Endoscopic ultrasonography in the evaluation of condition and prognosis of ulcerative colitis.

BACKGROUND: Ulcerative colitis (UC) is usually diagnosed through histopathology, enteroscopy, clinical symptoms, and physical findings; however, it is difficult to accurately evaluate disease severity. AIM: To investigate the value of endoscopic ultrasonography (EUS) in the evaluation of the severity and prognosis of UC. METHODS: Patients with UC who were seen in our hospital from March 2019 to December 2020 were eligible, and disease severity was evaluated according to the modified Truelove and Witts and Mayo scores. We performed EUS, calculated the UC endoscopic index of severity (UCEIS) and EUS-UC scores, and administered appropriate treatment. The UCEIS and EUS-UC scores of patients were assessed in relation to disease severity, and the correlations between UCEIS and EUS-UC scores and disease severity was also analyzed. The UCEIS and EUS-UC scores before and after treatment were also compared. RESULTS: A total of 79 patients were included in this study. According to the Mayo Index, 23, 32, and 24 patients had mild, moderate and severe UC, respectively. The UCEIS and EUS-UC scores were higher in moderate cases (4.98 ± 1.04 and 5.01 ± 0.99, respectively) than in mild cases (1.56 ± 0.82 and 1.64 ± 0.91, respectively, P < 0.05). Furthermore, the UCEIS and EUS-UC scores (7.31 ± 1.10 and 7.59 ± 1.02, respectively) were higher in severe cases than in moderate cases (P < 0.05). According to the modified Truelove and Witts scores, 21, 36, and 22 patients were classified as having mild, moderate and severe disease, respectively. The UCEIS and EUS-UC scores were significantly higher in moderate disease (4.79 ± 1.11 and 4.96 ± 1.23, respectively) than in mild disease (1.71 ± 0.78 and 1.69 ± 0.88, respectively, P < 0.05). Additionally, the UCEIS and EUS-UC scores in severe disease (7.68 ± 1.22 and 7.81 ± 0.90, respectively) were significantly higher than in moderate disease (P < 0.05). The UCEIS and EUS-UC scores were significantly and positively correlated with disease severity according to the modified Truelove and Witts score and Mayo score (P < 0.05). The UCEIS and EUS-UC scores after 2 mo of treatment (3.88 ± 0.95 and 4.01 ± 1.14, respectively) and after 6 mo of treatment (1.59 ± 0.63 and 1.64 ± 0.59, respectively) were lower than the respective scores before treatment (5.93 ± 1.79 and 6.04 ± 2.01) (P < 0.05). CONCLUSION: EUS can clarify the status of UC and accurately evaluate the treatment response, providing an objective basis for formulation and adjustment of the treatment plan.

mir-1 inhibits migration of gastric cancer cells.

Gastric cancer is the fourth most common malignancy world-wide that bears a high mortality by invasiveness and metastases. To this end, we examined the role of miR-1 in mobility and migration of gastric cancer cells. miR-1 was down-regulated and Sorcin, which supports invasion, was highly expressed in gastric cancer cell lines as compared to the control. The overexpression of miR-1 significantly inhibited the mobility and migration of gastric cancer cells, while, its knockdown exerted an oppoiste effect. In addition, while overexpression of miR-1 suppressed the expression of Sorcin, the siRNA knockdown of Sorcin significantly counteracted the effect of miR-1 inhibitor on cell invasion and migration of gastric cancer cells. A miR-1 mimic decreased while its inhibitor increased the MMP-7 and VEGF required for invasion. Taken together, the findings support the view that miR-1 controls the mobility and migration of gastric cancer cells and might be a therapeutic target for blocking gastric cancer invasion.

Nomogram predicting cancer-specific mortality in patients with esophageal adenocarcinoma: a competing risk analysis.

