Positive consequences of splenectomy for patients with schistosomiasis-induced variceal bleeding.

BACKGROUND: Patients with hepatic schistosomiasis are at high risk of gastroesophageal variceal bleeding, which is highly torrential and life threatening. This study aimed to assess the effects of splenectomy on patients with schistosomiasis-induced variceal bleeding, especially those influences related to overall survival (OS) rate. METHODS: From January 2005 to December 2018, 112 patients with schistosomiasis-induced varices were enrolled. In that period, all the patients with hepatic schistosomiasis who received endoscopic treatment for primary and secondary prophylaxis of gastroesophageal variceal bleeding were found eligible. The patients were divided into splenectomized group (n = 44, 39.3%) and control group (n = 68, 60.7%). RESULTS: Multivariate regression analysis of OS showed that splenectomy, hepatic carcinoma, and times of endoscopic treatment were independent prognostic factors for OS. Kaplan-Meier analysis revealed that the 5-year OS rate was 82.7% in splenectomized group versus 53.2% in control group (P = 0.037). The rate of no recurrence of variceal bleeding during 5-year (56.8% vs. 47.7%, P = 0.449) indicated that there was no significant difference between the two groups. Patients who received splenectomy had increased risk of portal vein thrombosis (52.3% vs. 29.4%, P = 0.012) and decreased proportion of severe ascites (20.5% vs 50.0%, P = 0.002). CONCLUSION: Splenectomy prior to endoscopic treatment provides a superior long-term survival for patients with schistosomiasis-induced variceal bleeding.

SCAP Mediated GDF15-Induced Invasion and EMT of Esophageal Cancer.

Background: GDF15 is a potential biomarker for patients with esophageal cancer (EC). However, the mechanistic role of GDF15 in the invasion and metastasis of EC remains poorly understood. Methods: We determined the expression and function of GDF15 in esophageal cancer cells (ESCCs) and in patient tissue samples using western blotting, migration, and invasion assays, immunohistochemistry, Co-IP assays, and quantitative real-time-PCR. In addition, a pulmonary metastatic nude mouse model was used to determine the function of GDF15. We then supplemented our experimental results with database analysis to validate our findings. Results: GDF15 was upregulated in EC, and was associated with poor differentiation, high metastasis rates, and worse prognosis. GDF15 knock-down reduced the migration and invasion of ESCCs. Co-IP assays demonstrated its association with SCAP, while GDF15 knock-down decreased SCAP levels. SCAP overexpression reversed the migration, invasion and EMT in GDF15-siRNA ESCCs. However, after incubation with ß-cyclodextrin (ß-CD), the ability of migration and invasion was weakened, EMT was reversed again. Migration, invasion, and EMT were enhanced in GDF15-siRNA ESCCs cultured in the presence of cholesterol and were similar to GDF15-siRNA ESCCs overexpressing SCAP. In vivo, knockdown of GDF15 inhibited lung metastasis of ESCCs and was reversed by SCAP overexpression or high cholesterol diet. Increased lung metastasis after SCAP overexpression was partially suppressed by intraperitoneal injection of ß-CD. In addition, we determined that GDF15 was a direct target of miR-1324, miR-1324 was down-regulated in EC tissues. MiR-1324 upregulation resulted in decreased GDF15 expression and metastasis in ESCCs. Conclusions: We demonstrated that SCAP mediated GDF15-induced the invasion and metastasis of EC by regulating cholesterol metabolism. In addition, GDF15 was shown to be a direct target of miR-1324.

Endoscopic treatment of gastroesophageal variceal bleeding after oxaliplatin-based chemotherapy in patients with colorectal cancer.

BACKGROUND : Oxaliplatin, used as first-choice treatment for colorectal cancer (CRC), induces sinusoidal endothelial injury and portal hypertension. This study investigated the characteristics of oxaliplatin-induced portal hypertension and evaluated the efficacy of endoscopic management of gastroesophageal variceal bleeding. METHODS : We performed a retrospective, multicenter, case-control study between January 2010 and December 2018. Patients who received oxaliplatin-based chemotherapy after CRC surgery and presented with portal hypertension and gastroesophageal varices were compared with consecutive patients with hepatitis B-related cirrhotic portal hypertension receiving endoscopic treatment for variceal bleeding. RESULTS : 39 patients with oxaliplatin-induced portal hypertension were identified, 35 of whom had a history of variceal bleeding. The median period between start of oxaliplatin-based chemotherapy and the occurrence of varices was 50.4 months (n = 39). A total of 26 patients with oxaliplatin-related portal hypertension and 230 patients with hepatitis B-related portal hypertension underwent endoscopic treatment. Kaplan-Meier analysis revealed that the 1-year rebleeding rate was significantly higher in the oxaliplatin group than in the hepatitis B group (43.3 % vs. 19.0 %, P = 0.001). Multivariable Cox regression analysis showed that oxaliplatin-based chemotherapy was an independent factor for 3-year rebleeding (hazard ratio [HR] 2.46, 95 % confidence interval [CI] 1.24-4.87; P = 0.01) and 3-year overall mortality (HR 9.43, 95 %CI 2.32-38.31; P = 0.002). CONCLUSIONS : Oxaliplatin-related portal hypertension was characterized by massive ascites, splenomegaly, gastric varices, concomitant arterioportal fistula, and relatively normal liver function. Endoscopic treatment to prevent variceal rebleeding in these patients was unsatisfactory compared with endoscopic treatment for hepatitis B-related portal hypertension.

Simvastatin Mitigates Apoptosis and Transforming Growth Factor-Beta Upregulation in Stretch-Induced Endothelial Cells.

Portal hypertension is a common clinical symptom of digestive disorders. With an increase in portal pressure, the portal vein will continue to dilate. We aimed to determine whether continuous stretch induced by portal hypertension may impair the function of endothelial cells (ECs) in the portal vein and aggravate the progress of portal hypertension and explore its mechanism. ECs were cultured on an elastic silicone membrane and subjected to continuous uniaxial stretch. Apoptosis and expression of TGF-ß in ECs under stretch were measured. We found that sustained stretch induced the apoptosis of ECs in a stretch length-dependent manner. Compared with the control, continuous stretch increased the nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2) expression and damaged the mitochondria, resulting in an evident increase in reactive oxygen species (ROS) levels; pretreatment with gp91ds-tat or MitoTEMPO decreased the ROS level in the intracellular levels. N-acetyl-cysteine (NAC) treatment before stretch not only reduced ROS levels but also mitigated the apoptosis of ECs; simvastatin had similar effects through targeting NOX2 and mitochondria. During the stretch, the phosphorylation of p38 mitogen-activated protein kinase (P38MAPK), c-Jun N-terminal kinase (JNK), and nuclear factor-kappa B (NF-κB) was obviously increased; pretreatment with P38MAPK or JNK inhibitors decreased the phosphorylation of NF-κB and TGF-ß expression. Pyrrolidine dithiocarbamate (PDTC) treatment before stretch also reduced TGF-ß expression. After pretreatment with NAC, the phosphorylation of P38MAPK, JNK, and NF-κB and TGF-ß expressions in ECs under stretch was suppressed; similar results were observed in simvastatin-treated ECs. This study demonstrated that simvastatin could mitigate EC apoptosis and TGF-ß upregulation induced by continuous stretch by reducing the level of ROS.