Immunotherapy for esophageal cancer:Where are we now and where can we go

Immune checkpoint inhibitor therapy has dramatically improved patient prognosis,and thereby transformed the treatment in various cancer types including esophageal squamous cell carcinoma(ESCC)in the past decade.Monoclonal antibodies that selectively inhibit programmed cell death-1(PD-1)activity has now become standard of care in the treatment of ESCC in metastatic settings,and has a high expectation to provide clinical benefit during perioperative period.Further,anti-cytotoxic T-lymphocyte–associated protein 4(CTLA-4)monoclonal antibody has also been approved in the treatment of recurrent/metastatic ESCC in combination with anti-PD-1 antibody.Well understanding of the existing evidence of immune-based treatments for ESCC,as well as recent clinical trials on various combinations with chemotherapy for different clinical settings including neoadjuvant,adjuvant,and metastatic diseases,may provide future prospects of ESCC treatment for better patient outcomes.

Present situation and prospect of immunotherapy for unresectable locally advanced esophageal cancer during peri-radiotherapy

Four major studies(Checkmate577,Keynote-590,Checkmate649 and Attraction-4)of locally advanced esophageal cancer published in 2020 have established the importance of immunotherapy,represented by anti-programmed death protein(PD)-1 in postoperative adjuvant treatment and advanced first-line treatment of locally advanced or advanced esophageal cancer and esophagogastric junction cancer,from the aspects of proof of concept,long-term survival,overall survival rate and progression-free survival.For unresectable or inoperable nonmetastatic esophageal cancer,concurrent radiotherapy and chemotherapy is the standard treatment recommended by various guidelines.Because its curative effect is still not ideal,it is necessary to explore radical radiotherapy and chemotherapy in the future,and it is considered to be promising to combine them with immunotherapeutic drugs such as anti-PD-1.This paper mainly discusses how to combine radical concurrent radiotherapy and chemotherapy with immunotherapy for unresectable local advanced esophageal cancer.

A prognosis model for predicting immunotherapy response of esophageal cancer based on oxidative stress-related signatures

Oxidative stress(OS)is intimately associated with tumorigenesis and has been considered a potential therapeutic strategy.However,the OS-associated therapeutic target for esophageal squamous cell carcinoma(ESCC)remains unconfirmed.In our study,gene expression data of ESCC and clinical information from public databases were downloaded.Through LASSO-Cox regression analysis,a risk score(RS)signature map of prognosis was constructed and performed external verification with the GSE53625 cohort.The ESTIMATE,xCell,CIBERSORT,TIMER,and ImmuCellAI algorithms were employed to analyze infiltrating immune cells and generate an immune microenvironment(IM).Afterward,functional enrichment analysis clarified the underlying mechanism of the model.Nomogram was utilized for forecasting the survival rate of individual ESCC cases.As a result,we successfully constructed an OS-related genes(OSRGs)model and found that the survival rate of high-risk groups was lower than that of low-risk groups.The AUC of the ROC verified the strong prediction performance of the signal in these two cohorts further.According to independent prognostic analysis,the RS was identified as an independent risk factor for ESCC.The nomogram and follow-up data revealed that the RS possesses favorable predictive value for the prognosis of ESCC patients.qRT-PCR detection demonstrated increased expression of MPC1,COX6C,CYB5R3,CASP7,and CYCS in esophageal cancer patients.In conclusion,we have constructed an OSRGs model for ESCC to predict patients’prognosis,offering a novel insight into the potential application of the OSRGs model in ESCC.

