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2.
Hum Reprod Update ; 26(3): 392-411, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32097456

RESUMO

BACKGROUND: Adenomyosis is a benign uterine disorder where endometrial glands and stroma are pathologically demonstrated within the uterine myometrium. The pathogenesis involves sex steroid hormone abnormalities, inflammation, fibrosis and neuroangiogenesis, even though the proposed mechanisms are not fully understood. For many years, adenomyosis has been considered a histopathological diagnosis made after hysterectomy, classically performed in perimenopausal women with abnormal uterine bleeding (AUB) or pelvic pain. Until recently, adenomyosis was a clinically neglected condition. Nowadays, adenomyosis may also be diagnosed by non-invasive techniques, because of imaging advancements. Thus, a new epidemiological scenario has developed with an increasing number of women of reproductive age with ultrasound (US) or magnetic resonance imaging (MRI) diagnosis of adenomyosis. This condition is associated with a wide variety of symptoms (pelvic pain, AUB and/or infertility), but it is also recognised that some women are asymptomatic. Furthermore, adenomyosis often coexists with other gynecological comorbidities, such as endometriosis and uterine fibroids, and the diagnostic criteria are still not universally agreed. Therefore, the diagnostic process for adenomyosis is challenging. OBJECTIVE AND RATIONALE: We present a comprehensive review on the diagnostic criteria of adenomyosis, including clinical signs and symptoms, ultrasound and MRI features and histopathological aspects of adenomyotic lesions. We also briefly summarise the relevant theories on adenomyosis pathogenesis, in order to provide the pathophysiological background to understand the different phenotypes and clinical presentation. The review highlights the controversies of multiple existing criteria, summarising all of the available evidences on adenomyosis diagnosis. The review aims also to underline the future perspective for diagnosis, stressing the importance of an integrated clinical and imaging approach, in order to identify this gynecological disease, so often underdiagnosed. SEARCH METHODS: PubMed and Google Scholar were searched for all original and review articles related to diagnosis of adenomyosis published in English until October 2018. OUTCOMES: The challenge in diagnosing adenomyosis starts with the controversies in the available pathogenic theories. The difficulties in understanding the way the disease arises and progresses have an impact also on the specific diagnostic criteria to use for a correct identification. Currently, the diagnosis of adenomyosis may be performed by non-invasive methods and the clinical signs and symptoms, despite their heterogeneity and poor specificity, may guide the clinician for a suspicion of the disease. Imaging techniques, including 2D and 3D US as well as MRI, allow the proper identification of the different phenotypes of adenomyosis (diffuse and/or focal). From a histological point of view, if the diagnosis of diffuse adenomyosis is straightforward, in more limited disease, the diagnosis has poor inter-observer reproducibility, leading to extreme variations in the prevalence of disease. Therefore, an integrated non-invasive diagnostic approach, considering risk factors profile, clinical symptoms, clinical examination and imaging, is proposed to adequately identify and characterise adenomyosis. WIDER IMPLICATIONS: The development of the diagnostic tools allows the physicians to make an accurate diagnosis of adenomyosis by means of non-invasive techniques, representing a major breakthrough, in the light of the clinical consequences of this disease. Furthermore, this technological improvement will open a new epidemiological scenario, identifying different groups of women, with a dissimilar clinical and/or imaging phenotypes of adenomyosis, and this should be object of future research.

3.
Curr Oncol Rep ; 22(2): 12, 2020 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-31997106

RESUMO

PURPOSE OF REVIEW: Uterine cancer comprises endometrial carcinoma and the uterine sarcoma. Endometrial carcinomas are the most frequent variant and have early symptoms and a solid diagnostic work up, resulting in a rather fair prognosis. However, in case of advanced stage disease and relapse, treatment options are limited and prognosis is impaired. Uterine sarcomas are rare, often lacking symptoms and no diagnostic tool for correct pre-operative diagnosis are available. Prognosis is poor. RECENT FINDINGS: Circulating biomarkers as a liquid biopsy could be beneficial as a diagnostic tool in uterine sarcomas. For both carcinomas and sarcomas, circulating biomarkers could be of use in predicting early disease recurrence. This review in endometrial carcinoma and uterine sarcoma focus on circulating biomarkers; such as proteins; circulating tumor cells; circulating tumor DNA; microRNA; and immune cells.

