Positive Alpha-fetoprotein Research Articles

Prognostic significance of postoperative serological incomplete conversion of AFP and PIVKA-II after hepatic resection for hepatocellular carcinoma: a multicenter analysis of 1755 patients.

The value of serum biomarkers, particularly alpha-fetoprotein (AFP) and protein induced by vitamin K absence or antagonist-II (PIVKA-II), gains increasing attention in prognostic evaluation and recurrence monitoring for patients with hepatocellular carcinoma (HCC). This study investigated the implications of serological incomplete conversion (SIC) of these 2 biomarkers as prognostic indicators for long-term outcomes after HCC resection. A multicenter observational study was conducted on a cohort of HCC patients presenting with AFP (>20ng/mL) or PIVKA-II (>40 mAU/mL) positivity who underwent curative-intent resection. Based on their postoperative AFP and PIVKA-II levels at first postoperative follow-up (4~8 weeks after surgery), these patients were stratified into the serological incomplete conversion (SIC) and serological complete conversion (SCC) groups. The study endpoints were recurrence and overall survival (OS). Among 1755 patients, 379 and 1376 were categorized as having SIC and SCC, respectively. The SIC group exhibited 1- and 5-year OS rates of 67.5% and 26.3%, with the corresponding recurrence rates of 53.2% and 79.0%, respectively; while the SCC group displayed 1- and 5-year OS rates of 95.8% and 62.5%, with the corresponding recurrence rates of 16.8% and 48.8%, respectively (both P < .001). Multivariate Cox regression analysis demonstrated that postoperative SIC was an independent risk factor for both increased recurrence (HR: 2.40, 95% CI, 2.04-2.81, P < .001) and decreased OS (HR: 2.69, 95% CI, 2.24-3.24, P < .001). The results emphasize that postoperative incomplete conversion of either AFP or PIVKA-II is a significant prognostic marker, indicating a higher risk for adverse oncologic outcomes following HCC resection. This revelation has crucial implications for refining postoperative adjuvant therapy and surveillance strategies for HCC patients.

Efficacy and safety in advanced hepatocellular carcinoma between patients with negative and positive APF treated with targeted and immunotherapy.

e16162 Background: Serum alpha-fetoprotein (AFP) is widely accepted as a crucial tool for clinical diagnosis and screening of HCC. However, there are cases where patients test negative for AFP but are confirmed to have Hepatocellular Carcinoma through imaging or pathological examinations. Despite these findings, there is limited research focusing on the medicine selection for AFP-negative patients. Methods: This retrospective cohort study, involving 223 untreated advanced HCC patients, and the first-line regimen consisted of targeted therapy and TKI+ICIs therapy. Patients are categorized into negative and positive AFP groups based on initial serum levels. Main efficacy endpoint was progression free survival (PFS), evaluated in accordance with RECIST v1.1. Adverse events (AEs) were recorded according to CTCAE v5.0. Results: According to the level of serum AFP, they were divided into negative group(100) and positive group(123). The two groups showed no statistically significant differences in age, gender, Child-Pugh score and other baseline clinical characteristics( P&gt; 0.05). At data cut-off at February 2023, median OS was not matured and mPFS in negative group was higher than positive group(8.2 vs 5.3months, P&lt; 0.0001). In the ICIs+TKI therapy cohort, mPFS in the negative AFP group(52) was significantly higher than in the positive AFP group(70) (10 vs. 5.8 months, P = 0.0021). Considering all patients in the negative AFP group as a subgroup, an analysis of survival benefits between those receiving targeted therapy and those receiving TKI+ICIs therapy revealed no significant difference in PFS( P&gt; 0.05). Moreover, AEs were compared between the negative and positive group, with no significant differences observed in Any Grade or Grade 3/4( P&gt; 0.05). Conclusions: Patients with negative AFP exhibited superior survival benefits compared to those with positive AFP in first-line therapy. Regarding PFS, the TKI+ICIS therapy did not demonstrate a better benefit over targeted therapy in the negative AFP subgroup.

Intracranial non-germinomatous germ cell tumors in children and adolescents: how can the experience from an uppermiddle-income country contribute to the worldwide effort to improve outcomes?

