Background Numerous studies have attempted to understand the molecular mechanisms of tumorigenesis and identify clinical biomarkers and molecular targets for esophageal squamous cell carcinoma (ESCC). However, there are still only a few biomarkers and targets. We focused on tumor suppressor micro-RNA (miR)s in the plasma of ESCC patients, and we investigated the usefulness of these tumor suppressor miRs as biomarkers and therapeutic agents for ESCC. Methods: Plasma samples of 94 ESCC patients and 86 healthy volunteers were analyzed in this study. Among the group of 2600 miRs candidates registered in miRbase, we selected 25 miRs candidates which are low expressed in ESCC tissues, have tumor suppressive functions, and unreported as a body fluid biomarker. We selected 5 miRs (miR-564/ 637/ 1182/ 3178/ 3619), whose signals were detectable in the blood of healthy volunteers by microarray analysis. By test-scale analysis using TaqMan assay and validation analysis, we identified miR-3619, which showed the most significant difference in ESCC patients compared to healthy volunteers (p < 0.001). Results: 1) Prognostic analysis revealed that a low miR-3619 plasma level was significantly associated with advanced stage and recurrence rate, and was an independent factor predicting poor prognosis in ESCC patients (p = 0.028, HR = 2.09). 2) Overexpression of miR-3619 mimic inhibited the proliferation of ESCC cells, induced the accumulation of apoptosis or G1/S phase cells, and reduced the cell migration and invasion abilities compared with negative control mimic. 3) We tested PIM-1xas candidate putative target genes for miR-3619 using microRNA database. PIM-1 protein expression levels were decreased in miR-3619-5p transfectants compared with NC. 4) In vivo, subcutaneous injection of miR-3619 could significantly inhibit tumor growth in mice. Administration of miR-3619 did not cause any clinical adverse events or side effects in blood-based parameters reflecting organ disorders. Conclusion: These results suggest that depleted tumor-suppressor miR-3619 in plasma could be one of blood-based biomarkers for predicting malignant potential of ESCC.
{"title":"260. LOW BLOOD LEVEL OF TUMOR SUPPRESSOR MIR-3619 AS A TARGET OF NUCLEIC ACID THERAPY TO PIM-1 IN ESOPHAGEAL CANCER","authors":"Hiroshi Arakawa, Shuhei Komatsu, Hajime Kamiya, Rei Ishida, Keiji Nishibeppu, Jun Kiuchi, Taisuke Imamura, Takuma Ohashi, Hirotaka Konishi, Atsushi Shiozaki, Hitoshi Fujiwara, Eigo Otsuji","doi":"10.1093/dote/doae057.039","DOIUrl":"https://doi.org/10.1093/dote/doae057.039","url":null,"abstract":"Background Numerous studies have attempted to understand the molecular mechanisms of tumorigenesis and identify clinical biomarkers and molecular targets for esophageal squamous cell carcinoma (ESCC). However, there are still only a few biomarkers and targets. We focused on tumor suppressor micro-RNA (miR)s in the plasma of ESCC patients, and we investigated the usefulness of these tumor suppressor miRs as biomarkers and therapeutic agents for ESCC. Methods: Plasma samples of 94 ESCC patients and 86 healthy volunteers were analyzed in this study. Among the group of 2600 miRs candidates registered in miRbase, we selected 25 miRs candidates which are low expressed in ESCC tissues, have tumor suppressive functions, and unreported as a body fluid biomarker. We selected 5 miRs (miR-564/ 637/ 1182/ 3178/ 3619), whose signals were detectable in the blood of healthy volunteers by microarray analysis. By test-scale analysis using TaqMan assay and validation analysis, we identified miR-3619, which showed the most significant difference in ESCC patients compared to healthy volunteers (p &lt; 0.001). Results: 1) Prognostic analysis revealed that a low miR-3619 plasma level was significantly associated with advanced stage and recurrence rate, and was an independent factor predicting poor prognosis in ESCC patients (p = 0.028, HR = 2.09). 2) Overexpression of miR-3619 mimic inhibited the proliferation of ESCC cells, induced the accumulation of apoptosis or G1/S phase cells, and reduced the cell migration and invasion abilities compared with negative control mimic. 3) We tested PIM-1xas candidate putative target genes for miR-3619 using microRNA database. PIM-1 protein expression levels were decreased in miR-3619-5p transfectants compared with NC. 4) In vivo, subcutaneous injection of miR-3619 could significantly inhibit tumor growth in mice. Administration of miR-3619 did not cause any clinical adverse events or side effects in blood-based parameters reflecting organ disorders. Conclusion: These results suggest that depleted tumor-suppressor miR-3619 in plasma could be one of blood-based biomarkers for predicting malignant potential of ESCC.","PeriodicalId":11354,"journal":{"name":"Diseases of the Esophagus","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142205045","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-02DOI: 10.1093/dote/doae057.013
