Superficial Esophageal Squamous Carcinoma Research Articles

Diagnostic Accuracy of JES Classification for Prediction of Invasion Depth in Superficial Esophageal Squamous Carcinoma: Meta-Analysis.

Prediction of the depth of invasion in superficial oesophageal squamous carcinoma (SESC) is an important factor for choosing the treatment. Recently, the Japan Esophageal Society (JES) designed a magnifying endoscopy classification based on the Inoue and Arima classifications. The aim of this study was to conduct a meta-analysis of the published literature on JES classification. Meta-Disc version 1.4, Review Manager 5.4 as well as stata 14.0 were used. The analysis combined sensitivity and specificity with the respective 95% CI, to draw a summary receiver operating characteristic curve (SROC), and estimated the area under curve (AUC) for overdiagnosis and underdiagnosis for each type B. Eight studies were included in the meta-analysis comprising 1279 patients. Type B1 has high sensitivity (0.86, 95%CI: 0.83-0.88) and specificity (0.84, 95%CI: 0.81-0.88) for the prediction of EP/LPM classifications. The AUC was calculated to be 0.92 with a high proportion of underdiagnosis (17%). The sensitivity and specificity of type B2 were 0.66 (95% CI, 0.6-0.72) and 0.84 (95% CI, 0.82-0.86) respectively. The overdiagnosis and underdiagnosis of type B2 were 14% and 39%. Type B3, sensitivity was low (0.49, 95% CI: 0.41-0.56), with high specificity and AUC (specificity: 0.99; AUC: 0.95). JES classification is a useful and reliable modality for predicting the depth of invasion of SESC, but other modalities should be considered for additional assessment when type B2 is detected. Key Words: JES classification, Superficial oesophageal squamous carcinoma, Depth of invasion, Magnifying endoscopy, Meta-analysis.

Role of Recurrent Laryngeal Nerve Lymph Node Dissection in Surgery of Early-Stage Esophageal Squamous Cell Carcinoma.

In esophageal cancer surgery, it is difficult to perform thorough dissection of lymph nodes along the recurrent laryngeal nerve (RLN-LN). However, there are limited data regarding the necessity of RLN-LN dissection in surgery for superficial esophageal squamous carcinoma (focused on T1b tumor) and its role in locoregional control and accurate nodal staging. Between 2001 and 2016, 567 patients with pT1N0 and 927 patients with cT1N0 squamous cell carcinoma were identified in a prospectively maintained, single institution esophagectomy registry. Sufficient or insufficient RLN-LN assessment group was defined by receiver operating characteristic curve analysis of the number of RLN-LN harvested. To mitigate bias, inverse probability weighting adjustment and several sensitivity analyses were performed. In the pT1N0 cohort, patients with sufficient (≥ 4) harvested RLN-LNs showed significantly superior 5-year recurrence-free survival (89.1% versus 74.8%, log-rank P < 0.001). Patients with insufficient RLN-LN dissection mainly developed locoregional failure at the upper mediastinal or cervical area (87% of total recurred cases). The survival impact of sufficient RLN-LN dissection was more prominent in subsets of upper-middle thoracic tumors or with deep submucosal invasion. In the analysis on cT1N0 cohort, sufficient RLN-LN assessment conferred a 1.5-fold increase in the discovery of positive-nodal disease (19.4% versus 27.8%, P = 0.008). Adequate RLN-LN dissection during surgery may help reduce the risk of recurrence and enhance the accuracy of nodal staging in early-stage esophageal squamous cell carcinoma. Therefore, meticulous surgical evaluation for this region should not be underrated, particularly in the high-risk subset with lymph node metastasis. Visual Abstract Graphical summary of key study findings. T wo cohorts (pT1 and cT1 ; both mainly comprised T1b ) were analyzed for separate purposes; the former controlled for pathologic stage was primarily analyzed in terms of survival and recurrence hazard, whereas the latter (controlled for clinical was used for stage migration ( and intention to treat analysis. Th e results show the significance of adequate bilateral RLN LN in the surgery for early stage ESCC (particularly those with T1b)T1b), in terms of accurate nodal staging, effective nodal clearance, and reduced regional.

Novel Endoscopic Criteria for Predicting Tumor Invasion Depth in Superficial Esophageal Squamous Carcinoma.

