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Ulcerative colitis is a chronic inflammatory disease of the colon that carries a significant disease burden in children. Therefore, new therapeutic approaches are being explored to help children living with this disease. Fecal microbiota transplantation (FMT) has been successful in some children with ulcerative colitis. However, the mechanism of its therapeutic effect in this patient population is not well understood. To characterize changes in gut microbial and metabolomic profiles after FMT, we performed 16S rRNA gene sequencing, shotgun metagenomic sequencing, virome analysis and untargeted metabolomics by gas chromatography-time of flight-mass spectrometry on stool samples collected before and after FMT from four children with ulcerative colitis who responded to this treatment. Alpha diversity of the gut microbiota increased after intervention, with species richness rising from 251 (S.D. 125) to 358 (S.D. 27). In responders, the mean relative abundance of bacteria in the class Clostridia shifted toward donor levels, increasing from 33% (S.D. 11%) to 54% (S.D. 16%). Patient metabolomic and viromic profiles exhibited a similar but less pronounced shift toward donor profiles after FMT. The fecal concentrations of several metabolites were altered after FMT, correlating with clinical improvement. Larger studies using a similar multi-omics approach may suggest novel strategies for the treatment of pediatric ulcerative colitis.

To examine characteristics and survival of patients who developed secondary ovarian cancer after external beam radiotherapy (EBRT) for a prior nonovarian pelvic malignancy. This is a population-based retrospective cohort study, querying the Surveillance, Epidemiology, and End Result program from 1975 to 2016. 167,269 women who received EBRT for 7 malignancies (anus, rectum, bladder, cervix, uterus, vulva, or vagina) were examined to identify subsequent secondary ovarian cancer diagnosis after EBRT. Then, within the ovarian cancer cohort (n = 147,618), characteristics and survival of patients with secondary ovarian cancer after EBRT were compared to those with ovarian cancer who did not receive prior EBRT. Following EBRT for a pelvic malignancy, 215 (1.3 per 1000) patients developed secondary ovarian cancer. Among those, the most frequent prior malignancy was cervical cancer (45.6%), followed by rectal cancer (20.9%). The median time from prior EBRT to secondary ovarian cancer was 8.8 years (interquartile range, 2.8–14.5). In multivariable analysis, patients with secondary ovarian cancer after EBRT were more likely to be older, and have a recent year of diagnosis, but less likely to have early-disease compared to ovarian cancer patients without prior EBRT (all, P < 0.05). In weighted model, patients with secondary ovarian cancer after EBRT had decreased overall survival compared to those with ovarian cancer without prior EBRT (5-year rates, 19.6% versus 39.9%, hazard ratio 1.62, 95% confidence interval 1.43–1.85). Similar association was observed in ages <70, ≥70, White, non-White, early-disease, and advanced-disease in sensitivity analyses. Radiotherapy-related secondary ovarian cancer may be associated with decreased overall survival. [ABSTRACT FROM AUTHOR]

Objective To examine trends and outcomes related to adjuvant systemic chemotherapy alone for high risk, early stage cervical cancer. Methods This retrospective observational study queried the National Cancer Institute's Surveillance, Epidemiology, and End Results Program from 2000 to 2016. Surgically treated women with American Joint Commission on Cancer stages T1--2 cervical cancer who had high risk factors (nodal metastasis and/or parametrial invasion) and received additional therapy were examined. Propensity score inverse probability of treatment weighting was used to assess the survival estimates for systemic chemotherapy versus external beam radiotherapy with chemotherapy. Results Among 2462 patients with high risk factors, 185 (7.5%) received systemic chemotherapy without external beam radiotherapy, of which the utilization significantly increased over time in multivariable analysis (adjusted odds ratio per 1 year increment 1.06, 95% confidence interval (CI) 1.02 to 1.09). In weighted models, adjuvant chemotherapy and combination therapy (external beam radiotherapy and chemotherapy) had comparable overall survival among patients aged <40 years (hazard ratio (HR) 0.73, 95% CI 0.41 to 1.33), in adenocarcinoma or adenosquamous histologies (HR 0.90, 95% CI 0.62 to 1.32), and in those with nodal metastasis alone without parametrial tumor invasion (HR 1.17, 95% CI 0.84 to 1.62). In contrast, systemic chemotherapy alone was associated with increased all cause mortality compared with combination therapy in patients aged ≥40 years (HR 1.57, 95% CI 1.19 to 2.06), with squamous histology (HR 1.63, 95% CI 1.19 to 2.22), and with parametrial invasion alone (HR 1.87, 95% CI 1.09 to 3.20) or parametrial invasion with nodal metastasis (HR 1.64, 95% CI 1.06 to 2.52). Conclusion Utilization of adjuvant systemic chemotherapy alone for high risk, early stage cervical cancer is increasing in the United States in the recent years. Our study suggests that survival effects of adjuvant systemic chemotherapy may vary based on patient and tumor factors. External beam radiotherapy with chemotherapy remains the standard for high risk, early stage cervical cancer, and use of adjuvant systemic chemotherapy without external beam radiotherapy should be considered with caution. [ABSTRACT FROM AUTHOR]