Latest insights into the global epidemiological features,screening,early diagnosis and prognosis prediction of esophageal squamous cell carcinoma

As a highly invasive carcinoma,esophageal cancer(EC)was the eighth most prevalent malignancy and the sixth leading cause of cancer-related death worldwide in 2020.Esophageal squamous cell carcinoma(ESCC)is the major histological subtype of EC,and its incidence and mortality rates are decreasing globally.Due to the lack of specific early symptoms,ESCC patients are usually diagnosed with advanced-stage disease with a poor prognosis,and the incidence and mortality rates are still high in many countries,especially in China.Therefore,enormous challenges still exist in the management of ESCC,and novel strategies are urgently needed to further decrease the incidence and mortality rates of ESCC.Although the key molecular mechanisms underlying ESCC pathogenesis have not been fully elucidated,certain promising biomarkers are being investigated to facilitate clinical decision-making.With the advent and advancement of highthroughput technologies,such as genomics,proteomics and metabolomics,valuable biomarkers with high sensitivity,specificity and stability could be identified for ESCC.Herein,we aimed to determine the epidemiological features of ESCC in different regions of the world,especially in China,and focused on novel molecular biomarkers associated with ESCC screening,early diagnosis and prognosis prediction.

Plasma DNA methylation detection for early screening,diagnosis,and monitoring of esophageal adenocarcinoma and squamous cell carcinoma

BACKGROUND The early diagnosis rate of esophageal cancer(EC),one of the most prevalent digestive tract cancers worldwide,remains low.AIM To investigate the utility of plasma SHOX2,SEPTIN9,EPO,and RNF180 methylation in the clinical diagnosis and monitoring of EC.Plasma samples were collected from 210 patients at Hubei Cancer Hospital,and TaqMan polymerase chain reaction was employed to detect plasma SHOX2,SEPTIN9,RNF180,and EPO methylation.The area under the curve was used to estimate their diagnostic value for EC.Cox and logistic regression analyses were used to estimate the independent screening risk factors for patients with EC.RESULTS The sensitivity and specificity of combined assessment of plasma SHOX2,SEPTIN9,RNF180,and EPO methylation for adenocarcinoma,squamous cell carcinoma(SCC),and EC detection were 66.67%and 86.27%,77.40%and 85.29%,and 76.19%and 86.27%,respectively;the area under the curve values for diagnosing adenocarcinoma,SCC,and EC were 0.737[95%confidence interval(CI):0.584–0.89],0.824(95%CI:0.775–0.891),and 0.864(95%CI:0.809–0.92),respectively.CONCLUSION According to our findings,plasma SHOX2,SEPTIN9,RNF180,and EPO methylation exhibits appreciated sensitivity for diagnosing EC.The precise measurement of plasma SHOX2,SEPTIN9,RNF180,and EPO methylation can improve EC diagnosis and therapy efficacy monitoring.

Detachable string magnetically controlled capsule endoscopy for the noninvasive diagnosis of esophageal diseases:A prospective,blind clinical study

BACKGROUND Traditional esophagogastroduodenoscopy(EGD),an invasive examination method,can cause discomfort and pain in patients.In contrast,magnetically controlled capsule endoscopy(MCE),a noninvasive method,is being applied for the detection of stomach and small intestinal diseases,but its application in treating esophageal diseases is not widespread.AIM To evaluate the safety and efficacy of detachable string MCE(ds-MCE)for the diagnosis of esophageal diseases.METHODS Fifty patients who had been diagnosed with esophageal diseases were pros-pectively recruited for this clinical study and underwent ds-MCE and conven-tional EGD.The primary endpoints included the sensitivity,specificity,positive predictive value,negative predictive value,and diagnostic accuracy of ds-MCE for patients with esophageal diseases.The secondary endpoints consisted of visualizing the esophageal and dentate lines,as well as the subjects'tolerance of the procedure.RESULTS Using EGD as the gold standard,the sensitivity,specificity,positive predictive value,negative predictive value,and diagnostic accuracy of ds-MCE for esophageal disease detection were 85.71%,86.21%,81.82%,89.29%,and 86%,respectively.ds-MCE was more comfortable and convenient than EGD was,with 80%of patients feeling that ds-MCE examination was very comfortable or comfortable and 50%of patients believing that detachable string v examination was very convenient.CONCLUSION This study revealed that ds-MCE has the same diagnostic effects as traditional EGD for esophageal diseases and is more comfortable and convenient than EGD,providing a novel noninvasive method for treating esophageal diseases.