Immunoglobulin G-mediated food intolerance and metabolic syndrome influence the occurrence of reflux esophagitis in Helicobacter pylori-infected patients

BACKGROUND Reflux esophagitis has an increasing prevalence and complex and diverse symptoms.Identifying its risk factors is crucial to understanding the etiology,prevention,and management of the disease.The occurrence of reflux esophagitis may be associated with food reactions,Helicobacter pylori(H.pylori)infection,and metabolic syndromes.AIM To investigate the risk factors for reflux esophagitis and analyze the effects of immunoglobulin(Ig)G-mediated food intolerance,H.pylori infection,and metabolic syndrome on reflux esophagitis.METHODS Outpatients attending the Second Medical Center of the PLA General Hospital between 2017 and 2021 were retrospectively enrolled.The patients’basic information,test results,gastroscopy results,H.pylori test results,and IgG-mediated food intolerance results were collected.Multivariate logistic regression analysis was used to analyze risk factors for reflux esophagitis.Statistical mediation analysis was used to evaluate the effects of IgG-mediated food intolerance and metabolic syndrome on H.pylori infection affecting reflux esophagitis.RESULTS A total of 7954 outpatients were included;the prevalence of reflux esophagitis,IgG-mediated food intolerance,H.pylori infection,and metabolic syndrome were 20.84%,61.77%,35.91%,and 60.15%,respectively.Multivariate analysis showed that the independent risk factors for reflux esophagitis included IgG-mediated food intolerance(OR=1.688,95%CI:1.497-1.903,P<0.00001)and metabolic syndrome(OR=1.165,95%CI:1.030-1.317,P=0.01484),and the independent protective factor for reflux esophagitis was H.pylori infection(OR=0.400,95%CI:0.351-0.456,P<0.00001).IgG-mediated food intolerance had a partially positive mediating effect on H.pylori infection as it was associated with reduced occurrence of reflux esophagitis(P=0.0200).Metabolic syndrome had a partially negative mediating effect on H.pylori infection and reduced the occurrence of reflux esophagitis(P=0.0220).CONCLUSION Patients with IgG-mediated food intolerance and metabolic syndrome were at higher risk of developing reflux esophagitis,while patients with H.pylori infection were at lower risk.IgG-mediated food intolerance reduced the risk of reflux esophagitis pathogenesis in patients with H.pylori infection;however,metabolic syndrome increased the risk of patients with H.pylori infection developing reflux esophagitis.

Dosimetric risk factors for radiation esophagitis in patients with breast cancer following regional nodal radiation

BACKGROUND Radiation esophagitis(RE)is one of the most common clinical symptoms of regional lymph node radiotherapy for breast cancer.However,there are fewer studies focusing on RE caused by hypofractionated radiotherapy(HFRT).AIM To analyze the clinical and dosimetric factors that contribute to the development of RE in patients with breast cancer treated with HFRT of regional lymph nodes.METHODS Between January and December 2022,we retrospectively analysed 64 patients with breast cancer who met our inclusion criteria underwent regional nodal intensity-modulated radiotherapy at a radiotherapy dose of 43.5 Gy/15F.RESULTS Of the 64 patients in this study,24(37.5%)did not develop RE,29(45.3%)developed grade 1 RE(G1RE),11(17.2%)developed grade 2 RE(G2RE),and none developed grade 3 RE or higher.Our univariable logistic regression analysis found G2RE to be significantly correlated with the maximum dose,mean dose,relative volume 20-40,and absolute volume(AV)20-40.Our stepwise linear regression analyses found AV30 and AV35 to be significantly associated with G2RE(P<0.001).The optimal threshold for AV30 was 2.39 mL[area under the curve(AUC):0.996;sensitivity:90.9%;specificity:91.1%].The optimal threshold for AV35 was 0.71 mL(AUC:0.932;sensitivity:90.9%;specificity:83.9%).CONCLUSION AV30 and AV35 were significantly associated with G2RE.The thresholds for AV30 and AV35 should be limited to 2.39 mL and 0.71 mL,respectively.