4.
Mod Pathol ; 33(2): 196-205, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31375764

RESUMO

Ductal carcinoma in situ of the breast includes several subtypes with a divergent biological behavior. Data regarding the composition of ductal carcinoma in situ-associated immune cells and their potential role in progression is limited. We studied ductal carcinoma in situ-associated immune response by characterizing immune cell subsets according to ductal carcinoma in situ subtypes. Ductal carcinoma in situ-associated tumor infiltrating lymphocyte (TIL) density was evaluated based on hematoxylin and eosin (H&E)-stained sections from 473 patients. Cases were subtyped based on ER, PR, and HER2. Patients were categorized as TIL-high or low. Ductal carcinoma in situ-associated immune cells of TIL-high cases were immunostained on whole slides with CD4, CD8, CD20, CD68, FOXP3, and PD-L1 (SP142 and SP263). In total, 131/473 patients (28.0%) were considered as TIL-high. The percentage of TIL-high cases was significantly higher in HER2+ and triple-negative ductal carcinoma in situ (P < 0.0001). Overall, no statistical difference in immune cell composition according to subtypes was found. However, individual subtype comparison showed that ER+ HER2+ cases had a significantly higher proportion of CD8+ T cells compared with triple-negative cases (P = 0.047). In TIL-high cases, PD-L1-SP142 expression on tumor cells was associated with subtype (P = 0.037); the lowest number of positive cases was observed in the HER2+ subtype (independent of ER). However, in TIL-high ductal carcinoma in situ, PD-L1 expression by both clones was limited. In conclusion, high numbers of TILs are predominantly observed in HER+ and triple negative ductal carcinoma in situ. The ER+ HER2+ subtype seems to attract a higher proportion of CD8+ T cells compared with the triple negative subtype. Among TIL-high cases, the HER2+ subgroup had the lowest PD-L1-SP142 expression on tumor cells. This suggests a more pronounced antitumor immunity in HER2+ ductal carcinoma in situ, which could play a role in its biological behavior.

5.
Artigo em Inglês | MEDLINE | ID: mdl-31875325

RESUMO

OBJECTIVES: To describe clinical and ultrasound characteristics of urinary bladder malignancies diagnosed on transvaginal ultrasound in women presenting with suspected gynecological problems. METHODS: This is a multicenter retrospective study of women with histological diagnosis of urinary bladder malignancy that was suspected on transvaginal ultrasound examination. The cases were collected from three centers which specialize in the use of pelvic ultrasound between January 2007 and October 2018. Clinical data were obtained from the computer databases and all tumor images were assessed by two authors (DJ and JK) to look for characteristic sonographic patterns. We have compared the characteristics of tumors seen in women presenting with symptoms suspicious of urinary bladder malignancy and those without such symptoms. RESULTS: Thirty women with a confirmed diagnosis of urinary bladder malignancy on histological examination were included. Median age at diagnosis was 70.5 years (range 36-88). The most common presenting symptom was postmenopausal bleeding which was recorded in 18 women (60%). Ten women (33%) had symptoms suspicious of bladder malignancy: six had unexplained visible hematuria, three had unexplained recurrent urinary tract infections and one woman had dysuria and microhematuria. On histological examination 23 women (77%) were diagnosed with primary bladder malignancy whilst seven women (23%) had metastases in the bladder from other primary tumors. Out of 23 primary tumors, 21 (91%) were of urothelial origin (12 low-grade and 9 high-grade). Most low-grade urothelial carcinomas appeared on ultrasound as irregular papillary growth (11/12, 92%) and they were moderately to highly vascular on color Doppler examination (8/12, 67%). The ultrasound appearances of primary non-urothelial and metastatic tumors varied without a clear common morphological tumor pattern. The tumors found in women with symptoms suggestive of bladder malignancy did not differ unequivocally from those detected in other women in their size, ultrasound morphology, vascularity or histological type. CONCLUSION: Urinary bladder malignancies can be detected in patients undergoing transvaginal ultrasound examination for suspected gynecological problems. Primary urothelial cancers have relatively uniform morphological pattern, whilst the appearances of other bladder malignancies are more variable. This article is protected by copyright. All rights reserved.

