The amount of preoperative endometrial tissue surface in relation to final endometrial cancer classification

Objective: To evaluate whether the amount of preoperative endometrial tissue surface is related to the degree of concordance with final low- and high-grade endometrial cancer (EC). In addition, to determine whether discordance is influenced by sampling method and impacts outcome. Methods: A retrospective cohort study within the European Network for Individualized Treatment of Endometrial Cancer (ENITEC). Surface of preoperative endometrial tissue samples was digitally calculated using ImageJ. Tumor samples were classified into low-grade (grade 1-2 endometrioid EC (EEC)) and high-grade (grade 3 EEC + non-endometroid EC). Results: The study cohort included 573 tumor samples. Overall concordance between pre- and postoperative diagnosis was 60.0%, and 88.8% when classified into low- and high-grade EC. Upgrading (preoperative low-grade, postoperative high-grade EC) was found in 7.8% and downgrading (preoperative high-grade, postoperative low-grade EC) in 26.7%. The median endometrial tissue surface was significantly lower in concordant diagnoses when compared to discordant diagnoses, respectively 18.7 mm2 and 23.5 mm2 (P = 0.022). Sampling method did not influence the concordance in tumor classification. Patients with preoperative high-grade and postoperative low-grade showed significant lower DSS compared to patients with concordant low-grade EC (P = 0.039). Conclusion: The amount of preoperative endometrial tissue surface was inversely related to the degree of concordance with final tumor low- and high-grade. Obtaining higher amount of preoperative endometrial tissue surface does not increase the concordance between pre- and postoperative low- and high-grade diagnosis in EC. Awareness of clinically relevant down- and upgrading is crucial to reduce subsequent over- or undertreatment with impact on outcome

Poor outcome in hypoxic endometrial carcinoma is related to vascular density

Background Identification of endometrial carcinoma (EC) patients at high risk of recurrence is lacking. In this study, the prognostic role of hypoxia and angiogenesis was investigated in EC patients. Methods Tumour slides from EC patients were stained by immunofluorescence for carbonic anhydrase IX (CAIX) as hypoxic marker and CD34 for assessment of microvessel density (MVD). CAIX expression was determined in epithelial tumour cells, with a cut-off of 1%. MVD was assessed according to the Weidner method. Correlations with disease-specific survival (DSS), disease-free survival (DFS) and distant disease-free survival (DDFS) were calculated using Kaplan–Meier curves and Cox regression analysis. Results Sixty-three (16.4%) of 385 ECs showed positive CAIX expression with high vascular density. These ECs had a reduced DSS compared to tumours with either hypoxia or high vascular density (log-rank p = 0.002). Multivariable analysis showed that hypoxic tumours with high vascular density had a reduced DSS (hazard ratio [HR] 3.71, p = 0.002), DDFS (HR 2.68, p = 0.009) and a trend for reduced DFS (HR 1.87, p = 0.054). Conclusions This study has shown that adverse outcome in hypoxic ECs is seen in the presence of high vascular density, suggesting an important role of angiogenesis in the metastatic process of hypoxic EC. Differential adjuvant treatment might be indicated for these patients.publishedVersio