Analysis of the Effectiveness of Biling Weitong Granules Combined with Trimethoprim and Vonoprazan in The Treatment of Reflux Esophagitis

Objective:To analyze the effectiveness of Biling Weitong Granules(BLWTG)combined with trimethoprim and vonoprazan in treating reflux esophagitis.Methods:Sixty patients with reflux esophagitis admitted to our hospital from March 2020 to March 2023 were selected as study subjects and randomly divided into a control group and an experimental group,with 30 cases in each group.The control group received only the combination treatment of trimethoprim and vonoprazan,while the experimental group was treated with BLWTG based on the control group.The acid reflux and heartburn symptom scores,quality-of-life scores,clinical efficacy,Chinese medicine symptom incidences,and the occurrence of adverse reactions before and after treatment in the two groups were compared.Results:After treatment,the acid reflux and heartburn symptom scores of patients in the experimental group were lower than those of the treatment control group,and the quality-of-life scores were higher than those of the treatment control group(P<0.05).The total clinical efficacy of the experimental group was 96.66%,which was significantly higher than that of the control group(73.33%,P<0.05).After treatment,the incidence of Chinese medicine symptoms,such as nausea and vomiting,abdominal distension and abdominal pain,and loss of appetite of the patients in the experimental group were significantly lower than those of the control group(P<0.05).During the treatment period,there was no significant difference in the incidence of adverse reactions between the two groups,which indicated that the safety of the two treatments was comparable(P>0.05).Conclusion:BLWTG combined with trimethoprim and vonoprazan was safe and reliable in treating reflux esophagitis,effectively relieving the symptoms and improving its clinical efficacy.This treatment is worthy of popularization.

Application of neoadjuvant chemoradiotherapy and neoadjuvant chemotherapy in curative surgery for esophageal cancer:A metaanalysis

BACKGROUND The effectiveness of neoadjuvant therapy in esophageal cancer(EC)treatment is still a subject of debate.AIM To compare the clinical efficacy and toxic side effects between neoadjuvant chemoradiotherapy(nCRT)and neoadjuvant chemotherapy(nCT)for locally advanced EC(LAEC).METHODS A comprehensive search was conducted using multiple databases,including PubMed,EMBASE,MEDLINE,Science Direct,The Cochrane Library,China National Knowledge Infrastructure,Wanfang Database,Chinese Science and Technology Journal Database,and Chinese Biomedical Literature Database Article.Studies up to December 2022 comparing nCRT and nCT in patients with EC were selected.RESULTS The analysis revealed significant differences between nCRT and nCT in terms of disease-free survival.The results indicated that nCRT provided better outcomes in terms of the 3-year overall survival rate(OSR)[odds ratio(OR)=0.95],complete response rate(OR=3.15),and R0 clearance rate(CR)(OR=2.25).However,nCT demonstrated a better 5-year OSR(OR=1.02)than nCRT.Moreover,when compared to nCRT,nCT showed reduced risks of cardiac complications(OR=1.15)and pulmonary complications(OR=1.30).CONCLUSION Overall,both nCRT and nCT were effective in terms of survival outcomes for LAEC.However,nCT exhibited better performance in terms of postoperative complications.

Effects of neoadjuvant chemotherapy vs chemoradiotherapy in the treatment of esophageal adenocarcinoma:A systematic review and meta-analysis

BACKGROUND Neoadjuvant therapy is an essential modality for reducing the clinical stage of esophageal cancer;however,the superiority of neoadjuvant chemotherapy(nCT)or neoadjuvant chemoradiotherapy(nCRT)is unclear.Therefore,a discussion of these two modalities is necessary.AIM To investigate the benefits and complications of neoadjuvant modalities.METHODS To address this concern,predefined criteria were established using the PICO protocol.Two independent authors performed comprehensive searches using predetermined keywords.Statistical analyses were performed to identify significant differences between groups.Potential publication bias was visualized using funnel plots.The quality of the data was evaluated using the Risk of Bias Tool 2(RoB2)and the GRADE approach.RESULTS Ten articles,including 1928 patients,were included for the analysis.Significant difference was detected in pathological complete response(pCR)[P<0.001;odds ratio(OR):0.27;95%CI:0.16-0.46],30-d mortality(P=0.015;OR:0.4;95%CI:0.22-0.71)favoring the nCRT,and renal failure(P=0.039;OR:1.04;95%CI:0.66-1.64)favoring the nCT.No significant differences were observed in terms of survival,local or distal recurrence,or other clinical or surgical complications.The result of RoB2 was moderate,and that of the GRADE approach was low or very low in almost all cases.CONCLUSION Although nCRT may have a higher pCR rate,it does not translate to greater long-term survival.Moreover,nCRT is associated with higher 30-d mortality,although the specific cause for postoperative complications could not be identified.In the case of nCT,toxic side effects are suspected,which can reduce the quality of life.Given the quality of available studies,further randomized trials are required.