Non-germinomatous germ cell tumors (NGGCT) accounts for one third of intracranial GCT. While the germinoma group have an excellent overall survival, the standard of practice for children with NGGCT is still under evaluation. Describe the results of the of the Brazilian consortium protocol. Since 2013, 15 patients with a diagnosis of NGGCT by histopathology and/or serum/cerebrospinal fluid (CSF) tumor markers, βHCG >200mlU/ml and/or positive alpha-fetoprotein were treated with neoadjuvant chemotherapy with carboplatin, cyclophosphamide and etoposide followed by ventricular radiotherapy (RTV) of 18Gy with boost (32Gy) to the primary site. Metastatic patients underwent craniospinal irradiation (CSI) and "slow responders" to the four initial cycles of CT, to autologous stem cell transplantation (ASCT) followed by CSI. Mean age, 13.1 years. Thirteen males. Primary sites: pineal (n=12), suprasellar (n=2) and bifocal (n=1). Four patients were metastatic at diagnosis. Eight patients had CSF and/or serum alpha-fetoprotein levels > 1,000ng/ml. Tumor responses after chemotherapy demonstrated complete in six cases and partial in seven, with "second-look" surgery being performed in five cases, and two patients presenting viable lesions being referred to ASCT. The main toxicity observed was hematological grades 3/4. Two patients with metastatic disease, one with Down Syndrome and AFP > 1,000ng/ml and the other with choriocarcinoma and pulmonary metastases, developed progressive disease resulting in death, as well as two other patients without evidence of disease, due to endocrinological disorders. Event-free and overall survival at 2 and 5 years were 80% and 72.7%, respectively, with a mean follow-up of 48 months (range, 7-107). Despite the small number of patients, in our series, treatment with six cycles of chemotherapy and RTV with focal boost for localized disease (n=11) and ACST for identified slow responders (n=2) seem to be effective strategies contributing to the overall effort to improve outcomes of this group of patients.

Development and validation of a nomogram to predict the recurrence of hepatocellular carcinoma patients with dynamic changes in AFP undergoing locoregional treatments.

Serum alpha-fetoprotein (AFP) is an important clinical indicator for screening, diagnosis, and prognosis of primary hepatocellular carcinoma (HCC). Our team's previous study showed that patients with negative AFP at baseline and positive AFP at relapse had a worse prognosis (N-P). Therefore, the aim of our study was to develop and validate a nomogram for this group of patients. A total of 513 patients with HCC who received locoregional treatments at Beijing You'an Hospital, Capital Medical University, from January 2012 to December 2019 were prospectively enrolled. Patients admitted from 2012 to 2015 were assigned to the training cohort (n = 335), while 2016 to 2019 were in the validation cohort (n =183). The clinical and pathological features of patients were collected, and independent risk factors were identified using univariate and multivariate Cox regression analysis as a basis for developing a nomogram. The performance of the nomogram was evaluated by C-index, receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA) curves in the training and validation cohorts. The content of the nomogram includes gender, tumor number, tumor size, lymphocyte, direct bilirubin (DBIL), gamma-glutamyl transferase (GGT), and prealbumin. The C-index (0.717 and 0.752) and 1-, 3-, and 5-year AUCs (0.721, 0.825, 0.845, and 0.740, 0.868, 0.837) of the training and validation cohorts proved the good predictive performance of the nomogram. Calibration curves and DCA curves suggested accuracy and net clinical benefit rates. The nomogram enabled to classify of patients with dynamic changes in AFP into three groups according to the risk of recurrence: low risk, intermediate risk, and high risk. There was a statistically significant difference in RFS between the three groups in the training and validation cohorts (P<0.001). The nomogram developed and validated in this study had good predictive power for patients with dynamic changes in AFP.

The Dynamic Changes of AFP From Baseline to Recurrence as an Excellent Prognostic Factor of Hepatocellular Carcinoma After Locoregional Therapy: A 5-Year Prospective Cohort Study.

BackgroundAlthough many studies have confirmed the prognostic value of preoperative alpha-fetoprotein (AFP) in patients with hepatocellular carcinoma (HCC), the association between AFP at baseline (b-AFP), subsequent AFP at relapse (r-AFP), and AFP alteration and overall survival in HCC patients receiving locoregional therapy has rarely been systematically elucidated.Patients and MethodsA total of 583 subjects with newly diagnosis of virus-related HCC who were admitted to Beijing You ‘an Hospital, Capital Medical University from January 1, 2012 to December 31, 2016 were prospectively enrolled. The influence of b-AFP, subsequent r-AFP, and AFP alteration on relapse and post-recurrence survival were analyzed.ResultsBy the end of follow-up, a total of 431 (73.9%) patients relapsed and 200 (34.3%) died. Patients with positive b-AFP had a 24% increased risk of recurrence compared with those who were negative. Patients with positive r-AFP had a 68% increased risk of death after relapse compared with those who were negative. The cumulative recurrence-death survival (RDS) rates for 1, 3, 5 years in patients with negative r-AFP were 85.6% (184/215), 70.2%(151/215), and 67.4%(145/215), while the corresponding rates were 75.1% (154/205), 51.2% (105/205), and 48.8% (100/205) in those with positive AFP (P<0.001). 35 (21.6%) of the 162 patients with negative b-AFP turned positive at the time of recurrence, and of this subset, only 12 (34.3%) survived. Of the 255 patients with positive b-AFP, 86 (33.7%) turned negative at the time of relapse, and of this subset, only 30 (34.9%) died. The 1-, 3-, and 5-year cumulative RDS rates were also compared among groups stratified by AFP at baseline and relapse. The present study found that patients with positive AFP at baseline and relapse, as well as those who were negative turned positive, had the shortest RDS and OS.ConclusionsNot only AFP at baseline but also subsequent AFP at relapse can be used to predict a post-recurrence survival, which can help evaluate mortality risk stratification of patients after relapse.