BackgroundAccurate prediction of tumor invasion depth in superficial esophageal squamous carcinoma (SESC) is essential for deciding the appropriate treatment strategy. We proposed novel endoscopic criteria to differentiate between mucosal and submucosal esophageal cancers and to evaluate the diagnostic accuracy and usefulness of the criteria.MethodsA total of 352 patients who underwent endoscopic or surgical resection for SESC between 1991 and 2010 were included. First, the novel endoscopic criteria were created based on the endoscopic features of 60 randomly selected patients as follows: for T1m cancers, I. flat or slightly elevated or depressed lesion with smooth/even surface of any size, II. slightly elevated lesion of ≤ 1 cm with granular or uneven surface, III. hyperemic flat lesion of ≤ 3 cm with granular or uneven surface, IV. slightly depressed lesion of ≤ 2 cm with uneven surface and for T1sm cancers, I. irregularly (unevenly) nodular or protruded lesion of any size, II. slightly elevated lesion of > 1 cm with granular or uneven surface, III. hyperemic flat lesion of > 3 cm with granular or uneven surface, IV. irregularly (unevenly) depressed lesion of > 2 cm, and V. ulcerative lesion of any size. Next, the endoscopic findings of the remaining 292 patients were reviewed according to the criteria.ResultsThe accuracy of novel endoscopic criteria was 79.5% (232/292). The sensitivity and specificity of mucosal cancers were 78.4% and 81.0%, respectively, whereas those for submucosal cancers were 81.0% and 78.4%, respectively. The accuracy for mucosal cancers was high (97.3%, 72/74) when the lesions were flat or slightly elevated/depressed with smooth/even surface regardless of size, whereas that for submucosal cancers was high (85.7%, 18/21) when the lesions were irregular/nodular protrusions regardless of size. In multivariate analysis, macroscopic type IIb lesion was identified as an independent factor affecting accuracy (P < 0.05). The difference in recurrence-free survival rates between endoscopically mucosal and submucosal cancers was significant (P = 0.026).ConclusionThe novel endoscopic criteria appear to be accurate and useful in predicting invasion depth in SESC. Our criteria might help not only to decide the treatment strategy between surgery and endoscopic resection but also to predict the outcomes of SESC.

Prediction of lymph node metastatic status in superficial esophageal squamous cell carcinoma using an assessment model combining clinical characteristics and pathologic results: A retrospective cohort study.

It is important to identify the risk of lymph node metastasis (LNM) in patients with superficial esophageal squamous carcinoma (SESC) who have received endoscopic resection (ER). We aimed to develop a risk-predicting model for metastasis of SESC to lymph nodes using clinicopathological features and pathological results. Clinical data on 539 consecutive patients who underwent esophagectomy for SESC in our hospital were collected. Their post-surgical pathological results were assessed and analyzed. Multivariate logistic regression was used to identify all independent risk factors associated with LNM that then were incorporated into the prediction model. LNM was identified in 53 of 366 patients and 30 of 173 patients by positive histopathological results in the training and validation cohorts. The risk factors associated with LNM were large tumor size, poor tumor grade, deep invasion, and presence of angiolymphatic invasion. The model achieved good discriminatory ability of 0.80 (95%CI, 0.74-0.86) and 0.81 (95%CI, 0.75-0.86) in predicting LNM in the training and validation cohorts respectively. A LNM-predicting nomogram was formed with an area under curve of 0.80 (95% CI, 0.74-0.86), which had well-fitted calibration curves. A prediction model was constructed to generates 3 categories for estimated LNM risk in SESC patients. It provides a practical way of estimation of LNM risk in SESC patients who had received ER.

Clinical implication of endoscopic gross appearance in superficial esophageal squamous carcinoma: revisited.

