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1.
Acta Derm Venereol ; 103: adv5087, 2023 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-36987537

RESUMO

Patients with psoriasis have a higher prevalence of cardiovascular risk factors. This study evaluated cardiovascular screening practices and statin prescribing habits among dermatologists, rheumatologists and primary care physicians (PCPs) through an online questionnaire, which was distributed through the Spanish scientific societies of the above-mentioned specialties. A total of 299 physicians (103 dermatologists, 94 rheumatologists and 102 PCPs) responded to the questionnaire. Of these, 74.6% reported screening for smoking, 37.8% for hypertension, 80.3% for dyslipidaemia, and 79.6% for diabetes mellitus. Notably, only 28.4% performed global screening, defined as screening for smoking, hypertension, dyslipidaemia, and diabetes mellitus by the same physician, and 24.4% reported calculating 10-year cardiovascular disease (CVD) risk, probably reflecting a lack of comprehensive cardiovascular risk assessment in these patients. This study also identified unmet needs for awareness of cardiovascular comorbidities in psoriasis and corresponding screening and treatment recommendations among PCPs. Of PCPs, 61.2% reported not being aware of the association between psoriasis and CVD and/or not being aware of its screening recommendations, and 67.6% did not consider psoriasis as a risk-enhancing factor when deciding on statin prescription. Thirteen dermatologists (12.6%) and 35 rheumatologists (37.2%) reported prescribing statins. Among those who do not prescribe, 49.7% would be willing to start their prescription.


Assuntos
Doenças Cardiovasculares , Diabetes Mellitus , Inibidores de Hidroximetilglutaril-CoA Redutases , Hipertensão , Médicos de Atenção Primária , Psoríase , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Reumatologistas , Dermatologistas , Psoríase/diagnóstico , Psoríase/tratamento farmacológico , Psoríase/epidemiologia , Prescrições , Hábitos , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/prevenção & controle
2.
J Obstet Gynaecol Res ; 47(8): 2737-2744, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33998104

RESUMO

INTRODUCTION: We analyzed the role of systematic pelvic and para-aortic lymphadenectomy in delayed debulking surgery after six neoadjuvant chemotherapy (NACT) cycles for advanced high-grade serous ovarian carcinoma. MATERIALS AND METHODS: We retrospectively reviewed patients with advanced ovarian carcinoma who underwent NACT with carboplatin-paclitaxel between 2008 and 2016. Patients were included only if they had FIGO IIIC-IVB high-grade serous carcinoma with clinically negative lymph nodes after six NACT cycles (carboplatin-paclitaxel) and underwent complete or near complete cytoreduction. Patients with partial lymphadenectomy or bulky nodes were excluded. Patients who underwent systematic pelvic and aortic lymphadenectomy and those who did not undergo lymph node dissection were compared. Progression-free and overall survivals were analyzed using the Kaplan-Meier method. RESULTS: Totally, 132 patients with FIGO IIIC-IVB epithelial ovarian carcinoma were surgically treated after NACT. Sixty patients were included (39 and 21 in the lymphadenectomy and nonlymphadenectomy group, respectively); 40% had suspicious lymph nodes before NACT. Patient characteristics, blood transfusion numbers, and complication incidence were similar between the groups. In the lymphadenectomy group, 12 patients (30.8%) had histologically positive lymph nodes and the surgical time was longer (229 vs. 164 min). The median overall survival in the lymphadenectomy and nonlymphadenectomy groups, respectively, was 56.7 (95% CI 43.4-70.1) and 61.2 (21.4-101.0) months (p = 0.934); the corresponding disease-free survival was 8.1 (6.2-10.1) and 8.3 (5.1-11.6) months (p = 0.878). Six patients exclusively presented with lymph node recurrence. CONCLUSIONS: Systematic lymphadenectomy after six NACT cycles may have no influence on survival.