BACKGROUND: Many factors are reported to be related to the prognosis of patients with esophageal adenocarcinoma (EAC), but few reliable and straightforward tools for clinicians to estimate individual mortalities have been developed. This study aimed to evaluate the probability of cancer-specific death for patients with EAC and to build nomograms for predicting long-term cancer-specific mortality and overall mortality for EAC patients. METHODS: Between 2004 and 2013, a total of 20,623 patients were identified from the surveillance, epidemiology, and end results (SEER) database and randomly divided into training (N=14,436) and validation (N=6,187) cohorts. The cumulative incidence functions (CIFs) of EAC-specific death and other causes were evaluated at the 1st, 3rd, and 5th year after diagnosis. We integrated the significant prognostic factors to construct nomograms and subjected them to internal and external validation. RESULTS: The CIFs of EAC-specific survival at 1, 3, and 5 years after diagnosis were 60.9%, 37.1%, and 31.3%, respectively. Predictors for cancer-specific mortality for EAC comprised tumor grade, tumor extension, the involvement of lymph nodes, distant metastasis, surgery of primary site, insurance recode, and marital status. For overall mortality, it also included the predictor of age at diagnosis. The nomograms were well-calibrated and had good discriminative ability with concordance indexes (c-indexes) of 0.733, 0.728, and 0.728 for 1-, 3- and 5-year prognosis prediction of EAC-specific mortality respectively, and 0.726, 0.720, 0.719 for 1-, 3-, and 5-year prognosis prediction of overall mortality respectively. CONCLUSIONS: We proposed and validated the effective and convenient nomograms to predict cancer-specific mortality and the overall mortality for patients with EAC, which only require the basic information available in clinical practice.

Prognostic Value of Lymphovascular Invasion in Patients with Stage III Colorectal Cancer: A Retrospective Study.

BACKGROUND Lymph node metastasis and tumor progression depend on lymphovascular invasion (LVI). This study aimed to investigate the prognostic role of LVI in patients with stage III colorectal cancer (CRC) and to develop a prognostic nomogram. MATERIAL AND METHODS A retrospective study included 437 patients with stage III CRC. The impact of LVI on overall survival (OS) was analyzed with the Kaplan-Meier method and Cox regression model. A nomogram was constructed, and its predictive accuracy was evaluated using the concordance index (C-index) and the calibration plot. RESULTS LVI was found in 19.7% of cases of stage III CRCs and was significantly correlated with high tumor grade (poor differentiation) and advanced tumor stage (all P<0.05). Patients age, a family history of cancer in a first-degree relative, pre-treatment levels of carcinoembryonic antigen (CEA), prognostic nutritional index (PNI), histological tumor grade, tumor-node-metastasis (TNM) stage, and LVI were independent prognostic indicators (all P<0.05). Compared with the LVI(-) group, patients in the LVI(+) group showed a 1.748-fold increased risk of death (P=0.004) and a significantly reduced OS rate (P<0.001). In the prognostic nomogram, the C-index was significantly increased with LVI compared with the TNM stage alone (0.742 vs. 0.593; P<0.001). Calibration plots showed good fitness of the nomogram for prediction of survival. Comparison of the nomograms with and without LVI showed that inclusion of LVI improved the C-index from 0.715 to 0.742. CONCLUSIONS LVI was an indicator of more aggressive biological behavior and poor prognosis in patients with stage III CRC.

Fibrinogen-like protein 2 prothrombinase may contribute to the progression of inflammatory bowel disease by mediating immune coagulation.