Early diagnosis of esophageal cancer:How to put“early detection”into effect?

This editorial comments on the article by Qu et al in a recent edition of World Journal of Gastrointestinal Oncology,focusing on the importance of early diagnosis in managing esophageal cancer and strategies for achieving“early detection”.The five-year age-standardized net survival for esophageal cancer patients falls short of expectations.Early detection and accurate diagnosis are critical strategies for improving the treatment outcomes of esophageal cancer.While advancements in endoscopic technology have been significant,there seems to be an excessive emphasis on the latest high-end endoscopic devices and various endoscopic resection techniques.Therefore,it is imperative to redirect focus towards proactive early detection strategies for esophageal cancer,investigate the most cost-effective screening methods suitable for different regions,and persistently explore practical solutions to improve the five-year survival rate of patients with esophageal cancer.

Simplified criteria for diagnosing superficial esophageal squamous neoplasms using Narrow Band Imaging magnifying endoscopy

AIM To simplify the diagnostic criteria for superficial esophageal squamous cell carcinoma(SESCC) on Narrow Band Imaging combined with magnifying endoscopy(NBI-ME).METHODS This study was based on the post-hoc analysis of a randomized controlled trial. We performed NBI-ME for 147 patients with present or a history of squamous cell carcinoma in the head and neck, or esophagus between January 2009 and June 2011. Two expert endoscopistsdetected 89 lesions that were suspicious for SESCC lesions, which had been prospectively evaluated for the following 6 NBI-ME findings in real time: "intervascular background coloration"; "proliferation of intrapapillary capillary loops(IPCL)"; and "dilation", "tortuosity", "change in caliber", and "various shapes(VS)" of IPCLs(i.e., Inoue's tetrad criteria). The histologic examination of specimens was defined as the gold standard for diagnosis. A stepwise logistic regression analysis was used to identify candidates for the simplified criteria from among the 6 NBI-ME findings for diagnosing SESCCs. We evaluated diagnostic performance of the simplified criteria compared with that of Inoue's criteria.RESULTS Fifty-four lesions(65%) were histologically diagnosed as SESCCs and the others as low-grade intraepithelial neoplasia or inflammation. In the univariate analysis, proliferation, tortuosity, change in caliber, and VS were significantly associated with SESCC(P < 0.01). The combination of VS and proliferation was statistically extracted from the 6 NBI-ME findings by using the stepwise logistic regression model. We defined the combination of VS and proliferation as simplified dyad criteria for SESCC. The areas under the curve of the simplified dyad criteria and Inoue's tetrad criteria were 0.70 and 0.73, respectively. No significant difference was shown between them. The sensitivity, specificity, and accuracy of diagnosis for SESCC were 77.8%, 57.1%, 69.7% and 51.9%, 80.0%, 62.9% for the simplified dyad criteria and Inoue's tetrad criteria, respectively.CONCLUSION The combination of proliferation and VS may serve as simplified criteria for the diagnosis of SESCC using NBIME.

Endoscopic submucosal dissection for superficial esophageal neoplasms

Endoscopic submucosal dissection(ESD) is currently accepted as the major treatment modality for superficial neoplasms in the gastrointestinal tract including the esophagus.An important advantage of ESD is its effectiveness in resecting lesions regardless of their size and severity of fibrosis.Based on excellent outcomes for esophageal neoplasms with a small likelihood of lymph node metastasis,the number of ESD candidates has increased.On the other hand,ESD still requires highly skilled endoscopists due to technical difficulties.To avoid unnecessary complications including perforation and postoperative stricture,the indications for ESD require careful consideration and a full understanding of this modality.This article,in the highlight topic series,provides detailed information on the indication,procedure,outcome,complications and their prevention in ESD of superficial esophageal neoplasms.

