ObjectiveTo investigate the impact of portal vein tumor thrombus （PVTT） classification on rebleeding in hepatocellular carcinoma （HCC） patients with different PVTT subtypes and esophagogastric variceal bleeding （EGVB）， and to provide a reference for formulating rational treatment regimens for such patients. MethodsA retrospective study was performed for 130 patients with HCC and PVTT who were treated due to EGVB in Beijing Ditan Hospital， Capital Medical University， from July 2020 to January 2025， and according to whether endoscopic treatment was performed， the patients were divided into endoscopic treatment group with 97 patients and conservative treatment group with 33 patients. Demographic and clinical data were collected from all patients， and the two groups were compared in terms of hemostasis success rate and rebleeding rate. The independent-samples t test was used for comparison of normally distributed continuous data between groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups； the chi-square test or the Fisher’s exact test was used for comparison of categorical data between groups. The Kaplan-Meier method was used to estimate the cumulative incidence rate of rebleeding in patients with different subtypes of PVTT. Propensity score matching （PSM） was performed for the endoscopic treatment group and the conservative treatment group to balance the baseline data of the two groups. The Cox proportional hazards model was used to perform univariate and multivariate analyses and identify independent risk factors for rebleeding. ResultsThe endoscopic treatment group had a significantly lower cumulative rebleeding rate within 6 months than the conservative treatment group （35.1% vs 57.6%， hazard ratio ［HR］=0.480， 95% confidence interval ［CI］： 0.272—0.851， P=0.019）. The PVTT Ⅲ—Ⅳ group had a significantly higher cumulative rebleeding rate within 6 months than the PVTT Ⅱ group （52.2% vs 37.5%， HR=1.744， 95%CI： 1.008 — 3.018， P=0.022）. After PSM， there was no significant difference in rebleeding rate between the endoscopic treatment group and the conservative treatment group （38.1% vs 14.3%，HR=1.500，95%CI：0.125 — 2.002， P=0.588）， while the PVTT Ⅲ—Ⅳ group had a significantly higher cumulative rebleeding rate than the PVTT Ⅱ group （58.8% vs 12.5%，HR=1.561，95%CI：1.195 — 12.499，P=0.033）. The multivariate Cox regression analysis showed that PVTT subtype （HR=1.412， 95%CI： 0.998 — 1.997， P=0.049）， platelet count （HR=1.006， 95%CI： 1.001 — 1.010， P=0.021）， C-reactive protein （HR=1.011， 95%CI： 1.001 — 1.021， P=0.026）， and ascites （HR=1.803， 95%CI： 1.059 — 3.068， P=0.030） were independent risk factors for rebleeding. ConclusionFor HCC patients with PVTT and EGVB， endoscopic treatment can successfully achieve hemostasis， while it fails to significantly reduce rebleeding rates. PVTT classification can affect the risk of rebleeding， and patients with PVTT types Ⅲ—Ⅳ have a relatively high rebleeding rate.

ObjectiveTo observe the long-term survival outcomes and complications of liver cirrhosis patients with spontaneous portosystemic shunt and type 1 isolated gastric varices （IGV-1） bleeding after secondary endoscopic preventive therapy， and to investigate the independent influencing factors for long-term prognosis. MethodsA total of 70 liver cirrhosis patients with spontaneous portosystemic shunt and IGV-1 bleeding who were admitted to Beijing Ditan Hospital， Capital Medical University， from January 5， 2015 to November 29， 2019 were enrolled as subjects， and related baseline data were collected， including age， sex， etiology， routine blood test results， liver function parameters， renal function parameters， coagulation parameters， Child-Pugh score， and the presence or absence of comorbidities such as cholestasis， hepatocellular carcinoma， thrombosis， ascites， and hepatic encephalopathy. All patients underwent secondary endoscopic