Although there has been significant advancement in the identification and management of colorectal cancer(CRC)in recent years,there is still room for improvement in the current standard treatment regimen.One area of c...Although there has been significant advancement in the identification and management of colorectal cancer(CRC)in recent years,there is still room for improvement in the current standard treatment regimen.One area of concern is the lack of reliable tumor markers to predict treatment efficacy and guide tailored care.Due to its dynamic,effective,and non-invasive benefits over tissue biopsy,the detection of minimal or molecular residual lesions(MRD)based on circulating tumor DNA(ctDNA)is beneficial to the clinical development of drugs for patients with CRC after radical treatment,as well as for continuous monitoring of tumor recurrence and malignancy molecular gene evolution.The detection of ctDNA can currently be used to guide individual postoperative auxiliary treatment decisions(upgrade or downgrade treatment)in CRC,stratify the risk of clinical recurrence more precisely,and predict the risk of recurrence in advance of imaging examination,according to a large number of observational or prospective clinical studies.With increasing clarity comes the possibility of selecting a regimen of treatment based on postoperative ctDNA,which also improves the accuracy of clinical recurrence risk assessment for CRC.Therefore,it is anticipated that the identification of ctDNA would alter the current framework for dealing with CRC and lead to individualized,stratified precision therapy;however,additional confirmation will require subsequent high-quality,prospective,large-scale randomized controlled studies.This article will provide an overview of the definition and clinical significance of MRD,the primary indications and technological challenges for MRD detection,along with the advancement in clinical research about ctDNA detection following radical resection of the CRC.展开更多
Objective:Neoantigens arising from gene mutations in tumors can induce specific immune responses,and neoantigen-based immunotherapies have been tested in clinical trials.Here,we characterized the efficacy of altered n...Objective:Neoantigens arising from gene mutations in tumors can induce specific immune responses,and neoantigen-based immunotherapies have been tested in clinical trials.Here,we characterized the efficacy of altered neoepitopes in improving immunogenicity against gastric cancer.Methods:Raw data of whole-exome sequencing derived from a patient with gastric cancer were analyzed using bioinformatics methods to identify neoepitopes.Neoepitopes were modified by P1Y(the first amino acid was replaced by tyrosine)and P2L(the second amino acid was replaced by leucine).T2 binding and stability assays were used to detect the affinities between the neoepitopes and the HLA molecules,as well as the stabilities of complexes.Dendritic cells(DCs)presented with neoepitopes stimulated naïve CD8+T cells to induce specific cytotoxic T lymphocytes.ELISA and carboxyfluorescein succinimidyl ester were used to detect IFN-γand TNF-αlevels,and T cell proliferation.Perforin was detected by flow cytometry.The cytotoxicity of T cells was determined using the lactate dehydrogenase assay.Results:Bioinformatics analysis,T2 binding,and stability assays indicated that residue substitution increased the affinity between neoepitopes and HLA molecules,as well as the stabilities of complexes.DCs presented with altered neoepitopes stimulated CD8+T cells to release more IFN-γand had a greater effect on promoting proliferation than wild-type neoepitopes.CD8+T cells stimulated with altered neoepitopes killed more wild-type neoepitope-pulsed T2 cells than those stimulated with wild-type neoepitopes,by secreting more IFN-γ,TNF-α,and perforin.Conclusions:Altered neoepitopes exhibited greater immunogenicity than wild-type neoepitopes.Residue substitution could be used as a new strategy for immunotherapy to target neoantigens.展开更多