Standard endoscopic appearance is essential for the diagnosis and treatment of superficial esophageal squamous carcinoma (SESC). The aim of this study was to investigate the association between the endoscopic gross appearance and the clinicopathologic characteristics of SESC. We retrospectively analyzed the clinicopathologic characteristics of SESC according to gross endoscopic appearance in 275 patients with SESC that underwent esophagectomy or endoscopic resection (ER). The proportion of type I or type III gross appearance, and that of types IIa, IIb, or IIc, were 26.2 and 73.8%, respectively. Type I or type III gross appearance was significantly associated with the female sex, submucosal invasion, lymphovascular invasion (LVI), and lymph node metastasis (LNM). In addition, younger age, larger tumor size, higher proportion of circumferential extension, type I or type III endoscopic gross appearance, submucosal invasion, moderate or poorly differentiated carcinoma, and LVI were significantly associated with LNM. Multivariate logistic regression analysis determined that independent predictors of LNM in patients with SESC included endoscopic gross appearance, submucosal invasion, and presence of LVI. Additionally, type I or type III endoscopic gross appearance lesions were more likely to have submucosal invasion than types IIa, IIb, or IIc. Risk factors for submucosal invasion included a gross appearance of type I or type III, moderately or poorly differentiated tumors, and presence of LVI. We found that SESC clinical features are correlated with the endoscopic appearance. Therefore, we suggest that the endoscopic gross appearance may be a candidate for additive criteria in the indications for ER.

Clinicopathologic analysis of lymph node status in superficial esophageal squamous carcinoma.

BackgroundEndoscopic approaches are gradually considered as a reliable treatment of intramucosal esophageal squamous carcinoma. However, endoscopic resection (ER) is limited by the potential lymph node metastasis (LNM) at various depths of mucosal and submucosal invasion.MethodsWe conducted a retrospective review of 498 patients with pT1 superficial esophageal squamous carcinoma (SESC) who underwent surgical resection from January 2008 to August 2015. Pathological characteristics of tumors including location, size, appearance, differentiation, invasion depth, and nodal status were reviewed, and risk factors were analyzed.ResultsLNM was found in 0.0, 2.7, 6.3, 18.2, 15.9, and 34.3 % of the m1, m2, m3, sm1, sm2, and sm3 lesions, respectively. Univariate logistic regression identified the presence of the tumor size > 2 cm (p < 0.05), the presence of the poor tumor differentiation (p < 0.05), and the depth of tumor invasion (p < 0.05) and angiolymphatic invasion (p < 0.05) to be the important risk factors associated with the prevalence of tumor-positive lymph nodes. These findings were confirmed in multivariate logistic regression as independent predictors for LNM.ConclusionsER is considered as a reliable treatment of m1 to m2 lesions. Radical surgical resection (SR) is the standard and irreplaceable therapy of sm1 to sm3 lesions. Patients with m3 lesions should undergo ER as the initial procedure for diagnosis. And this treatment is supported only by a successful description of the tumor’s characteristics, including (1) only muscularis mucosa invasion and without invasion of the resection margins and (2) without any risk predictors for LNM. Otherwise, SR is recommended.

Prevention of esophageal strictures after endoscopic submucosal dissection with the injection of botulinum toxin type A

The use of endoscopic submucosal dissection (ESD) for management of widespread superficial esophageal squamous carcinoma is closely associated with esophageal stenosis. We investigated the efficacy and feasibility of endoscopic injection of botulinum toxin type A (BTX-A) for preventing esophageal strictures after ESD for superficial esophageal squamous carcinoma. Sixty-seven patients with superficial esophageal squamous cell carcinomas with mucosal defects that exceeded one half of the circumference of the esophagus after ESD treatment were enrolled and randomly divided into 2 groups (group A, n= 33; group B, n= 34). Patients in group A (BTX-A group) were immediately injected with BTX-A after ESD, whereas patients in group B (control group) received ESD only. Endoscopy was performed when patients reported dysphagia symptoms and at 12 weeks post-ESD in patients without symptoms. Patients who experienced post-ESD esophageal strictures in both groups received bougie dilation. The number of patients who experienced esophageal strictures in group A (per protocol analysis, 6.1%, 2/33; intention to treat analysis, 11.4%, 4/35) was significantly less than that seen in group B (per protocol analysis, 32.4%, 11/34; intention to treat analysis, 37.8%, 14/37) (P< .05). Moreover, the number of bougie dilation procedures was significantly lower in group A (mean, 1.5; range, 0-2) than in group B (mean, 2.8; range, 0-5) (P< .05). Endoscopic injection of BTX-A was effective in preventing post-ESD esophageal strictures and decreasing the times of bougie dilation procedures. ( ChiCTR-TRC-12003188.).