A Model Based on Artificial Intelligence Algorithm for Monitoring Recurrence of HCC after Hepatectomy.

There is no satisfactory indicator for monitoring recurrence after resection of hepatocellular carcinoma (HCC). This retrospective study aimed to design and validate an HCC monitor recurrence (HMR) model for patients without metastasis after hepatectomy. A training cohort was recruited from 1179 patients with HCC without metastasis after hepatectomy between February 2012 and December 2015. An HMR model was developed using an AdaBoost classifier algorithm. The factors included patient age, TNM staging, tumor size, and pre/postoperative dynamic variations of alpha-fetoprotein (AFP). The diagnostic efficacy of the model was evaluated based on the area under the receiver operating characteristic curves (AUCs). The model was validated using a cohort of 695 patients. In preoperative patients with positive or negative AFP, the AUC of the validation cohort in the HMR model was .8877, which indicated better diagnostic efficacy than that of serum AFP (AUC, .7348). The HMR model predicted recurrence earlier than computed tomography/magnetic resonance imaging did by 191.58 ± 165 days. In addition, the HMR model can predict the prognosis of patients with HCC after resection. The HMR model established in this study is more accurate than serum AFP for monitoring recurrence after hepatectomy for HCC and can be used for real-time monitoring of the postoperative status in patients with HCC without metastasis.

941P Neoadjuvant radiotherapy improves overall survival in patients with resectable hepatocellular carcinomas

There is little evidence for the association between neoadjuvant radiotherapy (NRT) and improved overall survival (OS) in patients with resectable hepatocellular carcinomas (HCCs). This study aimed to determine whether NRT provides a survival benefit in these patients. We enrolled patients with resected HCC identified in the Surveillance, Epidemiology, and End Results database (2004–2015). Multiple imputation plus inverse probability of treatment weighting (IPTW) reduced selection bias. IPTW-adjusted Kaplan-Meier curves and IPTW-adjusted Cox proportional hazards models compared OS between different treatment groups. Sensitivity analyses tested the robustness of the estimates. Subgroup analysis identified the patients who could benefit most from NRT. We enrolled a total of 11920 patients diagnosed between 2004 and 2015 in the study. Of these, 134 patients underwent NRT, the others underwent surgery alone (SA). The median OS in NRT was not approached, whereas in SA it was 52.0 (interquartile range, 34.25, 100.75) months. The 5-year IPTW-adjusted rates of OS in NRT versus SA were 65.3% and 46.6%, respectively. In IPTW-adjusted Cox proportional hazards regression analysis, NRT was associated with a significant OS benefit (hazard ratio [HR], 0.549; 95% confidence interval [CI], 0.327-0.921; p = 0.023). The results were robust in sensitivity analysis (E-value 2.39). Subgroup analysis demonstrated improved OS in the NRT cohort among younger patients (HR, 0.46; 95% CI, 0.26-0.83), N0 status (HR, 0.51; 95% CI, 0.28-0.94), and alpha-fetoprotein (AFP)-positive patients (HR, 0.28; 95% CI, 0.12-0.65). Patients with resectable HCCs may derive a survival benefit from NRT. Younger age (<65 years), a positive AFP level and N0 status patients could benefit more from NRT. The present study establishes a reasonable basis for further prospective studies.

Abstract 1148: SynOV1.1: A synthetic gene circuit controlled oncolytic adenovirus demonstrating high tumor specificity, potent antitumor efficacy and high synergy with an anti-PD-L1 monoclonal antibody in preclinical hepatocellular carcinoma models