Tomoki Makino, Kota Momose, Kotaro Yamashita, Koji Tanaka, Hidetoshi Eguchi, Yuchiro Doki
(Background) Robot-assisted esophagectomy (RAMIE) has lately been introduced to many hospitals after its insurance approval. However, long-term outcome of RAMIE or its utility in treating cT3br-T4 esophageal cancer remains unclear. (Methods) A total of 188 esophageal cancer patients who underwent RAMIE between 2017 and 2022 were eligible in the present study. Among them, 20 cases with cT3br-T4 were reviewed to evaluate short-term outcome. Also, a comparison between RAMIE (n=66) and VATS (n=277) group with 2-year and longer follow-up time was made to evaluate their long-term outcomes. (Results) Background factors; age=71 (42-86), gender (M/F)= 145/43, tumor location (Ut/Mt/Lt, Ae)= 25/84/79, cT1/2/3/4= 36/31/101/20, cN0/1/2/3= 65/82/34/7, cM0/1= 155/33, and preoperative treatment (none/chemo/CRT/both)= 39/139/10. Surgical outcomes; operation time = 508 (273-833) min, console time=244 (108-479) min, estimated blood loss= 130 (0-2090) ml, overall postoperative morbidity (CD classification≧grade2) = 53.2% (pneumonia= 29.3%, atelectasis=9.0%, palsy of recurrent laryngeal nerve=10.1%, surgical site infection=5.9%, chylothorax=5.9%, and anastomotic leakage=5.9%). Postoperative hospital stay was 21 (12-385) days. The palsy rate of recurrent laryngeal nerve decreased from 9.1 to 0.7% after introducing intraoperative continuous nerve monitoring (NIM). In terms of RAMIE for cT3br-T4 cases (n=20), no convert to open or intraoperative complications were observed while all cases achieved R0 resection. Regarding survival comparison between the RAMIE (n=66) and the VATS (n=277) group, disease-free and overall survival were 74.8 vs 70.9% (P=0.4582), 76.4 vs 78.5% (p=0.7626), respectively. (Conclusion) NIM system reduced the palsy of recurrent laryngeal nerve during RAMIE while the comparable survival was identified between the two groups. Given its advantage, RAMIE seems to be particularly useful in treating cT3br-T4 cases. Our surgical videos of cT3br-T4 cases will be also presented in the meeting.
(背景）机器人辅助食管切除术（RAMIE）获得保险批准后，最近已被引入许多医院。然而，RAMIE的长期疗效或其在治疗cT3br-T4食管癌中的作用仍不明确。(方法）本研究共选取了188例在2017年至2022年间接受RAMIE治疗的食管癌患者。其中，对20例cT3br-T4病例进行了回顾性研究，以评估短期疗效。同时，对随访2年及更长时间的RAMIE组（n=66）和VATS组（n=277）进行比较，以评估其长期疗效。(结果）背景因素：年龄=71（42-86），性别（男/女）=145/43，肿瘤位置（Ut/Mt/Lt，Ae）=25/84/79，cT1/2/3/4=36/31/101/20，cN0/1/2/3=65/82/34/7，cM0/1=155/33，术前治疗（无/化疗/CRT/两者）=39/139/10。手术结果；手术时间=508（273-833）分钟，控制台时间=244（108-479）分钟，估计失血量=130（0-2090）毫升，术后总发病率（CD分类≧2级）=53.2%（肺炎=29.3%，肺不张=9.0%，喉返神经麻痹=10.1%，手术部位感染=5.9%，乳糜胸=5.9%，吻合口漏=5.9%）。术后住院时间为 21（12-385）天。引入术中连续神经监测（NIM）后，喉返神经麻痹率从9.1%降至0.7%。就cT3br-T4病例（20例）的RAMIE而言，没有观察到转为开放手术或术中并发症，所有病例都实现了R0切除。RAMIE 组（66 例）与 VATS 组（277 例）的生存率比较显示，无病生存率和总生存率分别为 74.8% vs 70.9% (P=0.4582)、76.4% vs 78.5% (P=0.7626)。(结论）NIM 系统减少了 RAMIE 期间喉返神经的麻痹，而两组患者的生存率相当。鉴于其优势，RAMIE似乎特别适用于治疗cT3br-T4病例。我们还将在会上展示 cT3br-T4 病例的手术视频。
{"title":"222. LONG-TERM SURVIVAL OF ROBOT-ASSISTED ESOPHAGECTOMY AND ITS UTILITY IN TREATING CT4B ESOPHAGEAL CANCER","authors":"Tomoki Makino, Kota Momose, Kotaro Yamashita, Koji Tanaka, Hidetoshi Eguchi, Yuchiro Doki","doi":"10.1093/dote/doae057.013","DOIUrl":"https://doi.org/10.1093/dote/doae057.013","url":null,"abstract":"(Background) Robot-assisted esophagectomy (RAMIE) has lately been introduced to many hospitals after its insurance approval. However, long-term outcome of RAMIE or its utility in treating cT3br-T4 esophageal cancer remains unclear. (Methods) A total of 188 esophageal cancer patients who underwent RAMIE between 2017 and 2022 were eligible in the present study. Among them, 20 cases with cT3br-T4 were reviewed to evaluate short-term outcome. Also, a comparison between RAMIE (n=66) and VATS (n=277) group with 2-year and longer follow-up time was made to evaluate their long-term outcomes. (Results) Background factors; age=71 (42-86), gender (M/F)= 145/43, tumor location (Ut/Mt/Lt, Ae)= 25/84/79, cT1/2/3/4= 36/31/101/20, cN0/1/2/3= 65/82/34/7, cM0/1= 155/33, and preoperative treatment (none/chemo/CRT/both)= 39/139/10. Surgical outcomes; operation time = 508 (273-833) min, console time=244 (108-479) min, estimated blood loss= 130 (0-2090) ml, overall postoperative morbidity (CD classification≧grade2) = 53.2% (pneumonia= 29.3%, atelectasis=9.0%, palsy of recurrent laryngeal nerve=10.1%, surgical site infection=5.9%, chylothorax=5.9%, and anastomotic leakage=5.9%). Postoperative hospital stay was 21 (12-385) days. The palsy rate of recurrent laryngeal nerve decreased from 9.1 to 0.7% after introducing intraoperative continuous nerve monitoring (NIM). In terms of RAMIE for cT3br-T4 cases (n=20), no convert to open or intraoperative complications were observed while all cases achieved R0 resection. Regarding survival comparison between the RAMIE (n=66) and the VATS (n=277) group, disease-free and overall survival were 74.8 vs 70.9% (P=0.4582), 76.4 vs 78.5% (p=0.7626), respectively. (Conclusion) NIM system reduced the palsy of recurrent laryngeal nerve during RAMIE while the comparable survival was identified between the two groups. Given its advantage, RAMIE seems to be particularly useful in treating cT3br-T4 cases. Our surgical videos of cT3br-T4 cases will be also presented in the meeting.","PeriodicalId":11354,"journal":{"name":"Diseases of the Esophagus","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142205046","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-02DOI: 10.1093/dote/doae057.354
