Sporadic gastrinoma with refractory benign esophageal stricture:A case report

BACKGROUND Gastrinoma is characterized by an excessive release of gastrin,leading to hypersecretion of gastric acid,subsequently resulting in recurrent peptic ulcers,chronic diarrhea,and even esophageal strictures.This case report aims to improve awareness and facilitate early diagnosis and treatment of gastrinoma by presenting a rare case of gastrinoma with refractory benign esophageal stricture(RBES).Additionally,it highlights the persistent challenges that gastroenterologists encounter in managing RBES.CASE SUMMARY This case demonstrates a patient with gastrinoma who developed RBES and complete esophageal obstruction despite management with maximal acid suppressive therapy,multiple endoscopic bougie dilations and endoscopic incisional therapy(EIT).CONCLUSION It is essential to diagnose gastrinoma as early as possible,as inadequately controlled acid secretion over an extended period increases the risk of developing severe esophageal strictures.In patients with esophageal strictures causing complete luminal obstruction,blind reopening EIT presents challenges and carries a high risk of perforation.

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.

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.

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 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.

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

Achalasia is generally accepted as a condition associated 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.

Prognosis value of heat-shock proteins in esophageal and esophagogastric cancer:A systematic review and meta-analysis

BACKGROUND Heat shock proteins(HSPs)are molecular chaperones that play an important role in cellular protection against stress events and have been reported to be overex-pressed in many cancers.The prognostic significance of HSPs and their regulatory factors,such as heat shock factor 1(HSF1)and CHIP,are poorly understood.AIM To investigate the relationship between HSP expression and prognosis in esophageal and esophagogastric cancer.METHODS A systematic review was conducted in accordance with PRISMA recommend-ations(PROSPERO:CRD42022370653),on Embase,PubMed,Cochrane,and LILACS.Cohort,case-control,and cross-sectional studies of patients with eso-phagus or esophagogastric cancer were included.HSP-positive patients were compared with HSP-negative,and the endpoints analyzed were lymph node metastasis,tumor depth,distant metastasis,and overall survival(OS).HSPs were stratified according to the HSP family,and the summary risk difference(RD)was calculated using a random-effect model.RESULTS The final selection comprised 27 studies,including esophageal squamous cell carcinoma(21),esophagogastric adenocarcinoma(5),and mixed neoplasms(1).The pooled sample size was 3465 patients.HSP40 and 60 were associated with a higher 3-year OS[HSP40:RD=0.22;95%confidence interval(CI):0.09-0.35;HSP60:RD=0.33;95%CI:0.17-0.50],while HSF1 was associated with a poor 3-year OS(RD=-0.22;95%CI:-0.32 to-0.12).The other HSP families were not associated with long-term survival.HSF1 was associated with a higher probability of lymph node metastasis(RD=-0.16;95%CI:-0.29 to-0.04).HSP40 was associated with a lower probability of lymph node dissemination(RD=0.18;95%CI:0.03-0.33).The expression of other HSP families was not significantly related to tumor depth and lymph node or distant metastasis.CONCLUSION The expression levels of certain families of HSP,such as HSP40 and 60 and HSF1,are associated with long-term survival and lymph node dissemination in patients with esophageal and esophagogastric cancer.

Importance of early detection of esophageal cancer before the tumor progresses too much for effective treatment

This editorial comments on an article by Qu et al published in the World Journal of Gastrointestinal Oncology.It focuses on the importance of early detection of esophageal cancer,including recurrence or secondary malignancy after chemoradiotherapy(CRT).Endoscopic resection is the first choice for treatment for esophageal cancer remaining within the mucous membrane,while surgery or radical CRT are treatment options for advanced stages depending on the patient’s general condition and desire.Although these treatments are potentially curative,they are more invasive than endoscopic resection.Early-stage esophageal cancer is often asymptomatic and difficult to detect.Uniform periodic endoscopy is unrealistic.Although less burdensome tests exist,including liquid biopsy and urinary biomarkers,these have not yet been widely used in clinical practice.Early detection is important after radical CRT because the local recurrence rate is higher than that after surgery.However,endoscopic resection or photodynamic therapy is indicated if detected in the early stages,and positive results have been reported.Early detection of esophageal cancer is crucial.Endoscopy is the main diagnostic method;however,new and less burdensome methods should be established to ensure early treatment for patients with esophageal cancer.

