Esophageal Squamous Cell Carcinoma Lesions Research Articles

Visibility of esophageal squamous cell carcinoma under iodine staining on texture and color enhancement imaging

AbstractObjectiveIodine staining on white light imaging (WLI) is the gold standard for detecting and demarcating esophageal squamous cell carcinoma (ESCC). We examined the effects of texture and color enhancement imaging (TXI) on improving the endoscopic visibility of ESCC under iodine staining.MethodsTwenty ESCC lesions that underwent endoscopic submucosal dissection were retrospectively included. The color difference between ESCC and the surrounding mucosa (ΔEe) on WLI, TXI, and narrow‐band imaging was assessed, and ΔEe under 1% iodine staining on WLI and TXI. Furthermore, the visibility grade determined by endoscopists was evaluated on each imaging.ResultThe median ΔEe was greater on TXI than on WLI (14.53 vs. 10.71, respectively; p < 0.005). Moreover, the median ΔEe on TXI under iodine staining was greater than the median ΔEe on TXI and narrow‐band imaging (39.20 vs. 14.53 vs. 16.42, respectively; p < 0.005 for both). A positive correlation in ΔEe under iodine staining was found between TXI and WLI (correlation coefficient = 0.61, p < 0.01). Moreover, ΔEe under iodine staining on TXI in each lesion was greater than the corresponding ΔEe on WLI. The visibility grade assessed by endoscopists on TXI was also significantly greater than that on WLI under iodine staining (p < 0.01).ConclusionsThe visibility of ESCC after iodine staining was greater on TXI than on WLI.

HRU-Net: A high-resolution convolutional neural network for esophageal cancer radiotherapy target segmentation

Background and objectiveThe effective segmentation of esophageal squamous carcinoma lesions in CT scans is significant for auxiliary diagnosis and treatment. However, accurate lesion segmentation is still a challenging task due to the irregular form of the esophagus and small size, the inconsistency of spatio-temporal structure, and low contrast of esophagus and its peripheral tissues in medical images. The objective of this study is to improve the segmentation effect of esophageal squamous cell carcinoma lesions. MethodsIt is critical for a segmentation network to effectively extract 3D discriminative features to distinguish esophageal cancers from some visually closed adjacent esophageal tissues and organs. In this work, an efficient HRU-Net architecture (High-Resolution U-Net) was exploited for esophageal cancer and esophageal carcinoma segmentation in CT slices. Based on the idea of localization first and segmentation later, the HRU-Net locates the esophageal region before segmentation. In addition, an Resolution Fusion Module (RFM) was designed to integrate the information of adjacent resolution feature maps to obtain strong semantic information, as well as preserve the high-resolution features. ResultsCompared with the other five typical methods, the devised HRU-Net is capable of generating superior segmentation results. ConclusionsOur proposed HRU-NET improves the accuracy of segmentation for squamous esophageal cancer. Compared to other models, our model performs the best. The designed method may improve the efficiency of clinical diagnosis of esophageal squamous cell carcinoma lesions.

Clinicopathological and genomic features of superficial esophageal squamous cell carcinomas in nondrinker, nonsmoker females.

Esophageal squamous cell carcinoma (ESCC) is sometimes detected in non-drinker and non-smoker females who are considered to have very low risk of ESCC development in daily practice. This study examined the clinicopathological and genomic characteristics of ESCCs in females with no history of drinking and smoking. The sample comprised 118 ESCC lesions occurring in 95 female patients who underwent endoscopic submucosal dissection at our department between January 2008 and December 2019. The patients were categorized into two groups: 51 lesions in 49 patients with no history of drinking and smoking (nondrinker/nonsmoker [NDNS] group) and 69 lesions in 45 patients with a history of drinking or smoking (drinker/smoker [DS] group). We analyzed the differences in clinicopathological and cancerous genomic characteristics between the groups. Significant genomic alterations were validated using immunohistochemistry. Multiple logistic regression revealed that older age, fewer multiple Lugol-voiding lesions (LVLs), and reflux esophagitis (RE) were independently associated with the occurrence of ESCCs in the NDNS group. ESCC lesions in the NDNS group were predominantly located in the mid-thoracic esophagus, posterior wall side, with 0-IIa, the aspect ratio of the lesion >2 (vertical/horizontal), and endoscopic keratinization. Genetic analysis showed that CDKN2A driver alterations were significantly more frequent and KMT2D alterations were significantly less frequent in the NDNS group than in the DS group. KMT2D alterations were strongly correlated with immunostaining. Older nondrinker, nonsmoker females with RE and fewer multiple LVLs may develop longitudinal 0-IIa ESCC with keratinization of the posterior wall of the mid-thoracic esophagus. ESCCs in nondrinker, nonsmoker females had fewer KMT2D alterations and more CDKN2A alterations, which may be a biomarker for treatment.

