-
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 -
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 -
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 -
Journal of the American Academy of... Dec 2015Animal-type melanoma is a rare subtype of melanoma with heavily pigmented dermal epithelioid and spindled melanocytes. Its classification as a subtype of melanoma versus... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Animal-type melanoma is a rare subtype of melanoma with heavily pigmented dermal epithelioid and spindled melanocytes. Its classification as a subtype of melanoma versus a borderline melanocytic tumor is debated.
OBJECTIVES
Our primary objective was to characterize the demographics, clinical presentation, histopathology, management, and outcomes of patients with animal-type melanoma.
METHODS
We performed a systematic review and meta-analysis of the English-language literature on animal-type melanoma.
RESULTS
We identified 190 cases of animal-type melanoma. They occurred equally in men and women, with Caucasians (53.7%) most commonly affected. The median Breslow depth was 3.8 mm; ulceration was reported present in 15.8%; and dermal mitoses greater than or equal to 1/mm(2) was reported in 27.4%. The most common initial management was wide local excision with sentinel lymph node biopsy (55.7%). In all, 78 patients underwent sentinel lymph node biopsy with 41.0% positivity rate. A total of 32 patients underwent completion lymph node dissection with 34.4% positivity rate. Locoregional recurrence was reported in 15 patients, recurrence with distant metastases in 6 patients, and death in 5 patients.
LIMITATIONS
Data were obtained from small studies with limited follow-up. There is no universally accepted definition of animal-type melanoma.
CONCLUSION
Prospective studies with complete staging information and molecular profiling may allow further characterization of this tumor.
Topics: Biopsy, Needle; Female; Humans; Immunohistochemistry; Incidence; Male; Melanocytes; Melanoma; Prognosis; Prospective Studies; Rare Diseases; Risk Assessment; Skin Neoplasms
PubMed: 26412164
DOI: 10.1016/j.jaad.2015.08.016 -
Scientific Reports Sep 2015Many types of KIT mutations have been observed in gastrointestinal stromal tumors (GISTs), but their prognostic and predictive significance are still unclear. A... (Meta-Analysis)
Meta-Analysis Review
Many types of KIT mutations have been observed in gastrointestinal stromal tumors (GISTs), but their prognostic and predictive significance are still unclear. A meta-analysis and literature review were conducted to estimate the contribution of KIT mutations in prognostic parameters and clinic-pathological significance of GISTs. A total of 18 relevant articles from PubMed, EMBASE and Web of Science databases were included in this study. The frequency of KIT mutation was significantly increased in the GIST patients with higher mitosis (≥5/50 high-power fields (HPFs) and larger size (≥5 cm) of tumors than in those with lower MI (≤5/50HPFs) and smaller size (≤5 cm) of GISTs respectively. The rate of KIT mutation was not significantly changed between GISTs in stomachs and in small intestines. KIT mutational status has prognostic significance for patients' outcome. GIST patients with KIT exon 9 mutations have higher risk of progression than those with exon 11 mutations. 5 year relapse-free survival (RFS) rate was significantly higher in patients with KIT exon 11 deletion than in those with other type of KIT exon 11 mutations. The deletion involving KIT exon 11, particularly codons 557-558, is a valuable predictor of prognosis for patients with GISTs.
Topics: Exons; Gastrointestinal Stromal Tumors; Genetic Association Studies; Genetic Predisposition to Disease; Humans; Mutation; Odds Ratio; Prognosis; Proto-Oncogene Proteins c-kit; Receptor, Platelet-Derived Growth Factor alpha; Risk
PubMed: 26349547
DOI: 10.1038/srep13718 -
Dermatologic Surgery : Official... Sep 2014The seventh edition of the American Joint Committee on Cancer guidelines recognize mitotic rate (MR) as a component of the staging criteria for cutaneous melanomas with... (Review)
Review
BACKGROUND
The seventh edition of the American Joint Committee on Cancer guidelines recognize mitotic rate (MR) as a component of the staging criteria for cutaneous melanomas with a Breslow depth ≤1 mm.
OBJECTIVE
This review discusses the evidence behind the threshold of 1 mitosis per square millimeter as a prognostic variable in thin melanomas, particularly because it relates to the decision to pursue a sentinel lymph node biopsy (SLNB).
MATERIALS AND METHODS
We performed a systematic review using the PubMed database to identify articles that contain prognostic information for thin melanomas based on MR and sentinel lymph node (SLN) status.