Human epidermal growth factor receptor 2(HER2)-overexpressing breast cancer is an aggressive phenotype with a poor prognosis,and can easily metastasize and recur.Currently,chemotherapy plus HER2-targeted therapy is th...Human epidermal growth factor receptor 2(HER2)-overexpressing breast cancer is an aggressive phenotype with a poor prognosis,and can easily metastasize and recur.Currently,chemotherapy plus HER2-targeted therapy is the standard systemic treatment for most of these patients.Given that neoadjuvant chemotherapy(NAC)has an efficacy equivalent to that of adjuvant chemotherapy and some additional benefits,many patients,especially those with more advanced tumors,prefer NAC and generally will not receive additional chemotherapy after surgery,irrespective of the pathological response.However,achieving pathological complete response to NAC is strongly correlated with prognosis,especially in triple-negative and HER2-overexpressing breast cancer.Therefore,postoperative treatment of these patients with residual diseases should be optimized to achieve favorable outcomes.The CREATE-X study has confirmed that additional chemotherapy can improve the outcomes of patients with HER2-negative residual disease after NAC.In addition,chemotherapy plays an indispensable role in the treatment of patients who receive surgery directly or who have recurrent lesions.Therefore,can additional chemotherapy improve prognosis of patients with HER2-overexpressing residual breast cancer?At present,no studies have compared the efficacy of additional chemotherapy plus trastuzumab with that of anti-HER2 therapy alone in residual cancer.The KATHERINE study revealed that trastuzumab emtansine(T-DM1)can reduce the risk of recurrence or death by 50%compared with trastuzumab in patients with HER2-positive residual invasive breast cancer after neoadjuvant therapy.T-DM1 is an antibody-drug conjugate of trastuzumab and the cytotoxic agent emtansine,and thus,to an extent,T-DM1 is equivalent to simultaneous application of chemotherapy and targeted therapy.However,high cost and low accessibility limit its use especially in low-and middle-income countries and regions.Hence,we proposed this perspective that additional chemotherapy plus trastuzumab should be given to HER2-overexpressing breast cancer patients with residual disease after NAC to improve their prognosis by discussing that the efficacy of additional chemotherapy plus trastuzumab is superior to that of anti-HER2 therapy alone and not inferior to T-DM1.Additional chemotherapy plus trastuzumab-based HER2-targeted therapy can be used as an alternative regimen to T-DM1 when T-DM1 is unavailable.However,further clinical research on the selection of chemotherapeutic agents is warranted.展开更多
A 91-year-old man was referred to our hospital with intermittent dysphagia. He had undergone esophagectomy for esophageal cancer(T3N2M0 Stage Ⅲ) 11 years earlier. Endoscopic examination revealed an anastomotic strict...A 91-year-old man was referred to our hospital with intermittent dysphagia. He had undergone esophagectomy for esophageal cancer(T3N2M0 Stage Ⅲ) 11 years earlier. Endoscopic examination revealed an anastomotic stricture; signs of inflammation,including redness,erosion,edema,bleeding,friability,and exudate with white plaques; and multiple depressions in the residual esophagus. Radiographical examination revealed numerous fine,gastrografinfilled projections and an anastomotic stricture. Biopsy specimens from the area of the anastomotic stricture revealed inflammatory changes without signs of malignancy. Candida glabrata was detected with a culture test of the biopsy specimens. The stricture was diagnosed as a benign stricture that was caused by esophageal intramural pseudodiverticulosis. Accordingly,endoscopic balloon dilatation was performed and antifungal therapy was started in the hospital. Seven weeks later,endoscopic examination revealed improvement in the mucosal inflammation; only the pseudodiverticulosis remained. Consequently,the patient was discharged. At the latest follow-up,the patient was symptomfree and the pseudodiverticulosis remained in the residual esophagus without any signs of stricture or inflammation.展开更多
Presence of occult minimal residual disease in patients with colorectal cancer(CRC)has a strong prognostic impact on survival.Minimal residual disease plays a major role in disease relapse and formation of metastases ...Presence of occult minimal residual disease in patients with colorectal cancer(CRC)has a strong prognostic impact on survival.Minimal residual disease plays a major role in disease relapse and formation of metastases in CRC.Analysis of circulating tumor cells(CTC)in the blood is increasingly used in clinical practice for disease monitoring of CRC patients.In this review article the role of CTC,disseminated tumor cells(DTC)in the bone marrow and micrometastases and isolated tumor cells(ITC)in the lymph nodes will be discussed,including literature published until September 2013.Occult disease is a strong prognostic marker for patient survival in CRC and defined by the presence of CTC in the blood,DTC in the bone marrow and/or micrometastases and ITC in the lymph nodes.Minimal residual disease could be used in the future to identify patient groups at risk,who might benefit from individualized treatment options.展开更多
