-
Archives of Gynecology and Obstetrics Aug 2022Endometrial hyperplasia (EH) is the precursor lesion for endometrioid adenocarcinoma of the endometrium (EC), which represents the most common malignancy of the female... (Review)
Review
Endometrial hyperplasia (EH) is the precursor lesion for endometrioid adenocarcinoma of the endometrium (EC), which represents the most common malignancy of the female reproductive tract in industrialized countries. The most important risk factor for the development of EH is chronic exposure to unopposed estrogen. Histopathologically, EH can be classified into EH without atypia (benign EH) and atypical EH/endometrial intraepithelial neoplasia (EIN). Clinical management ranges from surveillance or progestin therapy through to hysterectomy, depending on the risk of progression to or concomitant EC and the patient´s desire to preserve fertility. Multiple studies support the efficacy of progestins in treating both benign and atypical EH. This review summarizes the evidence base regarding risk factors and management of EH. Additionally, we performed a systematic literature search of the databases PubMed and Cochrane Controlled Trials register for studies analyzing the efficacy of progestin treatment in women with EH.
Topics: Endometrial Hyperplasia; Endometrial Neoplasms; Endometrium; Female; Humans; Progestins; Risk Factors
PubMed: 35001185
DOI: 10.1007/s00404-021-06380-5 -
Annals of Oncology : Official Journal... Apr 2016Borderline ovarian tumors (BOT) are epithelial tumors of the ovaries with both malignant and non-malignant aspects. On the one hand, they are characterized by cellular... (Review)
Review
BACKGROUND
Borderline ovarian tumors (BOT) are epithelial tumors of the ovaries with both malignant and non-malignant aspects. On the one hand, they are characterized by cellular proliferation and nuclear atypia but, on the other hand, they usually do not show infiltrative growth pattern. Balancing radicality between oncologic safety and treatment burden has already led to remarkable changes in the management pattern over the last decades and is still a challenging task.
DESIGN
This review is based on both a systematic review published by the authors and added with evidence gained from actually published literature.
RESULTS
As they frequently affect younger patients, the clinical management of BOT is complicated by aspects as preserving fertility and reducing postoperative morbidity. Over the past decades, the surgical therapy shifted from a radical approach to more conservative treatment. Today, fertility-sparing surgery is first-choice treatment in younger patients. In addition, minimal-invasive surgery has become the preferred surgical approach in these patients. Even recurrences are curable in most patients because only a minority of relapses transform to invasive cancer.
CONCLUSION
More studies on BOT are needed and longer follow-up and better characterization of high-risk subtypes are crucial to better understand long-term risk of BOT and avoid the rare but the fatal outcome in those few patients being undertreated by the current management strategies.
Topics: Disease Management; Female; Fertility Preservation; Humans; Neoplasm Staging; Ovarian Neoplasms; Ovariectomy; Ovary
PubMed: 27141065
DOI: 10.1093/annonc/mdw090 -
International Journal of Molecular... Apr 2022Ovarian endometriosis may increase the risk of malignancy. Several studies have suggested atypical endometriosis as the direct precursor of endometriosis-associated... (Review)
Review
Ovarian endometriosis may increase the risk of malignancy. Several studies have suggested atypical endometriosis as the direct precursor of endometriosis-associated ovarian cancer. We performed an advanced, systematic search of the online medical databases PubMed and Medline. The search revealed = 40 studies eligible for inclusion in this systematic review. Of these, = 39 were finally included. The results from included studies are characterized by high heterogeneity, but some consistency has been found for altered expression in phosphoinositide 3-kinase (PI3K)/AKT/mTOR pathway, ARID1a, estrogen and progesterone receptors, transcriptional, nuclear, and growth factors in atypical endometriosis. Although many targets have been proposed as biomarkers for the presence of atypical endometriosis, none of them has such strong evidence to justify their systematic use in clinical practice, and they all need expensive molecular analyses. Further well-designed studies are needed to validate the evidence on available biomarkers and to investigate novel serum markers for atypical endometriosis.
Topics: Biomarkers; Carcinoma, Ovarian Epithelial; Endometriosis; Female; Humans; Ovarian Neoplasms; Phosphatidylinositol 3-Kinases; Precancerous Conditions
PubMed: 35457244
DOI: 10.3390/ijms23084425 -
Journal of Osteopathic Medicine Feb 2022Management remains controversial due to the risk of upgrade for malignancy from flat epithelial atypia (FEA). Data about the frequency and malignancy upgrade rates are... (Meta-Analysis)
Meta-Analysis Review
CONTEXT
Management remains controversial due to the risk of upgrade for malignancy from flat epithelial atypia (FEA). Data about the frequency and malignancy upgrade rates are scant. Namely, observational follow-up is advised by many studies in cases of pure FEA on core biopsy and in the absence of an additional surgical excision. For cases of pure FEA, the American College of Surgeons no longer recommends surgical excision but rather recommends observation with clinical and imaging follow-up.
