Effects of preoperative chemotherapy on metastatic lymph nodes in esophageal squamous cell carcinoma

The aim of this study was to evaluate the effect of preoperative chemotherapy on metastatic lymph nodes and on the outcome of patients who underwent esophagectomy for advanced squamous cell carcinoma of the esophagus. Fifty-nine patients with potentially resectable squamous cell carcinoma of the esophagus were studied. Twenty patients (group A) were treated by preoperative chemotherapy with cisplatin, 5-fluorouracil, and leucovorin, followed by surgery. Thirty-nine patients underwent surgery alone (group B). A total of 2591 resected lymph nodes were histologically evaluated for metastasis and the effect of chemotherapy. The metastasis rate in the resected lymph nodes, the number of metastatic lymph nodes, and outcome of the patients were statistically analyzed between groups. In group A, the clinical and pathological response rates were 75% and 75% respectively. The metastasis rate in the resected lymph nodes was significantly higher in group B (P < 0.01). The mean number of metastatic lymph nodes was significantly lower in group A (P < 0.05). Furthermore, the mean number of metastatic lymph nodes was significantly lower in the chemotherapy responders than in non-responders. The survival rate in group A was better than in group B (P = 0.07). Preoperative chemotherapy reduced the number of metastatic lymph nodes and may contribute to improving the outcome of the patients who have undergone esophagectomy for squamous cell carcinoma of the esophagus.     

Caspase-3 expression in metastatic lymph nodes of esophageal squamous cell carcinoma is prognostic of survival

AIM:To assess whether differential expression of caspase-3 in paired metastatic lymph nodes(LNs)is prognostic of survival in patients with resectable esophageal squamous cell carcinoma(ESCC).METHODS:Capases-3 expression was evaluated immunohistochemically in 122 pairs of primary ESCCs and regional metastatic LNs assembled on tissue microarrays.The impact of caspase-3 expression on survival outcomes was analyzed by the Kaplan-Meier method and Cox proportional hazards regression model.RESULTS:The level of caspase-3 expression was significantly higher in LN metastases than in primary tumors(P<0.001).Caspase-3 expression in the primary tumors was associated with longer median survival(23 mo vs21 mo,P=0.033),whereas higher expression in paired metastatic LNs was associated with shorter median survival(20 mo vs 22 mo,P=0.043).Multivariate analysis showed that both were independent prognostic factors.CONCLUSION:Caspase-3 expression in metastatic LNs may be a potential independent predictor of poorer overall survival in patients with resected ESCC and LN metastasis.Protein expression in metastatic tumors may be a biomarker prognostic of survival.     

Clinicopathologic factors predicting lymph node metastasis in superficial esophageal squamous cell carcinoma

Abstract

Objective. Surgical resection is the treatment of choice for superficial esophageal squamous cell carcinoma (SESCC), but it is associated with high mortality and morbidity rates. Recently, endoscopic resection for SESCC has been indicated for patients with a low risk of lymph node metastasis (LNM). Therefore, to successfully treat SESCC with endoscopic resection, it is very important to identify patients with a low risk for LNM. The objective of this study was to investigate clinicopathologic factors that predict LNM in patients who underwent esophagectomy for SESCC. Methods. The study included 104 patients with SESCC from three university hospitals in Pusan, Korea. Clinicopathologic factors were evaluated to identify independent factors predicting LNM by univariate and multivariate analyses. Results. In univariate analysis, the depth of tumor invasion and lymphovascular invasion had significant influences on LNM (p = 0.001 and p < 0.001, respectively). Gross type, tumor size, and tumor differentiation were not predictive for LNM. In multivariate analysis, the depth of tumor invasion and lymphovascular invasion were signi?cantly associated with LNM in patients with SESCC (OR 9.04, p = 0.049; OR 11.61, p = 0.002, respectively). Conclusions. The depth of tumor invasion and lymphovascular invasion were independent predictors of LNM in patients with SESCC. Therefore, endoscopic resection could be performed in patients with SESCC that is limited to the mucosa, without lymphovascular invasion.     

Risk factors of lymph node metastasis in T1 esophageal squamous cell carcinoma

Background and Aim: To perform endoscopic mucosal resection (EMR) for T1 esophageal cancer, it is essential to estimate the lymph node status exactly. In order to evaluate the feasibility of EMR for esophageal cancers, we evaluated the clinicopathological features of T1 esophageal squamous carcinomas with an emphasis on the risk factors and distribution patterns of lymph node metastasis. Methods: From 1994 to 2006, a total of 200 patients with T1 esophageal carcinoma were treated surgically in our institution. Among them, clinicopathological features were evaluated for 197 consecutive patients with T1 squamous cell carcinoma. Results: The frequency of lymph node involvement was 6.25% (4/64) in mucosal cancers and 29.3% (39/133) in submucosal cancers (P < 0.001). In patients with M1 (n = 32) and M2 (n = 14) cancers, no lymph node metastasis was found. In multivariate analysis, size larger than 20 mm, endoscopically non‐flat type, and endo‐lymphatic invasion were significant independent risk factors for lymph node metastasis. The differentiation of tumor cell was not a risk factor for lymph node metastasis. Conclusions: We suggest that EMR may be attempted for flat superficial squamous esophageal cancers smaller than 20 mm. After EMR, careful histological examination is mandatory.     

