BackgroundCamrelizumab and chemotherapy demonstrated durable antitumor activity with a manageable safety profile as first-line treatment in patients with advanced esophageal squamous cell carcinoma (ESCC). This study aimed to evaluate the safety and efficacy of camrelizumab plus neoadjuvant chemotherapy, using pathologically complete response (pCR) as primary endpoint, in the treatment for locally advanced ESCC.MethodsPatients with locally advanced but resectable thoracic ESCC, staged as T1b-4a, N2-3 (≥3 stations), and M0 or M1 lymph node metastasis (confined to the supraclavicular lymph nodes) were enrolled. Eligible patients received intravenous camrelizumab (200 mg, day 1) plus nab-paclitaxel (100 mg/m2, day 1, 8, 15) and carboplatin (area under curve of 5 mg/mL/min, day 1) of each 21-days cycle, for two cycles before surgery. The primary endpoint is pCR rate in the per-protocol population. Safety was assessed in the modified intention-to-treat population that was treated with at least one dose of camrelizumab.ResultsFrom November 20, 2019 to December 22, 2020, 60 patients were enrolled. 55 (91.7%) patients completed the full two-cycle treatment successfully. 51 patients underwent surgery and R0 resection was achieved in 50 (98.0%) patients. pCR (ypT0N0) was identified in 20 (39.2%) patients and 5 (9.8%) patients had complete response of the primary tumor but residual disease in lymph nodes alone (ypT0N+). 58 patients (96.7%) had any-grade treatment-related adverse events (TRAEs), with the most common being leukocytopenia (86.7%). 34 patients (56.7%) had adverse events of grade 3 or worse, and one patient (1.7%) occurred a grade 5 adverse event. There was no in-hospital and postoperative 30-day as well as 90-day mortality.ConclusionsThe robust antitumor activity of camrelizumab and chemotherapy was confirmed and demonstrated without unexpected safety signals. Our findings established camrelizumab and chemotherapy as a promising neoadjuvant treatment for locally advanced ESCC.Trial registration numberChiCTR1900026240.

BackgroundRecent population structure studies of T. gondii revealed that a few major clonal lineages predominated in different geographical regions. T. gondii in South America is genetically and biologically divergent, whereas this parasite is remarkably clonal in North America and Europe with a few major lineages including Types I, II and III. Information on genotypes and mouse virulence of T. gondii isolates from China is scarce and insufficient to investigate its population structure, evolution, and transmission.Methodology/Principal FindingsGenotyping of 23 T. gondii isolates from different hosts using 10 markers for PCR-restriction fragment length polymorphism analyses (SAG1, SAG2, SAG3, BTUB, GRA6, c22-8, c29-2, L358, PK1 and Apico) revealed five genotypes; among them three genotypes were atypical and two were archetypal. Fifteen strains belong to the Chinese 1 lineage, which has been previously reported as a widespread lineage from swine, cats, and humans in China. Two human isolates fall into the type I and II lineages and the remaining isolates belong to two new atypical genotypes (ToxoDB#204 and #205) which has never been reported in China. Our results show that these genotypes of T. gondii isolates are intermediately or highly virulent in mice except for the strain TgCtwh6, which maintained parasitemia in mice for 35 days post infection although it possesses the uniform genotype of Chinese 1. Additionally, phylogenetic network analyses of all isolates of genotype Chinese 1 are identical, and there is no variation based on the sequence data generated for four introns (EF1, HP2, UPRT1 and UPRT7) and two dense granule proteins (GRA6 and GRA7).Conclusion/SignificanceA limited genetic diversity was found and genotype Chinese 1 (ToxoDB#9) is dominantly circulating in mainland China. The results will provide a useful profile for deep insight to the population structure, epidemiology and biological characteristics of T. gondii in China.

Objective:To compare perioperative and long-term outcomes of robot-assisted minimally invasive esophagectomy (RAMIE) and conventional minimally invasive esophagectomy (MIE) in the treatment for patients with esophageal squamous cell carcinoma (ESCC).Summary Background Data:RAMIE has emerged as an alternative to traditional open or thoracoscopic approaches. Efficacy and safety of RAMIE and MIE in the surgical treatment for ESCC remains uncertain given the lack of high-level clinical evidence.Methods:The RAMIE trial was designed as a prospective, multicenter, randomized, controlled clinical trial that compares the efficacy and safety of RAMIE and MIE in the treatment of resectable ESCC. From August 2017 to December 2019, eligible patients were randomly assigned to receive either RAMIE or MIE performed by experienced thoracic surgeons from 6 high-volume centers in China. Intent-to-treat analysis was performed.Results:Significantly shorter operation time was taken in RAMIE (203.8 vs 244.9 min, P<0.001). Compared with MIE, RAMIE showed improved efficiency of thoracic lymph node dissection in patients who received neoadjuvant therapy (15 vs 12, P = 0.016), as well as higher achievement rate of lymph node dissection along the left recurrent laryngeal nerve (79.5% vs 67.6%, P = 0.001). No difference was found in blood loss, conversion rate, and R0 resection. The 90-day mortality was 0.6% in each group. Overall complications were similar in RAMIE (48.6%) compared with MIE (41.8%) (RR, 1.16; 95% CI, 0.92–1.46; P = 0.196). Besides, the rate of major complications (Clavien-Dindo classification ≥ III) was also comparable (12.2% vs 10.2%, P = 0.551). RAMIE showed similar incidences of pulmonary complications (13.8% vs 14.7%; P = 0.812), anastomotic leakage (12.2% vs 11.3%; P = 0.801), and vocal cord paralysis (32.6% vs 27.1%, P = 0.258) to MIE.Conclusions:Early results demonstrate that both RAMIE and MIE are safe and feasible for the treatment of ESCC. RAMIE can achieve shorter operative duration and better lymph node dissection in patients who received neoadjuvant therapy. Long-term results are pending for further follow-up investigations.Trial Registration:ClinicalTrial.gov Identifier: NCT03094351.

BackgroundOCT4 and Survivin are important factors for cancer cell proliferation, renewal and dedifferentiation, and correlate with resistance to radiotherapy and chemotherapy in most human cancers, but their regulatory mechanisms are not well known.Methodology/Principal FindingsIn this study, 50 patients with esophageal squamous cell carcinoma (ESCC) were retrospectively analyzed. OCT4 was expressed in 13 cases (26%), and survivin was positively expressed in 31 cases (62%), examined by immunochemistry. OCT4 was found to be an independent predictive factor for median survival time, and the patients from the subgroup with both high expression of OCT4 and Survivin had the worst prognosis investigated by log-rank test. To further explore the molecular regulatory mechanism between OCT4 and Survivin, we constructed the specific small hairpin RNA (shRNA)-expressing vectors targeting OCT4 or/and Survivin and manipulated the expression of OCT4 and Survivin. By Western blotting and RT-PCR, we found that OCT4 could up-regulate Survivin expression in the esophageal cancer cell lines Eca109 and TE1. Simultaneously knockdown of OCT4 and Survivin expression induced cell apoptosis and G2-phase decrease of cell cycle by flow cytometry, and finally exerted an enhanced anti-proliferation potency in Eca109 and TE1 cell lines by MTT assay.ConclusionsThis study shows that OCT4 and Survivin expression were correlated with poor survival in patients with ESCC. OCT4 and Survivin may be regarded as targets in ESCC biotherapy.