Naoki Hashimoto
Aim. Reflux of duodenal contents can induce mucosal injury, stimulate cell proliferation, and promote tumorigenesis. We examined the expression of COX2 and p53 in rat esophageal lesions induced by duodenal content reflux. Methods. Thirty 8-week-old male Wistar rats were exposed to duodenal content esophageal reflux. All animals underwent an esophagoduodenal anastomosis (EDA) with total gastrectomy in order to produce chronic esophagitis. Ten rats were the sham. Control. They were sacrificed at the 40th week. Their esophagi were examined for HE, COX2, p53, and proliferating cell nuclear antigen (PCNA). Results. After 40 weeks of reflux, dysplasia, squamous cell carcinoma (SCC), and adenocarcinoma (ADC) were found. PCNA labeling index was higher in dysplastic and cancer tissue than that in normal. Overexpression of COX2 was shown in ADC and SCC. Wild-type p53 accumulation was found in ADC, and not in SCC. Conclusion. Reflux of duodenal contents into the esophagus led to ADC and SCC in rats. COX2 may play an important role in esophageal cancer by duodenal content reflux. Our present results suggest an association between wild-type p53 accumulation and COX2 expression in ADC, with no such relation seen in SCC.
{"title":"741. EXPRESSION OF COX2 AND P53 IN RAT ESOPHAGEAL CANCER INDUCED BY REFLUX OF DUODENAL CONTENTS","authors":"Naoki Hashimoto","doi":"10.1093/dote/doae057.354","DOIUrl":"https://doi.org/10.1093/dote/doae057.354","url":null,"abstract":"Aim. Reflux of duodenal contents can induce mucosal injury, stimulate cell proliferation, and promote tumorigenesis. We examined the expression of COX2 and p53 in rat esophageal lesions induced by duodenal content reflux. Methods. Thirty 8-week-old male Wistar rats were exposed to duodenal content esophageal reflux. All animals underwent an esophagoduodenal anastomosis (EDA) with total gastrectomy in order to produce chronic esophagitis. Ten rats were the sham. Control. They were sacrificed at the 40th week. Their esophagi were examined for HE, COX2, p53, and proliferating cell nuclear antigen (PCNA). Results. After 40 weeks of reflux, dysplasia, squamous cell carcinoma (SCC), and adenocarcinoma (ADC) were found. PCNA labeling index was higher in dysplastic and cancer tissue than that in normal. Overexpression of COX2 was shown in ADC and SCC. Wild-type p53 accumulation was found in ADC, and not in SCC. Conclusion. Reflux of duodenal contents into the esophagus led to ADC and SCC in rats. COX2 may play an important role in esophageal cancer by duodenal content reflux. Our present results suggest an association between wild-type p53 accumulation and COX2 expression in ADC, with no such relation seen in SCC.","PeriodicalId":11354,"journal":{"name":"Diseases of the Esophagus","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142205207","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-02DOI: 10.1093/dote/doae057.306
Michael Weitzendorfer, Eva Johanna Wallner, Charlotte Rabl, Klaus Emmanuel, Oliver Owen Koch
Background The aim of this study was to evaluate the value of salivary pepsin to assess the outcome of surgical treatment of patients with gastroesophageal reflux (GERD). Methods Forty-five consecutive patients with GERD despite proton pump inhibitor treatment received laparoscopic anti-reflux surgery (LARS). 24-hour esophageal pH-monitoring (MII-pH) and esophageal manometry (HRM) data were documented preoperatively and at 3-month follow-up. Clinical symptoms were rated with the Gastrointestinal Quality of Life Index (GIQLI) and gastrointestinal symptoms were evaluated by a standardized symptom checklist (SCL), assessing the severity and intensitiy of 14 different symptoms. Simultaneous to MII-pH the collection of 3 saliva samples per patient was performed. Treatment failure was defined as improvement of GIQLI and SCL of < 10 points, despite showing a normal DeMeester score. Results At baseline, all patients showed a pathological MII-pH measurement. Furthermore, all patients showed postoperatively a normal DeMeester score (mean 7.10 ± 4.56). Ten patients were defined as treatment failures with a change of pepsin concentration from a mean value of 198.73 ng/mL to 186.00 ng/mL (p>0.05). In patients defined as treatment success, mean pepsin value decreased from 205.83 ng/mL to 85.24 ng/mL (p<0.001). Conclusion Salivary pepsin could be a marker for treatment success after LARS. However, larger studies are required to reach firm conclusions.