Pain distress : the negative emotion associated with procedures in ICU patients

The intensity of procedural pain in intensive care unit (ICU) patients is well documented. However, little is known about procedural pain distress, the psychological response to pain. Post hoc analysis of a multicenter, multinational study of procedural pain. Pain distress was measured before and during procedures (0-10 numeric rating scale). Factors that influenced procedural pain distress were identified by multivariable analyses using a hierarchical model with ICU and country as random effects. A total of 4812 procedures were recorded (3851 patients, 192 ICUs, 28 countries). Pain distress scores were highest for endotracheal suctioning (ETS) and tracheal suctioning, chest tube removal (CTR), and wound drain removal (median [IQRs] = 4 [1.6, 1.7]). Significant relative risks (RR) for a higher degree of pain distress included certain procedures: turning (RR = 1.18), ETS (RR = 1.45), tracheal suctioning (RR = 1.38), CTR (RR = 1.39), wound drain removal (RR = 1.56), and arterial line insertion (RR = 1.41); certain pain behaviors (RR = 1.19-1.28); pre-procedural pain intensity (RR = 1.15); and use of opioids (RR = 1.15-1.22). Patient-related variables that significantly increased the odds of patients having higher procedural pain distress than pain intensity were pre-procedural pain intensity (odds ratio [OR] = 1.05); pre-hospital anxiety (OR = 1.76); receiving pethidine/meperidine (OR = 4.11); or receiving haloperidol (OR = 1.77) prior to the procedure. Procedural pain has both sensory and emotional dimensions. We found that, although procedural pain intensity (the sensory dimension) and distress (the emotional dimension) may closely covary, there are certain factors than can preferentially influence each of the dimensions. Clinicians are encouraged to appreciate the multidimensionality of pain when they perform procedures and use this knowledge to minimize the patient's pain experience.Peer reviewe

Preoperative risk stratification in endometrial cancer (ENDORISK) by a Bayesian network model: A development and validation study

Background: Bayesian networks (BNs) are machine-learning-based computational models that visualize causal relationships and provide insight into the processes underlying disease progression, closely resembling clinical decision-making. Preoperative identification of patients at risk for lymph node metastasis (LNM) is challenging in endometrial cancer, and although several biomarkers are related to LNM, none of them are incorporated in clinical practice. The aim of this study was to develop and externally validate a preoperative BN to predict LNM and outcome in endometrial cancer patients.Methods and findings: Within the European Network for Individualized Treatment of Endometrial Cancer (ENI-TEC), we performed a retrospective multicenter cohort study including 763 patients, median age 65 years (interquartile range [IQR] 58-71), surgically treated for endometrial cancer between February 1995 and August 2013 at one of the 10 participating European hospitals. A BN was developed using score-based machine learning in addition to expert knowledge. Our main outcome measures were LNM and 5-year disease-specific survival (DSS). Preoperative clinical, histopathological, and molecular biomarkers were included in the network. External validation was performed using 2 prospective study cohorts: the Molecular Markers in Treatment in Endometrial Cancer (MoMaTEC) study cohort, including 446 Norwegian patients, median age 64 years (IQR 59-74), treated between May 2001 and 2010; and the PIpelle Prospective ENDOmetrial carcinoma (PIPENDO) study cohort, including 384 Dutch patients, median age 66 years (IQR 60-73), treated between September 2011 and December 2013. A BN called ENDORISK (preoperative risk stratification in endometrial cancer) was developed including the following predictors: preoperative tumor grade; immunohistochemical expression of estrogen receptor (ER), progesterone receptor (PR), p53, and L1 cell adhesion molecule (L1CAM); cancer antigen 125 serum level; thrombocyte count; imaging results on lymphadenopathy; and cervical cytology. In the MoMaTEC cohort, the area under the curve (AUC) was 0.82 (95% confidence interval [CI] 0.76-0.88) for LNM and 0.82 (95% CI 0.77-0.87) for 5-year DSS. In the PIPENDO cohort, the AUC for 5-year DSS was 0.84 (95% CI 0.78-0.90). The network was well-calibrated. In the MoMaTEC cohort, 249 patients (55.8%) were classified with Conclusions: In this study, we illustrated how BNs can be used for individualizing clinical decision-making in oncology by incorporating easily accessible and multimodal biomarkers. The network shows the complex interactions underlying the carcinogenetic process of endometrial cancer by its graphical representation. A prospective feasibility study will be needed prior to implementation in the clinic.</div

Hyperoxemia and excess oxygen use in early acute respiratory distress syndrome : Insights from the LUNG SAFE study