Inflammation and coagulation are interdependent processes that enable each process to activate and propagate the other in inflammatory bowel disease (IBD). Thus, we investigated the role of a novel immune coagulant, fibrinogen-like protein 2 prothrombinase (FGL2), in patients and mice with IBD. 83 IBD patients and 40 normal controls were enrolled, and trinitro-benzene-sulfonic acid (TNBS)-induced colitis mice were used. Expression of FGL2 in the intestine was detected by immunohistochemistry. Using serial sections, staining was performed to detect tumor necrosis factor α (TNF-α) expression, and to demonstrate co-localization of FGL2 with macrophages and fibrin. Correlations between FGL2 expression with some common laboratory parameters were examined. FGL2 was seen primarily in inflammatory infiltrating cells, mainly macrophages, and microvascular vessels and had a strong co-localization with fibrin deposition. IBD patients and mice had increased expression of FGL2 compared with controls. Furthermore, FGL2 expression was correlated with intestinal and plasmatic TNF-α expression, mean platelet volume (MPV), platelet count (PLT), platelet-crit (PCT), and fibrinogen. Our data indicate that FGL2 may mediate immune coagulation in IBD patients. It may be considered as a novel molecule that contributes to the onset and development of IBD.

Effectiveness of Omega-3 Polyunsaturated Fatty Acids in Non-Alcoholic Fatty Liver Disease: A Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a clinical syndrome with the main characteristic of diffuse liver cells with fatty changes. The clinical evolution of NAFLD includes simple non-alcoholic fatty liver, non-alcoholic steatohepatitis (NASH), liver fibrosis and cirrhosis, and even hepatocellular carcinoma. METHODS AND FINDINGS: We conducted this review to identify the effectiveness of omega-3 polyunsaturated fatty acids (ω-3 PUFA) in NAFLD. We searched PubMed, Cochrane Library and Embase. All randomized controlled trials (RCTs) of ω-3 PUFA treatment for NAFLD were considered. Two reviewers assessed the quality of each study and collected data independently. Disagreements were resolved by discussion among the reviewers and any of the other authors of the paper. We performed a meta-analysis and reported summary estimates of outcomes as inverse variance (IV), fixed or random, with 95% confidence intervals (CIs). We included seven RCTs involving 442 patients (227 for the experimental group and 215 for the control group). All the patients were divided into two groups: one treated with ω-3 PUFA and the other was the control group (generally placebo). The demographics of the ω-3 PUFA and control groups were comparable. Beneficial changes in alanine aminotransferase (ALT) (IV 95% CI: -7.61 [-12.83 to -2.39], p = 0.004), total cholesterol (TC) (IV 95% CI: -13.41 [-21.44 to -5.38], p = 0.001), triglyceride (TG) (IV 95% CI: -43.96 [-51.21 to -36.71], p<0.00001) and high-density lipoprotein cholesterol (HDL-C) (IV 95% CI: 6.97 [2.05 to 11.90], p = 0.006) favored ω-3 PUFA treatment. Omega-3 PUFA tended towards a beneficial effect on aspartate aminotransferase (AST) (IV 95% CI: -6.89 [-17.71 to 3.92], p = 0.21), γ-glutamyl transferase (GGT) (IV 95% CI: -8.28 [-18.38 to 1.83], p = 0.11) and low-density lipoprotein cholesterol (LDL-C) (IV 95% CI: -7.13 [-14.26 to 0.0], p = 0.05). CONCLUSIONS: Supplementation with ω-3 PUFA is a practical and effective treatment for NAFLD to decrease ALT, TC and increase HDL-C, especially to decrease TG. Omega-3 PUFA also has a tendency toward a beneficial effect on AST, GGT and LDL-C. More high-quality, large RCTs are needed to validate our findings.

Infliximab Combined with Enteral Nutrition for Managing Crohn's Disease Complicated with Intestinal Fistulas.

Aim. This study was performed to evaluate the additional enteral nutrition (EN) in the efficacy of infliximab (IFX) compared with the conventional therapy in managing Crohn's disease (CD) complicated with intestinal fistulas. Methods. A total of 42 CD with intestinal fistulas were randomly divided into infliximab treatment group (n = 20) and conventional therapy group (n = 22). We evaluated the laboratory indexes, Crohn's disease activity index (CDAI), Crohn's disease simplified endoscopic score (SES-CD), and healing of fistula in the two groups before treatment, at 14 weeks, and at 30 weeks, respectively. Results. In the IFX treatment group, the CDAI score, the SES-CD, erythrocyte sedimentation rate, and C-reactive protein levels were significantly decreased during treatment compared with those before treatment. The body mass index and albumin levels were increased in both groups. Moreover, in the IFX treatment group, fistula healing was found in 8 at the 14th week and 18 at the 30th week, respectively, which was greater than that in the conventional therapy group. Conclusion. Our study suggested that infliximab combined with EN is an effective treatment for CD patients complicated with intestinal fistulas.