6.
Artigo em Inglês | MEDLINE | ID: mdl-31840873

RESUMO

OBJECTIVES: To develop a pre-operative risk model using endometrial biopsy results, clinical and ultrasound variables to predict the individual risk of lymph node metastases in women with endometrial cancer. METHODS: A mixed effects logistic regression model was developed on 1501 prospectively included women with endometrial cancer subjected to transvaginal ultrasound examination before surgery. Missing data, including missing lymph node status, was imputed. Discrimination, calibration and clinical utility were evaluated using leave-center-out cross-validation. The predictive performance was compared with risk classification from endometrial biopsy alone (high-risk = endometrioid cancer grade 3/non-endometrioid cancer) or combined endometrial biopsy and ultrasound (high-risk = endometrioid cancer grade 3/non-endometrioid cancer/deep myometrial invasion/cervical stromal invasion/extrauterine spread). RESULTS: Lymphadenectomy was performed in 691 women, of which 127 had lymph node metastases. The model included the predictors age, duration of abnormal bleeding, endometrial biopsy result, tumor extension and tumor size according to ultrasound and "undefined tumor with an unmeasurable endometrium". The model's AUC was 0.73 (95% CI 0.68 to 0.78), calibration slope 1.06 (95% CI 0.79 to 1.34) and calibration intercept 0.06 (95% CI 0.15 to 0.27). Using risk thresholds for lymph node metastases 5% vs. 20% the model had sensitivity 98% vs. 48% and specificity 11% vs. 80%. The model had higher sensitivity and specificity than high-risk according to endometrial biopsy alone (50% vs. 35% and 80% vs. 77%) or combined endometrial biopsy and ultrasound (80% vs. 75% and 53% vs. 52%). The model's clinical utility was higher than that of endometrial biopsy alone or combined endometrial biopsy and ultrasound at any given risk threshold. CONCLUSIONS: Based on endometrial biopsy results, clinical and ultrasound characteristics, the individual risk of lymph node metastases in women with endometrial cancer can be reliably estimated before surgery. The model is superior to risk classification by endometrial biopsy alone or in combination with ultrasound. This article is protected by copyright. All rights reserved.

7.
Sci Rep ; 9(1): 15250, 2019 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-31649317

RESUMO

Optimal preservation and biobanking of renal tissue is vital for good diagnostics and subsequent research. Optimal cutting temperature (OCT) compound is a commonly used embedding medium for freezing tissue samples. However, due to interfering polymers in OCT, analysis as mass spectrometry (MS) is difficult. We investigated if the replacement of OCT with Cryo-Gel as embedding compound for renal biopsies would enable proteomics and not disturb other common techniques used in tissue diagnostics and research. For the present study, fresh renal samples were snap-frozen using Cryo-Gel, OCT and without embedding compound and evaluated using different techniques. In addition, tissue samples from normal spleen, skin, liver and colon were analyzed. Cryo-Gel embedded tissues showed good morphological preservation and no interference in immunohistochemical or immunofluorescent investigations. The quality of extracted RNA and DNA was good. The number of proteins identified using MS was similar between Cryo-Gel embedded samples, samples without embedding compound and OCT embedded samples. However, polymers in the OCT disturbed the signal in the MS, while this was not observed in the Cryo-Gel embedded samples. We conclude that embedding of renal biopsies in Cryo-Gel is an excellent and preferable alternative for OCT compound for both diagnostic and research purposes, especially in those cases where proteomic analysis might be necessary.

