Esophageal Squamous Cell Neoplasia Research Articles

235 Accuracy of Post-Hoc High-Resolution Microendoscopy for Diagnosis of Esophageal Squamous Cell Neoplasia

235 Accuracy of Post-Hoc High-Resolution Microendoscopy for Diagnosis of Esophageal Squamous Cell Neoplasia

The Spatial Predilection for Early Esophageal Squamous Cell Neoplasia: A "Hot Zone" for Endoscopic Screening and Surveillance.

Early esophageal squamous cell neoplasias (ESCNs) are easily missed with conventional white-light endoscopy. This study aimed to assess whether early ESCNs have a spatial predilection and the patterns of recurrence after endoscopic treatment.We analyzed the circumferential and longitudinal location of early ESCNs, as well as their correlations with exposure to carcinogens in a cohort of 162 subjects with 248 early ESCNs; 219 of which were identified by screening and 29 by surveillance endoscopy. The circumferential location was identified using a clock-face orientation, and the longitudinal location was identified according to the distance from the incisor.The most common circumferential and longitudinal distributions of the early ESCNs were found in the 6 to 9 o’clock quadrant (38.5%) and at 26 to 30 cm from the incisor (41.3%), respectively. A total of 163 lesions (75%) were located in the lower hemisphere arc, and 149 (68.4%) were located at 26 to 35 cm from the incisor. One hundred eleven (51%) early ESCNs were centered within the “hot zone” (i.e., lower hemisphere arc of the esophagus at 26 to 35 cm from the incisor), which comprised 20% of the esophageal area. Exposure to alcohol, betel nut, or cigarette was risk factors for the development of early ESCNs in the lower hemisphere. After complete endoscopic treatment, the mean annual incidence of metachronous tumors was 10%. In addition, 43% of the metachronous recurrent neoplasias developed within the “hot zone.” Cox regression analysis revealed that the index tumor within the hot zone (hazard ratio [HR]: 3.19; 95% confidence interval [CI]: 1.17–8.68; P = 0.02) and the presence of numerous Lugol-voiding lesions in the esophageal background mucosa were independent predictors for metachronous recurrence (HR: 4.61; 95% CI: 1.36–15.56; P = 0.01).We identified a hot zone that may be used to enhance the detection of early ESCNs during endoscopic screening and surveillance, especially in areas that lack resources and have a high prevalence of ESCNs.

A tablet-interfaced high-resolution microendoscope with automated image interpretation for real-time evaluation of esophageal squamous cell neoplasia.

In recent years high-resolution microendoscopy (HRME) has shown potential to improve screening for esophageal squamous cell neoplasia. Furthering its utility in a clinical setting, especially in lower-resource settings, could be accomplished by reducing the size and cost of the system as well as incorporating the ability of real-time, objective feedback. This article describes a tablet-interfaced HRME with fully automated, real-time image analysis. The performance of the tablet-interfaced HRME was assessed by acquiring images from the oral mucosa in a normal volunteer. An automated, real-time analysis algorithm was developed and evaluated using training, test, and validation images from a previous invivo study of 177 patients referred for screening or surveillance endoscopy in China. The algorithm was then implemented in a tablet HRME that was used to obtain and analyze images from esophageal tissue in 3 patients. Images were displayed alongside the probability that the imaged region was neoplastic. The tablet-interfaced HRME demonstrated comparable imaging performance at a lower cost compared with first-generation laptop-interfaced HRME systems. In a post-hoc quantitative analysis, the algorithm identified neoplasia with a sensitivity and specificity of 95% and 91%, respectively, in the validation set compared with 84% and 95% achieved in the original study. The tablet-based HRME is a low-cost tool that provides quantitative diagnostic information to the endoscopist in real time. This could be especially beneficial in lower-resource settings for operators with less experience interpreting HRME images.

Radiofrequency Ablation Versus Endoscopic Submucosal Dissection in Treating Large Early Esophageal Squamous Cell Neoplasia.