Predictive value of preoperative serum squamous cell carcinoma antigen level for lymph node metastasis in early-stage cervical squamous cell carcinoma

To explore the predictive value of preoperative serum squamous cell carcinoma antigen (SCC-Ag) level for lymph node metastasis (LNM), particularly, in patients surgically treated for early-stage cervical squamous cell carcinoma.We enrolled 162 patients with cervical squamous cell carcinoma stages IB to IIA following the International Federation of Gynecology and Obstetrics (FIGO) 2009 classification. The patients had previously undergone radical surgery. Correlation of the SCC-Ag level with clinicopathological features and the predictive value of SCC-Ag for LNM were analyzed.High preoperative SCC-Ag level was correlated with FIGO stage (P = .001), tumor diameter >4 cm (P < .001), stromal infiltration (P < .001), LNM (P < .001) and lymphovascular space invasion (LVSI), (P = .045). However, it was not correlated with age, histological differentiation, parametrial involvement, and positive vaginal margin (P > .05). Univariate analysis revealed that FIGO stage (P = .015), tumor diameter (P = .044), stromal infiltration (χ² = 10.436, P = .005), SCC-Ag ≧ 2.75 ng/mL (χ² = 14.339, P < .001), LVSI (χ² = 12.866, P < .001), parametrial involvement (χ² = 13.784, P < .001) were correlated with LNM, but not with age, histological differentiation, and positive vaginal margin. Moreover, multivariate analysis demonstrated that SCC-Ag ≧2.75 ng/mL (P = .011, OR = 3.287) and LVSI (P = .009, OR = 7.559) were independent factors affecting LNM. The area under the receiver operator characteristic curve of SCC-Ag was 0.703 (P < .001), while 2.75 ng/mL was the best cutoff value for predicting LNM. The sensitivity and specificity of diagnosis were 69.4% and 65.9%, respectively.High SCC-Ag level was revealed to be an independent risk factor for the prognosis of squamous carcinoma of the cervix before an operation. Besides, SCC-Ag (2.75 ng/mL) can be utilized as a potential marker to predict LNM in early stage cervical cancer before an operation.     

Microinvasive squamous cell cervical carcinoma

Several histologic tumor-related features are the key factors for further treatment planning in microinvasive cervical cancer (MIC) after conization. To better define the indications for conservative treatment of MIC we conducted a literature review for prognostic factors for MIC and we carried out a prospective observational study evaluating most important pathologic factors and the relationships between tumor and edges of the cone and incidence of recurrences. In our experience seven recurrences were observed. Two distinct groups of patients were identified with a clearance lower or higher of 10 and 8 mm for apical and lateral margin respectively. Depth of infiltration and even lymph-vascular involvement have been confirmed as the most important histologic parameters to be evaluated. Apical and lateral clearance of the tumor are significantly correlated with the recurrence rate. If an adequate lateral border of healthy tissue is present on the specimen, conization may be considered as definitive treatment of MIC.     

Cytoplasmic hepatocyte growth factor immunoreactivity predicting lymph node metastasis in esophageal squamous cell carcinoma

Background

Esophageal squamous cell carcinoma (ESCC) is a highly malignant disease because of its aggressive biological behavior and metastatic potential. Although several molecular markers have been identified as prognostic factors and/or clinicopathological correlation for the patients of ESCC, it has not been established as the effective new treatment for ESCC patients yet. Hepatocyte growth factor (HGF) is a biomarker as known to promote cell proliferation, motility, and invasion in various human malignancies. But the correlation with cytoplasmic HGF and ESCC has been unclear in details.

Methods

We studied the correlation of HGF expression in ESCC tumor cells from 83 ESCC patients who were operated in our hospital using immunohistochemistry.

Results

High cytoplasmic HGF expression was detected in 50.6 % (42/83) of ESCC cases examined. HGF immunoreactivity was also focally detected in some cancer-associated fibroblasts. High HGF expression group was significantly correlated with lymph node metastasis (P = 0.029) and tumor differentiation (P = 0.018). Increased HGF immunoreactivity was also correlated with clinicopathological features associated with invasiveness of carcinoma cells (lymphatic invasion, venous invasion, distant metastasis, and pathological stage) but not with actual clinical outcome of the patients.