Publisher Copyright: © 2020 The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Background: Concerns exist regarding the prevalence and impact of unnecessary oxygen use in patients with acute respiratory distress syndrome (ARDS). We examined this issue in patients with ARDS enrolled in the Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE (LUNG SAFE) study. Methods: In this secondary analysis of the LUNG SAFE study, we wished to determine the prevalence and the outcomes associated with hyperoxemia on day 1, sustained hyperoxemia, and excessive oxygen use in patients with early ARDS. Patients who fulfilled criteria of ARDS on day 1 and day 2 of acute hypoxemic respiratory failure were categorized based on the presence of hyperoxemia (PaO2 > 100 mmHg) on day 1, sustained (i.e., present on day 1 and day 2) hyperoxemia, or excessive oxygen use (FIO2 ≥ 0.60 during hyperoxemia). Results: Of 2005 patients that met the inclusion criteria, 131 (6.5%) were hypoxemic (PaO2 < 55 mmHg), 607 (30%) had hyperoxemia on day 1, and 250 (12%) had sustained hyperoxemia. Excess FIO2 use occurred in 400 (66%) out of 607 patients with hyperoxemia. Excess FIO2 use decreased from day 1 to day 2 of ARDS, with most hyperoxemic patients on day 2 receiving relatively low FIO2. Multivariate analyses found no independent relationship between day 1 hyperoxemia, sustained hyperoxemia, or excess FIO2 use and adverse clinical outcomes. Mortality was 42% in patients with excess FIO2 use, compared to 39% in a propensity-matched sample of normoxemic (PaO2 55-100 mmHg) patients (P = 0.47). Conclusions: Hyperoxemia and excess oxygen use are both prevalent in early ARDS but are most often non-sustained. No relationship was found between hyperoxemia or excessive oxygen use and patient outcome in this cohort. Trial registration: LUNG-SAFE is registered with ClinicalTrials.gov, NCT02010073publishersversionPeer reviewe

Preoperative CA125 significantly improves risk stratification in high-Grade endometrial cancer

Patients with high-grade endometrial carcinoma (EC) have an increased risk of tumor spread and lymph node metastasis (LNM). Preoperative imaging and CA125 can be used in work-up. As data on cancer antigen 125 (CA125) in high-grade EC are limited, we aimed to study primarily the predictive value of CA125, and secondarily the contributive value of computed tomography (CT) for advanced stage and LNM. Patients with high-grade EC (n = 333) and available preoperative CA125 were included retrospectively. The association of CA125 and CT findings with LNM was analyzed by logistic regression. Elevated CA125 ((>35 U/mL), (35.2% (68/193)) was significantly associated with stage III-IV disease (60.3% (41/68)) compared with normal CA125 (20.8% (26/125), [p < 0.001]), and with reduced disease-specific-(DSS) (p < 0.001) and overall survival (OS) (p < 0.001). The overall accuracy of predicting LNM by CT resulted in an area under the curve (AUC) of 0.623 (p < 0.001) independent of CA125. Stratification by CA125 resulted in an AUC of 0.484 (normal), and 0.660 (elevated). In multivariate analysis elevated CA125, non-endometrioid histology, pathological deep myometrial invasion ≥50%, and cervical involvement were significant predictors of LNM, whereas suspected LNM on CT was not. This shows that elevated CA125 is a relevant independent predictor of advanced stage and outcome specifically in high-grade EC

Estudo prospectivo de extubação endotraqueal não programada em doentes de cuidados intensivos