Curative therapy was not previously available for patients with advanced non-small cell lung cancer(NSCLC);thus,the concept of minimal/measurable(or molecular)residual disease(MRD)was not applicable to these patients....Curative therapy was not previously available for patients with advanced non-small cell lung cancer(NSCLC);thus,the concept of minimal/measurable(or molecular)residual disease(MRD)was not applicable to these patients.However,advances in targeted and immunotherapy have revolutionized the treatment landscape for patients with advanced NSCLC,with emerging evidence of long-term survival and even the hope of complete remission(CR)by imaging examination.The latest research shows that patients with oligometastatic lung cancer can benefit from local treatment.After removing the lesions,the choice of follow-up therapy and monitoring of the lesions could remain uncertain.MRD plays a role in identifying early-stage NSCLC patients with high risks of recurrence and determining adjuvant therapy after radical treatment.In recent years,evidence has been accumulating regarding the use of circulating cell-free tumor DNA(ctDNA)to assess MRD in solid tumors.This study discussed the possible applications of ctDNA-based MRD monitoring in advanced NSCLC and described the current challenges and unresolved problems in the application of MRD in advanced NSCLC.展开更多
BACKGROUND The rate of positive resection margins(R1) in patients with low rectal cancer is substantial. Recommended remedies such as extended resection or chemoradiotherapy have their own serious drawbacks. It has be...BACKGROUND The rate of positive resection margins(R1) in patients with low rectal cancer is substantial. Recommended remedies such as extended resection or chemoradiotherapy have their own serious drawbacks. It has been reported that photodynamic therapy(PDT) as a remedial treatment for esophageal cancer.Colorectal cancer and esophageal cancer has many similarities,however,PDT as a salvage therapy for rectal cancer is rare.CASE SUMMARY Here,we describe a 56-year-old man who was admitted to the hospital due to a 6-mo history of hemafecia,which had been aggravated for 1 mo. Colonoscopy revealed a 3 × 4 cm ulcerated mass in the rectum 4 cm from the anus.Preoperative pathological examination showed villous adenoma,moderate-tohigh-grade dysplasia,good differentiation,and invasion of the mucosal muscle.The patient had R1 after ultra-low anterior resection,but he refused extended resection and experienced severe liver function impairment after 3 cycles of chemotherapy. Ultimately,the patient underwent PDT to remove R1. After five years of follow-up,there was no liver function impairment,recurrence,metastasis,sexual dysfunction,or abnormal defecation function.CONCLUSION This is the first case worldwide in which R1 of rectal cancer were successfully treated by PDT.展开更多
Multicollinearity constitutes shared variation among predictors that inflates standard errors of regression coefficients. Several years ago, it was proven that the common practice of mean centering in moderated regres...Multicollinearity constitutes shared variation among predictors that inflates standard errors of regression coefficients. Several years ago, it was proven that the common practice of mean centering in moderated regression cannot alleviate multicollinearity among variables comprising an interaction, but merely masks it. Residual centering (orthogonalizing) is unacceptable because it biases parameters for predictors from which the interaction derives, thus precluding interpretation of moderator effects. I propose and validate residual centering in sequential re-estimations of a moderated regression—sequential residual centering (SRC)—by revealing unbiased multicollinearity conditioning across the interaction and its related terms. Across simulations, SRC reduces variance inflation factors (VIF) regardless of distribution shape or pattern of regression coefficients across predictors. For any predictor, the reduced VIF is used to derive a lower standard error of its regression coefficient. A cancer sample illustrates SRC, which allows unbiased interpretations of symptom clusters. SRC can be applied efficiently to alleviate multicollinearity after data collection and shows promise for advancing synergistic frontiers of research.展开更多