Long-term outcomes and prognostic factors for patients with esophageal cancer following radiotherapy

AIM:To evaluate long-term outcomes and prognostic factors for esophageal squamous cell carcinoma(SCC) treated with three dimensional conformal radiotherapy(3D-CRT).METHODS:Between January 2005 and December 2006,153 patients(120 males,33 females) with pathologically confirmed esophageal SCC and treated with 3D-CRT in Cancer Hospital of Shantou University were included in this retrospective analysis.Median age was 60 years(range:37-84 years).The proportion of tumor location was as follows:upper thorax(including the cervical region),73(48%);middle thorax,73(48%);lower thorax,7(5%),respectively.The median radiation dose was 64 Gy(range:50-74 Gy).Fifty four cases(35%) received cisplatin-based concurrent chemotherapy.Univariate and multivariate analysis were performed to determine the association between the correlative factors and prognosis.RESULTS:The five-year overall survival rate was 26.3%,with a median follow-up of 49 mo(range:3-66 mo) for patients who were still alive.On univariate analysis,lesion location,lesion length by barium esophagogram,computed tomography imaging characteristics including Y diameter(anterior-posterior,AP,extent of tumor),gross tumor volume of primary lesion(GTV-E),volume of positive lymph nodes(GTV-LN),and the total target volume(GTV-T = GTV-E + GTVLN) were prognostic for overall survival.By multivariate analysis,only the Y diameter [hazard ratio(HR) 2.219,95%CI 1.141-4.316,P = 0.019] and the GTV-T(HR 1.372,95%CI 1.044-1.803,P = 0.023) were independent prognostic factors for survival.CONCLUSION:The overall survival of esophageal carcinoma patients undergoing 3D-CRT was promising.The best predictors for survival were GTV-T and Y diameter.

Radiobiological characteristics of cancer stem cells from esophageal cancer cell lines

AIM:To study the cancer stem cell population in esophageal cancer cell lines KYSE-150 and TE-1 and identify whether the resulting stem-like spheroid cells display cancer stem cells and radiation resistance characteristics.METHODS:A serum-free medium(SFM)suspension was used to culture esophageal cancer stem cell lines and enrich the esophageal stem-like spheres.A reverse transcription polymerase chain reaction assay was used to detect stem cell gene expression in the spheroid cells.Radiosensitivity of stem-like spheres and parental cells were evaluated by clonogenic assays.Furthermore,different cells after different doses of irradiation were tested to evaluate the change in sphere formation,cell cycle and CD44+CD271+expression of tumor stem-like spheroid cells using flow cytometry beforeand after irradiation.RESULTS:The cells were observed to generate an increased number of spheres in SFM with increasing cell passage.Radiation increased the rate of generation of stem-like spheres in both types of cells.The average survival fraction(SF2)of the cultured KYSE-150compared with TE-1 stem-like spheres after 2 Gy of radiation was 0.81±0.03 vs 0.87±0.01(P<0.05),while the average SF2 of KYSE-150 compared with TE-1 parental cells was 0.69±0.04 vs 0.80±0.03,P<0.05.In the esophageal parental cells,irradiation dose-dependently induced G2 arrest.Stem-like esophageal spheres were resistant to irradiation-induced G2arrest without significant changes in the percentage population of irradiated stem-like cells.Under irradiation at 0,4,and 8 Gy,the CD44+CD271+cell percentage for KYSE150 parental cells was 1.08%±0.03%vs1.29%±0.07%vs 1.11%±0.09%,respectively;the CD44+CD271+cell percentage for TE1 parental cells was 1.16%±0.11%vs 0.97%±0.08%vs 1.45%±0.35%,respectively.The differences were not statistically significant.Under irradiation at 0,4,and 8 Gy,the CD44+CD271+cell percentage for KYSE-150 stemlike spheres was 35.83%±1.23%vs 44.9%±1.67%vs 57.77%±1.88%,respectively;the CD44+CD271+cell percentage for TE1 stem-like spheres was 16.07%±0.91%vs 22.67%±1.12%,16.07%±0.91%vs33.27%±1.07%,respectively.The 4 and 8 Gy irradiated KYSE-150 and TE-1 stem-like spheres were compared with the 0 Gy irradiated group,and the differences were statistically significant(P<0.05).CONCLUSION:The KYSE-150 and TE-1 stem-like spheres are more radioresistant than their parental cells which may suggest that cancer stem cells are related to radioresistance.

