Staging Of Esophageal Cancer Research Articles

Accuracy of clinical staging for T2N0 oesophageal cancer: systematic review and meta-analysis.

Oesophageal cancer is the sixth commonest cause of overall cancer mortality. Clinical staging utilizes multiple imaging modalities to guide treatment and prognostication. T2N0 oesophageal cancer is a treatment threshold for neoadjuvant therapy. Data on accuracy of current clinical staging tests for this disease subgroup are conflicting. We performed a meta-analysis of all primary studies comparing clinical staging accuracy using multiple imaging modalities (index test) to histopathological staging following oesophagectomy (reference standard) in T2N0 oesophageal cancer. Patients that underwent neoadjuvant therapy were excluded. Electronic databases (MEDLINE, Embase, Cochrane Library) were searched up to September 2019. The primary outcome was diagnostic accuracy of combined T&N clinical staging. Publication date, first recruitment date, number of centers, sample size and geographical location main histological subtype were evaluated as potential sources of heterogeneity. The search strategy identified 1,199 studies. Twenty studies containing 5,213 patients met the inclusion criteria. Combined T&N staging accuracy was 19% (95% CI, 15-24); T staging accuracy was 29% (95% CI, 24-35); percentage of patients with T downstaging was 41% (95% CI, 33-50); percentage of patients with T upstaging was 28% (95% CI, 24-32) and percentage of patients with N upstaging was 34% (95% CI, 30-39). Significant sources of heterogeneity included the number of centers, sample size and study region. T2N0 oesophageal cancer staging remains inaccurate. A significant proportion of patients were downstaged (could have received endotherapy) or upstaged (should have received neoadjuvant chemotherapy). These findings were largely unchanged over the past two decades highlighting an urgent need for more accurate staging tests for this subgroup of patients.

Staging esophageal cancer: low EUS accuracy in t2n0 patients.

Background and study aims Esophageal cancer (EC) is one of the most lethal malignancies worldwide. Staging of EC is performed with computed tomography (CT), positron-emission tomography (PET), and endoscopic ultrasonography (EUS). Patient management mostly depends on lymph node status. Compared to histopathology, the accuracy of EUS for T and N parameters is about 85 % and 75 %, respectively. Errors in staging may change prognosis. The aim of this study was to assess the role of EUS in T2-N0 EC considering the experience of two high-volume digestive endoscopic centers. Methods Two prospectively collected databases were queried to identify all patients with EC, staged as cT2N0 by EUS, with no distant metastases at CT/PET scan and who underwent transthoracic esophagectomy. Preoperative EUS staging (cTNM) was compared to histopathology of the surgical specimen (pTNM) to evaluate accuracy. Results Of 729 consecutive patients with EC between January 2011 and September 2018, 72 (49 men) had cT2N0 disease. CT and PET scans confirmed the absence of distant metastasis. In 43 of 72 patients (60 %), the evaluation was correct, 23 of 72 (31,7 %) were understaged, and six of 72 patients (8,3 %) were overstaged. Among the understaged patients, eight were understaged by tumor depth (35 %), seven by nodal involvement (30 %), and eight by both (35 %). All six patients who were overstaged had T1b-N0 disease. EUS accuracy was 77 % in staging for tumor depth and 82 % in staging for nodal metastases. The positive predictive value (PPV) for cT2N0 EC was 60 % (43 pT2N0 /72 cT2N). Conclusions The accuracy of EUS staging of T2N0 EC is low, with only 60 % of patients undergoing appropriate therapy based on histopathology.

Clinical TNM staging for esophageal, gastric, and colorectal cancers in the era of neoadjuvant therapy: A systematic review of the literature.

