BACKGROUND Esophageal squamous cell carcinoma(ESCC)is a deadly malignancy with limited treatment options.Deubiquitinases(DUBs)have been confirmed to play a crucial role in the development of malignant tumors.JOSD2 is ...BACKGROUND Esophageal squamous cell carcinoma(ESCC)is a deadly malignancy with limited treatment options.Deubiquitinases(DUBs)have been confirmed to play a crucial role in the development of malignant tumors.JOSD2 is a DUB involved in con-trolling protein deubiquitination and influencing critical cellular processes in cancer.AIM To investigate the impact of JOSD2 on the progression of ESCC.METHODS Bioinformatic analyses were employed to explore the expression,prognosis,and enriched pathways associated with JOSD2 in ESCC.Lentiviral transduction was utilized to manipulate JOSD2 expression in ESCC cell lines(KYSE30 and RESULTS )Preliminary research indicated that JOSD2 was highly expressed in ESCC tissues,which was associated with poor prognosis.Further analysis demonstrated that JOSD2 was upregulated in ESCC cell lines compared to normal esophageal cells.JOSD2 knockdown inhibited ESCC cell activity,including proliferation and colony-forming ability.Moreover,JOSD2 knockdown decreased the drug resistance and migration of ESCC cells,while JOSD2 overexpression enhanced these phenotypes.In vivo xenograft assays further confirmed that JOSD2 promoted tumor proliferation and drug resistance in ESCC.Mechanistically,JOSD2 appears to activate the MAPK/ERK and PI3K/AKT signaling pathways.Mass spectrometry was used to identify crucial substrate proteins that interact with JOSD2,which identified the four primary proteins that bind to JOSD2,namely USP47,IGKV2D-29,HSP90AB1,and PRMT5.CONCLUSION JOSD2 plays a crucial role in enhancing the proliferation,migration,and drug resistance of ESCC,suggesting that JOSD2 is a potential therapeutic target in ESCC.展开更多
AIM To compare vonoprazan 10 and 20 mg vs lansoprazole 15 mg as maintenance therapy in healed erosive esophagitis(EE).METHODS A total of 607 patients aged ≥ 20 years, with endoscopically-confirmed healed EE following...AIM To compare vonoprazan 10 and 20 mg vs lansoprazole 15 mg as maintenance therapy in healed erosive esophagitis(EE).METHODS A total of 607 patients aged ≥ 20 years, with endoscopically-confirmed healed EE following 8 wk of treatment with vonoprazan 20 mg once daily, were randomized 1:1:1 to receive lansoprazole 15 mg(n = 201), vonoprazan 10 mg(n = 202), or vonoprazan 20 mg(n = 204), once daily. The primary endpoint of the study was the rate of endoscopically-confirmed EE recurrence during a 24-wk maintenance period. The secondary endpoint was the EE recurrence rate at Week 12 during maintenance treatment. Additional efficacy endpoints included the incidence of heartburn and acid reflux, and the EE healing rate 4 wk after the initiation of maintenance treatment. Safety endpoints comprised adverse events(AEs), vital signs, electrocardiogram findings, clinical laboratory results, serum gastrin and pepsinogen Ⅰ/Ⅱ levels, and gastric mucosa histopathology results.RESULTS Rates of EE recurrence during the 24-wk maintenance period were 16.8%, 5.1%, and 2.0% with lansoprazole 15 mg, vonoprazan 10 mg, and vonoprazan 20 mg, respectively. Vonoprazan was shown to be non-inferior to lansoprazole 15 mg(P < 0.0001 for both doses). In a post-hoc analysis, EE recurrence at Week 24 was significantly reduced with vonoprazan at both the 10 mg and the 20 mg dose vs lansoprazole 15 mg(5.1% vs 16.8%, P = 0.0002, and 2.0% vs 16.8%, P < 0.0001, respectively); by contrast, the EE recurrence rate did not differ significantly between the two doses of vonoprazan(P = 0.1090). The safety profiles of vonoprazan 10 and 20 mg were similar to that of lansoprazole 15 mg in patients with healed EE. Treatment-related AEs were reported in 11.4%, 10.4%, and 10.3% of patients in the lansoprazole 15 mg, vonoprazan 10 mg, and vonoprazan 20 mg arms, respectively.CONCLUSION Our findings confirm the non-inferiority of vonoprazan 10 and 20 mg to lansoprazole 15 mg as maintenance therapy for patients with healed EE.展开更多
