Superficial Esophageal Squamous Cell Carcinoma Research Articles

Utility of an artificial intelligence system for classification of esophageal lesions when simulating its clinical use

Previous reports have shown favorable performance of artificial intelligence (AI) systems for diagnosing esophageal squamous cell carcinoma (ESCC) compared with endoscopists. However, these findings don’t reflect performance in clinical situations, as endoscopists classify lesions based on both magnified and non-magnified videos, while AI systems often use only a few magnified narrow band imaging (NBI) still images. We evaluated the performance of the AI system in simulated clinical situations. We used 25,048 images from 1433 superficial ESCC and 4746 images from 410 noncancerous esophagi to construct our AI system. For the validation dataset, we took NBI videos of suspected superficial ESCCs. The AI system diagnosis used one magnified still image taken from each video, while 19 endoscopists used whole videos. We used 147 videos and still images including 83 superficial ESCC and 64 non-ESCC lesions. The accuracy, sensitivity and specificity for the classification of ESCC were, respectively, 80.9% [95% CI 73.6–87.0], 85.5% [76.1–92.3], and 75.0% [62.6–85.0] for the AI system and 69.2% [66.4–72.1], 67.5% [61.4–73.6], and 71.5% [61.9–81.0] for the endoscopists. The AI system correctly classified all ESCCs invading the muscularis mucosa or submucosa and 96.8% of lesions ≥ 20 mm, whereas even the experts diagnosed some of them as non-ESCCs. Our AI system showed higher accuracy for classifying ESCC and non-ESCC than endoscopists. It may provide valuable diagnostic support to endoscopists.

Current status of endoscopic detection, characterization and staging of superficial esophageal squamous cell carcinoma.

This review focuses on the current status of endoscopic detection, characterization and tumour category staging of oesophagealsquamous cell carcinoma. The diagnostic yield of white-light imaging is limited and narrow-band imaging has demonstrated a better performance for detecting oesophageal cancer. Narrow-band imaging has also shown similar sensitivity and superior specificity to iodine staining. Accurate differentiation between cancerous and non-cancerous lesions can be achieved by magnifying narrow-band imaging or iodine staining with confirmation of a pink-colour sign. A per-patient analysis of a randomized study showed similar sensitivities, specificities and overall accuracies of magnifying narrow-band imaging and iodine staining of 82.2%, 95.1% and 91.2%, and 80.5%, 94.3% and 90.5%, respectively. The diagnostic capability of endoscopic ultrasonography after conventional and narrow-band imaging in terms of tumour depth was evaluated in a multicentre prospective study. Endoscopic ultrasonography did not significantly improve the accuracy for distinguishing between mucosal or submucosal microinvasive cancer and deeper cancers from 72.9 to 74.0%, suggesting that additional endoscopic ultrasonography did not improve the diagnostic accuracy. In addition, endoscopic ultrasonography increased the incidence of overdiagnosis, defined as a diagnosis of cancer depth greater than the actual depth, by 6.6%. The risk of overdiagnosis by endoscopic ultrasonography was reconfirmed in two systematic reviews. Narrow-band imaging is currently considered as the standard modality for the detection and characterization of oesophageal cancer. The risk of overdiagnosis should be considered when applying endoscopic ultrasonography for the evaluation of tumour invasion depth of superficial oesophageal squamous cell carcinoma.

Endoscopic imaging modalities for diagnosing the invasion depth of superficial esophageal squamous cell carcinoma: a systematic review.

Endoscopic diagnosis of the invasion depth of superficial esophageal squamous cell carcinoma (ESCC) is an important determinant of the treatment strategy. The three endoscopic imaging modalities commonly used to predict the invasion depth of superficial ESCC in Japan are non-magnifying endoscopy (non-ME), magnifying endoscopy (ME), and endoscopic ultrasonography (EUS). However, which of these three modalities is most effective remains unclear. We performed a systematic review of the literature to compare the diagnostic accuracy of the three modalities for prediction of the invasion depth of superficial ESCC. We used Medical Subject Heading terms and free keywords to search the PubMed, Cochrane Central, and Ichushi databases to identify direct comparison studies published from January 2000 to August 2020. The results of direct comparison studies were used to compare the diagnostic accuracy of each modality. The primary outcome was defined as the proportion of overdiagnosis of pT1b-SM2/3 cancers, and the main secondary outcome was the proportion of underdiagnosis of pT1b-SM2/3 cancers. Other secondary outcomes were the sensitivity and specificity values of the modalities. Four articles were finally selected for qualitative evaluation. Although ME showed no significant advantages over non-ME in terms of sensitivity and specificity, it had a slightly lower proportion of overdiagnosis. EUS had sensitivity and specificity similar to those of non-ME and ME, but EUS had a higher proportion of overdiagnosis. Non-ME and ME are useful for the diagnosis of cancer invasion depth. EUS may increase overdiagnosis, and caution is required in determining its indications.