AimClinical staging is vital for selecting appropriate candidates and designing neoadjuvant treatment strategies for advanced tumors. The aim of this review was to evaluate diagnostic abilities of clinical TNM staging for gastrointestinal, gastrointestinal cancers.MethodsWe conducted a systematic review of recent publications to evaluate the accuracy of diagnostic modalities on gastrointestinal cancers. A systematic literature search was performed in PubMed/MEDLINE using the keywords “TNM staging,” “T4 staging,” “distant metastases,” “esophageal cancer,” “gastric cancer,” and “colorectal cancer,” and the search terms used in Cochrane Reviews between January 2005 to July 2020. Articles focusing on preoperative diagnosis of: (a) depth of invasion; (b) lymph node metastases; and (c) distant metastases were selected.ResultsAfter a full‐text search, a final set of 55 studies (17 esophageal cancer studies, 26 gastric cancer studies, and 12 colorectal cancer studies) were used to evaluate the accuracy of clinical TNM staging. Positron emission tomography–computed tomography (PET‐CT) and/or magnetic resonance imaging (MRI) were the best modalities to assess distant metastases. Fat and fiber mode of CT may be useful for T4 staging of esophageal cancer, CT was a partially reliable modality for lymph node staging in gastric cancer, and CT combined with MRI was the most reliable modality for liver metastases from colorectal cancer.ConclusionThe most reliable diagnostic modality differed among gastrointestinal cancers depending on the type of cancer. Therefore, we propose diagnostic algorithms for clinical staging for each type of cancer.

Survival benefit of perioperative chemotherapy for T1-3N0M0 stage esophageal cancer: a SEER database analysis.

BackgroundThe effect of perioperative chemotherapy on patients with lymph node-negative esophageal cancer (EC) is controversial. This study explored which EC patients, staged under the T1-3N0M0, would benefit from perioperative chemotherapy.MethodsData on patients with diagnosed primary EC were retrieved from Surveillance, Epidemiology and End Results (SEER) database. Propensity score-matched (PSM) method was performed to balance baseline covariates. Multivariate Cox regression analysis and Kaplan-Meier curve were used to assess potential survival difference between patients undergoing surgery plus perioperative chemotherapy (SA + CT) and those undergoing surgery alone (SA).ResultsIn a total of 2,711 EC patients (T1–3N0M0), 166 patients underwent SA + CT and 2,545 patients received SA. In the multivariable analysis, T stage was significantly related to prognosis of EC patients before and after matching. Subgroup analysis showed that perioperative chemotherapy was associated with poor cancer-specific survival (CSS) for stage T1 patients. There was no effect of perioperative chemotherapy on overall survival (OS) or CSS for T2 patients, whereas a remarkable improvement in OS and CSS was observed for T3 patients. Survival analysis showed that T3 stage EC patients obtained survival benefit from SA + CT. Prognosis in the SA group was significantly better than in the SA + CT group for T1 patients. However, T2 patients showed no significant increase in survival after undergoing SA + CT compared with SA.ConclusionsT3 patients benefit more from SA + CT. However, perioperative chemotherapy does not present survival benefit to T1–2 patients, and it is an adverse prognostic factor for T1 patients.

A Comparison of the Current N2 Classification and a Modified N2 Categorization in TNM Staging of Esophageal Cancer Patients.

ObjectiveTo compare the effectiveness of the current N classification and a modified N2 categorization in TNM staging of esophageal cancer (EC) patients.MethodologyA total of 2753 EC patients were enrolled in the study: 2283 EC patients from the Surveillance, Epidemiology, and End Results (SEER) database and 470 separate Chinese patients were used to verify the results of the SEER database. X-tile software was employed to determine the optimal cutoff points of the number of metastatic lymph nodes (LNs) in the N2 category. Univariate and multivariate Cox regression analyses were performed to identify the survival risk factors.ResultPatients in the N2 category were divided into two groups based on the number of metastatic LNs. Patients with three and four metastatic LNs were categorized as N2a, while those with five and six metastatic LNs were categorized as N2b. The 3-year overall survival (OS) rate in the SEER database was 71.5%, 42.3%, 23.6%, 17.2%, and 10.7% for patients with N0, N1, N2a, N2b, and N3, respectively (P<0.001). Furthermore, a separate Chinese cohort was enrolled to validate the revised N2 category. Additionally, the 3-year OS rate was 71.5%, 42.3%, 23.6%, 17.2%, and 10.7% for patients with N0, N1, N2a, N2b, and N3, respectively (P<0.001).ConclusionThe current N2 category should be further divided into two groups (N2a and N2b) to provide more accurate prognosis information that could further help in developing personalized therapeutic strategies.

Esophagectomy combined with off-pump coronary artery bypass grafting through left posterolateral incision is safe and feasible for esophageal cancer associated with coronary artery disease.