RESULTS
Although the threshold of a single mitosis correlates with a statistically significant decrease in survival rates for patients with thin melanomas, the clinical relevance remains questionable particularly because it relates to the decision to pursue an SLNB.
CONCLUSION
A single mitosis in thin melanomas does not increase the risk of a positive SLN so much that SLN biopsy should be routinely performed for this cohort.
Topics: Humans; Lymphatic Metastasis; Melanoma; Mitotic Index; Patient Selection; Prognosis; Sentinel Lymph Node Biopsy; Skin Neoplasms
PubMed: 25072127
DOI: 10.1097/01.DSS.0000452619.94264.ff -
Asian Pacific Journal of Cancer... 2012The vascular endothelial growth factor (VEGF) mediates vasculogenesis and angiogenesis through promoting endothelial cell growth, migration and mitosis, and has... (Review)
Review
BACKGROUND
The vascular endothelial growth factor (VEGF) mediates vasculogenesis and angiogenesis through promoting endothelial cell growth, migration and mitosis, and has involvement in cancer pathogenesis, progression and metastasis. However, the prognostic value of VEGF in patients with prostate cancer remains controversial.
OBJECTIVES
The aim of our study was to evaluate the prognostic value of VEGF in prostate cancer, and summarise the results of related research on VEGF.
METHODS
In accordance with an established search strategy, 11 studies with 1,529 patients were included in our meta-analysis. The correlation of VEGF-expression with overall survival and progression-free survival was evaluated by hazard ratio, either given or calculated.
RESULTS
The studies were categorized by introduction of the author, demographic data in each study, prostate cancer-relatived information, VEGF cut-off value, VEGF subtype, methods of hazard ratio (HR) estimation and its 95% confidence interval (CI). High VEGF-expression in prostate cancer is a poor prognostic factor with statistical significance for OS (HR=2.32, 95%CI: 1.40-3.24). However, high VEGF-expression showed no effect on poor PFS (HR=1.30, 95%CI: 0.88-1.72). Using Begg's, Egger's test and funnel plots, we confirmed lack of publication bias in our analysis.
CONCLUSION
VEGF might be regarded as a prognostic maker for prostate cancer, as supported by our meta-analysis. To achieve a more definitive conclusion enabling the clinical use of VEGF in prostate cancer, we need more high-quality interventional original studies following agreed research approaches or standards.
Topics: Biomarkers, Tumor; Clinical Trials as Topic; Humans; Male; Meta-Analysis as Topic; Prognosis; Prostatic Neoplasms; Vascular Endothelial Growth Factor A
PubMed: 23317235
DOI: 10.7314/apjcp.2012.13.11.5665 -
Journal Der Deutschen Dermatologischen... Sep 2011TNM classifications are the basis for diagnostic and therapeutic procedures in oncology. Histopathological reports have to enable a proper indexing of tumor specific...
Histopathological diagnostics of malignant melanoma in accordance with the recent AJCC classification 2009: Review of the literature and recommendations for general practice.
BACKGROUND
TNM classifications are the basis for diagnostic and therapeutic procedures in oncology. Histopathological reports have to enable a proper indexing of tumor specific findings into recent classifications.
METHODS
A systematic review of the literature was performed to identify reports dealing with the assessment of mitotic rate and the processing and evaluation of sentinel node biopsies in malignant melanoma. On the basis of this review an expert panel of dermatopathologists and general pathologists discussed and agreed recommendations for general practice.
RESULTS
Following recommendations were agreed with a broad consensus (93-100 % agreement): The determination of the mitotic rate in primary melanoma is performed on HE slides. The evaluation of an area of 1 mm(2) is sufficient. Only dermal mitoses are considered. The counted number of mitoses is provided as an integer value. The mitotic rate shall be determined in primary melanomas of ≤1.00 mm vertical tumor thickness according to the hot-spot method and provided as an integer value in relation to an area of 1 mm(2) . The determination of the mitotic rate in the case of thicker primary melanomas is desirable. In general, for the evaluation of each sentinel lymph node, 4 slides should be prepared. For diagnostic purposes, immunohistochemistry (preferably with antibodies against S100ß, Melan A and HMB-45) should be performed in addition to HE staining. The pathology report should provide information about micro-metastases and their longest extension (one-tenth of a millimeter).
CONCLUSIONS
These recommendations are suitable for standardizing the histopathological diagnosis of malignant melanoma and for providing a common basis for clinical decisions and scientific research.