Assuntos
Terapia Neoadjuvante , Neoplasias Ovarianas , Quimioterapia Adjuvante , Procedimentos Cirúrgicos de Citorredução , Feminino , Humanos , Excisão de Linfonodo , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/cirurgia , Estudos Retrospectivos
3.
Int J Gynecol Cancer ; 29(1): 188-194, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30640703

RESUMO

OBJECTIVES: To evaluate the clinical outcomes of epithelial ovarian carcinoma patients who underwent cardiophrenic lymph node resection. METHODS: We retrospectively reviewed the records of all surgically treated patients with advanced epithelial ovarian carcinoma (stages IIIC-IV) who underwent cardiophrenic lymph node resection between 2002 and 2018. Only those in whom cardiophrenic lymph node involvement was the only detectable extra-abdominal disease were included. Patients with suspected cardiophrenic lymph node metastasis on staging images underwent a transdiaphragmatic incision to access the para-cardiac space after complete abdominal cytoreduction achievement. Data on disease-free survival, overall survival, and surgical procedures performed concurrently with cardiophrenic lymph node resection were collected. RESULTS: Of the total 456 patients, 29 underwent cardiophrenic lymph node resection; of these, 24 patients met the inclusion criteria. Twenty-two, one, and one patients had high grade serous epithelial ovarian carcinoma, low grade epithelial ovarian carcinoma, and ovarian carcinosarcoma, respectively. Ten patients had recurrent disease (recurrence group). Fourteen patients underwent cytoreduction during primary treatment (primary debulking group); four underwent cytoreduction after neoadjuvant chemotherapy. Cardiophrenic lymph node resection was performed on the right side in 19 patients, left side in three, and bilaterally in two. The average procedural duration was 28 minutes, with minimal blood loss and no severe complications. Twenty-one patients had cardiophrenic lymph node positivity. The median disease-free intervals were 17 and 12 months in the recurrent and primary debulking surgery groups, respectively. The mediastinum was the first recurrence site in 10 patients. Five patients developed brain metastases. Five patients had an overall survival beyond 50 months. CONCLUSIONS: Although rare, the cardiophrenic lymph nodes may be a site of metastasis of ovarian cancer. Although their presence might indicate future recurrence, some patients may achieve long-term survival. Resection should be considered in cases of suspicious involvement to confirm extra-abdominal disease and achieve complete cytoreduction.


Assuntos
Procedimentos Cirúrgicos de Citorredução/mortalidade , Excisão de Linfonodo/mortalidade , Linfonodos/cirurgia , Recidiva Local de Neoplasia/cirurgia , Neoplasias Ovarianas/cirurgia , Pericárdio/cirurgia , Adulto , Idoso , Carcinossarcoma/secundário , Carcinossarcoma/cirurgia , Cistadenocarcinoma Seroso/secundário , Cistadenocarcinoma Seroso/cirurgia , Diafragma , Feminino , Seguimentos , Humanos , Linfonodos/patologia , Metástase Linfática , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Neoplasias Ovarianas/patologia , Pericárdio/patologia , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
5.
Int J Gynecol Cancer ; 26(9): 1673-1678, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27552404

RESUMO

BACKGROUND: Laparoscopy is considered the method of choice in the operative treatment of type I endometrial carcinoma (EC). However, there is a paucity of data regarding the safety of endoscopy for type II EC because these malignancies have several biological similarities with ovarian cancer. OBJECTIVES: This study aimed to evaluate the feasibility, operative outcomes, and oncologic safety of laparoscopic surgery in patients with type II EC. METHODS: A retrospective study with histologically confirmed serous or clear-cell EC without peritoneal carcinomatosis treated by laparoscopy (G1) or laparotomy (G2) was conducted. Procedures included hysterectomy, bilateral salpingo-oophorectomy, omentectomy, and pelvic and para-aortic lymphadenectomy. RESULTS: From 2009 to 2015, 89 patients were included; 53 women underwent laparoscopy and 36 underwent laparotomy. No relevant epidemiological or oncologic difference between groups was observed. The mean number of removed pelvic nodes was 16 [±10] and 12 [±13] in group 1 (G1) and group 2 (G2), respectively (P = 0.127). The mean number of dissected para-aortic nodes was significantly greater in the laparoscopic group (11 [±9] vs 6 [±9], P = 0.006). Para-aortic metastasis was significantly more often observed in the endoscopy group (26% vs 13%, P = 0.04). Adjuvant therapies were given to 86% of the patients in the study and 75% in the control group (P = 0.157). No excessive blood loss, casualty related to surgery, intraoperative complication, or conversion to laparotomy occurred in G1. Ten (18%) women from G1 and 36% (13/36) in G2 developed relevant postoperative complications (P = 0.03). The median duration of follow-up was 38 months for the laparoscopy and 47 months for the open surgery (P = 0.12). The 5-year overall and disease-free survival were similar, 86% versus 78% and 58% versus 51% for G1 and G2, respectively (P = 0.312). CONCLUSIONS: Laparoscopy is oncologically at least not inferior to laparotomy for the surgical treatment of type II EC. Endoscopic techniques are feasible, effective, result in significantly less morbidity, and improved quality staging. Although statistical significance was not reached, laparoscopy was associated with superior oncologic results.


