Median Alpha-fetoprotein Research Articles

Prothrombin induced by vitamin K absence or antagonist-II and alpha foetoprotein to predict development of hepatocellular carcinoma in Caucasian patients with hepatitis C-related cirrhosis treated with direct-acting antiviral agents.

Prothrombin induced by vitamin K absence or antagonist-II (PIVKA-II) and alpha fetoprotein (AFP) are biomarkers for hepatocellular carcinoma (HCC). However, their performance in patients with cirrhosis related to hepatitis C virus (HCV) treated with direct-acting antiviral agents (DAA) is unknown. To evaluate PIVKA-II and AFP as HCC predictors in DAA-treated patients with HCV-related cirrhosis METHODS: In this single centre study, patients with cirrhosis from chronic HCV infection and with a sustained virological response (SVR) to DAA were tested for PIVKA-II and AFP (Fujirebio, Japan) at the start of DAA treatment (baseline), end of treatment (EOT) and at HCC diagnosis. We included 400 patients with mean age 65 (24-92); 56% were men. From baseline to EOT, PIVKA-II did not change (35 vs 35mAU/mL, P=0.43) while AFP significantly decreased (12 vs 6ng/mL, P<0.0001). After 52 (3-66) months from baseline, 34 (8.5%) patients developed de novo HCC; median AFP 9 (2-12868) ng/mL and PIVKA-II 80 (22-1813) mAU/mL. EOT-PIVKA-II (HR 3.05, P<0.0001) and AFP (HR 2.77, P=0.001) independently predicted HCC together with diabetes (HR 6.12, P<0.001) and GGT (HR 1.01, P=0.03). The 4-year cumulative probability of HCC was 24% vs 2% in patients with EOT-PIVKA-II > or ≤41mAU/mL (P<0.0001), and 26% vs 9% for EOT-AFP > or ≤15ng/mL (P=0.02). By combining EOT-PIVKA-II and AFP, the 4-year probabilities of HCC were 3% in patients testing negative for both markers, 18% in patients positive for both, and 38% in patients positive for at least one (P<0.0001). In patients with HCV-related cirrhosis treated with DAA, PIVKA-II and AFP independently predicted HCC, while their combination improved risk stratification.

Early Changes in Alpha-Fetoprotein Are a Useful Predictor of Efficacy of Atezolizumab plus Bevacizumab Treatment in Patients with Advanced Hepatocellular Carcinoma

Introduction: The aim of this study was to investigate the early changes in alpha-fetoprotein (AFP) and des-γ-carboxy prothrombin (DCP) levels in patients with advanced hepatocellular carcinoma (HCC) treated with atezolizumab plus bevacizumab and to evaluate the relationship between changes in these tumor markers and treatment efficacy. Methods: Of 58 consecutive patients who started atezolizumab plus bevacizumab at our institution, 50 patients with information on antitumor response obtained at 6 weeks after therapy were enrolled in this study and their treatment outcomes were retrospectively evaluated. Results: According to the Response Evaluation Criteria in Solid Tumors at 6 weeks, the objective response (OR) rate was 22.0% and the disease control (DC) rate was 78.0%. In patients who achieved OR at 6 weeks, median AFP and DCP ratios at weeks 1, 2, 3, and 6 were significantly lower than those in patients who did not achieve OR. AFP ratios in patients who did not achieve DC at 6 weeks (Non-6W-DC group) were significantly higher than in those who achieved DC at week 6 (6W-DC group). Median overall survival in the Non-6W-DC group was significantly shorter than in the 6W-DC group (156 days vs. not reached, p = 0.0008). An AFP ratio of 1.4 or higher at 3 weeks had a specificity of 88.0% and a sensitivity of 88.9% for predicting Non-6W-DC. Median progression-free survival was significantly shorter in patients with an AFP ratio of 1.4 or higher at 3 weeks than in those with an AFP ratio of <1.4 (42 days vs. 210 days, p = 0.0003). Conclusion: Early changes in AFP might be useful for predicting the antitumor efficacy of atezolizumab plus bevacizumab in patients with advanced HCC. An AFP ratio of 1.4 or higher at 3 weeks might be an early predictor of refractoriness to atezolizumab plus bevacizumab therapy.

