Early-stage Esophageal Cancer Research Articles

Combined detection of IL-6 and IL-8 is beneficial to the diagnosis of early stage esophageal squamous cell cancer: a preliminary study based on the screening of serum markers using protein chips.

BackgroundThe diagnosis rate of early stage esophageal squamous cell carcinoma (ESCC) is low due to the lack of specific tumor markers. Seeking for these markers is beneficial to improve the early diagnosis rate and the prognosis of patients. This study profiles the differentially expressed proteins of early stage ESCC patients via the AAH-BLG-507 protein chip, which further consolidates the clinical evidence of ESCC diagnosis.Materials and methodsIn this study, 20 serum samples were collected from Taihe Hospital between August 2016 and June 2017. Ten of them carried ESCC, while the rest were healthy controls. To profile the proteins’ expression level, the AAH-BLG-507 protein chip was used, and both highly expressed and lowly expressed proteins were fished out. Meanwhile, their biological roles were examined by using Gene Ontology (GO) database and String database, and they were further verified by ELISA.ResultsResults showed that the expression levels of AXL, ARTN, Ang2, BDNF, BMP7, cripto-1, CCL28, E-selectin, IL-6, IL-8 and SHH in the serum of early ESCC were significantly upregulated (P<0.05), particularly IL-6 and IL-8. The expression levels of TSP1 and MMP-8 were markedly downregulated (P<0.05). Analysis showed that these proteins were mainly involved in angiogenesis, signal transduction, cell proliferation and migration, indicating the close relationship with the development of ESCC.ConclusionIt suggested that IL-6 and IL-8 proteins could be considered as the markers for ESCC diagnosis.

RA09.07: SURGICAL MANAGEMENT OF EARLY ESOPHAGEAL CANCER BASED ON LYMPH NODE METASTASIS RISK.

Abstract Background Esophagectomy and lymph node dissection is still the main treatment for esophageal cancer. Endoscopic mucosal resection and submucosal dissection are increasingly becoming a treatment of choice to preserve the integrity of the esophagus and decrease the surgical trauma in early esophageal cancer. However, lymph node metastasos (LNM) risk is still a debate focus for the decision of treatment selection. Our objective was to evaluate the prevalence, pattern and risk factors of LNM in early stage esophageal cancer to improve surgical treatment allocation. Methods We identified patients with pathological T1 stage esophageal cancer who underwent esophagectomy and lymph node dissection. The pattern of LNM was analyzed and the risk factors related to LNM were assessed by univariate and multivariable logistic regression analysis.The nomogram model was used to estimate the individual risk of lymph node metastasis. Results In 143 patients, LNM rates were: all patients 17.5%, T1a 8.0%, and T1b 22.5% for T1b. Depth of tumor infiltration (P &lt; 0.05), tumor size (P &lt; 0.01), tumor location (P &lt; 0.05), and tumor differentiation (P &lt; 0.01) were independent risk factors related to LNM. These four parameters allowed the compilation of a nomogram to estimate the individual risk of LNM. Fig. Nomogram to estimate the individual risk of LNM. Each characteristic of the included parameters scores a specific number of points (points per parameter). The summarized total points score indicates the probability of LNM. For a middle esophageal cancer with middle differentiated (G2), 3 cm tumor (&gt; 2.5cm) that invades the submucosa (pT1b), the calculated total scores is 129.5 = 87.5 + 21 + 0 + 21, hence the corresponding LNM risk is 20%. Conclusion T1 esophageal cancer has a relatively high LNM rate, and the depth of tumor infiltration, tumor size, tumor location and tumor differentiation are correlated with LNM. Nomograms that include factors can be used to predict individual LNM risk. The LNM risk and extent must be considered comprehensively in decision-making of a better surgical treatment and lymph node dissection strategy. Disclosure All authors have declared no conflicts of interest.