Radiofrequency ablation (RFA) and endoscopic submucosal dissection (ESD) can potentially be applied for early esophageal squamous cell neoplasia (ESCN); however, no study has directly compared these 2 modalities.We retrospectively enrolled the patients with flat-type “large” (length ≥3 cm extending ≥1/2 of the circumference of esophagus) early ESCNs treated endoscopically. The main outcome measurements were complete response at 12 months, and adverse events.Of a total of 65 patients, 18 were treated with RFA and 47 with ESD. The procedure time of RFA was significantly shorter than that of ESD (126.6 vs 34.8 min; P < 0.001). The complete resection rate of ESD and complete response rate after primary RFA were 89.3% and 77.8%, respectively. Based on the histological evaluation of the post-ESD specimens showed 14 of 47 (29.8%) had histological upstaging compared with the pre-ESD biopsies, and 4 of them had lymphovascular invasion requiring chemoradiation or surgery. After additional therapy for residual lesions, 46 (97.9%) patients in the ESD group and 17 (94.4%) patients in the RFA group achieved a complete response at 12 months. Four patients (8.5%) developed major procedure-related adverse events in the ESD group, but none in the RFA group. In patients with lesions occupying more than 3/4 of the circumference, a significantly higher risk of esophageal stenosis was noted in the ESD group compared with RFA group (83% vs 27%, P = 0.01), which required more sessions of dilatation to resolve the symptoms (median, 13 vs 3, P = 0.04). There were no procedure-related mortality or neoplastic progression in either group; however, 1 patient who received ESD and 1 who received RFA developed local recurrence during a median follow-up period of 32.4 (range, 13–68) and 18.0 (range, 13–41) months, respectively.RFA and ESD are equally effective in the short-term treatment of early flat large ESCNs; however, more adverse events occur with ESD, especially in lesions extending more than 3/4 of the circumference. RFA does not allow for pathology to evaluate the curability after ablation, and thus currently the use for invasive ESCNs should be conservative until longer follow-up studies are available.

The effectiveness of radiofrequency ablation on eradicating widespread early 0-IIb esophageal squamous cell carcinoma and precancerous lesions

Objective To evaluate the effectiveness of radiofrequency ablation (RFA) on eradicating widespread early 0-Ⅱb esophageal squamous cell carcinoma (ESCC) and precancerous lesions. Methods Retrospective analysis was performed on 33 patients with early 0-Ⅱb ESCC, high and middle-grade dysplasis (HGD, MGD) between October 2008 and June 2011 at Cancer Institute and Hospital, Chinese Academy of Medical Sciences for the proportion of patients with histological complete response (CR) and adverse events after 12 months. Results In 33 patients, of whom 26 were male, 7 were female, mean age being 61years old with MGD (10), HGD (17), EESCC (6). USL length was 3-12(mean 7.9)cm.Treatment area(TA)length was 5-14(mean 9.9)cm, and the esophagus was involved 11/12 circumference. Primary RFA treatment time was 11-57(mean 30)min and average hospitalization day was 3 days. CR was 69.7%(23/33) after one RFA session in 3 months, and was 93.9% (31/33) after 12 months. There were 4(12%)severe strictures, who received dilation 3-12 (mean 7) times, and symptoms were relieved. There was no other complication. Conclusion RFA is effective, safe and less technique-demanding in treating patients with widespread 0-Ⅱb esophageal squamous cell neoplasia and precancerous lesions, extending the indications of endoscopic treatment. Key words: Radiofrequency ablation; Esophageal neoplasms; Early esophageal squamous cell carcinoma; Precancerous lesions

Endoscopic balloon-based radiofrequency ablation for long-segment early esophageal squamous cell neoplasia

Summary Esophageal cancer is a common and highly lethal disease. In the Asia-Pacific region, esophageal squamous cell neoplasias are the major forms of the disease. Recent advances in endoscopic therapy enable curative treatment of early esophageal squamous cell neoplasias, however, the technique is complicated and requires a high level of expertise, especially for those with long-segment lesions. Endoscopic radiofrequency ablation is a rapidly evolving treatment modality and has been shown to have good efficacy and safety for the treatment of dysplasia in cases of Barrett’s esophagus. Theoretically, it can also be used to treat squamous dysplasia. We report a case of a 48-year-old man with an 8-cm-long circumferential squamous high-grade dysplasia over the esophagus (from 21 cm to 29 cm below the incisor) that was treated successfully and safely with balloon-based radiofrequency ablation. The procedure took only around 30 minutes to complete. There were no major adverse events during and after the procedure. In addition, we examined the histology of the esophageal coagulum, which showed an extensive cauterization effect with focal dysplasia within the ablated epithelium. Follow-up endoscopy at 1 month, 3 months, and 6 months showed no residual lesion, and biopsies also confirmed complete remission.