Abstract Hepatocellular carcinoma (HCC) is yet the fourth most common cause of cancer-related death although its treatment has been significantly advanced in recent years. Oncolytic viruses are among a novel class of immunotherapies that have shown promise to HCC patients with convincing abilities to selectively replicate in and kill cancer cells as well as to boost tumor immunogenicity. In order to further enhance the safety and efficacy of oncolytic viruses, SynOV1.1, a recombinant replication-competent serotype 5-based adenovirus, was constructed by deleting E1B and partial E3 genes, and incorporating a synthetic sensory switch circuit. The gene circuit was designed to enhance tumor-specific expression of E1A gene and an immune effector, human granulocyte-macrophage colony-stimulating factor (hGM-CSF) by sensing cancer-specific alpha-fetoprotein (AFP) promoter and two microRNA inputs. The specificity of SynOV1.1 to selectively kill target tumor cells and the ability to specifically express hGM-CSF in the target cells were confirmed in numerous human and mouse HCC cell lines with an IC50 approximately 3 to 35-fold less than that of normal cell lines. In vivo, intratumoral injections of SynOV1.1 in immune-deficient mice bearing human HCC cells resulted in a significant reduction of tumor volume (approximately 80%) as compared with the controls (approximately 30% for sorafenib). To further evaluate the effects of antitumor and immune stimulation, SynOV1.1m (SynOV1.1 murine surrogate) was intratumorally injected to the immune-competent mice bearing mouse HCC cells (ie., mHepa1-6), which showed SynOV1.1m induced a greater antitumor effect as well as a more robust tumor-specific immune response as compared to the controls. In addition, SynOV1.1m could significantly inhibit the growth of non-injected distal tumors after it was injected into a mHepa1-6 tumor on the other side of the mouse body, indicating that a systemic immune response was induced by SynOV1.1m. The combination of SynOV1.1m and an anti-mPD-L1 monoclonal antibody (mAb) was further explored and showed a synergistic anti-tumor effect as compared to SynOV1.1m or anti-mPD-L1 mAb alone. Preclinical safety of SynOV1.1 was examined in various toxicology species including golden hamsters, tumor-bearing mice and cynomolgus monkey, in all of which SynOV1.1 was found safe. Overall, preclinical pharmacology and toxicology data support clinical investigation of SynOV1.1 alone or in combination with atezolizumab in advanced HCC patients with positive serum AFP levels. Citation Format: Qiang Liu, Yubing Cao, Man Zhang, Shuguang Peng, Yiqi Liu, Huiya Huang, Bin Chen. SynOV1.1: A synthetic gene circuit controlled oncolytic adenovirus demonstrating high tumor specificity, potent antitumor efficacy and high synergy with an anti-PD-L1 monoclonal antibody in preclinical hepatocellular carcinoma models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1148.

Clinical features, treatments and survival of HER2 positive gastric cancer with elevated alpha-fetoprotein: An analysis of 16 cases.

e16000 Background: Gastric cancer with elevated alpha-fetoprotein (AFP) is a special type of gastric cancer with elevated serum AFP. It is often misdiagnosed as primary hepatic cancer due to abnormal AFP and liver metastasis. The AFP level is related to the prognosis of these patients in whom there is prone to high HER2 positive rate. Therefore, anti-HER2 treatment is optional, as well as the emerging immunotherapy with immune checkpoint inhibitors. Methods: Gastric cancer patients with HER2 and serum AFP examination were collected in our hospital from May 2017 till now. Serum AFP level over 7 ng/ml was defined as elevated AFP. The clinical characteristics, treatments and survival of the patients with HER2 positive and elevated AFP were picked and analyzed. Results: Among 135 gastric cancer patients with elevated AFP, 16 (11.9%) were HER-2 positive (12 with HER2 3+, 3 with HER2 2+/FISH+ and 1 with HER2 gene amplification in NGS). The mean serum AFP is 201.4± 476.7ng/ml (range: 7.74 -1335). There were 9 males and 7 females. The mean age was 55 years (range: 38-90). The tumors were located in stomach cardia and fundus in 5 cases, body in 5 cases, antrum in 4 cases, body and antrum in 1 case and whole stomach in 1 case. There were 2 patients in stage III and 14 patients in stage IV with metastasis to lymph node metastasis in 15, liver in 9, abdominal cavity in 3 and peritoneum in 3. As for the treatments, three patients underwent surgery, one of whom with exploratory laparotomy (no antitumor treatment after surgery, died from infection). In 13 advanced patients, 12 patients received systemic antitumor therapies (8 with chemotherapy+Trastuzumab+ immunotherapy, 2 with chemotherapy+Trastuzumab, 1 with chemotherapy+ immunotherapy and 1 with chemotherapy). The chemotherapy regimens were XELOX in 5 cases, SOX in 4 cases and FLOT in 2 cases. The response rate was 50% (6 in 12 patients) and the disease control rate was 100%. The median PFS was 7.5 months in first line therapy with six patients without progression disease yet. The longest PFS with PR lasted for 16.5 months with chemotherapy, trastuzumab and immune checkpoint inhibitor. Conclusions: Gastric cancer with HER2 positive and elevated serum AFP is a disease with special clinical characteristics. Patients with advanced diseases can be treated with chemotherapy, trastuzumab +/- immune checkpoint inhibitors. This combination is expected to become a new regimen to improve survival of such special patients.

