A multi-center, single-arm, phase II study of anlotinib plus paclitaxel and cisplatin as the first-line therapy of recurrent/advanced esophageal squamous cell carcinoma.

BACKGROUND: Anlotinib, a tyrosine kinase inhibitor, has shown encouraging anti-tumor activity in esophageal squamous cell carcinoma (ESCC). This study was designed to assess the efficacy and safety of anlotinib plus paclitaxel and cisplatin (TP) as first-line therapy for advanced ESCC. METHODS: In a multi-center, single-arm, phase II clinical trial, patients (aged > 18 years) with ESCC, which was judged to be locally advanced, recurrent, or metastatic, received 10 mg oral anlotinib once daily on days 1-14, 135 mg/m2 intravenous paclitaxel on day 1, and 60-75 mg/m2 intravenous cisplatin on days 1-3 every 3 weeks for a maximum of 4-6 cycles as the initial therapy in five centers in China. Subsequently, patients received anlotinib monotherapy (10 mg) as maintenance therapy until tumor progression or intolerable toxicity. The primary endpoint was progression-free survival (PFS). RESULTS: Forty-seven patients were enrolled in this study between October 2019 and March 2021. The median follow-up was 14.04 months (IQR, 9.30-19.38). Of 46 with assessable efficacy, the median PFS and median overall survival were 8.38 months (95% CI, 6.59-10.17) and 18.53 months (95% CI, 13.11-23.95), respectively. The objective response rate was 76.1% (95% CI, 61.2-87.4%), with 4 (8.7%) complete responses and 31 (67.4%) partial responses. The disease control rate was 91.3% (95% CI, 79.2-97.6%). The median duration of response was 6.80 months (95% CI, 4.52-9.08), and 1 patient had an ongoing response for 23 months. Subgroup analysis revealed no association between clinical factors and survival or response. Of the 47 patients with assessable safety, the main grade ≥ 3 treatment-emergent adverse events (TEAEs) were neutropenia (17.0%), bone marrow suppression (12.8%), and vomiting (10.6%). No treatment-related deaths or serious TEAEs were observed. Notably, higher c-Kit levels were an independent factor for superior PFS (HR = 0.032; 95% CI, 0.002-0.606; P = 0.022). CONCLUSIONS: The study demonstrated a manageable safety profile and durable clinical response of anlotinib plus TP as first-line therapy in advanced ESCC, which suggested a potential therapeutic option for this population. TRIAL REGISTRATION: ClinicalTrials.gov NCT04063683. Registered 21 August 2019.

MicroRNA-96-5p represses breast cancer proliferation and invasion through Wnt/ß-catenin signaling via targeting CTNND1.

Low miR-96-5p expression is characteristic of many cancers but its role in breast cancer (BCa) remains poorly defined. Here, the role of miR-96-5p in BC development was assessed. We demonstrate that exogenously expressing miR-96-5p inhibits the proliferative, migratory and invasive capacity of BCa cells. Mechanistically, miR-96-5p in BCa cells was found to target and downregulate catenin delta 1 (CTNND1) leading to decreased ß-catenin expression, a loss of WNT11 signaling, reduced cyclin D1 levels and lower MMP7 expression. Exogenously expressing CTNND1 alleviated these effects. In summary, we are the first to reveal that miR-96-5p inhibits the proliferative, invasive and migratory phenotypes of BCa cells the targeting of CTNND1 and subsequent Wnt/ß-catenin signaling. These data highlight miR-96-5p as a novel target for BC treatment.

Pancreatic fistula after pancreaticoduodenectomy: Risk factors and preventive strategies.

PURPOSE: Postoperative pancreatic fistula (POPF) after pancreaticoduodenectomy (PD) is a worrisome and life-threatening complication. This study aimed to investigate the risk factors and preventive strategies for POPF after PD. MATERIALS AND METHODS: We retrospectively reviewed 301 consecutive patients who underwent PD at our hospitals between January 2011 and December 2017. We analyzed the pancreatic fistula rate according to the clinical characteristics, pathologic and laboratory findings, and the anastomotic methods and summarized the prevention measures. RESULTS: Postoperative morbidities included pancreatic leakage in 10.30% (31/301), delayed gastric emptying in 22.92% (69/301), abdominal infection in 6.98% (21/301), post-PD hemorrhage in 4.65% (14/301), and bile leakage in 4.98% (15/301), and the mortality rate was 2.33% (7/301). POPF was the most prominent factor for preoperative morbidity. Significant risk factors for pancreatic fistula were a soft pancreas, small pancreatic duct, tumor location, and interrupted anastomosis. Of these, soft texture, pancreatic duct <4 mm, and end-to-end anastomosis through hand suture closure were independent risk factors on multivariate analysis, while interrupted anastomosis, internal stent, and somatostatin use were risk factors in the high-risk pancreas subgroup. CONCLUSIONS: Our study demonstrated that pancreatic fistula is related to a soft texture and small pancreatic duct. The surgeon must consider these risk factors when performing PD. Thus, we propose a risk- and indication-adapted choice of anastomosis or an individualized approach for the pancreatic remnant to reduce the pancreatic fistula rate.