Study on the Application of Refined Nursing Care in The Care for Elderly Patients with Reflux Esophagitis

Objective: To investigate the application effect of refined nursing care in the care for elderly patients with reflux esophagitis. Methods: Following the difference in nursing style, 84 cases of elderly patients with reflux esophagitis admitted to our hospital from May 2022 to May 2023 were randomly grouped into a control group and a research group, with 42 cases each. The control group was given conventional nursing care and the research group was given refined nursing care. The psychological state and treatment adherence of the two groups of patients after the nursing intervention were compared. Results: After the nursing intervention, the self-rating anxiety scale (SAS) and self-rating depression scale (SDS) scores of the research group were lower than those of the control group (P < 0.05). The treatment compliance of the research group was better than the control group (P < 0.05). Conclusion: The implementation of refined nursing care for elderly patients with reflux esophagitis exhibited a significant effect on improving the patient’s psychological state, treatment compliance, and rehabilitation.

Animal models of eosinophilic esophagitis,review and perspectives

Eosinophilic oesophagitis(EoE)is an allergen/immune-mediated chronic esophageal disease characterized by esophageal mucosal eosinophilic infiltration and esophageal dysfunction.Although the disease was originally attributed to a delayed allergic reaction to allergens and a Th2-type immune response,the exact pathogenesis is complex,and the efficacy of existing treatments is unsatisfactory.Therefore,the study of the pathophysiological process of EOE has received increasing attention.Animal models have been used extensively to study the molecular mechanism of EOE pathogenesis and also provide a preclinical platform for human clinical intervention studies of novel therapeutic agents.To maximize the use of existing animal models of EOE,it is important to understand the advantages or limitations of each modeling approach.This paper systematically describes the selection of experimental animals,types of allergens,and methods of sensitization and excitation during the preparation of animal models of EoE.It also discusses the utility and shortcomings of each model with the aim of providing the latest perspectives on EoE models and leading to better choices of animal models.

Clinical features of gastroesophageal reflux disease and erosive esophagitis:Insights from patients undergoing esophagogastroduodenoscopy in resource-limited Ethiopia

BACKGROUND Gastroesophageal reflux disease(GERD)is a common disease worldwide with varying clinical presentations and risk factors.Prevalence data for Africa is lacking,but an increasing trend is expected due to demographic and epidemiological transitions.Although endoscopic studies for general gastrointestinal disorders have shown some patients with erosive esophagitis(EE),no studies in Ethiopia have investigated the clinical characteristics,risk factors,and severity of GERD using esophagogastroduodenoscopy(EGD).AIM To assess the clinical features of GERD in Ethiopian patients who underwent EGD and determine the severity and risk factors of EE.METHODS We conducted a multicenter,retrospective cross-sectional study of 221 patients diagnosed with GERD and endoscopic findings of EE at Trauma Associated Severe Hemorrhage and Amniotic Membrane Stem Cell between January 2019 and August 2022.Data were collected from electronic medical records and phone call interviews.We used descriptive statistics and binary logistic regression analysis with SPSS version 26 to identify the association between variables with a statistical significance set at P value<0.05.RESULTS The mean±SD age of the patients was 44.8(±15.9)years,with a male-to-female ratio of 1.6:1.The most commonly reported symptom was epigastric pain(80.5%),followed by heartburn(43%).Los Angeles(LA)-A EE was diagnosed in 71.1%of patients,followed by LA-B(14.9%),LA-C(7.7%),and LA-D(5.9%).Multivariate analysis showed that age 50 or above,presence of bleeding,and endoscopic findings of duodenitis/duodenopathy were significantly associated with severe EE(P<0.05).Stricture and Barrett’s esophagus were observed in 4.5%and 1.36%of patients with EE,respectively.CONCLUSION Most of the patients had milder EE with fewer complications.However,severe EE was more prevalent in older patients and those with duodenitis/duodenopathy.