VALUE OF SERUM MIDKINE LEVEL IN PATIENTS WITH LIVER CIRRHOSIS AND HEPATOCELLULAR CARCINOMA

Background: Hepatocellular carcinoma (HCC) is the fourth most common cause of cancer-related death worldwide. Risk factors for HCC include chronic hepatitis B and hepatitis C, alcohol addiction, metabolic liver disease and exposure to dietary toxins such as aflatoxins and aristolochic acid. Objective: To determine the value of serum Medkine level as a potential biomarker for patients with hepatocellular carcinoma. Patients and methods: This study was conducted at the Gastroenterology and Hepatology Unit, Department of Internal Medicine Al-Azhar and Misr University for Science and Technology. 90 Egyptian patients were recruited and were divided into 3 Group I included 30 patients with liver cirrhosis, HCC was excluded in these patients at time of recruitment in the study, exclusion of HCC was based on the absence of any hepatic focal lesion in abdominal ultrasonography scanning. Group II included 40 patients with HCC. Diagnosis of HCC was based on the appearance of typical vascular pattern of enhancement in triphasic spiral CT scan of the abdomen. Control Group included 20 age and sex-matched apparently healthy subjects. Results: Different liver function tests showed no statistically difference between two groups except for ALK. Ph and gamma glutamyltransferase (GGT) which were significant higher in group II than group I. There was a highly statistically significance difference regarding alpha-fetoprotein (AFP) which was higher in group II than group I and control group. Serum AFP levels were found to be significantly correlated with larger tumor size in this study. In addition, patients with advanced-stage hepatocellular carcinomas had significantly higher median AFP serum levels (BCLC B/C) than that of early-stage tumors (BCLC 0/A) (237ng/mL versus 23ng/mL). However, no significant correlation was found between serum midkine (MDK) levels with tumor size, number or serum levels of AFP, and no significant association was found between serum MDK levels and BCLC stages. The best cutoff values for MDK and AFP to discriminate HCC cases from those with liver cirrhosis were 0.39 and 10ng/mL, respectively, with sensitivities (90% versus 77.5%), specificities (60% versus 80%). The overall diagnostic performance of MDK for HCC diagnosis was much better than that of AFP. On comparing the sensitivities and specificities of MDK at the cutoff 0.39ng/mL to those of AFP at different cutoff values (10 and 400), the overall diagnostic performance of MDK for HCC diagnosis was much better than that of AFP. Conclusion: Alpha-fetoprotein and midkine may have a complementary role in hepatocellular carcinoma surveillance and screening. Midkine increased the diagnostic yield in alpha-fetoprotein -negative hepatocellular carcinoma and the presence of either elevated alpha-fetoprotein or midkine increased the sensitivity of hepatocellular carcinoma detection. Midkine was also superior to alpha-fetoprotein in the diagnosis of NASH-related hepatocellular carcinoma and this finding postulated an exciting novel role for midkine in NASH-related carcinogenesis.

Surgical Resection of Huge Hepatocellular Carcinoma. Prognostic Factors and Outcomes in a Mexican Cohort Study

Surgery is the best choice for curative treatment for hepatocellular carcinoma (HCC), that includes liver resection (LR) or liver transplantation (LT). Tumors larger than 10 cm are considered huge HCC. Huge HCC doesn't fit any criteria for LT. Although surgical resection may be associated with higher morbidity it's still the best chance of survival in this subgroup of patients. The purpose of our study is to analyze prognostic factors and outcomes in a Mexican population. We analyzed patients who underwent LR for huge HCC between January 2015 to January 2021. Prognostic factors included in the study were age, HCC size, serum alpha fetoprotein (AFP) and vascular invasion. Only patients with Child-Pugh grade A in absence of extrahepatic disease was offered major LR. The future liver remnant volume was calculated by CT scan volumetry. Morbidity, disease free-survival and overall survival was evaluated. Fifty two patients underwent major LR: male 30 (57.6%) and female 22 (42.3%). The median age was 65 years (range, 25-76 years), median HCC size was 16 cm (range, 14-45 cm), median AFP was 85 ng/mL (range, 18-19,500 ng/mL). Lymphovascular invasion was found in 58% of liver specimens. The overall morbidity was 12% and perioperative mortality was seen in 1 (1.95%) due to heart failure. The overall 1-year and 3-year survival were 88.4% and 51.9% respectively. Factors of adverse outcome after major LR in patients with huge HCC were the presence of lymphovascular invasion, AFP > 1,000 ng/mL, and age > 65 years.

Feasibility of SBRT for hepatocellular carcinoma in Brazil - a prospective pilot study.