preventive therapy for rebleeding and were followed up for 5 years. The primary endpoints were ectopic embolism rate and all-cause mortality rate， and the secondary endpoints were liver-related mortality and liver-related complications. The independent-samples t test or the Mann-Whitney U test was used for comparison of continuous data between groups， and the chi-square test was used for comparison of categorical data between groups. The Cox regression analysis was used to investigate the prognostic factors for 1-， 3-， and 5-year survival time， and the Logistic regression analysis was used to identify the independent risk factors for liver disease-related complications. ResultsThe incidence rate of ectopic embolism was 0% within 5 years of follow-up. The 1-， 3-， and 5-year all-cause mortality rates were 5.7%， 24.3%， and 32.9%， respectively. There were 2 cases of liver-related death in year 1， 8 cases in year 3， and 12 cases in year 5， resulting in a liver disease-related mortality rate of 17.14% （12/70）. Compared with the survival group， the death group had significantly higher incidence rates of hepatocellular carcinoma （0.00% vs 17.39%， χ²=8.669， P=0.003） and ascites （38.30% vs 52.17%， χ²=7.272， P=0.026）， and compared with the death group， the survival group had significantly lower 5-year incidence rates of rebleeding （10.64% vs 100.00%， χ²=51.383， P<0.001）， ascites （8.51% vs 52.17%， χ²=21.574， P<0.001）， and hepatic encephalopathy （0.00% vs 21.74%， χ²=12.029， P=0.002）. The multivariate Cox regression analysis showed that during the 1-year follow-up， comorbidity with hepatocellular carcinoma before surgery （hazard ratio ［HR］=14.601， 95% confidence interval ［CI］： 2.049 — 104.098， P=0.007） and PT （HR=1.662， 95%CI： 1.090 — 2.535， P=0.018） were independent risk factors for survival， and HGB level （HR=0.863， 95%CI： 0.747 — 0.998， P=0.046） was a protective factor for prolonged survival； during the long-term follow-up for 3 or 5 years， preoperative comorbidities with hepatocellular carcinoma （3 years： HR=40.174， 95%CI： 8.939 — 180.559， P<0.001； 5 years： HR=26.739， 95%CI： 6.993 — 102.243， P<0.001） and ascites （3 years： HR=3.638， 95%CI： 1.751 — 7.575， P=0.001； 5 years： HR=2.555， 95%CI： 1.419 — 4.598， P=0.002） were independent risk factors for mortality. The Logistic regression analysis showed that during the follow-up for 3 years， comorbidity with ascites before surgery （odds ratio ［OR］=0.255， 95%CI： 0.102 — 0.636， P=0.003） was associated with a lower risk of rebleeding， while comorbidity with hepatocellular carcinoma before surgery （OR=16.231， 95%CI： 1.298 — 202.878， P=0.031） was an independent risk factor for rebleeding； prothrombin time was a protective factor against hepatic encephalopathy （OR=0.790， 95%CI： 0.648 — 0.964， P=0.020）； during the follow-up for 5 years， aggravation of ascites after surgery （OR=5.578， 95%CI： 1.474 — 21.103， P=0.011） was an independent risk factor for rebleeding， and aggravation of ascites after surgery （OR=175.046， 95%CI： 14.306 — 2 141.909， P<0.001） were independent risk factors for the development of ascites in the future. ConclusionComorbidity with hepatocellular carcinoma before surgery and prothrombin time are independent risk factors for 1-year survival， whereas a high HGB level is a protective factor for increasing 1-year survival. Preoperative comorbidities with hepatocellular carcinoma and ascites are independent risk factors for the long-term prognosis of patients with spontaneous portosystemic shunt and IGV-1 bleeding and can significantly shorten survival time. Preoperative comorbidity with ascites can reduce the occurrence of rebleeding， while postoperative hepatocellular carcinoma and aggravation of ascites after surgery are independent risk factors for rebleeding； aggravation of ascites after surgery is an independent risk factor for the development of ascites in the future.