Bioinformatics and network pharmacology identify promotional effects and potential mechanisms of ethanol on esophageal squamous cell carcinoma and experimental validation

Ethanol is an important risk factor for esophageal squamous cell carcinoma (ESCC); however, the molecular mechanisms behind how ethanol promotes ESCC development remain poorly understood. In this study, ethanol-ESCC-associated target genes were constructed and screened using network pharmacology and subjected to Kyoto Encyclopedia of Genes and Genomes (KEGG) and bioinformatics analysis. A mouse ethanol-exposed esophageal cancer model was constructed with 4-nitroquinoline-1-oxide (4-NQO) to assess its survival and tumor lesion status, and the mechanism of ethanol-promoted ESCC lesions was verified by qRT–PCR and Western blotting. The results showed that 126 ethanol-ESCC crossover genes were obtained, which were significantly enriched in the PI3K/AKT signaling pathway. Bioinformatics results showed that the target genes TNF, IL6, IL1β and JUN were highly expressed in esophageal tumor samples and positively correlated with tumor proliferation and apoptosis genes, and the genetic information of these genes was mutated to different degrees. Animal model experiments showed that ethanol decreased the survival rate and aggravated the occurrence of esophageal cancer in mice. qRT–PCR showed that ethanol promoted the expression of TNF, IL6, IL1β and JUN mRNA in mouse esophageal tumor tissues, and Western blotting showed that ethanol promoted p-PI3K and p-AKT protein expression in mouse esophageal tumor tissues. In conclusion, ethanol promotes esophageal carcinogenesis by increasing the expression of TNF, IL6, IL1β and JUN and activating the PI3K/AKT signaling pathway.

Novel Photodynamic Therapy for Esophageal Squamous Cell Carcinoma following Radiotherapy.

Radiotherapy (RT) or chemoradiotherapy (CRT) are frequently selected as treatments for esophageal squamous cell carcinoma (ESCC). However, salvage treatment remains challenging when endoscopic resection is not indicated for residual or recurrent ESCC following RT or CRT. Recently, owing to the emergence of second-generation photodynamic therapy (PDT) using talaporfin sodium, PDT can be performed with less phototoxicity and therefore has regained popularity in the treatment of ESCC. In this study, the effectiveness and safety of second-generation PDT in patients with residual or recurrent ESCC following RT or CRT were examined. Local complete response (L-CR) rates, procedure-related adverse events, and prognosis were evaluated. In 12 patients with 20 ESCC lesions, the L-CR rates were 95.0%. Perforation, postoperative bleeding, and photosensitivity were not observed. Esophageal stricture following PDT developed in one patient, but this could be addressed using balloon dilation. During a median follow-up period of 12 (range, 3-42) months, the 3-year cause-specific survival rate was 85.7%. Even in patients with a Charlson comorbidity index score ≥ 3, the 2-year overall survival rates were 100%. In conclusion, PDT was an efficacious and a safe salvage treatment in patients with local residual or recurrent ESCC following RT or CRT.

Diclofenac exhibits cytotoxic activity associated with metabolic alterations and p53 induction in ESCC cell lines and decreases ESCC tumor burden in vivo.

Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive forms of human malignancy, often displaying limited therapeutic response. Here, we examine the non-steroidal anti-inflammatory drug diclofenac (DCF) as a novel therapeutic agent in ESCC using complementary in vitro and in vivo models. DCF selectively reduced viability of human ESCC cell lines TE11, KYSE150, and KYSE410 as compared with normal primary or immortalized esophageal keratinocytes. Apoptosis and altered cell cycle profiles were documented in DCF-treated TE11 and KYSE 150. In DCF-treated TE11, RNA-Sequencing identified differentially expressed genes and Ingenuity Pathway Analysis predicted alterations in pathways associated with cellular metabolism and p53 signaling. Downregulation of proteins associated with glycolysis was documented in DCF-treated TE11 and KYSE150. In response to DCF, TE11 cells further displayed reduced levels of ATP, pyruvate, and lactate. Evidence of mitochondrial depolarization and superoxide production was induced by DCF in TE11 and KYSE150. In DCF-treated TE11, the superoxide scavenger MitoTempo improved viability, supporting a role for mitochondrial reactive oxygen species in DCF-mediated toxicity. DCF treatment resulted in increased expression of p53 in TE11 and KYSE150. p53 was further identified as a mediator of DCF-mediated toxicity in TE11 as genetic depletion of p53 partially limited apoptosis in response to DCF. Consistent with the anticancer activity of DCF in vitro, the drug significantly decreased tumor burdene in syngeneic ESCC xenograft tumors and 4-nitroquinoline 1-oxide-mediated ESCC lesions in vivo. These preclinical findings identify DCF as an experimental therapeutic that should be explored further in ESCC.

Inverse relations between Helicobacter pylori infection and risk of esophageal precancerous lesions in drinkers and peanut consumption.

BACKGROUND Helicobacter pylori (H. pylori) is a Gram-negative bacterium found in the upper digestive tract. Although H. pylori infection is an identified risk factor for gastric cancer, its role in esophageal squamous cell carcinoma (ESCC) remains a topic of much debate.AIMTo evaluate the association between H. pylori infection and the risk of precancerous lesions of ESCC, and further explore the association between dietary factors and the risk of H. pylori infection.METHODSTwo hundred patients with esophageal precancerous lesions (EPL) aged 63.01 ± 6.08 years and 200 healthy controls aged 62.85 ± 6.03 years were included in this case-control study. Epidemiological data and qualitative food frequency data were investigated. Enzyme-linked immunosorbent assay measuring serum immunoglobulin G antibodies was used to determine H. pylori seropositivity. An unconditional logistic regression model was used to assess the association between H. pylori infection and EPL risk dichotomized by gender, age, and the use of tobacco and alcohol, as well as the association between dietary factors and the risk of H. pylori infection.RESULTSA total of 47 (23.5%) EPL cases and 58 (29.0%) healthy controls had positive H. pylori infection. An inverse relation between H. pylori infection and the risk of EPL was found in the group of drinkers after adjustment for covariates [odds ratio (OR) = 0.32, 95% confidence interval (95%CI): 0.11-0.95]. Additionally, peanut intake was significantly associated with a decreased risk of H. pylori infection (OR = 0.39, 95%CI: 0.20-0.74).CONCLUSIONOur study suggested that H. pylori infection may decrease the risk of EPL for drinkers in a rural adult Chinese population, and the consumption of peanut may reduce the risk of H. pylori infection. These findings should be framed as preliminary evidence, and further studies are required to address whether the mechanisms are related to the localization of lesions and alcohol consumption.