BACKGROUND The diagnosis of residual tumors using endoscopic ultrasound(EUS)after neoadjuvant therapy for esophageal cancer is considered challenging.However,the reasons for this difficulty are not well understood.AIM...BACKGROUND The diagnosis of residual tumors using endoscopic ultrasound(EUS)after neoadjuvant therapy for esophageal cancer is considered challenging.However,the reasons for this difficulty are not well understood.AIM To investigate the ultrasound imaging features of residual tumors and identify the limitations and potential of EUS.METHODS This exploratory prospective observational study enrolled 23 esophageal squamous cell carcinoma patients receiving esophagectomy after neoadjuvant therapy[15 patients after neoadjuvant chemotherapy(NAC)and 8 patients after chemoradiotherapy(CRT)]at the Department of Surgery,Chiba University Hospital,between May 2020 and October 2021.We diagnosed the T stage for specimens using ultrasound just after surgery and compared ultrasound images with the cut surface of the fixed specimens of the same level of residual tumor.The ratio of esophageal muscle layer defect measured by ultrasound was compared with clinicopathological factors.Furthermore,the rate of reduction for the muscle layer defect was evaluated using EUS images obtained before and after neoadjuvant therapy.RESULTS The accuracy of T stage rate was 61%(n=14/23),which worsened after CRT(38%,n=3/8)than after NAC(73%,n=11/15)because of overstaging.Moreover,pT0 could not be diagnosed in all cases.The detection rate of residual tumor for specimens using ultrasound retrospectively was 75%(n=15/20).There was no correlation between after-NAC(79%,n=11/14)and after-CRT(67%,n=4/6)detection rate.The detection of superficial and submucosal types was poor.The pathologic tumor size and pathological response were correlated.Tumor borders were irregular and echogenicity was mixed type after CRT.There was a correlation between the pT stage(pT0/1 vs pT2/3)and the length of muscle layer circumference(P=0.025),the length of muscle layer defect(P<0.001),and the ratio of muscle layer defect(P<0.001).There was also a correlation between the pT stage and the rate of muscle layer defect reduction measured by EUS(P=0.001).CONCLUSION Compared to pathological images,some tumors are undetectable by ultrasound.Focusing on the esophageal muscle layer might help diagnose the depth of the residual tumor.展开更多
基金supported by grants from Sanming Project of Medicine in Shenzhen(No.SZSM202211017)Shenzhen Key Medical Discipline Construction Fund(No.SZXK014).
文摘Although there has been significant advancement in the identification and management of colorectal cancer(CRC)in recent years,there is still room for improvement in the current standard treatment regimen.One area of concern is the lack of reliable tumor markers to predict treatment efficacy and guide tailored care.Due to its dynamic,effective,and non-invasive benefits over tissue biopsy,the detection of minimal or molecular residual lesions(MRD)based on circulating tumor DNA(ctDNA)is beneficial to the clinical development of drugs for patients with CRC after radical treatment,as well as for continuous monitoring of tumor recurrence and malignancy molecular gene evolution.The detection of ctDNA can currently be used to guide individual postoperative auxiliary treatment decisions(upgrade or downgrade treatment)in CRC,stratify the risk of clinical recurrence more precisely,and predict the risk of recurrence in advance of imaging examination,according to a large number of observational or prospective clinical studies.With increasing clarity comes the possibility of selecting a regimen of treatment based on postoperative ctDNA,which also improves the accuracy of clinical recurrence risk assessment for CRC.Therefore,it is anticipated that the identification of ctDNA would alter the current framework for dealing with CRC and lead to individualized,stratified precision therapy;however,additional confirmation will require subsequent high-quality,prospective,large-scale randomized controlled studies.This article will provide an overview of the definition and clinical significance of MRD,the primary indications and technological challenges for MRD detection,along with the advancement in clinical research about ctDNA detection following radical resection of the CRC.