Current perspectives on pancreatic serous cystic neoplasms:Diagnosis, management and beyond

Pancreatic cystic neoplasms have been increasingly recognized recently. Comprising about 16% of all resected pancreatic cystic neoplasms, serous cystic neoplasms are uncommon benign lesions that are usually asymptomatic and found incidentally. Despite overall low risk of malignancy, these pancreatic cysts still generate anxiety, leading to intensive medical investigations with considerable financial cost to health care systems. This review discusses the general background of serous cystic neoplasms, including epidemiology and clinical characteristics, and provides an updated overview of diagnostic approaches based on clinical features, relevant imaging studies and new findings that are being discovered pertaining to diagnostic evaluation. We also concisely discuss and propose management strategies for better quality of life.

Endoscopic submucosal tunnel dissection for largesuperficial esophageal squamous cell neoplasms

Endoscopic submucosal dissection(ESD)is a wellestablished treatment for superficial esophageal squamous cell neoplasms(SESCNs)with no risk of lymphatic metastasis.However,for large SESCNs,especially when exceeding two-thirds of the esophageal circumference,conventional ESD is time-consuming and has an increased risk of adverse events.Based on the submucosal tunnel conception,endoscopic submucosal tunnel dissection(ESTD)was first introduced by us to remove large SESCNs,with excellent results.Studies from different centers also reported favorable results.Compared with conventional ESD,ESTD has a more rapid dissection speed and R0 resection rate.Currently in China,ESTD for large SESCNs is an important part of the digestive endoscopic tunnel technique,as is peroral endoscopic myotomy for achalasia and submucosal tunnel endoscopic resection for submucosal tumors of the muscularis propria.However,not all patients with SESCNs are candidates for ESTD,and postoperative esophageal strictures should also be taken into consideration,especially for lesions with a circumference greater than three-quarters.In this article,we describe our experience,review the literature of ESTD,and provide detailed information on indications,standard procedures,outcomes,and complications of ESTD.

Esophageal squamous cell carcinoma-precursor lesions and early diagnosis

Squamous cell carcinoma of the esophagus (SCCE) carries a poor prognosis due to late diagnosis.Early detection is highly desirable,since surgical and endoscopic resection offers the only possible cure for esophageal cancer.Population screening should be undertaken in high risk areas,and in low or moderate risk areas for people with risk factors (alcoholics,smokers,mate drinkers,history of head and neck cancer,achalasia and lye stricture of the esophagus).Esophageal balloon cytology is an easy and inexpensive sampling technique,but the current methods are insufficient for primary screening due to sampling errors.Conventional endoscopy with biopsy remains the standard procedure for the identification of pre-malignant and early malignant changes in esophageal mucosa and endoscopic detection.It may be enhanced by several techniques such as dye and optic chromoendoscopy,magnifying endoscopy,and optical-based spectroscopic and imaging modalities.Since more than 80% of SCCE deaths occur in developing countries,where expensive techniques such as narrow band imaging (NBI) and autofluorescence imaging are unavailable,the most cost-effective tool for targeting biopsies may be Lugol dye chromoendoscopy,since it is easy,accurate,inexpensive and available worldwide.In ideal conditions,or in developed countries,is it reasonable to think that optimal detection will require a combination of techniques,such as the combination of Lugol’s chromoendoscopy and NBI to identify esophageal areas that require further characterization by a high resolution technique.The efficacy and cost-effectiveness will determine whether these modalities will become part of standard endoscopy practice.

Short term results of endoscopic submucosal dissection in superficial esophageal squamous cell neoplasms

AIM: To evaluate the efficacy of endoscopic submucosal dissection for superficial esophageal squamous cell neoplasms. METHODS: Between July 2007 and March 2009, 27 consecutive superficial esophageal squamous cell neoplasms in 25 enrolled patients were treated by endoscopic submucosal dissection. The therapeutic efficacy, complications, and follow-up results were assessed. RESULTS: The mean size of the lesions was 21 ± 13 mm (range 2-55 mm); the mean size of the resection specimens was 32 ± 12 mm (range 10-70 mm). The enblock resection rate was 100% (27/27), and en block resection with tumor-free lateral/basal margins was 88.9% (24/27). Perforation occurred in 1 patient who was managed by conservative medical treatments. None of the patients developed local recurrence or distant metastasis in the follow-up period. CONCLUSION: Endoscopic submucosal dissection is applicable to superficial esophageal squamous cell neoplasms with promising results.