Exposure to Eosinophilic Esophagitis Limits Esophageal Carcinogenesis in a Murine Model

IntroductionEpidemiological data suggest that eosinophilic esophagitis (EoE) patients do not develop esophageal cancer. Here, we paired murine models of EoE and esophageal squamous cell carcinoma (ESCC) to perform the first functional interrogation of the relationship between EoE and esophageal cancer.MethodsC57B6 mice were treated with MC903/Ovalbumin (OVA) to induce EoE and the esophageal carcinogen 4‐nitroquinoline 1‐oxide (4NQO) to induce ESCC according to the experimental scheme shown in Fig 1A. Esophagi of mice treated with vehicle controls (n=6), MC903/OVA alone (n=4), 4NQO alone (n=10), and MC903 in combination with 4NQO (n=5) were dissected. Tumor frequency was recorded and tumor load (tumor size x tumor number) was determined under a dissecting microscope. H&E stained tissues were evaluated for esophageal lesions. CD45‐positive immune cells were isolated from the spleens of mice with EoE or naïve controls then co‐cultured with the murine‐derived esophageal cell line AKR. After 24‐72 hours of co‐culture, live/dead dye was used to assess AKR viability.Results10/10 mice treated with 4NQO alone developed ESCC as expected in this robust tumor model. In mice co‐treated with MC903/OVA and 4NQO, ESCC was detected in 4/5 mice with a significant decrease in tumor load as compared to mice treated with 4NQO alone (Fig 1B, C). 6/6 mice treated with MC903/OVA alone and 4/4 mice treated with propylene glycol (vehicle for 4NQO) failed to display tumors (Fig 1C). We further evaluated esophageal epithelium of 4NQO‐treated animals to characterize distribution of ESCC lesions. While squamous dysplasia (pre‐malignant), early ESCC and late ESCC were present in all tumor‐bearing animals; there was a decrease in early ESCC and a lack of late ESCC lesions in 4NQO‐treated mice that were exposed to MC903/OVA‐induced EoE (Fig 1D). Moreover, the total percentage of esophageal epithelium occupied by neoplastic lesions was significantly diminished in mice co‐treated with 4NQO and MC903/OVA (Fig 1E). To investigate how EoE limits esophageal carcinogenesis, we exposed AKR esophageal tumor cells to CD45‐positive cells isolated from spleens of strain‐matched donor mice with or without EoE (Fig 2A). We found a robust induction of cell death in tumor cells exposed to immune cells from EoE donor mice compared to those exposed to immune cells from vehicle‐treated controls at 48 hours (n=3, p<0.05) (Fig 2B, C).ConclusionsThese data indicate that exposure to EoE activates an anti‐tumoral immune response that limits esophageal carcinogenesis. These studies have the potential for significant implications related to the clinical care of patients affected by EoE and ESCC.

Repeat endoscopic submucosal dissection as salvage treatment for local recurrence of esophageal squamous cell carcinoma after initial endoscopic submucosal dissection

Local recurrence of esophageal squamous cell carcinoma (ESCC) after endoscopic resection does not have an established treatment. The efficacy and safety of repeat endoscopic submucosal dissection (ESD) for recurrent ESCC were determined in the study. Forty-three consecutive patients with 45 locally recurrent superficial ESCC lesions undergoing repeat ESD and 909 first ESD lesions for propensity score matching (PSM) at Zhongshan Hospital between January 2011 and January 2020 were retrospectively enrolled. After PSM (1:2), operation-related parameters were compared between repeat ESD and first ESD. In the repeat ESD group, the Kaplan-Meier method and log-rank tests were used for identification of risk factors for local recurrence after repeat ESD. As compared with propensity score-matched first ESD, rates of complete resection (86.7% vs 97.8%, P= .02) and curative resection (86.7% vs 96.7%, P= .06) were lower and procedure duration (54.8 ± 21.7 minutes vs 46.2 ± 20.6 minutes, P= .67) and hospital stay (4.3 ± 1.8 days vs 2.9 ± 1.4 days, P= .25) were longer in the repeat ESD group. The en-bloc resection rate (93.3% vs 98.8%, P > .11) remained comparable. Adverse events including bleeding (4.4% vs 0%, P= .11), perforation (.0% vs .0%, P > .99), and stricture (6.7% vs 2.2%, P= .33) presented with no difference. The 5-year overall survival rate and recurrence-free survival rate for repeat ESD was 100% and 86.0%, respectively. Multiplicity was significantly associated with recurrence after repeat ESD (P= .01). Repeat esophageal ESD showed favorable short- and long-term outcomes and thus provides an alternative choice for recurrent superficial ESCC.