{"title":"586. VALUE OF PEPSIN IN SALIVA TO ASSESS THE POSTOPERATIVE OUTCOME OF PATIENTS WITH GERD","authors":"Michael Weitzendorfer, Eva Johanna Wallner, Charlotte Rabl, Klaus Emmanuel, Oliver Owen Koch","doi":"10.1093/dote/doae057.306","DOIUrl":"https://doi.org/10.1093/dote/doae057.306","url":null,"abstract":"Background The aim of this study was to evaluate the value of salivary pepsin to assess the outcome of surgical treatment of patients with gastroesophageal reflux (GERD). Methods Forty-five consecutive patients with GERD despite proton pump inhibitor treatment received laparoscopic anti-reflux surgery (LARS). 24-hour esophageal pH-monitoring (MII-pH) and esophageal manometry (HRM) data were documented preoperatively and at 3-month follow-up. Clinical symptoms were rated with the Gastrointestinal Quality of Life Index (GIQLI) and gastrointestinal symptoms were evaluated by a standardized symptom checklist (SCL), assessing the severity and intensitiy of 14 different symptoms. Simultaneous to MII-pH the collection of 3 saliva samples per patient was performed. Treatment failure was defined as improvement of GIQLI and SCL of &lt; 10 points, despite showing a normal DeMeester score. Results At baseline, all patients showed a pathological MII-pH measurement. Furthermore, all patients showed postoperatively a normal DeMeester score (mean 7.10 ± 4.56). Ten patients were defined as treatment failures with a change of pepsin concentration from a mean value of 198.73 ng/mL to 186.00 ng/mL (p&gt;0.05). In patients defined as treatment success, mean pepsin value decreased from 205.83 ng/mL to 85.24 ng/mL (p&lt;0.001). Conclusion Salivary pepsin could be a marker for treatment success after LARS. However, larger studies are required to reach firm conclusions.","PeriodicalId":11354,"journal":{"name":"Diseases of the Esophagus","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142205208","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-02DOI: 10.1093/dote/doae057.374
Maria do Carmo Girão, Francisca Brito Silva, Francisco Cabral, Paulo Ramos, Cecília Monteiro, Rui Casaca
Background The American Joint Committee for Cancer (AJCC) and the Japanese Esophagus Society (JES) differ in the N classification for esophageal cancer, with the former considering the presence of disease in the supraclavicular lymph nodes as M1, and the latter classifying it as loco-regional disease in thoracic esophageal tumors. Patients who would be excluded from a curative intent treatment strategy by the AJCC classification may be candidates for surgery with lymphadenectomy of nodal groups 101 and 104 (JES). Our goal is to understand the impact of three-field lymphadenectomy on morbidity, loco-regional control and overall survival in patients with esophageal cancer. Methods A retrospective cohort study was conducted using data from a prospective database from a single center, which included all consecutive patients undergoing esophagectomy for cancer with either two-field total thoracic lymphadenectomy or three-field lymphadenectomy, between January 2019 and December 2023. Three-field lymphadenectomy was performed for clinical supraclavicular and recurrent nerve nodal involvement and for proximal third tumors. We assessed the morbidity and mortality of both types of surgery, and loco-regional and distant recurrence and overall survival for both groups. Results Of the 279 esophagectomies for cancer, 137 were included for analysis. The median age was 65 years, with 84% males. 58,4% had squamous cell carcinoma and 41,6% adenocarcinoma. 34.3% of the patients had a 3-field lymphadenectomy, 27,7% of these for supraclavicular N+ and 34% for recurrent nerve N+. Conclusion In this large single-center cohort, patients with significant lymph node involvement, treated with esophagectomy and three-field lymphadenectomy, demonstrated comparable loco-regional control and overall survival to more favorable cases, with no statistically significant increase in morbidity and mortality.