Influence of radiation dose and predicted tumor invasion depth on local recurrence after definitive chemoradiotherapy for stage 0\u2013I esophageal squamous cell carcinoma: a propensity score-weighted, retrospective, observational study

BackgroundThe optimal radiation dose for treating non-metastatic superficial esophageal squamous cell carcinoma is unknown. In this retrospective observational study, we investigated the influence of radiation dose and pretreatment endoscopic prediction of tumor invasion depth on local recurrence after definitive chemoradiotherapy in patients with superficial esophageal squamous cell carcinoma.MethodsWe analyzed 134 patients with clinical Tis–T1N0M0 esophageal squamous cell carcinoma who underwent chemoradiotherapy at our institution between 2006 and 2019. Patients were grouped into standard-dose (50.0–50.4 Gy) and high-dose (60.0 Gy) radiotherapy groups. The outcomes of interest were local recurrence and major local recurrence (endoscopically unresectable local recurrent tumors). Kaplan–Meier analysis and the log-rank test were used with propensity score and inverse probability of treatment weighting. Cox proportional hazards analysis was performed to identify predictors of local recurrence and major local recurrence.ResultsThe median follow-up times were 52 and 84 months for the standard-dose and high-dose groups, respectively. The adjusted 3-year local recurrence and major local recurrence rates in the standard-dose and high-dose groups were 33.8 and 9.6% (adjusted hazard ratio, 4.00 [95% confidence interval: 1.64–9.73]; adjusted log-rank p = 0.001) and 12.5 and 4.7% (adjusted hazard ratio, 3.13 [95% confidence interval: 0.91–10.81]; adjusted log-rank p = 0.098), respectively. Cox proportional hazards analysis showed that standard-dose radiotherapy and endoscopic findings of deep submucosal invasion are independently associated with local recurrence and major local recurrence.ConclusionsHigh-dose radiotherapy is more beneficial for local tumor control than standard-dose radiotherapy in patients with non-metastatic superficial esophageal squamous cell carcinoma. The use of high-dose radiotherapy may merit consideration for tumors with deep submucosal invasion.

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

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

Endoscopic Diagnosis and Treatment of Superficial Esophageal Squamous Cell Cancer: Present Status and Future Perspectives.

This review provides information regarding the preoperative examinations, indications for endoscopic resection (ER), and curability assessment in subjects with superficial esophageal squamous cell carcinoma (SCC). Narrow-band imaging (NBI) is a more sensitive modality for detecting esophageal cancer than conventional observation, and esophageal observation using NBI is thus recommended for the detection of superficial esophageal cancer. It is also important to adjust the volume of air in the esophagus during observation. Workup by non-magnifying followed by magnifying endoscopy is a common process for diagnosing the invasion depth of superficial esophageal SCCs in Japan. Endoscopic ultrasonography carries a risk of overdiagnosis, and its routine use is therefore not recommended. The Japanese endoscopic submucosal dissection/endoscopic mucosal resection guidelines for esophageal cancer considered the indications for ER based on the results of studies focusing on clinical MM/SM1 cancers, and concluded that clinical MM/SM1 carcinomas, except circumferential carcinoma, were an indication for ER. The curative effect of ER should be assessed based on histologic examination of the resected specimens. ER should be conducted based on a thorough understanding of the preoperative diagnosis, indication, curability, and additional treatment of esophageal SCC.

Endoscopic submucosal dissection versus esophagectomy for t1 esophageal squamous cell carcinoma: a propensity score-matched analysis.

