RESUMO
OBJECTIVE: Our aim was to characterize the pathological, molecular and clinical outcomes of clear cell carcinoma of the endometrium (CCC). METHODS: CCC underwent ProMisE (Proactive Molecular Risk Classifier for Endometrial Cancer) classification identifying four molecular subtypes: i) 'POLEmut' for ECs with pathogenic POLE mutations, ii) 'MMRd', if there is loss of mismatch repair proteins by immunohistochemistry (IHC), iii) 'p53wt' or iv) 'p53abn' based on p53 IHC staining. Clinicopathologic parameters, immune markers (CD3, CD8, CD79a, CD138, PD-1), ER, L1CAM, and outcomes were assessed. RESULTS: 52 CCCs were classified, including 1 (2%) POLEmut, 5 (10%) MMRd, 28 (54%) p53wt and 18 (35%) p53abn. Women with p53abn and p53wt CCCs were older than women with MMRd and POLEmut subtypes. p53wt CCC were distinct from typical p53wt endometrioid carcinomas; more likely to arise in older, thinner women, with advanced stage disease, LVSI and lymph node involvement, and a higher proportion ER negative, L1CAM overexpressing tumors with markedly worse outcomes. High levels of immune infiltrates (TILhigh) were observed in 75% of the CCC cohort. L1CAM overexpression was highest within p53abn and p53wt subtypes of CCC. CONCLUSION: CCC is a heterogeneous disease encompassing all four molecular subtypes and a wide range of clinical outcomes. Outcomes of patients with POLEmut, MMRd and p53abn CCC are not distinguishable from those of other patients with these respective subtypes of EC; p53wt CCC, however, differ from endometrioid p53wt EC in clinical, pathological, molecular features and outcomes. Thus, p53wt CCC of endometrium appear to be a distinct clinicopathological entity within the larger group of p53wt ECs.
Assuntos
Adenocarcinoma de Células Claras/classificação , Neoplasias do Endométrio/classificação , Adenocarcinoma de Células Claras/genética , Adenocarcinoma de Células Claras/metabolismo , Adenocarcinoma de Células Claras/patologia , Adulto , Idoso , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Estudos de Coortes , Reparo de Erro de Pareamento de DNA , Neoplasias do Endométrio/genética , Neoplasias do Endométrio/metabolismo , Neoplasias do Endométrio/patologia , Feminino , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Análise de Sobrevida , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismoRESUMO
Chronic obstructive pulmonary disease and emphysema are common destructive inflammatory diseases that are leading causes of death worldwide. Here we show that emphysema is an autoimmune disease characterized by the presence of antielastin antibody and T-helper type 1 (T(H)1) responses, which correlate with emphysema severity. These findings link emphysema to adaptive immunity against a specific lung antigen and suggest the potential for autoimmune pathology of other elastin-rich tissues such as the arteries and skin of smokers.
Assuntos
Autoimunidade , Elastina/imunologia , Enfisema/etiologia , Enfisema/imunologia , Fumar/efeitos adversos , Linfócitos B/imunologia , Humanos , Pulmão , Doença Pulmonar Obstrutiva Crônica/etiologia , Doença Pulmonar Obstrutiva Crônica/imunologia , Fumar/imunologia , Linfócitos T/imunologia , Linfócitos T Reguladores/imunologiaRESUMO
OBJECTIVE: To highlight a novel surgical approach for the management of undescended ovaries in those presenting with infertility, to allow for potential transvaginal egg retrieval. The video demonstrates a novel surgical approach for mobilization and oophoropexy of undescended ovaries to allow for future transvaginal egg retrieval in the context of artificial reproductive technology (ART). DESIGN: Case report. Institutional Review Board approval is not required because this was not a human study. Patient consent was obtained for video footage. SETTING: Hospital. PATIENTS: We present a 26-year-old nulligravid woman with a unicornuate uterus, a high riding-right ovary, and an undescended left ovary with prior laparoscopic remnant uterine horn resection. Because of her 9 years of infertility and a prior unsuccessful ovarian mobilization and oophoropexy, she was referred for consideration of a repeat laparoscopic bilateral ovarian mobilization and oophoropexy. INTERVENTION: Surgical intervention for undescended ovaries. MAIN OUTCOME MEASURES: Postoperative ovarian location and postoperative pain. RESULTS: The patient reported minimal pain postoperatively at 6 weeks. Multiple follow-up imaging revealed both ovaries behind the uterus (antral follicle counts 15), with easy transvaginal access for future ART. CONCLUSION: Undescended ovary is uncommon and usually requires no treatment. However, intervention may be required in the context of infertility and ART, where transvaginal egg retrieval is impossible because of the location of the ovaries. This is the first educational video to our knowledge highlighting a novel surgical approach for the management of undescended ovaries.