The aim of the study was to evaluate the feasibility and safety of stereotactic body radiotherapy (SBRT) for the treatment of hepatocellular carcinoma in Brazil. SBRT is an evolving treatment in HCC patients not candidates to other local therapies. Its adoption in clinical practice has been heterogeneous, with lack of data on its generalizability in the Brazilian population. We conducted a prospective pilot study involving HCC patients after failure or ineligibility for transarterial chemoembolization. Patients received SBRT 30 to 50 Gy in 5 fractions using an isotoxic prescription approach. This study is registered at clinicaltrials.gov NCT02221778. From Nov 2014 through Aug 2019, 26 patients received SBRT with 40 Gy median dose. Underlying liver disease was hepatitis C, hepatitis B and alcohol-related in, respectively, 50%, 23% and 19% of patients. Median lesion size was 3.8 cm (range, 1.5-10 cm), and 46% had multiple lesions. Thirty-two percent had tumor vascular thrombosis; median pretreatment alpha-fetoprotein (AFP) was 171.7 ng/mL (range, 4.2-5,494 ng/mL). 1y-local progression-free survival (PFS) was 86% (95% CI: 61% to 95%), with higher local control in doses ≥ 45Gy (p = 0.037; HR = 0.12). 1y-liver PFS, distant PFS and OS were, respectively, 52%, 77% and 79%. Objective response was seen in 89% of patients, with 3 months post-SBRT median AFP of 12 ng/mL (2.4-637 ng/mL). There were no grade 3 or 4 clinical toxicities. Grade 3 or 4 laboratory toxicities occurred in 27% of patients. SBRT is feasible and safe in patients unresponsive or ineligible for TACE in Brazil. Our study suggests doses ≥ 45 Gy yields better local control.

Clinical Features and Treatment Outcomes in Patients with Extracranial Germ Cell Tumors: A Tertiary Centre Experience

Background: Germ cell tumors are histologically heterogeneous group of tumors with high cure rate if diagnosed early. The aim of study was to evaluate the extracranial germ cell tumors presenting to our institute with regards to gender, age, clinical presentation, pathology, management, acute toxicity and survival. Material and Methods: This retrospective study was conducted at Department of Radiation Oncology, All India Institute of Medical Sciences (AIIMS), Patna. Results: Total of 75 patients with germ cell tumor (GCT) were analysed. Distribution of males and females were 50.7% and 49.3% respectively. The median age of presentation of males and females was 31 years and 15 years respectively. At the time of presentation, 47.3% male and 16.2% of female patients had metastatic disease. The median alpha-fetoprotein (AFP), beta subunit of human chorionic gonadotropin (βHCG), and lactate dehydrogenase (LDH) were 112 ng/ml, 668 mIU/ml, and 550 U/L respectively. At median followup of 34 months, 32% of the patient developed recurrence. The median disease-free survival (DFS) and overall survival (OS) were 57 months and 71 months respectively. Multivariate analysis showed that the histological subtypes (p = 0.001) and risk groups (p = 0.029) were the independent prognostic factors for DFS, while metastatic status at presentation (p = 0.037), upfront surgical intervention (p =0.039), and histopathological subtypes (p = 0.009) were the independent prognostic factor for OS. Conclusion: GCT is primarily a disease of young and adolescents. Early diagnosis, well-orchestrated multidisciplinary management leads to favourable outcome and survival.

Prognostic Value of Alpha-Fetoprotein in Patients Who Achieve a Complete Response to Transarterial Chemoembolization for Hepatocellular Carcinoma.

PurposeAlpha-fetoprotein (AFP) is a prognostic marker for hepatocellular carcinoma (HCC). We investigated the prognostic value of AFP levels in patients who achieved complete response (CR) to transarterial chemoembolization (TACE) for HCC.Materials and MethodsBetween 2005 and 2018, 890 patients with HCC who achieved a CR to TACE were recruited. An AFP responder was defined as a patient who showed elevated levels of AFP (>10 ng/mL) during TACE, but showed normalization or a >50% reduction in AFP levels after achieving a CR.ResultsAmong the recruited patients, 569 (63.9%) with naïve HCC and 321 (36.1%) with recurrent HCC after complete resection were treated. Before TACE, 305 (34.3%) patients had multiple tumors, 219 (24.6%) had a maximal tumor size >3 cm, and 22 (2.5%) had portal vein tumor thrombosis. The median AFP level after achieving a CR was 6.36 ng/mL. After a CR, 473 (53.1%) patients experienced recurrence, and 417 (46.9%) died [median progression-free survival (PFS) and overall survival (OS) of 16.3 and 62.8 months, respectively]. High AFP levels at CR (>20 ng/mL) were independently associated with a shorter PFS [hazard ratio (HR)=1.403] and OS (HR=1.284), together with tumor multiplicity at TACE (HR=1.518 and 1.666, respectively). AFP non-responders at CR (76.2%, n=359 of 471) showed a shorter PFS (median 10.5 months vs. 15.5 months, HR=1.375) and OS (median 41.4 months vs. 61.8 months, HR=1.424) than AFP responders (all p=0.001).ConclusionHigh AFP levels and AFP non-responders were independently associated with poor outcomes after TACE. AFP holds clinical implications for detailed risk stratification upon achieving a CR after TACE.