RA04.06: ESOPHAGECTOMY IN PATIENTS WITH EARLY STAGE ESOPHAGEAL CANCER AFTER NON-CURATIVE ENDOSCOPIC SUBMUCOSAL DISSECTION

Abstract Background Early stage esophageal cancer has a low risk of lymph node metastasis. Therefore, an organ preserving endoscopic submucosal resection for tumors staged uT1 N0 has already been established. In case of non-curative dissection according to oncologic criteria esophagectomy has to be performed to achieve an oncologic resection. Methods Between 2010 and 2016 42 patients with early stage esophageal cancer underwent endoscopic submucosal dissections (ESD). We retrospectively evaluated the operative and pathologic outcome as well as disease free and overall survival in patients, who were operated on with esophagectomy because of non-curative endoscopic resection. Results 5 of 42 (11.9%) had to be operated on: 3 patients with open abdominothoracal resektion with intrathoracal anastomosis, 1 patient with an open approach and a cervical anastomosis and 1 patient with an laparoscopic/thoracoscopic approach but open intrathoracic anastomosis. Reasons for ongoing resection were three times R1 endoscopic resection, one L1 infiltration and one sm1-infiltration in a squamous cell carcinoma. There was no perioperative mortality. One anastomotic leakage was treated interventionally, one thoracic surgical site infection conservatively. One anastomotic leakage had to be resected, put on a saliva fistula and reconstructed with a colonic interponate. No recurrence of cancer is observed so far. Conclusion Esophagectomy after non-curative ESD shows no evidence for a worse oncologic outcome. There is no higher peri- and postoperative risk. This legitimates our step-up approach. Disclosure All authors have declared no conflicts of interest.

Endoscopic Treatment of Early-Stage Esophageal Cancer.

Esophageal cancer is a leading cause of global cancer-related mortality. Here, we discuss the major endoscopic treatment modalities for management of early esophageal cancer (EEC). Advances in endoscopic imaging and therapy have shifted the paradigm of managing early esophageal cancers. Though esophagectomy remains the preferred management for advanced cancers, guidelines now recommend endoscopic resection followed by ablative therapy for early (Tis and T1a) cancers. Available data suggests endoscopic treatment is comparable to surgery with regard to overall and cancer-specific survival with lower procedural morbidity and mortality. Endoscopic modalities are emerging as frontline treatment options for patients with early esophageal cancers. Accurate clinical staging with assessment of disease extent, tumor grade, and risk of nodal metastases is crucial when determining eligibility for endoscopic management of EEC. High-quality routine surveillance endoscopy is critical in patients who have undergone resection and/or ablation.

Abstract 3168: Serglycin promotes migration and invasion of esophageal cancer cells

Abstract Esophageal cancer is the eighth most common cancer in the world and it ranks sixth in mortality rate among cancer diseases. While patients with early stage esophageal cancer without metastasis have a better chance of being cured by surgery, most patients present with locally advanced or metastatic disease. Unfortunately, some common cancer biomarkers such as carcinoembryonic antigen (CEA) and CA19-9 have low sensitivity and specificity in esophageal cancer. A better understanding of the molecular mechanisms underlying esophageal cancer progression is needed to identify novel diagnostic markers and therapeutic targets for intervention. We previously identified serglycin (SRGN) as the top upregulated gene in a highly invasive esophageal squamous cell carcinoma (ESCC) cell subline. Serglycin is a proteoglycan with a core protein and glycosaminoglycan (GAG) chains. Its significance in tumorigenesis is not well understood. The GAG chains have the ability of binding specific growth factors and ligands, which may play an important role in facilitating cancer cell migration and invasion. Immunohistochemical analysis showed that serglycin expression was higher in ESCC compared with normal esophageal epithelium, and in lymph node metastases compared with primary ESCC. Ectopic overexpression of serglycin in ESCC cells enhanced their migration and invasion potential in vitro. Knockdown of serglycin reduced ESCC cell migration and invasion. In invasion chamber assays, conditioned medium (CM) from SRGN-overexpressing ESCC cells stimulated the migration and invasion ability of less invasive ESCC cells. Conditioned medium from ESCC cells expressing serglycin that lacks the GAG attachment site had no such effects. Chemokine antibody array analysis showed that midkine (MDK), a heparin-binding growth factor, was the top upregulated protein in the CM of SRGN-overexpressing cells. Analysis of TCGA and GTEx datasets showed that MDK expression was higher in many cancer types such as breast cancer, colon adenocarcinoma, glioblastoma and lung cancer, than in corresponding normal tissues. Western blot analysis showed that forced expression of serglycin, but not serglycin without the GAG binding domain, led to increase of MDK in the CM of multiple ESCC cell lines. Forced expression of serglycin also increased the expression level of phosphorylated extracellular signal-regulated kinase (p-ERK) in ESCC cells. Taken together, serglycin may play an important role in the progression ESCC by promoting migration and invasion of cancer cells. These effects may be mediated through activation of the ERK signaling pathway. Whether MDK is involved in this regulatory mechanism warrants further investigation. [This study was supported by Research Grants Council of the Hong Kong SAR, China, GRF Project No. 17111016] Citation Format: Yun ZHU, Bin Li, Wenwen Xu, Aky Lam, Simon Law, ALM Cheung. Serglycin promotes migration and invasion of esophageal cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3168.