Endoscopic submucosal dissection (ESD) has been a preferred treatment option for superficial esophageal squamous cell carcinoma (SESCC). To compare the outcomes of ESD and esophagectomy in the treatment of SESCC, especially for lesions invading muscularis mucosa or submucosa (pT1a-MM/T1b). We retrospectively analyzed data from patients with SESCC who underwent ESD or esophagectomy between 2015 and 2021. After propensity score matching, overall survival (OS), disease-specific survival (DSS), recurrence-free survival (RFS), and treatment-related events were compared between the ESD and esophagectomy groups. Furthermore, we performed a Cox regression analysis to identify factors associated with survival. OS and DSS were significantly higher in the ESD group (n = 508) than that in the esophagectomy group (n = 466). After matching, 404 patients (202 per group) were included in the study. No significant differences were found between the ESD and esophagectomy groups in OS (p = 0.566), RFS (p = 0.586), and DSS (p = 0.912). The ESD group showed less blood loss, shorter procedure duration and hospital stay, lower hospital cost, and fewer adverse events. However, a lower R0 resection rate was observed in the ESD group compared to the esophagectomy group. Subgroup analysis showed comparable survival outcomes between the two groups. In Cox regression analysis, age was the independent factor associated with OS. In the treatment of SESCC, ESD showed sufficient safety and advantages. Even for pT1a-MM/pT1b SESCC, ESD may be an alternative treatment to esophagectomy.

Field Effect of Alcohol, Cigarette Smoking, and Their Cessation on the Development of Multiple Dysplastic Lesions and Squamous Cell Carcinoma: A Long-term Multicenter Cohort Study.

Multiple developments of squamous dysplasia and squamous cell carcinoma (SCC) in the upper aerodigestive tract have been explained by field cancerization phenomenon and were associated with alcohol and cigarette use. Second primary SCC development after curative treatment impairs patients' quality of life and survival; however, how these consumption and cessation affect field cancerization is still unknown. This is a multicenter cohort study including 331 patients with superficial esophageal SCC (ESCC) treated endoscopically and pooled data from 1022 healthy subjects for comparison. Physiological condition in the background esophageal mucosa was classified into 3 groups based on the number of Lugol-voiding lesions (LVLs) per endoscopic view: grade A, 0; grade B, 1-9; or grade C, ≥10 LVLs. Lifestyle surveys were conducted using a self-administered questionnaire. Patients were counseled on the need for alcohol and smoking cessation by physicians and were endoscopically surveyed every 6 months. LVL grades were positively associated with alcohol drinking intensity, flushing reactions, smoking, and high-temperature food and were negatively associated with eating green and yellow vegetables and fruit. Second primary ESCC and head/neck SCC were significantly more prevalent in the grade C LVL (cumulative 5-y incidences 47.1%, 95% confidence interval [CI]= 38.0-57.2 and 13.3%, 95% CI= 8.1-21.5, respectively). Alcohol and smoking cessation significantly reduced the development of second primary ESCC (adjusted hazard ratios 0.47, 95%= CI 0.26-0.85 and 0.49, 95% CI= 0.26-0.91, respectively). Alcohol drinking, smoking, flushing reaction, and high-temperature food were closely associated with field cancerization, and cessation of alcohol and smoking significantly reduced the risk of development of second primary cancer. UMIN Clinical Trials Registry ID:UMIN000001676.

Establishment of a Preoperative Laboratory Panel to identify Lymph Node Metastasis in Superficial Esophageal Cancer.

Background and Aims: In superficial esophageal squamous cell carcinoma (SESCC), the lymph node status is considered as one of the essential factors to determine the primary treatment strategy. Nevertheless, current noninvasive staging methods before surgical intervention have limited accuracy. This study aimed to establish a simple and noninvasive serum-testing panel that facilitates the preoperative prediction of pathological nodal status in SESCC patients.Methods: Data for preoperative hematological parameters were retrospectively collected from 256 SESCC patients who underwent esophagectomy from December 2017 to May 2020. The random forest classification and decision tree algorithms were applied to identify the optimal combination of serum parameters for accurately identifying positive nodal metastasis.Results: Twelve candidate parameters were identified for statistical significance in predicting positive nodal metastasis. A multi-analyte panel was established by using a random forest classification method, incorporating four optimal parameters: Hematocrit (HCT), Activated Partial Thromboplastin Time (APTT), Retinol-Binding Proteins (RBP), and Mean Platelet Volume (MPV). A schematic decision tree was yielded from the above panel with an 89.1% accuracy of classification capability.Conclusions: This study established a simple laboratory panel in discerning the preoperative lymph nodal status of SESCC patients. With further validation, this panel may serve as a simple tool for clinicians to choose appropriate intervention (surgery versus endoscopic resection) for SESCC patients.