Low-Cost High-Resolution Microendoscopy for the Detection of Esophageal Squamous Cell Neoplasia: An International Trial

Esophageal squamous cell neoplasia has a high mortality rate as a result of late detection. In high-risk regions such as China, screening is performed by Lugol's chromoendoscopy (LCE). LCE has low specificity, resulting in unnecessary tissue biopsy with a subsequent increase in procedure cost and risk. The purpose of this study was to evaluate the accuracy of a novel, low-cost, high-resolution microendoscope (HRME) as an adjunct to LCE. In this prospective trial, 147 consecutive high-risk patients were enrolled from 2 US and 2 Chinese tertiary centers. Three expert and 4 novice endoscopists performed white-light endoscopy followed by LCE and HRME. All optical images were compared with the gold standard of histopathology. By using a per-biopsy analysis, the sensitivity of LCE vs LCE + HRME was 96% vs 91% (P = .0832), specificity was 48% vs 88% (P < .001), positive predictive value was 22% vs 45% (P < .0001), negative predictive value was 98% vs 98% (P = .3551), and overall accuracy was 57% vs 90% (P < .001), respectively. By using a per-patient analysis, the sensitivity of LCE vs LCE + HRME was 100% vs 95% (P = .16), specificity was 29% vs 79% (P < .001), positive predictive value was 32% vs 60%, 100% vs 98%, and accuracy was 47% vs 83% (P < .001). With the use of HRME, 136 biopsies (60%; 95% confidence interval, 53%-66%) could have been spared, and 55 patients (48%; 95% confidence interval, 38%-57%) could have been spared any biopsy. In this trial, HRME improved the accuracy of LCE for esophageal squamous cell neoplasia screening and surveillance. HRME may be a cost-effective optical biopsy adjunct to LCE, potentially reducing unnecessary biopsies and facilitating real-time decision making in globally underserved regions. ClinicalTrials.gov, NCT 01384708.

Clinical Availability of Low-cost High-resolution Microendoscopy for the Detection of Esophageal Squamous Cell Neoplasia

Clinical Availability of Low-cost High-resolution Microendoscopy for the Detection of Esophageal Squamous Cell Neoplasia

Clinical Significance of Early Detection of Esophageal Cancer in Patients with Head and Neck Cancer

Background/AimsThe efficacy of surveillance for esophageal squamous cell neoplasia (ESCN) in patients with head and neck squamous cell carcinoma (HNSCC) remains controversial. Our study aimed to provide clinical data concerning the necessity of surveillance for detecting early ESCN in patients with HNSCC.MethodsWe retrospectively reviewed the data from 714 patients who were pathologically confirmed as having HNSCC (n=236 oral cavity cancers, 137 oropharyngeal cancers, 87 hypopharyngeal cancers, and 254 laryngeal cancers).ResultsOf 714 patients, during a median follow-up of 31 months, 48 ESCNs (37 synchronous and 11 metachronous) were detected in 36 patients (5%). Fifteen synchronous lesions (40.3%) were early ESCN, whereas nine metachronous lesions (81.8%) were early ESCN. The 3-year survival rates of HNSCC only and HNSCC combined with ESCN were 71.2% and 48.2%, respectively (p<0.001). Among 36 patients with ESCN, the 3-year survival rates for early and advanced ESCN were 77.7% and 21.7%, respectively (p=0.01). In the multivariate analysis, alcohol consumption and hypopharyngeal cancer were significant factors associated with the development of ESCN.ConclusionsHN-SCC patients with early ESCN were similar in prognosis with patients without ESCN, in contrast to patients with advanced ESCN. Therefore, surveillance for the early detection of ESCN in patients with HNSCC, especially in alcohol drinkers and those with hypopharyngeal cancer, is warranted.