Endoscopic submucosal dissection for superficial esophageal squamous cell neoplasms

Endoscopic resection is an effective treatment for noninvasive esophageal squamous cell neoplasms(ESCNs).Endoscopic mucosal resection(EMR)has been developed for small localized ESCNs as an alternative to surgical therapy because it shows similar effectiveness and is less invasive than esophagectomy.However,EMR is limited in resection size and therefore piecemeal resection is performed for large lesions,resulting in an imprecise histological evaluation and a high frequency of local recurrence.Endoscopic submucosal dissection(ESD)has been developed in Japan as one of the standard endoscopic resection techniques for ESCNs.ESD enables esophageal lesions,regardless of their size,to be removed en bloc and thus has a lower local recurrence rate than EMR.The development of new devices and the establishment of optimal strategies for esophageal ESD have resulted in fewer complications such as perforation than expected.However,esophageal stricture after ESD may occur when the resected area is larger than three-quarters of the esophageal lumen or particularly when it encompasses the entire circumference;such a stricture requires multiple sessions of endoscopic balloon dilatation.Recently,oral prednisolone has been reported to be useful in preventing post-ESD stricture.In addition,a combination of chemoradiotherapy(CRT)and ESD might be an alternative therapy for submucosal esophageal cancer that has a risk of lymph node metastasis because esophagectomy is extremely invasive;CRT has a higher local recurrence rate than esophagectomy but is less invasive.ESD is likely to play a central role in the treatment of superficial esophageal squamous cell neoplasms in the future.

National guidelines for diagnosis and treatment of esophageal carcinoma 2022 in China(English version)

Contents1.Overview 2.Guidelines for diagnosis of esophageal cancer 2.1 Signs and symptoms 2.1.1 Clinical symptoms 2.1.2 Signs 2.2 Examinations 2.2.1 Imaging 2.2.2 Endoscopy 2.2.3 Other tests 2.3 Clinical diagnosis 2.4 Screening of high-risk group of esophageal cancer 2.5 Classification and staging of esophageal cancer.

Endoscopic submucosal dissection for early esophageal neoplasms using the stag beetle knife

AIM To determine short-and long-term outcomes of endoscopic submucosal dissection(ESD) using the stag beetle(SB) knife, a scissor-shaped device.METHODS Seventy consecutive patients with 96 early esophageal neoplasms, who underwent ESD using a SB knife at Kure Medical Center and Chugoku Cancer Center, Japan, between April 2010 and August 2016, were retrospectively evaluated. Clinicopathological characteristics of lesions and procedural adverse events were assessed. Therapeutic success was evaluated on the basis of en bloc, histologically complete, and curative or non-curative resection rates. Overall and tumor-specific survival, local or distant recurrence, and 3-and 5-year cumulative overall metachronous cancer rates were also assessed.RESULTS Eligible patients had dysplasia/intraepithelial neoplasia(22%) or early cancers(squamous cell carcinoma, 78%). The median procedural time was 60 min and on average, the lesions measured 24 mm in diameter, yielding 33-mm tissue defects. The en bloc resection rate was 100%, with 95% and 81% of dissections deemed histologically complete and curative, respectively. All procedures were completed without accidental incisions/perforations or delayed bleeding. During follow-up(mean, 35 ± 23 mo), no local recurrences or metastases were observed. The 3-and 5-year survival rates were 83% and 70%, respectively, with corresponding rates of 85% and 75% for curative resections and 74% and 49% for noncurative resections. The 3-and 5-year cumulative rates of metachronous cancer in the patients with curative resections were 14% and 26%, respectively.CONCLUSION ESD procedures using the SB knife are feasible, safe, and effective for treating early esophageal neoplasms, yielding favorable short-and long-term outcomes.