OBJECTIVES
The aim of this study is to perform a systematic review and meta-analysis to calculate the pooled upgrade of pure FEA following core needle biopsies.
METHODS
A search of MEDLINE and Embase databases were conducted in December 2020. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. A fixed- or random-effects model was utilized. Heterogeneity among studies was estimated by utilizing the I2 statistic and considered high if the I2 was greater than 50%. The random-effects model with the DerSimonian and Laird method was utilized to calculate the pooled upgrade rate and its 95% confidence interval.
RESULTS
A total of 1924 pure FEA were analyzed among 59 included studies. The overall pooled upgrade rate to malignancy was 8.8%. The pooled upgrade rate for mammography only was 8.9%. The pooled upgrade rate for ultrasound was 14%. The pooled upgrade rate for mammography and ultrasound combined was 8.8%. The pooled upgrade rate for MRI-only cases was 27.3%.
CONCLUSIONS
Although the guidelines for the management of pure FEA are variable, our data support that pure FEA diagnosed at core needle biopsy should undergo surgical excision since the upgrade rate >2%.
Topics: Breast; Breast Neoplasms; Carcinoma, Intraductal, Noninfiltrating; Female; Humans; Mammography
PubMed: 35150124
DOI: 10.1515/jom-2021-0206 -
The Cochrane Database of Systematic... Sep 2020In the absence of treatment, endometrial hyperplasia (EH) can progress to endometrial cancer, particularly in the presence of histologic nuclear atypia. The development... (Meta-Analysis)
Meta-Analysis
BACKGROUND
In the absence of treatment, endometrial hyperplasia (EH) can progress to endometrial cancer, particularly in the presence of histologic nuclear atypia. The development of EH results from exposure of the endometrium to oestrogen unopposed by progesterone. Oral progestogens have been used as treatment for EH without atypia, and in some cases of EH with atypia in women who wish to preserve fertility or who cannot tolerate surgery. EH without atypia is associated with a low risk of progression to atypia and cancer; EH with atypia is where the cells are structurally abnormal, and has a higher risk of developing cancer. Oral progestogen is not always effective at reversing the hyperplasia, can be associated with side effects, and depends on patient adherence. The levonorgestrel-intrauterine system (LNG-IUS) is an alternative method of administration of progestogen and may have some advantages over non-intrauterine progestogens.
OBJECTIVES
To evaluate the effectiveness and safety of the levonorgestrel intrauterine system (LNG-IUS) in women with endometrial hyperplasia (EH) with or without atypia compared to medical treatment with non-intrauterine progestogens, placebo, surgery or no treatment.
SEARCH METHODS
We searched the following databases: the Cochrane Gynaecology and Fertility Group (CGF) Specialised Register, CENTRAL, MEDLINE, Embase, CINAHL and PsycINFO, and conference proceedings of 10 relevant organisations. We handsearched references in relevant published studies. We also searched ongoing trials in ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry, and other trial registries. We performed the final search in May 2020.
SELECTION CRITERIA
Randomised controlled trials (RCTs) and cross-over trials of women with a histological diagnosis of endometrial hyperplasia with or without atypia comparing LNG-IUS with non-intrauterine progestogens, placebo, surgery or no treatment.
DATA COLLECTION AND ANALYSIS
Two review authors independently performed study selection, risk of bias assessment and data extraction. Our primary outcome measures were regression of EH and adverse effects associated with the LNG-IUS device (such as pelvic inflammatory disease, device expulsion, uterine perforation) when compared to treatment with non-intrauterine progestogens, placebo, surgery or no treatment. Secondary outcomes included hysterectomy, hormone-related adverse effects (such as bleeding/spotting, pelvic pain, breast tenderness, ovarian cysts, weight gain, acne), withdrawal from treatment due to adverse effects, satisfaction with treatment, and cost or resource use. We rated the overall quality of evidence using GRADE methods.