Background： Helicohacterpylori （H. pylori） frequently colonizes the stomach. Gastroesophageal reflux disease （GERD） is a common and costly disease. But the relationship ofH. pylori and GERD is still unclear. This...Background： Helicohacterpylori （H. pylori） frequently colonizes the stomach. Gastroesophageal reflux disease （GERD） is a common and costly disease. But the relationship ofH. pylori and GERD is still unclear. This study aimed to explore the effect ofH. p.vlori and its eradication on reflux esophagitis therapy. Methods： Patients diagnosed with reflux esophagitis by endoscopy were enrolled; based on rapid urease test and Warth-Starry stain, they were divided into H. pylori positive and negative groups. H. pylori positive patients were randomly given H. pylori eradication treatment for 10 days, then esomeprazole 20 mg bid for 46 days. The other patients received esomeprazole 20 mg bid therapy for 8 weeks. After treatment, three patient groups were obtained： H. pylori positive eradicated, H. pylori positive uneradicated, and H. pylori negative. Before and after therapy, reflux symptoms were scored and compared. Healing rates were compared among groups. The x2 test and t-test were used, respectively, for enumeration and measurement data. Results： There were 176 H. pylori positive （with 92 eradication cases） and 180 negative cases. Healing rates in the H. pylori positive eradicated and H. pylori positive uneradicated groups reached 80.4% and 79.8% （P = 0.911）, with reflux symptom scores of 0.22 and 0.14 （P = 0.588）. Healing rates of esophagitis in the 14. pylori positive uneradicated and H. pylori negative groups were, respectively, 79.8% and 82.2% （P = 0.848）; reflux symptom scores were 0.14 and 0.21 （P = 0.546）. Conclusions： Based on esomeprazole therapy, H. pylori infection and eradication have no significant effect on reflux esophagitis therapy.展开更多
INTRODUCTIONThe origins of oesophageal surgery ,like most surgical treatments ,are based in the treatment of traumatic injury .The Smith Surgical Papyrus describes the examination, diagnosis and treatment of 'a ga...INTRODUCTIONThe origins of oesophageal surgery ,like most surgical treatments ,are based in the treatment of traumatic injury .The Smith Surgical Papyrus describes the examination, diagnosis and treatment of 'a gaping wound of throat, penetrating the gullet' [1].展开更多
AIM: To investigate two distinct clinical phenotypes of reflux esophagitis and intra-hernial ulcer (Cameron lesions) in patients with large hiatal hernias. METHODS: A case series study was performed with 16 831 patien...AIM: To investigate two distinct clinical phenotypes of reflux esophagitis and intra-hernial ulcer (Cameron lesions) in patients with large hiatal hernias. METHODS: A case series study was performed with 16 831 patients who underwent diagnostic esophagogastroduodenoscopy for 2 years at an academic referral center. A hiatus diameter ≥ 4 cm was defined as a large hernia. A sharp fold that surrounded the cardia was designated as an intact gastroesophageal flap valve (GEFV), and a loose fold or disappearance of the fold was classified as an impaired GEFV. We studied the associations between large hiatal hernias and the distinct clinical phenotypes (reflux esophagitis and Cameron lesions), and analyzed factors that distinguished the clinical phenotypes. RESULTS: Large hiatal hernias were found in 49 (0.3%) of 16 831 patients. Cameron lesions and reflux esopha-gitis were observed in 10% and 47% of these patients, and 0% and 8% of the patients without large hiatal hernias, which indicated significant associations between large hiatal hernias and these diseases. However, there was no coincidence of the two distinct disorders. Univariate analysis demonstrated significant associations between Cameron lesions and the clinico-endoscopic factors such as nonsteroidal anti-inflammatory drug (NSAID) intake (80% in Cameron lesion cases vs 18% in non-Cameron lesion cases, P=0.015) and intact GEFV (100% in Cameron lesion cases vs 18% in non-Cameron lesion cases, P=0.0007). In contrast, reflux esophagitis was linked with impaired GEFV (44% in reflux esophagitis cases vs 8% in non-reflux esophagitis cases, P = 0.01). Multivariate regression analysis confirmed these significant associations. CONCLUSION: GEFV status and NSAID intake distinguish clinical phenotypes of large hiatal hernias. Cameron lesions are associated with intact GEFV and NSAID intake.展开更多
Metastases of esophageal carcinoma to the skeletal muscle are rare,but the incidence may be increasing because of better diagnosis resulting from widespread use of positron emission tomography/computed tomography(PET/...Metastases of esophageal carcinoma to the skeletal muscle are rare,but the incidence may be increasing because of better diagnosis resulting from widespread use of positron emission tomography/computed tomography(PET/CT).A cohort of 205 patients with esophageal carcinoma treated at our center who had PET/CT between 2006 and 2010 was retrospectively evaluated for the presence of skeletal muscle metastases.Four patients had skeletal muscle metastases of esophageal carcinoma,including two patients with squamous cell carcinoma.In another patient with squamous cell carcinoma of the esophagus and synchronous skeletal muscle metastases,muscle metastases were subsequently shown to be related to second primary pancreatic adenocarcinoma.In all cases,skeletal muscle metastases were the first manifestation of systemic disease.In three patients palliation was obtained with the combination of external beam radiation therapy,systemic chemotherapy or surgical resection.Skeletal muscle metastases are a rare complication of esophageal carcinoma.展开更多