Huoxue Tongjiang decoction-resisted reflux esophagitis by activation stem cell factor/c-kit/interstitial cell of cajal pathway and regulating the T-helper 17/regulatory T-cells balance in rats

Background:Huoxue Tongjiang decoction(HXTJD)is an effective prescription for treating reflux esophagitis(RE).We investigated the effects of HXTJD on esophageal motility and mucosal inflammation in a rat RE model.Methods:Chemical composition of HXTJD was analyzed by ultrahigh-performance liquid chromatography Q-Orbitrap mass spectrometry(MS).The change rates of mean contraction tension forces,mean amplitudes,and mean frequencies for the lower esophageal sphincter(LES)were recorded using the isolated tissue bath system,mechanical tension transducer,and PowerLab physiological recorder.After weighing the stomach,the phenol red labeling method was used to measure the gastric emptying rate.The LES ultrastructure was observed through transmission electron microscopy.Immunofluorescence and western blotting were used to detect the number of interstitial cells of Cajal(ICC)and the expression levels of c-kit protein,connexin43(Cx43),and stem cell factor(SCF).Flow cytometric analysis and enzyme-linked immunosorbent assay were conducted to detect the percentages of T helper 17(Th17)cells and regulatory T(Treg)cells and the serum concentrations of interleukin 6(IL-6),interleukin 17(IL-17),and interleukin 10(IL-10)in the rats.Results:We identified 28 chemical constituents in HXTJD.Regarding esophageal motility,we revealed that HXTJD increased the mean contraction tension forces,mean amplitudes,and mean frequency change rate of LES and the gastric emptying rate;decreased stomach weight;and improved the LES ultrastructure.Additionally,HXTJD increased the number of ICC-positive cells,and c-kit,Cx43,and SCF expression levels.Regarding esophageal inflammation,HXTJD significantly decreased the percentage of Th17 cells,and IL-6 and IL-17 concentrations,and increased the percentage of Treg cells and IL-10 concentration.Conclusion:HXTJD was found to be efficacious in the rat RE model.It may promote esophageal motility and alleviate the inflammatory response by activating the SCF/c-kit/ICC pathway and regulating the Th17/Treg cell balance.

The Therapeutic Effect of Biling Weitong Granules Combined with Oryz-Aspergillus Enzyme and Pancreatin Tablet on Reflux Esophagitis with Functional Dyspepsia

Objective:To investigate the therapeutic effect of Biling Weitong Granules combined with oryz-aspergillus enzyme and pancreatin tablets on patients with reflux esophagitis with functional dyspepsia.Methods:Sixty patients diagnosed with reflux esophagitis with functional dyspepsia who were admitted to the Affiliated Hospital of Hebei University between June 2020 and June 2023 were selected and divided into two groups:the control group and the observation group,each consisting of 30 cases.The control group received oryz-aspergillus enzyme and pancreatin tablets only,while the observation group received Biling Weitong Granules in addition to the tablets.The clinical efficacy,Chinese medicine syndrome points,esophageal kinetic indexes,gastrointestinal hormone levels,and therapeutic safety of both groups were evaluated.Results:The total efficiency of the observation group reached 93.33%,significantly higher than the 73.33%of the control group(P<0.05).After treatment,patients in the observation group exhibited significantly lower scores for Chinese medicine symptoms such as early satiety,belching,abdominal distension,abdominal pain,and loss of appetite compared to the control group(P<0.05).Furthermore,the observation group showed significantly higher upper esophageal sphincter pressure,lower esophageal sphincter pressure,and distal esophageal contraction scores compared to the control group(P<0.05).Additionally,levels of gastric motility hormone,vasoactive intestinal peptide,and gastrin were significantly higher in the observation group compared to the control group(P<0.05).Throughout the treatment period,there was no significant difference in the incidence of adverse reactions between the two groups,indicating comparable safety of the two treatment modalities(P>0.05).Conclusion:The combination of Biling Weitong Granules with oryz-aspergillus enzyme and pancreatin tablets demonstrates significant efficacy in the treatment of reflux esophagitis with functional dyspepsia,with a better safety profile.This finding warrants further clinical promotion.