Quantifying esophageal motion during free-breathing and breath-hold using fiducial markers in patients with early-stage esophageal cancer

IntroductionCardiac toxicity after definitive chemoradiotherapy for esophageal cancer is a critical issue. To reduce irradiation doses to organs at risk, individual internal margins need to be identified and minimized. The purpose of this study was to quantify esophageal motion using fiducial makers based on four-dimensional computed tomography, and to evaluate the inter-CBCT session marker displacement using breath-hold.Materials and methodsSixteen patients with early stage esophageal cancer, who received endoscopy-guided metallic marker placement for treatment planning, were included; there were 35 markers in total, with 9, 15, and 11 markers in the upper thoracic, middle thoracic, and lower thoracic/esophagogastric junction regions, respectively. We defined fiducial marker motion as motion of the centroidal point of the markers. Respiratory esophageal motion during free-breathing was defined as the amplitude of individual marker motion between the consecutive breathing and end-expiration phases, derived from four-dimensional computed tomography. The inter-CBCT session marker displacement using breath-hold was defined as the amplitudes of marker motion between the first and each cone beam computed tomography image. Marker motion was analyzed in the three regions (upper thoracic, middle thoracic, and lower thoracic/esophagogastric junction) and in three orthogonal directions (right-left; anterior-posterior; and superior-inferior).ResultsRespiratory esophageal motion during free-breathing resulted in median absolute maximum amplitudes (interquartile range), in right-left, anterior-posterior, and superior-inferior directions, of 1.7 (1.4) mm, 2.0 (1.5) mm, and 3.6 (4.1) mm, respectively, in the upper thoracic region, 0.8 (1.1) mm, 1.4 (1.2) mm, and 4.8 (3.6) mm, respectively, in the middle thoracic region, and 1.8 (0.8) mm, 1.9 (2.0) mm, and 8.0 (4.5) mm, respectively, in the lower thoracic/esophagogastric region. The inter-CBCT session marker displacement using breath-hold resulted in median absolute maximum amplitudes (interquartile range), in right-left, anterior–posterior, and superior-inferior directions, of 1.3 (1.0) mm, 1.1 (0.7) mm, and 3.3 (1.8) mm, respectively, in the upper thoracic region, 0.7 (0.7) mm, 1.1 (0.4) mm, and 3.4 (1.4) mm, respectively, in the middle thoracic region, and 2.0 (0.8) mm, 2.6 (2.2) mm, and 3.5 (1.8) mm, respectively, in the lower thoracic/esophagogastric region.ConclusionsDuring free-breathing, esophageal motion in the superior-inferior direction in all sites was large, compared to the other directions, and amplitudes showed substantial inter-individual variability. The breath-hold technique is feasible for minimizing esophageal displacement during radiotherapy in patients with esophageal cancer.

Esophagectomy after endoscopic submucosal dissection for esophageal carcinoma.

Endoscopic submucosal dissection (ESD) has been used to treat early stage esophageal cancer, but reports about additional esophagectomy after ESD and postoperative outcomes are lacking. Complete removal of cancer tissue together with lymph nodes was the advantage of esophagectomy; however, invasiveness, organ loss, postoperative complications, and worse postoperative quality of life were serious disadvantages. The purpose of this study was to find the clear indication of additional esophagectomy after ESD, and help the other patients avoid excessive surgery. We reviewed the clinicopathologic data and outcomes consecutive patients who had esophageal cancer confirmed by endoscopic biopsy and who were treated with ESD and subsequent esophagectomy between October 2011 and December 2016 in our department. The esophagectomy necessity following ESD was defined and the groups with necessity (+) vs. (-) were compared retrospectively. The esophagectomy necessity outcomes were retrospectively analyzed to judge whether the surgery option was correct. Total 214 patients with esophageal and esophagogastric cancer have undergone ESD treatment in our center, of which 32 patients (23 men and 9 women; mean age, 60±8 years) ultimately required esophagectomy after ESD. All patients had complete resection (R0) from esophagectomy. Postoperative TNM staging included TisN0M0 (6 patients), T1aN0M0 (6 patients), T1bN0M0 (18 patients), T1bN1M0 (1 patient), and T2N3M0 (1 patient). Necessity of esophagectomy after ESD was associated with residual margin status. There was a significant difference in ESD specimen margin status between the esophagectomy necessity (+) vs. (-) groups (positive/negative margin: 8/3 vs. 2/9 patients; P=0.03). Esophagectomy should be delayed at least 30 days after ESD to enable resolution of esophageal edema (P=0.017) (206±68 vs. 163±56 mL, P=0.057). Median follow-up was 16.8 months (range, 11.2-54.5 months); 3 patients were lost to follow-up (9%) and 1 patient died of metastasis after esophagectomy. All other patients were alive with excellent postoperative disease-free survival. Indications for esophagectomy after ESD include ESD failure, cancer recurrence, esophageal rupture, esophageal stricture refractory to endoscopic dilation, and residual tumor at the ESD specimen margin. Stage T1b alone is not an indication for esophagectomy. According to our study, we recommend that esophagectomy should be delayed ≥30 dafter ESD unless urgent esophagectomy is indicated.