Neoadjuvant radiotherapy to improve overall survival in resectable hepatocellular carcinoma.

e16178 Background: There is little evidence for the association between neoadjuvant radiotherapy (NRT) and improved overall survival (OS) in patients with resectable hepatocellular carcinomas (HCCs). This study aimed to determine whether NRT provides a survival benefit in these patients. Methods: We enrolled patients with resected HCC identified in the Surveillance, Epidemiology, and End Results database (2004–2015). Multiple imputation plus inverse probability of treatment weighting (IPTW) reduced selection bias. IPTW-adjusted Kaplan-Meier curves and IPTW-adjusted Cox proportional hazards models compared OS between different treatment groups. Sensitivity analyses tested the robustness of the estimates. Subgroup analysis identified the patients who could benefit most from NRT. Results: We enrolled a total of 11920 patients diagnosed between 2004 and 2015 in the study. Of these, 134 patients underwent NRT, the others underwent surgery alone (SA). The median OS in NRT was not approached, whereas in SA it was 52.0 (interquartile range, 34.25, 100.75) months. The 5-year IPTW-adjusted rates of OS in NRT versus SA were 65.3% and 46.6%, respectively. In IPTW-adjusted Cox proportional hazards regression analysis, NRT was associated with a significant OS benefit (hazard ratio [HR], 0.549; 95% confidence interval [CI], 0.327-0.921; p = 0.023). The results were robust in sensitivity analysis (E-value 2.39). Subgroup analysis demonstrated improved OS in the NRT cohort among younger patients (HR, 0.46; 95% CI, 0.26-0.83), N0 status (HR, 0.51; 95% CI, 0.28-0.94), and alpha-fetoprotein (AFP)-positive patients (HR, 0.28; 95% CI, 0.12-0.65). Conclusions: Patients with resectable HCCs may derive a survival benefit from NRT. Younger age ( &lt; 65 years) with a positive AFP level at N0 status could be indicators for NRT. These findings enlighten current guidelines to consider NRT in patients with resectable HCCs. The present study establishes a reasonable basis for further prospective studies.

A Comparison of Lenvatinib versus Sorafenib in the First-Line Treatment of Unresectable Hepatocellular Carcinoma: Selection Criteria to Guide Physician's Choice in a New Therapeutic Scenario.

Hepatocellular carcinoma (HCC) is the fifth most common malignancy across the world. Alongside improvement in local approaches for early stages, the prognosis of patients with advanced disease remains poor. The tyrosine kinase inhibitor sorafenib was the first drug approved for advanced HCC. During the past decade, this has been extensively explored in real-life settings, such as Eastern Cooperative Oncology Group performance status 2, Child-Pugh B liver function, chronic kidney disease, HIV infection, transplant recipients and the elderly. After 10 years, the multikinase inhibitor lenvatinib was approved in first-line setting. The Phase III REFLECT trial established the non-inferiority of lenvatinib compared with sorafenib in terms of overall survival, meanwhile exploratory analysis suggests a potential benefit over sorafenib for patients with HBV chronic infection and positive alpha-fetoprotein value. Experience with lenvatinib for patients not matching the REFLECT trial criteria remains promising but still retrospective. Indeed, the treatment sequence after lenvatinib still remains a crucial issue, considering that standard second-line options were tested only in patients who progressed to sorafenib. Overall, the choice between lenvatinib and sorafenib should take into account key selection criteria from randomized trials, evidence to date in special clinical situations, the physician’s experience and patient’s preference. Fast approval of atezolizumab plus bevacizumab as first-line treatment for advanced HCC brought an additional element in this scenario. Undoubtedly, lenvatinib and sorafenib remain available options for patients who are not suitable or those progressed to combination immunotherapy. It is conceivable that new systemic options will contribute to design a new treatment algorithm for HCC in the near future. Meanwhile, prospective studies and biomarker analysis are needed to help physicians in the choice between lenvatinib and sorafenib.

REC8 promotes tumor migration, invasion and angiogenesis by targeting the PKA pathway in hepatocellular carcinoma.