Tolvaptan regulates aquaporin-2 and fecal water in cirrhotic rats with ascites.

AIM: To investigate the role of tolvaptan in regulating aquaporin (AQP)-2 expression and fecal water content in cirrhotic rats with ascites. METHODS: Cirrhosis with ascites was induced in rats by repetitive dorsal injection of CCl4 for 14 wk. In total, 84 cirrhotic rats with ascites divided into three groups (vehicle, 3 mg/kg and 5 mg/kg tolvaptan), and then further divided into five subgroups (days 1, 2, 3, 4, and 5). Blood samples were obtained to measure vasopressin and sodium concentrations. Rats were killed and colonic mucosa was scraped for analysis of protein expression and AQP-2 transcriptional level. The whole layer was fixed for hematoxylin&eosin (HE) staining and feces were collected for determination of fecal water content. CONCLUSION: Compared with vehicle, vasopressin decreased significantly in the tolvaptan groups from day 2 to a similar level in each treatment group. AQP-2 showed significant upregulation in cirrhotic rats with ascites compared with an untreated control group (100% ± 22.9% vs 22.2% ± 10.23%, P < 0.01). After administration of tolvaptan, AQP-2 expression began to decrease significantly from day 2 in each treatment group, but no significant difference was finally found between the treatment groups. Fecal water content in the distal colon was increased by 5 mg/kg tolvaptan on day 1 (66.8% ± 9.3% vs 41.4% ± 6.3%, in the vehicle group, P < 0.05). Fecal water content returned to baseline at day 4 at the latest in both treatment groups, and did not correspond to the change in AQP-2 expression. HE staining of the colonic mucosa showed no mucosal damage related to tolvaptan. CONCLUSION: Upregulation of AQP-2 in the distal colon is found in cirrhotic rats with ascites. Tolvaptan inhibits its expression and may decrease water reabsorption and induce diarrhea.

Prophylactic use of transjugular intrahepatic portosystemic shunt aids in the treatment of refractory ascites: metaregression and trial sequential meta-analysis.

GOALS: The aim of this study was to explore whether prophylactic use of transjugular intrahepatic portosystemic shunt (TIPS) could aid in the treatment of refractory ascites on the basis of current randomized controlled trials. BACKGROUND: TIPS is more effective for refractory ascites versus large-volume paracentesis. At present, however, the survival advantage is not clear within populations of undifferentiated patients. STUDY: Correlative studies were searched through online journal databases, and a manual search was done from 1974 to 2012. Six trials involving 390 patients were included. RESULTS: TIPS could ameliorate refractory ascites on the basis of short-term analysis [odds ratio (OR) 8.66; 95% confidence interval (CI), 5.27-14.24] and long-term analysis (OR 6.07; 95% CI, 3.60-10.22). Hepatic encephalopathy (HE) appeared more common in the TIPS arm (OR 2.95; 95% CI, 1.87-4.66). Mortality in the 2 groups did not show any difference (OR 0.82; 95% CI, 0.46-1.50). Trial sequential analysis confirmed the effect of TIPS upon ascites control and upon the risk of HE recurrence, whereas insufficient trials were available to distinguish between the arms on mortality. Metaregression analysis showed that the level of urine sodium, serum bilirubin, and portal pressure gradient reduction value could be used as survival predictors. Subgroup analysis showed an elevated survival effect in TIPS (OR 0.45; 95% CI, 0.24-0.81), and patients survived longer with recurrent ascites (OR 0.40; 95% CI, 0.19-0.83). CONCLUSIONS: TIPS was confirmed to improve ascites control in both the short term and the long term. Although HE frequently appeared in the TIPS group, patients with better hepatic and renal function survived longer when they were treated with TIPS. Serum bilirubin and urine sodium could be used as pre-TIPS predictors for patient survival. Portal pressure gradient reduction values could be used as post-TIPS predictors of survival.