RESUMO: A extubação endotraqueal não programada (ENP) é uma ocorrência frequente em doentes submetidos a ventilação mecânica ou em fase de desmame ventilatório, associando-se a um aumento da morbilidade e mortalidade, devido à própria ENP ou a acidentes relacionados com a reentubação. Este trabalho propõe­se analizar a magiutude do problema numa UCI assim como determinar as variáveis com valor predictivo da necessidadc de reentubação.Foram incluídos no estudo todos os doentes requerendo entubação endotraqueal>48 horas admitidos entre Maio 1993 e Janeiro de 1996 (n=750). As ENP classificaram-se em extubações acidentais (EA) durante mobilizações, etc. - e em autoextubações (AE) sempre que devidas à intervenção activa do doente. Foram analizados a idade, sexo, SAPS, tipo de suporte ventilatório (suporte ventilatório âtotalâ ou desmame), diâmetro do tubo, dias de ventilação, mortalidade, causa da reentubação e nível de sedação. As modalidades de desmame foram: Pressão Assistida (PA), CPAP ou peça em T, conforrne protocolo pré-definido, e os critérios para iniciar desmame foram: 1) PMI>25cmH2O; 2) FR 10 ml/Kg; 4) SatO2>com FiO2=0,4; 5) Temp48 horas foi 34,4%, sendo de 13% nas AE e de 23% nas EA. As únicas variáveis com valor predictive foram os dias de ventilação e a modalidade de desmame.Concluiu-se que a reentubação depende fundamental mente do tipo de suporte ventilatório. A probabilidade de necessitar de reentubação é maior durante o suporte ventilatório âtotalâ do que em fase de desmame, sendo sugerido que nalguns doentes o tempo de ventilação é demasiadamente prolongado. COMENTÃRIO: Para todos os que trabalham em euldados intenslvos, a escolha de um processo de desmame ventilatório que pennita conduzir à rápída extubação e à eventual alta dos doentes ventilados continua a ser um dos problemas que mais tempo e energias consome. O trabalho apresentado, partindo de uma situação que se verifica com alguma frequência (1.2) - a extubação não programada-levanta várias questões.As primeiras são de ordem prãtica e mais imediatas. Perante um episódio de extubação não programada, quais os critérios e parâmetros que permitem condescender na reentubação dos doentes? Segundo os dados apresentados, a necessidade de reentubação depende fundamentalmente da fase de desmame, sendo que os doentes com modalidades mais autónomas-CPAP e peça em T-tem maior probabilidade de se manterem extubados (2-3).A segunda ordem de questões deriva precisamente dos resultados apresentados. Será que o desmame ventilatório é prolongado para além do tempo necessário? Os números parecem confirmar esta afi rmação. No presente estudo, apenas 15,6% dos doentes em desmame necessitaram de reentubação, passando estc número para 8,3% nos submetidos a modalidades mais autónomas.Um estudo anterior (4) responsabilizou o período de desmame por cerca de 40% do tempo total de ventilação. Se forem tomadas em consideração as complicações relacionadas eo custo económico destes doentes, fácilmente se conclui que são necessárias algumas mudanças nas estratégias normalmente utilizadas.Foram publicados alguns trabalhos (5-7) que prõpoem actuações protocolizadas para o desmame e extubação dos doentes ventilados. As estratégias e protocolos utilizados permitiram reduzir o tempo de desmame e o custo económico de uma forma significativa. A forma de mudar as atitudes começa pela divulgação dos dados conhecidos, sendo no entanto imperative que os protocolos nao suplantem o julgamento clinico, servindo antes como instrumentos dinâmicos. Embora esta mudança de atitude leve necessáriamente algum tempo, talvez em breve deixemos de ouvir a frase âdesmamar lentamente conforme toleradoâ e passemos a ouvir âo doente está estável e cumpre parâmetres protocolizados-vamos extubá-lo!â(8)

Tumor de células de la granulosa en paciente premenopaúsica

El tumor de celulas de la granulosa es una entidad rara que representa el 5% delas neoplasias ováricas. El debut clínico más frecuente es en forma de metrorragia postmenopáusica, secundaria a la producción de estrógenos por la tumoración. Presentamos el caso de una paciente de 46 años con polimenorreas de 6 meses de evolución. En la ecografía transvaginal destacaba una línea endometrial engrosada sugestiva de pólipo endometrial y una formación quística compleja anexial. Se realizó anexectomía por laparoscopia y estudio endometrial por histeroscopia. Tras el estudio anatomo-patológico se informó de tumor de células de la granulosa y de hiperplasia endometrial compleja con atípias. Con este diagnóstico se realizó una histerctomia abdominal total, anexectomía unilateral, linfadenectomía pélvica bilateral y paraaórtica, omentectomía inframesocólica y citología peritoneal persistiendo, tras la valoración anatomo-patológica, una hiperplasia endometrial compleja con atípias. La baja incidencia de estos tumores dificulta el establecimiento de pautas terapeúticas estandarizadas por lo que obliga a individualizar la toma de decisiones en cada uno de ellos