Abstract 2346: Clinical manifestation, staging and prognosis of hepatocellular carcinoma in Gambian patients

Abstract INTRODUCTION: The clinical manifestations of patients with Hepatocellular carcinoma (HCC) have changed significantly in the last decades in countries that have adopted screening tests. In developing countries due to the rarity of surveillance/screening programs coupled with diagnostic challenges of HCC, most patients present late. OBJECTIVE: To evaluate the clinical manifestations, staging and prognostic factors of HCC in Gambian patients. METHODS: Patients with suspected HCC referred to the main liver clinic at the Medical Research Council were recruited from June 2011 to September 2019. The diagnostic criteria for HCC comprised of ultrasound demonstration of liver mass greater than or equal to 2 cm combined with alpha-fetoprotein (AFP) level of greater than or equal to 200 ng/ml and/or histopathological confirmation. Clinical, radiological, fibroelastrography and laboratory data were collected in all patients. Kaplan -Meier, univariate and multivariate cox regression analyses were used to assess factors related to survival in these patients. RESULTS: Five hundred and seventy three patients were recruited into the study. The mean age of HCC patient was 40 years and mostly males (81%). The most common constitutional symptoms were weight loss (84.1%), easy fatiguability (86.3%) while the most common gastrointestinal symptoms were early satiety (79.9%) and abdominal pain (81.8%). The most common signs were hepatomegaly (76.6%) and abdominal tenderness (48.1%). Multi-focal lesions were more common on ultrasound scan (63.4%) compared to single lesions, and the median fibroelastography score was 74 kpa in these patients. Hepatitis B surface Antigen (HBsAg) carriage was present in 69.6% of HCC patients with a median AFP of 4044 ng/ml. WHO performance status 1, BCLC stage C and Child-Pugh stage A were most common among this patient group. HBsAg-positive patients with HCC were mostly males, much younger, most likely to have jaundice, dark urine, abdominal tenderness, raised transaminases, haemoglobin and international normalised ratio (INR) levels and decreased platelet counts. HCC patients who were HBsAg-negative tended to be older, more likely to have weight loss, easy fatiguability, hypertension and had a much better median survival (42.5 days vs 35 days). Both prognostic staging systems had good stratification of survival. Independent factors that affect survival were abdominal pain, jaundice at the time of presentation, hyponatremia and hypoglycaemia. CONCLUSIONS: HBV is a significant factor in HCC in The Gambia. Young males who are the main work-force are disproportionately affected, are more likely to be symptomatic and have much shorter survival. In resource limited countries like The Gambia where screening programmes and therapeutic interventions are limited, the prognosis and survival of patients with HCC patients is poor, emphasizing the need for early preventative strategies. Citation Format: Sheikh Omar Bittaye, Ramou Njie, Muhammed Tekanyi, Abubacarr Kambi, Saydiba Tamba, Gibril Fatty, Yusupha Bah, Abdoulie Jatta, Lamin Sanneh, Momodou Musa Sisawo. Clinical manifestation, staging and prognosis of hepatocellular carcinoma in Gambian patients [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2346.

Experience With LDLT in Patients With Hepatocellular Carcinoma and Portal Vein Tumor Thrombosis Postdownstaging.

Median survival in patients with hepatocellular carcinoma (HCC) and portal vein tumor thrombosis (PVTT) is 2-6 months; conventionally liver transplantation is contraindicated. We studied outcomes following living donor liver transplantation (LDLT) post-PVTT downstaging (DS) with stereotactic body radiotherapy (SBRT), and tumor ablation (with transarterial chemo- or radio-embolization). Of 2348 consecutive LDLTs, 451 were for HCC, including 25 with PVTT (mainly Vp1-3) after successful DS and 20 with Vp1/2 PVTT without previous treatment. DS was attempted in 43, was successful in 27 (63%), and 25 underwent LDLT. Median alpha fetoprotein (AFP) at diagnosis and pre-LDLT were 78.1 ng/mL (3-58 200) and 55 ng/mL (2-7320), respectively. Mean DS to LDLT time was 10.2 weeks (5-16). Excluding 2 postoperative deaths, 1- and 5-year overall survival (OS) and recurrence-free survival (RFS) were 82%, 57%, and 77%, 51%, respectively, comparable to survival in 382 HCC patients without PVTT undergoing upfront LDLT (5-y OS 65%, P = 0.06; RFS 66%, P = 0.33, respectively). There was a trend toward better OS in DS+LDLT versus non-DS LDLT group (5-y OS/RFS-48%/40%). OS was significantly better than in HCC-PVTT patients receiving no intervention or palliative Sorafenib alone (1-y OS of 0%) or Sorafenib with TARE/SBRT (2-y OS of 17%) at our center during the study period. Initial AFP <400 ng/mL and AFP fall (initial minus pre-LDLT) >2000 ng/mL predicted better RFS; Grade III/IV predicted worse OS in DS patients. HCC patients with PVTT can achieve acceptable survival with LDLT after successful DS. Low initial AFP level, a significant drop in AFP with DS and low tumor grade, favorably influence survival in these patients.