{"title":"776. THREE-FIELD LYMPHADENECTOMY IN ESOPHAGEAL CANCER: EXPERIENCE OF A PORTUGUESE TERTIARY CENTER","authors":"Maria do Carmo Girão, Francisca Brito Silva, Francisco Cabral, Paulo Ramos, Cecília Monteiro, Rui Casaca","doi":"10.1093/dote/doae057.374","DOIUrl":"https://doi.org/10.1093/dote/doae057.374","url":null,"abstract":"Background The American Joint Committee for Cancer (AJCC) and the Japanese Esophagus Society (JES) differ in the N classification for esophageal cancer, with the former considering the presence of disease in the supraclavicular lymph nodes as M1, and the latter classifying it as loco-regional disease in thoracic esophageal tumors. Patients who would be excluded from a curative intent treatment strategy by the AJCC classification may be candidates for surgery with lymphadenectomy of nodal groups 101 and 104 (JES). Our goal is to understand the impact of three-field lymphadenectomy on morbidity, loco-regional control and overall survival in patients with esophageal cancer. Methods A retrospective cohort study was conducted using data from a prospective database from a single center, which included all consecutive patients undergoing esophagectomy for cancer with either two-field total thoracic lymphadenectomy or three-field lymphadenectomy, between January 2019 and December 2023. Three-field lymphadenectomy was performed for clinical supraclavicular and recurrent nerve nodal involvement and for proximal third tumors. We assessed the morbidity and mortality of both types of surgery, and loco-regional and distant recurrence and overall survival for both groups. Results Of the 279 esophagectomies for cancer, 137 were included for analysis. The median age was 65 years, with 84% males. 58,4% had squamous cell carcinoma and 41,6% adenocarcinoma. 34.3% of the patients had a 3-field lymphadenectomy, 27,7% of these for supraclavicular N+ and 34% for recurrent nerve N+. Conclusion In this large single-center cohort, patients with significant lymph node involvement, treated with esophagectomy and three-field lymphadenectomy, demonstrated comparable loco-regional control and overall survival to more favorable cases, with no statistically significant increase in morbidity and mortality.","PeriodicalId":11354,"journal":{"name":"Diseases of the Esophagus","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142205234","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-02DOI: 10.1093/dote/doae057.304
Ya Zeng, Xi Su, Tongfang Zhou, Yunfeng Wang, Jingyi Jia, Jie Gao, Yuezhen Deng, Xiaolong Fu, Xuwei Cai
Purpose Distant metastasis is the primary cause of mortality among patients with esophageal cancer. Although FRG1 is known to play a role in the metastasis of various cancers, its specific function in esophageal squamous cell carcinoma (ESCC) has yet to be elucidated. In this study, we aimed to explore the role and potential molecular mechanism of FRG1 in the metastasis of ESCC. Methods Whole-exome sequencing was performed in ESCC patients who experienced distant metastasis (DM group) and those without metastasis within two years (non-DM group). Bioinformatics analysis and Immunohistochemistry (IHC) validation were conducted. In vitro, FRG1-overexpressed ESCC cell lines were established with lentivirus and validated by western blots. The wound-healing assay, transwell migration and invasion assay were performed in esophageal cancer cell lines. Additionally, RNA sequencing was conducted in ESCC cells to identify potential pathways involved. Results Mutations in FRG1 were more frequently observed in DM group compared to those in non-DM group. IHC revealed that the expression of FRG1 in DM group was significantly lower than non-DM group. In vitro, our results showed that ESCC cells with low FRG1 expression exhibited enhanced migration and invasion capabilities. Conversely, overexpression of FRG1 inhibited migration and invasion in ESCC cells. Mechanistically, RNA sequencing analysis showed a total of 93 differential expression genes between FRG1-overexpressed cells and the negative control. Notably, most differential genes were mainly enriched in the PPAR pathway and tyrosine metabolism pathway. Conclusion Our findings suggest that low FRG1 expression in patients may be indicative of rapid distant metastasis. The significant impact of FRG1's abnormal expression on the migration and invasion of ESCC cells highlights its potential as a therapeutic target for treating esophageal squamous cell carcinoma.
{"title":"582. LOW EXPRESSION OF FRG1 PROMOTES MIGRATION AND INVASION IN ESOPHAGEAL CANCER","authors":"Ya Zeng, Xi Su, Tongfang Zhou, Yunfeng Wang, Jingyi Jia, Jie Gao, Yuezhen Deng, Xiaolong Fu, Xuwei Cai","doi":"10.1093/dote/doae057.304","DOIUrl":"https://doi.org/10.1093/dote/doae057.304","url":null,"abstract":"Purpose Distant metastasis is the primary cause of mortality among patients with esophageal cancer. Although FRG1 is known to play a role in the metastasis of various cancers, its specific function in esophageal squamous cell carcinoma (ESCC) has yet to be elucidated. In this study, we aimed to explore the role and potential molecular mechanism of FRG1 in the metastasis of ESCC. Methods Whole-exome sequencing was performed in ESCC patients who experienced distant metastasis (DM group) and those without metastasis within two years (non-DM group). Bioinformatics analysis and Immunohistochemistry (IHC) validation were conducted. In vitro, FRG1-overexpressed ESCC cell lines were established with lentivirus and validated by western blots. The wound-healing assay, transwell migration and invasion assay were performed in esophageal cancer cell lines. Additionally, RNA sequencing was conducted in ESCC cells to identify potential pathways involved. Results Mutations in FRG1 were more frequently observed in DM group compared to those in non-DM group. IHC revealed that the expression of FRG1 in DM group was significantly lower than non-DM group. In vitro, our results showed that ESCC cells with low FRG1 expression exhibited enhanced migration and invasion capabilities. Conversely, overexpression of FRG1 inhibited migration and invasion in ESCC cells. Mechanistically, RNA sequencing analysis showed a total of 93 differential expression genes between FRG1-overexpressed cells and the negative control. Notably, most differential genes were mainly enriched in the PPAR pathway and tyrosine metabolism pathway. Conclusion Our findings suggest that low FRG1 expression in patients may be indicative of rapid distant metastasis. The significant impact of FRG1's abnormal expression on the migration and invasion of ESCC cells highlights its potential as a therapeutic target for treating esophageal squamous cell carcinoma.","PeriodicalId":11354,"journal":{"name":"Diseases of the Esophagus","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142205047","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-02DOI: 10.1093/dote/doae057.300
Antonella Cianferoni, Evan S Dellon, Christoph Schlag, Changming Xia, Sandy Durrani, Tiffany Pela, Amr Radwan, Juby A Jacob-Nara