8.
Artigo em Inglês | MEDLINE | ID: mdl-31503381

RESUMO

OBJECTIVES: this prospective observational study compared the value of magnetic resonance imaging (MRI) complementary to transvaginal ultrasonography (TV-US) to our standard preoperative assessment of patients with endometriosis referred for surgery in a tertiary care academic center. Based on the extent to which endometriosis affects reproductive organs, bowel, ureters, bladder or other abdominal organs, the surgery will be carried out by gynecologists only or by a multidisciplinary team involving abdominal surgeons and/or urologists. METHODS: In 74 women with clinically suspected deep endometriosis (DE) the standard preoperative imaging, i.e. an expert transvaginal ultrasonography (TV-US), complemented by an intravenous urography (IVU) for the evaluation of the ureters, and a double contrast barium enema (DCBE) for the evaluation of the rectum, sigmoid and caecum was compared with an expert TV-US complemented by a 'one-stop' abdominal and pelvic magnetic resonance imaging (MRI). The findings of the laparoscopy were the reference standard to provide an answer to the question if a 'one-stop' abdominal/pelvic MRI is equally reliable as our standard radiological imaging as a complement to transvaginal ultrasonography for preoperative triaging of patients with suspected urological and intestinal involvement by DE in tertiary care centers. RESULTS: The standard preoperative imaging as well as the combined findings of the TV-US and the MRI allowed a correct stratification for a monodisciplinary approach by gynecologists or a multidisciplinary approach in 90.5% of the patients. Both TV-US and DCBE underestimated the severity of the rectal involvement in 2.7%, whereas TV-US and/or DCBE overestimated it in 6.8% of the patients. CONCLUSIONS: In conclusion, complementary to an expert transvaginal ultrasound (TV-US) a 'one-stop' magnetic resonance imaging (MRI) predicts the intra-operative findings equally well as the standard radiological imaging (IVU and DCBE) in patients referred for endometriosis surgery in a tertiary care academic center. This article is protected by copyright. All rights reserved.

9.
Transplantation ; 2019 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-31517782

RESUMO

INTRODUCTION: C4d staining in peritubular capillaries (PTCs) is a well-established feature of antibody-mediated rejection (AMR). The relevance of C4d staining outside PTCs is not well understood. We investigated the significance of arteriolar C4d staining in c-aAMR. METHODS: All for-cause renal allograft biopsies performed in 2007-2014 at the Erasmus MC and meeting the criteria for suspicious/diagnostic c-aAMR using the Banff Classification 2015, were included. For comparison, renal allograft biopsies from a matched control group and native renal biopsies were analyzed. Arteriolar C4d staining was semi-quantitatively scored as negative (0), small deposits in 1 arteriole (1+), small/large deposits in >1 arterioles (2+) or at least extensive deposits in most arterioles (3+). RESULTS: Thirty-four of 40 (85%) patients with c-aAMR showed arteriolar C4d staining. A significant difference in arteriolar C4d score was observed between cases and matched controls (p=0.01) and a trend toward significance difference between cases and native renal biopsies (p=0.05). In the cases, arteriolar C4d staining was significantly associated with severity of arteriolar hyalinosis (ah) (p=0.004) and ≥2 arteriolar C4d staining was independently associated with better graft outcome in a multivariate Cox regression analysis (hazard ratio 0.260, 95%-Cl: 0.104-0.650, p=0.004). CONCLUSION: This pilot study shows that arteriolar C4d staining is more common in biopsies with c-aAMR compared to those without and that it is associated with ah. ≥2 arteriolar C4d staining is associated with superior graft outcome. However, larger studies are needed to examine these findings in more detail to asses if arteriolar C4d staining is truly related to antibody-mediated injury.