Conclusions

Results of our present study indicated that HGF cytoplasmic expression in ESCC was associated with increased potential for lymph node metastasis and carcinoma differentiation. These findings indicated that endogenous HGF did play an important role in progression and invasion of ESCC via c-Met/HGF autocrine loop together with HGF paracrine mechanisms.     

Radiation-induced esophageal squamous cell carcinoma in situ

A report of radiation-induced squamous cell carcinoma in situ of the esophagus is presented. This report indicates that the patient developed the carcinoma in situ many years after chest wall irradiation for breast cancer treatment. A review of the literature with respect to carcinogenesis after radiotherapy is included and recommendations for the follow-up of patients having mediastinal radiation are suggested.     

Impact of extracapsular lymph node involvement on tumor progression in esophageal squamous cell carcinoma after neoadjuvant therapy and effects on lymph nodes induced by chemotherapy and chemoradiotherapy

Background

Neoadjuvant therapy followed by surgery can improve long-term survival and reduce local recurrence in patients with esophageal squamous cell carcinoma (ESCC). Extracapsular lymph node involvement (ECLNI) reflects tumor progression in gastrointestinal malignancies. The aim of this study was to clarify the correlation between ECLNI and clinical outcome in ESCC following neoadjuvant therapy.

Methods

A total of 36 patients with ESCC who underwent neoadjuvant therapy followed by surgery were enrolled in this study (CT: n = 16; CRT: n = 20). The correlation between ECLNI and clinicopathological variables was investigated. In addition, we also evaluated whether differences in pathological response existed between primary tumors and metastatic lymph nodes (LNs), and whether chemotherapy (CT) and chemoradiotherapy (CRT) had different effects on LNs.

Results

Of 36 patients, 22.2 % had detectable ECLNI. ECLNI was significantly correlated with tumor size (>40 mm), LN density (≧20 %), advanced stage, lymphatic invasion, non-R0 resection, and poor pathological response. Patients with ECLNI had a significantly poorer prognosis than those without ECLNI (P = 0.0040). No differences in pathological response were observed between primary tumors and metastatic LNs for each type of therapy. The median number of dissected LNs was 21, 45, and 14 in the surgery alone (n = 22), CT, and CRT groups, respectively (P < 0.05). More severe morphologic changes in LNs appeared to be induced by CRT than by CT.

Conclusion

ECLNI was correlated with poor prognosis in patients with ESCC after neoadjuvant therapy. CT and CRT had different effects on LNs.     

Risk analysis of lymph node metastasis in 285 patients with superficial esophageal squamous cell carcinoma

<正>Objective To identify risk factors of lymph node metastasis in superficial esophageal squamous cell carcinoma(ESCC),and to provide evidence for treatment choice under endoscope.Methods From January 2007 to December 2011,285 patients with pathologically diagnosed ESCC who received surgery and had clear record of lymph nodes resection were enrolled.The clinical pathological data of these patients were analyzed,including     

Delineating the extent of esophageal squamous cell carcinoma

Esophagus - Lugol chromoendoscopy has been conventionally used for the detection and delineation of esophageal squamous cell carcinoma (SCC). However, the boundaries of some lesions are unclear...     

Expression and prognostic significance of esophageal squamous cell carcinoma associated long non-coding RNA-1 in esophageal squamous cell carcinoma

正Objective To analyze the expression and prognostic significance of esophageal squamous cell carcinoma associated long non-coding RNA-1 (ESCCAL-1) in esophageal squamous cell carcinoma (ESCC) tissues.Methods From August 2011 to May 2013, 73 patients with ESCC,who received radical resection in the First Affiliated Hospital of Zhengzhou University and Henan Cancer Hospi-     

