Clinical utility of chromogranin A and octreotide in large cell neuro endocrine carcinoma of the uterine corpus

Primary neuroendocrine tumors of the female genital tract have been described in the cervix, ovaries and uterus. Large cell neuroendocrine carcinoma (LCNC) of the uterine corpus is the least common and appears to behave the most aggressively. We report a rare case of a large cell neuroendocrine tumor of the endometrium. These tumors are not well characterized, unlike neuroendocrine tumors of the uterine cervix. Consequently, the optimal management remains still unclear. The treatment of our case consisted of surgery, radiotherapy, chemotherapy, and octreotide. Despite the aggressive treatment, the patient died of disease progression 12 months after the initial diagnosis. We discuss the diagnosis, prognosis, and treatment options for LCNC of the genital tract, and potential future therapeutics

The unfinished agenda of communicable diseases among children and adolescents before the COVID-19 pandemic, 1990-2019: a systematic analysis of the Global Burden of Disease Study 2019

BACKGROUND: Communicable disease control has long been a focus of global health policy. There have been substantial reductions in the burden and mortality of communicable diseases among children younger than 5 years, but we know less about this burden in older children and adolescents, and it is unclear whether current programmes and policies remain aligned with targets for intervention. This knowledge is especially important for policy and programmes in the context of the COVID-19 pandemic. We aimed to use the Global Burden of Disease (GBD) Study 2019 to systematically characterise the burden of communicable diseases across childhood and adolescence. METHODS: In this systematic analysis of the GBD study from 1990 to 2019, all communicable diseases and their manifestations as modelled within GBD 2019 were included, categorised as 16 subgroups of common diseases or presentations. Data were reported for absolute count, prevalence, and incidence across measures of cause-specific mortality (deaths and years of life lost), disability (years lived with disability [YLDs]), and disease burden (disability-adjusted life-years [DALYs]) for children and adolescents aged 0-24 years. Data were reported across the Socio-demographic Index (SDI) and across time (1990-2019), and for 204 countries and territories. For HIV, we reported the mortality-to-incidence ratio (MIR) as a measure of health system performance. FINDINGS: In 2019, there were 3·0 million deaths and 30·0 million years of healthy life lost to disability (as measured by YLDs), corresponding to 288·4 million DALYs from communicable diseases among children and adolescents globally (57·3% of total communicable disease burden across all ages). Over time, there has been a shift in communicable disease burden from young children to older children and adolescents (largely driven by the considerable reductions in children younger than 5 years and slower progress elsewhere), although children younger than 5 years still accounted for most of the communicable disease burden in 2019. Disease burden and mortality were predominantly in low-SDI settings, with high and high-middle SDI settings also having an appreciable burden of communicable disease morbidity (4·0 million YLDs in 2019 alone). Three cause groups (enteric infections, lower-respiratory-tract infections, and malaria) accounted for 59·8% of the global communicable disease burden in children and adolescents, with tuberculosis and HIV both emerging as important causes during adolescence. HIV was the only cause for which disease burden increased over time, particularly in children and adolescents older than 5 years, and especially in females. Excess MIRs for HIV were observed for males aged 15-19 years in low-SDI settings. INTERPRETATION: Our analysis supports continued policy focus on enteric infections and lower-respiratory-tract infections, with orientation to children younger than 5 years in settings of low socioeconomic development. However, efforts should also be targeted to other conditions, particularly HIV, given its increased burden in older children and adolescents. Older children and adolescents also experience a large burden of communicable disease, further highlighting the need for efforts to extend beyond the first 5 years of life. Our analysis also identified substantial morbidity caused by communicable diseases affecting child and adolescent health across the world. FUNDING: The Australian National Health and Medical Research Council Centre for Research Excellence for Driving Investment in Global Adolescent Health and the Bill & Melinda Gates Foundation

Exploring Novel Precision Medicine Approaches in High Grade Serous Ovarian Cancer

In this dissertation, we aimed to bring together a team of clinical experts, translational researchers, biostaticians and bioinformaticians to develop and implement innovative scientific methodologies in precision medicine applied to High Grade Serous Ovarian Cancer (HGS OvCa). We used a variety of translational and computational methods in order to generate impactful outcomes. These pipelines produced statistically robust results, with particular emphasis on drawing clinical and biological correlations. The results presented here contribute to the body of evidence necessary to substantiate these findings in a clinical setting. Bioassays, PDX models and ancillary specimen evaluation of previous clinical trials will help to validate our candidate biomarkers. Enhanced understanding of the molecular pathology of disease grounded in acquisition of genomic knowledge will facilitate the development of targeted treatment in cancer. Because clinical trials must be developed with correct metrics, patient selection and drug efficacy should incorporate adaptive designs.Doctorat en Sciences médicales (Santé Publique)info:eu-repo/semantics/nonPublishe

Delayed and clinically isolated port site carcinosarcoma recurrence as an early indicator of disseminated disease