10.
Anticancer Res ; 39(8): 3981-3989, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31366479

RESUMO

Uterine sarcomas are rare but very aggressive. Uterine myomas, on the other hand, are the most common benign tumors of the uterus. Currently there is no diagnostic technique available to distinguish them with certainty. This study aimed to summarize the published literature concerning protein-based biomarkers in the peripheral blood that can assist in this difficult differential diagnosis. In total, 48 articles, published between 1990 and 2017, were included. Most studies (n=37) concerned soft tissue sarcomas, while 11 discussed uterine sarcomas specifically. Vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), interleukins (IL), cancer antigen 125 (CA 125), lactate dehydrogenase, gangliosides (LDH) and growth differentiation factor 15 (GDF-15) are the most studied proteins in soft tissue sarcomas, including uterine sarcomas. Future research on improving sarcoma diagnosis should include these proteins.


Assuntos
Leiomioma/sangue , Neoplasias/sangue , Sarcoma/sangue , Neoplasias Uterinas/sangue , Biomarcadores Tumorais/sangue , Diferenciação Celular/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Leiomioma/patologia , Neoplasias Musculares/sangue , Neoplasias Musculares/patologia , Neoplasias/patologia , Sarcoma/patologia , Neoplasias Uterinas/patologia
11.
Transplantation ; 103(10): 2065-2074, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31343579

RESUMO

BACKGROUND: Interleukin 21 (IL-21) is involved in regulating the expansion and effector function of a broad range of leukocytes, including T cells and B cells. In transplantation, the exact role of IL-21 in the process of allograft rejection is unknown. To further explore this, the aim of this study is to test the effect of an IL-21 receptor (IL-21R) blocking antibody on the early phase of allograft rejection in a humanized skin transplantation model in mice reconstituted with human T and B cells. METHODS: Immunodeficient Balb/c IL2rγRag2 mice were transplanted with human skin followed by adoptive transfer of human allogeneic splenocytes. Control animals were treated with a phosphate buffered saline vehicle while the other group was treated with a humanized anti-IL-21R antibody (αIL-21R). RESULTS: In the phosphate buffered saline-treated animals, human skin allografts were infiltrated with lymphocytes and developed a thickened epidermis with increased expression of the inflammatory markers Keratin 17 (Ker17) and Ki67. In mice treated with αIL-21R, these signs of allograft reactivity were significantly reduced. Concordantly, STAT3 phosphorylation was inhibited in this group. Of note, treatment with αIL-21R attenuated the process of T and B cell reconstitution after adoptive cellular transfer. CONCLUSIONS: These findings demonstrate that blockade of IL-21 signaling can delay allograft rejection in a humanized skin transplantation model.

13.
J Heart Lung Transplant ; 38(5): 570-579, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30819647

RESUMO

BACKGROUND: Chronic lung allograft dysfunction (CLAD) hampers long-term survival after lung transplantation. Common fibrosis-related mechanisms in idiopathic pulmonary fibrosis and CLAD instigated the consideration of investigating the differential regulation of pleural mesothelium and transforming growth factor-ß1 (TGF-ß1) in restrictive allograft syndrome (RAS). METHODS: TGF-ß1 was assessed in bronchoalveolar lavage (BAL) fluid using enzyme-linked immunoassay and via immune staining of explant biopsies. To assess the role of the pleura, explanted bronchiolitis obliterans syndrome (BOS) and RAS lungs were compared using computed tomography scans, calretinin stainings, Western blot, and quantititative real-time PCR. Last, a pleural mesothelial cell line was used to assess mesothelial-to-mesenchymal transition and its inhibition. RESULTS: TGF-ß1 was increased in BAL of RAS patients (p = 0.035), and was present in the (sub)pleural area of biopsies. Explanted RAS lungs demonstrated an increased volume fraction of pleura (p = 0.0004), a higher proportion of calretinin-positive stainings (p = 0.0032), and decreased E-cadherin (p = 0.019) and increased α-smooth muscle actin (p = 0.0089) mRNA expression and protein levels in isolated pleural tissue. Moreover, TGF-ß1 stimulation of pleural mesothelial cells led to a phenotypical switch to mesenchymal cells, accompanied with an increased migratory capacity. Interleukin-1α was able to accentuate TGF-ß1‒induced mesothelial-to-mesenchymal transition. None of the tested drugs could inhibit mesothelial-to-mesenchymal transition at the used concentrations. CONCLUSIONS: Our results support an interplay between TGF-ß1 and the pleural mesothelium in the pathophysiology of RAS.

