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.

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.

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 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.

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.

Distal esophageal spasm:Update on diagnosis and management in the era of high-resolution manometry

Distal esophageal spasm (DES) is a rare major motility disorder in the Chicago dassification of esophageal motility disorders (CC).DES is diagnosed by finding of≥20%premature contractions,with normal lower esophageal sphincter (LES)relaxation on high-resolution manometry (HRM) in the latest version of CCv3.0.This feature differentiates it from achalasia type 3,which has an elevated LES relaxation pressure.Like other spastic esophageal disorders,DES has been linked to conditions such as gastroesophageal reflux disease,psychiatric conditions,and narcotic use.In addition to HRM,ancillary tests such as endoscopy and barium esophagram can provide supplemental information to differentiate DES from other conditions.Functional lumen imaging probe (FLIP),a new cutting-edge diagnostic tool,is able to recognize abnormal LES dysfunction that can be missed by HRM and can further guide LES targeted treatment when esophagogastric junction outflow obstruction is diagnosed on FLIP.Medical treatment in DES mostly targets symptomatic relief and often fails.Botulinum toxin injection during endoscopy may provide a temporary therapy that wears off over time.Myotomy through peroral endoscopic myotomy or via surgical Heller myotomy can provide long term relief in cases with persistent symptoms.

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.

Esophagectomy for a traumatic esophageal perforation with delayed diagnosis

Esophageal perforations are rare,and traumatic perforations are even more infrequent.Due to the rarity of this condition and its nonspecific presentation,the diagnosis and treatment of this type of perforation are delayed in more than 50% of patients,which leads to a high mortality rate.An 18-year-old male patient was brought to the emergency room with a penetrating neck injury,caused by a gunshot wound.He was taken to the operating room and underwent surgical exploration of the neck and a chest tube was inserted to treat the hemo-and pneumothorax.During the procedure,a 2 cm lesion was detected in the esophagus,and the patient underwent a primary repair.A contrast leakage into his right hemithorax was noticed on the 4th postoperative day;he was submitted to new surgery,and a subtotal esophagectomy and jejunostomy were performed.He was discharged from the hospital in good condition 20 d after the last procedure.The discussion around this topic focuses on the importance of the timing of diagnosis and the subsequent treatment.In early diagnosed patients,more conservative therapeutics should be performed,such as primary repair,while in those with delayed diagnosis,the patient should be submitted to more aggressive and def initive treatment.

Thresholds of gastroesophagea reflux i the diagnosis of esophageal reflux diseases

AIMS To establish optimal thresholds of pH variation(pH fluc- tuations and reflux episodes)in separating physiological and pathological gastroesophageal reflux(GER),and to evaluate their significance in the diagnosis of GER disease. METHODS Twenty-four-hour intraesophageal pH monitoring and endoscopy were performed in 400 patients with GER symptoms and in 100 healthy controls. RESULTS The results showed that the percentages of the time with pH fluctuations in patients with and without esophagitis,and in healthy controls were,on average,12.65%,9.5% and 2. 76% in 24h,respectively,and the respective percentages of the time with reflux episodes in the same groups in 24h were,on average,3.12%,2.04% and 0.18%,respectively.Using a receiver-operating-characteristic curve analysis,<6.7% of the time with pH fluctuations and<0.1% of the time with reflux episodes were defined as the combined thresholds for physiologi- cal versus pathological reflux.The sensitivity of the combuned thresholds for the detection of GER patients with and without esophagitis was 96.7% and 90.0%,respectively,and their specificity for the diagnosis of patients with abnormal GER disease was 100%. CONCLUSIONS pH flucuations and reflux episodes,when e- valuated together,are more useful for classifying patients with GER and their combined thresholds yield higher diagnostic accura- cy in assessing patients with GER disease.