REC8 is a member of the cohesin family, and its abnormal activation has been detected in cancer cells. This study explored the role and possible mechanism of REC8 in hepatocellular carcinoma (HCC). A total of 40 pairs of HCC and adjacent tissues were collected, and the clinical significance of REC8 expression in HCC was evaluated. REC8 expression in human HCC tissues and HCC cell lines was investigated by quantitative real-time PCR, Western blotting, immunohistochemistry and immunofluorescence staining. The biological functions of REC8 in HCC cell lines were detected by wound-healing assay, Matrigel invasion assay and tube formation assay. The proteins interacting with REC8 were identified by mass spectrometry after immunoprecipitation screening. There was a correlation between the high expression of REC8 and positive alpha-fetoprotein levels. The expression level of REC8 protein in HCC tissues was higher than that in adjacent tissues. REC8 has mainly located in the nucleus of HCC tissue cells and HCC cell lines, but it was expressed in the cytoplasm of adjacent normal tissue cells and hepatocytes. The results of wound healing, transwell invasion and tubular formation assays indicated that the overexpression of REC8 accelerated the metastasis of HCC in vitro; however, metastasis was suppressed after REC8 was silenced by small interference RNA. A total of 57 differentially expressed proteins were identified by mass spectrometry, and it was found that REC8 and PKA RII-α staining was colocalized in the nucleus. The expression levels of MMP-9 and VEGF-C were decreased after treatment with the PKA inhibitor H89. Overall, REC8 promotes the migration, invasion and angiogenesis of HCC cells through the PKA pathway.

Rare subtype of hepatoblastoma in a young adult: difficulties in the histopathological differentiation from hepatocellular carcinoma

Background: Hepatoblastoma is a primary malignant tumor of the liver usually occurring in children, whereas it is very rare in adults, affecting males slightly more. Case Presentation: We report a case of a 20-year old female patient with a palpable liver mass and significantly elevated alphafetoprotein (AFP), Serum Glutamic Oxaloacetic Transaminase, and Serum Glutamic-Pyruvic Transaminase values. The microscopic examination revealed a mixed cell population of small cells with an oval-shaped nucleus and scant relatively basophilic cytoplasm co-existing with larger cells with eosinophilic or clear cytoplasm, round nuclei, arranged in trabeculae of six or more cells separated by thin fibrous septa. The immunohistochemical assessment of the tumor cells revealed positivity for AFP, Glypican-3, Glutamate Synthetase, polyclonal Carcinoembryonic antigen, Cytokeratin (CK8/18), and Epithelial Specific Antigen/Ep-CAM, membranous and focally nuclear positivity for b-catenin, focal positivity for CK19 and vimentin and faintly focal positivity for Sallike protein-4 and Cluster Differentiation 99. The cell proliferation rate Ki-67 was high, at about 85% and concerning the prognostic markers, there was a positive expression of Cyclin D1 at approximately 80% of the tumor cells, whereas c-myc was negative. These findings drove us to the diagnosis of hepatoblastoma, macrotrabecular subtype. Conclusion: Although the age, medical history, clinical findings, and the laboratory investigations of the patient suggested hepatocellular carcinoma, on the histological examination the mixed blastematous morphology of the tumor combined with the results of the immunohistochemical assay, lead to the diagnosis of hepatoblastoma.

Hepatoid Adenocarcinoma of the Lung.

Hepatoid adenocarcinoma of the lung (HAL) is an comparatively rare malignant tumor originating from the lung with shorter survival. HAL morphologically and pathologically exhibits hepatocellular carcinoma (HCC)-like characteristics, while its clinical features resemble pulmonary adenocarcinoma. High concentration of alpha-fetoprotein (AFP) is often detected in the serum of HAL patients with no hepatic occupying lesion. Patients with AFP-negative HAL survive a few months longer than those with positive AFP test. HAL is a rare type of carcinoma, so there is a lack of systematic and extensive statistical research. The treatment strategy for HAL is similar to common lung adenocarcinoma. Complete surgical resection and adjuvant chemotherapy are the current major treatments for HAL patients. There are also a few of case reports suggesting that HAL patients may benefit from immunotherapy and targeted therapy. This review focuses on the clinical and pathological features, immunohistochemical staining characteristics, treatment and prognosis of HAL.

Gastric Adenocarcinoma with Enteroblastic Differentiation: A Rare Find

Abstract Casestudy: Gastric adenocarcinoma with enteroblastic differentiation (GAED), also called clear cell gastric carcinoma, is a subtype of alpha-fetoprotein (AFP) producing adenocarcinoma. GAED is not a well-documented malignancy. Due to rarity, it is often skipped from the list of gastric adenocarcinoma subtypes. We report a case of Gastric adenocarcinoma with enteroblastic differentiation in a 69-year-old male, who had an endoscopy that revealed an ulcerated, circumferential, malignant-appearing mass at the distal esophagus. The patient then underwent proximal gastrectomy with distal esophagectomy. Received was a portion of the proximal stomach and distal esophagus. On gross examination, a 2.6 cm ulcerated mass was present at the gastroesophageal junction with white, friable, and focally necrotic cut surface. H&amp;E stained slides demonstrated a malignant tumor composed of cuboidal to columnar neoplastic cells with clear cytoplasm and prominent nucleoli. The neoplastic cells were arranged in tubular, solid, and trabecular growth patterns. There were also areas of admixed conventional moderately differentiated adenocarcinoma with overlying glandular dysplasia and focal intestinal metaplasia. Immunohistochemical stains demonstrated tumor positivity for CDX2 (strong) and AFP (focal). Neuroendocrine markers were negative within the tumor. In Conclusion, GAED is a rare malignancy with distinctive clinicopathologic features and associated aggressive behavior. Morphology and immunohistochemical stains are helpful in making the diagnosis of this rare malignancy.