15.
J Ultrasound Med ; 38(10): 2673-2683, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30801764

RESUMO

OBJECTIVES: To evaluate the intra- and inter-rater agreement for myometrial lesions using Morphologic Uterus Sonographic Assessment terminology. METHODS: Thirteen raters with high (n = 6) or medium experience (n = 7) assessed 30 3-dimensional ultrasound clips with (n = 20) and without (n = 10) benign myometrial lesions. Myometrial lesions were reported as poorly or well defined and then systematically evaluated for the presence of individual features. The clips were blindly assessed twice (at a 2-month interval). Intra- and inter-rater agreements were calculated with κ statistics. RESULTS: The reporting of poorly defined lesions reached moderate intra-rater agreement (κ = 0.49 [high experience] and 0.47 [medium experience]) and poor inter-rater agreement (κ = 0.39 [high experience] and 0.25 [medium experience]). The reporting of well-defined lesions reached good to very good intra-rater agreement (κ = 0.73 [high experience] and 0.82 [medium experience]) and good inter-rater agreement (κ = 0.75 [high experience] and 0.63 [medium experience]). Most individual features associated with ill-defined lesions reached moderate intra- and inter-rater agreement among highly experienced raters (κ = 0.41-0.60). The least reproducible features were myometrial cysts, hyperechoic islands, subendometrial lines and buds, and translesional flow (κ = 0.11-0.34). Most individual features associated with well-defined lesions reached moderate to good intra- and inter-rater agreement among all observers (κ = 0.41-0.80). The least reproducible features were a serosal contour, asymmetry, a hyperechoic rim, and fan-shaped shadows (κ = 0.00-0.35). CONCLUSIONS: The reporting of well-defined lesions showed excellent agreement, whereas the agreement for poorly defined lesions was low, even among highly experienced raters. The agreement on identifying individual features varied, especially for features associated with ill-defined lesions. Guidelines on minimum requirements for features associated with ill-defined lesions to be interpreted as poorly defined lesions may improve agreement.

16.
Transplant Direct ; 5(1): e418, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30656216

RESUMO

Background: Belatacept-based therapy in kidney transplant recipient has been shown to increase long-term renal allograft and patient survival compared with calcineurin inhibitor-based therapy, however, with an increased risk of acute T cell-mediated rejection (aTCMR). An improved understanding of costimulation blockade-resistant rejections could lead to a more personalized approach to belatacept therapy. Here, immunomic profiles of aTCMR biopsies of patients treated with either tacrolimus or belatacept were compared. Methods: Formalin-fixed paraffin-embedded renal transplant biopsies were used for immunohistochemistry and gene expression analysis using the innovative NanoString technique. To validate NanoString, transcriptomic profiles of patients with and without biopsy-proven aTCMR were compared. Biopsies from 31 patients were studied: 14 tacrolimus-treated patients with aTCMR, 11 belatacept-treated patients with aTCMR, and 6 controls without rejection. Results: A distinct pattern was seen in biopsies with aTCMR compared to negative controls: 78 genes had a higher expression in the aTCMR group (false discovery rate P value <.05 to 1.42e-05). The most significant were T cell-associated genes (CD3, CD8, and CD4; P < 1.98e-04), γ-interferon-inducible genes (CCL5, CXCL9, CXCL11, CXCL10, TBX21; P < 1.33e-04) plus effector genes (GNLY, GZMB, ITGAX; P < 2.82e-03). Immunophenotypical analysis of the classic immune markers of the innate and adaptive immune system was comparable between patients treated with either tacrolimus or belatacept. In addition, the transcriptome of both groups was not significantly different. Conclusions: In this small pilot study, no difference was found in immunomics of aTCMR biopsies of tacrolimus- and belatacept-treated patients. This suggests that clinically diagnosed aTCMR reflects a final common pathway of allorecognition which is unaffected by the type of immunosuppressive therapy.

