Esophagus最新文献

Background: The American Joint Committee on Cancer (AJCC) 8th edition and Japanese classification 12th edition can be applied for esophageal cancer staging. This retrospective study aimed to compare these two staging systems in patients with surgically treated esophageal squamous cell carcinoma (ESCC).

Methods: We retrospectively reviewed 2,853 patients who underwent esophagectomy and lymphadenectomy from 1994 to 2020. Patients were divided into the upfront (n = 2156) and neoadjuvant (n = 697) groups.

Results: The mean age of the patients was 63.5 ± 8.2 years with a median follow-up of 7.6 years. Comparing both staging systems showed that patients were more likely to be staged lower by the Japanese classification. Survival curves for overall survival (OS) and disease-free survival in the upfront group were well separated in the two staging systems (p < 0.01), and the HR for survival significantly increased as the stage increased. In the neoadjuvant group, there were crossovers of survival curves between stages II and III in the AJCC, and crossovers between stages I and II, and stages III and IV in the Japanese classification. The HR for OS demonstrated less statistical differences in the neoadjuvant group.

Conclusion: The AJCC 8th edition and Japanese classification 12th edition predicted survival well for patients received the upfront surgery, whereas both showed crossovers of survival curves for patients undergoing neoadjuvant therapy. More accurate staging systems for patients with ESCC who received neoadjuvant therapy and surgery are needed.

Background: Herein, we aimed to examine the relationship between sarcopenia, neutrophil-lymphocyte ratio (NLR), Charlson comorbidity index (CCI), and prognostic nutritional index (PNI) in patients with superficial esophageal carcinoma who underwent definitive chemoradiotherapy (CRT).

Methods: We retrospectively analyzed 100 patients (87 males) diagnosed with cT1N0M0 esophageal squamous cell carcinoma. The included patients underwent CRT as an initial treatment. Muscle mass was assessed using the psoas muscle index (PMI). All patients received concurrent chemotherapy (5-fluorouracil plus cisplatin/nedaplatin) and radiotherapy (60 Gy). The duration of follow-up (median range) was 78 (2.5-197) months. During the follow-up period, 23 recurrences occurred, along with 37 deaths (11 deaths from esophageal cancer; only one treatment-related death).

Results: The 5-year survival rate was 78.0%. The median (range) PMI was 6.55 (3.90-10.9) and 4.62 (2.28-6.60) cm²/m² in males and females, respectively. The PNI was 46.6 (36.2-60.4), NLR was 2.45 (0.61-18.1), and CCI was 0 (0-10). Patients were divided into low PMI (sarcopenia) and high PMI (non-sarcopenia) groups. In the univariate survival time analysis, the low PMI group had a significant hazard ratio (HR) of 2.70 (p = 0.0049), the low Geriatric Nutritional Risk Index (GNRI) group had an HR of 2.30 (p = 0.0161), and the CCI ≥ 1 group had an HR of 2.19 (p = 0.0199). According to the multivariate analysis using these three factors and age (≥ 65 years), PMI was an independent prognostic factor (HR, 2.23; p = 0.0313).

Conclusions: PMI is a notable predictor of prognosis in patients undergoing CRT for T1N0M0 esophageal cancer.

Background: Esophageal cancer is highly prevalent in China, predominantly represented by squamous cell carcinoma. This retrospective study sought to evaluate the diagnostic efficacy of four staining protocols in identifying early stage esophageal squamous cell carcinoma (ESCC).

Methods: A consecutive series of ninety biopsy samples of esophageal mucosa, collected retrospectively from March 2016 to December 2019, were obtained at Beijing Chao-Yang Hospital, a tertiary care facility in Beijing, China. These samples were categorized into four groups: non-neoplastic squamous lesions (Non-NSL), low-grade dysplasia (LGD), high-grade dysplasia (HGD), and early stage ESCC. Baseline, molecular analyses (p53 by immunohistochemistry and Ki-67 by immunohistochemistry), and staining analyses (hematoxylin & eosin (HE) and periodic acid-Schiff (PAS) were conducted across the categories. The staining protocols included HE, HE + p53 + Ki-67, HE + p53 + Ki-67 + PAS, and HE + p53/PAS + Ki-67/PAS.