Quality control indices for standardized diagnosis and treatment of esophageal cancer in China (2022 edition)

Esophageal cancer(EC)is particularly common in China.With the continuing progress of multi-disciplinary therapy including early screening,minimally invasive techniques,radiotherapy and chemotherapy,the 5-year survival of EC has been improved in China.However,there are considerable disparities in the diagnosis and treatment quality among different regions.The Esophageal Cancer Expert Committee of the National Cancer Quality Control Center(NCQCC)considers a set of authoritative quality control standards as an opportunity to eliminate the disparities and improve the overall survival and quality of life of EC.To further promote the quality control for standardized diagnosis and treatment of EC,the National Cancer Center commissioned the Esophageal Cancer Quality Control Expert Committee to draft and formulate the Chinese Quality Control Indices for Standardized Diagnosis and Treatment of Esophageal Cancer(2022 edition).The Indices includes 21 items that cover all key areas in the diagnosis and treatment of esophageal cancer,such as medical oncology,radiation oncology,endoscopy,and pathology.

Prediction,prevention and management of gastroesophageal reflux after per-oral endoscopic myotomy:An update

Achalasia cardia,the most prevalent primary esophageal motility disorder,is predominantly characterized by symptoms of dysphagia and regurgitation.The principal therapeutic approaches for achalasia encompass pneumatic dilatation(PD),Heller's myotomy,and the more recent per-oral endoscopic myotomy(POEM).POEM has been substantiated as a safe and efficacious modality for the management of achalasia.Although POEM demonstrates superior efficacy compared to PD and an efficacy parallel to Heller's myotomy,the incidence of gastroesophageal reflux disease(GERD)following POEM is notably higher than with the aforementioned techniques.While symptomatic reflux post-POEM is relatively infrequent,the significant occurrence of erosive esophagitis and heightened esophageal acid exposure necessitates vigilant monitoring to preclude long-term GERD-related complications.Contemporary advancements in the field have enhanced our comprehension of the risk factors,diagnostic methodologies,preventative strategies,and therapeutic management of GERD subsequent to POEM.This review focuses on the limitations inherent in the 24-h pH study for evaluating post-POEM reflux,potential modifications in the POEM technique to mitigate GERD risk,and the strategies for managing reflux following POEM.

Current status in the treatment options for esophageal achalasia

Recent advances in the treatment of achalasia include the use of high-resolution manometry to predict the outcome of patients and the introduction of peroral endoscopic myotomy(POEM).The first multicenter randomized,controlled,2-year follow-up study conducted by the European Achalasia Trial group indicated that laparoscopic Heller myotomy(LHM)was not superior to pneumatic dilations(PD).Publications on the long-term success of laparoscopic surgery continue to emerge.In addition,laparoscopic single-site surgery is applicable to advanced laparoscopic operations such as LHM and anterior fundoplication.The optimal treatment option is an ongoing matter of debate.In this review,we provide an update of the current progress in the treatment of esophageal achalasia.Unless new conclusive data prove otherwise,LHM is considered the most durable treatment for achalasia at the expense of increased reflux-associated complications.However,PD is the first choice for non-surgical treatment and is more costeffective.Repeated PD according to an"on-demand"strategy based on symptom recurrence can achieve long-term remission.Decision making should be based on clinical evidence that identifies a subcategory of patients who would benefit from specific treatment options.POEM has shown promise but its long-term efficacy and safety need to be assessed further.

Childhood achalasia: A comprehensive review of disease, diagnosis and therapeutic management

Achalasia is an esophageal motility disorder character-ized by failure of lower esophageal sphincter(LES) relaxation and is rare in children. The most common symptoms are vomiting, dysphagia, regurgitation, and weight loss. Definitive diagnosis is made with barium swallow study and esophageal manometry. In adults, endoscopic biopsy is recommended to exclude malig-nancy however; it is not as often indicated in children. Medical management often fails resulting in recurrent symptoms and the ultimate definitive treatment is sur-gical. Laparoscopic Heller myotomy with or without an anti-reflux procedure is the treatment of choice and has become standard of care for children with achala-sia. Peroral endoscopic myotomy is a novel therapy uti-lized with increasing frequency for achalasia treatment in adults. More experience is needed to determine the safety, efficacy, and feasibility of peroral endoscopic myotomy in children.

Endoscope-guided pneumatic dilation for treatment of esophageal achalasia

Pneumatic dilation(PD) is considered to be the first line nonsurgical therapy for achalasia.The principle of the procedure is to weaken the lower esophageal sphincter by tearing its muscle fibers by generating radial force.The endoscope-guided procedure is done without fluoroscopic control.Clinicians usually use a lowcompliance balloon such as Rigiflex dilator to perform endoscope-guided PD for the treatment of esophageal achalasia.It has the advantage of determining mucosal injury during the dilation process,so that a repeat endoscopy is not needed to assess the mucosal tearing.Previous studies have shown that endoscope-guided PD is an efficient and safe nonsurgical therapy with results that compare well with other treatment modalities.Although the results may be promising,long-term follow-up is required in the near future.