基金This work was supported by grants from the Science and Technology Project in Fujian Province of China(Grant No.2018I0004)Joint Funds for the innovation of Science and Technology,Fujian Province of China(Grant No.2018Y9108).
文摘Objective:Neoantigens arising from gene mutations in tumors can induce specific immune responses,and neoantigen-based immunotherapies have been tested in clinical trials.Here,we characterized the efficacy of altered neoepitopes in improving immunogenicity against gastric cancer.Methods:Raw data of whole-exome sequencing derived from a patient with gastric cancer were analyzed using bioinformatics methods to identify neoepitopes.Neoepitopes were modified by P1Y(the first amino acid was replaced by tyrosine)and P2L(the second amino acid was replaced by leucine).T2 binding and stability assays were used to detect the affinities between the neoepitopes and the HLA molecules,as well as the stabilities of complexes.Dendritic cells(DCs)presented with neoepitopes stimulated naïve CD8+T cells to induce specific cytotoxic T lymphocytes.ELISA and carboxyfluorescein succinimidyl ester were used to detect IFN-γand TNF-αlevels,and T cell proliferation.Perforin was detected by flow cytometry.The cytotoxicity of T cells was determined using the lactate dehydrogenase assay.Results:Bioinformatics analysis,T2 binding,and stability assays indicated that residue substitution increased the affinity between neoepitopes and HLA molecules,as well as the stabilities of complexes.DCs presented with altered neoepitopes stimulated CD8+T cells to release more IFN-γand had a greater effect on promoting proliferation than wild-type neoepitopes.CD8+T cells stimulated with altered neoepitopes killed more wild-type neoepitope-pulsed T2 cells than those stimulated with wild-type neoepitopes,by secreting more IFN-γ,TNF-α,and perforin.Conclusions:Altered neoepitopes exhibited greater immunogenicity than wild-type neoepitopes.Residue substitution could be used as a new strategy for immunotherapy to target neoantigens.
文摘Human epidermal growth factor receptor 2(HER2)-overexpressing breast cancer is an aggressive phenotype with a poor prognosis,and can easily metastasize and recur.Currently,chemotherapy plus HER2-targeted therapy is the standard systemic treatment for most of these patients.Given that neoadjuvant chemotherapy(NAC)has an efficacy equivalent to that of adjuvant chemotherapy and some additional benefits,many patients,especially those with more advanced tumors,prefer NAC and generally will not receive additional chemotherapy after surgery,irrespective of the pathological response.However,achieving pathological complete response to NAC is strongly correlated with prognosis,especially in triple-negative and HER2-overexpressing breast cancer.Therefore,postoperative treatment of these patients with residual diseases should be optimized to achieve favorable outcomes.The CREATE-X study has confirmed that additional chemotherapy can improve the outcomes of patients with HER2-negative residual disease after NAC.In addition,chemotherapy plays an indispensable role in the treatment of patients who receive surgery directly or who have recurrent lesions.Therefore,can additional chemotherapy improve prognosis of patients with HER2-overexpressing residual breast cancer?At present,no studies have compared the efficacy of additional chemotherapy plus trastuzumab with that of anti-HER2 therapy alone in residual cancer.The KATHERINE study revealed that trastuzumab emtansine(T-DM1)can reduce the risk of recurrence or death by 50%compared with trastuzumab in patients with HER2-positive residual invasive breast cancer after neoadjuvant therapy.T-DM1 is an antibody-drug conjugate of trastuzumab and the cytotoxic agent emtansine,and thus,to an extent,T-DM1 is equivalent to simultaneous application of chemotherapy and targeted therapy.However,high cost and low accessibility limit its use especially in low-and middle-income countries and regions.Hence,we proposed this perspective that additional chemotherapy plus trastuzumab should be given to HER2-overexpressing breast cancer patients with residual disease after NAC to improve their prognosis by discussing that the efficacy of additional chemotherapy plus trastuzumab is superior to that of anti-HER2 therapy alone and not inferior to T-DM1.Additional chemotherapy plus trastuzumab-based HER2-targeted therapy can be used as an alternative regimen to T-DM1 when T-DM1 is unavailable.However,further clinical research on the selection of chemotherapeutic agents is warranted.