MAIN RESULTS
Thirteen RCTs (1657 women aged 22 to 75 years) met the inclusion criteria. Two studies had insufficient data for meta-analysis, thus the quantitative analysis included 11 RCTs. All trials evaluated treatment duration of six months or less. The evidence ranged from very low to moderate quality: the main limitations were risk of bias (associated with lack of blinding and poor reporting of study methods), inconsistency and imprecision. LNG-IUS versus non-intrauterine progestogens Primary outcomes Regression of endometrial hyperplasia The LNG-IUS probably improves regression of EH compared with non-intrauterine progestogens at short-term follow-up (up to six months) (OR 2.94, 95% CI 2.10 to 4.13; I² = 0%; 10 RCTs, 1108 participants; moderate-quality evidence). This suggests that if regression of EH following treatment with a non-intrauterine progestogen is assumed to be 72%, regression of EH following treatment with LNG-IUS would be between 85% and 92%. Regression of EH may be improved by LNG-IUS compared with non-intrauterine progestogens at long-term follow-up (12 months) (OR 3.80, 95% CI 1.75 to 8.23; 1 RCT, 138 participants; low-quality evidence), Adverse effects associated with LNG-IUS There was insufficient evidence to determine device-related adverse effects; only one study reported on expulsion with insufficient data for analysis. Secondary outcomes The LNG-IUS may be associated with fewer hysterectomies (OR 0.26, 95% CI 0.15 to 0.46; I² = 19%; 4 RCTs, 452 participants; low-quality evidence), fewer withdrawals from treatment due to hormone-related adverse effects (OR 0.41, 95% CI 0.12 to 1.35; I² = 0%; 4 RCTs, 360 participants; low-quality evidence) and improved patient satisfaction with treatment (OR 5.28, 95% CI 2.51 to 11.10; I² = 0%; 2 RCTs, 202 participants; very low-quality evidence) compared to non-intrauterine progestogens. The LNG-IUS may be associated with more bleeding/spotting (OR 2.13, 95% CI 1.33 to 3.43; I² = 78%; 3 RCTs, 428 participants) and less nausea (OR 0.52, 95% CI 0.28 to 0.95; I² = 0%; 3 RCTs, 428 participants) compared to non-intrauterine progestogens. Data from single trials for mood swings and fatigue had a similar direction of effect as for bleeding/spotting, nausea and weight gain. There was insufficient evidence to determine cost or resource use. LNG-IUS versus no treatment Regression of endometrial hyperplasia One study demonstrated that the LNG-IUS is associated with regression of EH without atypia (OR 78.41, 95% CI 22.86 to 268.97; I² = 0%; 1 RCT, 190 participants; moderate-quality evidence) compared with no treatment. This study did not report on any other review outcome.
AUTHORS' CONCLUSIONS
There is moderate-quality evidence that treatment with LNG-IUS used for three to six months is probably more effective than non-intrauterine progestogens at reversing EH in the short term (up to six months) and long term (up to two years). Adverse effects (device-related and hormone-related) were poorly and incompletely reported across studies. Very low quality to low-quality evidence suggests the LNG-IUS may reduce the risk of hysterectomy, and may be associated with more bleeding/spotting, less nausea, less withdrawal from treatment due to adverse effects, and increased satisfaction with treatment, compared to non-intrauterine progestogens. There was insufficient evidence to reach conclusions regarding device-related adverse effects, or cost or resource use.
Topics: Adult; Aged; Bias; Contraceptive Agents, Female; Endometrial Hyperplasia; Female; Humans; Hysterectomy; Intrauterine Device Expulsion; Intrauterine Devices, Medicated; Levonorgestrel; Middle Aged; Nausea; Patient Dropouts; Patient Satisfaction; Progestins; Randomized Controlled Trials as Topic; Remission Induction; Time Factors; Uterine Hemorrhage; Weight Gain; Young Adult
PubMed: 32909630
DOI: 10.1002/14651858.CD012658.pub2 -
Neuro-oncology Oct 2017With the release of the 2016 edition of the World Health Organization (WHO) Classification of Central Nervous System Tumors, brain invasion in meningiomas has been added... (Review)
Review
With the release of the 2016 edition of the World Health Organization (WHO) Classification of Central Nervous System Tumors, brain invasion in meningiomas has been added as a stand-alone criterion for atypia and can therefore impact grading and indirectly adjuvant therapy. Regarding this rising clinical importance, we have reviewed the current knowledge about brain invasion with emphasis on its implications on current and future clinical practice. We found various definitions of brain invasion and approaches for evaluation in surgically obtained specimens described over the past decades. This heterogeneity is reflected by weak correlation with prognosis and remains controversial. Similarly, associated clinical factors are largely unknown. Preoperative, imaging-guided detection of brain invasion is unspecific, and intraoperative assessment using standard and new high-magnification microscopic techniques remains imprecise. Despite the increasing knowledge about molecular alterations of the tumor/ brain surface, pharmacotherapeutic options targeting brain invasive meningiomas are lacking. Finally, we summarize the impact of brain invasion on histopathological grading in the WHO classifications of brain tumors since 1979.In conclusion, standardized neurosurgical sampling and neuropathological analyses could improve diagnostic reliability and reproducibility of future studies. Further research is needed to improve pre- and intraoperative visualization of brain invasion and to develop adjuvant, targeted therapies.