Su1970 Frequency of Lateral Spread in Esophageal Squamous Cell Neoplasia

Su1970 Frequency of Lateral Spread in Esophageal Squamous Cell Neoplasia

Mo1134 Accuracy of a High Resolution, Low-Cost Microendoscope for the Early Detection of Esophageal Squamous Cell Neoplasia: a Prospective, International, Multicenter Trial

Mo1134 Accuracy of a High Resolution, Low-Cost Microendoscope for the Early Detection of Esophageal Squamous Cell Neoplasia: a Prospective, International, Multicenter Trial

Relevant risk factors and prognostic impact of positive resection margins after endoscopic submucosal dissection of superficial esophageal squamous cell neoplasia

Endoscopic submucosal dissection (ESD) for the treatment of esophageal mucosal lesions has a risk of resection margin residues. The related risk factors and prognosis of post-ESD resection margin residues have not been fully evaluated. The aim of this study was to investigate the associated risk factors and the prognostic impact of resection margin residues after ESD of superficial esophageal squamous cell neoplasia. We conducted a retrospective analysis of medical records at our hospital, including the clinical, endoscopic, and pathological data from patients who underwent ESD for the treatment of superficial esophageal squamous cell neoplasia from January 2008 to December 2012. In addition, we conducted a statistical analysis of the following factors: sex, age, location, the proportion of circumferential extension, the maximum diameter of the resected specimen, macroscopic type, the depth of invasion, and the endoscopists. A total of 145 patients were included in the study. Overall, 148 lesions were completely resected. There were 17 patients (17 lesions) presenting with positive resection margin after ESD and the positive rate was 11.5 %. A total of 16 patients were followed-up. Among the patients who had resection margin residues, three underwent surgical esophageal resection, one underwent radiotherapy, two received ESD, and one received endoscopic mucosal resection. The remaining nine patients were periodically followed-up, and no recurrences were found. The results of a one-dimensional analysis suggested that there were significant differences in the maximum diameters of the resected specimens, macroscopic type, and the depth of invasion between the positive resection margin group and the negative resection margin group. The results of a multivariate regression analysis suggested that the maximum diameter of the resected specimens and the depth of invasion were risk factors for resection margin residues. The maximum diameter of the resected specimens and the depth of tumor invasion are risk factors for post-ESD positive resection margins, which suggests that larger lesions and a greater depth of invasion increases the chance of residual tumor after ESD.

Feasibility and efficacy of argon plasma coagulation for early esophageal squamous cell neoplasia

We present 19 cases in which argon plasma coagulation (APC) was used as curative initial treatment for 5 low-grade esophageal squamous intraepithelial neoplasias (ESINs), 12 high-grade ESINs, and 2 early esophageal squamous cell carcinomas (ESCCs). Complete response was defined as the absence of tumor from any biopsy taken from the ablated lesion. At follow-up endoscopy 2 - 4 months after APC, 94.7 % of patients had achieved complete response in a single treatment session. Only one patient with high-grade ESIN showed local recurrence. This patient underwent additional APC and showed complete response at 12 months after initial APC. At the 12-month follow-up endoscopy, again 94.7 % had a complete response. The exception was one patient with local recurrence, who underwent additional APC. After the 12-month follow-up endoscopy, no patient showed local recurrence during a median follow-up of 22 months. No stricture requiring endoscopic dilation occurred after the procedure. This study suggests that APC is a feasible and effective treatment modality for ESIN and early ESCC.

Su1483 Current Dose and Technique Recommendation for Radiofrequency Ablation of Early Flat-Type Esophageal Squamous Cell Neoplasia Based on Outcomes From a Prospective Dose-Ranging Trial

The optimal dose/technique for radiofrequency ablation (RFA) for Barrett's esophagus (BE) was derived in dose escalation trials and further vetted in clinical trials and practice. By contrast, little is known about the optimal dose/technique for RFA for early esophageal squamous cell neoplasia (ESCN), defined as moderate- or high-grade intraepithelial neoplasia (MGIN, HGIN), and flat esophageal squamous cell carcinoma (ESCC, T1m2).

