UPF1 promotes chemoresistance to oxaliplatin through regulation of TOP2A activity and maintenance of stemness in colorectal cancer

UPF1 is proved to dysregulate in multiple tumors and influence carcinogenesis. However, the role of UPF1 in oxaliplatin resistance in colorectal cancer (CRC) remains unknown. In our study, UPF1 is upregulated in CRC in mRNA and protein levels and overexpression of UPF1 predicts a poor overall survival (OS) and recurrence-free survival (RFS) in CRC patients and is an independent risk factor for recurrence. UPF1 promotes chemoresistance to oxaliplatin in vitro and in vivo. UPF1-induced oxaliplatin resistance can be associated with interaction between zinc finger of UPF1 and Toprim of TOP2A and increasing phosphorylated TOP2A in a SMG1-dependent manner. Moreover, UPF1 maintains stemness in a TOP2A-dependent manner in CRC. Taken together, UPF1 was overexpressed and predicted a poor prognosis in CRC. UPF1 enhanced chemoresistance to oxaliplatin in CRC, which may result from regulation of TOP2A activity and maintenance of stemness. Our findings could provide a new therapy strategy for chemoresistance to oxaliplatin in CRC patients.

753 Sesamoid Alignment After MIS Chevron Osteotomy and Its Role to Prevent Hallux Valgus Recurrence

Introduction Incomplete correction of the sesamoid position after corrective osteotomy is a risk factor for recurrence of the hallux valgus deformity. This study was done to report the results of sesamoid alignment after chevron osteotomy. Method 92 patients (111 feet) had minimally invasive (MIS) distal chevron osteotomy and release of fibular sesamoid ligaments done, sesamoid position was assessed in the weight-bearing views of the foot, tibial sesamoid position in relation to the mechanical axis of the first metatarsal was classified as grades 0-3 where the normal position was graded (0) and the most lateral sublaxation was graded (3). There were 2 groups; the reduced (grade 0-1) & the dislocated (grade 2,3) groups. Preoperative and post-operative radiographs were compared. Postoperative images were done 6-8 weeks post-operatively to ensure osteotomy healing. Results Sesamoids alignment was corrected following the MIS chevron osteotomy; 84 feet (75.7%) were from the dislocated group and 27 feet (24.3%) were from the reduced group pre-operatively improved to 102 feet (91.9%) reduced and only 9 feet (8.1%) dislocated following the procedure with P-value < 0.00001. To ensure inter-observer reliability, images were assessed by 2 observers with Cohen’s Kappa coefficient 0.477. Conclusions MIS chevron osteotomy can produce significant improvement of sesamoid position which is crucial to prevent recurrence of hallux valgus.

Inferior Surface Leukoplakia of Vocal Folds: Risk of Recurrence: A Preliminary Study

Objectives: This study aimed to identify vocal fold leukoplakia (VFL) lesions on the inferior surface as a risk factor for recurrence. Methods: This was a retrospective study with data collected from 2001 to 2018. The study comprised 37 patients with VFL, divided into the nonrecurrent and recurrent groups. We examined the clinicopathological characteristics and the surgical procedures performed in each patient. Results: Among the 37 patients, 15 (40.5%) had residual (3) or recurrent (12) VFL. Of those patients with and without recurrence, 8 of 12 (66.7%) and 6 of 22 (27.3%), respectively, had inferior surface lesions of the vocal fold at the initial operation ( P = .036). Recurrences were significantly higher in patients with inferior surface lesions. Other evaluated factors did not show significance for recurrence. Conclusion: The presence of VFL lesions on the inferior surface is a significant risk factor for recurrence.

The Impact of Pulmonary Vascular Obstruction on the Risk of Recurrence of Pulmonary Embolism: A French Prospective Cohort

Background We aimed to assess whether high pulmonary vascular obstruction index (PVOI) measured at the time of pulmonary embolism (PE) diagnosis is associated with an increased risk of recurrent venous thromboembolism (VTE). Study Design and Methods French prospective cohort of patients with a symptomatic episode of PE diagnosed with spiral computerized tomography pulmonary angiography (CTPA) or ventilation-perfusion (V/Q) lung scan and a follow-up of at least 6 months after anticoagulation discontinuation. PVOI was assessed based on the available diagnostic exam (V/Q lung scan or CTPA). All patients had standardized follow-up and independent clinicians adjudicated all deaths and recurrent VTE events. Main outcome was recurrent VTE after stopping anticoagulation. Results A total of 418 patients with PE were included. During a median follow-up period of 3.6 (1.2–6.0) years, 109 recurrences occurred. In multivariate analysis, PVOI ≥ 40% was an independent risk factor for recurrence (hazard ratio 1.77, 95% confidence interval 1.20–2.62, p < 0.01), whether PE was provoked by a major transient risk factor or not. A threshold at 41% was identified as the best value associated with the risk of recurrence 6 months after stopping anticoagulation (area under curve = 0.64). Conclusion PVOI ≥ 40% at PE diagnosis was an independent risk factor for recurrence VTE. Further prospective validation studies are needed.