Risk factors for esophageal squamous cell carcinoma and its histological precursor lesions in China: a multicenter cross-sectional study

BackgroundDespite research efforts, the causative factors that contribute to esophageal squamous cell carcinoma (ESCC) in high-risk areas have not yet been understood. In this study, we, therefore, aimed to describe the risk factors associated with ESCC and its precursor lesions.MethodsWe performed an endoscopic examination of 44,857 individuals aged 40–69 years from five high incidence regions of China in 2017–2018. Participants were classified as 4 groups of normal control, esophagitis, low-grade intraepithelial neoplasia (LGIN) and high-grade intraepithelial neoplasia/esophageal squamous cell carcinoma (HGIN/ESCC) using an unconditional logistic regression determine risk factors.ResultsWe identified 4890 esophagitis, 1874 LGIN and 437 HGIN/ESCC cases. Crude odds ratios (ORs) and adjusted odds ratios were calculated using unconditional logistic regression. Drinking well and surface water, salty diet, and positive family history of cancer were the common risk factors for esophagitis, LGIN and HGIN/ESCC. History of chronic hepatitis/cirrhosis was the greatest risk factor of esophagitis (adjusted OR 2.96, 95%CI 2.52–3.47) and HGIN/ESCC (adjusted OR 1.91, 95%CI 1.03–3.22). Pesticide exposure (adjusted OR 1.20, 95%CI 1.05–1.37) was essential risk factor of LGIN.ConclusionsAmong individuals aged 40–69 years in high incidence regions of upper gastrointestinal cancer, the results provided important epidemiological evidence for the prevention of different precancerous lesions of ESCC.

Endoscopic Features of Superficial Esophageal Squamous Cell Carcinoma in Patients with Very Low Risk Factors (Female, Nondrinking, and Nonsmoking): A Case-Control Study

Background: Although esophageal squamous cell carcinoma (ESCC) is more likely to develop in patients with any risk factor (male, drinking, or smoking), it is sometimes detected in patients with very low risk factors (female, nondrinking, and nonsmoking). We examined the endoscopic features of superficial ESCC in patients with very low risk factors. Methods: In this single-center case-control study, 666 patients with 666 superficial ESCC lesions were divided into 2 groups: those with very low risk factors (very low-risk group, n = 34) and those with any risk factors (any-risk group, n = 632). After case-control selection at a 1:5 ratio, the very low-risk group comprised 34 patients and the any-risk group comprised 170 patients. We compared the baseline characteristics, endoscopic findings, and treatment results (including pathological diagnosis) between the 2 groups. Results: There were no statistically significant differences between the 2 groups in age, tumor size, tumor location, tumor morphology, or treatment results (including tumor depth and lymphovascular invasion). A longitudinal lesion with an attachment of white keratinized epithelium was more likely to be detected in the very low-risk group than the any-risk group (61.8 vs. 17.6%, respectively; p < 0.001). Conclusions: ESCC in patients with very low risk factors is rare but can be encountered in daily practice. A longitudinal lesion with an attachment of white keratinized epithelium is its main characteristic, which is slightly different from that of patients with any risk factors.

Use of a convolutional neural network for classifying microvessels of superficial esophageal squamous cell carcinomas.