Controversy still exists as to whether surgical treatment has any impact on the long-term survival of esophageal cancer (EC) patients with coronary artery disease treated with curative esophagectomy combined with off-pump coronary artery bypass grafting (OPCABG). Therefore, the aim of this study was to introduce and assess the effect of esophagectomy combined with OPCABG on both short- and long-term outcomes. From January 2010 to January 2015, 1428 EC or esophagogastric junction cancer patients underwent surgical treatment at Henan Chest Hospital, Zhengzhou, China. The clinical data of 25 patients who underwent EC resection through a left thoracotomy following OPCABG and the perioperative characteristics and follow-up results were analyzed. The majority of the patients were male, and the EC stage was predominantly cT2N0-1M0 II. The most common pathological types were squamous cell carcinoma. The EC surgeries consisted of 15 chest anastomosis procedures and 10 cervical anastomosis procedures with aortocoronary graft implantation (mean: 2.36 grafts per patient). The mean total operative time was 330.8 ± 83.5minutes. The median intensive care unit and hospital lengths of stay were 1.72 and 21.16days, respectively. Resection without macroscopic residual disease (R0) was achieved in all of the patients. The most frequent complications included pulmonary infections (24%), arrhythmias (24%), pleural effusion (12%), and esophageal anastomotic leakage (8%). There were no postoperative deaths or myocardial infarctions within 30 days after the surgery. The overall 1-, 3-, and 5-year survival rates were 88%, 40%, and 24%, respectively, with a median survival time of 43months. In the short-term, radical resection of EC following OPCABG is a safe and feasible treatment with low postoperative mortality rates. In the long-term, simultaneous surgery is acceptable and is associated with favorable overall and disease-free survival.

Factors influencing development of non-cardiac chest pain after endoscopic submucosal dissection for esophageal neoplasms: a retrospective case-control study of 309 patients from a single center.

Endoscopic submucosal dissection (ESD) is widely used for early stage esophageal cancer and precancerous lesions. Non-cardiac chest pain (NCCP) is a frequent complication of ESD. However, little is known about its incidence and associated factors. This study investigated the pain incidence and predictive factors for pain development after ESD for esophageal neoplasms. We enrolled a total of 309 patients with esophageal neoplasms, who underwent ESD in our center from January 2018 to June 2019. Sociodemographic and clinicopathological information for all patients was collected, and patients were divided into either a pain-free group (n = 156) or a pain group (n = 153) according to whether there was onset of NCCP 24-48hours after surgery. We made comparisons between groups using Student's t test or the χ2 test. Logistic-regression analysis was used to screen for risk factors. There were statistically significant differences in histories of previous surgery (P = 0.039), lesion size (P = 0.026), operation time (P = 0.009), and postoperative fever (P = 0.001). History of previous surgery (P = 0.043) and postoperative fever (P = 0.007) were independent risk factors for chest pain after esophageal ESD treatment. Chest pain and fever prolonged postoperative hospitalization time (P = 0.005, P = 0.001) and increased hospitalization cost (P = 0.034, P < 0.001). A history of previous surgery and postoperative fever was associated with the occurrence of NCCP after ESD in patients with esophageal neoplasms. NCCP and fever after esophageal ESD increased both hospitalization time and cost.

Digestive Oncology in the COVID-19 Pandemic Era

Introduction: Since the rise of the COVID-19 pandemic there has been widespread concern regarding the possible delay in the diagnosis/treatment of cancer patients. We aimed to assess the impact of the COVID-19 pandemic on the diagnosis, treatment, and outcome of patients with digestive cancer. Methods: This was a retrospective study including patients with an inaugural digestive cancer diagnosis discussed for the first time at our center during the weekly digestive oncology reunion (DOR) meeting. The study group was enlisted from March to August 2020, and a control group was sourced from the equivalent period of 2018. Patients with a previous digestive cancer diagnosis/discussion in the DOR were excluded. The following data were collected: demographics, referral origin, tumor staging, first DOR discussion timing, treatment, and outcome. Results: A total of 235 patients were included: 107 in the study group (65.4% male, mean age 71.59 years); 128 in the control group (54.7% male, mean age 68.16 years). The mean number of clinical discussions per week was higher in 2018 (13.65 vs. 10.67, p = 0.040), without a difference in the mean number of patients discussed for the first time (inaugural diagnosis) between groups (p = 0.670). In the 2020 study group, more patients were referred to DOR from the emergency room (ER), fewer from the outpatient clinic/hospital wards (p < 0.001), and more were referred after urgent surgery (p = 0.022). There was no difference in the mean waiting time from diagnosis to first DOR discussion (p = 0.087). Tumor staging in colorectal, gastric, and esophageal cancer was not significantly different between the groups (p = 0897, p = 0.168, and p = 0.717). More patients in the study group presented with stage IV pancreatic cancer (p = 0.043). There was no difference in the time span from DOR until the beginning of neoadjuvant chemotherapy (p = 0.680) or elective surgery (p = 0.198), or from surgery until adjuvant chemotherapy (p = 0.396). Also, there was no difference in 30-day mortality from the first DOR date between the groups (p = 0.742). Conclusion: During the COVID-19 era there was a reduced number of clinical discussions in the DOR, but the number of debated patients with an inaugural digestive cancer diagnosis was similar. In the study group more patients were referred to DOR from the ER, and were referred after urgent surgery, suggesting a delayed demand for clinical attention. Study group patients were not significantly affected by the pandemic regarding timely DOR discussion, beginning of treatment, or 30-day mortality, reflecting the maintenance of the quality of care for digestive cancer patients.

