Value Analysis of Four-Dimensional Color Ultrasound Combined with Maternal Serological Index in Prenatal Screening for Fetal Anomalies.

Objective: This study aimed to assess the efficacy of combining four-dimensional (4D) color ultrasound with maternal serological index testing in prenatal screening for fetal anomalies. Methods: A retrospective analysis was conducted on data from 864 pregnant women who underwent prenatal checkups at the hospital between January 2020 and January 2021. During the mid-pregnancy period, serological tests were performed to determine levels of alpha-fetoprotein (AFP), free ß-subunit of human chorionic gonadotropin (Free-HCG ß), pregnancy-associated plasma protein A (PAPP-A), and vitamin B12 (VitB12). Additionally, 4D color ultrasound examinations were conducted. The gold standard for evaluation was the results of delivery or labor induction. AFP, Free-HCG ß, PAPP-A, and VitB12 levels were compared between the anomaly group and the normal group. The diagnostic efficacy of single and combined detection of serological indexes and 4D color ultrasound was analyzed, with the calculation of the areas under the curve (AUC) for different detection methods. Results: Among the 864 pregnant women, 44 cases (5.09%) exhibited fetal anomalies, while 820 cases (94.91%) did not. The anomaly group showed significantly higher multiples of the median (MOM) values for AFP and Free-HCG ß (P < .001) and significantly lower PAPP-A MOM and VitB12 levels (P < .001) compared to the normal group. The sensitivity of single detections for AFP MOM, Free-HCG ß MOM, PAPP-A MOM, VitB12, 4D color ultrasound, and combined detection were 63.64%, 68.18%, 65.91%, 54.55%, 77.27%, and 97.93%, respectively. The corresponding AUC values were 0.805, 0.829, 0.818, 0.761, 0.885, and 0.974. Conclusions: The combination of 4D color ultrasound with maternal serological index testing demonstrated high sensitivity in prenatal screening for fetal anomalies.

Clinical Value of Serum miR-124 and miR-200C Combined with Ultrasound NT in Screening Down Syndrome in Elderly Puerperae in the Second Trimester.

Objective: To evaluate the clinical value of serum miR-124 and miR-200C combined with ultrasound NT in screening Down syndrome (DS) in elderly puerperae during the second trimester. Methods: 84 elderly pregnant women at high risk of DS were included (DS group: 58, non-DS group: 26). Serum markers (uE3, ß-hCG, AFP, miR-124, and miR-200C) were measured. Differences in markers between groups were analyzed, and a prediction model was used for DS evaluation. Results: The DS group showed higher smoking, drinking, and radiation exposure rates (P < .05). MOM values of ß-hCG and AFP were higher, while MOM value of uE3 was lower in the DS group (P < .05). MiR-124 and miR-200C were up-regulated in the DS group (P < .05). The prediction model and ROC curve analysis indicated the diagnostic value of the markers for DS (AUC = 0.779, 0.817, 0.780, 0.884, 0.887, P < .05). MiR-124 had the highest diagnostic specificity. Conclusion: MiR-124 and miR-200C can serve as auxiliary serum markers for early screening of DS in elderly puerperae during the second trimester.

[Ramucirumab Treatment for Unresectable Advanced Hepatocellular Carcinoma-A Review of Clinical Trial Data and Real-World Evidence in Japan].

Ramucirumab was approved in June 2019 in Japan for the treatment of patients with unresectable advanced hepatocellular carcinoma(HCC)with serum alpha-fetoprotein ≥400 ng/mL, whose disease had worsened following chemotherapy. According to the Japan Society of Hepatology clinical practice guidelines for HCC revised in 2021, treatment with ramucirumab is recommended as second-line or subsequent systemic therapy for patients with Child-Pugh class A liver function and serum alpha-fetoprotein ≥400 ng/mL who have discontinued treatment with sorafenib because of radiologic progression or adverse events. To assess the efficacy and safety of treatment with ramucirumab in Japanese clinical practice for patients with unresectable advanced HCC, we reviewed evidence from original articles published after 2019, when ramucirumab was approved as a treatment for HCC in Japan. In addition, we evaluated a pooled data analysis of 2 global phase 3 studies(REACH and REACH-2), in which ramucirumab was administered as second-line therapy after the treatment of sorafenib in patients with unresectable advanced HCC, and the results of the REACH-2 expansion cohort of patients who received ramucirumab after systemic therapy other than sorafenib.