Assuntos
Carcinoma/terapia , Neoplasias do Endométrio/cirurgia , Laparoscopia/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos
7.
J Minim Invasive Gynecol ; 22(6): 938-43, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25917277

RESUMO

OBJECTIVE: To evaluate the operative and oncologic outcomes of an innovative technique for organ morcellation in patients scheduled for laparoscopic treatment of uterine malignancies. BACKGROUND: Endoscopy is currently considered the standard of care for the operative treatment of endometrial cancer; however, the use of minimal invasive surgery (MIS) is restricted in patients with a bulky uterus or narrow vagina. Conventional unprotected intraperitoneal uterine fragmentation is indeed contraindicated in these cases. Consequently, oncologically safe methods to render these patients eligible for MIS are urgently needed. INTERVENTION: Prospective study of women with histologically proven endometrial cancer in which uterus removal was a realistic concern owing to both organ size and proportionality. The patients underwent laparoscopic staging, including retroperitoneal lymphadenectomy, total hysterectomy, and bilateral salpingo-oophorectomy, followed by vaginal morcellation of the uterus inside a protective pouch (LapSac). RESULTS: In our series of 30 cases, we achieved successful completion in all patients, without conversion to laparotomy. No surgery-related casualty or intraoperative morbidity was observed. The mean organ size was 246 g (range, 148-420 g), and the average additional operative time related to vaginal morcellation was 16 minutes (range, 9-28 minutes). Proper histopathological staging according to 2009 FIGO staging guidelines could be performed in all specimens. Two patients (6%) presented with significant postoperative complications, 1 each with vesicovaginal fistula and vaginal vault dehiscence. Fourteen patients (46%) needed adjuvant therapy. After a median follow-up of 20 months (range, 6-38 months), the 12-month and 24-month overall survival was 100% and 73.4% (95% confidence interval, 51%-96%), respectively. Four patients with positive lymph nodes died of distant metastasis. No case of pelvic or local relapse was observed. CONCLUSION: Vaginal morcellation following oncologic principles is a feasible method that permits rapid uterine extraction and potentially avoids unnecessary laparotomies. This series suggests that the technique may be oncologically safe and also can be used in cases of uterine pathology of uncertain malignancy.


Assuntos
Neoplasias do Endométrio/cirurgia , Histerectomia/métodos , Laparoscopia , Morcelação/métodos , Neoplasias Uterinas/cirurgia , Vagina , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Endométrio/patologia , Estudos de Viabilidade , Feminino , Humanos , Laparoscopia/métodos , Excisão de Linfonodo/métodos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/cirurgia , Segurança do Paciente , Estudos Prospectivos , Neoplasias Uterinas/patologia
9.
Sci Rep ; 13(1): 4075, 2023 03 11.
Artigo em Inglês | MEDLINE | ID: mdl-36906619

RESUMO

A multitude of natural and synthetic chemicals are present in our environment.Through the study of a compound's cytotoxicity, researchers can carefully set regulations regarding how much of a certain chemical in the ambient environment is tolerable. In the past, research has focused on point measurements such as the LD50. Instead, we consider entire time-dependent cellular response curves through the application of functional mixed effects models. We identify differences in such curves corresponding to the chemical's mode of action-i.e. how the compound attacks human cells. Through such analysis, we identify curve features to be used for cluster analysis via application of both k-means and self organizing maps. The data is analyzed by making use of functional principal components as a data driven basis and separately by considering B-splines for identifying local-time features. Our analysis can be used to drastically speed up future cytotoxicity research.


