Revealing molecular and cellular heterogeneity in hypopharyngeal carcinogenesis through single-cell RNA and TCR/BCR sequencing.

Introduction: Hypopharyngeal squamous cell carcinoma (HSCC) is one of the malignant tumors with the worst prognosis in head and neck cancers. The transformation from normal tissue through low-grade and high-grade intraepithelial neoplasia to cancerous tissue in HSCC is typically viewed as a progressive pathological sequence typical of tumorigenesis. Nonetheless, the alterations in diverse cell clusters within the tissue microenvironment (TME) throughout tumorigenesis and their impact on the development of HSCC are yet to be fully understood. Methods: We employed single-cell RNA sequencing and TCR/BCR sequencing to sequence 60,854 cells from nine tissue samples representing different stages during the progression of HSCC. This allowed us to construct dynamic transcriptomic maps of cells in diverse TME across various disease stages, and experimentally validated the key molecules within it. Results: We delineated the heterogeneity among tumor cells, immune cells (including T cells, B cells, and myeloid cells), and stromal cells (such as fibroblasts and endothelial cells) during the tumorigenesis of HSCC. We uncovered the alterations in function and state of distinct cell clusters at different stages of tumor development and identified specific clusters closely associated with the tumorigenesis of HSCC. Consequently, we discovered molecules like MAGEA3 and MMP3, pivotal for the diagnosis and treatment of HSCC. Discussion: Our research sheds light on the dynamic alterations within the TME during the tumorigenesis of HSCC, which will help to understand its mechanism of canceration, identify early diagnostic markers, and discover new therapeutic targets.

Preoperative Concurrent Chemoradiotherapy Versus Neoadjuvant Chemotherapy for Locally Advanced Gastric Cancer: Phase II Randomized Study.

Objective: We evaluated and compared the efficacy and safety of neoadjuvant chemoradiotherapy (NACRT) versus neoadjuvant chemotherapy (NACT) for locally advanced gastric cancer (LAGC) in a single-center randomized phase II trial. Methods: Patients with LAGC were enrolled and received either NACT or NACRT, followed by gastrectomy and adjuvant chemotherapy. The primary endpoint was an R0 resection rate. Results: We enrolled 75 patients: 75.7% (NACT, 28/37 patients) and 76.3% (NACRT, 29/38 patients) underwent surgery; R0 resection rates were 73.0% (27/37) and 73.7% (28/38), respectively. The NACRT group had significantly better major pathological response than the NACT group (37.9% vs 17.9%, p = 0.019). Between-group postoperative complications were not significantly different. The median follow-up was 59.6 months; 5-year overall survival (OS) rate was 50.1% (NACT) and 61.9% (NACRT); neither group reached the median OS; median progression-free survival was 37.3 and 63.4 months, respectively. Conclusions: S-1-based NACRT did not improve the R0 resection rate, although it presented better tumor regression with similar safety to NACT. Trial registration: ClinicalTrial.gov NCT02301481.

Additional laparoscopic gastrectomy after noncurative endoscopic submucosal dissection for early gastric cancer: A single-center experience.

BACKGROUND: The necessity of additional gastrectomy for early gastric cancer (EGC) patients who do not meet curative criteria after endoscopic submucosal dissection (ESD) is controversial. AIM: To examine the clinicopathologic characteristics of patients who underwent additional laparoscopic gastrectomy after ESD and to determine the appropriate strategy for treating those after noncurative ESD. METHODS: We retrospectively studied 45 patients with EGC who underwent additional laparoscopic gastrectomy after noncurative ESD from January 2013 to January 2019 at the Cancer Hospital of the Chinese Academy of Medical Sciences. We analyzed the patients' clinicopathological data and identified the predictors of residual cancer (RC) and lymph node metastasis (LNM). RESULTS: Surgical specimens showed RC in ten (22.2%) patients and LNM in five (11.1%). Multivariate analysis revealed that positive horizontal margin [odds ratio (OR) = 13.393, 95% confidence interval (CI): 1.435-125, P = 0.023] and neural invasion (OR = 14.714, 95%CI: 1.087-199, P = 0.043) were independent risk factors for RC. Undifferentiated type was an independent risk factor for LNM (OR = 12.000, 95%CI: 1.197-120, P = 0.035). Tumors in all patients with LNM showed submucosal invasion more than 500 µm. Postoperative complications after additional laparoscopic gastrectomy occurred in five (11.1%) patients, and no deaths occurred among patients with complications. CONCLUSION: Gastrectomy is necessary not only for patients who have a positive margin after ESD, but also for cases with neural invasion, undifferentiated type, and submucosal invasion more than 500 µm. Laparoscopic gastrectomy is a safe, minimally invasive, and feasible procedure for additional surgery after noncurative ESD. However, further studies are needed to apply these results to clinical practice.