Therapeutic efficacy of nivolumab plus sorafenib therapy in patients with unresectable hepatocellular carcinoma.

BACKGROUND: Immune checkpoint inhibitor therapy is the backbone of numerous combination regimens for improving the therapeutic response of patients with hepatocellular carcinoma (HCC). We aimed to investigate the therapeutic efficacy of nivolumab plus sorafenib therapy in patients with unresectable HCC. METHODS: Patients with unresectable HCC who received sorafenib and followed at Taipei Tzu Chi Hospital from January 2016 to May 2022 were selected for this study, and those treated with nivolumab plus sorafenib and those with sorafenib alone were propensity score matched. The primary outcome was overall survival (OS) presented as a hazard ratio calculated using Cox proportional hazards regression models. RESULTS: In the analysis, 36 patients receiving nivolumab plus sorafenib and 36 receiving sorafenib alone were propensity score matched. The median OS for those receiving nivolumab plus sorafenib and sorafenib alone were 3.6 years and 1.2 years, respectively (p = 0.031). The hazard ratio of OS for nivolumab plus sorafenib compared to sorafenib alone was 0.36 (95 %CI, 0.19-0.70; p = 0.003). Furthermore, patients receiving nivolumab plus sorafenib with a baseline α-fetoprotein(AFP) < 10 ng/mL and early reduction in AFP had a 100 % objective response rate and disease control rate. CONCLUSION: In patients with unresectable HCC, nivolumab plus sorafenib resulted in better OS outcomes than sorafenib.

Sorafenib and hepatocellular carcinoma: is alpha-fetoprotein a biomarker predictive of tumor biology and primary resistance?

Background: Alpha-fetoprotein (AFP) is the only biomarker with proven prognostic value in advanced hepatocellular carcinoma. Preliminary data indicate crosstalk between AFP and VEGF signaling. Methods: The authors looked at 69 patients with advanced hepatocellular carcinoma who were previously tested for VEGFR2 expression, had available baseline AFP serum concentrations and were treated with sorafenib within clinical trials. Results: Shorter progression-free survival and overall survival were associated with increased AFP level and elevated VEGFR2 staining. At multivariate analysis of AFP level was the only independent prognostic factor for progression-free survival and overall survival. Conclusion: The authors' study confirms the adverse prognostic role of elevated baseline AFP and also suggests a possible role of AFP in primary resistance to sorafenib therapy.

Lay abstract Alpha-fetoprotein (AFP) is a plasma protein commonly used as a tumor marker for hepatocellular carcinoma. Sorafenib is a targeted therapy used to block the growth of cancer cells in several ways. It affects various proteins on the surface of cancer cells as well as targets inside the cell. Some of these targets are involved in tumor angiogenesis (growth of new blood vessels). In the present analysis, elevated AFP plasma levels before starting sorafenib therapy were correlated with inferior survival compared with patients with low AFP levels, thus suggesting a possible role of AFP in resistance to sorafenib therapy. Using a specific antibody, the authors also studied the expression on cancer cells of VEGFR2, which is a protein involved in angiogenesis and one of the targets of sorafenib. No correlation was found between AFP level and VEGFR2 expression. The underlying mechanisms involved in resistance to sorafenib therapy still need to be clarified and deserve further studies.

Systemic immune-inflammation index predicts prognosis of sequential therapy with sorafenib and regorafenib in hepatocellular carcinoma.

BACKGROUND: Regorafenib has shown promising results as a second-line therapy for patients with hepatocellular carcinoma (HCC) who progressed on sorafenib. Although there have been several data regarding the efficacy of sequential therapy with sorafenib and that of regorafenib in real-life, specific inflammation markers for predicting the prognosis have not been studied. This study aimed to investigate prognostic value of systemic inflammatory markers in patients with HCC who received sorafenib-regorafenib sequential therapy. METHODS: We retrospectively analyzed medical data of patients who received regorafenib for the treatment of HCC after sorafenib failure. Progression free survival (PFS) and overall survival (OS) were assessed using the Kaplan-Meier survival curves. Univariate and multivariate analyses were performed to analyze the factors associated with survival. RESULTS: A total of 58 patients who received at least one dose of regroafenib and fulfilled the eligibility criteria, good performance status (Eastern Cooperative Oncology Group [ECOG] 0-1) and preserved liver function (Child-Pugh-A), were included in the analysis. The median PFS was 3 months (95% confidence interval [CI] = 0.981-5.019) and the median OS was 8 months (95% CI = 5.761-10.239). Elevated systemic immune-inflammation index (SII ≥340) was independently associated with poor OS. In multivariate analysis, the SII (hazard ratio [HR] = 2.211, 95% CI = 1.089-4.489, P = 0.028) and alpha-fetoprotein (AFP) (HR = 2.750, 95% CI = 1.259-6.010, P = 0.011) were independent predictors of OS. CONCLUSION: Elevated SII is associated with poor OS in patients with HCC who received sequential therapy with sorafenib and regorafenib. In addition, when selecting a treatment strategy, the SII can be used in combination with the AFP level as a promising prognostic tool for HCC.