Background Improvements in histologic, symptomatic, and endoscopic aspects of eosinophilic oesophagitis (EoE) were observed in patients treated with dupilumab weekly (qw) enrolled in the 3-part, phase 3 LIBERTY EoE TREET study (NCT03633617), regardless of prior inadequate response, intolerance, and/or contraindication to swallowed topical corticosteroids (STC). Here we assess the efficacy of dupilumab qw versus placebo in this STC non-responsive/intolerant subgroup, stratifying further by those with/without history of food elimination diets, proton pump inhibitor (PPI) use at randomisation, or history of oesophageal dilation. Methods This analysis includes patients who received dupilumab 300 mg qw or placebo for 24 weeks in Part B and an additional 28 weeks dupilumab in Part C. Co-primary endpoints (Weeks 24 and 52) include: proportions of patients achieving peak eosinophil count (PEC) ≤6 eosinophils/high-power field (eos/hpf) and absolute change in Dysphagia Symptom Questionnaire (DSQ) score. Secondary endpoints assessed included proportions of patients achieving PEC ≤1 eos/hpf, <15 eos/hpf, % change in PEC, and absolute change in Endoscopic Reference Score, and EoE-Histologic Scoring System grade/stage scores. Results Dupilumab 300 mg qw improved proportions of patients achieving co-primary endpoints, ≤6 eos/hpf and absolute change in DSQ score, and secondary endpoints, ≤1 eos/hpf and <15 eos/hpf at Week 24 versus placebo, regardless of history of food elimination diets, PPI use at randomisation, or history of dilation (Table). Improvements were maintained or continued to improve at Week 52. A similar trend was observed for other secondary endpoints assessed. Placebo-treated patients who switched to dupilumab in Part C demonstrated similar efficacy to patients treated with dupilumab in Part B. Dupilumab safety was consistent with the known dupilumab safety profile. Conclusion Dupilumab qw demonstrated sustained improvements in histologic and symptomatic aspects of EoE up to 52 weeks in adults and adolescents with an inadequate response, intolerance, and/or contraindication to STC, regardless of history of food elimination diets, PPI use, or history of oesophageal dilation. Improvements in endoscopic aspects of EoE up to 52 weeks were also observed.
{"title":"578. DUPILUMAB EFFICACY IN EOSINOPHILIC OESOPHAGITIS PATIENTS TREATED WITH PRIOR THERAPY AND INADEQUATE RESPONSE, INTOLERANCE, OR CONTRAINDICATION TO SWALLOWED TOPICAL CORTICOSTEROIDS","authors":"Antonella Cianferoni, Evan S Dellon, Christoph Schlag, Changming Xia, Sandy Durrani, Tiffany Pela, Amr Radwan, Juby A Jacob-Nara","doi":"10.1093/dote/doae057.300","DOIUrl":"https://doi.org/10.1093/dote/doae057.300","url":null,"abstract":"Background Improvements in histologic, symptomatic, and endoscopic aspects of eosinophilic oesophagitis (EoE) were observed in patients treated with dupilumab weekly (qw) enrolled in the 3-part, phase 3 LIBERTY EoE TREET study (NCT03633617), regardless of prior inadequate response, intolerance, and/or contraindication to swallowed topical corticosteroids (STC). Here we assess the efficacy of dupilumab qw versus placebo in this STC non-responsive/intolerant subgroup, stratifying further by those with/without history of food elimination diets, proton pump inhibitor (PPI) use at randomisation, or history of oesophageal dilation. Methods This analysis includes patients who received dupilumab 300 mg qw or placebo for 24 weeks in Part B and an additional 28 weeks dupilumab in Part C. Co-primary endpoints (Weeks 24 and 52) include: proportions of patients achieving peak eosinophil count (PEC) ≤6 eosinophils/high-power field (eos/hpf) and absolute change in Dysphagia Symptom Questionnaire (DSQ) score. Secondary endpoints assessed included proportions of patients achieving PEC ≤1 eos/hpf, &lt;15 eos/hpf, % change in PEC, and absolute change in Endoscopic Reference Score, and EoE-Histologic Scoring System grade/stage scores. Results Dupilumab 300 mg qw improved proportions of patients achieving co-primary endpoints, ≤6 eos/hpf and absolute change in DSQ score, and secondary endpoints, ≤1 eos/hpf and &lt;15 eos/hpf at Week 24 versus placebo, regardless of history of food elimination diets, PPI use at randomisation, or history of dilation (Table). Improvements were maintained or continued to improve at Week 52. A similar trend was observed for other secondary endpoints assessed. Placebo-treated patients who switched to dupilumab in Part C demonstrated similar efficacy to patients treated with dupilumab in Part B. Dupilumab safety was consistent with the known dupilumab safety profile. Conclusion Dupilumab qw demonstrated sustained improvements in histologic and symptomatic aspects of EoE up to 52 weeks in adults and adolescents with an inadequate response, intolerance, and/or contraindication to STC, regardless of history of food elimination diets, PPI use, or history of oesophageal dilation. Improvements in endoscopic aspects of EoE up to 52 weeks were also observed.","PeriodicalId":11354,"journal":{"name":"Diseases of the Esophagus","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142205050","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Andrés R Latorre-Rodríguez, Madison Golla, Ashwini Arjuna, Ross M Bremner, Sumeet K Mittal
Summary The implications of impaired esophagogastric junction relaxation (i.e. esophagogastric junction outflow obstruction and achalasia) in lung transplants recipients (LTRs) are unclear. Thus, we examined the prevalence and clinical outcomes of LTRs with an abnormally elevated integrated relaxation pressure (IRP) on high-resolution manometry before lung transplantation (LTx). After IRB approval, we reviewed data on LTRs who underwent LTx between January 2019 and August 2022 with a preoperative median IRP >15 mmHg. Differences in overall survival and chronic lung allograft dysfunction (CLAD)–free survival between LTRs with a normalized median IRP after LTx (N-IRP) and those with persistently high IRP (PH-IRP) were assessed using Kaplan–Meier curves and the log-rank test. During the study period, 352 LTx procedures were performed; 44 (12.5%) LTRs had an elevated IRP before LTx, and 37 (84.1%) completed a postoperative manometry assessment (24 [70.6%] males; mean age, 65.2 ± 9.1 years). The median IRP before and after LTx was 18.7 ± 3.8 mmHg and 12 ± 5.6 mmHg, respectively (P < 0.001); the median IRP normalized after LTx in 24 (64.9%) patients. Two-year overall survival trended lower in the N-IRP group than the PH-IRP group (77.2% vs. 92.3%, P = 0.086), but CLAD-free survival (P = 0.592) and rates of primary graft dysfunction (P = 0.502) and acute cellular rejection (P = 0.408) were similar. An abnormally elevated IRP was common in LTx candidates; however, it normalized in roughly two-thirds of patients after LTx. Two-year survival trended higher in the PH-IRP group, despite similar rates of primary graft dysfunction and acute cellular rejection as well as similar CLAD-free survival between the groups.