Hepatocellular Carcinoma Brain Metastases: A Single-Institution Experience

Brain metastases (BMs) from hepatocellular carcinoma (HCC) are rare, with a paucity of reported cases. In the present retrospective cohort report, we assessed the proportion of BMs arising from HCC and characterized the related details, including patient demographics, clinical characteristics, treatment modalities, and survival outcomes. We retrospectively identified and reviewed the medical records of 14 patients with BMs from HCC seen at our institution from 2008 to2018. Among all patients with BMs, the proportion originating from primary liver cancer was 0.39%. In every case (n= 14), the liver cancer was HCC. The median age at the BM diagnosis was 64 years (range, 37-82 years). The median alpha-fetoprotein level at the diagnosis of BM was 540 ng/mL (range, 3-10,000 ng/mL). The median interval from the HCC diagnosis to the development of BMs was 31.1 months (range, 3.17-107 months). Of the 14 patients, 8 (57%) had had metastases to the brain parenchyma and 6 had had skull or dural metastases. For patients with brain parenchymal metastases, the median number of metastases was 1 (range, 1-5). Of the 14 patients, 13 have died, with a median overall survival after the BM diagnosis of 2.83 months (range, 0.430-24.0 months). At the latest follow-up examination, the survival for the 14th patient was 142 months after the BM diagnosis. Resection of BMs with radiosurgery was associated with increased survival compared with radiosurgery alone (10.9 months vs. 2.8 months; P= 0.04). HCC BMs are rare and constitute a small fraction of the total incidence of BMs. The prognostic data we have provided can aid medical providers in caring for patients with HCC BMs.

The Modified Response Evaluation Criteria in Solid Tumors (RECIST) Yield a More Accurate Prognoses Than the RECIST 1.1 in Hepatocellular Carcinoma Treated with Transarterial Radioembolization.

Background/AimsThe Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and modified RECIST (mRECIST) criteria have been used to assess treatment responses for hepatocellular carcinoma (HCC) patients. We investigated which criteria provides better survival predictions in HCC patients treated with transarterial radioembolization (TARE).MethodsIn total, 102 patients with unresectable intrahepatic HCC, who were treated with TARE between 2012 and 2017, were reviewed retrospectively. The treatment response after TARE was evaluated at 1, 3, and 6 months by the mRECIST and RECIST 1.1. Responders were defined as patients with complete or partial responses by each criterion.ResultsThe median age of 83 men and 19 women was 64.3 years. The median alpha-fetoprotein and des-gamma-carboxy prothrombin levels were 37.1 ng/mL and 1,780.0 mAU/mL, respectively. The median maximal tumor size was 8.3 cm, and multiple tumors were observed in 36 patients (35.3%). During the follow-up period (median, 20.7 months), 21 patients (20.6%) died, with a mean survival time of 55.5 months. The cumulative survival rate was 96.1% at 6 months and 89.3% at 12 months. Responders, defined by the mRECIST at 1, 3, and 6 months after TARE, showed better survival outcomes than nonresponders (hazard ratio [HR]=5.736, p=0.008 at 1 month; HR=3.145, p=0.022 at 3 months, and HR=2.887, p=0.061 at 6 months). The survival rates of responders and nonresponders defined by the RECIST 1.1 were similar (all p>0.05).ConclusionsResponse evaluations that use the mRECIST provide more accurate prognoses than those that use the RECIST 1.1 in HCC patients treated with TARE.

Value of serum alpha-fetoprotein for the prognostic evaluation of hepatitis B virus-related acute-on-chronic liver failure treated with artificial liver

Objective: To investigate the value of alpha-fetoprotein (AFP) level on survived hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) patients treated with artificial liver. Methods: Clinical indicators of HBV-ACLF patients who were previously treated with plasma exchange-based artificial liver at our department were retrospectively collected. The difference of serum AFP level between the survival and the death group was compared at 30, 90 and 180 days after artificial liver treatment. The ROC curves of the subjects were plotted, and the sensitivity and specificity of AFP for the survival prediction of the patients at 30, 90 and 180 days after artificial liver surgery were calculated. AFP was divided into a high AFP group and a low AFP group using median value. AFP and postoperative survival predictive value at 30, 90, and 180 days were analyzed. Results: A total of 93 cases were included in this study. The AFP of the survival group at 30, 90, and 180 days was (231.0 ± 286.2) ng / ml, (237.69 ± 297) ng / ml, (229.44 ± 286.46) ng/ml, and the death group was (76.4 ± 104.7) ng/ml, (103.13 ± 116.99) ng / ml, (136.34 ± 2.9.29) ng/ml, respectively. AFP of the death group was significantly lower than the corresponding survival group (P < 0.05). Receiver operating characteristic (ROC) curve analyses indicated that the area under the curve (AUC) and its 95% confidence interval at 30, 90, and 180 days after artificial liver surgery were 0.739 (0.611 ~ 0.867), 0.675 (0.550 ~ 0.80), 0.653 (0.524 ~ 0.781), respectively. The median serum AFP value was 110 ng/ml, and the survival analysis showed that the survival time of the high AFP group was significantly higher than the low AFP group at 30 d (P = 0.01), 90 d (P = 0.04) and 180 d (P = 0.03) after artificial liver surgery. Conclusion: Serum AFP can be used as a predictor of survival for HBV-ACLF patients after artificial liver therapy and its clinical value needs to be further verified by the larger sample size.