242 Diagnosis of Early Barrett's Neoplasia and Esophageal Squamous Cell Neoplasia by Electrical Bio-Impedance Spectroscopy in Human Tissue

Detection of early esophageal cancer in surrounding normal tissue can be challenging even for experienced examiners. Early detection is essential to determine the following treatment. Early stages of esophageal cancers can be treated by endoscopic resection (ER) whereas advanced neoplasias might lead to esophagectomy. Diagnosis is usually made by biopsies of suspicious lesions or untargeted quadrant biopsies. The electrical properties in inflammatory tissue and dysplasia can be sensed by electrical bioimpedance technique.

Outcomes from a prospective trial of endoscopic radiofrequency ablation of early squamous cell neoplasia of the esophagus

Radiofrequency ablation (RFA) is safe and effective for eradicating neoplasia in Barrett's esophagus. To evaluate RFA for eradicating early esophageal squamous cell neoplasia (ESCN) defined as moderate-grade squamous intraepithelial neoplasia (MGIN) and high-grade squamous intraepithelial neoplasia (HGIN) and early flat-type esophageal squamous cell carcinoma (ESCC). Prospective cohort study. Tertiary referral center. Esophageal unstained lesions (USLs) were identified using Lugol's chromoendoscopy. Inclusion criteria were at least 1 flat (type 0-IIb) USL 3 cm or larger, USL-bearing esophagus 12 cm or less, and a consensus diagnosis of MGIN, HGIN, or ESCC by 2 expert GI pathologists. Exclusion criteria were previous endoscopic resection or ablation, stricture, or any nonflat mucosa. Circumferential RFA creating a continuous treatment area (TA) including all USLs. At 3-month intervals thereafter, chromoendoscopy with biopsies followed by focal RFA of USLs, if present. Complete response (CR) at 12 months defined as absence of MGIN, HGIN, or ESCC in the TA, CR after 1 RFA session, neoplastic progression from baseline, and adverse events. Twenty-nine patients (14 male, mean age 60.3 years) with MGIN (n = 18), HGIN (n = 10), or ESCC (n = 1) participated. Mean USL length was 6.2 cm (TA 8.2 cm). At 3 months after 1 RFA session, 86% of patients (25/29) had a CR. At 12 months, 97% of patients (28/29) had a CR. There was no neoplastic progression. There were 4 strictures, all dilated to resolution. Single-center study with limited number of patients. In patients with early ESCN (MGIN, HGIN, flat-type ESCC), RFA was associated with a high rate of histological complete response (97% of patients), no neoplastic progression, and an acceptable adverse event profile.

Low-Cost Microendoscopy for the Diagnosis of Esophageal Squamous Cell Neoplasia in Northern China: An Evaluation of Interobserver Agreement and Accuracy

Low-Cost Microendoscopy for the Diagnosis of Esophageal Squamous Cell Neoplasia in Northern China: An Evaluation of Interobserver Agreement and Accuracy

Su1504 Endoscopic Submucosal Dissection of Superficial Esophageal Squamous Cell Neoplasia by Scissors-Like Forceps: A Safer Technique

Su1504 Endoscopic Submucosal Dissection of Superficial Esophageal Squamous Cell Neoplasia by Scissors-Like Forceps: A Safer Technique

Endoscopic submucosal dissection in patients with early esophageal squamous cell carcinoma: results from a prospective Western series

Although endoscopic submucosal dissection (ESD) is becoming accepted as an established treatment for superficial esophageal squamous cell neoplasia, the majority of data on this endoscopic modality has been provided by Japanese series. To assess the efficacy and safety of ESD for esophageal squamous cell neoplasia in a consecutive series of patients treated in a Western setting. Single-center, prospective observational study. From January 2005 to July 2008, 20 patients with superficial esophageal squamous cell neoplasia were treated by ESD. Rates of en bloc resection, complete resection, and complications were evaluated as short-term outcomes. Overall survival, local or distant recurrence, and postoperative stricture rates were evaluated as long-term outcomes. ESD was performed in 20 patients (mean age 64 years, range 46-81 years; 16 men). The mean size of the lesion was 32 mm (range 15-60 mm); it was 30 mm or larger in 14 patients (70%). The mean time of ESD was 89 minutes (range 58-180 minutes). En bloc resection with resection-free margins was achieved in 18 patients (90%), whereas 2 patients presented with incomplete or indeterminate resection. Two cases (10%) of mediastinal emphysema without overt perforation and 1 case (5%) of post-ESD symptomatic stricture were reported. No local or distant post-ESD recurrence occurred in those with resection-free margins at a median follow-up of 18 months. Small number of patients and limited follow-up. This Western series study confirms that ESD is a potentially curative treatment for superficial esophageal squamous cell neoplasia. Early and late complication rates were comparable to those of Japanese series. ESD should be probably considered as the treatment of choice in all large lesions amenable to endoscopic treatment.