Upper esophageal sphincter abnormalities are strongly predictive of treatment response in patients with achalasia

AIM: To investigate the relationship between upper esophageal sphincter abnormalities achalasia treatment METHODS: We performed a retrospective study of 41 consecutive patients referred for high resolution esophageal manometry with a final manometric diagnosis of achalasia. Patients were sub-divided by presence or absence of Upper esophageal sphincter(UES) abnormality, and clinical and manometric profiles were compared.Correlation between UES abnormality and sub-type(i.e.,hypertensive, hypotensive or impaired relaxation) and a number of variables, including qualitative treatment response, achalasia sub-type, co-morbid medical illness,psychiatric illness, surgical history, dominant presentingsymptom, treatment type, age and gender were also evaluated.RESULTS: Among all 41 patients, 24(58.54%) had a UES abnormality present. There were no significant differences between the groups in terms of age, gender or any other clinical or demographic profiles. Among those with UES abnormalities, the majority were either hypertensive(41.67%) or had impaired relaxation(37.5%) as compared to hypotensive(20.83%), although this did not reach statistical significance(P = 0.42). There was no specific association between treatment response and treatment type received; however, there was a significant association between UES abnormalities and treatment response. In patients with achalasia and concomitant UES abnormalities, 87.5% had poor treatment response, while only 12.5% had favorable response. In contrast, in patients with achalasia and no UES abnormalities, the majority(78.57%) had good treatment response, as compared to 21.43% with poor treatment response(P = 0.0001). After controlling for achalasia sub-type, those with UES abnormality had 26 times greater odds of poor treatment response than those with no UES abnormality(P = 0.009). Similarly, after controlling for treatment type, those with UES abnormality had 13.9 times greater odds of poor treatment response compared to those with no UES abnormality(P = 0.017).CONCLUSION: The presence of UES abnormalities in patients with achalasia significantly predicted poorer treatment response as compared to those with normal UES function.

Achalasia combined with esophageal intramural hematoma:Case report and literature review

A 62-year-old male patient was admitted to our hospital due to severe chest pain,odynophagia,and hematemesis.Chest computed tomography showed an esophageal submucosal tumor.Esophagogastroduodenoscopy(EGD) revealed a longitudinal purplish bulging tumor of the esophagus.Endoscopic ultrasound(EUS) showed a mixed echoic tumor with partial liquefaction from the submucosal layer.The patient was diagnosed with esophageal intramural hematoma as well as achalasia by upper gastrointestinal endoscopy,esophagography and esophageal manometry.The patient was managed conservatively with intravenous nutrition,and oral feeding was discontinued.Follow-up EGD and EUS showed complete recovery of the esophageal wall,and finally,the patient underwent endoscopic dilatation for achalasia.The patient was symptom free at the time when we wrote this manuscript.

2011 update on esophageal achalasia

There have been some breakthroughs in the diagnosis and treatment of esophageal achalasia in the past few years.First,the introduction of high-resolution manometry with pressure topography plotting as a new diagnostic tool has made it possible to classify achalasia into three subtypes.The most favorable outcome is predicted for patients receiving treatment for type Ⅱ achalasia (achalasia with compression).Patients with typeⅠ(classic achalasia) and type Ⅲ achalasia (spastic achalasia) experience a less favorable outcome.Second,the first multicenter randomized controlled trial published by the European Achalasia Trial group reported 2-year follow-up results indicating that laparoscopic Heller myotomy was not superior to endoscopic pneumatic dilation (PD).Although the follow-up period was not long enough to reach a convincing conclusion,it merits the continued use of PD as a generally available technique in gastroenterology.Third,the novelendoscopic technique peroral endoscopic myotomy is a promising option for treating achalasia,but it requires increased experience and cautious evaluation.Despite all this good news,the bottom line is a real break-through from the basic studies to identify the actual cause of achalasia that may impede treatment success is still anticipated.