Correlating serum alpha-fetoprotein in hepatocellular carcinoma with response to Yttrium-90 transarterial radioembolization with glass microspheres (TheraSphere™)

BackgroundFew studies have assessed the relationship between serum alpha-fetoprotein (AFP) and yttrium-90 (Y-90) radioembolization response in hepatocellular carcinoma (HCC). The objective of the study was to evaluate whether peri-procedural serum AFP was correlated with Y-90 therapy response in HCC. MethodsPatients undergoing Y-90 radioembolization with glass microspheres (TheraSphere™) for HCC between 2006 and 2013 at a single center were evaluated. The relationship between AFP and 6-month radiographic improvement (complete or partial response by modified RECIST criteria), overall (OS), and disease-specific survival (DSS) were analyzed. ResultsSeventy-four patients underwent a total of 124 Y-90 infusions. Median age was 65 years, median AFP was 37 ng/mL (range: 2–112,593 ng/mL) and median model for end-stage liver disease score was 6.2 (range:1.8–11.2). Increased AFP was not associated with radiographic improvement (odds ratio (OR) = 0.99, 95% confidence interval (CI) = 0.75–1.30, p = 0.92). Median OS was 15.2 months and was increased in patients with low AFP compared to high AFP (30.8 months vs. 7.8 months, p < 0.001). On multivariable regression analysis, increased AFP was associated with worse OS (OR = 1.11, 95%CI = 1.01–1.22, p = 0.034) and DSS (OR = 1.13, 95%CI = 1.03–1.25, p = 0.018). ConclusionPre-infusion AFP independently predicted survival after Y-90 treatment for HCC, but not radiographic response, and can help guide treatment decisions.

Impact of Tumor Size as a Prognostic Factor After One Stage Liver Resection for Solitary Hepatocellular Carcinoma in Cirrhotic Patients

Aim: This study is to assess tumor size as a prognostic factor predicting outcomes after one staged hepatectomy for cirrhotic patients with solitary hepatocellular carcinoma. Patients and methods: The study included 41 patients with single hepatocellular carcinoma (HCC) of different sizes who underwent single-stage hepatectomy. Patients were divided according to their tumor size into 2 groups, group A involved patient with tumors ≤ 5 cm and group B which involved patients with tumors > 5 cm. The effect of the tumor size on overall survival and disease-free survival was studied in both groups. Results: The mean age of the studied groups was 59.60±6.89 years. Hepatitis C infection was found 82.9% of patients. Six patients (17.1%) received treatment of HCV. All patients were of Child-Pugh class A (77.1% were scores 5 and 22.9% were score 6). The median Alpha-fetoprotein (AFP) level was 240 ng/ml. The mean operative time was 186.4±52.4 min. During the follow-up period (12-24 months), 12 patients (34.3%) developed recurrence. The mean time of recurrence was 15.50±4.23 months. Cumulative disease-free survival (DFS) at the end of the study was 65.7%. The cumulative overall survival (OAS) proportion at the end of the study was 74.3%. Conclusion: Our results suggest that surgical resection for large HCC is safe and effective and that the first-line treatment for large HCC to be considered is surgical resection in selected patients. Our study showed that hepatectomy for large HCC could be performed with an acceptable morbidity and mortality rate. With the improvement in patient selection and treatment strategy, solitary large HCC is not a contraindication to surgical therapy.

Endoarterial Treatment in Combination With Percutaneous Thermoablation for Medium-sized and Oligonodular Hepatocellular Carcinomas