Can the depth of invasion of early esophageal cancer be predicted based on endoscopic evidence?

Esophageal cancer is one of the leading causes of cancer-related death worldwide. Its poor prognosis is related to an often late diagnosis. An earlier diagnosis and treatment however, is related to a better outcome. Early stage esophageal cancer can be diagnosed and treated endoscopically with minimally invasive techniques, which is associated with lower mortality and morbidity than surgery. Whether esophageal carcinoma can be treated endoscopically depends mainly on the risk of lymph node metastasis, which itself correlates to the invasion depth of the tumor. The question is whether endoscopy can accurately determine the invasion depth and thus the treatment modality. Articles used for this review were identified by searches of PubMed and references of relevant articles. Lesion morphology has some predictive value for the depth of invasion for squamous cell carcinoma (SCC) and esophageal adenocarcinoma (EAC). An intramucosal cancer generally has a flat appearance (Paris 0-IIa, 0-IIb,). By contrast, a submucosally invasive cancer often has an excavated (0-IIc, 0-III) and sometimes a polypoid morphology (0-I). In SCC, classification of surface vessels and intrapapillary capillary loops (IPCLs) allows accurate assessment of invasion depth. Generally, mucosal lesions are an indication for endoscopic treatment. However recent studies have shown that tumors with submucosal infiltration and low risk profile for metastasis can also be treated safely by endoscopic resection. Endoscopic assessment allows a rather accurate estimation of invasion depth of early esophageal cancer. To determine the final treatment modality however the final histological staging obtained by endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD) is crucial.

Contrast-enhanced computed tomography combined with Chitosan-Fe3O4 nanoparticles targeting fibroblast growth factor receptor and vascular endothelial growth factor receptor in the screening of early esophageal cancer.

Esophageal cancer is a malignant tumor with a relatively high invasiveness, metastatic potential and worldwide incidence among human cancers. The majority of patients with esophageal cancer are diagnosed in a late tumor stage due to a lack of advanced and sensitive protocols for the diagnosis of patients with early-stage esophageal cancer. In the current study, contrast-enhanced computerized tomography (CECT) combined with Chitosan-Fe3O4 nanoparticles targeting fibroblast growth factor receptor (FGFR) and vascular endothelial growth factor receptor (VEGFR; CECT-CNFV) were used to diagnose patients with suspected esophageal cancer. A Chitosan-Fe3O4-parceled bispecific antibody targeting FGFR and VEGFR was produced and its affinity to esophageal cancer cells was determined both in vitro and in vivo. A total of 320 patients with suspected esophageal cancer were voluntarily recruited to evaluate the efficacy of CECT-CNFV in the diagnosis of early-stage esophageal cancer. All participants were subjected to CT and CECT-CNFV to detect whether tumors were present in the esophageal area. A Chitosan-Fe3O4 nanoparticles contrast agent was orally administered at 20 min prior to CT and CECT-CNFV. The results demonstrated that CECT-CNFV improved diagnostic sensitivity and provided a novel protocol for the diagnosis of tumors in patients with suspected gastric cancer at an early-stage. Furthermore, the resolution ratio of images was enhanced by CECT-CNFV, which enabled the visualization of tiny tumor nodules in esophageal tissue. Clinical data demonstrated that CECT-CNFV diagnosed 200 patients with suspected early-stage esophageal cancer and 120 patients as tumor free. In addition, CECT-CNFV exhibited higher signal enhancement of tumor nodules than CT, suggesting a higher accuracy and accumulation of nanoparticle contrast agent within the tumor nodules of esophageal tissue. Notably, the survival rate of patients with esophageal cancer diagnosed at an early-stage by CECT-CNFV was higher than the mean five-year survival rate (P<0.01). In conclusion, CECT-CNFV enhanced the sensitivity and accuracy of CT in the diagnosis of early-stage esophageal cancer. Thus, CECT-CNFV may improve the accuracy of CT in the diagnosis of mural enhancement in patients with esophageal cancer.