Future directions—minimally invasive approaches to esophageal resection: a narrative review

: From the time of the first transthoracic esophagectomy to the present day, techniques for esophageal resection have evolved considerably. While open surgical techniques are still often employed, minimally invasive esophagectomy (MIE) has seen a tremendous rise in adoption in many centers worldwide and has in fact surpassed open esophagectomy. Robotic assisted minimally invasive esophagectomy (RAMIE) continues to increase steadily in recent years as well. Along with improved care algorithms including neoadjuvant and adjuvant treatments, minimally invasive approaches to esophageal resection have also contributed to a contemporaneous decrease in perioperative morbidity and mortality, as well as improvements in overall survival in esophageal cancer. Regardless of techniques or technologies employed, a continued reduction in complications such as anastomotic leak rate and pulmonary complications will be imperative in order to truly advance the field of esophageal resection. Importantly, endoscopic therapies such as endoscopic mucosal and submucosal resections (EMR/ESR) have garnered a substantial role in the treatment of early stage esophageal cancer. Novel robotic endoscopic platforms are in early development as well. The future of esophagectomy will no doubt continue to involve applications of new technology, including robotics and other novel developments.

Platinum versus immunotherapy for unresectable esophageal cancer: A protocol for systematic review and meta analysis.

Background:Esophageal cancer is one of the most common malignant tumors, with early metastasis, highly malignant characteristics. Morbidity ranks 7th among all malignant tumors, and mortality ranks 6th. Esophageal adjuvant therapy can significantly improve overall survival in unresectable esophageal cancer patients. With the breakthrough and progress of immunotherapy, the possibility of curing esophageal cancer has greatly increased. Some clinical trials have reported that compared with traditional platinum-based chemotherapy, the use of programmed death 1 (PD-1) and programmed death ligand 1 (PD-L1) inhibitors alone can benefit patients and effectively prolong their overall survival. We compare the efficacy of single immunotherapy with traditional platinum-based chemotherapy in a systematic review and meta-analysis to provide a reliable basis for clinicians.Methods:We will search PubMed, Medline, Embase, Web of Science, Cancerlit, Google Scholar, and the Cochrane Central Register of Controlled Trials for related studies published before December 1, 2019 without language restrictions. Two review authors will search and assess relevant studies independently. Randomized controlled trials (RCTs) or quasi-RCTs, and prospective cohort studies will be included. We will perform subgroup analysis in sex, age, ethnicity, and tumor stage of esophageal cancer patients.Results:The results of this study will be published in a peer-reviewed journal.Conclusion:The results of this systematic review and meta-analysis will provide a basis for clinicians to formulate the best chemotherapy regimen for patients, as well as a research clue for clinical researchers in this field. The results of this study will expand the treatment options for esophageal patients, but due to the nature of the disease and intervention, large sample clinical trials are not abundant, so we will include some high-quality small sample trials, which may cause high heterogeneity.INPLASY registration number:INPLASY2020110012.

