Efficacy of mifepristone and GnRH-a in patients with endometriosis after operation

Objective: The effect of mifepristone and GnRH-a on patients with endometriosis after operation. Methods: 100 cases of endometriosis treated by laparoscopic surgery in our hospital from May 2017 to October 2019 were divided into GnRH-a group (34 cases), mifepristone group (33 cases) and non-drug group (33 cases) according to the numerical random method, and the treatment effect of the three groups was compared. Result: After the drug treatment, the cumulative recurrence rate of non misoprostone group and GnRH-a group was 18.18% and 21.21%, P > 0.05 between the two groups, and 33.33% between the two groups, P < 0.05. After treatment, FSH, LH and other hormone indexes in mifepristone group were compared with those before treatment (P > 0.05), while E2 levels were compared with those before treatment (P < 0.05); FSH, LH, E2 levels in GnRH-a group were compared with those before treatment (P < 0.05), and those in mifepristone group were compared with those after treatment (P < 0.05). After treatment, the complete remission rate of the patients in the non misoprostone group and the GnRH-a group were 51.52% and 55.88%, respectively, P > 0.05 for the comparison between the groups, and 36.36% for the comparison between the patients in the non misoprostone group and the GnRH-a group, P < 0.05 for the comparison between the two groups. There was no significant difference between the two groups (P > 0.05). Conclusion: Mifepristone and GnRH-a have good effect on patients with endometriosis after operation. They can effectively reduce the recurrence rate and adverse reactions after EMT.

Liver stiffness and insulin resistance in predicting recurrence for early stage hepatoma patients after curative resection

Curative resection is recommended for patient with early stage hepatocellular carcinoma (HCC), however, the prognosis is limited by high recurrence rate. This study was to investigate liver stiffness (LS) and metabolic factor in prediction of HCC recurrence for patients with early stage HCC who had undergone curative resection. Consecutive patients with suspicion of HCC who had undergone curative resection were prospectively enrolled. Transient elastography was performed to determine LS pre-operatively. The demographics, clinical characteristics and histological findings were recorded. All patients were followed up regularly until recurrence, death or last visit. Ninety-four patients with early stage HCC were enrolled. LS positively correlated with fibrosis stage (r = 0.666). In a median follow-up of 3.2 years, forty patients developed recurrences including 22 recurrences after 1-year post resection. The 5-year cumulative recurrence rate was 44.2%. LS was the independent factor associated with recurrence. Patients with LS > 8.5 kPa had higher 5-year cumulative recurrence rate (59.8% vs 25.1%, p = 0.007). For the prediction of recurrence after 1-year post resection, LS > 8.5 kPa (hazard ratio 2.72) and homeostatic model assessment for insulin resistance index (HOMA-IR) (hazard ratio 1.24) were independent factors in multivariate analysis. Those patients with both LS > 8.5 kPa and HOMA-IR > 2.3 had the highest recurrence rate after 1-year post resection.

Co-Upregulation of 14-3-3ζ and P-Akt is Associated with Oncogenesis and Recurrence of Hepatocellular Carcinoma

Background/Aims: 14-3-3ζ is involved in the regulation of PI3K/Akt pathway which is closely associated with carcinogenesis. However, the clinical significance of combined detection of 14-3-3ζ and p-Akt in hepatocellular carcinoma (HCC) remains unclear. Methods: Two-hundred pairs of HCC and adjacent liver specimens were subjected to tissue microarray. The association of 14-3-3ζ and p-Akt levels with the postoperative survival and recurrence in HCC patients was analyzed with univariate and multivariate methods. Moreover, the effects of 14-3-3ζ overexpression on the growth of HCC and the expressions of p-Akt and HIF-1α were assessed in a xenograft mouse model. Results: Elevated levels of 14-3-3ζ and p-Akt were detected in HCC and a positive correlation between the levels of 14-3-3ζ and p-Akt was verified. HCC patients with satellite nodules, microvascular invasion, portal vein tumor thrombosis, poor tumor differentiation and an advanced tumor stage tended to have higher levels of 14-3-3ζ and p-Akt. In addition, the postoperative 3-, 5-, and 7-year overall survival rates in HCC patients with 14-3-3ζhigh and p-Akthigh were significantly lower compared with those with 14-3-3ζlow and p-Aktlow, and the cumulative recurrence rate in HCC patients with 14-3-3ζhigh and p-Akthigh was significantly higher than that in those with 14-3-3ζlow and p-Aktlow. The multivariate Cox proportional hazard analysis indicated that concomitant upregulation of 14-3-3ζ and p-Akt was an independent factor that predicted poor survival and high recurrence in HCC patients. Furthermore, animal experiment showed that overexpression of 14-3-3ζ accelerated the growth of HCC xenograft tumors and induced the expressions of p-Akt and HIF-1α in vivo. Conclusion: Co-upregulation of 14-3-3ζ and p-Akt predicts poor prognosis in patients with HCC, and 14-3-3ζ-induced activation of the Akt signaling pathway contributes to HCC progression.