Assuntos
Análise por Conglomerados , Testes de Toxicidade , Humanos
10.
Heliyon ; 9(6): e17495, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37408903

RESUMO

DNA mismatch repair protein deficiency (MMRd) in endometrial carcinoma is associated with the risk of Lynch syndrome and response to immune checkpoint inhibitors. It is also related to microsatellite instability and corresponds to a molecular subtype of endometrial tumor with an unclear prognosis. Here, we evaluated the clinicopathological characteristics and prognosis of 312 consecutive endometrial carcinoma cases submitted to complete surgical staging at a single institution. We compared MMRd and mismatch repair protein-proficient (MMRp) tumors and examined the effects of the MMR protein loss type (MLH1/PMS2 vs. MSH2/MSH6) and influence of L1CAM and p53 expression. The median follow-up period was 54.5 (range, 0-120.5) months. No difference was observed between MMRd [n = 166 (37.2%)] and MMRp [n = 196 (62.8%)] cases in terms of age, body mass index, FIGO stage, tumor grade, tumor size, depth of myometrial infiltration, or lymph node metastasis. More MMRd than MMRp tumors had endometrioid histology (87.9% vs. 75.5%) and despite MMRd had more lymphovascular space invasion (LVSI; 27.2% vs. 16.9%), they presented fewer recurrences and no difference in lymph node metastasis and disease-related death. Relative to those with MLH1/MSH6 loss, tumors with MSH2/MSH6 loss were diagnosed at earlier FIGO stages, were smaller, and had less ≥50% myometrial invasion, LVSI and lymph node metastasis. Outcomes, however, did not differ between these groups. L1CAM positivity and mutation-type p53 expression were more common in MMRp than in MMRd tumors and did not differ between the MLH1/PMS2 and MSH2/MSH6 loss groups. In the entire cohort, L1CAM and mutation p53 expression were associated with worse prognosis, but only non-endometrioid histology, FIGO stage III/IV, and deep myometrial infiltration were significant predictors. In the subgroup of endometrioid carcinomas, only FIGO stage III/IV was associated with poor outcomes. The risk of lymph node metastasis was associated with tumor size, non-endometrioid histology, and multifocal LVSI. For MMRd tumors, only tumor size and myometrial invasion depth were predictive of lymph node involvement. In our cohort, MMRd tumors were associated with greater recurrence-free, but not overall, survival. The precise identification of MMRd status, present in a substantial proportion of endometrial cancer cases, is a challenge to be overcome for proper patient management. MMRd status serves as a marker for Lynch syndrome, and a significant number of these tumors are high risk and candidate to immunotherapy.

11.
Cancers (Basel) ; 15(11)2023 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-37296925

RESUMO

Belantamab-mafodotin (belamaf) is a novel antibody-drug conjugate targeting B-cell maturation antigen that showed anti-myeloma activity in patients with relapsed and refractory multiple myeloma (RRMM). We performed an observational, retrospective, and multicenter study aimed to assess the efficacy and safety of single-agent belamaf in 156 Spanish patients with RRMM. The median number of prior therapy lines was 5 (range, 1-10), and 88% of patients were triple-class refractory. Median follow-up was 10.9 months (range, 1-28.6). The overall response rate was 41.8% (≥CR 13.5%, VGPR 9%, PR 17.3%, MR 2%). The median progression-free survival was 3.61 months (95% CI, 2.1-5.1) and 14.47 months (95% CI, 7.91-21.04) in patients achieving at least MR (p < 0.001). Median overall survival in the entire cohort and in patients with MR or better was 11.05 months (95% CI, 8.7-13.3) and 23.35 (NA-NA) months, respectively (p < 0.001). Corneal events (87.9%; grade ≥ 3, 33.7%) were the most commonly adverse events, while thrombocytopenia and infections occurred in 15.4% and 15% of patients, respectively. Two (1.3%) patients discontinued treatment permanently due to ocular toxicity. Belamaf showed a noticeably anti-myeloma activity in this real-life series of patients, particularly among those achieving MR or better. The safety profile was manageable and consistent with prior studies.