Topics: Brain Neoplasms; Humans; Meningeal Neoplasms; Meningioma; Neoplasm Grading; Neoplasm Invasiveness; World Health Organization
PubMed: 28419308
DOI: 10.1093/neuonc/nox071 -
Thyroid : Official Journal of the... Feb 2018Indeterminate categories of thyroid cytopathology (categories B-III and B-IV of the Bethesda system) are integrated by a heterogeneous spectrum of cytological scenarios... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Indeterminate categories of thyroid cytopathology (categories B-III and B-IV of the Bethesda system) are integrated by a heterogeneous spectrum of cytological scenarios that are generally clustered for analysis and management recommendations. It has been suggested that aspirates exhibiting nuclear atypia have a higher risk of malignancy. This study aimed to assess whether cytologically indeterminate thyroid nodules with nuclear atypia have a significantly higher cancer risk than those without nuclear atypia.
METHODS
On June 30, 2016, PubMed and EMBASE were searched for articles in English or Spanish using a search strategy developed by an endocrinologist and a librarian. Case reports were excluded, and no date limits were used. The references of all included studies were also screened for relevant missing studies. Studies were included if the prevalences of malignancy of cytologically indeterminate thyroid nodules with histological confirmation with and without nuclear atypia were reported. Studies were excluded if they had: (i) nodules suspicious for malignancy; (ii) nodules with non-indeterminate (B-III or B-IV) cytology on repeated biopsy, if performed; (iii) nodules not consecutively evaluated; or (iv) cohorts overlapping with another larger series. Two investigators independently assessed the eligibility and risk of bias of the studies. PRISMA and MOOSE guidelines were followed. Summary data were extracted from published reports by one investigator and independently reviewed by another. Data were pooled using a random-effects model. Heterogeneity was explored using subgroup analysis and mixed-effect model meta-regression. The odds ratio for malignancy of cytologically indeterminate thyroid nodules with nuclear atypia over cytologically indeterminate thyroid nodules without nuclear atypia was calculated.
RESULTS
Of 2571 retrieved studies, 20 were eligible. The meta-analysis was conducted on summary data of 3532 cytologically indeterminate thyroid nodules: 1162 with and 2370 without nuclear atypia. The odds ratio for malignancy in cytologically indeterminate thyroid nodules with nuclear atypia was 3.63 [confidence interval 3.06-4.35]. There was no evidence of publication bias, and heterogeneity was insignificant (I < 0.01%, p = 0.40).
CONCLUSIONS
Nuclear atypia is a significant indicator of malignancy in cytologically indeterminate thyroid nodules and needs to be standardized and implemented into clinical practice.
Topics: Cytodiagnosis; Humans; Risk; Thyroid Gland; Thyroid Neoplasms; Thyroid Nodule
PubMed: 29160163
DOI: 10.1089/thy.2017.0419 -
Surgery For Obesity and Related... 2013Because the number of patients with a previous bariatric procedure continues to rise, it is advisable for bariatric surgeons to know how to manage the rare event of the... (Review)
Review
BACKGROUND
Because the number of patients with a previous bariatric procedure continues to rise, it is advisable for bariatric surgeons to know how to manage the rare event of the development of an esophagogastric cancer. The aim of the study was to perform a systematic review of all reported cases of esophagogastric cancers after bariatric surgery.
METHODS
Systematic review of English and French written literature in MEDLINE and EMBASE database.
RESULTS
Globally, 28 articles describing 33 patients were retrieved. Neoplasms were diagnosed at a mean of 8.5 years after bariatric surgery (range 2 months-29 years). There were 11 esophageal and 22 gastric cancers; although adenocarcinoma represented most cases (90.6%), a tubulovillous adenoma with high-grade atypia, an intramural gastrointestinal stromal tumor, and a diffuse large B-cell lymphoma of the gastric fundus were also reported. Node involvement was reported in 14 cases, and distal metastases in 5. The most frequently reported symptoms were dysphagia and food intolerance, vomiting, epigastric pain, and weight loss. Surgery was performed in 28 patients, although 4 underwent only chemotherapy and/or radiotherapy and 1 received palliative care. Reported mortality rate was 48.1%.