Role of adjuvant chemoradiotherapy after endoscopic treatment of early-stage esophageal cancer: a systematic review.

Esophagectomy combined with lymphadenectomy is currently recommended for patients with high-risk early-stage esophageal cancer after endoscopic treatment (i.e. submucosal tumor invasion [sm2-3], presence of lymphovascular invasion and/or poor tumor differentiation) given the high risk of lymph node metastases. Unfortunately, some patients do not have the physiologic capability to endure surgery. For these patients chemoradiotherapy (CRT) following endoscopic treatment could be an alternative. The aim of this systematic review was to evaluate the evidence on the safety and efficacy of endoscopic treatment combined with CRT in patients with high-risk early-stage esophageal cancer. A systematic literature search was performed to identify studies reporting on the safety and efficacy of CRT following endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD) in patients with esophageal cancer invading the muscularis mucosae or submucosa. Primary outcomes were locoregional recurrence (LRR), disease-free survival (DFS) and overall survival (OS). The secondary outcome was the occurrence of treatment-related adverse events. Six studies were included, comprising a total of 168 patients with early-stage esophageal cancer that underwent endoscopic treatment followed by CRT. Most studies were retrospective case series and included small numbers of patients (11 to 66). All patients had T1a(m3) or T1b(sm1-3) esophageal squamous cell carcinoma. Adjuvant treatment consisted of cisplatin and 5-fluorouracil with concurrent radiotherapy; doses ranging from 40 to 60 Gy. The overall LRR rate ranged between 0-9%. Reported 3-year DFS and OS rates ranged between 69-100% and 87-100%, respectively. In all studies ESD and/or EMR was safely performed without serious complications. The observed CRT treatment-related toxicity (grade ≥3) ranged between 0% and 32%. This review demonstrates that the current available literature lacks large prospective adequately powered studies and does not allow any firm conclusion regarding the role of endoscopic treatment combined with adjuvant CRT for patients with high-risk early-stage esophageal cancer.

Early-stage esophageal squamous cell carcinoma treated with californium-252 neutron brachytherapy: clinical report on 16 cases.

Californium-252 (²⁵²Cf) neutron brachytherapy is a form of high linear energy transfer radiotherapy, which has proven effective when used in combination with external beam radiotherapy to treat intracavitary cancers of the cervix, colon/rectum and esophagus. No study has been reported for treatment of intracavitary cancers with neutron brachytherapy alone. The aim of the study was to observe and analyze the long-term curative effects and complications for early stage thoracic esophageal cancer patients treated with neutron brachytherapy alone. From December 2001 to August 2006, 16 patients of early stage squamous cell carcinoma underwent neutron brachytherapy. The total radiation dose to the reference point was 20-28 Gy-eq in 5 to 7 fractions with 4 Gy-eq/fraction. The 1-, 3-, and 5-year follow-up rates were 100%. The 2-, 3-, 4-, and 5-year survival rates were 100%, 87.5%, 87.5%, and 75%, respectively. The early complication rates for grades 1 and 2 radiation esophagitis were 75% and 25%, respectively. The late complication rates for grades 0 and 1 (according to the RTOG/EORTC standard) were 87.5% and 12.5%, respectively. Barium esophagography after treatments confirmed that the complete response rate was 100%. Fourteen patients were confirmed by endoscopy to have either normal mucosa or inflammation change. Neutron brachytherapy alone was an effective and safe treatment for early stage esophageal squamous cell cancer.

Post-operative radiotherapy is associated with improved survival in esophageal cancer with positive surgical margins.