A randomized trial comparing multiband mucosectomy and cap-assisted endoscopic resection for endoscopic piecemeal resection of early squamous neoplasia of the esophagus.

BACKGROUND AND AIM: Piecemeal endoscopic resection for esophageal high grade intraepithelial neoplasia (HGIN) or early squamous cell carcinoma (ESCC) is usually performed by cap-assisted endoscopic resection. This requires submucosal lifting and multiple snares. Multiband mucosectomy (MBM) uses a modified variceal band ligator without submucosal lifting. In high-risk areas where ESCC is common and endoscopic expertise is limited, MBM may be a better technique. We aimed to compare MBM to the cap-assisted technique for piecemeal endoscopic resection of esophageal ESCCs. METHODS: Patients with mucosal HGIN/ESCC (2 - 6 cm, maximum two-thirds of esophageal circumference) were included. Lesions, delineated by 1.25 % Lugol staining, were randomized to MBM or cap-assisted piecemeal resection. Endpoints were procedure time and costs, complete endoscopic resection, adverse events, and absence of HGIN/ESCC at 3-month and 12-month follow-up.  RESULTS: Endoscopic resection was performed in 84 patients (59 men, mean age 60) using MBM (n = 42) or the endoscopic resection cap (n = 42). There were no differences in baseline characteristics. Endoscopic complete resection was achieved in all lesions. Procedure time was significantly shorter with MBM (11 vs. 22 minutes, P < 0.0001). One perforation, seen after using the endoscopic resection cap, was treated conservatively. Total costs of disposables were lower for MBM (€200 vs. €251, P = 0.04). At 3-month and 12-month follow-ups none of the patients had HGIN/ESCC at the resection site. CONCLUSION: Piecemeal endoscopic resection of esophageal ESCC with MBM is faster and cheaper than with the endoscopic resection cap. Both techniques are highly effective and safe. MBM may have significant advantages over the endoscopic resection cap technique, especially in countries where ESCC is extremely common but limited endoscopic expertise and resources exist. (Netherlands trial register: NTR 3246.).

[Comparative study of endoscopic mucous resection with transparent cap and endoscopic multi-band mucosectomy for early esophageal cancer and precancerous lesion].

OBJECTIVE: To evaluate the efficacy and safety of endoscopic mucous resection with transparent cap (EMR-Cap) and endoscopic multi-band mucosectomy (MBM) in the treatment of early esophageal cancer and precancerous lesion. METHODS: A retrospective study was performed to review 30 EMR-Cap cases from December 2008 to December 2009 and 32 MBM cases from January 2010 to January 2011 of early esophageal cancer and precancerous lesions. The differences between these two techniques in efficacy, safety, and cost were compared. RESULTS: In EMR-Cap group, the median resection time was 26(10-56) min and median procedure time was 43(22-81) min, significantly longer than those in MBM group [10(7-18) min and 32(28-45) min, P=0.036 and 0.038, respectively]. There were no significant differences between the two groups in total thickness and depth of resected lesions (P>0.05). In EMR-Cap group, the median cost was significantly higher than that of MBM group [(5466±354) vs. (4014±368) RMB, P=0.008)]. CONCLUSIONS: EMR-Cap and MBM are minimally invasive, safe and effective methods in the treatment of early esophageal cancer and precancerous lesions. Compared to the EMR-Cap, MBM is simple with shorter treatment time and lower cost.