CONCLUSIONS
To date, it is not possible to quantify the incidence of esophagogastric cancer after bariatric surgery because of the paucity of reported data. Nevertheless, because the main concern is the delay in diagnosis, it is of critical importance to carefully evaluate any new or modified upper digestive tract symptom occurring during bariatric surgery follow-up.
Topics: Aged; Bariatric Surgery; Esophageal Neoplasms; Female; Humans; Male; Middle Aged; Obesity; Risk Factors; Stomach Neoplasms
PubMed: 23265766
DOI: 10.1016/j.soard.2012.10.002 -
Medicine Apr 2017Fine-needle aspiration (FNA) is the most dependable tool to triage thyroid nodules for medical or surgical management. However, Bethesda class III cytology, namely... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Fine-needle aspiration (FNA) is the most dependable tool to triage thyroid nodules for medical or surgical management. However, Bethesda class III cytology, namely "follicular lesion of undetermined significance" (FLUS) or "atypia of undetermined significance" (AUS), is a major limitation of the US-FNA in assessing thyroid nodules. As the most important imaging method, ultrasound (US) has a high efficacy in diagnosing thyroid nodules. This meta-analysis aimed to assess the role of US in evaluating Bethesda class III thyroid nodules.
METHODS
With keywords "Undetermined Significance," "Bethesda Category III," "Bethesda system," "Cytological Subcategory," "AUS/FLUS," "Atypia of Undetermined Significance," and "Ultrasound/US," papers in PubMed, Cochrane Library, Medline, Web of Science, Embase, and Google Scholar from inception to December 2016 were searched. A meta-analysis of these trials was then performed for evaluating the diagnostic value of thyroid ultrasound in Bethesda Category III thyroid nodules.
RESULTS
Fourteen studies including 2405 nodules were analyzed. According to the criteria for US diagnosis of thyroid nodules in each article, with any one of suspicious features as indictors of malignancy, US had a pooled sensitivity of 0.75 (95% CI 0.72-0.78) and a pooled specificity of 0.48 (95% CI 0.45-0.50) in evaluating Bethesda Class III Nodules. The pooled diagnostic odds ratio was 10.92 (95% CI 6.04-19.74). The overall area under the curve was 0.84 and the Q* index was 0.77. With any 2 or 3 of US suspicious features as indictors of malignancy, the sensitivity and specificity were 0.77 (95% CI 0.71-0.83) and 0.54 (95% CI 0.51-0.58), 0.66 (95% CI 0.59-0.73) and 0.71 (95% CI 0.68-0.74), respectively.
CONCLUSIONS
US was helpful for differentiating benign and malignant Bethesda class III thyroid nodules, with the more suspicious features, the more likely to be malignant.
Topics: Biopsy, Fine-Needle; Diagnosis, Differential; Humans; Odds Ratio; Retrospective Studies; Sensitivity and Specificity; Thyroid Neoplasms; Thyroid Nodule; Ultrasonography
PubMed: 28422844
DOI: 10.1097/MD.0000000000006564 -
Precursor lesions of vulvar squamous cell carcinoma - histology and biomarkers: A systematic review.Critical Reviews in Oncology/hematology Mar 2020The precursor lesion of vulvar squamous cell carcinoma (VSCC), namely vulvar intraepithelial neoplasia (VIN), is classified as: human papillomavirus (HPV)-related high...
The precursor lesion of vulvar squamous cell carcinoma (VSCC), namely vulvar intraepithelial neoplasia (VIN), is classified as: human papillomavirus (HPV)-related high grade squamous intraepithelial lesion (HSIL), and HPV-independent differentiated VIN (dVIN). Traditionally, histology and immunohistochemistry (IHC) have been the basis of diagnosis and classification of VIN. HSIL shows conspicuous histological atypia, and positivity on p16-IHC, whereas dVIN shows less obvious histological atypia, and overexpression or null-pattern on p53-IHC. For both types of VIN, other diagnostic immunohistochemical markers have also been evaluated. Molecular characterization of VIN has been attempted in few recent studies, and novel genotypic subtypes of HPV-independent VSCC and VIN have been identified. This systematic review appraises the VSCC precursors identified so far, focusing on histology and biomarkers (immunohistochemical and molecular). To gain further insights into the carcinogenesis and to identify additional potential biomarkers, gene expression omnibus (GEO) datasets on VSCC were analyzed; the results are presented.
Topics: Biomarkers, Tumor; Carcinoma in Situ; Carcinoma, Squamous Cell; Female; Humans; Papillomaviridae; Papillomavirus Infections; Vulvar Neoplasms; Uterine Cervical Dysplasia
PubMed: 32058913
DOI: 10.1016/j.critrevonc.2020.102866