The morphological diagnosis of microvessels on the surface of superficial esophageal squamous cell carcinomas using magnifying endoscopy with narrow-band imaging is widely used in clinical practice. Nevertheless, inconsistency, even among experts, remains a problem. We constructed a convolutional neural network-based computer-aided diagnosis system to classify the microvessels of superficial esophageal squamous cell carcinomas and evaluated its diagnostic performance. In this retrospective study, a cropped magnifying endoscopy with narrow-band images from superficial esophageal squamous cell carcinoma lesions was used as the dataset. All images were assessed by three experts, and classified into three classes, Type B1, B2, and B3, based on the Japan Esophagus Society classification. The dataset was divided into training and validation datasets. A convolutional neural network model (ResNeXt-101) was trained and tuned with the training dataset. To evaluate diagnostic accuracy, the validation dataset was assessed by the computer-aided diagnosis system and eight endoscopists. In total, 1777 and 747 cropped images (total, 393 lesions) were included in the training and validation datasets, respectively. The diagnosis system took 20.3s to evaluate the 747 images in the validation dataset. The microvessel classification accuracy of the computer-aided diagnosis system was 84.2%, which was higher than the average of the eight endoscopists (77.8%, P<0.001). The area under the receiver operating characteristic curves for diagnosing Type B1, B2, and B3 vessels were 0.969, 0.948, and 0.973, respectively. The computer-aided diagnosis system showed remarkable performance in the classification of microvessels on superficial esophageal squamous cell carcinomas.

Long-term outcomes of endoscopic versus surgical resection for MM-SM1 esophageal squamous cell carcinoma using propensity score analysis.

Esophageal squamous cell carcinoma (ESCC) confined to the muscularis mucosae (MM) or up to 200µm of the submucosa (SM1) confers the risk for lymph node metastasis, and is defined as relative indication for endoscopic submucosal dissection (ESD) by the Japan Esophageal Society guidelines. Although additional surgical treatment after ESD is recommended, long-term outcomes of ESD compared with those of surgery have not been clarified. This study aimed to evaluate the long-term outcomes of ESD and surgery for cN0M0 relative indication lesions of ESCC. Between 2006 and 2016, patients with relative indication lesions of ESCC who underwent ESD or surgery at nine participating hospitals were examined retrospectively. Using propensity score matching, we evaluated survival curves for and hazard ratios associated with endoscopic submucosal dissection and surgery. In total, 155 lesions in the ESD group and 106 lesions in the surgery group met the pathological criteria of relative indication for endoscopic resection. After matching, 50 matched pairs of patients who underwent ESD or surgery were selected. The 5-year overall survival rates were 84.5% [95% confidence interval (CI) 68-93] in the ESD group and 79% [95% CI 60-90] in the surgery group. The hazard ratio of mortality for ESD compared with that for surgery estimated by Cox regression analysis was 0.79 (95% CI 0.3-2.06, p = 0.63). Compared with surgery, ESD does not compromise long-term outcomes. ESD alone or ESD with chemotherapy and/or radiotherapy may be an option for the treatment of MM and SM1 ESCC.

Effect of horizontal margin status and risk of local recurrence after endoscopic submucosal dissection for superficial esophageal cancer.

Background and AimEndoscopic submucosal dissection (ESD) sometimes results in en bloc resection with a positive or inconclusive horizontal margin (HM1 or HMX, respectively) on histological evaluation. The specific risk for such situations is unclear. We therefore investigated the outcome of ESD with HM1 or HMX.MethodsThis single‐center retrospective study was performed at Osaka International Cancer Institute. A total of 886 esophageal squamous cell carcinoma lesions in 749 patients treated from April 2005 to June 2015 were evaluated according to the following inclusion criteria: en bloc resection with no residual lesion, HM1 or HMX status, no prior treatment, and no additional treatment. We classified HM1 and HMX into type A, in which cancer was exposed on the HM, and type B, in which the HM status was unclear because of mechanical or thermal damage. We further classified type B according to the distance between the cancer and the edge of the specimen: type B1, <1 mm and type B2, ≥1 mm.ResultsThe resection margin was judged as HM1 or HMX in 5.0% (39/767; 95% confidence interval, 3.5–6.6%) of the en bloc resected specimens. Of 39 lesions, 30 fulfilled the inclusion criteria. Local recurrence developed in 8 of 30 lesions (26.7%). The local recurrence rates for types A, B1, and B2 were 40% (6/15 lesions), 28.5% (2/7 lesions), and 0.0% (0/8 lesions), respectively.ConclusionsAlthough a statistical analysis was not conducted because of the limited events, the pathological HM status may be a useful predictor of local recurrence.