Results: Patients with HGD and ESCC were significantly older and had larger lesions. Elevated p53 and Ki-67 mutation rates were observed in HGD and ESCC, while increased PAS positivity was noted in RE and LGD. The p53, Ki-67, and PAS staining results showed mostly no correlation among the four groups. Abnormal Ki-67 basal layer distribution pattern correlated with histological grades, with higher proportions in HGD and ESCC. HE + p53 + Ki-67 + PAS and HE + p53/PAS + Ki-67/PAS demonstrated complete consistency with the reference standard, with weighted κ values of 1. HE + p53 + Ki-67 + PAS and HE + p53/PAS + Ki-67/PAS protocols exhibited 100% accuracy, sensitivity, and specificity for diagnosing ESCC or ESCC combined with HGD, outperforming the other protocols.

Conclusions: Incorporating specific staining protocols, particularly HE + p53 + Ki-67 + PAS and HE + p53/PAS + Ki-67/PAS, enhances the diagnostic accuracy for early stage ESCC, showing promise in advancing the pathology diagnostic pathway.

Background: Intratumoral Fusobacterium nucleatum (Fn) infection is closely associated with poor prognosis in esophageal cancer (EC) due to its impact on the tumor microenvironment (TME). The tumor cell-intrinsic cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway is critical for regulating immune cell activation in the TME. However, the link between intratumoral Fn infection and the activation of the cGAS-STING pathway in tumor cells, as well as its effects on EC progression, remains largely unknown.

Methods: In the present study, we investigated the impact of intratumoral Fn infection on the activation of the tumor cell-intrinsic cGAS-STING pathway and EC progression by analyzing our own EC cohort and performing in vitro experiments using co-cultures of EC-cell lines and Fn.

Results: The expression of tumor cell-intrinsic STING was significantly associated with worse prognosis in Fn-high EC patients. Exposure to Fn significantly activated the STING pathway in EC cells. RNA-seq analysis revealed that exposure to Fn markedly activated cytokine-chemokine-related signaling pathways and induced the expression of several cytokines and chemokines in STING-expressing EC cells. Among the differentially expressed cytokine and chemokine genes in EC cells co-cultured with Fn, analysis of TCGA datasets demonstrated that the expression of CCL20, CXCL10, and CSF2 may be associated with poor prognosis in EC patients.

Conclusion: We revealed that the activation of the STING signaling pathway and the subsequent expression of cytokines and chemokines in EC cells induced by Fn infection may be closely associated with poor prognosis in EC patients.

Background: Although combinations of immune-checkpoint inhibitors (ICI) with chemotherapy have been approved for esophageal squamous cell carcinoma (ESCC), it remains unclear whether immunochemotherapy (ICT) offers advantages over the simple addition of individual monotherapies. This study aimed to investigate whether ICT exhibits a synergistic effect in patients with advanced ESCC.

Methods: Reconstructed individual patient data of 3330 patients were electronically extracted from the Kaplan-Meier (KM) curves of eight randomized-controlled trials (ATTRACTION-3, CheckMate648, KEYNOTE-181, KEYNOTE-590, RATIONALE-302, RATIONALE-306, ESCORT, and ESCORT-1st). The observed progression-free survival (PFS) curve of each constituent monotherapies was used to estimate simulated PFS curves expected under a model of independent drug action. If the observed curve demonstrated significantly better PFS than the simulated curve, the combination of ICI and chemotherapy may have a synergistic effect, implying a superior outcome compared to simply adding the component monotherapy.

Results: The 1-year, 2-year, and median PFS of the observed and simulated KM curves were 26.3% vs. 24.8%, 14.6% vs. 12.0%, and 6.9 vs. 6.4 months, respectively. The one-sample log-rank test showed no significant differences between the observed and simulated KM curves (p = 0.073).