Modified nodal stage of esophageal cancer based on the evaluation of the hazard rate of the negative and positive lymph node

BackgroundThe study aimed to propose a modified N stage of esophageal cancer (EC) on the basis of the number of positive lymph node (PLN) and the number of negative lymph node (NLN) simultaneously.MethodData from 13,491 patients with EC registered in the SEER database were reviewed. The parameters related to prognosis were investigated using a Cox proportional hazards regression model. A modified N stage was proposed based on the cut-off number of the re-adjusted ratio of the number of PLN (numberPLN) to the number of NLN (numberNLN), which were derived from the comparison of the hazard rate (HR) of numberPLN and numberNLN. The modified N stage was confirmed using the cross-validation method with the training and validation cohort, and it was also compared to the N stage from the American Joint Committee on Cancer (AJCC) staging system (7th edition) using Receiver Operating Characteristic (ROC) curve analysis.ResultsThe numberPLN on prognosis was 1.042, while numberNLN was 0.968. The modified N stage was defined as follows: N1 stage: the ratio range was from 0 to 0.21; N2 stage: more than 0.21, but no more than 0.48; N3 stage: more than 0.48. The log-rank test indicated that significant survival differences were confirmed among the N1, N2 and N3 sub-groups of patients in the training population. The difference of all the patients using the modified N stage method were more significant than AJCC N stage. The result of ROC analysis indicated that the modified N stage could represent the N stage of EC more accurately.ConclusionThe modified N stage based on the re-adjusted ratio of numberPLN to numberNLN can evaluate tumor stage more accurately than the traditional N stage.

Unraveling the identity of gastric cardiac cancer.

The classification of gastric cardiac carcinoma (GCC) is controversial. It is currently grouped with esophageal adenocarcinoma (EAC) as an adenocarcinoma of the gastroesophageal junction (GEJ). Recently, diagnostic criteria for adenocarcinoma in the GEJ were established and GCC was separated from EAC. We viewed published evidence to clarify the GCC entity for better patient management. GCC arises in the cardiac mucosa located from 3 cm below and 2 cm above the GEJ line. Compared with EAC, GCC is more like gastric cancer and affects a higher proportion of female patients, younger patients, those with a lower propensity for reflux disease, a wider histopathologic spectrum, and more complex genomic profiles. Although GCC pathogenesis mechanisms remain unknown, the two-etiology proposal is appealing: in high-risk regions, the Correa pathway with Helicobacter pylori infection, chronic inflammation, low acid and intestinal metaplasia, dysplasia and carcinoma may apply, while in low-risk regions the sequence from reflux toxin-induced mucosal injury and high acid, to intestinal metaplasia, dysplasia and carcinoma may occur. In early GCC a minimal risk of nodal metastasis argues for a role of endoscopic therapy, whereas in advanced GCC, gastric cancer staging rules and treatment strategy appear to be more appropriate than the esophageal cancer staging scheme and therapy for better prognosis stratification and treatment. In this brief review we share recent insights into the epidemiology, histopathology and genetics of GCC and hope that this will stimulate further investigations in order to improve the clinical management of patients with GCC.

SASS6 Promotes Proliferation of Esophageal Squamous Carcinoma Cells by Inhibiting the p53 Signaling Pathway

SASS6 encodes for the Homo sapiens SAS-6 centriolar assembly protein and is important for proper centrosome formation. Although centrosomes are amplified in a wide variety of tumor types, abnormally high SASS6 expression had previously only been identified in colon cancer. However, the role of SASS6 in esophageal squamous cell carcinoma (ESCC) pathogenesis has not yet been elucidated. The aim of this study was to investigate the role and mechanisms of SASS6 in ESCC. The expression level of PNCK mRNA was detected in specimens of ESCC (n = 20) and paired paracancerous tissues (n = 20) by qPCR, and that of PNCK protein was detected in specimens of ESCC paraffin tissue (n = 316) and corresponding paraffin paracancerous tissue (n = 94) by immunohistochemistry. The correlations of PNCK protein expression level with clinical stage and survival prognosis in ESCC patients were also investigated, respectively. Celigo Cell Counting and MTT assay were used to measure cell viability. Apoptosis and colony formation were detected by flow cytometric analysis and colony assay. The bioluminescence imaging was used to evaluate the effects of SASS6 knockdown on tumor growth using a xenograft animal model. The global gene expression profile was determined in wild type and SASS6-depleted ESCC cells via transcriptomics analysis. Mechanically, the changes of p53 signaling pathway were detected by Western blotting. We found that the mRNA and protein levels of SASS6 were increased in human ESCC samples. In addition, SASS6 protein expression was associated with the esophageal cancer stage and negatively impacted survival of patients with ESCC. Furthermore, silencing of SASS6 inhibited cell growth and promoted apoptosis of ESCC cells in vitro and inhibited xenograft tumor formation in vivo. A genetic cluster and pathway analysis showed that SASS6 regulates the p53 signaling pathway. Western blot analysis demonstrated that CCND2, GADD45A, and EIF4EBP1 protein expression decreased and that TP53 protein expression increased in the shSASS group when compared with the control group. SASS6 promoted the proliferation of esophageal cancer by inhibiting the p53 signaling pathway. Thus, SASS6 has potential as a novel tumor marker and therapeutic target for ESCC.