Correlation of fibrinogen-like protein 2 with progression of acute pancreatitis in rats.

AIM: To examine fibrinogen-like protein 2 (fgl2) expression during taurocholate-induced acute pancreatitis progression in rats and its correlation with pancreatic injury severity. METHODS: Forty-eight male Sprague-Dawley rats were randomly divided into the severe acute pancreatitis (SAP) group (n = 24) and the sham operation (SO) group (n = 24). Sodium taurocholate (4% at doses of 1 mL/kg body weight) was retrogradely injected into the biliopancreatic ducts of the rats to induce SAP. Pancreatic tissues were prepared immediately after sacrifice. At the time of sacrifice, blood was obtained for determination of serum amylase activity and isolation of peripheral blood mononuclear cells (PBMCs). Pancreatic tissue specimens were obtained for routine light microscopy including hematoxylin and eosin staining, and the severity of pancreatic injury was evaluated 1, 4 and 8 h after induction. Expression of fgl2 mRNA was measured in the pancreas and PBMCs using reverse transcription polymerase chain reaction. Expression of fgl2 protein was evaluated in pancreatic tissues using Western blotting and immunohistochemical staining. Masson staining was also performed to observe microthrombosis. RESULTS: At each time point, levels of fgl2 mRNAs in pancreatic tissues and PBMCs were higher (P < 0.05) in the SAP group than in the SO group. For pancreatic tissue in SAP vs SO, the levels were: after 1 h, 3.911 ± 1.277 vs 1.000 ± 0.673; after 4 h, 9.850 ± 3.095 vs 1.136 ± 0.609; and after 8 h, 12.870 ± 3.046 vs 1.177 ± 0.458. For PBMCs in SAP vs SO, the levels were: after 1 h, 2.678 ± 1.509 vs 1.000 ± 0.965; after 4 h, 6.922 ± 1.984 vs 1.051 ± 0.781; and after 8 h, 13.533 ± 6.575 vs 1.306 ± 1.179. Levels of fgl2 protein expression as determined by Western blotting and immunohistochemical staining were markedly up-regulated (P < 0.001) in the SAP group compared with those in the SO group. For Western blotting in SAP vs SO, the results were: after 1 h, 2.183 ± 0.115 vs 1.110 ± 0.158; after 4 h, 2.697 ± 0.090 vs 0.947 ± 0.361; and after 8 h, 3.258 ± 0.094 vs 1.208 ± 0.082. For immunohistochemical staining in SAP vs SO, the results were: after 1 h, 1.793 ± 0.463 vs 0.808 ± 0.252; after 4 h, 4.535 ± 0.550 vs 0.871 ± 0.318; and after 8 h, 6.071 ± 0.941 vs 1.020 ± 0.406. Moreover, we observed a positive correlation in the pancreas (r = 0.852, P < 0.001) and PBMCs (r = 0.735, P < 0.001) between fgl2 expression and the severity of pancreatic injury. Masson staining showed that microthrombosis (%) in rats with SAP was increased (P < 0.001) compared with that in the SO group and it was closely correlated with fgl2 expression in the pancreas (r = 0.842, P < 0.001). For Masson staining in SAP vs SO, the results were: after 1 h, 26.880 ± 9.031 vs 8.630 ± 3.739; after 4 h, 53.750 ± 19.039 vs 8.500 ± 4.472; and after 8 h, 80.250 ± 12.915 vs 10.630 ± 7.003. CONCLUSION: Microthrombosis due to fgl2 overexpression contributes to pancreatic impairment in rats with SAP, and fgl2 level may serve as a biomarker during early stages of disease.