Objective:This study analyzes the clinicopathological features and prognostic factors of early-stage gastric mixed adenoneuroendocrine carcinoma (G-MANEC), which is an exceedingly rare malignancy, in an effort to provide evidence-based insights for clinical decision-making.Methods:A retrospective observational study was conducted using the clinical data of 36 patients with early-stage G-MANEC who underwent surgical resection at Zhongshan Hospital, Fudan University, from July 2014 to May 2022. The observed indicators included clinicopathological data and follow-up information on recurrence, metastasis, and overall survival (OS).Results:Among the 36 patients there were 21 males and 15 females, aged 32-84 (65±11) years. The most common initial symptoms were abdominal pain and distension (19/36, 52.8%), followed by incidental findings during physical examinations (7/36, 19.4%). Tumors were located in the proximal stomach in 13 cases (36.1%), the middle stomach in 4 cases (11.1%), and the distal stomach in 19 cases (52.8%). Average tumor diameter was (2.48±1.18) cm. Gross morphology included elevated type in 12 cases (33.3%), flat type in 20 cases (55.6%), and depressed type in 4 cases (11.1%). Ulceration was present in 12 cases (33.3%). There were 11 cases (30.6%) at T1a stage and 25 cases (69.4%) at T1b stage. Lymph node metastasis was positive in 10 cases (27.8%), and the differentiation grades of the adenocarcinoma component were Grade I, II, and III in 3 (8.3%), 10 (27.8%), and 23 (63.9%) cases, respectively. Furthermore, the proportion of neuroendocrine carcinoma component was ≥50% in 18 cases (50.0%) and <50% in 18 cases (50.0%). Lymphovascular or perineural invasion was present in 18 cases (50.0%). Lauren classification included mixed type in 10 cases (27.8%), intestinal type in 19 cases (52.8%), and diffuse type in 7 cases (19.4%), and chromogranin A (CgA) positivity was found in 20 cases (55.6%). Additionally, the Ki-67 index positivity was found in 26 cases (72.2%). Total gastrectomy was performed in 12 cases (33.3%) and partial gastrectomy in 24 cases (66.7%), with a median follow-up duration of 77.5 months. The 3-year and 5-year OS rates were 88.89% and 79.67%, respectively. Univariate analysis revealed that age, gross morphology, ulceration, proportion of neuroendocrine carcinoma component, lymphovascular or perineural invasion, and chromogranin A (CgA) positivity showed statistical significance in their association with OS ( P<0.10). Multivariate Cox regression analysis further identified ulceration (HR=7.74, 95%CI: 1.24-48.30, P=0.028) and CgA positivity (HR=21.76, 95%CI: 1.86-53.97, P=0.014) as independent risk factors of OS. Conclusions:Patients with early-stage G-MANEC are typically asymptomatic, and those with ulceration or positive CgA immunohistochemical staining tend to have a poor prognosis.

ObjectiveTo investigate the safety and efficacy of puncture cyanoacrylate selective seal （PCSS） under endoscopic ultrasound in the treatment of gastroesophageal varices （GOV）. MethodsA total of 100 patients with liver cirrhosis who underwent endoscopic therapy for the secondary prevention of GOV bleeding in Beijing Ditan Hospital， Capital Medical University， from March 1 to December 31， 2023 were enrolled and randomly divided into PCSS group and traditional endoscopy group. The patients were followed up for 6 months after surgery， and the two groups were compared in terms of clinical outcome and complications. The primary outcome measure was the rate of alleviation or disappearance of GOV， and the secondary outcome measure was variceal rebleeding and death. The independent-samples t test was used for comparison of normally distributed or approximately normally distributed quantitative data between two groups， and the Wilcoxon non-parametric test was used for comparison of non-normally distributed quantitative data between two groups； the chi-square test or the Fisher’s exact test was used for comparison of qualitative data between two groups. ResultsThere were 50 patients in the PCSS group， among whom 1 patient was lost to follow-up， and there were 50 patients in the traditional endoscopy group， among whom 3 patients were lost to follow-up. There were no significant differences between the two groups in baseline data such as age， sex， Child-Pugh class， varices grade， and GOV typing （all P>0.05）. Compared with the traditional endoscopy group， the PCSS group had significantly better results of the number of endoscopic treatment sessions （t=-15.671， P=0.001）， the total amount of tissue adhesive used （t=-2.830， P=0.006）， and the rate of alleviation or eradication of varices sclerosis （χ²=7.078， P=0.029）. Both groups had low rates of postoperative rebleeding， adverse reactions， and complications， and there were no significant differences between the two groups （all P>0.05）. ConclusionCompared with traditional endoscopy， PCSS can significantly enhance treatment outcome while maintaining safety standards.