文摘A 91-year-old man was referred to our hospital with intermittent dysphagia. He had undergone esophagectomy for esophageal cancer(T3N2M0 Stage Ⅲ) 11 years earlier. Endoscopic examination revealed an anastomotic stricture; signs of inflammation,including redness,erosion,edema,bleeding,friability,and exudate with white plaques; and multiple depressions in the residual esophagus. Radiographical examination revealed numerous fine,gastrografinfilled projections and an anastomotic stricture. Biopsy specimens from the area of the anastomotic stricture revealed inflammatory changes without signs of malignancy. Candida glabrata was detected with a culture test of the biopsy specimens. The stricture was diagnosed as a benign stricture that was caused by esophageal intramural pseudodiverticulosis. Accordingly,endoscopic balloon dilatation was performed and antifungal therapy was started in the hospital. Seven weeks later,endoscopic examination revealed improvement in the mucosal inflammation; only the pseudodiverticulosis remained. Consequently,the patient was discharged. At the latest follow-up,the patient was symptomfree and the pseudodiverticulosis remained in the residual esophagus without any signs of stricture or inflammation.
文摘Presence of occult minimal residual disease in patients with colorectal cancer(CRC)has a strong prognostic impact on survival.Minimal residual disease plays a major role in disease relapse and formation of metastases in CRC.Analysis of circulating tumor cells(CTC)in the blood is increasingly used in clinical practice for disease monitoring of CRC patients.In this review article the role of CTC,disseminated tumor cells(DTC)in the bone marrow and micrometastases and isolated tumor cells(ITC)in the lymph nodes will be discussed,including literature published until September 2013.Occult disease is a strong prognostic marker for patient survival in CRC and defined by the presence of CTC in the blood,DTC in the bone marrow and/or micrometastases and ITC in the lymph nodes.Minimal residual disease could be used in the future to identify patient groups at risk,who might benefit from individualized treatment options.
基金supported by Jilin Scientific and Technological Development Program(CN)(No.20190303146SF)。
文摘Curative therapy was not previously available for patients with advanced non-small cell lung cancer(NSCLC);thus,the concept of minimal/measurable(or molecular)residual disease(MRD)was not applicable to these patients.However,advances in targeted and immunotherapy have revolutionized the treatment landscape for patients with advanced NSCLC,with emerging evidence of long-term survival and even the hope of complete remission(CR)by imaging examination.The latest research shows that patients with oligometastatic lung cancer can benefit from local treatment.After removing the lesions,the choice of follow-up therapy and monitoring of the lesions could remain uncertain.MRD plays a role in identifying early-stage NSCLC patients with high risks of recurrence and determining adjuvant therapy after radical treatment.In recent years,evidence has been accumulating regarding the use of circulating cell-free tumor DNA(ctDNA)to assess MRD in solid tumors.This study discussed the possible applications of ctDNA-based MRD monitoring in advanced NSCLC and described the current challenges and unresolved problems in the application of MRD in advanced NSCLC.