Comparative Study of Conventional and Ultrahigh-resolution Optical Coherence Tomography Imaging in Esophageal Neoplasia

Early diagnosis of esophageal cancer can be enhanced by the application of optical coherence tomography (OCT) to gastrointestinal endoscopy. One of the most salient examples is the use of OCT to augment the detection of dysplasia during Barrett's esophagus (BE) surveillance, the established precursor to esophageal adenocarcinoma (EAC). 1 Reid BJ Li X Galipeau PC et al. Barrett’s oesophagus and oesophageal adenocarcinoma: time for a new synthesis. Nat Rev Cancer. 2010; 10: 87-101https://doi.org/10.1038/nrc2773 Crossref PubMed Scopus (303) Google Scholar , 2 Pohl H Welch HG The role of overdiagnosis and reclassification in the marked increase of esophageal adenocarcinoma incidence. J Natl Cancer Inst. 2005; 97: 142-146https://doi.org/10.1093/jnci/dji024 Crossref PubMed Scopus (1069) Google Scholar A previously commercially available balloon-based imaging catheter system, also known as volumetric laser endomicroscopy (VLE), was designed to provide circumferential esophageal imaging at the time of endoscopy. The VLE system uses a 1300 nm wavelength-swept laser and provides images with an axial resolution of 7 µm up to a depth of 3 mm. VLE is capable of resolving microarchitectural features associated with early neoplasia in BE including irregular glandular morphology and increased surface signal intensity. 3 Leggett CL Gorospe EC Chan DK et al. Comparative diagnostic performance of volumetric laser endomicroscopy and confocal laser endomicroscopy in the detection of dysplasia associated with Barrett’s esophagus. Gastrointest Endosc. 2016; 83: 880-888.e2https://doi.org/10.1016/j.gie.2015.08.050 Abstract Full Text Full Text PDF PubMed Scopus (86) Google Scholar Scoring systems that incorporate these features are associated with a sensitivity of 76-83% and specificity of 71-79% in the diagnosis of BE neoplasia. 3 Leggett CL Gorospe EC Chan DK et al. Comparative diagnostic performance of volumetric laser endomicroscopy and confocal laser endomicroscopy in the detection of dysplasia associated with Barrett’s esophagus. Gastrointest Endosc. 2016; 83: 880-888.e2https://doi.org/10.1016/j.gie.2015.08.050 Abstract Full Text Full Text PDF PubMed Scopus (86) Google Scholar , 4 Swager AF Tearney GJ Leggett CL et al. Identification of volumetric laser endomicroscopy features predictive for early neoplasia in Barrett’s esophagus using high-quality histological correlation. Gastrointest Endosc. 2017; 85: 918-926.e7https://doi.org/10.1016/j.gie.2016.09.012 Abstract Full Text Full Text PDF PubMed Scopus (52) Google Scholar Similarly, esophageal OCT has been used in the diagnosis and staging of squamous cell carcinoma (ESCC) where layer effacement predicts the depth of invasion. 5 Trindade AJ Benias PC Inamdar S et al. Use of volumetric laser endomicroscopy for determining candidates for endoscopic therapy in superficial esophageal squamous cell carcinoma. United European Gastroenterol J. 2018; 6: 838-845https://doi.org/10.1177/2050640618761701 Crossref PubMed Scopus (5) Google Scholar In the last decade, ultra-high resolution (UHR) OCT systems that operate at 800 nm and achieve an axial resolution closer to 2.5 µm have been developed. Our group previously described a super-achromatic OCT capsule designed for UHR esophageal imaging. 6 Li K Liang W Mavadia-Shukla J et al. Super-achromatic optical coherence tomography capsule for ultrahigh-resolution imaging of esophagus. J Biophotonics. 2019; 12e201800205https://doi.org/10.1002/jbio.201800205 Crossref PubMed Scopus (16) Google Scholar In the present study, we compare the imaging capability of UHR OCT to VLE in distinguishing microarchitectural features associated with esophageal neoplasia by imaging ex vivo esophageal resection specimens obtained from patients undergoing clinical endoscopy.