Thoracoscopic esophagectomy in total pharyngolaryngoesophagectomy for esophageal cancer; A case series

BackgroundTotal pharyngolaryngoesophagectomy (TPLE) is associated with major complications and is extremely invasive. In 2011, our institution introduced thoracoscopic esophagectomy in the left hemi-prone position and laparoscopic reconstruction with a gastric tube in patients undergoing TPLE. Herein, we describe the use of this operative method in 26 patients, focusing on the technical aspects of the surgery. Materials and methodsFrom January 2011 to December 2018, 26 patients underwent minimally invasive TPLE with gastric tube reconstruction in our institute. The thoracoscopic procedure was performed with the patient in the semi-prone position. The patient was then moved to the supine position, and the laparoscopic procedure and pharyngolaryngectomy were started simultaneously. After pharyngolaryngectomy, microvascular anastomoses or free jejunal flap interposition were performed at the site of the gastric tube reconstruction. The data from these 26 patients were retrospectively analyzed. ResultsThe median age was 66 years, and 3.8% of the patients were female. The Union for International Cancer Control stages of esophageal cancer were 0 (n = 2), I (n = 4), II (n = 7), III (n = 8), and IV (n = 5). Eight patients had concomitant esophageal cancer and head and neck cancer. Reconstruction with only a narrow gastric tube was used in 16 patients, while free jejunal flap interposition was used in 10 patients. The surgical procedures resulted in minimal complications. Postoperative complications of Clavien-Dindo grade ≥1 included anastomotic leakage in two patients and pneumonia in one. ConclusionThoracoscopic esophagectomy in the left hemi-prone position and laparoscopic reconstruction with a gastric tube in patients undergoing TPLE was safe and effective. The complications were improved via the development of various procedures. Further improvement is necessary before this thoracoscopic approach is established as a standard procedure for TPLE.

Use of endoscopic ultrasound in pre-treatment staging of esophageal cancer did not alter management plan.

BackgroundInitial staging of esophageal cancer relies on EUS in addition to FDG-PET/CT. It is our hypothesis that with the advancement of FDG-PET/CT staging, endoscopic ultrasound may not be required for initial staging in all cases. The purpose of this study is to analyze whether EUS affects initial treatment stratification in patients diagnosed with esophageal cancer.MethodsA retrospective database at the University of Virginia was queried for patients diagnosed with esophageal squamous cell carcinoma and adenocarcinoma who underwent EGD with EUS and FDG-PET/CT at their initial evaluation from 10/2013 to 5/2017. Two thoracic surgeons were asked to determine appropriate management for each case. Options included surgical resection, neoadjuvant chemoradiotherapy followed by resection, definitive chemoradiotherapy, or chemotherapy with or without palliative radiation. Both surgeons received the FDG-PET/CT report along with the EGD report. For each case, one or both surgeons were randomly allocated to review EUS results in addition to the clinical information. The treatment decisions of each thoracic surgeon were compared to determine if EUS reports impacted clinical management. Simple and weighted correlation coefficients (kappa) were calculated to compare agreement of treatment choices between the two surgeons using McNemars test. Conditional logistic regression was used to assess the influence of EUS on the treatment recommendations.ResultsA total of 50 patients (44 male and 6 female) were enrolled and data was collected. The thoracic surgeons agreed on treatment decisions in 39 cases and disagreed on 11 cases. Agreement between surgeons was good despite lack of EUS information for one surgeon on each case (weighted Kappa =0.73, 95% CI: 0.57–0.89). Using conditional logistic regression, EUS did not have a statistically independent association with agreement on treatment plan (P for model =0.17).ConclusionsEUS did not have a statistically independent association with agreement on treatment plan for newly diagnosed esophageal cancer (P for model =0.17). Our findings suggest that EUS may not be necessary in the algorithm for the initial staging of every case of esophageal cancer. Selective, rather than mandatory use of EUS seems warranted.

Circ_0072088 Promotes Proliferation, Migration, and Invasion of Esophageal Squamous Cell Cancer by Absorbing miR-377.