N-linked glycoproteomic profiling in esophageal squamous cell carcinoma

BACKGROUNDMass spectrometry-based proteomics and glycomics reveal post-translational modifications providing significant biological insights beyond the scope of genomic sequencing.AIMTo characterize the N-linked glycoproteomic profile in esophageal squamous cell carcinoma (ESCC) via two complementary approaches.METHODSUsing tandem multilectin affinity chromatography for enrichment of N-linked glycoproteins, we performed N-linked glycoproteomic profiling in ESCC tissues by two-dimensional gel electrophoresis (2-DE)-based and isobaric tags for relative and absolute quantification (iTRAQ) labeling-based mass spectrometry quantitation in parallel, followed by validation of candidate glycoprotein biomarkers by Western blot.RESULTS2-DE-based and iTRAQ labeling-based quantitation identified 24 and 402 differentially expressed N-linked glycoproteins, respectively, with 15 in common, demonstrating the outperformance of iTRAQ labeling-based quantitation over 2-DE and complementarity of these two approaches. Proteomaps showed the distinct compositions of functional categories between proteins and glycoproteins with differential expression associated with ESCC. Western blot analysis validated the up-regulation of total procathepsin D and high-mannose procathepsin D, and the down-regulation of total haptoglobin, high-mannose clusterin, and GlcNAc/sialic acid-containing fraction of 14-3-3ζ in ESCC tissues. The serum levels of glycosylated fractions of clusterin, proline-arginine-rich end leucine-rich repeat protein, and haptoglobin in patients with ESCC were remarkably higher than those in healthy controls.CONCLUSIONOur study provides insights into the aberrant N-linked glycoproteome associated with ESCC, which will be a valuable resource for future investigations.     

PGP9.5 overexpression in esophageal squamous cell carcinoma

BACKGROUND/AIMS: PGP9.5 is a ubiquitin hydrolase widely expressed in neuronal tissue at all stages of neuronal differentiation and has been used as a neuroendocrine marker. Recently, it has been proved that PGP9.5 expression was highly observed in squamous cell carcinoma of lung cancer, suggesting that it might be a tumor marker for squamous cell carcinoma. To better characterize its role in digestive tract cancers, we examined PGP9.5 expression retrospectively in esophageal cancers. METHODOLOGY: We examined PGP9.5 expression retrospectively in 40 resected esophageal cancers (squamous cell carcinoma) and 10 gastric cancers (adenocarcinoma) using immunohistochemistry. RESULTS: Of 40 esophageal cancer specimens, 19 (48%) exhibited positive staining with PGP9.5 in most tumor cells, while no PGP9.5 expression was observed in any of the 10 gastric cancers. CONCLUSIONS: Although the precise mechanism underlying the effect of PGP9.5 on oncogenicity remains to be proven, it was confirmed that it may be a potential marker for esophageal squamous cell carcinoma.     

食管癌淋巴结转移的危险因素分析

目的探讨食管癌淋巴结转移的危险因素。 方法回顾性分析2015年7月至2017年9月,新疆自治区人民医院胸外科行手术治疗食管癌的224例患者的病例资料,比较淋巴结转移组(转移组)与非淋巴结转移组(非转移组)的关系,并进行多因素Logistic回归进行分析,探讨淋巴结转移的危险因素。 结果患者症状期较长、肿瘤长度、分化程度、肿瘤分期T与淋巴结转移有显著相关性(P<0.05)。 结论肿瘤低分化、肿瘤长度>5 cm、肿瘤侵润深度T₃～T₄、患者症状期>6个月是淋巴结转移的危险因素,应尽可能选择经右胸入路胸腹腔镜辅助下食管癌根治术,并清扫双侧喉返神经淋巴结。     

食管鳞状细胞癌类器官的应用

类器官(organoid)作为一种新型的研究模型能够稳定保持肿瘤多细胞团的异质性特征,高度还原原位肿瘤组织的生理结构和功能。既能适用于高通量的临床药物筛选,提供个性化治疗的策略;又能构建病理模型,作为研究肿瘤发生、多个阶段发展和转移机制的有力工具。目前,食管、胃、肠、肝、胰、前列腺和乳腺等结构的类器官和相应的肿瘤类器官已有报道,开拓了体外培养的新平台。肿瘤类器官模型具有易操作、成本相对低廉且可以与其他先进技术相结合应用等明显优势,有望在相关领域广泛应用。本文对食管鳞状细胞癌类器官的培养技术及应用现状进行了总结。     

Molecular biology of esophageal squamous cell carcinoma

Esophageal squamous cell carcinoma (ESCC) is the predominant histologic subtype of esophageal cancer and characterized by high mortality rate and geographic differences in incidence. With the advances in the field of molecular biology, our understanding of the pathogenesis, epidemiology and behavior of ESCC continues to evolve. The recent development includes research in etiopathogenesis (viruses and cancer susceptibility genes), keratins, tumor related genes (oncogenes, tumor suppressor genes, genes involved in metastasis and apoptosis genes), proliferation-related factors (nuclear proteins, flow cytometry/morphometry, argyrophilic nucleolar organizer region) and factors related to metastases (cell adhesion molecules and enzymes related to degradation of extracellular matrix). There are ranges of molecular techniques potentially available to complement the traditional approaches in the management of ESCC. On the other hand, critics are needed in the interpretation and translation of these research findings from laboratories to clinics. Further investigations, education and collaborations between the various scientific and clinical disciplines are important to successful application of these molecular findings aiming at improving management of patients with ESCC.