Medical expenditure for esophageal cancer in China:a 10-year multicenter retrospective survey(2002-2011)

Background: Esophageal cancer is associated with substantial disease burden in China, and data on the economic burden are fundamental for setting priorities in cancer interventions. The medical expenditure for the diagnosis and treatment of esophageal cancer in China has not been fully quantified. This study aimed to examine the medical expenditure of Chinese patients with esophageal cancer and the associated trends.Methods: From 2012 to 2014, a hospital-based multicenter retrospective survey was conducted in 37 hospitals in 13 provinces/municipalities across China as a part of the Cancer Screening Program of Urban China. For each esophageal cancer patient diagnosed between 2002 and 2011, clinical information and expense data were extracted by using structured questionnaires. All expense data were reported in Chinese Yuan(CNY; 1 CNY = 0.155 USD) based on the2011 value and inflated using the year-specific health care consumer price index for China.Results: A total of 14,967 esophageal cancer patients were included in the analysis. It was estimated that the overall average expenditure per patient was 38,666 CNY, and an average annual increase of 6.27% was observed from 2002(25,111 CNY) to 2011(46,124 CNY). The average expenditures were 34,460 CNY for stage Ⅰ,39,302 CNY for stage Ⅱ,40,353 CNY for stage Ⅲ, and 37,432 CNY for stage IV diseases(P < 0.01). The expenditure also differed by the therapy type, which was 38,492 CNY for surgery, 27,933 CNY for radiotherapy, and 27,805 CNY for chemotherapy(P < 0.05).Drugs contributed to 45.02% of the overall expenditure.Conclusions: These conservative estimates suggested that medical expenditures for esophageal cancer in China substantially increased in the last 10 years, treatment for early-stage esophageal cancer costs less than that for advanced cases, and spending on drugs continued to account for a considerable proportion of the overall expenditure.

Intensify standardized therapy for esophageal and stomach cancer in tumor hospitals

INTRODUCTIONCancer treatment situation in tumor hospitals inChina has its own unique characteristics which arenot found in other parts of the world. Because ofthe huge population and high incidence rates ofesophageal and stomach cancer[1-5], the number ofcancer patients waiting for admission isinconceivably large.

Radiotherapy of double primary esophageal carcinoma

INTRODUCTIONDouble primary esophageal carcinoma is defined ashaving two loci of squamous cell cancersimultaneously or consecutively developing indifferent sites of esophagus.This rare diseaseappears mostly in the literature as case reports,reports about its treatment are even moreinfrequent.Here we present our experiences