Metformin suppresses the esophageal carcinogenesis in rats treated with NMBzA through inhibiting AMPK/mTOR signaling pathway.

Metformin is a widely used antidiabetic drug for the management of type 2 diabetes mellitus. Recently, epidemiological studies demonstrate that metformin has anticancer effects on esophageal squamous cell carcinoma (ESCC) and other cancers. However, the effects and potential mechanisms of metformin on ESCC remain elusive. In this study, we used N-nitroso-N-methylbenzylamine (NMBzA), a special carcinogen for esophagi, to develop a rat ESCC model, in which the carcinogenesis progression of ESCC in rat was induced and promoted. We investigated the effects of metformin on carcinogenesis of ESCC in this model. Our results revealed that metformin significantly decreased the incidence and precancerous lesions of ESCC and inhibited proliferation and promoted apoptosis of esophageal epithelial cells in rat treated with NMBzA. Moreover, metformin also increased apoptosis and inhibited migration, colony formation and tumor sphere formation of human ESCC cells in vitro. Immunohistochemistry and western blotting showed that without interfering the metabolism of NMBzA, metformin inhibited the inflammation of esophagi via reducing the expressions of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) and interleukin-6 (IL-6). Treatment of metformin led to activation of AMP-activated protein kinase (AMPK) and attenuated signaling of the downstream molecules such as p-mTOR, p-p70S6K and cyclin D1 expression both in vivo and in vitro. Taken together, our study demonstrated that metformin suppressed the carcinogenesis of ESCC through inhibiting AMPK/mammalian target of the rapamycin (mTOR) signaling pathway, resulting in its chemopreventive effects on the carcinogenesis of ESCC.

Risk factors for intraoperative perforation during endoscopic submucosal dissection of superficial esophageal squamous cell carcinoma.

AIMTo identify the risk factors and clarify the subsequent clinical courses.METHODSThis study retrospectively analyzed consecutive patients with esophageal squamous cell carcinoma (ESCC) treated using endoscopic submucosal dissection (ESD) between April 2008 and October 2012. We divided the ESCC lesions into perforation cases and non-perforation cases, and compared characteristics and endoscopic findings between the two groups. "Intraoperative perforation" was defined as the detection of a perforation site during ESD and the presence of mediastinal emphysema.RESULTSIn total, 147 patients with 156 ESCC lesions were treated by ESD. Intraoperative perforation was recorded for nine lesions (5.8%) from nine patients. Multivariate analysis identified mucosal deficiency larger than 75% of the circumference of the esophagus as an independent risk factor for intraoperative perforation (OR = 7.37, 95%CI: 1.45-37.4, P = 0.016). The predominant site of perforation was the left wall [6/9 (67%)]. Six of nine perforation sites were successfully closed by clips during the procedures. Two of nine cases required drainage for pleural effusions; however, all nine cases recovered with conservative treatment and without surgical intervention. At the median follow up of 42 mo after ESD, no cases of local recurrence or distant organ metastasis had been observed.CONCLUSIONThis study suggests that mucosal deficiency larger than 75% of the luminal circumference is a risk factor for intraoperative perforation during ESD for ESCC.

Increased expression of high-mobility group A2: A novel independent indicator of poor prognosis in patients with esophageal squamous cell carcinoma.