Decreased Expression of NRF2 Target Genes after Alcohol Exposure in the Background Esophageal Mucosa of Patients with Esophageal Squamous Cell Carcinoma.

Patients with esophageal squamous cell carcinoma (ESCC) might have a specific mechanism for the carcinogenesis by alcohol consumption in the background esophageal mucosa, and nuclear factor erythroid 2-related factor 2 (NRF2), which plays a protective role against esophageal carcinogenesis, and barrier dysfunction might be associated with this phenomenon. This study aimed to confirm this hypothesis. Twenty patients with superficial ESCCs (ESCC patients) and 20 age- and sex-matched patients without ESCC (non-ESCC patients) were enrolled. Biopsy samples were obtained from non-neoplastic esophageal mucosa: one for histological evaluation, one for quantitative real-time polymerase chain reaction (PCR), and two for the mini-Ussing chamber system to measure transepithelial electrical resistance (TEER) and, thereafter, for PCR. The TEER after acetaldehyde or both acetaldehyde and ethanol exposure did not differ significantly between ESCC and non-ESCC patients. Unlike non-ESCC patients, mRNA levels of NRF2 target genes and claudin4 in ESCC patients tended to decrease after the exposure, with a significant difference between no exposure and both acetaldehyde and ethanol exposure in NRF2 target genes (p < 0.05). Furthermore, in ESCC patients, the decreased tendency of mRNA levels of NRF2 target genes after the exposure was more pronounced in high-risk states, such as aldehyde dehydrogenase 2 (ALDH2) Lys alleles (Glu/Lys + Lys/Lys), Lugol-voiding lesion grade C, and drinking history. In conclusion, the protective role of NRF2 against carcinogenesis from alcohol exposure might be disrupted in the background esophageal mucosa of ESCC patients, which might lead to a high incidence of metachronous ESCC.

Salvage Endoscopic Submucosal Dissection for Local Recurrence of Superficial Esophageal Squamous Cell Cancer after Photodynamic Therapy.

Photodynamic therapy is useful as organ-preservation salvage therapy for residual recurrence of esophageal squamous cell carcinoma after chemoradiation therapy. However, the high residual recurrence rate of photodynamic therapy poses a problem. We herein report a patient who underwent photodynamic therapy for recurrence of superficial esophageal squamous cell carcinoma after chemoradiation therapy. The patient later exhibited another episode of recurrence of superficial esophageal squamous cell carcinoma, and R0 curative resection was obtained with endoscopic submucosal dissection. This suggests that endoscopic submucosal dissection may be an effective treatment option that can achieve R0 resection even for residual superficial cancer after salvage photodynamic therapy.

Treatment of Superficial Esophageal Cancer: An Update

Superficial esophageal squamous cell carcinoma (SESCC) is an esophageal squamous cell carcinoma confined to the mucosa or superficial submucosa. Recent Korean Guidelines recommend an endoscopic resection as the first-line treatment for SESCC without a distant or lymph node metastasis (LNM) after excluding those with an obvious submucosal invasion. Before endoscopic treatment of SESCC, Lugol chromoendoscopy or image-enhanced endoscopy is recommended to define the extent of the lesion, and endoscopic ultrasound is recommended to determine the T stage. The tumor size, macroscopic type of tumor, pathologic differentiation, depth of tumor, and lymphovascular invasion (LVI) are risk factors of LNM in SESCC. No additional treatment is necessary after an en bloc complete resection of SESCC invading no more than the lamina propria without LVI. Although the risk of LNM in a SESCC invading into muscularis mucosa without LVI is low, a close follow-up is recommended without additional treatment. On the other hand, additional treatment is recommended in the case of a tumor with submucosal invasion or an LVI positive or positive vertical resection margin. Adjuvant therapy includes esophagectomy or chemoradiotherapy (CRT), but it is unclear which treatment is better. The 5-year overall survival rates were reportedly 90-100% for esophagectomy and 75-85% for CRT. Nevertheless, patients with high-risk features including poorly differentiated histology, LVI positive, perineural invasion positive, T1b-SM2/T1b-SM3 cancer, and vertical resection margin positive need to be treated with an additional esophagectomy. Elderly patients, those with a physical condition and co-morbidities, and those with LNM or cancer-specific mortality require additional treatment after a non-curative endoscopic resection of SESCC.