Post-treatment persistent alpha-fetoprotein elevation in a patient with testicular cancer.

BACKGROUND: Persistent alpha-fetoprotein elevation in a patient following orchiectomy and chemotherapy for non-seminomatous testicular germ cell tumor is a rare condition when persistence of the tumor and false positivity of tumor marker elevation has to be differentiated. This situation often leads to over-treatment and potential toxicity with adverse events which can be severe. CASE: A case of a patient with the abovementioned disease and course of treatment is presented. As no radiological signs of the disease were present and the level of alpha-fetoprotein was mild and stable, the tumor marker elevation was evaluated as false positive. Possible causes of the tumor marker elevation were identified as other serious diseases are known to cause such a false positivity. The level of alpha-fetoprotein remained unchanged despite alcohol abstinence and hepatoprotective treatment by silymarin. Hepatitis B and C serological tests were negative, and no other malignant tumor was identified. Finding of terminal ileum circular wall thickening and stratification with a reaction of surrounding visceral fat and lymph nodes persisting in CT scans suggests the presence of inflammatory bowel disease, possibly explaining the alpha-fetoprotein elevation. The patient has no evidence of the disease more than 14 months after the end of chemotherapy treatment with no change in the elevation of alpha-fetoprotein. CONCLUSION: After the treatment, when no other indication of testicular cancer than an elevated alpha-fetoprotein level is present, the patient should be managed by ongoing surveillance.

Lenvatinib is independently associated with the reduced risk of progressive disease when compared with sorafenib in patients with advanced hepatocellular carcinoma.

BACKGROUND AND AIMS: Recently, lenvatinib demonstrated non-inferiority to sorafenib in terms of overall survival (OS) in a randomized phase III study that was conducted at 154 sites in 20 countries. Here, we investigated treatment outcomes and safety of lenvatinib compared with sorafenib and identified independent predictors of poor outcomes, including shorter progression-free survival (PFS) and OS in Korean patients with unresectable hepatocellular carcinoma (HCC). METHODS: Patients with advanced HCC treated with lenvatinib or sorafenib at Yonsei Liver Center, Severance Hospital, Yonsei University College of Medicine between October 2018 to October 2019 were considered eligible. Response evaluation was performed according to the modified Response Evaluation Criteria in Solid Tumors. RESULTS: The lenvatinib arm had a significantly lower proportion of patients who received prior anti-HCC treatments (47.7% vs 78.7%; P < 0.001) than those in the sorafenib arm. Univariate analysis showed that ECOG 1 (vs 0), serum albumin, alpha-fetoprotein (AFP), previous anti-HCC treatments, and lenvatinib (vs sorafenib) were significant predictors of progressive disease (all P < 0.05). In the subsequent multivariate analysis, ECOG 1 (vs 0) (hazard ratio [HR] = 4.721, 95% confidence interval [CI] 1.371-16.259; P = 0.014), higher AFP level (HR = 1.000, 95% CI 1.000-1.000; P = 0.015), and lenvatinib treatment (vs sorafenib) (HR = 0.461, 95% CI 0.264-0.804; P = 0.006) independently predicted a higher probability of progressive disease. CONCLUSIONS: Patients treated with lenvatinib demonstrated significantly longer PFS than those treated with sorafenib. Furthermore, no significant differences were observed in mortality rates between the two groups, which indicated that lenvatinib is non-inferior to sorafenib in terms of OS.

Real world clinical practice in treating advanced hepatocellular carcinoma: When East meets West.