The optimal treatment for early-stage esophageal cancer with positive surgical margins after an upfront esophagectomy is not well-defined. This study investigates the effect of post-operative radiotherapy (PORT) on overall survival (OS) in clinical stage I-II patients with positive margins. We identified patients diagnosed between 2004 and 2012 with clinical stage I-II esophageal carcinoma from the National Cancer Data Base (NCDB) who underwent an upfront esophagectomy. For those patients with positive margins, administration of PORT was recorded, and OS was compared by the Kaplan-Meier estimator and log-rank test. Multivariable Cox regression analysis was performed to identify variables associated with improved survival. Among the 3,490 patients identified, 209 (5.8%) had positive margins. One hundred forty-two (67.9%) patients did not receive PORT while 67 (32.1%) did receive PORT. Compared to those receiving PORT, patients who did not receive PORT were significantly older (68.5 vs. 64.0 years, P=0.003), more likely to have pN0 disease (50.7% vs. 35.4%, P=0.026), and less likely to receive postoperative chemotherapy (21.1% vs. 86.6%, P<0.001). On multivariable logistic regression, only receipt of chemotherapy predicted for receipt of PORT (OR: 25.6, 95% CI: 9.9-65.8, P<0.001). OS was significantly higher for patients receiving PORT compared to those who did not (median OS: 32.2 vs. 16.9 months, log-rank P=0.008). Multivariable analysis confirmed an association with PORT and improved OS (HR: 0.39, 95% CI: 0.27-0.60, P<0.001). Subset analysis demonstrated that the OS benefit of PORT persisted in those patients who received adjuvant chemotherapy (HR: 0.33, 95% CI: 0.19-0.57, P<0.001). PORT is associated with improved OS in clinical stage I-II esophageal cancer patients after an upfront esophagectomy with positive margins. In the absence of prospective randomized data, our findings suggest that PORT should be strongly considered in the setting of early-stage esophageal cancer resected with positive margins.

Endoscopic analysis of early esophageal cancer and precancerous lesions in Kazakh patients

To explore the value of endoscopic narrow-band imaging in the diagnosis of early-stage esophageal cancer and precancerous lesions in Kazakh patients. A total of 106 Kazakh patients with esophageal mucosa lesions diagnosed by routine endoscopy in our hospital from January 2014 to July 2016 were enrolled in this analysis with 30 randomly selected patients with normal endoscopic findings of the esophageal mucosa as the control group. The morphological changes of papillary capillary loop (IPCL) of the esophageal epithelium in the two groups were observed by narrow-band imaging magnifying endoscopy. Pathological examinations were performed for all the patients with esophageal mucosa lesions. In patients with esophageal mucosa lesions, 10 were diagnosed to have early esophageal cancer, 16 had low-grade tumors, 11 had high-grade tumors and 69 had esophagitis. IPCL typing results showed IPCL type I in all the control subjects, predominantly type IV in patients with early esophageal carcinoma, type II and III in patients with low-grade tumor, type III in patients with high-grade tumor, and type II in patients with esophagitis. The location and size of the esophageal lesions can be observed clearly by narrow-band imaging magnifying endoscopy. The histopathology of the esophageal mucosa can be analyzed with IPCL classification for diagnosis of early esophageal cancer and precancerous lesions in Kazakhs.

Endoscopic Treatment Versus Esophagectomy for Early-Stage Esophageal Cancer: a Population-Based Study Using Propensity Score Matching

BackgroundEndoscopic treatment (ET) is an alternative for selected patients with early-stage esophageal cancer. The primary aim of this study was to compare overall survival (OS) and esophageal cancer-specific survival (ECSS) of such patients after ET or esophagectomy. MethodsPropensity score matching (PSM) and Cox regression analysis were used to compare OS and ECSS of 2661 patients with ET or esophagectomy for early-stage (Tis–T1N0M0) disease. Patient information was retrieved from the Surveillance, Epidemiology, and End Results database. Subgroup analyses by T stage and tumor histology were also performed. ResultsThere were significant differences in age, sex ratio, year of diagnosis, cancer site, cancer stage, differentiation grade, tumor histology, tumor size, lymph nodes examined, and receipt of radiation therapy in the two treatment groups. PSM created 621 patient pairs. Multivariate analysis found no significant differences in OS (HR = 1.216, P = 0.279) or ECSS (HR = 0.692, P = 0.179) in the esophagectomy and ET groups. The results were similar for subgroup analyses limited to stage Tis, T1a, and T1b patients. ET was also associated with similar OS and ECSS in esophageal adenocarcinoma and squamous cell carcinoma patients. ConclusionIn this population-based study using PSM, patients with stage Tis and T1N0M0 esophageal cancer with ET had OS and ECSS comparable to those treated by esophagectomy after adjusting for clinical variables. The results support ET as an alternative to esophagectomy in early esophageal cancer.