Blue laser imaging identifies endoscopic findings corresponding to metachronous esophageal squamous cell carcinoma.

This study aimed to evaluate endoscopic findings using non-magnifying blue laser imaging (BLI) to determine the risk factors for metachronous esophageal squamous cell carcinoma (ESCC). All consecutive patients who underwent endoscopic submucosal dissection (ESD) for primary superficial ESCC (SESCC) without a history of ESCC between January 2013 and January 2016 were enrolled. Three highly experienced endoscopists investigated seven endoscopic findings using non-magnifying BLI as follows: (1) a brownish area with unclear margin, (2) white flat deposits, (3) multiple foci of dilated vessels, (4) low capillary permeability, (5) multiple glycogenic acanthosis, (6) horizontal lines, and (7) a nonuniform color tone. Furthermore, Lugol-voiding lesions (LVLs) were graded according to the number of LVLs per endoscopic view (A, no lesions; B, 1-9 lesions; C, ≥ 10 lesions). A total of 102 SESCC patients who underwent ESD were included. Multivariate analyses showed that multiple foci of dilated vessels, low capillary permeability, and a nonuniform color tone were significantly associated with metachronous ESCC (hazard ratio [HR] 2.30; 95% confidence interval [CI] 1.01-5.46;P = 0.049, HR 5.25; 95% CI 1.86-15.01;P = 0.002 and HR 3.17; 95% CI 1.11-9.43; P = 0.032, respectively). The three-year cumulative incidence of metachronous ESCC was significantly higher in patients with low capillary permeability and a nonuniform color tone than in patients without these findings. (41.1% vs. 6.0%, 45.0% vs. 12.7%, respectively, P < 0.001 for both). BLI findings of multiple foci of dilated vessels, low capillary permeability, and a nonuniform color tone in the background esophageal mucosa were risk factors for patients with metachronous ESCC after ESD.

Evaluation of long-term survival in patients with severe comorbidities after endoscopic submucosal dissection for esophageal squamous cell carcinoma.

Endoscopic submucosal dissection (ESD) is becoming widely popular as a less invasive treatment option for superficial esophageal squamous cell carcinoma. However, data on long-term survival after esophageal ESD in patients with severe comorbidities are limited. This study aimed to evaluate long-term survival after ESD in such patients. Altogether, 584 consecutive patients underwent esophageal ESD at our institution from May 2004 to September 2016. Based on the American Society of Anesthesiologists Physical Status (ASA-PS) classification system, patients were grouped according to severe (ASA-PS ≥ 3) or non-severe comorbidities (ASA-PS 1/2). The overall survival (OS), disease-specific survival (DSS), and risk factors for mortality were compared between the groups using a propensity score matching analysis. In a matched cohort of 69 pairs, the 5-year OS rate was poorer in ASA-PS 3 patients than in ASA-PS 1/2 patients (63.9% vs. 92.5%, P < 0.01), while the 5-year DSS rate was similar between the groups (100% vs. 100%). The mortality rate was significantly higher in ASA-PS 3 patients than in ASA-PS 1/2 patients (hazard ratio 3.47; 95% confidence interval 1.79-6.74; P < 0.01). Death due to exacerbation of comorbidities was significantly more frequent in ASA-PS 3 patients than in ASA-PS 1/2 patients (42.4% vs. 8.3%, P < 0.04). Because of the exacerbation of comorbidities, patients with severe comorbidities had poorer long-term outcomes after esophageal ESD than those with non-severe comorbidities. Further studies will be necessary to evaluate esophageal ESD in patients with severe comorbidities.