17.
Proteomics Clin Appl ; 13(3): e1800181, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30417587

RESUMO

PURPOSE: The objective of present study is to determine serum levels and placental distribution of two interacting proteins calcyclin and heat shock protein 90 in preeclampsia. EXPERIMENTAL DESIGN: Maternal serum levels of calcyclin and heat shock protein 90 are compared throughout pregnancy from the first trimester till term among women with preeclampsia (n = 43) and age-matched normotensive pregnant controls (n = 46). A serum-based 2D LC-MS assay using Parallel Reaction Monitoring is applied to quantify both calcyclin and heat shock protein 90. RESULTS: Serum levels of calcyclin are significantly lower in patients with preeclampsia in the second trimester of pregnancy as compared to controls (p < 0.05). Serum levels of heat shock protein 90 are significantly higher in patients with preeclampsia in the third trimester as compared to controls (p < 0.001). CONCLUSION AND CLINICAL RELEVANCE: Both interacting proteins calcyclin and heat shock protein 90 are notably changed in preeclamptic patients compared to controls. Calcyclin is already decreased before the onset of preeclampsia in the second trimester and HSP90 is strongly increased in the third trimester. This suggests that these proteins may play a role in the pathogenesis of preeclampsia and ought to be investigated in large cohort studies as molecular biomarkers.


Assuntos
Proteínas de Choque Térmico HSP90/sangue , Placenta/metabolismo , Pré-Eclâmpsia/sangue , Proteína A6 Ligante de Cálcio S100/sangue , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Espectrometria de Massas , Pré-Eclâmpsia/patologia , Gravidez , Proteômica , Trofoblastos/metabolismo
18.
Gynecol Oncol ; 150(3): 438-445, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30029961

RESUMO

OBJECTIVES: The aim is to estimate agreement between two-dimensional transvaginal ultrasound (2D-TVS) and three-dimensional volume contrast imaging (3D-VCI) in diagnosing deep myometrial invasion (MI) and cervical stromal involvement (CSI) of endometrial cancer and to compare the two methods regarding inter-rater reliability and diagnostic accuracy. METHODS: Fifteen ultrasound experts assessed off-line de-identified 3D-VCI volumes and 2D-TVU video clips from 58 patients with biopsy-confirmed endometrial cancer regarding the presence of deep (≥50%) MI and CSI. Video clips and 3D volumes were assessed independently. Interrater reliability was measured using kappa statistics. Histological diagnosis after hysterectomy served as gold standard. Accuracy measurements were correlated to rater experience using Spearman's rank correlation coefficient (ρ). RESULTS: Agreement between 2D-TVU and 3D-VCI for diagnosing MI was median 76% (range 64-93%) and for CSI median 88% (range 79-97%). Interrater reliability was better for 2D-TVU than for 3D-VCI (Fleiss' kappa 0.41 vs. 0.31 for MI and 0.55 vs. 0.45 for CSI). Median accuracy for diagnosing deep MI was 76% (range 59-84%) with 2D-TVU and 69% (range 52-83%) for 3D-VCI; the corresponding figures for CSI were 88% (range 81-93%) and 86% (range 72-95%). Accuracy was significantly correlated to how many cases the raters assessed annually. CONCLUSIONS: Off-line assessment of MI and CSI in women with endometrial cancer using 3D-VCI has lower interrater reliability and lower accuracy than 2D-TVU video clip assessment. Since accuracy was correlated to the number of cases assessed annually it is advised to centralize these examinations to high-volume centres.