BACKGROUND Although the overall incidence of tuberculosis in underdeveloped areas has increased in recent years, esophageal tuberculosis(ET) is still rare. Intestinal tuberculosis(ITB) is relatively more common, but t...BACKGROUND Although the overall incidence of tuberculosis in underdeveloped areas has increased in recent years, esophageal tuberculosis(ET) is still rare. Intestinal tuberculosis(ITB) is relatively more common, but there are few reports of ET complicated with ITB. We report a case of secondary ET complicated with ITB in a previously healthy patient.CASE SUMMARY A 27-year-old female was hospitalized for progressive dysphagia, retrosternal pain, acid regurgitation, belching, heartburn, and nausea. Upper gastrointestinal endoscopy showed a mid-esophageal ulcerative hyperplastic lesion. Endoscopic ultrasonography showed a homogeneous hypoechoic lesion, with adjacent enlarged lymph nodes. Biopsy histopathology showed inflammatory exudation,exfoliated epithelial cells and interstitial granulation tissue proliferation.Colonoscopy revealed a rat-bite ulcer in the terminal ileum and a superficial ulcer in the ascending colon, near the ileocecal region. The ileum lesion biopsy showed focal granulomas with caseous necrosis. Polymerase chain reaction for Mycobacterium tuberculosis was positive in the esophageal and ileum lesion biopsies. The T-cell spot tuberculosis test was also positive. The patient was diagnosed with secondary ET infiltrated by mediastinal lymphadenopathy and complicated with ITB, possibly from the Mycobacterium tuberculosis-infected esophageal lesion. After 2 mo of anti-tuberculosis therapy, her symptoms improved significantly, and upper gastrointestinal endoscopy showed healing ulcers.CONCLUSION When dysphagia or odynophagia occurs in patients at high-risk for tuberculosis,ET should be considered.展开更多
基金Supported by Tianjin Key Medical Discipline(Specialty)Construction Project,No.TJYXZDXK-009ATianjin Medical University Cancer Hospital National Natural Science Foundation Cultivation Program,No.220108+3 种基金National Natural Science Foundation of China,No.82373134Science and Technology Development Fund of Tianjin Education Commission for Higher Education,No.2022KJ228Chinese Anti-Cancer Association-Heng Rui Anti-angiogenesis Targeted Tumor Research Fund,No.2021001045and Scientific Research Translational Foundation of Wenzhou Safety(Emergency)Institute of Tianjin University,No.TJUWYY2022025.
文摘BACKGROUND Esophageal squamous cell carcinoma(ESCC)is a deadly malignancy with limited treatment options.Deubiquitinases(DUBs)have been confirmed to play a crucial role in the development of malignant tumors.JOSD2 is a DUB involved in con-trolling protein deubiquitination and influencing critical cellular processes in cancer.AIM To investigate the impact of JOSD2 on the progression of ESCC.METHODS Bioinformatic analyses were employed to explore the expression,prognosis,and enriched pathways associated with JOSD2 in ESCC.Lentiviral transduction was utilized to manipulate JOSD2 expression in ESCC cell lines(KYSE30 and RESULTS )Preliminary research indicated that JOSD2 was highly expressed in ESCC tissues,which was associated with poor prognosis.Further analysis demonstrated that JOSD2 was upregulated in ESCC cell lines compared to normal esophageal cells.JOSD2 knockdown inhibited ESCC cell activity,including proliferation and colony-forming ability.Moreover,JOSD2 knockdown decreased the drug resistance and migration of ESCC cells,while JOSD2 overexpression enhanced these phenotypes.In vivo xenograft assays further confirmed that JOSD2 promoted tumor proliferation and drug resistance in ESCC.Mechanistically,JOSD2 appears to activate the MAPK/ERK and PI3K/AKT signaling pathways.Mass spectrometry was used to identify crucial substrate proteins that interact with JOSD2,which identified the four primary proteins that bind to JOSD2,namely USP47,IGKV2D-29,HSP90AB1,and PRMT5.CONCLUSION JOSD2 plays a crucial role in enhancing the proliferation,migration,and drug resistance of ESCC,suggesting that JOSD2 is a potential therapeutic target in ESCC.