{"title":"Impaired esophagogastric junction relaxation and lung transplantation outcomes","authors":"Andrés R Latorre-Rodríguez, Madison Golla, Ashwini Arjuna, Ross M Bremner, Sumeet K Mittal","doi":"10.1093/dote/doae030","DOIUrl":"https://doi.org/10.1093/dote/doae030","url":null,"abstract":"Summary The implications of impaired esophagogastric junction relaxation (i.e. esophagogastric junction outflow obstruction and achalasia) in lung transplants recipients (LTRs) are unclear. Thus, we examined the prevalence and clinical outcomes of LTRs with an abnormally elevated integrated relaxation pressure (IRP) on high-resolution manometry before lung transplantation (LTx). After IRB approval, we reviewed data on LTRs who underwent LTx between January 2019 and August 2022 with a preoperative median IRP &gt;15 mmHg. Differences in overall survival and chronic lung allograft dysfunction (CLAD)–free survival between LTRs with a normalized median IRP after LTx (N-IRP) and those with persistently high IRP (PH-IRP) were assessed using Kaplan–Meier curves and the log-rank test. During the study period, 352 LTx procedures were performed; 44 (12.5%) LTRs had an elevated IRP before LTx, and 37 (84.1%) completed a postoperative manometry assessment (24 [70.6%] males; mean age, 65.2 ± 9.1 years). The median IRP before and after LTx was 18.7 ± 3.8 mmHg and 12 ± 5.6 mmHg, respectively (P &lt; 0.001); the median IRP normalized after LTx in 24 (64.9%) patients. Two-year overall survival trended lower in the N-IRP group than the PH-IRP group (77.2% vs. 92.3%, P = 0.086), but CLAD-free survival (P = 0.592) and rates of primary graft dysfunction (P = 0.502) and acute cellular rejection (P = 0.408) were similar. An abnormally elevated IRP was common in LTx candidates; however, it normalized in roughly two-thirds of patients after LTx. Two-year survival trended higher in the PH-IRP group, despite similar rates of primary graft dysfunction and acute cellular rejection as well as similar CLAD-free survival between the groups.","PeriodicalId":11354,"journal":{"name":"Diseases of the Esophagus","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140834973","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
John Plate, Mogens Bove, Helen M Larsson, Elisabeth Norder Grusell, Nabanita Chatterjee, Leif E Johansson, Henrik Bergquist
Summary Eosinophilic esophagitis (EoE) and gastroesophageal reflux disease (GERD) share many histopathological features; therefore, markers for differentiation are of diagnostic interest and may add to the understanding of the underlying mechanisms. The nitrergic system is upregulated in GERD and probably also in EoE. Esophageal biopsies of patients with EoE (n = 20), GERD (n = 20), and healthy volunteers (HVs) (n = 15) were exposed to antibodies against inducible nitric oxide synthase (iNOS), nitrotyrosine, eosinophilic peroxidase, eotaxin-3, and galectin-3. The stained object glasses were randomized, digitized, and blindly analyzed regarding the expression of DAB (3,3′-diaminobenzidine) by a protocol developed in QuPath software. A statistically significant overexpression of iNOS was observed in patients with any of the two inflammatory diseases compared with that in HVs. Eotaxin-3 could differentiate HVs versus inflammatory states. Gastroesophageal reflux patients displayed the highest levels of nitrotyrosine. Neither iNOS nor nitrotyrosine alone were able to differentiate between the two diseases. For that purpose, eosinophil peroxidase was a better candidate, as the mean levels increased stepwise from HVs via GERD to EoE. iNOS and nitrotyrosine are significantly overexpressed in patients with EoE and GERD compared with healthy controls, but only eosinophil peroxidase could differentiate the two types of esophagitis. The implications of the finding of the highest levels of nitrotyrosine among gastroesophageal reflux patients are discussed.