Radiofrequency ablation for early esophageal squamous cell neoplasia

Esophageal cancer is the sixth most common cause of cancer death in the world [1]. Over 80% of esophageal cancers occur in developing countries [1], and in these areas, 90% of these cancers are esophageal squamous cell carcinoma (ESCC) [2]. The precursor lesion of ESCC is squamous intraepithelial neoplasia (squamous dysplasia), defined histologically as nuclear atypia (enlargement, pleomorphism and hyperchromasia), loss of normal cellular polarity, and abnormal tissue maturation [3,4]. WHO subclassifies squamous intraepithelial neoplasia into low-grade intraepithelial neoplasia (LGIN) and high-grade intraepithelial neoplasia (HGIN), depending on the extent of the nuclear atypia and the involvement of the epithelium [4]. In China, where ESCC and its precursors are very common in some areas, a three-tier system is used, including LGIN (mild dysplasia, involving the lower third of the epithelium), medium-grade intraepithelial neoplasia (MGIN, moderate dysplasia, involving the lower two-thirds of the epithelium), and HGIN (severe dysplasia, involving the full thickness of the epithelium) [3]. Follow-up studies in China have shown that the rate of progression to ESCC differs significantly between LGIN (5.3% over 3.5 years), MGIN (26.7%), and HGIN (65.2%), and because of their significant risk of progression, MGIN and HGIN are targets for screening and therapy [5,6]. Current treatment of esophageal squamous cell neoplasia (ESCN, including squamous intraepithelial neoplasia and invasive squamous cell carcinoma) involves surgery for lesions invading into the deep submucosa or beyond and endoscopic treatment for lesions restricted to the epithelial layer (intraepithelial neoplasia; m1) or the lamina propria (m2). Lesions invading into the muscularis mucosae (m3) or superficial submucosa (sm1) are considered the “grey zone” between endoscopic and surgical treatment. One option for endoscopic treatment of early ESCN involves endoscopic resection (ER) of unstained lesions (USLs) after Lugol’s chromoscopy, as USLs are predictive for the presence of neoplasia. ER allows for histological staging of infiltration depth, tumor differentiation, lymph-vascular invasion, while completely removing the visible lesion. USLs larger than 15 mm require either piecemeal resection with the standard cap-based ER techniques or endoscopic submucosal dissection (ESD) for complete resection. Widespread ER/ESD, however, is technically demanding, with procedure times of many hours, and is associated with severe esophageal stenosis for lesions that encompass >75% of the circumference and a significant risk for esophageal perforation and bleeding. Complete endoscopic resection is also not necessarily the best approach for all patients with early ESCN. Large flat type lesions (i.e. type 0-IIb), which carry a very low risk for deeper invasion, can be effectively treated by an endoscopic ablation technique that is much easier to apply and is associated with a very low rate of complications, such as esophageal stenosis. A safe, effective and technically easy to administer ablation method is especially attractive for geographic areas where ESCN is endemic and most endoscopists have a lower level of expertise in ER/ESD. In China, there are many high-risk areas for ESCN, such as the Taihang mountain range in North-central China and areas in Sichuan, Shandong, Jiangsu and Fujian Provinces and the Xinjiang Uygur Autonomous Region [7]. These high-risk areas in China are estimated to include a total of over 100 million people, and invasive ESCN occurs here at rates approaching or surpassing 100/100,000 people per year [2], an incidence approximately 30-fold of that of Barrett’s related esophageal adenocarcinoma in the Western world [8]. The Chinese government is supporting widespread endoscopic screening using Lugol’s chromoscopy in these high-risk areas and in 2010 it is estimated that 57,000 subjects will undergo such a screening endoscopy. From this screening process, it is estimated that 5% of patients will have MGIN, HGIN, or early cancer limited to the epithelium and will be eligible for endoscopic therapy.