A 71-year-old woman with suspected endometrial cancer underwent robotic-assisted hysterectomy, bilateral salpingo-oophorectomy, pelvic and para-aortic lymph node dissection, and infracolic omentectomy revealing a stage II uterine carcinosarcoma with components of serous adenocarcinoma and undifferentiated spindle cell sarcoma. There was no evidence of distant metastasis at the time of surgery. However pelvic washings were positive for malignant cells. She received adjuvant chemotherapy and vaginal cuff brachytherapy. Forty months later she developed a subcutaneous mass at the location of previous port site which was confirmed to be recurrence of the uterine primary. She subsequently developed additional distant metastases to the abdominal wall, lungs, and bone. Port site metastasis (PSM) was the earliest indicator of disseminated metastatic disease in this patient. We review challenges in the management of patients with PSM and propose that PSM be considered as a sign of systemic disease even when presenting as an apparently isolated recurrence

Monoamniotic twin cord entanglement: A case report with color flow Doppler ultrasonography for antenatal diagnosis

BACKGROUND: Monoamniotic twinning is a rare event with a high perinatal mortality rate from cord accidents. To date, only a few cases have been reported in which cord entanglement was diagnosed with Doppler ultrasonography. CASE: In a monoamniotic twin pregnancy, umbilical cord entanglement was diag- nosed at 20 weeks' gestation by color flow Doppler ultrasonography. The entanglement was associated with growth discordance between the twins and subsequent death of the smaller fetus. CONCLUSION: The rarity of this condition hinders our understanding of the pathophysiology and development of management protocols.SCOPUS: cp.jinfo:eu-repo/semantics/publishe

The Hispanic Paradox in endometrial cancer: A National Cancer Database study

To compare the overall survival of non-Hispanic white and Hispanic women with endometrial cancer. We performed an observational retrospective cohort study of Hispanic and non-Hispanic women with endometrial cancer from the 2004-2014 National Cancer Database. Baseline characteristics were compared with the Chi-squared test for categorical variables or the Mann-Whitney U test for ordinal or continuous variables. The Kaplan-Meier method was used to estimate unadjusted survival times, which were compared with the log-rank test. Missing data was imputed using multiple imputation with chained equations. A multivariable parametric accelerated failure time model for survival was used. Sensitivity analyses were performed using matched cohort analyses of the overall cohort, and of subgroups based on stage or type. 112,574 non-Hispanic and 6313 Hispanic women met inclusion criteria. Five-year survival was slightly higher for Hispanic women (83.1% (82.1-84.3%) versus 81.4% (81.2-81.7%), P=0.002). Hispanic women were younger, treated at lower volume hospitals, and more often diagnosed with a type II histology and stage II-IV disease compared to non-Hispanic women (all P<0.001). With multivariable adjustment for measured confounders, Hispanic women lived 8% longer than non-Hispanic women (time-ratio (95% CI) 1.08 (1.02-1.14), P=0.01). When bias-reducing matched cohort analyses were used for sensitivity analyses, Hispanic women did not have significantly different survival than non-Hispanic women. Hispanic ethnicity was not associated with a clinically meaningful difference in survival among women with endometrial cancer

Survival After Pelvic Exenteration for Cervical Cancer: A National Cancer Database Study

To determine overall survival (OS) and factors associated with OS after pelvic exenteration for cervical cancer. Women with cervical cancer who underwent exenteration (n = 517) were identified from the 1998 to 2011 National Cancer Database. Kaplan-Meier and multivariate Cox proportional-hazards survival analyses were performed to test for associations of potential explanatory variables with OS. Analyzed confounders included age, insurance status, income, distance from home to treatment center, stage, exenteration type, surgical margin status, and treatment with adjuvant radiation and/or chemotherapy. Among the entire cohort with clinical follow-up (n = 313), median OS was 24 months. Stage (P = 2.5 × 10), lymph node status (P = 1.3 × 10), insurance status (P = 1.5 × 10), and histologic type (P = 0.04) were significantly associated with OS by the log-rank test. Unadjusted median OS was 24.2 and 61.8 months for women with squamous and adenocarcinoma histologies, respectively. By multivariate Cox regression, age, insurance status, stage, margin status, and adjuvant radiation were associated with OS. Histology was not independently associated with OS on multivariate regression. Among women with node-negative disease, median OS was 73.2 months. Exenteration may be curative for more than half of women with node-negative cervical cancer. Stage, insurance status, lymph node status, and surgical margin are independently associated with differential OS after exenteration

Metastatic Uterine Leiomyosarcoma Involving Bilateral Ovarian Stroma without Capsular Involvement Implies a Local Route of Hematogenous Dissemination

Uterine sarcomas spread via lymphatic and hematogenous dissemination, direct extension, or transtubal transport. Distant metastasis often involves the lungs. Ovarian metastasis is uncommon. Here we present an unusual case of a large, high-grade uLMS with metastatic disease internal to both ovaries without capsular involvement or other abdominal diseases, and discovered in a patient with distant metastases to the lungs, suggesting likely hematogenous dissemination of uLMS to the ovaries in this case. Knowledge of usual uLMS metastases may influence surgical management in select cases