Longitudinal intravital imaging of mouse placenta.

Studying placental functions is crucial for understanding pregnancy complications. However, imaging placenta is challenging due to its depth, volume, and motion distortions. In this study, we have developed an implantable placenta window in mice that enables high-resolution photoacoustic and fluorescence imaging of placental development throughout the pregnancy. The placenta window exhibits excellent transparency for light and sound. By combining the placenta window with ultrafast functional photoacoustic microscopy, we were able to investigate the placental development during the entire mouse pregnancy, providing unprecedented spatiotemporal details. Consequently, we examined the acute responses of the placenta to alcohol consumption and cardiac arrest, as well as chronic abnormalities in an inflammation model. We have also observed viral gene delivery at the single-cell level and chemical diffusion through the placenta by using fluorescence imaging. Our results demonstrate that intravital imaging through the placenta window can be a powerful tool for studying placenta functions and understanding the placental origins of adverse pregnancy outcomes.

Adjuvant Chemotherapy After Preoperative Chemoradiation Improves Survival in Patients With Locally Advanced Rectal Cancer.

BACKGROUND: Practice guidelines differ in their support of adjuvant chemotherapy use in patients who received preoperative chemoradiation for rectal cancer. OBJECTIVE: The purpose of this study was to evaluate the impact of adjuvant chemotherapy among patients with locally advanced rectal cancer who received neoadjuvant chemoradiation and surgery. DESIGN: This was a retrospective study. Multivariable Cox proportional hazard modeling was used to evaluate the adjusted survival differences. SETTINGS: Data were collected from the National Cancer Database. PATIENTS: Adults with pathologic stage II and III rectal adenocarcinoma who received neoadjuvant chemoradiation and surgery were included. MAIN OUTCOME MEASURES: Overall survival was measured. RESULTS: Among 12,696 patients included, 4023 (32%) received adjuvant chemotherapy. The use of adjuvant chemotherapy increased over the study period from 23% to 36%. Although older age and black race were associated with a lower likelihood of receiving adjuvant chemotherapy, patients with higher education level and stage III disease were more likely to receive adjuvant chemotherapy (all p < 0.05). At 7 years, overall survival was improved among patients who received adjuvant chemotherapy (60% vs. 55%; p < 0.001). After risk adjustment, the use of adjuvant chemotherapy was associated with improved survival (HR = 0.81 (95% CI, 0.72-0.91); p < 0.001). In the subgroup of patients with stage II disease, survival was also improved among patients who received adjuvant chemotherapy (68% vs 58% at 7 y; p < 0.001; HR = 0.70 (95% CI, 0.57-0.87); p = 0.002). Among patients with stage III disease, the use of adjuvant chemotherapy was associated with a smaller but persistent survival benefit (56% vs 51% at 7 y; p = 0.017; HR = 0.85 (95% CI, 0.74-0.98); p = 0.026). LIMITATIONS: The study was limited by its potential for selection bias and inability to compare specific chemotherapy regimens. CONCLUSIONS: The use of adjuvant chemotherapy among patients with rectal cancer who received preoperative chemoradiation conferred a survival benefit. This study emphasizes the importance of adjuvant chemotherapy in the management of rectal cancer and advocates for its increased use in the setting of neoadjuvant therapy. See Video Abstract at http://link.lww.com/DCR/A428.