Does delayed esophagectomy after endoscopic resection affect outcomes in patients with stage T1 esophageal cancer? A propensity score-based analysis.

Although endoscopic resection (ER) may be sufficient treatment for early-stage esophageal cancer, additional treatment is recommended when there is a high risk of cancer recurrence. It is unclear whether delaying esophagectomy by performing and assessing the success of ER affects outcomes as compared with immediate esophagectomy without ER. Additionally, long-term survival after sequential ER and esophagectomy required further investigation. Between 2011 and 2015, 48 patients with stage T1 esophageal cancer underwent esophagectomy after ER with curative intent at our institution. Two-to-one propensity score methods were used to identify 96 matched-control patients who were treated with esophagectomy only using baseline patient, tumor characteristics and surgical approach. Time from initial evaluation to esophagectomy, relapse-free survival, overall survival, and postoperative complications were compared between the propensity-matched groups. In the ER+esophagectomy group, the time from initial evaluation to esophagectomy was significantly longer than in the esophagectomy only group (114vs. 8days, p<0.001). The incidence of dense adhesion (p=0.347), operative time (p=0.867), postoperative surgical complications (p=0.966), and postoperative length of hospital stay (p=0.125) were not significantly different between the groups. Moreover, recurrence-free survival and overall survival were also similar between the two groups (p=0.411 and p=0.817, respectively). Treatment of stage T1 esophageal cancer with ER prior to esophagectomy did not increase the difficulty of performing esophagectomy or the incidence of postoperative complications and did not affect survival after esophagectomy. These results suggest that ER can be recommended for patients with stage T1 cancer even if esophagectomy is warranted eventually.

Medical expenditure for esophageal cancer in China: a 10-year multicenter retrospective survey (2002\u20132011)

BackgroundEsophageal cancer is associated with substantial disease burden in China, and data on the economic burden are fundamental for setting priorities in cancer interventions. The medical expenditure for the diagnosis and treatment of esophageal cancer in China has not been fully quantified. This study aimed to examine the medical expenditure of Chinese patients with esophageal cancer and the associated trends.MethodsFrom 2012 to 2014, a hospital-based multicenter retrospective survey was conducted in 37 hospitals in 13 provinces/municipalities across China as a part of the Cancer Screening Program of Urban China. For each esophageal cancer patient diagnosed between 2002 and 2011, clinical information and expense data were extracted by using structured questionnaires. All expense data were reported in Chinese Yuan (CNY; 1 CNY = 0.155 USD) based on the 2011 value and inflated using the year-specific health care consumer price index for China.ResultsA total of 14,967 esophageal cancer patients were included in the analysis. It was estimated that the overall average expenditure per patient was 38,666 CNY, and an average annual increase of 6.27% was observed from 2002 (25,111 CNY) to 2011 (46,124 CNY). The average expenditures were 34,460 CNY for stage I, 39,302 CNY for stage II, 40,353 CNY for stage III, and 37,432 CNY for stage IV diseases (P < 0.01). The expenditure also differed by the therapy type, which was 38,492 CNY for surgery, 27,933 CNY for radiotherapy, and 27,805 CNY for chemotherapy (P < 0.05). Drugs contributed to 45.02% of the overall expenditure.ConclusionsThese conservative estimates suggested that medical expenditures for esophageal cancer in China substantially increased in the last 10 years, treatment for early-stage esophageal cancer costs less than that for advanced cases, and spending on drugs continued to account for a considerable proportion of the overall expenditure.

Preoperative endoscopic titanium clip placement facilitates intraoperative localization of early-stage esophageal cancer or severe dysplasia