Influence of endoscopic submucosal dissection on esophageal motility

AIM: To assess esophageal motility after esophageal endoscopic submucosal dissection (ESD). METHODS: Twelve patients (6 men and 6 women) aged 53-64 years (mean age, 58 years) who underwent regular examination 3-12 mo after esophageal ESD for neoplasms of the esophageal body were included in this study. The ESD procedure was performed under deep sedation using a combination of propofol and fentanyl, and involved a submucosal injection to lift the lesion and use of a dual-knife and an insulated-tip knife to create a circumferential incision around the lesion extending into the submucosa. Esophageal motility was examined using a high-resolution manometry system. Dysphagia was graded using a five-point scale according to the Mellow and Pinkas scoring system. Patient symptoms and the results of esophageal manometry were then analyzed. RESULTS: Of the 12 patients enrolled, 1 patient hadgrade 2 dysphagia, 1 patient had grade 1 dysphagia, and 3 patients complained of sporadic dysphagia. Ineffective esophageal motility was observed in 5 of 6 patients with above semi-circumference of resection extension. Of these 5 patients, 1 patient complained of grade 2 dysphagia (with esophageal stricture), one patient complained of grade 1 dysphagia, and 3 patients complained of sporadic dysphagia. Normal esophageal body manometry was observed in all 6 patients with below semi-circumference of resection extension. The 6 patients with normal esophageal motility did not complain of dysphagia. CONCLUSION: Extensive esophageal ESD may cause esophageal dysmotility in some patients, and might also have an influence on dysphagia although without esophageal stricture.

Risk factors of electrocoagulation syndrome after esophageal endoscopic submucosal dissection

AIM To investigate post endoscopic submucosal dissection electrocoagulation syndrome(PEECS) of the esophagus.METHODS We analyzed 55 consecutive cases with esophageal endoscopic submucosal dissection for superficial esophageal squamous neoplasms at a tertiary referral hospital in South Korea. Esophageal PEECS was defined as "mild" meeting one of the following criteria without any obvious perforation: fever(≥ 37.8 ℃), leukocytosis(> 10800 cells/μl), or regional chest pain more than 5/10 points as rated on a numeric pain intensity scale. The grade of PEECS was determined as "severe" when meet two or more of above criteria.RESULTS We included 51 cases without obvious complications in the analysis. The incidence of mild and severe esophageal PEECS was 47.1% and 17.6%, respectively. Risk factor analysis revealed that resected area, procedure time, and muscle layer exposure were significantly associated with PEECS. In multivariate analysis, a resected area larger than 6.0 cm^2(OR = 4.995, 95%CI: 1.110-22.489, P = 0.036) and muscle layer exposure(OR = 5.661, 95%CI: 1.422-22.534, P = 0.014) were independent predictors of esophageal PEECS. All patients with PEECS had favorable outcomes with conservative management approaches, such as intravenous hydration or antibiotics.CONCLUSION Clinicians should consider the possibility of esophageal PEECS when the resected area exceeds 6.0 cm^2 or when the muscle layer exposure is noted.

Radiotherapy combined with nimotuzumab for elderly esophageal cancer patients:A phaseⅡclinical trial

Objective:To investigate the safety and efficacy of nimotuzumab combined with radiotherapy for elderly patients with non-resectable esophageal carcinoma(EC).Methods:Eligible patients were aged 70 years or older and had treatment-naive,histologically proven inoperable locally advanced EC.Enrolled patients received radiotherapy with a total dose of 50-60 Gy in 25-30 fractions,concurrent with weekly infusion of nimotuzumab.The primary end point was the rate of more than grade 3 toxicities.Results:From June 2011 to July 2016,46 patients with stageⅡ-IV EC with a median age of 76.5 years were enrolled.There were 10,28 and 8 patients with stageⅡ,III and IV disease,respectively.The common acute toxicities included esophagitis(grade 1-2,75.4%;grade 3,8.7%),pneumonitis(grade 1,4.3%;grade 2,6.5%;grade3,2.2%),leukopenia(grade 1-2,60.9%;grade 3-4,4.4%),gastrointestinal reaction(grade 1-2,17.3%;grade 3,2.2%),thrombocytopenia(grade 1-2,21.7%;grade 3,2.2%),and radiothermitis(grade 1-2,39.2%).The incidence of grade 3-4 adverse effects was 17.4%.No grade 5 toxicities were observed.Clinical complete response,partial response,stable disease,and progressive disease were observed in 1(2.2%),31(67.4%),12(26.1%),and 2(4.3%)patients,respectively.The median overall survival(OS)and progression-free survival(PFS)were 17 and 10 months,respectively.The 2-,3-,and 5-year OS and PFS rates were 30.4%,21.7%,19.6%,and 26.1%,19.6%,19.6%,respectively.Conclusions:Nimotuzumab combined with radiotherapy is a safe and effective therapy for elderly patients who are not surgical candidates.Further studies are warranted to confirm its therapeutic effects in elderly EC patients.