12.
Gynecol Oncol ; 126(3): 443-7, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22634019

RESUMO

OBJECTIVE: Evaluate feasibility and safety of a novel technique for uterine morcellation in patients scheduled for laparoscopic treatment of gynecologic malignances. BACKGROUND: The laparoscopic management of uterine malignancies is progressively gaining importance and popularity over laparotomy. Nevertheless, minimal invasive surgery is of limited use when patients have enlarged uterus or narrow vagina. In these cases, conventional uterus morcellation could be a solution but should not be recommended due to risks of tumor dissemination. METHODS: Prospective pilot study of women with endometrial cancer in which uterus removal was a realistic concern due to both organ size and proportionality. Brief technique description: after completion of total laparoscopic hysterectomy and bilateral anexectomy, a nylon with polyurethane Lapsac® is vaginally inserted into the abdomen; the specimen is placed inside the pouch that will be closed and rotated 180° toward the vaginal vault and, posteriorly, pushed into the vaginal canal; in the transvaginal phase, the surgeon pulls the edges of the bag up to vaginal introitus and all vaginal walls will be covered; inside the pouch, the operator performs a uterus bisection-morcellation. RESULTS: In our series of 8 cases, we achieved successful completion in all patients, without conversion to laparotomy. Average operative time, blood loss and length of hospitalization were favorable. One patient presented with a vesicovaginal fistula. CONCLUSION: The vaginal morcellation following oncologic principles is a feasible method that permits a rapid uterine extraction and may avoid a number of unnecessary laparotomies. Further studies are needed to confirm the oncological safety of the technique.


Assuntos
Adenocarcinoma/cirurgia , Carcinossarcoma/cirurgia , Neoplasias do Endométrio/cirurgia , Laparoscopia/métodos , Excisão de Linfonodo , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Aorta , Carcinossarcoma/patologia , Neoplasias do Endométrio/patologia , Feminino , Humanos , Histerectomia/efeitos adversos , Histerectomia/métodos , Laparoscopia/efeitos adversos , Metástase Linfática , Pessoa de Meia-Idade , Ovariectomia/efeitos adversos , Ovariectomia/métodos , Pelve , Projetos Piloto , Estudos Prospectivos , Salpingectomia/efeitos adversos , Salpingectomia/métodos , Vagina/cirurgia
13.
Artif Intell Med ; 112: 102020, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33581832

RESUMO

Artificial intelligence is a broad field that comprises a wide range of techniques, where deep learning is presently the one with the most impact. Moreover, the medical field is an area where data both complex and massive and the importance of the decisions made by doctors make it one of the fields in which deep learning techniques can have the greatest impact. A systematic review following the Cochrane recommendations with a multidisciplinary team comprised of physicians, research methodologists and computer scientists has been conducted. This survey aims to identify the main therapeutic areas and the deep learning models used for diagnosis and treatment tasks. The most relevant databases included were MedLine, Embase, Cochrane Central, Astrophysics Data System, Europe PubMed Central, Web of Science and Science Direct. An inclusion and exclusion criteria were defined and applied in the first and second peer review screening. A set of quality criteria was developed to select the papers obtained after the second screening. Finally, 126 studies from the initial 3493 papers were selected and 64 were described. Results show that the number of publications on deep learning in medicine is increasing every year. Also, convolutional neural networks are the most widely used models and the most developed area is oncology where they are used mainly for image analysis.


Assuntos
Inteligência Artificial , Aprendizado Profundo , Bases de Dados Factuais , Humanos , Processamento de Imagem Assistida por Computador , Redes Neurais de Computação
14.
BMJ Open ; 10(10): e037443, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-33004392