{"title":"Expression of inducible nitric oxide synthase, nitrotyrosine, eosinophilic peroxidase, eotaxin-3, and galectin-3 in patients with gastroesophageal reflux disease, eosinophilic esophagitis, and in healthy controls: a semiquantitative image analysis of 3,3′-diaminobenzidine-stained esophageal biopsies","authors":"John Plate, Mogens Bove, Helen M Larsson, Elisabeth Norder Grusell, Nabanita Chatterjee, Leif E Johansson, Henrik Bergquist","doi":"10.1093/dote/doae034","DOIUrl":"https://doi.org/10.1093/dote/doae034","url":null,"abstract":"Summary Eosinophilic esophagitis (EoE) and gastroesophageal reflux disease (GERD) share many histopathological features; therefore, markers for differentiation are of diagnostic interest and may add to the understanding of the underlying mechanisms. The nitrergic system is upregulated in GERD and probably also in EoE. Esophageal biopsies of patients with EoE (n = 20), GERD (n = 20), and healthy volunteers (HVs) (n = 15) were exposed to antibodies against inducible nitric oxide synthase (iNOS), nitrotyrosine, eosinophilic peroxidase, eotaxin-3, and galectin-3. The stained object glasses were randomized, digitized, and blindly analyzed regarding the expression of DAB (3,3′-diaminobenzidine) by a protocol developed in QuPath software. A statistically significant overexpression of iNOS was observed in patients with any of the two inflammatory diseases compared with that in HVs. Eotaxin-3 could differentiate HVs versus inflammatory states. Gastroesophageal reflux patients displayed the highest levels of nitrotyrosine. Neither iNOS nor nitrotyrosine alone were able to differentiate between the two diseases. For that purpose, eosinophil peroxidase was a better candidate, as the mean levels increased stepwise from HVs via GERD to EoE. iNOS and nitrotyrosine are significantly overexpressed in patients with EoE and GERD compared with healthy controls, but only eosinophil peroxidase could differentiate the two types of esophagitis. The implications of the finding of the highest levels of nitrotyrosine among gastroesophageal reflux patients are discussed.","PeriodicalId":11354,"journal":{"name":"Diseases of the Esophagus","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140835311","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Matthew Marshall-Webb, Jennifer C Myers, David I Watson, Tim Bright, Taher I Omari, Sarah K Thompson
Mucosal impedance is a marker of esophageal mucosal integrity and a novel technique for assessing esophageal function and pathology. This article highlights its development and clinical application for gastroesophageal reflux disease (GERD), Barrett’s esophagus, and eosinophilic esophagitis. A narrative review of key publications describing the development and use of mucosal impedance in clinical practice was conducted. A low mean nocturnal baseline impedance (MNBI) has been shown to be an independent predictor of response to anti-reflux therapy. MNBI predicts medication-responsive heartburn better than distal esophageal acid exposure time. Patients with equivocal evidence of GERD using conventional methods, with a low MNBI, had an improvement in symptoms following the initiation of PPI therapy compared to those with a normal MNBI. A similar trend was seen in a post fundoplication cohort. Strong clinical utility for the use of mucosal impedance in assessing eosinophilic esophagitis has been repeatedly demonstrated; however, there is minimal direction for application in Barrett’s esophagus. The authors conclude that mucosal impedance has potential clinical utility for the assessment and diagnosis of GERD, particularly when conventional investigations have yielded equivocal results.
粘膜阻抗是食管粘膜完整性的标志，也是评估食管功能和病理的一种新技术。本文重点介绍了它在胃食管反流病（GERD）、巴雷特食管和嗜酸性粒细胞食管炎方面的发展和临床应用。我们对描述粘膜阻抗在临床实践中的发展和应用的主要出版物进行了叙述性综述。低平均夜间基线阻抗（MNBI）已被证明是抗反流治疗反应的独立预测指标。MNBI 比食管远端酸暴露时间更能预测药物反应性烧心。与 MNBI 正常的患者相比，采用传统方法诊断胃食管反流病证据不明确但 MNBI 较低的患者在开始 PPI 治疗后症状有所改善。胃底折叠术后人群中也出现了类似的趋势。使用粘膜阻抗评估嗜酸性粒细胞食管炎的强大临床实用性已被反复证明，但在巴雷特食管中的应用方向却很少。作者总结道，粘膜阻抗在胃食管反流病的评估和诊断中具有潜在的临床实用性，尤其是在常规检查结果不明确的情况下。
{"title":"Mucosal impedance as a diagnostic tool for gastroesophageal reflux disease: an update for clinicians","authors":"Matthew Marshall-Webb, Jennifer C Myers, David I Watson, Tim Bright, Taher I Omari, Sarah K Thompson","doi":"10.1093/dote/doae037","DOIUrl":"https://doi.org/10.1093/dote/doae037","url":null,"abstract":"Mucosal impedance is a marker of esophageal mucosal integrity and a novel technique for assessing esophageal function and pathology. This article highlights its development and clinical application for gastroesophageal reflux disease (GERD), Barrett’s esophagus, and eosinophilic esophagitis. A narrative review of key publications describing the development and use of mucosal impedance in clinical practice was conducted. A low mean nocturnal baseline impedance (MNBI) has been shown to be an independent predictor of response to anti-reflux therapy. MNBI predicts medication-responsive heartburn better than distal esophageal acid exposure time. Patients with equivocal evidence of GERD using conventional methods, with a low MNBI, had an improvement in symptoms following the initiation of PPI therapy compared to those with a normal MNBI. A similar trend was seen in a post fundoplication cohort. Strong clinical utility for the use of mucosal impedance in assessing eosinophilic esophagitis has been repeatedly demonstrated; however, there is minimal direction for application in Barrett’s esophagus. The authors conclude that mucosal impedance has potential clinical utility for the assessment and diagnosis of GERD, particularly when conventional investigations have yielded equivocal results.","PeriodicalId":11354,"journal":{"name":"Diseases of the Esophagus","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140810918","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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