Phosphatidylinositol-3,4,5-trisphosphate dependent Rac exchange factor 1 is a diagnostic and prognostic biomarker for hepatocellular carcinoma.

BACKGROUNDPhosphatidylinositol-3,4,5-trisphosphate dependent Rac exchange factor 1 (P-Rex1) was reported to be a risk factor in several cancers, including breast cancer, lung cancer, and melanoma, but its expression and role in hepatocellular carcinoma (HCC) have not yet been fully studied.AIMTo explore the expression of P-Rex1 in HCC, and further evaluate its potential application in the diagnosis and prognosis of HCC, especially in hepatitis B virus (HBV)-related patients.METHODSP-Rex1 expression in HCC was evaluated by real-time-quantitative polymerase chain reaction. The expression of P-Rex1 was subjected to correlation analysis with clinical features, such as lymph node invasion, distant metastasis, HBV infection, patient's age and gender. Receiver operating characteristic analysis was used to examine the potential role of P-Rex1 as a diagnostic biomarker in HCC. Kaplan-Meier analysis was used to determine the association between P-Rex1 expression and overall survival, progression-free survival and relapse-free survival. Bioinformatic analysis was used to validate the clinical findings.RESULTSP-Rex1 expression was significantly increased in HCC tumors than adjacent tissues. The expression of P-Rex1 was higher in HCC patients with lymph node invasion, distant metastasis, HBV infection and positive alpha-fetoprotein, respectively. The receiver operating characteristic analysis showed that P-Rex1 was a diagnostic biomarker with a higher area under the curve value, especially in patients with HBV infection. Survival analysis showed that patients with higher P-Rex1 expression had a favorable survival rate, even in early-stage patients.CONCLUSIONP-Rex1 expression was highly increased in HCC, and the expression level of P-Rex1 was positively correlated with tumor progression. P-Rex1 has a higher efficiency in the diagnosis of HBV-related HCC, and could also be used as a favorable prognostic factor for HCC patients.

Value of neutrophil-to-lymphocyte ratio in the diagnosis and prognosis evaluation of primary hepatocellular carcinoma

Objective To investigate the value of neutrophil-to-lymphocyte ratio (NLR) in the diagnosis and prognosis evaluation of primary hepatocellular carcinoma. Methods The clinical data of 100 patients pathologically diagnosed as primary liver cancer who were admitted to the First Medical Center of Chinese PLA General Hospital from January 2013 to December 2015 were retrospectively analyzed. Serum alpha fetoprotein (AFP), a conventional marker for hepatocellular carcinoma diagnosis was used as the control. The fourfold table diagnostic test was applied to analyze the sensitivity and specificity of serum NLR in the diagnosis of hepatocellular carcinoma, and the correlation with the degree of tumor differentiation was also analyzed. Results The proportion of patients with high NLR (≥1.70) [56% (56/100)] was higher than the proportion of patients with positive AFP [44% (44/100)] in all 100 hepatocellular carcinoma patients, but the difference was not statistically significant (χ2 = 2.88, P = 0.08). Among AFP-positive patients, the median survival time of patients with low and high NLR was 59 and 48 months, respectively, and the difference was statistically significant (χ2 = 3.91, P = 0.048), and high NLR was an independent risk factor affecting the prognosis of hepatocellular carcinoma patients (HR = 1.232, 95% CI 1.055-1.438, P = 0.008). Conclusions The detection of NLR combined with AFP can improve the diagnostic rate of hepatocellular carcinoma before surgery. High NLR is an independent risk factor affecting the prognosis of patients with primary hepatocellular carcinoma. Key words: Liver neoplasms; Neutrophil-to-lymphocyte ratio; Diagnosis; Prognosis

A Model Based on Artificial Intelligence Algorithm for Monitoring Recurrence of HCC after Hepatectomy: A Multicenter Study