Protein Supplementation in a Prehabilitation Program in Patients Undergoing Surgery for Endometrial Cancer

Enhanced recovery after surgery (ERAS) and prehabilitation programs are multidisciplinary care pathways to reduce stress response and improve perioperative outcomes, which also include nutritional interventions. The aim of this study is to assess the impact of protein supplementation with 20 mg per day before surgery in a prehabilitation program in postoperative serum albumin, prealbumin, and total proteins in endometrial cancer patients undergoing laparoscopic surgery. Methods: A prospective study including patients who underwent laparoscopy for endometrial cancer was conducted. Three groups were identified according to ERAS and prehabilitation implementation (preERAS, ERAS, and Prehab). The primary outcome was levels of serum albumin, prealbumin, and total protein 24–48 h after surgery. Results: A total of 185 patients were included: 57 in the preERAS group, 60 in the ERAS group, and 68 in the Prehab group. There were no basal differences in serum albumin, prealbumin, or total protein between the three groups. After surgery, regardless of the nutritional intervention, the decrease in the values was also similar. Moreover, values in the Prehab group just before surgery were lower than the initial ones, despite the protein supplementation. Conclusions: Supplementation with 20 mg of protein per day does not impact serum protein levels in a prehabilitation program. Supplementations with higher quantities should be studied

Impact of prehabilitation during neoadjuvant chemotherapy and interval cytoreductive surgery on ovarian cancer patients: a pilot study

Background: Cytoreductive surgery followed by systemic chemotherapy is the standard of treatment in advanced ovarian cancer where feasible. Neoadjuvant chemotherapy (NACT) followed by surgery is applicable where upfront cytoreductive surgery is not feasible because of few certain reasons. Nevertheless, surgical interventions and the chemotherapy itself may be associated with postoperative complications usually entailing slow postoperative recovery. Prehabilitation programs consist of the patient's preparation before surgery to improve the patient's functional capacity. The aim of this study was to evaluate the impact of a prehabilitation program during neoadjuvant treatment and interval cytoreductive surgery for ovarian cancer patients. Methods: A retrospective observational pilot study of patients with advanced ovarian cancer treated with NACT and interval cytoreductive surgery was conducted. The prehabilitation group received a structured intervention based on physical exercise, nutritional counseling, and psychological support. Nutritional parameters were assessed preoperatively and postoperatively, and functional parameters and perioperative and postoperative complications were also recorded. Results: A total of 29 patients were included in the study: 14 in the prehabilitation group and 15 in the control group. The patients in the prehabilitation program showed higher mean total protein levels in both preoperative (7.4 vs. 6.8, p = 0.004) and postoperative (4.9 vs. 4.3, p = 0.005) assessments. Up to 40% of controls showed intraoperative complications vs. 14.3% of patients in the prehabilitation group, and the requirement of intraoperative blood transfusion was significantly lower in the prehabilitation group (14.3% vs. 53.3%, p = 0.027). The day of the first ambulation, rate of postoperative complications, and length of hospital stay were similar between the groups. Finally, trends towards shorter time between diagnosis and interval cytoreductive surgery (p = 0.097) and earlier postoperative diet restart (p = 0.169) were observed in the prehabilitation group. Conclusion: Prehabilitation during NACT in women with ovarian cancer candidates to interval cytoreductive surgery may improve nutritional parameters and thereby increase postoperative recovery. Nevertheless, the results of this pilot study are preliminary, and further studies are needed to determine the clinical impact of prehabilitation programs