Conclusions: The observed PFS with ICT was comparable to the simulated PFS estimated from the data for each monotherapy. Although it is unclear whether potential synergies exist for ICT, these findings suggest that the benefits of ICI and chemotherapy do not interfere with each other, thereby providing theoretical support for the efficacy of ICT.

Background: Endoscopic treatment for second primary malignancies after esophagectomy has been increasingly performed; however, evidence regarding the outcomes of endoscopic submucosal dissection (ESD) for superficial cancer of the remnant esophagus after esophagectomy (SCREE) is limited.

Methods: We retrospectively extracted cases of ESD for SCREE from our institutional database, which included 739 consecutive esophageal ESD procedures performed between January 2009 and September 2023. Information on prior treatment, clinical features of the lesions, and outcomes was evaluated.

Results: Overall, 20 patients (median age: 74 years) with 27 lesions were enrolled. ESD was performed at a median of 15 months after esophagectomy. All lesions were flat, with a median tumor diameter of 12 mm. The median ESD procedure time was 70 min. En bloc resection was achieved for all 27 lesions, with one minor perforation complication. The R0 resection rate was 96% (26 of 27). Endoscopic balloon dilation (EBD) of the anastomotic site at the beginning of ESD was required in 30% (8 of 27) of the cases. Among them, EBD was significantly more frequently performed in cases after partial esophagectomy (64%, 7 of 11) than in cases after other types of surgery. The resection speed was significantly faster in lesions after total pharyngo-laryngo-esophagectomy and slower in lesions after subtotal esophagectomy, located in the upper region, and near the anastomosis.

Conclusions: Our study demonstrated the feasibility of ESD for SCREE although EBD or a longer procedure duration may be required depending on the pre-ESD surgical technique and location of the lesions.

Background: Physical activity has the potential to promote tumor regression in patients with esophageal cancer receiving neoadjuvant chemotherapy (NAC); however, the benefits of light-intensity physical activity (LIPA) are unclear. This study aimed to investigate the impact of LIPA on tumor regression in male patients with esophageal cancer during NAC and its optimal cutoff value.

Methods: This retrospective single-center observational study included all male patients who underwent NAC or curative esophagectomy. We assessed the physical activity of patients using an accelerometer and calculated the time spent on LIPA. Tumor regression was defined as grade ≥ 1b according to the Japanese classification of esophageal cancer. The impact of LIPA on tumor regression was analyzed using multivariate analysis, and the optimal cutoff value was identified using the receiver operating characteristic curve.

Results: Sixty-nine male patients with esophageal cancer who underwent NAC were analyzed. The mean age was 68 years, mean body mass index was 22.4, and 80% of the patients were diagnosed with clinical stage 3 or 4 disease. Every extra 30-min increase in LIPA during the treatment phase was associated with tumor regression (adjusted OR 1.41 [1.02-2.04]). The optimal cutoff value of LIPA was 156.11 min/day, and patients with rich LIPA (≥ 156.11 min/day) were less likely to suffer from anorexia and malnutrition during NAC.

Conclusion: This study demonstrated that LIPA during NAC has a potential of promoting tumor regression with a cutoff value of 156.5 min/day. Further clinical research is required to determine the prognostic benefits of LIPA in patients receiving NAC.

Background: EG-840TP is a novel small-caliber therapeutic endoscope with a large working channel. We aimed to evaluate the treatment outcomes of peroral endoscopic myotomy using EG-840TP compared to those using a conventional therapeutic endoscope (GIF-H290T).

Methods: Patients who underwent peroral endoscopic myotomy for achalasia and non-achalasia esophageal motility disorders were enrolled between March 2021 and March 2023. Procedure times and other treatment outcomes were compared between patients treated with EG-840TP and GIF-H290T using propensity score matching analysis. In the subgroup analysis, patients were divided into subsets based on myotomy length, morphology, esophageal dilation, and operator skill, and the procedure time was compared between the matched groups.