Topics: Biomarkers, Tumor; Germany; Humans; Lymphatic Metastasis; Melanoma; Mitotic Index; Neoplasm Invasiveness; Neoplasm Micrometastasis; Neoplasm Staging; Sentinel Lymph Node Biopsy; Skin; Skin Neoplasms; United States
PubMed: 21651721
DOI: 10.1111/j.1610-0387.2011.07714.x -
Clinical Toxicology (Philadelphia, Pa.) Jun 2010Colchicine is used mainly for the treatment and prevention of gout and for familial Mediterranean fever (FMF). It has a narrow therapeutic index, with no clear-cut... (Review)
Review
INTRODUCTION
Colchicine is used mainly for the treatment and prevention of gout and for familial Mediterranean fever (FMF). It has a narrow therapeutic index, with no clear-cut distinction between nontoxic, toxic, and lethal doses, causing substantial confusion among clinicians. Although colchicine poisoning is sometimes intentional, unintentional toxicity is common and often associated with a poor outcome.
METHODS
We performed a systematic review by searching OVID MEDLINE between 1966 and January 2010. The search strategy included "colchicine" and "poisoning" or "overdose" or "toxicity" or "intoxication."
TOXICOKINETICS
Colchicine is readily absorbed after oral administration, but undergoes extensive first-pass metabolism. It is widely distributed and binds to intracellular elements. Colchicine is primarily metabolized by the liver, undergoes significant enterohepatic re-circulation, and is also excreted by the kidneys. THERAPEUTIC AND TOXIC DOSES: The usual adult oral doses for FMF is 1.2-2.4 mg/day; in acute gout 1.2 mg/day and for gout prophylaxis 0.5-0.6 mg/day three to four times a week. High fatality rate was reported after acute ingestions exceeding 0.5 mg/kg. The lowest reported lethal doses of oral colchicine are 7-26 mg.
DRUG INTERACTIONS
CYP 3A4 and P-glycoprotein inhibitors, such as clarithromycin, erythromycin, ketoconazole, ciclosporin, and natural grapefruit juice can increase colchicine concentrations. Co-administration with statins may increase the risk of myopathy.
MECHANISMS OF TOXICITY
Colchicine's toxicity is an extension of its mechanism of action - binding to tubulin and disrupting the microtubular network. As a result, affected cells experience impaired protein assembly, decreased endocytosis and exocytosis, altered cell morphology, decreased cellular motility, arrest of mitosis, and interrupted cardiac myocyte conduction and contractility. The culmination of these mechanisms leads to multi-organ dysfunction and failure. REPRODUCTIVE TOXICOLOGY AND LACTATION: Colchicine was not shown to adversely affect reproductive potential in males or females. It crosses the placenta but there is no evidence of fetal toxicity. Colchicine is excreted into breast milk and considered compatible with lactation.
CLINICAL FEATURES
Colchicine poisoning presents in three sequential and usually overlapping phases: 1) 10-24 h after ingestion - gastrointestinal phase mimicking gastroenteritis may be absent after intravenous administration; 2) 24 h to 7 days after ingestion - multi-organ dysfunction. Death results from rapidly progressive multi-organ failure and sepsis. Delayed presentation, pre-existing renal or liver impairment are associated with poor prognosis. 3) Recovery typically occurs within a few weeks of ingestion, and is generally a complete recovery barring complications of the acute illness.
DIAGNOSIS
History of ingestion of tablets, parenteral administration, or consumption of colchicine-containing plants suggest the diagnosis. Colchicine poisoning should be suspected in patients with access to the drug and the typical toxidrome (gastroenteritis, hypotension, lactic acidosis, and prerenal azotemia).
MANAGEMENT
Timely gastrointestinal decontamination should be considered with activated charcoal, and very large, recent (<60 min) ingestions may warrant gastric lavage. Supportive treatments including administration of granulocyte colony-stimulating factor are the mainstay of treatment. Although a specific experimental treatment (Fab fragment antibodies) for colchicine poisoning has been used, it is not commercially available.
CONCLUSION
Although colchicine poisoning is relatively uncommon, it is imperative to recognize its features as it is associated with a high mortality rate when missed.
Topics: ATP Binding Cassette Transporter, Subfamily B, Member 1; Adult; Charcoal; Clarithromycin; Clinical Trials as Topic; Colchicine; Colony-Stimulating Factors; Drug Interactions; Drug Overdose; Drug-Related Side Effects and Adverse Reactions; Familial Mediterranean Fever; Female; Granulocyte Colony-Stimulating Factor; Humans; Male
PubMed: 20586571
DOI: 10.3109/15563650.2010.495348