BackgroundAccurate intraoperative localization of esophageal lesions is essential for successful surgical resection. We tested whether preoperative endoscopic placement of titanium clips could facilitate intraoperative localization of early-stage esophageal cancer or severe dysplasia.MethodsA prospective randomized clinical trial was performed between May 2012 and July 2014. All enrolled patients received preoperative endoscopy and esophageal endoscopic ultrasound, as well as pathological study on the biopsy specimen, to confirm early stage esophageal cancer or severe dysplasia. One day before the surgical operation, patients in the experimental group received the preoperative endoscopic titanium labeling of esophageal lesions. Then, during the surgical operation, palpitation of titanium clips was used to localize the lesions in these patients. In patients in the control group, palpitation of nodules or esophageal wall mucosal thickening, together with the consideration of the results from preoperative endoscopic and ultrasound studies, was applied to estimate the location of the esophageal lesions. Study outcomes included the proportions of patients having successful intraoperative pre-resection lesion localization, post-esophagectomy lesion visualization, negative upper surgical margin, change of surgical approaches, and positive postoperative pathological diagnosis.ResultsA total of 27 patients were enrolled into the study, with 14 in the experimental group and 13 in the control group. Compared to the patients in the control group, a higher proportion of patients in the experimental group had statistically significant successful intraoperative esophageal lesion localization (100 versus 15.3% in the experimental versus control group).ConclusionsPreoperative endoscopic titanium clip placement could facilitate intraoperative localization of early-stage esophageal cancer or severe dysplasia.Trial registrationCurrent study was registered in Chinese Clinical Trial Registry and World Health Organization International Clinical Trials Registry Platform, ChiCTR-INR-17010949. Registered 22 March 2017, retrospectively registered.

Endoscopic submucosal dissection and endoscopic mucosal resection for early stage esophageal cancer

Endoscopic submucosal dissection and endoscopic mucosal resection for early stage esophageal cancer

Using the National Cancer Database to create a scoring system that identifies patients with early-stage esophageal cancer at risk for nodal metastases

ObjectivesEndoscopic resection is gaining popularity as a treatment for early-stage esophageal adenocarcinoma, particularly for T1a tumors. The goal of this study was to create a scoring system to reflect the risk of nodal metastases in early-stage esophageal adenocarcinoma to be used after endoscopic resection to better individualize treatment. MethodsThe National Cancer Database was queried for patients with T1a or T1b esophageal adenocarcinoma who underwent esophagectomy. We identified variables affecting nodal metastases using multivariable logistic regression, which we then used to create a scoring system. We stratified the model for T1a or T1b tumors, tested model discrimination, and validated the models by refitting in 1000 bootstrap samples. C-statistics greater than 0.7 were considered relevant. ResultsWe identified 1283 patients with T1a or T1b tumors; 146 had nodal metastases (11.4%). Tumor category (pT1a vs pT1b), grade, and size and the presence of angiolymphatic invasion significantly affected the risk of nodal metastases. We assigned points to each variable and added them to get a risk score. In patients with T1a tumors, less than 3% of patients with a risk score of 3 or less had nodal metastases, whereas 16.1% of patients with a risk score of 5 or greater had nodal metastases. In patients with T1b tumors, less than 5% of patients with a risk score of 2 or less had nodal metastases, whereas 41% of patients with a score of 6 or greater had nodal metastases (c-statistic = 0.805). ConclusionsThe proposed scoring system seems to be useful in discriminating risk of nodal metastases in patients with T1a or T1b esophageal adenocarcinoma and may be useful in directing patients who received endoscopic resection to esophagectomy or careful follow-up.

Successful video-assisted thoracoscopic surgery in prone position in patients with esophageal cancer and aberrant right subclavian artery: report of three cases

BackgroundAn aberrant right subclavian artery (ARSA) with an associated nonrecurrent right inferior laryngeal nerve (NRILN) is a relatively rare anomaly that occurs at a frequency of 0.3 to 2.0% of the general population. NRILN has been mainly documented in the head and neck region; it has been rarely described in patients with esophageal cancer, especially those undergoing thoracoscopic surgery. Video-assisted thoracoscopic surgery for esophageal cancer (VATS-E) is becoming more widespread as a reliable minimally invasive surgical procedure associated with reduced perioperative complications.Case presentationHerein, we report three cases of esophageal cancer with ARSA and NRILN which underwent successful VATS-E. Case 1, a 53-year-old male who had early stage esophageal cancer was performed VATS-E. Upper gastrointestinal (GI) series showed “Bayonet sign” (T1aN0M0, pStageIA in UICC). Case 2, a 75-year-old male who had advanced esophageal cancer was performed neoadjuvant chemotherapy and following VATS-E. This case had right thoracic duct and “Bayonet sign” on upper GI series (T1bN2M0, pStage IIIA in UICC). Case3, a 72-year-old male who had advanced esophageal cancer was performed neoadjuvant chemotherapy and following VATS-E (T3N2M0, pStageIIIB in UICC). All of these three cases were performed VATS-E and discharged without any complication.ConclusionVATS-E in the prone position is a feasible procedure that can reduce the risk of complications with an enlarged and clear view, and knowledge of this type of anomaly is very important for surgeons who perform esophagectomy.