Results: A total of 154 patients were enrolled in this study, and 39 patients treated using each type of scope were matched. The EG-840TP group tended to have a shorter procedure time than the GIF-H290T group. There were no significant differences between the groups in terms of short-term clinical success or perioperative adverse events. In the subgroup analysis, the procedure time of the EG-840TP group was significantly shorter than that of the GIF-H290T group when patients had a straight esophagus (44 min vs. 54 min, p = 0.0015) and the operator was a non-expert (49 min vs. 64 min, p = 0.031).

Conclusions: POEM using EG-840TP showed procedure time, clinical success, and adverse events equivalent to those of a conventional therapeutic endoscope. However, EG-840TP potentially contributed to a shorter procedure time in patients with a straight esophagus or in non-expert operators than GIF-H290T.

Background: Circ_DLG1 is found to be aberrantly expressed in esophageal squamous cell carcinoma (ESCC) tissues, but its role in the progression of ESCC remains to be elucidated.

Methods: The expression of circ_DLG1, miR-338-3p and mitogen-activated protein kinase kinase kinase 9 (MAP3K9) was measured by qRT-PCR. Cell cycle, viability, migration and invasion were investigated using flow cytometry, MTT assay and transwell assay, respectively. The protein levels of MAP3K9, p38, phosphor p38 (p-p38), ERK1/2 (ERKs), phosphor ERKs (p-ERKs) were detected by western blot. Dual-luciferase reporter assay and RIP assay were performed to verify the putative relationship between miR-338-3p and circ_DLG1 or MAP3K9. Animal experiments were performed to ascertain the role of circ_DLG1 in vivo.

Results: Circ_DLG1 expression was elevated in ESCC tissues, plasma and cells. Circ_DLG1 knockdown inhibited cell proliferation, migration and invasion. MAP3K9 was highly expressed in ESCC, and its overexpression rescued the effects of circ_DLG1 knockdown on cell proliferation and metastasis. Besides, circ_DLG1 positively regulated MAP3K9 expression by competitively targeting miR-338-3p. Also, miR-338-3p inhibition or MAP3K9 overexpression recovered the inhibiting effect of circ_DLG1 knockdown on the phosphorylated levels of p38 and ERKs. In addition, circ_DLG1 knockdown blocked the tumor growth in vivo by regulating the miR-338-3p/MAP3K9 axis.

Conclusion: Circ_DLG1 promoted malignant progression of ESCC by mediating the miR-338-3p/MAP3K9/p38/ERK pathway, indicating that targeted inhibition of the circ_DLG1/miR-338-3p/MAP3K9/p38/ERK axis might be an effective strategy for the treatment of ESCC.

Background: Neoadjuvant chemotherapy is standard for advanced esophageal squamous cell carcinoma, though often ineffective. Therefore, predicting the response to chemotherapy before treatment is desirable. However, there is currently no established method for predicting response to neoadjuvant chemotherapy. This study aims to build a deep-learning model to predict the response of esophageal squamous cell carcinoma to preoperative chemotherapy by utilizing multimodal data integrating esophageal endoscopic images and clinical information.

Methods: 170 patients with locally advanced esophageal squamous cell carcinoma were retrospectively studied, and endoscopic images and clinical information before neoadjuvant chemotherapy were collected. Endoscopic images alone and endoscopic images plus clinical information were each analyzed with a deep-learning model based on ResNet50. The clinical information alone was analyzed using logistic regression machine learning models, and the area under a receiver operating characteristic curve was calculated to compare the accuracy of each model. Gradient-weighted Class Activation Mapping was used on the endoscopic images to analyze the trend of the regions of interest in this model.

Results: The area under the curve by clinical information alone, endoscopy alone, and both combined were 0.64, 0.55, and 0.77, respectively. The endoscopic image plus clinical information group was statistically more significant than the other models. This model focused more on the tumor when trained with clinical information.

Conclusions: The deep-learning model developed suggests that gastrointestinal endoscopic imaging, in combination with other clinical information, has the potential to predict the efficacy of neoadjuvant chemotherapy in locally advanced esophageal squamous cell carcinoma before treatment.