RESUMO

INTRODUCTION: Invasive aspergillosis is the most important cause of morbidity and mortality in patients with haematological diseases. At present, voriconazole is the first-line treatment for invasive fungal disease. The pharmacokinetic interindividual variability of voriconazole depends on genetic factors. CYP450 is involved in 70%-75% of total metabolism of voriconazole, mainly CYP3A4 and CYP2C19, with the remaining 25%-30% of metabolism conducted by monooxygenase flavins. CYP2C19 single nucleotide polymorphisms could explain 50%-55% of variability in voriconazole metabolism. MATERIALS AND METHODS: The main objective is to compare efficiency of pre-emptive voriconazole genotyping with routine practice. The primary outcome is serum voriconazole on the fifth day within the therapeutic range. The secondary outcome is the combined variables of therapeutic failure and adverse events within 90 days of first administration, associated with voriconazole. A total of 146 patients at risk of invasive aspergillosis who will potentially receive voriconazole will be recruited, and CYP2C19 will be genotyped. If the patient ultimately receives voriconazole, they will be randomised (1:1 experimental/control). In the experimental arm, patients will receive a dose according to a pharmacogenetic algorithm, including CYP2C19 genotype and clinical and demographic information. In the control arm, patients will receive a dose according to clinical practice guidelines. In addition, a Spanish National Healthcare System (NHS) point-of-view cost-effectiveness evaluation will be performed. Direct cost calculations for each arm will be performed. CONCLUSION: This trial will provide information about the viability and cost-effectiveness of the implementation of a pre-emptive voriconazole genotyping strategy in the Spanish NHS. ETHICS AND DISSEMINATION: A Spanish version of this protocol has been evaluated and approved by the La Paz University Hospital Ethics Committee and the Spanish Agency of Medicines and Medical Devices. Trial results will be submitted for publication in an open peer-reviewed medical speciality-specific publication. TRIAL REGISTRATION NUMBER: Eudra-CT: 2019-000376-41 and NCT04238884; Pre-results.


Assuntos
Aspergilose , Doenças Hematológicas , Aspergilose/tratamento farmacológico , Aspergilose/genética , Genótipo , Humanos , Estudos Multicêntricos como Assunto , Farmacogenética , Voriconazol/uso terapêutico
15.
PLoS One ; 15(3): e0229543, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32134921

RESUMO

Few reports have described the clinical and prognostic characteristics of endometrial cancer, which is increasing worldwide, in large patient series in Brazil. Our objective was to analyze the clinicopathological characteristics, prognostic factors, and outcomes of patients with endometrial cancer treated and followed at a tertiary Brazilian institution over a 10-year period.This retrospective study included 703 patients diagnosed with endometrial cancer who were treated at a public academic tertiary hospital between 2008 and 2018. The following parameters were analyzed: age at diagnosis, race, body mass index, serum CA125 level before treatment; histological type and grade, and surgical stage. Outcomes were reported relative to histological type, surgical staging, serum CA125, lymph-vascular space involvement (LVSI), and lymph-node metastasis. The median patient age at diagnosis was 63 (range, 27-93) years (6.4% were <50 years). Minimally invasive surgeries were performed in 523 patients (74.4%). Regarding histological grade, 468 patients (66.5%) had low-grade endometrioid histology and 449 patients (63.9%) had stage I tumors. Tumors exceeded 2.0 cm in 601 patients (85.5%). Lymphadenectomy was performed in 551 cases (78.4%). LVSI was present in 208 of the patients' tumors (29.5%). Ninety-three patients (13.2%) had recurrent tumors and 97 (13.7%) died from their malignant disease. The robust prognostic value of FIGO stage and lymph node status were confirmed. Other important survival predictors were histological grade and LVSI [overall survival: hazard ratio (HR) = 3.75, p < 0.001 and HR = 2.01, p = 0.001; recurrence: HR = 2.49, p = 0.004 and HR = 3.22, p = 0.001, respectively). Disease-free (p = 0.087) and overall survival (p = 0.368) did not differ significantly between patients with stage II and III disease. These results indicate that prognostic role of cervical involvement should be explored further. This study reports the characteristics and outcomes of endometrial cancer in a large population from a single institution, with systematic surgical staging, a predominance of minimally invasive procedures, and well-documented outcomes. Prognostic factors in the present study population were generally similar to those in other countries, though our patients' tumors were larger than in studies elsewhere due to later diagnosis. Our unexpected finding of similar prognoses of stage II and III patients raises questions about the prognostic value of cervical involvement and possible differences between carcinomas originating in the lower uterine segment versus those originating in the body and fundus. The present findings can be used to guide public policies aimed at improving the diagnosis and treatment of endometrial cancer in Brazil and other similar countries.