Objective:This study analyzes the clinicopathological features and prognostic factors of early-stage gastric mixed adenoneuroendocrine carcinoma (G-MANEC), which is an exceedingly rare malignancy, in an effort to provide evidence-based insights for clinical decision-making.Methods:A retrospective observational study was conducted using the clinical data of 36 patients with early-stage G-MANEC who underwent surgical resection at Zhongshan Hospital, Fudan University, from July 2014 to May 2022. The observed indicators included clinicopathological data and follow-up information on recurrence, metastasis, and overall survival (OS).Results:Among the 36 patients there were 21 males and 15 females, aged 32-84 (65±11) years. The most common initial symptoms were abdominal pain and distension (19/36, 52.8%), followed by incidental findings during physical examinations (7/36, 19.4%). Tumors were located in the proximal stomach in 13 cases (36.1%), the middle stomach in 4 cases (11.1%), and the distal stomach in 19 cases (52.8%). Average tumor diameter was (2.48±1.18) cm. Gross morphology included elevated type in 12 cases (33.3%), flat type in 20 cases (55.6%), and depressed type in 4 cases (11.1%). Ulceration was present in 12 cases (33.3%). There were 11 cases (30.6%) at T1a stage and 25 cases (69.4%) at T1b stage. Lymph node metastasis was positive in 10 cases (27.8%), and the differentiation grades of the adenocarcinoma component were Grade I, II, and III in 3 (8.3%), 10 (27.8%), and 23 (63.9%) cases, respectively. Furthermore, the proportion of neuroendocrine carcinoma component was ≥50% in 18 cases (50.0%) and <50% in 18 cases (50.0%). Lymphovascular or perineural invasion was present in 18 cases (50.0%). Lauren classification included mixed type in 10 cases (27.8%), intestinal type in 19 cases (52.8%), and diffuse type in 7 cases (19.4%), and chromogranin A (CgA) positivity was found in 20 cases (55.6%). Additionally, the Ki-67 index positivity was found in 26 cases (72.2%). Total gastrectomy was performed in 12 cases (33.3%) and partial gastrectomy in 24 cases (66.7%), with a median follow-up duration of 77.5 months. The 3-year and 5-year OS rates were 88.89% and 79.67%, respectively. Univariate analysis revealed that age, gross morphology, ulceration, proportion of neuroendocrine carcinoma component, lymphovascular or perineural invasion, and chromogranin A (CgA) positivity showed statistical significance in their association with OS ( P<0.10). Multivariate Cox regression analysis further identified ulceration (HR=7.74, 95%CI: 1.24-48.30, P=0.028) and CgA positivity (HR=21.76, 95%CI: 1.86-53.97, P=0.014) as independent risk factors of OS. Conclusions:Patients with early-stage G-MANEC are typically asymptomatic, and those with ulceration or positive CgA immunohistochemical staining tend to have a poor prognosis.

ObjectiveTo investigate the safety and efficacy of endoscopic ultrasound-guided tissue adhesive injection with the assistance of metal clips in the treatment of cirrhotic patients with gastric varices and gastric-renal shunt （GRS）. MethodsThe patients who attended Beijing Ditan Hospital， Capital Medical University， due to liver cirrhosis and gastric varices from February to June 2023 were enrolled， and all patients were confirmed to have GRS and received endoscopic ultrasound-guided tissue adhesive injection with the assistance of metal clips. The primary evaluation index was alleviation or disappearance of varicose veins after surgery， and the secondary evaluation indices were surgical completion and complications. ResultsA total of 11 patients were enrolled in this study， among whom there were 7 male patients and 4 female patients， with a median age of 55 years. Of all patients， 1 had Child class A liver function， 7 had Child class B liver function， and 3 had Child class C liver function. The maximum （median） diameter of the shunt was 8 mm， and the minimum （median） diameter of the shunt was 4 mm. The median blood flow velocity of the target vessel was 11 cm/s before treatment and 5 cm/s after occlusion with metal clips. The median amount of tissue adhesive injected was 2 mL， and the amount of lauromacrogol used was 1 mL. Disappearance of blood flow signals was observed in all patients after surgery （100%）， and the success rate of surgery was 100%. No patient experienced rebleeding after follow-up for 6 weeks. Gastroscopy at 1 month after surgery showed that gastric varices were eradicated or almost disappeared in 9 patients and were alleviated in 2 patients. ConclusionEndoscopic ultrasound-guided tissue adhesive injection with the assistance of metal clips is a feasible， safe， and effective treatment method for cirrhotic patients with gastric varices and GRS.

Exosomes are nano-sized phospholipid bilayer vesicles containing abundant and complex biomolecules, such as DNA, mRNAs, microRNAs (miRNAs), lipids, and proteins. Exosomes can be secreted and ingested by most types of cells to transfer information through intercellular transport. After uptake by recipient cells, exosomes release bioactive substances to regulate the biological processes of recipient cells, such as promoting tumor growth and metastasis. Changes of exosomes and their contents are associated with a variety of diseases. In recent years, the role of exosomal miRNAs in the development and progression of hepatocellular carcinoma (HCC) caused by viral hepatitis has attracted wide attention, and exosomal miRNAs from different sources play different roles in this process. This article briefly reviews the research on the role of exosomal miRNAs in the development and progression of viral hepatitis-related HCC and proposes that exosomal miRNAs may be the targets for immunotherapy for HCC microenvironment.