Comparison of Magnifying Endoscopy with Blue Light Imaging and Narrow Band Imaging for Determining the Invasion Depth of Superficial Esophageal Squamous Cell Carcinoma by the Japanese Esophageal Society’s Intrapapillary Capillary Loop Classification

Blue light imaging (BLI) and narrow-band imaging (NBI) are two modalities that enable narrow-band light observation. We aimed to compare the diagnostic ability of magnifying endoscopy with BLI (ME-BLI) and NBI (ME-NBI) for determining the invasion depth of superficial esophageal squamous cell carcinoma (SESCC) by the Japanese Esophageal Society’s intrapapillary capillary loop (IPCL) classification. We enrolled 81 patients between 2014 and 2018, and the still endoscopic images for diagnosing the invasion depth at the same part in ME-BLI and ME-NBI were registered. Two blinded investigators reviewed them and diagnosed the invasion depth by the IPCL classification. Subsequently, the diagnostic yields in two modalities were compared. The overall accuracies for the invasion depth by the IPCL classification in ME-BLI and ME-NBI did not differ significantly (67.9–71.6% vs. 72.8–74.1%). In the analysis based on the invasion depth, the sensitivities and positive predictive values in tumors invading the muscularis mucosa or submucosa ≤200 µm were low (23.1–30.8% and 16.7–25.0%, respectively) in both modalities. In conclusion, the diagnostic ability for determining the invasion depth of SESCC by the IPCL classification was relatively similar in ME-BLI and ME-NBI, but diagnosis by magnifying endoscopy alone might not be satisfactory.

Long-term outcomes of esophageal squamous cell carcinoma with invasion depth of pathological T1a-muscularis mucosae and T1b-submucosa by endoscopic resection followed by appropriate additional treatment.

Endoscopic resection (ER) is indicated for a wide range of superficial esophageal squamous cell carcinomas (ESCCs). We examined the long-term outcomes in patients with pathological (p) invasion of ESCC into the T1a-muscularis mucosae (MM) and T1b-submucosa (SM) after ER, for which data on prognosis are limited. Of the 1217 patients with superficial ESCC who underwent ER, 225 patients with a pathological diagnosis of ESCC invasion into the MM, minute submucosal invasion ≤200 µm (SM1), or massive submucosal invasion (SM2) were included. In patients with lymphovascular invasion, droplet infiltration, or SM2 invasion, additional treatments, including chemoradiation (CRT) or esophagectomy with two- to three-field lymph node dissection, were recommended. The median observation period was 66 months (interquartile range 48-91 months). In total, there were 151, 28, and 46 pT1a-MM, pT1b-SM1, and pT1b-SM2 cases, respectively. Metastatic recurrence was observed in 1.3%, 10.7%, and 6.5% patients with pT1a-MM, pT1b-SM1, and pT1b-SM2 ESCCs, respectively. Of the eight patients with metastatic recurrence, six were successfully treated, and two died of ESCC. The 5-year overall survival rates were 84.1%, 71.4%, and 67.4%, the 5-year relapse-free survival rates were 82.8%, 64.3%, and 65.2%, and the 5-year disease-specific survival rates were 100%, 96.4%, and 99.1% in patients with pT1a-MM, pT1b-SM1, and pT1b-SM2 ESCCs, respectively. Multivariate analysis showed that additional CRT and esophagectomy, and T1b-SM2 were positively and negatively associated with overall survival, respectively. Endoscopic resection preceding appropriate additional treatments resulted in favorable outcomes. Many cases of metastatic recurrence in this cohort could be successfully treated.

Artificial intelligence for detecting superficial esophageal squamous cell carcinoma under multiple endoscopic imaging modalities: A multicenter study.

Diagnosis of esophageal squamous cell carcinoma (ESCC) is complicated and requires substantial expertise and experience. This study aimed to develop an artificial intelligence (AI) system for detecting superficial ESCC under multiple endoscopic imaging modalities. Endoscopic images were retrospectively collected from West China Hospital, Sichuan University as a training dataset and an independent internal validation dataset. Images from other four hospitals were used as an external validation dataset. The AI system was compared with 11 experienced endoscopists. Furthermore, videos were collected to assess the performance of the AI system. A total of 53933 images from 2621 patients and 142 videos from 19 patients were used to develop and validate the AI system. In the internal and external validation datasets, the performance of the AI system under all or different endoscopic imaging modalities was satisfactory, with sensitivity of 92.5-99.7%, specificity of 78.5-89.0%, and area under the receiver operating characteristic curves of 0.906-0.989. The AI system achieved comparable performance with experienced endoscopists. Regarding superficial ESCC confined to the epithelium, the AI system was more sensitive than experienced endoscopists on white-light imaging (90.8% vs 82.5%, P=0.022). Moreover, the AI system exhibited good performance in videos, with sensitivity of 89.5-100% and specificity of 73.7-89.5%. We developed an AI system that showed comparable performance with experienced endoscopists in detecting superficial ESCC under multiple endoscopic imaging modalities and might provide valuable support for inexperienced endoscopists, despite requiring further evaluation.