Prognosis of radiotherapy for esophageal cancer in elderly patients exceeding seventy-five years old

BACKGROUND Esophageal cancer(EC)often occurs in the elderly,with approximately 33%of patients aged≥75 years at the time of diagnosis.AIM To evaluate the prognostic factors for radiotherapy(RT)in elderly patients with unresectable EC.METHODS We retrospectively analyzed the clinical characteristics,toxic reactions,and survival information of EC patients aged≥75 years who underwent intensity-modulated RT at Lu’an Hospital of Anhui Medical University between January 2016 and September 2023.Kaplan-Meier analysis was used to draw the overall survival(OS)curves,and Cox regression analysis was employed to evaluate the influence of various clinical factors on the prognosis.RESULTS A total of 139 patients were enrolled.The median follow-up time was 52.0 months.The median OS was 20.0 months.The 1-year,2-year,3-year,and 5-year OS rates were 69.8%,38.7%,28.2%,and 17.5%,respectively.Univariate analysis showed that age,radiation dose,and chemotherapy had no significant impact on prognosis.Multivariate analysis indicated that clinical stage[Ⅲ-Ⅳa vsⅠ-Ⅱ,hazard ratio(HR)=2.421,95%confidence interval(CI):1.242-4.718,P=0.009;IVb vsⅠ-Ⅱ,HR=4.222,95%CI:1.888-9.438,P<0.001),Charlson comorbidity index(CCI)(0 vs≥1,HR=1.539,95%CI:1.015-2.332,P=0.042),and nutritional risk screening 2002(NRS2002)(<3 vs≥3,HR=2.491,95%CI:1.601-3.875,P<0.001)were independent prognostic factors for OS.CONCLUSION Our results suggest that CCI and NRS2002 were independent prognostic factors of OS for unresectable elderly EC patients undergoing RT.For elderly patients with EC,full attention should be given to biological age-related indicators,such as comorbidities and nutrition,when formulating treatment protocols.These factors should be considered in future clinical practice.

Targeting oxidative stress with natural products: A novel strategy for esophageal cancer therapy

Esophageal cancer(ESC)is a malignant tumor that originates from the mucosal epithelium of the esophagus and is part of the digestive tract.Although the exact pathogenesis of ESC has not been fully elucidated,excessive oxidative stress is an important characteristic that leads to the development of many cancers.Abnormal expression of several proteins and transcription factors contributes to oxidative stress in ESCs,which alters the growth and proliferation of ESCs and promotes their metastasis.Natural compounds,including alkaloids,terpenes,polyphenols,and xanthine compounds,can inhibit reactive oxygen species production in ESCs.These compounds reduce oxidative stress levels and subsequently inhibit the oc-currence and progression of ESC through the regulation of targets and pathways such as the cytokine interleukins 6 and 10,superoxide dismutase,the NF-+ACY-kappa+ADs-B/MAPK pathway,and the mammalian Nrf2/ARE target pathway.Thus,targeting tumor oxidative stress has become a key focus in anti-ESC therapy.This review discusses the potential of Natural products(NPs)for treating ESCs and summarizes the application prospects of oxidative stress as a new target for ESC treatment.The findings of this review provide a reference for drug development targeting ESCs.Nonetheless,further high-quality studies will be necessary to determine the clinical efficacy of these various NPs.