BACKGROUND AND AIMS: The Barcelona Clinic Liver Cancer (BCLC) stage C (BCLC C) of hepatocellular carcinoma (HCC) includes a heterogeneous population for which sorafeninb is one of the recommended therapies. We aim to evaluate the real world clinical treatment and survival of BCLC stage C patients in an Asian cohort. METHODS: This is a retrospective cohort study that enrolled 427 consecutive BCLC stage C patients diagnosed between 2011 and 2017 by using the HCC registry data for our hospital. All patients were managed via a multidisciplinary team (MDT) approach. RESULTS: Hepatitis B surface antigen positive was noted in 50.6% of the patients. The patients were classified as performance status (PS)1 alone (n = 83; 19.4%), PS2 alone (n = 23; 5.4%), or macrovascular invasion (MVI) or extrahepatic spread (EHS) (n = 321; 75.2%). The median overall survival (OS) was 11.0 months in the whole cohort. The most frequent treatments were transcatheter arterial embolization (TAE) in the PS1 (45.8%) and PS2 patients (52.2%) and sorafenib (32.4%) in the MVI or EHS patients. The independent prognostic factors were the PS, Child-Pugh class, MVI or EHS, alpha fetoprotein levels, and treatment type. CONCLUSIONS: We reported the real world management in BCLC stage C patients in an Asian cohort through the use of personalized management via a MDT approach.

Experience With Early Sorafenib Treatment With mTOR Inhibitors in Hepatocellular Carcinoma Recurring After Liver Transplantation.

BACKGROUND: Sorafenib (SOR) is currently used for hepatocellular carcinoma (HCC) recurring after liver transplantation (LT) when HCC is unsuitable for surgical/locoregional treatments. We evaluated safety and effectiveness of early introduction of SOR after HCC-recurrence. METHODS: All patients with HCC-recurrence after LT treated with SOR in 2 centers were included (January 2008 to June 2018). Baseline and on-treatment data were collected. RESULTS: Fifty patients early treated with SOR for HCC-recurrence after LT (74% mammalian target of rapamycin inhibitor [mTORi], 54% HCC-treated at baseline) were enrolled. During 7.3 (0.3-88) months of SOR, all patients had at least one adverse event (AE), 56% graded 3-4. SOR was reduced in 68%, being AEs the main cause of reduction, and discontinued in 84% (60% symptomatic progression, 33% AE). Objective response was obtained in 16% and stable disease in 50%. Median time to radiological progression was 6 months (95% confidence Interval [CI], 4-8). Thirty-three patients (69%) died, 94% for HCC progression. Median overall survival (OS) was 18 months (95% CI, 8-27); 5-year OS was 18% (95% CI, 4%-32%). Baseline predictors of OS were SOR+mTORi (hazard ratio [HR], 0.4; 95% CI, 0.2-0.9; P = 0.04), previous curative treatments (HR, 0.3; 95% CI, 0.2-0.7; P = 0.003) and alpha-fetoprotein > 100 ng/mL (HR, 2.5; 95% CI, 1.1-5.0, P = 0.02). At multivariate analysis, HCC curative treatment was the only independent predictor (HR, 0.4; 95% CI 0.2-1.0; P = 0.04). CONCLUSIONS: Early and combined treatment with SOR and mTORi resulted in a favorable safety profile, while its effectiveness should be confirmed by meta-analysis of previous studies or by larger studies. Curative treatment for HCC resulted the only independent predictor of OS.

Improved survival prediction and comparison of prognostic models for patients with hepatocellular carcinoma treated with sorafenib.