AIM:To observe the clinical effect of different concentration of fluorometholone eye drops on severe mixed vernal keratoconjunctivitis in children.METHODS: A total of 50 cases(100 eyes)of children with severe mixed vernal keratoconjunctivitis treated in the outpatient department of our hospital from March to September, 2022 were selected and randomly divided into two groups. Group A consisted of 25 cases(50 eyes)who were treated with 0.1% fluorometholone eye drops combined with 0.05% cyclosporine eye drops(Ⅱ), while 25 patients(50 eyes)in group B were treated with 0.02% fluorometholone eye drops combined with 0.05% cyclosporine eye drops(Ⅱ). After 1mo of treatment, SPEED questionnaire score, corneal fluorescein staining(FL)score, tear break-up time(TBUT), Schirmer I test(SⅠt), R-scan, non-invasive tear meniscus height(NIKTMH), corneal optical density and other ocular parameters of the two groups were observed, and the occurrence of adverse reactions were recorded.RESULTS: After 1mo of treatment, there were significant differences in SPEED score, FL score and R-scan results between the two groups(all P<0.05), and no differences in TBUT, SⅠt and NIKTMH results(all P>0.05). However, there were statistical significance in corneal optical density in different corneal depth and diameter ranges(all P<0.05). After 1mo of treatment, there was no significant difference in intraocular pressure between the two groups(16.21±2.90mmHg vs. 16.05±2.75mmHg, P>0.05), and no obvious adverse reactions occurred during treatment.CONCLUSION: The 0.1% fluorometholone eye drops can effectively treat severe mixed vernal keratoconjunctivitis in children, and its effect is better than 0.02% fluorometholone eye drops.

Objective To analyze the rebleeding rate in hepatocellular carcinoma (HCC) patients with portal vein tumor thrombus (PVTT) after endoscopic treatment of esophagogastric variceal bleeding and then assessed the risk factors of the rebleeding in the patients. Methods This study retrospectively recruited 169 hepatitis B-associated HCC patients complicated with PVTT and esophagogastric variceal bleeding treated by endoscopy in Department of Gastroenterology, Beijing Ditan Hospital from September 2008 to December 2016. Among them, 47 patients had PVTT Ⅱ, 67 patients had PVTT Ⅲ, and 55 patients had PVTT Ⅳ. Their clinicopathological and follow-up data were retrieved from the medical records and statistically analyzed. Continuous data were compared among groups using ANOVA or Kruskal-Wallis H test. Categorial data were compared among groups using Chi-square test or corrected Fisher test. The Kaplan-Meier curves and Log-rank test were performed to analyze the rebleeding rate and cumulative survival rates after treatment. The univariate multivariate Cox regression analyses were used to identify the risk factors affecting the rebleeding of patients. Results Compared with PVTT Ⅱ and Ⅲ, PVTT Ⅳ patients had a higher serum level of the direct bilirubin ( Z =6.153, P =0.046). The endoscopy treatment successfully blocked esophagogastric variceal bleeding in all patients. There was no significant difference in the rebleeding rates within six months and a year after the treatment (all P > 0.05). It was also no statistically significant difference in cumulative survival rates in six months and l-, 2-, and 3-year after the treatment in PVTT Ⅱ, Ⅲ, and Ⅳ patients (all P > 0.05). Cox multivariate regression analysis showed that hepatic encephalopathy ( HR =3.643, 95% CI : 2.099-6.325, P < 0.001), γ-glutamyltransferase ( HR =1.002, 95% CI : 1.000-1.005, P =0.029), AFP ( HR =1.000, 95% CI : 1.000-1.000, P =0.002) and numbers of tumor lesions ( HR =1.647, 95% CI : 1.011-2.684, P =0.045) were all independent risk factors for 1-year rebleeding in these PVTT patients with esophagogastric variceal bleeding after endoscopic treatment. Conclusion Endoscopic hemostasis is a feasible treatment option for HCC patients with PVTT and esophagogastric variceal bleeding. However, there was no significant difference in the rebleeding and cumulative survival rates in these patients. Furthermore, hepatic encephalopathy, γ-glutamyltransferase, AFP and numbers of tumor lesions were all independent risk factors for 1-year rebleeding in these patients.