Impact of baseline steroids on the efficacy of neoadjuvant immunochemotherapy in locally advanced esophageal squamous cell carcinoma

BACKGROUND Immunochemotherapy involving the combination of programmed cell death 1/programmed cell death ligand 1 inhibitors with chemotherapy has advanced the treatment of locally advanced esophageal squamous cell carcinoma(ESCC).The use of corticosteroids as pretreatment might reduce immunotherapy efficacy.AIM To investigate the impact of baseline corticosteroid use on neoadjuvant immunochemotherapy(nIC)outcomes in locally advanced ESCC patients.METHODS Patients with locally advanced ESCC who received nIC at Sun Yat-sen University Cancer Center and the Third Affiliated Hospital of Sun Yat-sen University were included.Patients were divided into dexamethasone and antihistamine groups on the basis of the administered pretreatment.Antiallergic efficacy and safety were evaluated,as well as its impact on short-term efficacy[complete pathological response(pCR),major pathological response(MPR)]and long-term efficacy[overall survival(OS),progression-free survival(PFS)]of nIC.RESULTS From September 2019 to September 2023,142 patients were analyzed.No severe treatment-related adverse events or deaths were observed.Allergy occurrence was greater in the antihistamine group(P=0.014).Short-term efficacy was not significantly different:The pCR rates were 29.9%and 40.0%,and the MPR rates were 57.9%and 65.7%in the dexamethasone and antihistamine groups,respectively.The long-term efficacy was not significantly different:The 2 years OS rates were 95.2%and 93.5%,and the 2 years PFS rates were 90.3%and 87.8%.Subgroup analysis revealed no difference in OS between the 20 mg dexamethasone group and the<20 mg dexamethasone group,but PFS was significantly greater in the 20 mg dexamethasone group(93.9%vs 56.4%,P=0.001).CONCLUSION Dexamethasone or antihistamines can be used before nIC in locally advanced ESCC without affecting short-or long-term efficacy.Administering 20 mg dexamethasone before nIC may improve PFS in ESCC.

Effectiveness and safety of combined nimotuzumab and S-1 chemotherapy with concurrent radiotherapy for locally advanced esophageal cancer in malnourished and elderly patients:A prospective phaseⅡstudy

Objective:Definitive chemoradiotherapy(dCRT)is the standard treatment for unresectable locally advanced esophageal cancer.However,this treatment is associated with substantial toxicity,and most malnourished or elderly patients are unable to complete this therapy.Therefore,there is a need for a more suitable radiotherapy combination regimen for this population.This study was aimed to evaluate the efficacy and safety of a combination regimen comprising chemotherapy with nimotuzumab and S-1 and concurrent radiotherapy for patients with fragile locally advanced esophageal cancer with a high Nutritional Risk Screening 2002(NRS-2002)score.Methods:Eligible patients with unresectable esophageal carcinoma who had an NRS-2002 score of 2 or higher were enrolled.They were treated with S-1 and nimotuzumab with concurrent radiotherapy,followed by surgery or definitive radiotherapy.The primary endpoint was the locoregional control(LRC)rate.Results:A total of 55 patients who met the study criteria were enrolled.After completion of treatment,surgery was performed in 15 patients and radiotherapy was continued in 40 patients.The median follow-up period was 33.3[95%confidence interval(95%CI,31.4−35.1)]months.The LRC rate was 77.2%(95%CI,66.6%−89.4%)at 1 year in the entire population.The overall survival(OS)rate and event-free survival(EFS)rate were 57.5%and 51.5%at 3 years,respectively.Surgery was associated with better LRC[hazard ratio(HR)=0.16;95%CI,0.04−0.70;P=0.015],OS(HR=0.19;95%CI,0.04−0.80;P=0.024),and EFS(HR=0.25;95%CI,0.08−0.75;P=0.013).Most adverse events were of grade 1 or 2,and no severe adverse events occurred.Conclusions:For malnourished or elderly patients with locally advanced esophageal cancer,radiotherapy combined with nimotuzumab and S-1 is effective and has a good safety profile.