BACKGROUND: The 'Prediction Of Survival in Advanced Sorafenib-treated HCC' (PROSASH) model addressed the heterogeneous survival of patients with hepatocellular carcinoma (HCC) treated with sorafenib in clinical trials but requires validation in daily clinical practice. This study aimed to validate, compare and optimize this model for survival prediction. METHODS: Patients treated with sorafenib for HCC at five tertiary European centres were retrospectively staged according to the PROSASH model. In addition, the optimized PROSASH-II model was developed using the data of four centres (training set) and tested in an independent dataset. These models for overall survival (OS) were then compared with existing prognostic models. RESULTS: The PROSASH model was validated in 445 patients, showing clear differences between the four risk groups (OS 16.9-4.6 months). A total of 920 patients (n = 615 in training set, n = 305 in validation set) were available to develop PROSASH-II. This optimized model incorporated fewer and less subjective parameters: the serum albumin, bilirubin and alpha-foetoprotein, and macrovascular invasion, extrahepatic spread and largest tumour size on imaging. Both PROSASH and PROSASH-II showed improved discrimination (C-index 0.62 and 0.63, respectively) compared with existing prognostic scores (C-index ≤0.59). CONCLUSIONS: In HCC patients treated with sorafenib, individualized prediction of survival and risk group stratification using baseline prognostic and predictive parameters with the PROSASH model was validated. The refined PROSASH-II model performed at least as good with fewer and more objective parameters. PROSASH-II can be used as a tool for tailored treatment of HCC in daily practice and to define pre-planned subgroups for future studies.

Hepatoprotective effect of boldine against diethylnitrosamine-induced hepatocarcinogenesis in wistar rats.

Discovering the utmost effective and targeted chemotherapy for hepatocellular carcinoma is still a significant challenge. In the present study, diethylnitrosamine was used as a liver carcinogen and boldine a compound of boldo. We anticipated the hypothesis that boldine endow antiproliferative and promote apoptosis on hepatocarcinoma rats. We analyzed that boldine alters the tumor biomarkers and liver markers enzyme levels. Also, we determined boldine modulate the enzymatic and nonenzymatic antioxidant activities, as well as messenger RNA and protein expressions of Bcl2, Bax, and cleaved caspase 3 by reverse transcription polymerase chain reaction and Western blot analysis, respectively. It was also manifested by histopathology studies in liver tissues of HCC rats. Our finding suggested that boldine has antioxidant activity, and moreover, also contributes apoptotic nature by upregulating the protein expression of Bax, and cleaved caspase 3. Our data accomplishes that boldine a candidate drug has dynamic therapeutic activity and suitable for the treatment of HCC.

Sorafenib with concurrent multiple-line therapies improves overall survival in advanced stage hepatocellular carcinoma.

The efficacy of sorafenib in combination with transarterial chemoembolization (TACE) or multiple-line therapies in patients with advanced hepatocellular carcinoma (HCC) remains unclear. This study aimed to investigate the overall survival (OS) of patients with advanced HCC in response to different combination therapies.We analyzed the treatment and OS of 401 patients with Barcelona clinic liver cancer stage C HCC between 2012 and 2017. Mortality was analyzed using multivariate Cox regression, and OS was analyzed by the Kaplan-Meier method.The mean age was 59 years and males were predominant. During a median follow-up time of 8.6 months (range, 1-80 months), 346 (86.2%) patients died. In the multivariate Cox regression analysis, primary tumor size ≥5 cm, serum alpha-fetoprotein ≥200, and serum albumin ≥3.5 were significantly associated with mortality. In addition, compared with sorafenib alone, multiple-line treatments with sorafenib and multiple-line treatments without sorafenib yielded significantly decreased mortality. In the Kaplan-Meier analysis, sorafenib with TACE, multiple-line treatments with sorafenib, third-line treatments with sorafenib, and multiple-line treatments without sorafenib yielded a significantly better median OS than sorafenib alone.Sorafenib with concurrent multiple-line therapies significantly improved OS. These combination therapies will provide important information for immunotherapy combination with locoregional therapies in advanced HCC.

Efficacy of Sorafenib for the Treatment of Post-Transplant Hepatocellular Carcinoma Recurrence.

BACKGROUND: The role of sorafenib in patients with hepatocellular carcinoma (HCC) recurrence after liver transplantation (LT) has been rarely studied. The aim of this study was to evaluate the efficacy of sorafenib in post-LT era. METHODS: Consecutive patients with post-transplant HCC recurrence not eligible to resection or locoregional therapy were included. Patients receiving best supportive care (BSC) until 2007 were compared with those treated by sorafenib thereafter. RESULTS: Of a total of 65 patients, 20 patients received BSC and 45 received sorafenib. Clinical characteristics were similar between two groups except that sorafenib group received tacrolimus and mammalian target-of-rapamycin inhibitors more frequently than BSC group. Treatment with sorafenib conferred a survival advantage as compared with BSC for survival after recurrence (median, 14.2 vs. 6.8 months; P = 0.01). In multivariate analyses, high serum α-fetoprotein level, synchronous intrahepatic recurrence and distant metastasis at the time of recurrence, and BSC were independently associated with poorer survival after recurrence. Sorafenib treatment was associated with better survival after recurrence as compared with BSC (hazard ratio, 0.25; 95% confidence interval, 0.10-0.62; P = 0.002). In addition, sorafenib group showed tolerable toxicity in the post-transplant setting. CONCLUSION: Sorafenib may be beneficial in patients with post-transplant HCC recurrence.