Naturally Occurring Autoantibodies to Oxidation-Specific Epitopes in Patients with Venous Thromboembolism

Background: Naturally occurring IgM autoantibodies (NAb) recognize oxidation-specific epitopes which are altered self structures on apoptotic cells, oxidized LDL, or vessel wall proteins. Oxidation-specific epitopes are proinflammatory antigens and potential markers for chronic inflammatory conditions. The risk of venous thromboembolism (VTE) is associated with (pro)inflammatory states such as dyslipoproteinemia, obesity or cancer. We hypothesize that natural antibodies may target epitopes which are also involved in the pathogenesis of VTE. In pursuing a “proof of concept”, we studied Nab in patients with a high venous thrombotic risk and evaluated their association with the risk of recurrent VTE. Methods: We determined Nab levels in 663 patients with a first unprovoked deep vein thrombosis and/or pulmonary embolism who were prospectively followed after discontinuation of anticoagulation in the Austrian Study on Recurrent Venous Thromboembolism, a multicentre cohort study. We excluded those with coagulation inhibitor deficiencies, lupus anticoagulant, cancer, pregnancy, long-term antithrombotic therapy, or homozygosity/double heterozygosity for factor V Leiden and/or the prothrombin mutation. Study end point was recurrent VTE. Nab target different oxidation-specific epitopes including phosphorylcholine-containing oxidized phospholipids which were generated by oxidation of low density lipoproteins (LDL) with CuSO4. Levels of IgM against oxidized (Ox) LDL were determined in venous blood drawn three weeks after discontinuation of anticoagulants by chemiluminescent enzyme linked immunoabsorbent assay and expressed as relative light units (RLU)/100ms. To determine the effect of anti-OxLDL IgM on the recurrence risk, models for time-to-event-data were used. Their direct effect on the recurrence risk was estimated by a cause-specific Cox proportional-hazards model, followed by a Fine-Gray model to account for competing events (death, restart of antithrombotics) and expressed by subdistribution hazard ratios (SHR). Anti-OxLDL IgM levels are given as median (25th, 75th percentiles). Results: Levels of anti-OxLDL IgM in patients with a first unprovoked VTE were 20.17 RLU/100ms (12.26, 34.72). Levels did not correlate with either age (rs=-0.16) or BMI (rs=-0.16). Levels correlated with sex [higher in women; 24.24 (14.6, 40.0) vs. 16.76 (10.46, 27.9) RLU/100ms, p<0.001]. 151 (22.8%) of 663 patients (mean age 48 years, 54% women) had recurrence during a median of 67 months. Anti-OxLDL IgM levels were higher in patients without recurrence [20.84 (12.32, 36.85) vs. 17.60 (11.97, 26.93) RLU/100ms, p=0.02]. For each doubling of anti-OxLDL IgM levels, the SHR of recurrence was 0.85 (95% CI 0.74-0.98; p = 0.02) and was 0.95 (0.82-1.1; p=0.5) after adjustment for sex. Patients with anti-OxLDL IgM levels within the second tercile (14.6 - <28.64 RLU/100ms) had a similar recurrence risk as patients with levels within the first tercile (<14.60 RLU/100ms) (SHR 0.93, 95% CI 0.65–1.33, p=0.7). The recurrence risk was significantly lower in patients with anti-OxLDL IgM levels within the third tercile (>28.64 RLU/100ms) (SHR 0.58, 95% CI 0.38–0.87, p<0.01). After adjustment for sex, the recurrence risk was still lower among patients with high anti-OxLDL IgM (SHR 0.75, 95% CI 0.49–1.14, p=0.2) but without statistical significance. We stratified patients according to an anti-OxLDL IgM level corresponding to the 60th percentile (14.6 RLU/100ms). The cumulative probability of recurrence after 5 years in patients with anti-OxLDL IGM > 60th percentile was 12.3% (8.5-16.9%) and was 20.3% (16.4-24.6%) among those with lower levels (p<0.001) (Figure). The corresponding SHR was 0.55 (0.38-0.78; p <0.001) for higher anti-OxLDL IgM and was 0.67 (95% CI 0.47-0.96; p=0.03) after adjustment for sex. Conclusions: An association exists between anti-OxLDL IgM and VTE recurrence which is consistent with a protective function of NAb via their ability to bind proinflammatory oxidation-specific epitopes. Figure: Cumulative recurrence rate in patients with VTE according to anti-OxLDL IgM levels below (blue line) or above (red line) the 60th percentile. Dotted lines are 95% CI. Figure:. Cumulative recurrence rate in patients with VTE according to anti-OxLDL IgM levels below (blue line) or above (red line) the 60th percentile. Dotted lines are 95% CI. Disclosures No relevant conflicts of interest to declare.