文摘AIM To compare vonoprazan 10 and 20 mg vs lansoprazole 15 mg as maintenance therapy in healed erosive esophagitis(EE).METHODS A total of 607 patients aged ≥ 20 years, with endoscopically-confirmed healed EE following 8 wk of treatment with vonoprazan 20 mg once daily, were randomized 1:1:1 to receive lansoprazole 15 mg(n = 201), vonoprazan 10 mg(n = 202), or vonoprazan 20 mg(n = 204), once daily. The primary endpoint of the study was the rate of endoscopically-confirmed EE recurrence during a 24-wk maintenance period. The secondary endpoint was the EE recurrence rate at Week 12 during maintenance treatment. Additional efficacy endpoints included the incidence of heartburn and acid reflux, and the EE healing rate 4 wk after the initiation of maintenance treatment. Safety endpoints comprised adverse events(AEs), vital signs, electrocardiogram findings, clinical laboratory results, serum gastrin and pepsinogen Ⅰ/Ⅱ levels, and gastric mucosa histopathology results.RESULTS Rates of EE recurrence during the 24-wk maintenance period were 16.8%, 5.1%, and 2.0% with lansoprazole 15 mg, vonoprazan 10 mg, and vonoprazan 20 mg, respectively. Vonoprazan was shown to be non-inferior to lansoprazole 15 mg(P < 0.0001 for both doses). In a post-hoc analysis, EE recurrence at Week 24 was significantly reduced with vonoprazan at both the 10 mg and the 20 mg dose vs lansoprazole 15 mg(5.1% vs 16.8%, P = 0.0002, and 2.0% vs 16.8%, P < 0.0001, respectively); by contrast, the EE recurrence rate did not differ significantly between the two doses of vonoprazan(P = 0.1090). The safety profiles of vonoprazan 10 and 20 mg were similar to that of lansoprazole 15 mg in patients with healed EE. Treatment-related AEs were reported in 11.4%, 10.4%, and 10.3% of patients in the lansoprazole 15 mg, vonoprazan 10 mg, and vonoprazan 20 mg arms, respectively.CONCLUSION Our findings confirm the non-inferiority of vonoprazan 10 and 20 mg to lansoprazole 15 mg as maintenance therapy for patients with healed EE.
文摘Background： Helicohacterpylori （H. pylori） frequently colonizes the stomach. Gastroesophageal reflux disease （GERD） is a common and costly disease. But the relationship ofH. pylori and GERD is still unclear. This study aimed to explore the effect ofH. p.vlori and its eradication on reflux esophagitis therapy. Methods： Patients diagnosed with reflux esophagitis by endoscopy were enrolled; based on rapid urease test and Warth-Starry stain, they were divided into H. pylori positive and negative groups. H. pylori positive patients were randomly given H. pylori eradication treatment for 10 days, then esomeprazole 20 mg bid for 46 days. The other patients received esomeprazole 20 mg bid therapy for 8 weeks. After treatment, three patient groups were obtained： H. pylori positive eradicated, H. pylori positive uneradicated, and H. pylori negative. Before and after therapy, reflux symptoms were scored and compared. Healing rates were compared among groups. The x2 test and t-test were used, respectively, for enumeration and measurement data. Results： There were 176 H. pylori positive （with 92 eradication cases） and 180 negative cases. Healing rates in the H. pylori positive eradicated and H. pylori positive uneradicated groups reached 80.4% and 79.8% （P = 0.911）, with reflux symptom scores of 0.22 and 0.14 （P = 0.588）. Healing rates of esophagitis in the 14. pylori positive uneradicated and H. pylori negative groups were, respectively, 79.8% and 82.2% （P = 0.848）; reflux symptom scores were 0.14 and 0.21 （P = 0.546）. Conclusions： Based on esomeprazole therapy, H. pylori infection and eradication have no significant effect on reflux esophagitis therapy.