Endoscopic resection of esophageal squamous cell carcinoma: Current indications and treatment outcomes.

Endoscopic resection (ER) is an alternate minimally invasive treatment for superficial esophageal squamous cell carcinoma (SESCC). We aimed to review the clinical indications and treatment outcomes of ER for SESCC. Endoscopic mucosal resection is relatively easy and efficient for SESCC ≤ 15 mm. In contrast, endoscopic submucosal dissection (ESD) is recommended to achieve en bloc resection for lesions >15 mm, in view of the accurate pathological evaluation. The Japan Gastroenterological Endoscopy Society guidelines recommend ER for non‐circumferential cT1a‐EP/LPM (epithelium/lamina propria mucosae), cT1a‐MM/T1b‐SM1 (muscularis mucosa/superficial submucosa ≤ 200μm) SESCC, and whole‐circumferential T1a‐EP/LPM SESCC ≤ 50 mm (upon implementing preventive measures for stenosis), considering the risk‐benefit balance of ER. It defines pT1a‐EP/LPM without lymphovascular invasion as a curative endoscopic resection. The guidelines recommend additional esophagectomy or chemoradiotherapy for pT1b SESCC or any SESCC, with lymphovascular invasion. However, there is no recommendation for or against the administration of additional treatments for pT1a‐MM without lymphovascular invasion, owing to limited evidence. Researchers have reported on high en bloc and R0 resection rates of ESD, and a randomized controlled trial demonstrated that clip‐line traction‐assisted ESD could significantly reduce the ESD procedural time. Moreover, steroid treatment has been developed to prevent post‐ESD esophageal strictures. There have been reports on favorable long‐term outcomes of ESD. However, most of them are retrospective studies. Further robust data in prospective trials are warranted to achieve a definitive evidence of ESD, which will be beneficial to patients with SESCC.

820 EFFICACY AND SAFETY OF ENDOSCOPIC SUBMUCOSAL DISSECTION FOR SUPERFICIAL ESOPHAGEAL SQUAMOUS CELL CARCINOMA AND PRECANCEROUS LESIONS

Abstract With the development of endoscopic technology, endoscopic mucosal dissection (ESD) has become one of the standard treatments for superficial esophageal squamous cell carcinoma and precancerous lesion (SESCC-PL). However, the efficacy and safety of ESD in some special SESCC-PL patients is still unclear. The purpose of this study was to analyze the efficacy and safety of ESD in patients with SESCC-PL, especially for some special patients. Methods Firstly, according to the depth of lesions, all patients were divided into three groups: the epithelium and lamina propria group (M1-M2), the muscularis mucosae and submucosal superficial layer group (M3-SM1) and the submucosal deep layer group (≥SM2). Secondly, according to the age of patients, all patients were divided into two groups: elderly group (≥ 65 years old) and non-elderly group (&amp;lt;65 years old). Finally, all patients were divided into two groups: patients with liver cirrhosis group and patients without liver cirrhosis group. The efficacy and safety of ESD for these patients were analyzed. Results There was no significant difference in operation time, resection speed, en bloc resection rate, bleeding rate, muscularis propria injury rate, perforation rate and intraoperative esophageal stricture rate in three groups with different depths of lesion. However, the R0 resection rate among the three groups decreased with the increase of lesion depth (P &amp;lt; 0.001). There was no significant difference in all surgical indexes between the non-elderly group and the elderly group (all P &amp;gt; 0.05). And there was also no significant difference in all surgical indexes including bleeding rate between the patients with liver cirrhosis and without liver cirrhosis (all P &amp;gt; 0.05). Conclusion This study proved that ESD is safe and effective for all kinds of patients with SESCC-PL, especially for patients with lesion depth ≥ M3, elderly patients and patients with liver cirrhosis, ESD can still achieve a satisfactory treatment effect and a good survival prognosis. Liver cirrhosis is not a contraindication to ESD.