Risk factors for Mallory-Weiss Tear during endoscopic submucosal dissection of superficial esophageal neoplasms

BACKGROUND Adverse events during endoscopic submucosal dissection(ESD)of superficial esophageal neoplasms,such as perforation and bleeding,have been welldocumented.However,the Mallory-Weiss Tear(MWT)during esophageal ESD remains under investigation.AIM To investigate the incidence and risk factors of the MWT during esophageal ESD.METHODS From June 2014 to July 2017,patients with superficial esophageal neoplasms who received ESD in our institution were retrospectively analyzed.The clinicopathological characteristics of the patients were collected.Patients were divided into an MWT group and non-MWT group based on whether MWT occurred during ESD.The incidence of MWTs was determined,and the risk factors for MWT were then further explored.RESULTS A total of 337 patients with 373 lesions treated by ESD were analyzed.Twenty patients developed MWTs during ESD(5.4%).Multivariate analysis identified that female sex(OR=5.36,95%CI:1.47-19.50,P=0.011)and procedure time longer than 88.5 min(OR=3.953,95%CI:1.497-10.417,P=0.005)were independent risk factors for an MWT during ESD.The cutoff value of the procedure time for an MWT was 88.5 min(sensitivity,65.0%;specificity,70.8%).Seven of the MWT patients received endoscopic hemostasis.All patients recovered satisfactorily without surgery for the laceration.CONCLUSION The incidence of MWTs during esophageal ESD was much higher than expected.Although most cases have a benign course,fatal conditions may occur.We recommend inspection of the stomach during and after the ESD procedure for timely management in cases of bleeding MWTs or even perforation outside of the procedure region.

Endoscopic ultrasound using ultrasound probes for the diagnosis of early esophageal and gastric cancers

Endoscopic ultrasound (EUS) devices were first designed and manufactured more than 30 years ago, and since then investigators have reported EUS is effective for determining both the staging and the depth of invasion of esophageal and gastric cancers. We review the present status, the methods, and the findings of EUS when used to diagnose and stage early esophageal and gastric cancer. EUS using high-frequency ultrasound probes is more accurate than conventional EUS for the evaluation of the depth of invasion of superficial esophageal carcinoma. The rates of accurate evaluation of the depth of invasion by EUS using high-frequency ultrasound probes were 70%-88% for intramucosal cancer, and 83%-94% for submucosal invasive cancer. But the sensitivity of EUS using high-frequency ultrasound probes for the diagnosis of submucosal invasive cancer was relatively low, making it difficult to confirm minute submucosal invasion. The accuracy of EUS using high-frequency ultrasound probes for early gastric tumor classification can be up to 80% compared with 63% for conventional EUS, although the accuracy of EUS using high-frequency ultrasound probes relatively decreases for those patients with depressed-type lesions, undifferentiated cancer, concomitant ulceration, expanded indications, type 0-I?lesions, and lesions located in the upper-third of the stomach. A 92% overall accuracy rate was achieved when both the endoscopic appearance and the findings from EUS using high-frequency ultrasound probes were considered together for tumor classification. Although EUS using high-frequency ultrasound probes has limitations, it has a high depth of invasion accuracy and is a useful procedure to distinguish lesions in the esophagus and stomach that are indicated for endoscopic resection.

New insights in diagnosis and treatment of gastroenteropancreatic neuroendocrine neoplasms

Gastroenteropancreatic neuroendocrine neoplasms(GEP-NENs)are rare epithelial neoplasms derived from pluripotent endocrine cells along the gastrointestinal tract and pancreas.GEP-NENs are classified into well-differentiated neuroendocrine tumors and poorly differentiated neuroendocrine carcinomas.Despite overlapping morphological features,GEP-NENs vary in molecular biology,epigenetic,clinical behavior,treatment response,and prognosis features and remain an unmet clinical challenge.In this review,we introduce recent updates on the histopathologic classification,including the tumor grading and staging system,molecular genetics,and systemic evaluation of the diagnosis and treatment of GEP-NENs at different anatomic sites,together with some insights into the diagnosis of challenging and unusual cases.We also discuss the application of novel therapeutic approaches for GEP-NENs,including peptide receptor radionuclide therapy,targeted therapy,and immunotherapy with immune checkpoint inhibitors.These findings will help improve patient care with precise diagnosis and individualized treatment of patients with GEP-NENs.