Background & Aims: The association of transcatheter arterial chemotherapy infusion (TAC) with percutaneous ablation (PT) has been introduced as a method to increase the size of the ablative zone and treat satellites micronodules. The aim of this study was to evaluate the efficacy of PT and TAC performed in a single session for hepatocellular carcinomas (HCCs) between 30 and 50 mm or oligonodular HCC up to 30 mm. Methods: Thirty patients with a histologically proven HCC, uninodular between 30 and 50 mm or oligonodular (n≤3) up to 30 mm, treatment-naive and non-metastatic, received the combination treatment (“PT+TAC group”). A “control” group consisted of 34 patients with uninodular HCC up to 30 mm without any poor prognostic criteria treated with PT alone (“PT group”). Results: The majority of patients were cirrhotic (90% vs 91%, respectively for the PT+TAC and PT groups), Child-Pugh A (83% vs 85%), with a Performans Status of 0 (80% vs 79%). There was no significant difference in the median alpha-fetoprotein level (15 vs 9.3 μg/l, p=0.39). The 1-, 3-, and 5-year OS was no significantly different in both groups: 100%, 82% and 48.5% in the PT+TAC group vs 94.1%, 72.7% and 65.2% in the PT group (p=0.88). The 1-, 3-, and 5-year relapse-free survival was significantly lower in the PT+TAC group: 59.3%, 18.5% and 5.6% vs 89.3%, 46.4% and 24.5%, in the PT group (p=0.02). Conclusion: The combination treatment for HCC between 30 and 50 mm or oligonodular up to 30 mm, showed a similar OS, compared to uninodular HCC up to 30 mm without poor prognostic criteria, treated with PT alone, at the price of earlier tumor recurrence.

Pediatric ovarian immature teratoma: Histological grading and clinical characteristics

BackgroundOvarian immature teratomas (ITs) are relatively rare among all pediatric ovarian tumors. The histological grading for ovarian ITs, which ranges from 1 to 3, is based on the proportion of immature neuroepithelial component. Higher-grade ITs in adults are treated as malignant neoplasms and require adjuvant chemotherapy. However, there is no consensus on the therapeutic management of pediatric ovarian ITs. The aim of our study was to analyze the histological grades and clinical characteristics of ovarian ITs in pediatric patients. MethodsThis retrospective chart review consisted of seven patients, including one, three, and three patients with histological grade 1, 2, and 3 pediatric ovarian ITs, respectively, who were treated at our institute between 2000 and 2016. Collected data comprised age, alpha-fetoprotein (AFP) level, clinical stage, tumor size, treatment, and prognosis. ResultsThe median age and AFP levels of patients with grade 1, 2, and 3 ovarian ITs were 8, 7, and 10 years and 37, 112, and 221 ng/ml, respectively. All cases were Children Oncology Group (COG) stage I and International Federation of Gynecology and Obstetrics (FIGO) stage IA. All patients had unilateral tumors in the right ovary. The median tumor sizes of the grade 1, 2, and 3 IT patients were 104, 160, and 100 cm2, respectively. All patients underwent primary open surgery alone. Two patients, including one patient each with grade 2 and 3 ITs, underwent tumor enucleation as ovary-sparing surgery, whereas the remaining five patients underwent unilateral salpingo-oophorectomy. The median follow-up was seven years, and all cases achieved event-free survival. ConclusionsClinical characteristics of patients with grade 3 ovarian ITs were relatively older and had higher AFP levels than those with lower-grade ITs. According to our patient’s clinical course and prognosis, COG stage I pediatric ITs should be treated by surgery alone and that postoperative chemotherapy is unnecessary even for those with grade 3 ITs as well as patients with rather low AFP levels. Level of evidenceIV

Second Trimester Biochemical Markers as Possible Predictors of Pathological Placentation: A Retrospective Case-Control Study

Objective: We aimed to evaluate the association between second trimester biochemical markers and pathological placentation. Methods: This was a retrospective case-control study (2007–2014) of singleton gestations at a university-affiliated tertiary center. Women with pathologic placentation were subdivided into three groups: placenta accreta (group A), placenta previa (group B), or both (group C). We compared second trimester biochemical screening markers taken between 16 + 0 and 19 + 6 weeks of gestation between groups A, B, and C, and women with normal placentation (group D). Obstetrical and neonatal outcomes, risk factors for pathologic placentation, and second trimester biochemical marker values were compared between groups. Results: Overall, 301 deliveries were evaluated: 64 (21%) in group A, 66 (22%) in group B, 17 (6%) in group C, and 153 (51%) in group D. Each of the pathological placentation groups individually had a higher median alpha-fetoprotein (AFP) and human chorionic gonadotropin (hCG) multiples of median (MoM) than the controls, with the highest values of AFP and hCG observed among women with placenta accreta and the lowest values among the controls. When a multivariant analysis was applied, the hCG levels remained significantly correlated with pathological placentation. Receiver operation characteristic curves for AFP, hCG, or both were computed. For AFP the area under the ROC curve (AUC) was 0.573 (95% CI 0.515–0.630, p < 0.0274) and a cut-off value above 0.99 MoM demonstrated a sensitivity and specificity of 71 and 46%, respectively, for the prediction of pathological placentation. For hCG, the AUC was 0.662 (95% CI 0.605–0.715, p < 0.0001) and a cut-off value of 1.25 MoM demonstrated a sensitivity and specificity of 53 and 68%. When both markers were plotted, the AUC was 0.668 (95% CI 0.611–0.721, p < 0.0001) and sensitivity and specificity were 63 and 64%, respectively. A percentile MoM cut-off approach distinguished between two groups: a high-risk group (patients with AFP or hCG or both above the 75th percentile, odds ratio (OR) for pathological placentation 2.27, 95% CI 1.42–3.63), and a low-risk group (patients with AFP or hCG or both below the 25th percentile, OR for pathological placentation 0.38, 95% CI 0.24–0.60). Conclusion: Second trimester biomarkers such as hCG and AFP can be used to raise a suspicion towards characterizing women into high-risk and low-risk groups for pathological placentation.