Assuntos
Neoplasias do Endométrio/patologia , Endométrio/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Índice de Massa Corporal , Brasil , Antígeno Ca-125/sangue , Carcinoma Endometrioide/sangue , Carcinoma Endometrioide/patologia , Neoplasias do Endométrio/sangue , Feminino , Humanos , Metástase Linfática/patologia , Vasos Linfáticos/patologia , Pessoa de Meia-Idade , Estadiamento de Neoplasias/métodos , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos
16.
Math Biosci Eng ; 15(5): 1077-1098, 2018 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-30380300

RESUMO

We consider a model based on the logistic equation and linear kinetics to study the effect of toxicants with various initial concentrations on a cell population. To account for parameter uncertainties, in our model the coefficients of the linear and the quadratic terms of the logistic equation are affected by noise. We show that the stochastic model has a unique positive solution and we find conditions for extinction and persistence of the cell population. In case of persistence we find the stationary distribution. The analytical results are confirmed by Monte Carlo simulations.


Assuntos
Sobrevivência Celular/efeitos dos fármacos , Citotoxinas/toxicidade , Modelos Biológicos , Linhagem Celular , Simulação por Computador , Humanos , Modelos Lineares , Modelos Logísticos , Cadeias de Markov , Conceitos Matemáticos , Método de Monte Carlo , Processos Estocásticos
17.
PLoS One ; 13(12): e0209294, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30557309

RESUMO

BACKGROUND: Risk stratification of endometrial carcinomas is primarily based on surgical staging that requires extensive retroperitoneal lymph node dissection. One of the most powerful predictor of lymph node involvement is the lymph vascular space invasion (LVSI). The objective of this study was to determine the potential of L1 Cell Adhesion Molecule (L1CAM) to predict LVSI and its association with other risk factors in endometrioid endometrial carcinomas. MATERIALS AND METHODS: We studied 47 consecutive patients aged 37-88 (61.34±10.52). Twenty-three patients (48.9%) were submitted to complete surgical staging. Nine patients (19.1%) underwent surgical staging without para-aortic dissection. Seven (14.9%) were submitted to hysterectomy with no lymph node dissection. Eight patients (17.0%) only had the biopsy material for analysis. The 32 patients submitted to lymphadenectomy were staged according to the FIGO system and classified among the risk categories of the ESMO-ESGO-ESTRO guidelines. The following histological characteristics were analyzed: tumor size (mm), depth of myometrial infiltration, presence of microcystic, elongated, and fragmented (MELF) pattern of myoinvasion, and lymph vascular space invasion (LVSI). Immunohistochemical analyses of mismatch repair (MMR) proteins MLH1, MSH2, MSH6, and PMS2, p53, and L1CAM were performed in formalin-fixed paraffin embedded whole tumor tissue sections. RESULTS: LVSI was identified in 26/41 (63,4%) of the cases. L1CAM was positive in 8/47 (17%) cases, all of them positive for LVSI and within the high-risk category of ESMO-ESGO-ESTRO. L1CAM-positive cases were associated with high histological grade and p53 aberrant immunohistochemical profile. Besides, it showed a trend to larger tumors, greater depth of myometrial infiltration, and with a higher frequency of the MELF pattern of myoinvasion. LVSI was also associated with FIGO stage, tumor size, depth of myometrial infiltration, and tumor grade. CONCLUSIONS: L1CAM is highly associated with LVSI and could be used as a pre-operative predictor of lymph node involvement in endometrioid endometrial carcinomas.


Assuntos
Carcinoma Endometrioide/metabolismo , Neoplasias do Endométrio/metabolismo , Metástase Linfática/diagnóstico , Invasividade Neoplásica/diagnóstico , Molécula L1 de Adesão de Célula Nervosa/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/metabolismo , Carcinoma Endometrioide/patologia , Carcinoma Endometrioide/cirurgia , Estudos de Coortes , Neoplasias do Endométrio/patologia , Neoplasias do Endométrio/cirurgia , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Dados Preliminares , Período Pré-Operatório
18.
Clinics (Sao Paulo) ; 73(suppl 1): e522s, 2018 09 21.
Artigo em Inglês | MEDLINE | ID: mdl-30281698