Objective: There is no satisfactory indicator for monitoring recurrence after resection in hepatocellular carcinoma (HCC). For patients without metastasis after hepatectomy, an HCC monitor recurrence (HMR) model was designed and validated by a multicenter retrospective study. Methods: A training cohort was recruited of 1179 patients with HCC without metastasis after hepatectomy from February 2012 to December 2015. An HMR model was proposed with an AdaBoost classifier algorithm; factors included patient age, TNM staging, tumor size, and pre/postoperative dynamic variations of alpha-fetoprotein (AFP). The diagnostic efficacy of the model was evaluated relative to that of the traditional AFP monitoring recurrence model based on the areas under the respective receiver operating characteristic curves (AUCs). Prediction of recurrence was evaluated relative to computed tomography/magnetic resonance imaging (CT/MRI). The model was validated via an internal cohort comprising 695 patients, and two external cohorts of 30 and 33 patients, respectively. Results: In preoperative patients with positive or negative AFP, the AUCs of the HMR model (0.8708-0.9609) indicated better diagnostic efficacy compared with serum AFP (0.7348-0.8196). The HMR model predicted recurrence earlier than did CT/MRI, by 77.64 to 191.58 days. Conclusion: The HMR model was more accurate than serum AFP for monitoring recurrence after hepatectomy of HCC, and can be used for real-time monitoring of the postoperative status of patients with HCC without metastasis. The HMR model should help individualize strategies for reexaminations, and guide adjuvant treatment schemes for patients with HCC. Funding Statement: This work was supported by grants from the National Natural Science Foundation of China (grant no. 81602468 & 81800556). Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: The Ethics Committee of Sun Yat-Sen University Cancer Center (SYSUCC) approved this study. Every participant provided signed informed consent.

FNAC of Hepatic Malignancy and it’s Clinical Correlation.

Background: Hepatic malignancy is an important clinical condition which is associated with poor outcome. Clinicalassessment of a patient with hepatic malignancy is crucial to sort out the primary and secondary, and so biochemicaland radiological investigations are needed. Hence fine needle aspiration cytology (FNAC) of the lesion is essentialwhich is a minimal invasive procedure to combat a deadly disease.&#x0D; Objective: The aim of this prospective cross sectional observational study was clinical assessment of primary andsecondary hepatic malignancy and its co-relation with FNAC of hepatic malignancy.&#x0D; Methods: Patients admitted in Medicine Department, Dhaka medical College, with hepatic malignancy from January2013 to June 2014 and then confirmed by FNAC (USG guided) of liver mass were included in the study. A total 100patients were enrolled in the study in a non-random convenient sampling method.&#x0D; Result: In this study 42 patients were found having primary Hepatocellular Carcinoma (HCC) and 58 patients hadsecondary hepatic malignancy. FNAC confirmed secondary hepatic malignancy (n=58) as metastatic adenocarcinoma43(74.1%), metastatic small cell carcinoma 9(15.5%), Gastro Intestinal Stromal Tumour (GIST) 2(3.4%), squamouscell carcinoma 2(3.4%) &amp; Non Hodgkins lymphoma 2(3.4%). Most of the patients of primary hepatic malignancybetween 20-40 years 18(42.9%) and secondary hepatic malignancy between 40-60 years 35(60.3%). Incidence in maleis more in both primary 31(73.8%) and secondary 38(65.5%) hepatic malignancy. Both HCC and secondariespredominantly presents with abdominal pain, 39(92.9%) cases of HCC and 47(81.0%) of secondaries. Incidence ofmultiple lesion in ultrasonogram is more in both primary 30(71.4%) and secondary 47(81.0%) hepatic malignancy.Positive HBsAg, Positive Anti HBc (total), Positive Anti HCV were found in 15(35.7%), 11(26.2%) and 9(21.4%) casesof HCC respectively. Positive Alpha Feto Protein (AFP) was found insignificant in this study.&#x0D; Conclusion: Fine Needle Aspiration (FNA) is a useful diagnostic test for evaluating patients with discrete hepaticmasses. Correlation with clinical, radiological and cytological findings is helpful in arriving at the correct diagnosisand therefore increases overall accuracy and cost-effectiveness of the procedure.&#x0D; Bangladesh Crit Care J September 2019; 7(2): 81-85

Surface Modification for Detection of Liver Cancer Biomarker

Materials modification with surface functional group for bioactive film or sensor surface is important in many applications. A suitable surface for each system can be shown high efficiency of detection. In this work, two different surfaces via covalent binding are created on gold substrate for finding the suitable surface in medical applications. The liver cancer biomarker, alpha-fetoprotein (AFP) was detected on two surfaces; one is carboxy dextran and another is a modified polymethyl metacrylate (PMMA). The substrates were improved by physical and chemical binding for AFP antibody immobilization. Contact angle and surface Plasmon resonance (SPR) were used to study the characteristic of surfaces. The result was found that the carboxy dextran gave higher detection than PMMA. Moreover, the dextran surface was studied in real serum samples. It was shown the significantly different between positive and negative AFP serum which is preliminary results for testing in more clinical samples further.