Serum AFP levels in patients suffering from 47 different types of cancers and noncancer diseases.

Alpha-fetoprotein (AFP) is a glycoprotein and belongs to the gene family of serum albumins. The serum AFP levels were found to be elevated in the sera of liver cancer patients in 1964 and were subsequently developed and used as a liver cancer biomarker. However, elevated serum AFP levels have been observed in patients suffering from other cancer and noncancer diseases. Up to date, a systematic comparison of the serum AFP levels in different diseases has not been reported. In current study, 66,682 clinical lab test results of serum AFP levels from healthy individuals and patients with 47 different types of diseases during the past 5 years were retrieved and analyzed. Based on the mean (SD), median, and p (-Log10p) values, we found that patients suffering from liver, breast, esophagus, cervical, pancreatic, endometrial, gastric, lung, rectum cancers in addition to noncancer diseases cirrhosis, nephrotic syndrome, and gastritis had significantly (p<0.05) increased, whereas patients suffering from multiple myeloma, Wilms' tumor, and other 22 types of noncancer diseases had significantly decreased median serum AFP levels than that of healthy controls. Moreover, patients with liver cancer, cirrhosis, lymphoma, bone fracture, and Wilms' tumor had highest mean serum AFP levels and the biggest SD values. In summary, the increased serum AFP levels were most evident but not specific for liver cancer patients. The potential clinical use of the increased or decreased serum AFP levels for other types of cancer and noncancer diseases and the molecular mechanisms behind our current findings need to be investigated.

Outcomes of Patients With PBC Developing HCC

Introduction: Patients with Primary biliary cholangitis (PBC) are at increased risk of developing Hepatocellular carcinoma (HCC). Studies report that risk factors for HCC in PBC include male sex and advanced histologic stage. We aim to describe the occurrence and outcomes of HCC in our population of PBC patients. Methods: Clinical data from 114 patients with primary biliary cholangitis seen at our center between January 1, 2006 and December 31, 2017 was retrospectively reviewed for occurrence of HCC and factors associated with this occurrence. Results: Seven patients with PBC developed HCC (6.1%). Baseline characteristics are listed in Table 1. Median mass size was 2.95 cm (1.3-2.6 cm) and median Alpha Fetoprotein (AFP) was 3.05 (2.4-1366 ng/ml). Five patients underwent liver transplantation. The two patients that were not transplanted underwent Transcatheter arterial chemoembolization (TACE). Median time to liver transplantation from diagnosis of PBC was 13 years (7 to 24 years). No patients had recurrence of PBC after liver transplantation. Conclusion: The occurrence of HCC in our patient population is congruent with that reported in prior studies. Although male sex has also been linked to increased occurrence of HCC in PBC, our patients who developed HCC were all females. AFP levels are commonly used to screen for HCC, however, most patients (75%) in our study with PBC who developed HCC had a normal AFP level. It is worth noting that all the patients who developed HCC in our cohort were non-responders to UDCA.2842 Figure 1. No Caption available.

Second-trimester maternal serum screening for fetal Down syndrome: As a screening test for hemoglobin Bart's disease: A prospective population-based study.

The purpose of this study is to determine the effectiveness of second-trimester maternal serum screening for Down syndrome as a screening test for fetal hemoglobin (Hb) Bart's disease among an unselected population. A secondary analysis of a large prospective database (20254 pregnancies) was conducted to compare the levels of maternal serum screening, alpha-fetoprotein (AFP), free beta-human chorionic gonadotropin, and unconjugated estriol between pregnancies with Hb Bart's disease and unaffected pregnancies. The median AFP levels were much higher among affected fetuses (1.96 vs 1.12 multiple of the median; P<.001), yielding a sensitivity of 81.6% and specificity of 86.4%. Thus, AFP measurement is effective in predicting fetal Hb Bart's disease among an unselected population when using a cutoff value of 1.5 multiple of the median. The serum free beta-human chorionic gonadotropin levels were slightly, but significantly, higher in the affected pregnancies, while the serum unconjugated estriol levels were minimally, but significantly, lower among the affected pregnancies. Second-trimester maternal serum AFP levels were significantly elevated in cases of fetal Hb Bart's disease. Pregnancies with unexplained elevated serum AFP levels in areas of high prevalence of Hb Bart's disease should always undergo a detailed ultrasound examination to detect any early signs of fetal anemia before development of hydrops fetalis.