RESUMO

OBJECTIVE: The purpose of this study was to evaluate the clinical outcome and costs after the implementation of robotic surgery in the treatment of endometrial cancer, compared to the traditional laparoscopic approach. METHODS: In this prospective randomized study from 2015 to 2017, eighty-nine patients with endometrial carcinoma that was clinically restricted to the uterus were randomized in robotic surgery (44 cases) and traditional laparoscopic surgery (45 cases). We compared the number of retrieved lymph nodes, total time of surgery, time of each surgical step, blood loss, length of hospital stay, major and minor complications, conversion rates and costs. RESULTS: The ages of the patients ranged from 47 to 69 years. The median body mass index was 31.1 (21.4-54.2) in the robotic surgery arm and 31.6 (22.9-58.6) in the traditional laparoscopic arm. The median tumor sizes were 4.0 (1.5-10.0) cm and 4.0 (0.0-9.0) cm in the robotic and traditional laparoscopic surgery groups, respectively. The median total numbers of lymph nodes retrieved were 19 (3-61) and 20 (4-34) in the robotic and traditional laparoscopic surgery arms, respectively. The median total duration of the whole procedure was 319.5 (170-520) minutes in the robotic surgery arm and 248 (85-465) minutes in the traditional laparoscopic arm. Eight major complications were registered in each group. The total cost was 41% higher for robotic surgery than for traditional laparoscopic surgery. CONCLUSIONS: Robotic surgery for endometrial cancer presented equivalent perioperative morbidity to that of traditional laparoscopic surgery. The duration and total cost of robotic surgery were higher than those of traditional laparoscopic surgery.


Assuntos
Neoplasias do Endométrio/cirurgia , Laparoscopia/métodos , Procedimentos Cirúrgicos Robóticos/métodos , Idoso , Feminino , Humanos , Laparoscopia/efeitos adversos , Laparoscopia/economia , Tempo de Internação , Pessoa de Meia-Idade , Duração da Cirurgia , Período Perioperatório , Estudos Prospectivos , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Procedimentos Cirúrgicos Robóticos/economia , Resultado do Tratamento
19.
Maedica (Bucur) ; 13(2): 147-151, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30069243

RESUMO

Carney complex (CNC) is a rare autosomal dominant syndrome. Spotty skin pigmentation is the major clinical manifestation of CNC, followed by cardiac myxomas, benign tumors that usually present with features from the classical triad of obstructive cardiac, embolic and non-specific constitutional symptoms (NCS). NCS are caused by the overproduction of interleukin-6 (IL-6), a pro-inflammatory cytokine which mediates the induction of intercellular adhesion molecule 1 (ICAM-1) and promotes endothelial dysfunction and atherosclerosis. Thus, myxomas may be directly linked to an increased risk of atherosclerotic events. We report here a case of a 74-year-old woman with left atrial myxoma, skin pigmentary abnormalities, thyroid disorder and extensive atherosclerosis, with non-embolic occlusion of infrarenal abdominal aorta.

20.
Math Biosci Eng ; 14(3): 581-606, 2017 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-28092954

RESUMO

The effect of various toxicants on growth/death and morphology of human cells is investigated using the xCELLigence Real-Time Cell Analysis High Troughput in vitro assay. The cell index is measured as a proxy for the number of cells, and for each test substance in each cell line, time-dependent concentration response curves (TCRCs) are generated. In this paper we propose a mathematical model to study the effect of toxicants with various initial concentrations on the cell index. This model is based on the logistic equation and linear kinetics. We consider a three dimensional system of differential equations with variables corresponding to the cell index, the intracellular concentration of toxicant, and the extracellular concentration of toxicant. To efficiently estimate the model's parameters, we design an Expectation Maximization algorithm. The model is validated by showing that it accurately represents the information provided by the TCRCs recorded after the experiments. Using stability analysis and numerical simulations, we determine the lowest concentration of toxin that can kill the cells. This information can be used to better design experimental studies for cytotoxicity profiling assessment.


Assuntos
Simulação por Computador , Modelos Teóricos , Testes de Toxicidade/métodos , Algoritmos , Sobrevivência Celular/efeitos dos fármacos , Substâncias Perigosas/toxicidade , Humanos , Cinética , Reprodutibilidade dos Testes
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