Circular RNA (circRNA) is an endogenous noncoding RNA. Accumulative investigations have confirmed that circRNAs play a vital role in carcinogenesis and tumor progression. Herein, we examined the expression and mechanism of circ_0072088 in esophageal squamous cell carcinoma (ESCC). As a result, circ_0072088 was significantly overexpressed in ESCC tissues and cells, which was closely associated with tumor size, invasion depth, clinical stage, and lymph node metastasis of esophageal cancer. Nuclear and cytoplasmic separation as well as FISH assays showed that circ_0072088 was mainly localized in the cytoplasm of ESCC cells. RNase R treatment assay revealed that circ_0072088 was steadier than linear ZFR mRNA. circ_0072088 promoted ESCC cell proliferation, migration and invasion in vitro, and cell proliferation in vivo. Mechanistically, circ_0072088 upregulated VEGF gene expression by acting as the sponge of miRNA-377. In conclusion, circ_0072088 might be used as a diagnostic biomarker and therapeutic target for ESCC.

A prospective analysis of the diagnostic accuracy of 3\u2009T MRI, CT and endoscopic ultrasound for preoperative T staging of potentially resectable esophageal cancer

BackgroundPatients with esophageal cancer (EC) undergo endoscopic ultrasound and CT based cancer staging. Recent technical developments allow improved MRI quality with diminished motion artifact that may allow MRI to compare favorable to CT for noninvasive staging. Hence the purpose of the study was to assess image quality and diagnostic accuracy of 3 T MRI versus CT and EUS for preoperative T-staging of potentially resectable esophageal cancer.MethodsBetween October-2014 and December-2017, esophageal cancer patients with T-staging by EUS were enrolled in this prospective study. Post-operative histopathologic T-staging was the reference standard. All participants underwent MRI [T2- multi-shot turbo spin echo sequence (msTSE), diffusion-weighted imaging (DWI), and 3D gradient-echo based sequence (3D-GRE)] and CT [non-contrast and multiphase contrast-enhanced CT scanning] 5.6 + 3.6 days after endoscopy. Surgery was performed within 3.6 + 3.5 days after imaging. Two blinded endoscopists (reader 1 and 2) and radiologists (reader 3 and 4) independently evaluated EUS and CT/MRI, respectively. Considering the clinical relevance, patients were dichotomized into early (T1 and T2) vs late (T3 and T4) stage cancer before assessment. For statistical purpose, the binary decision was defined as the ability of the imaging technique to diagnose early stage/not early stage esophageal cancer. Diagnostic performance of EUS, MRI and CT was compared using McNemar’s test with Bonferroni correction; kappa values were assessed for reader performance.Results74 study participants (60 ± 8 yrs.; 56 men) with esophageal cancer were evaluated, of whom 85%(63/74) had squamous cell carcinoma, 61%(45/74) were at early stage and 39%(29/74) were at late stage cancer, as determined by histopathology. Intra- and Inter-reader agreement for pre-operative vs post-operative T-staging was excellent for all imaging modalities. Compared to CT, MRI showed significantly higher accuracy for both the readers (reader3: 96% vs 82%, p = 0.0038, reader4: 95% vs 80%, p = 0.0076, for MRI vs CT, respectively). Further, MRI outperformed EUS with higher specificity (reader 1 vs 3: 59% vs 93%, p = 0.0015, reader 2 vs 4: 66% vs 93%, p = 0.0081, for EUS vs MRI respectively), and accuracy (reader 1 vs 3: 81% vs 96%, p = 0.0022, reader 2 vs 4: 85% vs 95%, p = 0.057, for EUS vs MRI, respectively).ConclusionFor resectable esophageal cancer, MRI had better diagnostic performance for tumor staging compared to CT and EUS.Trial registrationChiCTR, ChiCTR-DOD, Registered 2nd October 2014, http://www.chictr.org.cn/showproj.aspx?proj=9620

Identification of hub genes associated with esophageal cancer progression using bioinformatics analysis.