Survival and prognostic evaluation of superficial esophageal cancer after surgery

To calculate the survival rate of patients with superficial esophageal squamous carcinoma who received esophageal resection and to explore factors that affect prognosis. There were 285 patients with pTis-T1 esophageal carcinoma who underwent esophagectomy during 2007-2011. Their cumulative survival rates were calculated using life tables. Nine factors that may have impact on postoperative survival of superficial esophageal carcinoma were selected. The Kaplan-Meier method and COX's regression model were used to select prognostic factors, estimate prognostic index, and establish risk stratification. The 1-, 3- and 5-year overall survival rates of superficial esophageal carcinoma patients were 97%, 86%, and 82%, respectively. Tumor length, stenosis, depth of invasion, differentiation degree, lymph node metastasis, and vascular tumor thrombus were associated with prognosis according to univariate analysis. Depth of invasion (OR=2.065, P=0.029), lymph node metastasis (OR=2.049, P=0.041), differentiation degree (OR=3.828, P=0.000), stenosis(OR=2.129, P=0.048), and vascular tumor thrombus (OR=4.222, P=0.004) were independent prognostic factors in multivariate analysis. A prognostic models was thus established and all the patients were divided into low-risk, moderate-risk and high-risk group, with the 3-year survival rates being 95%, 84%, and 51%, and 5-year survival rates being 93%, 79%, and 44%, respectively. Patients with superficial esophageal cancer have relatively favorable prognosis. Depth of invasion, differentiation degree, stenosis, lymph node metastasis, and vascular tumor thrombus may be independent factors of poor prognosis. Survival rate of moderate- and high-risk patients is yet to be improved.

Relationships between Micro-Vascular and Iodine-Staining Patterns in the Vicinity of the Tumor Front of Superficial Esophageal Squamous Carcinoma.

ObjectiveThe aim of the present study was to clarify differences between micro-vascular and iodine-staining patterns in the vicinity of the tumor fronts of superficial esophageal squamous cell carcinomas (ESCCs).MethodsTen consecutive patients with ESCCs who were treated by endoscopic submucosal dissection (ESD) were enrolled. At the edge of the iodine-unstained area, we observed 183 sites in total using image-enhanced magnifying endoscopy. We classified the micro-vascular and iodine-staining patterns into three types: Type A, in which the line of vascular change matched the border of the iodine-unstained area; Type B, in which the border of the iodine-unstained area extended beyond the line of vascular change; Type C, in which the line of vascular change extended beyond the border of the iodine-unstained area. Then, by examining histopathological sections, we compared the diameter of intra-papillary capillary loops (IPCLs) in cancerous areas and normal squamous epithelium.ResultsWe investigated 160 sites that the adequate quality of pictures were obtained. There was no case in which the line of vascular change completely matched the whole circumference of the border of an iodine-unstained area. Among the 160 sites, type A was recognized at 76 sites (47.5%), type B at 79 sites (49.4%), and type C at 5 sites (3.1%). Histological examination showed that the mean diameter of the IPCLs in normal squamous epithelium was 16.2±3.7μm, whereas that of IPCLs in cancerous lesions was 21.0±4.4μm.ConclusionsThe development of iodine-unstained areas tends to precede any changes in the vascularity of the esophageal surface epithelium.

ROLE OF NARROW BAND IMAGING FOR DIAGNOSIS OF EARLY‐STAGE ESOPHAGOGASTRIC CANCER: CURRENT CONSENSUS OF EXPERIENCED ENDOSCOPISTS IN ASIA–PACIFIC REGION

In Asian countries, squamous cell carcinoma is the most common type of esophageal cancer, and the incidence of gastric cancer remains have plateaued. To synthesize current information and to illustrate its clinical benefit of narrow band imaging (NBI) for diagnosis of superficial esophageal squamous carcinoma (SESCC) and early gastric cancer (EGC), a consensus conference was held by a panel of nine experts from Asian-Pacific countries. The expert's agreement suggested importance of interpretation of both vascular architecture and surface structure of the lesions and proper processor settings for endoscopic images. Zoom endoscopy was not regarded as absolutely necessary for detection of SESCC, but magnifying observation provided valuable information for characterization of detected lesions in the esophagus and the stomach. In general, NBI is useful for detection and characterization of SESCC, whereas it is beneficial mainly for characterization of EGC. Chromoendoscopy was found to be still worthwhile in certain situations, such as determination of the extent of SESCC by Lugol's staining, or detection and delineation of EGC by indigo carmine. NBI could replace chromoendoscopy in routine examination because it is easy to use and adds much information to conventional WLI, but it cannot eliminate chromoendoscopy when we make a final diagnosis for treatment decision-making. Consequently, the benefit of NBI or magnifying NBI is specific for the organ and the purpose of the examination, thus optimum indication and usage should be understood for maximum clinical benefit.