Assuntos
Neoplasias do Endométrio/diagnóstico por imagem , Neoplasias do Endométrio/patologia , Imageamento Tridimensional , Ultrassonografia/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Meios de Contraste , Neoplasias do Endométrio/cirurgia , Feminino , Humanos , Pessoa de Meia-Idade , Miométrio/diagnóstico por imagem , Miométrio/patologia , Invasividade Neoplásica , Estadiamento de Neoplasias/métodos , Variações Dependentes do Observador , Reprodutibilidade dos Testes , Estudos Retrospectivos
19.
Artigo em Inglês | MEDLINE | ID: mdl-29506961

RESUMO

Transvaginal ultrasonography has become the primary test in the diagnosis of pelvic endometriosis and adenomyosis. A review of the literature on the diagnostic accuracy of ultrasonography in pelvic endometriosis and adenomyosis, as well as a comparison with magnetic resonance imaging, will be presented. Criteria for diagnosis of an endometrioma according to robust prospective data together with guidelines as to adequate reporting of the location of deep infiltrating endometriosis will be given. The sonographic features of adenomyosis including the differential diagnosis between focal adenomyosis and a uterine fibroid are reviewed. The available data in the literature on ultrasound diagnosis of pelvic endometriosis and adenomyosis, their clinical relevance, and their limitations are discussed.


Assuntos
Adenomiose/diagnóstico por imagem , Endometriose/diagnóstico por imagem , Ultrassonografia/métodos , Adenomiose/patologia , Diagnóstico Diferencial , Endometriose/patologia , Feminino , Humanos , Imagem por Ressonância Magnética , Estudos Observacionais como Assunto , Estudos Prospectivos , Estudos Retrospectivos , Sensibilidade e Especificidade
20.
J Ultrasound Med ; 37(6): 1467-1472, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29219200

RESUMO

OBJECTIVES: To assess interobserver reproducibility in detecting tubal ectopic pregnancies by reading data sets from 3-dimensional (3D) transvaginal ultrasonography (TVUS) and comparing it with real-time 2-dimensional (2D) TVUS. METHODS: Images were initially classified as showing pregnancies of unknown location or tubal ectopic pregnancies on real time 2D TVUS by an experienced sonologist, who acquired 5 3D volumes. Data sets were analyzed offline by 5 observers who had to classify each case as ectopic pregnancy or pregnancy of unknown location. The interobserver reproducibility was evaluated by the Fleiss κ statistic. The performance of each observer in predicting ectopic pregnancies was compared to that of the experienced sonologist. Women were followed until they were reclassified as follows: (1) failed pregnancy of unknown location; (2) intrauterine pregnancy; (3) ectopic pregnancy; or (4) persistent pregnancy of unknown location. RESULTS: Sixty-one women were included. The agreement between reading offline 3D data sets and the first real-time 2D TVUS was very good (80%-82%; κ = 0.89). The overall interobserver agreement among observers reading offline 3D data sets was moderate (κ = 0.52). The diagnostic performance of experienced observers reading offline 3D data sets had accuracy of 78.3% to 85.0%, sensitivity of 66.7% to 81.3%, specificity of 79.5% to 88.4%, positive predictive value of 57.1% to 72.2%, and negative predictive value of 87.5% to 91.3%, compared to the experienced sonologist's real-time 2D TVUS: accuracy of 94.5%, sensitivity of 94.4%, specificity of 94.5%, positive predictive value of 85.0%, and negative predictive value of 98.1%. CONCLUSIONS: The diagnostic accuracy of 3D TVUS by reading offline data sets for predicting ectopic pregnancies is dependent on experience. Reading only static 3D data sets without clinical information does not match the diagnostic performance of real time 2D TVUS combined with clinical information obtained during the scan.


Assuntos
Imageamento Tridimensional/métodos , Gravidez Tubária/diagnóstico por imagem , Ultrassonografia/métodos , Estudos de Coortes , Endoscopia/métodos , Feminino , Humanos , Variações Dependentes do Observador , Valor Preditivo dos Testes , Gravidez , Estudos Prospectivos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Vagina/diagnóstico por imagem
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