基金Supported by the National Natural Science Foundation of China,No.81773293 and No.81873640the Natural Science Foundation of Hunan Province,No.2015JJ4083and No.2018JJ3758+1 种基金the Xiang Cai She Zhi 2017(67)the Science and Technology Plan Fund in Hunan Province,China,No.2015GK3117 and No.2017WK2063
文摘BACKGROUND The rate of positive resection margins(R1) in patients with low rectal cancer is substantial. Recommended remedies such as extended resection or chemoradiotherapy have their own serious drawbacks. It has been reported that photodynamic therapy(PDT) as a remedial treatment for esophageal cancer.Colorectal cancer and esophageal cancer has many similarities,however,PDT as a salvage therapy for rectal cancer is rare.CASE SUMMARY Here,we describe a 56-year-old man who was admitted to the hospital due to a 6-mo history of hemafecia,which had been aggravated for 1 mo. Colonoscopy revealed a 3 × 4 cm ulcerated mass in the rectum 4 cm from the anus.Preoperative pathological examination showed villous adenoma,moderate-tohigh-grade dysplasia,good differentiation,and invasion of the mucosal muscle.The patient had R1 after ultra-low anterior resection,but he refused extended resection and experienced severe liver function impairment after 3 cycles of chemotherapy. Ultimately,the patient underwent PDT to remove R1. After five years of follow-up,there was no liver function impairment,recurrence,metastasis,sexual dysfunction,or abnormal defecation function.CONCLUSION This is the first case worldwide in which R1 of rectal cancer were successfully treated by PDT.
文摘Multicollinearity constitutes shared variation among predictors that inflates standard errors of regression coefficients. Several years ago, it was proven that the common practice of mean centering in moderated regression cannot alleviate multicollinearity among variables comprising an interaction, but merely masks it. Residual centering (orthogonalizing) is unacceptable because it biases parameters for predictors from which the interaction derives, thus precluding interpretation of moderator effects. I propose and validate residual centering in sequential re-estimations of a moderated regression—sequential residual centering (SRC)—by revealing unbiased multicollinearity conditioning across the interaction and its related terms. Across simulations, SRC reduces variance inflation factors (VIF) regardless of distribution shape or pattern of regression coefficients across predictors. For any predictor, the reduced VIF is used to derive a lower standard error of its regression coefficient. A cancer sample illustrates SRC, which allows unbiased interpretations of symptom clusters. SRC can be applied efficiently to alleviate multicollinearity after data collection and shows promise for advancing synergistic frontiers of research.
文摘BACKGROUND The diagnosis of residual tumors using endoscopic ultrasound(EUS)after neoadjuvant therapy for esophageal cancer is considered challenging.However,the reasons for this difficulty are not well understood.AIM To investigate the ultrasound imaging features of residual tumors and identify the limitations and potential of EUS.METHODS This exploratory prospective observational study enrolled 23 esophageal squamous cell carcinoma patients receiving esophagectomy after neoadjuvant therapy[15 patients after neoadjuvant chemotherapy(NAC)and 8 patients after chemoradiotherapy(CRT)]at the Department of Surgery,Chiba University Hospital,between May 2020 and October 2021.We diagnosed the T stage for specimens using ultrasound just after surgery and compared ultrasound images with the cut surface of the fixed specimens of the same level of residual tumor.The ratio of esophageal muscle layer defect measured by ultrasound was compared with clinicopathological factors.Furthermore,the rate of reduction for the muscle layer defect was evaluated using EUS images obtained before and after neoadjuvant therapy.RESULTS The accuracy of T stage rate was 61%(n=14/23),which worsened after CRT(38%,n=3/8)than after NAC(73%,n=11/15)because of overstaging.Moreover,pT0 could not be diagnosed in all cases.The detection rate of residual tumor for specimens using ultrasound retrospectively was 75%(n=15/20).There was no correlation between after-NAC(79%,n=11/14)and after-CRT(67%,n=4/6)detection rate.The detection of superficial and submucosal types was poor.The pathologic tumor size and pathological response were correlated.Tumor borders were irregular and echogenicity was mixed type after CRT.There was a correlation between the pT stage(pT0/1 vs pT2/3)and the length of muscle layer circumference(P=0.025),the length of muscle layer defect(P<0.001),and the ratio of muscle layer defect(P<0.001).There was also a correlation between the pT stage and the rate of muscle layer defect reduction measured by EUS(P=0.001).CONCLUSION Compared to pathological images,some tumors are undetectable by ultrasound.Focusing on the esophageal muscle layer might help diagnose the depth of the residual tumor.