Assuntos
Infertilidade , Laparoscopia , Doenças Ovarianas , Anormalidades Urogenitais , Humanos , Feminino , Adulto , Doenças Ovarianas/cirurgia , Anormalidades Urogenitais/cirurgia , Laparoscopia/métodos , Infertilidade/cirurgiaRESUMO
OBJECTIVE: To correlate maternal and fetal outcomes of pregnancies affected by preterm premature rupture of membranes (PPROM) at < 24 weeks' gestational age with the amount of residual amniotic fluid as determined by sonographic evaluation. METHODS: We searched the local maternal-fetal medicine database for the records of all women with PPROM prior to 24 completed weeks of pregnancy. The quantity of residual amniotic fluid determined by ultrasound was recorded and women were separated into two groups: (A) deepest vertical pocket (DVP) ≥ 1 cm, or (B) DVP < 1 cm (severe oligohydramnios). Hospital chart review was undertaken to determine latency to delivery, perinatal death, and maternal complications. Data were analyzed using Fisher exact and Wilcoxon-Mann-Whitney U tests. RESULTS: We identified 31 subjects, of whom nine elected termination of pregnancy (6 in group A, 3 in group B). Six of 10 subjects in group A had a live delivery without neonatal death, whereas only one of 12 subjects in group B had a live delivery (P = 0.020). Additional complications included placental abruption in 63% in group A and 45% in group B, chorioamnionitis in 50% and 70%, respectively, and postpartum endometritis in 0% and 9%, respectively. None of these differences were statistically significant. There were no cases of maternal sepsis or maternal death in either group. Group A was associated with a later GA at delivery (27.5 weeks vs. 23 weeks, P = 0.07), with the GA at rupture of the membranes similar for both groups. CONCLUSION: These results indicate that a higher level of residual amniotic fluid after periviable PPROM is associated with fetal survival and increased latency to delivery without an increase in maternal complications. This information will be valuable in counselling pregnant women with PPROM < 24 weeks.
Assuntos
Líquido Amniótico/diagnóstico por imagem , Ruptura Prematura de Membranas Fetais , Idade Gestacional , Resultado da Gravidez , Parto Obstétrico , Feminino , Morte Fetal/epidemiologia , Humanos , Mortalidade Infantil , Recém-Nascido , Recém-Nascido Prematuro , Oligo-Hidrâmnio/diagnóstico por imagem , Gravidez , Fatores de Tempo , UltrassonografiaRESUMO
BACKGROUND: The patterns of airway remodeling and the biomarkers that distinguish different subtypes of severe asthma are unknown. OBJECTIVES: We sought to characterize subjects with severe asthma with and without chronic persistent airflow obstruction with respect to airway wall remodeling (histopathologic and radiologic) and specific sputum biomarkers. METHODS: Subjects with severe asthma with chronic persistent (n = 16) or intermittent (n = 18) obstruction were studied. Endobronchial biopsy specimens were analyzed for airway smooth muscle area, epithelial detachment, basement membrane thickness, and submucosal fibrosis. Levels of eosinophil cationic protein, myeloperoxidase, matrix metalloproteinase 9, tissue inhibitor of matrix metalloproteinase 1 (ELISA), and 27 cytokines (multiplex assay) and differential cell counts were measured in induced sputum. Airway thickness was measured by means of high-resolution computed tomographic scanning. RESULTS: Chronic persistent obstruction was associated with earlier age of onset, longer disease duration, more inflammatory cells in the sputum, and greater smooth muscle area (15.65% +/- 2.69% [n = 10] vs 8.96% +/- 1.99% [n = 14], P = .0325). No differences between groups were found for any of the biomarker molecules measured in sputum individually. However, principal component analysis revealed that the dominant variables in the chronic persistent obstruction group were IL-12, IL-13, and IFN-gamma, whereas IL-9, IL-17, monocyte chemotactic protein 1, and RANTES were dominant in the other group. Airway imaging revealed no differences between groups. CONCLUSION: Subjects with severe asthma with chronic persistent obstruction have increased airway smooth muscle with ongoing T(H)1 and T(H)2 inflammatory responses. Neither airway measurements on high-resolution computed tomographic scans nor sputum analysis seem able to identify such patients.
Assuntos
Asma/patologia , Doença Pulmonar Obstrutiva Crônica/patologia , Sistema Respiratório/patologia , Adulto , Feminino , Granulócitos/metabolismo , Humanos , Masculino , Metaloproteinase 9 da Matriz/metabolismo , Pessoa de Meia-Idade , Músculo Liso/patologia , Sistema Respiratório/diagnóstico por imagem , Escarro/imunologia , Inibidor Tecidual de Metaloproteinase-1/metabolismo , Tomografia Computadorizada por Raios XRESUMO
Exposure to tobacco smoke activates innate and adaptive immune responses that in long-term smokers have been linked to diseases of the lungs, cardiovascular system, joints, and other organs. The destruction of lung tissue that underlies smoking-induced emphysema has been associated with T helper 1 cells that recognize the matrix protein elastin. Factors that result in the development of such autoreactive T cells in smokers remain unknown but are crucial for further understanding the pathogenesis of systemic inflammatory diseases in smokers. Here, we show that lung myeloid dendritic cells were sufficient to induce T helper 1 and T helper 17 responses in CD4 T cells. T helper 1 and 17 cells are invariably present in lungs from patients with emphysema but not in lungs from normal individuals. Interleukin-17A, a canonical T helper 17 cytokine, enhanced secretion of CCL20, a chemoattractant for dendritic cells, and matrix metalloproteinase 12, a potent elastolytic proteinase, from lung macrophages. Thus, although diverse lung factors potentially contribute to T helper effector differentiation in vivo, lung myeloid dendritic cells direct the generation of pathogenic T cells and support a feedback mechanism that sustains both inflammatory cell recruitment and lung destruction. This mechanism may underlie disease in other elastin-rich organs and tissues.