (severe vs. mild/absent), and tumor necrosis (positive vs. negative). Age and tumor size were not associated with LR risk. The subgroup analysis showed that breast-conserving surgery versus mastectomy and positive versus negative surgical margins were significantly associated with an increased LR risk only in malignant PTs.
CONCLUSIONS
The risk of LR was significantly increased from benign to borderline to malignant PTs. Mitoses, tumor border, stromal cellularity, stromal atypia, stromal overgrowth, tumor necrosis, type of surgery, and surgical margin status may be risk factors for LR. Different management strategies could be considered for different PT grades.
Topics: Breast Neoplasms; Female; Humans; Neoplasm Recurrence, Local; Phyllodes Tumor; Risk Factors
PubMed: 30617873
DOI: 10.1245/s10434-018-07134-5 -
Topics in Current Chemistry (Cham) May 2019As the emergence of resistance to clinical cancer treatments poses a significant problem in cancer management, there is a constant need to explore novel anticancer...
Systematic Review on Cytotoxic and Anticancer Potential of N-Substituted Isatins as Novel Class of Compounds Useful in Multidrug-Resistant Cancer Therapy: In Silico and In Vitro Analysis.
As the emergence of resistance to clinical cancer treatments poses a significant problem in cancer management, there is a constant need to explore novel anticancer agents which have the ability to overcome multidrug resistance (MDR) mechanisms. The search for the development of novel isatin-based antitumor agents accelerated after the approval by the Food and Drug Administration (FDA) of sunitinib malate, a C-3 isatin derivative, as a multitargeted receptor tyrosine kinase inhibitor. However, it is interesting to note that, over the last decade, various N-substituted analogs of isatin with intact carbonyl functionalities have been found to show more promising anticancer potential than its C-3 derivatives. Microtubule-targeting agents are a class of anticancer drugs which affect mitosis by targeting microtubules and suppressing their dynamic behavior. This review presents a systematic compilation of the in vitro cytotoxic and anticancer properties of various N-substituted isatins and illustrates their mechanism of action to overcome MDR by acting as microtubule-destabilizing agents. Predictions of the biological activities and cytotoxic effects of potential N-substituted isatins against various cancer cell lines have also been performed using the PASS computer-aided drug discovery program. Findings from such in vitro and in silico studies will act as a guide for the development of structure-activity relationship and will facilitate the design and exploration of more potent analogs of isatin with high potency and lower side effects for treatment of drug-resistant cancer. Mechanism of action of N-substituted isatin as microtubule-destabilizing agent on tumor cells. N-Substituted isatins bind to colchicine binding site on β-tubulin, which inhibits microtubule polymerization and thereby destabilizes microtubule dynamics, resulting in mitotic arrest leading to tumor cell growth suppression.
Topics: Antineoplastic Agents; Cell Proliferation; Computer Simulation; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Drug Screening Assays, Antitumor; Humans; In Vitro Techniques; Isatin; Microtubules; Quantitative Structure-Activity Relationship
PubMed: 31073777
DOI: 10.1007/s41061-019-0240-9 -
Virchows Archiv : An International... Apr 2021Myoid gonadal stromal tumor represents a rare testicular neoplasm displaying smooth muscular and gonadal stromal differentiation. This entity has very few cases reported...
Myoid gonadal stromal tumor represents a rare testicular neoplasm displaying smooth muscular and gonadal stromal differentiation. This entity has very few cases reported in the literature that describe heterogeneous clinical and pathological characteristics. Bayesian statistics provides a useful framework to combine information from diverse sources. We here presented a case series-the largest so far reported-of myoid gonadal stromal tumor (4 cases) with extensive morphologic, immunohistochemical, and molecular characterization, performed a systematic review of the literature (that identified 9 papers), and used a Bayesian data analysis to understand the characteristics of this disease. Our study collectively described 16 cases. This neoplasm is mainly found in adults (mean age about 40 years) and often has a size of about 3 cm. By morphology, the tumor can infiltrate testicular tubules and is composed of spindle cells; few mitoses can be seen (usually 2/10 HPF). Neoplastic cells are diffusely positive with α-smooth muscle actin with a tram-track staining pattern. S100 protein, FOXL2, and SF1 are also characteristically positive. Moreover, this neoplasm can display epithelial differentiation, in about half of the cases. In conclusion, we foresee the use of this statistical approach in pathology: our analysis allowed a more precise description of this rare entity.
Topics: Adult; Bayes Theorem; Biomarkers, Tumor; Humans; Immunohistochemistry; Male; Middle Aged; Sex Cord-Gonadal Stromal Tumors; Testicular Neoplasms
PubMed: 33140129
DOI: 10.1007/s00428-020-02957-8