Development of pre and post-operative models to predict early recurrence of hepatocellular carcinoma after surgical resection.

BACKGROUND & AIMS: Resection is the most widely used potentially curative treatment for patients with early hepatocellular carcinoma (HCC). However, recurrence within 2 years occurs in 30-50% of patients, being the major cause of mortality. Herein, we describe 2 models, both based on widely available clinical data, which permit risk of early recurrence to be assessed before and after resection. METHODS: A total of 3,903 patients undergoing surgical resection with curative intent were recruited from 6 different centres. We built 2 models for early recurrence, 1 using preoperative and 1 using pre and post-operative data, which were internally validated in the Hong Kong cohort. The models were then externally validated in European, Chinese and US cohorts. We developed 2 online calculators to permit easy clinical application. RESULTS: Multivariable analysis identified male gender, large tumour size, multinodular tumour, high albumin-bilirubin (ALBI) grade and high serum alpha-fetoprotein as the key parameters related to early recurrence. Using these variables, a preoperative model (ERASL-pre) gave 3 risk strata for recurrence-free survival (RFS) in the entire cohort - low risk: 2-year RFS 64.8%, intermediate risk: 2-year RFS 42.5% and high risk: 2-year RFS 20.7%. Median survival in each stratum was similar between centres and the discrimination between the 3 strata was enhanced in the post-operative model (ERASL-post) which included 'microvascular invasion'. CONCLUSIONS: Statistical models that can predict the risk of early HCC recurrence after resection have been developed, extensively validated and shown to be applicable in the international setting. Such models will be valuable in guiding surveillance follow-up and in the design of post-resection adjuvant therapy trials. LAY SUMMARY: The most effective treatment of hepatocellular carcinoma is surgical removal of the tumour but there is often recurrence. In this large international study, we develop a statistical method that allows clinicians to estimate the risk of recurrence in an individual patient. This facility enhances communication with the patient about the likely success of the treatment and will help in designing clinical trials that aim to find drugs that decrease the risk of recurrence.

Survival and tolerance to sorafenib in Child-Pugh B patients with hepatocellular carcinoma: a prospective study.

Sorafenib has been widely used to treat unresectable hepatocellular carcinoma (HCC) but most studies have been done in Child-Pugh A (CP-A) patients with well-preserved liver function. We evaluated the overall survival (OS) and tolerance to sorafenib in a large cohort of Child-Pugh B (CP-B) HCC patients as compared to CP-A HCC patients. We prospectively studied 130 patients with advanced HCC who started sorafenib between January 2011 and December 2015. Patients were classified as CP-A (n = 65) or CP-B (n = 65). The average OS for all 130 patients was 10 months. CP-A patients had a median survival rate significantly longer than CP-B patients: 12 months vs. 6 months. The OS found in our group of CP-B patients was 6.5 months, which is higher than that found in most studies done so far. When stratified, our CP-B patients had better OS than ever reported. The dose of the drug was interrupted due to adverse events (AEs) in 38 (29%) of the patients, of whom 20 (30%) were CP-A patients and 18 (28%) were CP-B patients. This real-life cohort of CP-B HCC patients treated with sorafenib had a higher survival than that described in the literature, with a satisfactory safety profile. Despite the high prevalence of severe AEs in CP-B patients, there were fewer treatment interruptions in this group, indicating that Child-Pugh B patients can tolerate treatment and may benefit from sorafenib.

Transarterial chemoembolization for unresectable hepatocellular carcinoma: A comparison of the efficacy and safety of 2 embolic agents.