The underlying causes of esophageal cancer (EC) are unknown. To explore the molecular mechanisms that lead to EC, gene expression profiles of large cohorts of patients with EC were obtained from The Cancer Genome Atlas and the Gene Expression Omnibus (GEO) databases (GSE5364, GSE20347 and GSE23400). The present study identified 83 upregulated and 22 downregulated genes between EC and normal tissue using R statistical software and the GEO2R web tool. The Database for Annotation, Visualization and Integrated Discovery was used to identify the associated pathways, and for functional annotation of the differentially expressed genes (DEGs). Protein-protein interactions of these DEGs were analyzed based on the Search Tool for the Retrieval of Interacting Genes database, and hub genes were visualized using Cytoscape software. An online Kaplan-Meier plotter survival analysis tool was utilized to evaluate the prognostic value of hub gene expression in patients with EC. Further analysis of an additional dataset from GEO (GSE21293) revealed that these genes were associated with infiltration and metastasis in EC. In addition, the Gene Expression Profiling Interactive Analysis tool was used to evaluate expression levels of hub genes in patients with EC for different pathological stages. The Ualcan analysis tool was used to evaluate the expression levels of hub genes for different histological types. Overall, ubiquitin conjugating enzyme E2 C, cyclin dependent kinase inhibitor 3, CDC28 protein kinase regulatory subunit 2, kinesin family member 20A (KIF20A) and RAD51 associated protein 1 (RAD51AP1) were upregulated in EC tissues compared with normal tissues, and upregulation of these genes was a poor prognostic factor for patients with EC, indicating that these genes may mediate EC cell infiltration and metastasis. Among the hub genes, KIF-20A had potential value for predicting the pathological stage of EC. KIF20A and RAD51AP1 were more informative biomarkers of esophageal squamous cell carcinoma. Further studies are required to explore the value of these genes in the treatment of EC.

Updates in staging and pathologic evaluation of esophageal carcinoma following neoadjuvant therapy.

Esophageal carcinoma comprises two major subtypes-squamous cell carcinoma and adenocarcinoma, the incidences of which vary widely across the world and also depend on the location within the esophagus. The staging of esophageal cancer (EC) also remains unique among various gastrointestinal carcinomas, as it takes into account the location, histologic type, and grade. Its management has been evolving over the years and the recent American Joint Committee on Cancer staging system has been updated to reflect the changing practice and new data. It is clear that preoperative neoadjuvant therapy is increasingly being used for the treatment of locally advanced esophageal carcinomas, followed by surgical resection that improves survival. A variety of histologic changes can be seen after neoadjuvant therapy, which can be challenging for the pathologists. The presence of residual tumor in the surgically resected specimen and lymph node following neoadjuvant therapy is associated with poor prognosis. Hence, a thorough pathologic assessment of tumor regression grade and accurate tumor staging is required by pathologists to provide valuable prognostic information to guide further management. Tumor regression grading in ECs needs to be improved and standardized.

Adenocarcinoma of the gastro-esophageal junction: is centralization policy always a good idea?

: This study aims to review the available literature on the volume-outcome relationship in esophageal cancer. Given the controversies surrounding the treatment of gastro-esophageal junction (GEJ) cancer this review focusses on these specific tumors. Literature shows that staging of esophageal cancer should be performed by dedicated, specialized radiologists and endoscopists. This certainly applies to GEJ tumors since slight staging differences have major treatment impact. Since early neoplastic signs are subtle, state-of-the-art endoscopes and sufficient endoscopist and pathologist expertise are necessary for the treatment of Barret’s dysplasia or early cancer. In addition, given the possible complications of endoscopic resections, an expert center having surgical and endoscopic experience of treating complications is advisable. Most literature focusses on the relationship between hospital resection volume and surgical postoperative mortality and long-term survival. Several large meta-analyses show clear survival benefit and lower postoperative mortality rates in high-volume hospitals. The included literature was however heterogeneous with definitions of high-volume hospitals ranging from 2.33 to as much as 87 annual esophagectomies. Hospital volume seems to positively affect total esophageal cancer related costs. Literature also suggests centralization is necessary up to a certain threshold but not infinitely; a plateau might be reached in the volume-outcome relationship at an annual hospital volume of 50 or 60. However, more evidence is necessary to determine optimal cut-off values. Several studies suggest that much of the hospital volume benefit is explained by higher surgeon volume in high-volume hospitals, but the extent remains a matter of debate. Also, in the palliative setting a survival benefit of being treated in high-volume centers has been shown. The results of this review underline the importance of centralization of all aspects of the multimodal treatment of gastro-esophageal cancer. Especially for GEJ carcinomas highly specialized medical personnel is necessary. However, given the heterogeneity of the volume-outcome literature, clear international volume thresholds are difficult to establish.