Evolving strategies: Enhancements in managing eosinophilic esophagitis in pediatric patients

Eosinophilic esophagitis is a newly recognized disease first described about 50 years ago.The definition,diagnosis,and management have evolved with new published consensus guidelines and newly approved treatment available to pediatricians,enabling a better understanding of this disease and more targeted treatment for patients.We describe the definition,presentation,and diagnosis of eosinophilic esophagitis including management,challenges,and future directions in children.The definition,diagnosis,and management of eosinophilic esophagitis have evolved over the last 50 years.Consensus guidelines and newly approved biologic treatment have enabled pediatricians to better understand this disease and allow for more targeted treatment for patients.We describe the definition,presentation,diagnosis,management,and treatment in addition to the challenges and future directions of eosinophilic esophagitis management in children.

Optimal extent of lymphadenectomy improves prognosis and guides adjuvant chemotherapy in esophageal cancer: A propensity scorematched analysis

BACKGROUND The optimal extent of lymphadenectomy in esophageal squamous cell carcinoma(ESCC)patients remained debatable.AIM To explore the ideal number of cleared lymph nodes in ESCC patients undergoing upfront surgery.METHODS In this retrospective,propensity score-matched study,we included 1042 ESCC patients who underwent esophagectomy from November 2008 and October 2019.Patients who underwent neoadjuvant therapy were excluded.We collected pa-tients’clinicopathological features and information regarding lymph nodes,in-cluding the total number of resected lymph nodes(NRLN),and pathologically diagnosed positive lymph nodes(RPLN).SPSS and R software were used for statistical analysis.RESULTS Among the included 1042 patients,two cohorts:≤21(n=664)and>21 NRLN(n=378)were identified.The final prognostic model included four variables:T stage,N,venous thrombus,and the number of removed lymph nodes.Among them,NRLN>21 was determined as an independent prognosticator after surgery for esophageal cancer(hazards regression=0.66,95%confidence interval:0.50-0.87,P=0.004).A nomogram was created based on the regression coefficients of the variables in the final model.In the training cohort,the predictive model dis-played an uncorrected five-year overall survival C-index of 0.659,with a bootstrap-corrected C-index of 0.654.In the subgroup analysis,adjuvant chemotherapy was beneficial in the subgroup with NRLN>21 and RPLN≤0.16 and NRLN≤21 and RPLN>0.16.CONCLUSION NRLN>21 was an independent prognostic factor after ESCC surgery.The combination of NRLN and RPLN may provide a reference for adjuvant chemotherapy use in potential beneficiaries.

Cetuximab combined with chemotherapy for simultaneous esophageal squamous cell carcinoma and colon adenocarcinoma:A case report

BACKGROUND Multiple primary carcinomas(MPCs)are defined as two or more independent primary cancers that occur simultaneously or sequentially in the same individual.Synchronous MPCs are rarer than solitary cancers or metachronous MPCs.Accurate diagnoses of synchronous MPCs and the choice of treatment are critical for successful outcomes in these cases.CASE SUMMARY A 64-year-old patient presented with dysphagia,without obvious cause.A diagnosis of synchronous esophageal squamous cell carcinoma and colon adenocarcinoma with liver metastasis was confirmed based on examination and laboratory results.After multi-disciplinary consultations,combination chemotherapy(a 3-wk cycle with oxaliplatin 212 mg administered on day 1 and capecitabine 1.5 g twice daily on days 1-14)and esophageal cancer radiotherapy were initiated.Based on the results of genetic testing,we switched to a regimen of leucovorin+fluorouracil+oxaliplatin and cetuximab regimen for 8 cycles.Subsequently,capecitabine and bevacizumab were administered until the most recent follow-up,at which the tumor remained stable.CONCLUSION Successful cetuximab chemotherapy treatment provides a reference for the nonoperative and homogeneous treatment of different pathological types of synchronous MCPs.