文摘INTRODUCTIONThe origins of oesophageal surgery ,like most surgical treatments ,are based in the treatment of traumatic injury .The Smith Surgical Papyrus describes the examination, diagnosis and treatment of 'a gaping wound of throat, penetrating the gullet' [1].
文摘AIM: To investigate two distinct clinical phenotypes of reflux esophagitis and intra-hernial ulcer (Cameron lesions) in patients with large hiatal hernias. METHODS: A case series study was performed with 16 831 patients who underwent diagnostic esophagogastroduodenoscopy for 2 years at an academic referral center. A hiatus diameter ≥ 4 cm was defined as a large hernia. A sharp fold that surrounded the cardia was designated as an intact gastroesophageal flap valve (GEFV), and a loose fold or disappearance of the fold was classified as an impaired GEFV. We studied the associations between large hiatal hernias and the distinct clinical phenotypes (reflux esophagitis and Cameron lesions), and analyzed factors that distinguished the clinical phenotypes. RESULTS: Large hiatal hernias were found in 49 (0.3%) of 16 831 patients. Cameron lesions and reflux esopha-gitis were observed in 10% and 47% of these patients, and 0% and 8% of the patients without large hiatal hernias, which indicated significant associations between large hiatal hernias and these diseases. However, there was no coincidence of the two distinct disorders. Univariate analysis demonstrated significant associations between Cameron lesions and the clinico-endoscopic factors such as nonsteroidal anti-inflammatory drug (NSAID) intake (80% in Cameron lesion cases vs 18% in non-Cameron lesion cases, P=0.015) and intact GEFV (100% in Cameron lesion cases vs 18% in non-Cameron lesion cases, P=0.0007). In contrast, reflux esophagitis was linked with impaired GEFV (44% in reflux esophagitis cases vs 8% in non-reflux esophagitis cases, P = 0.01). Multivariate regression analysis confirmed these significant associations. CONCLUSION: GEFV status and NSAID intake distinguish clinical phenotypes of large hiatal hernias. Cameron lesions are associated with intact GEFV and NSAID intake.
文摘Metastases of esophageal carcinoma to the skeletal muscle are rare,but the incidence may be increasing because of better diagnosis resulting from widespread use of positron emission tomography/computed tomography(PET/CT).A cohort of 205 patients with esophageal carcinoma treated at our center who had PET/CT between 2006 and 2010 was retrospectively evaluated for the presence of skeletal muscle metastases.Four patients had skeletal muscle metastases of esophageal carcinoma,including two patients with squamous cell carcinoma.In another patient with squamous cell carcinoma of the esophagus and synchronous skeletal muscle metastases,muscle metastases were subsequently shown to be related to second primary pancreatic adenocarcinoma.In all cases,skeletal muscle metastases were the first manifestation of systemic disease.In three patients palliation was obtained with the combination of external beam radiation therapy,systemic chemotherapy or surgical resection.Skeletal muscle metastases are a rare complication of esophageal carcinoma.
文摘BACKGROUND Although the overall incidence of tuberculosis in underdeveloped areas has increased in recent years, esophageal tuberculosis(ET) is still rare. Intestinal tuberculosis(ITB) is relatively more common, but there are few reports of ET complicated with ITB. We report a case of secondary ET complicated with ITB in a previously healthy patient.CASE SUMMARY A 27-year-old female was hospitalized for progressive dysphagia, retrosternal pain, acid regurgitation, belching, heartburn, and nausea. Upper gastrointestinal endoscopy showed a mid-esophageal ulcerative hyperplastic lesion. Endoscopic ultrasonography showed a homogeneous hypoechoic lesion, with adjacent enlarged lymph nodes. Biopsy histopathology showed inflammatory exudation,exfoliated epithelial cells and interstitial granulation tissue proliferation.Colonoscopy revealed a rat-bite ulcer in the terminal ileum and a superficial ulcer in the ascending colon, near the ileocecal region. The ileum lesion biopsy showed focal granulomas with caseous necrosis. Polymerase chain reaction for Mycobacterium tuberculosis was positive in the esophageal and ileum lesion biopsies. The T-cell spot tuberculosis test was also positive. The patient was diagnosed with secondary ET infiltrated by mediastinal lymphadenopathy and complicated with ITB, possibly from the Mycobacterium tuberculosis-infected esophageal lesion. After 2 mo of anti-tuberculosis therapy, her symptoms improved significantly, and upper gastrointestinal endoscopy showed healing ulcers.CONCLUSION When dysphagia or odynophagia occurs in patients at high-risk for tuberculosis,ET should be considered.