Radiotherapy of 180 cases of operable esophageal carcinoma

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Treatment guideline of radiotherapy for Chinese esophageal carcinoma (draft)

Esophageal carcinoma is one of the most common human cancers in China. Radiotherapy plays an important role in combination therapy of esophageal carcinoma. With regret, there is still no unified standard for the treatment of esophageal carcinoma in China, and there are many controversies in the treatment regimens, indications, methods and efficacy. Clinically, the clinical practice guidelines of the National Comprehensive Cancer Network (NCCN) of the United States were often consulted, but the data of them were mainly from the patients from Europe and America, and they might not be applicable for Chinese patients. In order to standardize clinical process of radiotherapy for esophageal carcinoma in China, the Esophageal Carcinoma Cooperative Group of Radiation Oncology Society of Chinese Medical Association wrote a consensus and controversies on the radiotherapy for esophageal carcinoma (draft) after years of research and discussion. We hope it be tried out and discussed with advice and valuable suggestions, in order to accelerate the process of standardization of esophageal carcinoma treatment in China.

Effect of neoadjuvant chemoradiotherapy on prognosis and surgery for esophageal carcinoma

AIM:To investigate the role of neoadjuvant chemoradiotherapy in prognosis and surgery for esophageal carcinoma by a meta-analysis.METHODS:PubMed and manual searches were done to identify all published randomized controlled trials(RCTs) that compared neoadjuvant chemoradiotherapy plus surgery(CRTS) with surgery alone(S) for esophageal cancer.According to the test of heterogeneity,a fi xed-effect model or a random effect model was used and the odds ratio(OR) was the principal measure of effects.RESULTS:Fourteen RCTs that included 1737 patients were selected with quality assessment ranging from A to C(Cochrane Reviewers' Handbook 4.2.2).OR(95% CI,P value),expressed as CRTS vs S(values>1 favor CRTS arm),was 1.19(0.94-1.48,P=0.28) for 1-year survival,1.33(1.07-1.65,P=0.69) for 2-year survival,1.76(1.42-2.19,P=0.11) for 3-year survival,1.41(1.06-1.87,P=0.11) for 4-year survival,1.64(1.28-2.12,P=0.40) for 5-year survival,0.82(0.39-1.73,P<0.0001) for rate of resection,1.53(1.33-2.84,P=0.007) for rate of complete resection,1.78(1.14-2.78,P=0.79) for operative mortality,1.12(0.89-2.48,P=0.503) for all treatment mortality,1.33(0.94-1.88,P=0.04) for the rate of adverse treatment,1.38(1.23-1.63,P=0.0002) for local-regional cancer recurrence,1.28(0.85-1.58,P=0.60) for distant cancer recurrence,and 1.27(0.86-1.65,P=0.19) for all cancer recurrence.A complete pathological response to chemoradiotherapy occurred in 10%-45.5% of patients.The 5-year survival benefi t was most pronounced when chemotherapy and radiotherapy were given concurrently(OR:1.45,95% CI:1.26-1.79,P=0.015) instead of sequentially(OR:0.85,95% CI:0.64-1.35,P=0.26).CONCLUSION:Compared with surgery alone,neoadjuvant chemoradiotherapy can improve the long-term survival and reduce local-regional cancer recurrence.Concurrent administration of neoadjuvant chemoradiotherapy was superior to sequential chemoradiotherapy.