Application of an artificial intelligence system for endoscopic diagnosis of superficial esophageal squamous cell carcinoma

BACKGROUND Upper gastrointestinal endoscopy is critical for esophageal squamous cell carcinoma(ESCC)detection;however,endoscopists require long-term training to avoid missing superficial lesions.AIM To develop a deep learning computer-assisted diagnosis(CAD)system for endoscopic detection of superficial ESCC and investigate its application value.METHODS We configured the CAD system for white-light and narrow-band imaging modes based on the YOLO v5 algorithm.A total of 4447 images from 837 patients and 1695 images from 323 patients were included in the training and testing datasets,respectively.Two experts and two non-expert endoscopists reviewed the testing dataset independently and with computer assistance.The diagnostic performance was evaluated in terms of the area under the receiver operating characteristic curve,accuracy,sensitivity,and specificity.RESULTS The area under the receiver operating characteristics curve,accuracy,sensitivity,and specificity of the CAD system were 0.982[95%confidence interval(CI):0.969-0.994],92.9%(95%CI:89.5%-95.2%),91.9%(95%CI:87.4%-94.9%),and 94.7%(95%CI:89.0%-97.6%),respectively.The accuracy of CAD was significantly higher than that of non-expert endoscopists(78.3%,P<0.001 compared with CAD)and comparable to that of expert endoscopists(91.0%,P=0.129 compared with CAD).After referring to the CAD results,the accuracy of the non-expert endoscopists significantly improved(88.2%vs 78.3%,P<0.001).Lesions with Paris classification type 0-IIb were more likely to be inaccurately identified by the CAD system.CONCLUSION The diagnostic performance of the CAD system is promising and may assist in improving detectability,particularly for inexperienced endoscopists.

Combination of concurrent endoscopic submucosal dissection and modified peroral endoscopic myotomy for an achalasia patient with synchronous early esophageal neoplasms

with an increased risk for developing esophageal squamous cell carcinoma. In our paper, we introduced an achalasia patient combined with synchronous early esophageal neoplasms. We performed a combination of concurrent endoscopic submucosal dissection (ESD) and peroral endoscopic myotomy (POEM). No complications other than postoperative pain that needed morphine treatment for two days had occurred. Dysphagia was significantly improved. Neither reflux nor cough occurred. The short-term efficacy and safety of our case is favorable and suggests that concurrent ESD and POEM could be a treatment option to such patients.

Comments on National guidelines for diagnosis and treatment of esophageal carcinoma 2022 in China(English version)

Esophageal cancer has always been one of the most common malignant tumors in the world, and China is one of the regions with the highest incidence. Although the incidence and mortality of esophageal cancer in China have shown a downward trend in recent years, according to the statistics of the prevalence of malignant tumor in China in2015, its morbidity and mortality rate still rank 6th and 4th among all malignant tumors, respectively.

Endoscopic techniques for diagnosis and treatment of gastroentero-pancreatic neuroendocrine neoplasms:Where we are

BACKGROUND The correct localization of the primary tumor site and a complete histological diagnosis represent the milestones for the proper management of gastro-enteropancreatic neuroendocrine neoplasms(GEP-NENs).AIM To analyze current evidence on the role of endoscopy in the diagnosis/treatment of GEP-NENs.METHODS An extensive bibliographical search was performed in PubMed to identify guidelines and primary literature(retrospective and prospective studies,systematic reviews,case series)published in the last 15 years,using both medical subject heading(MeSH)terms and free-language keywords:gastro-enteropancreatic neuroendocrine neoplasms;endoscopy;ultrasound endoscopy;capsule endoscopy;double-balloon enteroscopy;diagnosis;therapy;staging.RESULTS In the diagnostic setting,endoscopic ultrasonography(EUS)represents the diagnostic gold standard for pancreatic NENs and the technique of choice for the locoregional staging of gastric,duodenal and rectal NENs.The diagnosis of small bowel NENs(sbNENs)has been improved with the advent of video capsule endoscopy and double-balloon enteroscopy,which allow for direct visualization of the entire small bowel;however,data regarding the efficacy/safety of these techniques in the detection of sbNENs are scanty and often inconclusive.From a therapeutic point of view,endoscopic removal is the treatment of choice for the majority of gastric NENs(type 1/2),for well-differentiated localized nonmetastatic duodenal NENs<1 cm,confined to the submucosa layer and for<10 mm,stage T1–T2,rectal NENs.EUS-guided pancreatic locoregional ablative treatments have been proposed in recent studies with promising results in order to control symptoms or reduce tumor burden in selected patients.CONCLUSION Standard axial endoscopy and EUS still play a pivotal role in several GEP-NENs.Advanced techniques for increasing the rate of R0 resection should be reserved for high-volume referral centers.