Feasibility of endoscopic resection in superficial esophageal squamous carcinoma

Endoscopic resection in patients with superficial esophageal squamous carcinoma (SESC) is limited by the presence of lymph node metastasis (LNM), highlighting the importance of determining which patients have virtually no risk of LNM. To investigate the clinicopathological parameters predicting LNM in patients who underwent esophagectomy for SESCs and to identify the best candidate patients for endoscopic resection. Retrospective, single-center study. Tertiary-care center. A total of 190 patients who underwent esophagectomy for SESCs between 1991 and 2009. Esophagectomy with lymph node dissection. LNM. Of 190 patients, 39 (20.5%) had LNM. The rates of LNM in patients with m1, m2, m3, sm1, sm2, and sm3 lesions were 0.0% (0/18), 8.7% (4/46), 25.0% (6/24), 15.0% (3/20), 26.0% (7/27), and 37.3% (19/51), respectively. On multivariate analysis, lymphovascular invasion (LVI) (P<.001), superficial tumor size (P=.004), and lower LMM (lamina muscularis mucosae) invasion width (P<.001) were independent predictors of LNM in patients with SESC invading the LMM. Among 63 patients with mucosal or sm1 cancer 3 cm or smaller, only 1 had LNM without LVI showing a lower LMM invasion width greater than 3.0 mm. Retrospective analysis. Endoscopic resection should be performed for mucosal cancer of 3 cm or less without positive lymph nodes. Moreover, if pathological examination of the endoscopically resected specimens shows invasion of the sm1 layer and a lower LMM invasion width of 3.0 mm or less, indicating an absence of LVI, the patient can be carefully observed without additional treatment.

Feasibility of endoscopic resection in superficial esophageal squamous carcinoma

Feasibility of endoscopic resection in superficial esophageal squamous carcinoma

Confocal endomicroscopy for in vivo detection of microvascular architecture in normal and malignant lesions of upper gastrointestinal tract

Confocal laser endomicroscopy allows subsurface analysis of gastrointestinal mucosa during ongoing endoscopy. The present study assessed the feasibility of in vivo detecting superficial vascular architecture by confocal endomicroscopy in normal upper gastrointestinal mucosa and malignant lesions. Early gastric cancer in eight patients, superficial esophageal carcinoma in six patients, and asymptomatic normal control in 10 patients were studied by confocal endomicroscopy. The characteristic of endomicroscopic microvascular architecture from normal and malignant mucosa was described and images were evaluated. Confocal endomicroscopy enabled clear visualization of the vascular networks of gastroesophageal mucosa. Honeycomb-like and coil-shaped regular microvascular architecture surrounding gastric pits were visible in the normal gastric body and antrum, respectively. Differentiated gastric cancerous mucosa showed hypervascularity and various caliber microvessels with irregular shapes. Undifferentiated gastric cancers disclosed a hypovascularity and irregular short branch vessels. Normal squamous epithelium had regular intraepithelial papillary capillary loops (IPCLs) directed toward the luminal surface. In superficial esophageal squamous carcinoma, dilated IPCLs were visible at the upper layer of the squamous mucosa. In esophageal adenocarcinoma, abnormal microvascular architecture showed tortuous and various calibers blood vessels. Of all the images, 41% were graded as good quality. The mean kappa value for interobserver agreement for the prediction of cancerous mucosa was 0.792. Confocal laser endomicroscopy system could yield very clear images of superficial microvascular network in the gastroesophageal mucosal layer both in malignant and normal mucosa. Endomicroscopic observation of vascular architecture may be of assistance in the identification of early gastroesophageal cancers.