The aim of this study was to compare the efficacy and safety of 2 different embolic agents, namely gelatin sponge particle (GSP) and Lipiodol, for transarterial chemoembolization (TACE) of unresectable hepatocellular carcinoma (HCC).We retrospectively reviewed 87 consecutive patients with unresectable HCC who underwent Lipiodol TACE with lobaplatin and 87 consecutive patients with unresectable HCC who underwent GSP TACE with lobaplatin between January 2013 and June 2017 in our institution as the initial treatment. Both groups were compared considering the clinical and laboratory outcomes and imaging findings before and after TACE. Tumor response and adverse events were also evaluated.There was significant difference in the rate of complete and overall response between the groups (P = .029 and .001, respectively), specifically when the tumor size was >5 cm (P = .001). The disease control rate was significantly better in the GSP group than in the Lipiodol group (94.3% vs. 86.4%, P = .011). The response differences in higher stages were significant between the 2 groups (P = .035 and .007, respectively). The grades of adverse events were also significantly different between the groups (P = .000).GSP-as an embolic agent in TACE for HCC-could significantly increase the rate of tumor response 1 month after treatment, especially in large tumors, without any significant increase in severe adverse events, when compared to Lipiodol.

Labor induction versus expectant management at early term in pregnancies with second trimester elevated human chorionic gonadotropin or alpha fetoprotein.

AIM: Elevated human chorionic gonadotropin (HCG) and alpha fetoprotein (AFP) have been linked to placental dysfunction and associated morbidities. We aimed to compare the induction of labor with expectant management at term in those pregnancies for the prevention of neonatal and maternal morbidities. METHODS: Women with second trimester HCG ≥ 2 and/or AFP ≥ 2 multiples of the median, without additional maternal or fetal complications, from their 38th gestational week were offered the choice of labor induction or expectant management. The primary outcomes were maternal composite outcome (composed of cesarean deliveries, pre-eclampsia or placental abruption) and neonatal composite outcome (composed of antenatal or neonatal death, Apgar score at 5 min < 7, admission to the neonatal intensive care unit, need for phototherapy, respiratory abnormalities, birth trauma or neonatal infection). RESULTS: Of 305 women, 124 women chose to undergo labor induction, and 181 women chose expectant management. The composite maternal outcome in the expectant management group was twice the rate of the labor induction group, although it did not reach statistical significance (18 [10%] vs 6 [5%]; P = 0.1; relative risk [expectant/induced] 2.04; 95% confidence interval 0.8-5.0). Increased rate of phototherapy led to increased neonatal composite outcomes in the labor induction group compared with the expectant management group (34 [27%] vs 27 [15%], respectively = 0.007). CONCLUSION: In pregnancies with elevated AFP and/or HCG, early term labor induction initiated a trend towards improvement in maternal outcome but increased the rate of mild neonatal morbidity. The statistical insignificance of the large effect on the maternal outcome might reflect the lack of statistical power. Further research is needed to address this limitation.

Changes in serum α-fetoprotein level predicts treatment response and survival in hepatocellular carcinoma patients and literature review.

BACKGROUND: Oxaliplatin-based chemotherapy is an alternative systemic treatment for patients with metastatic hepatocellular carcinoma (HCC) who were refractory or intolerant to sorafenib. To date, there have been no biomarkers reported to monitor the therapeutic efficacy and to predict the outcomes of HCC patients receiving oxaliplatin-based chemotherapy. METHODS: Eighty-one HCC patients with elevated baseline α-fetoprotein (AFP) levels and extrahepatic spreading who received oxaliplatin-based chemotherapy between 2012 and 2014 were retrospectively enrolled in this study. Two AFP tests were performed, at baseline and 2-4 weeks after the initiation of chemotherapy. The change in AFP levels was calculated for survival analysis. RESULTS: In the AFP decline group (decreased compared to baseline), the median progression-free survival (PFS) and overall survival (OS) were 7.0 months and 12.3 months, respectively. In the AFP nondecline group, the median PFS and OS were 2.3 months and 3.0 months, respectively. The difference in OS between the two groups was significant (p < 0.005). In the multivariate analysis for disease progression, the best response to chemotherapy and AFP decline were independent factors, with p values of 0.004 and 0.009, respectively. In the multivariate analysis for OS, the baseline Child-Pugh score, best response to chemotherapy, and AFP decline were independent prognostic factors, with p values of 0.01, 0.001, and 0.008, respectively. Additionally, the unit change in AFP level was predictive of PFS and OS with p values of 0.007 and 0.001, respectively. CONCLUSION: The change in AFP levels 2-4 weeks after initiating oxaliplatin-based chemotherapy is useful to predict treatment response and survival.