Although high-mobility group A2 (HMGA2) protein has been reported to participate in cancer progression and metastasis, its clinical relationship with tumor invasion, lymph node metastasis, and prognosis in esophageal squamous cell carcinoma (ESCC) remains unclear. The purpose of this study is to analyze the clinical and prognostic significance of HMGA2 in ESCC patients after curative resection. The expression of HMGA2 protein was evaluated by using immunohistochemistry in a tissue microarray (TMA) containing ESCC lesions and adjacent normal esophageal epithelial tissues from 96 patients who had undergone curative resection. TMA was constructed by Shanghai Biochip Co. Ltd., Shanghai, China. The relationship between HMGA2 expression and clinicopathological parameters and prognosis was further analyzed. HMGA2 expression was significantly higher in ESCC tissues compared with that of the adjacent noncancerous tissues (P < 0.001). High expression of HMGA2 was significantly related to tumor size, lymph node metastasis, and advanced tumor-node-metastasis stage (P < 0.05). Patients with low expression of HMGA2 had a better prognosis than those with high expression (χ2 = 5.069, P = 0.024). Univariate analysis showed that age (P = 0.041), depth of tumor invasion (P = 0.031), lymph node status (P = 0.001), and HMGA2 expression (P = 0.024) were correlated with prognosis. Multivariate analysis showed that HMGA2 expression (hazard ratio [HR]: 0.539; 95% confidence interval [95% CI]: 0.302-0.963, P = 0.037) and lymph node metastasis (HR: 0.504; 95% CI: 0.310-0.820, P = 0.006) were independent prognostic factors for overall survival. High HMGA2 expression was related to lymph node metastasis and poor prognosis in ESCC. Our results indicated that HMGA2 could act as a potential biomarker for prognosis evaluation of ESCC patients.

Human leukocyte antigen G is associated with esophageal squamous cell carcinoma progression and poor prognosis

Human leukocyte antigen G (HLA-G) is a non-classical HLA class I molecule thought to play a key role in maternal-fetal tolerance and cancer immune evasion. This study aimed to investigate the HLA-G expression in lesion sections and plasma sHLA-G levels of primary esophageal squamous cell carcinoma (ESCC) patients and its clinical significance in diagnosis and prognosis of ESCC. 60 ESCC patients and 28 healthy controls were recruited, and the positive expression of HLA-G in ESCC lesions and adjacent normal tissues were 70% (42/60) and 8.6% (5/60) (P<0.05), respectively, while no expression was found in normal controls. HLA-G1 and HLA-G5 were determined to be dominating isoforms measured by RT-PCR. There was a significant difference in plasma sHLA-G levels between patients with ESCC (15.04U/ml, range 4.33–250.00U/ml) and healthy controls (6.81U/ml, range 0–29.27U/ml) (P<0.01). The plasma IL-10 level was higher in ESCC patients than the controls (23.86pg/ml vs. 12.81pg/ml, P<0.01). HLA-G expression in lesion tissues was correlated with cancer cell differentiation (P=0.033), lymph node metastasis (P=0.035) of ESCC. However, no obvious correlations were demonstrated between the plasma sHLA-G levels and the clinicopathological parameters. There was a significant correlation between sHLA-G and IL-10 expression (r=0.353, P=0.006) in patients with Esophageal squamous cell carcinoma. HLA-G positive expression showed poorer prognosis of ESCC. HLA-G positive expression might serve as a potential marker in the diagnosis or prediction of ESCC.

A Case of Esophageal Squamous Cell Cancer in an Endoscopically Normal Esophagus

Esophageal squamous cell carcinoma (ESCC) has traditionally been detected in the later stages of disease which requires aggressive treatment. Newer endoscopic methods have allowed gastroenterologists to detect ESCC lesions and start treatment earlier with the hope to avoid more difficult treatments such as esophagectomy, chemotherapy and radiation. This report follows a patient from detection of ESCC through successful treatment of the ESCC lesions . J Med Cases. 2014;5(4):224-226 doi: http://dx.doi.org/ 10.14740 /jmc1724w

A Case of Esophageal Squamous Cell Cancer in an Endoscopically Normal Esophagus

Esophageal squamous cell carcinoma (ESCC) has traditionally been detected in the later stages of disease which requires aggressive treatment. Newer endoscopic methods have allowed gastroenterologists to detect ESCC lesions and start treatment earlier with the hope to avoid more difficult treatments such as esophagectomy, chemotherapy and radiation. This report follows a patient from detection of ESCC through successful treatment of the ESCC lesions . J Med Cases. 2014;5(4):224-226 doi: http://dx.doi.org/ 10.14740 /jmc1724w