Elevated AFP Research Articles

Prognostic Evaluation of Conversion Therapy Following Hepatic Arterial Infusion Chemotherapy or Immunotherapy in Patients with Advanced or Transarterial Chemoembolization Unsuitable Intermediate-Stage Hepatocellular Carcinoma-A retrospective cohort study.

Patients with advanced-stage or intermediate-stage hepatocellular carcinoma (HCC) unsuitable for transarterial chemoembolization (TACE) had poor prognoses. Recent advancements in hepatic arterial infusion chemotherapy (HAIC) and immune checkpoint inhibitors (ICIs) have demonstrated higher tumor response rates, which improved overall survival (OS). HAIC achieves an OS rate of approximately 14.5-15.3 months with a 39.1-42.5% tumor response rate. In comparison, ICIs have a 12-14 month OS rate with a 26-33% tumor response rate. Given these promising responses, this study evaluates the efficacy of conversion therapy with curative intent following HAIC or ICIs, focusing on survival outcomes. We retrospectively analyzed 80 patients with advanced or TACE-unsuitable intermediate HCC. Patients completed two HAIC or four ICI cycles, followed by Response Evaluation Criteria in Solid Tumors (RECIST) criteria imaging. Based on demographics, cirrhosis status, Barcelona Clinic Liver Cancer classification (BCLC) stage, treatment responses, and treatment modality, survival impacts were analyzed. OS was compared between HAIC and immunotherapy groups. The effect of conversion therapy with curative intent on survival outcomes was analyzed using a Cox regression model. Among the 80 patients, 26 achieved positive response (CR/PR) with HAIC or ICIs, and 9 of them subsequently underwent conversion therapy with curative intent. Key prognostic factors included Child-Pugh stage B vs. A (HR=2.21, p=0.041), BCLC stage C vs. B (HR=4.38, p=0.011), and elevated AFP levels (HR=5.02, p<0.001). Positive responders saw substantial survival benefits (HR=0.26, p=0.001). Patients undergoing conversion therapy exhibited significantly enhanced survival. Median OS was 13.58 months with standard therapy, while the curative intent surgery group did not reach the median OS (p=0.002). For CR/PR patients, 48-month survival was 75.0% for the curative surgery group versus 38.0% for standard treatment. Conversion therapy with curative intent following HAIC or ICIs might enhances survival in patients with advanced or TACE-unsuitable intermediate-stage HCC.

Mediastinal Teratoma with Angiosarcomatous Overgrowth in a Background of Vasculogenic Mesenchymal Tumor

Abstract Introduction/Objective Vasculogenic mesenchymal tumor refers to neoplastic reiteration of embryonic vasculogenesis. It is most commonly associated with nonseminomatous germ cell tumors of the mediastinum, in particular yolk sac tumor. In rare instances these lesions progress to angiosarcoma. Herein, we describe a case of angiosarcoma in a background of vasculogenic mesenchymal tumor in the setting of a mediastinal teratoma. Methods/Case Report A 33-year-old male, with a past medical history of anxiety, and right orchiectomy for testicular torsion, presented with shortness of breath, chest pain, and left arm swelling. Imaging studies demonstrated a mediastinal mass. Biopsy of the mass showed a germ cell tumor most compatible with a teratoma in the limited specimen. The patient received two rounds of chemotherapy and additional treatments were discontinued due to poor tolerance. Subsequent imaging showed continued increase in the size along with mass effect causing moderate to severe compression of the superior vena cava. Subsequently, the patient underwent resection of the mass. Grossly the mass was predominantly encapsulated with areas of capsular disruption. Sectioning revealed heterogeneous cut surfaces with fleshy, cystic, and necrotic areas. Morphologically the tumor was composed predominantly of teratomatous elements with areas of anastomosing atypical vascular channels within a hypocellular stroma suggestive of vascular genic mesenchymal as well as areas reminiscent of Masson lesion. Focally within these areas were malignant spindle cell proliferations compatible with angiosarcoma. The patient had an elevated AFP; however, no yolk sac tumor component was identified after thorough sampling. Final diagnosis of teratoma with angiosarcoma in a background of vasculogenic mesenchymal tumor was rendered after expert consultation. Results (if a Case Study enter NA) NA Conclusion Somatic-type malignancy and sarcomatous overgrowth are known to occur in mediastinal germ cell tumors; however, classification of the sarcomatous overgrowth can be challenging. Vasculogenic mesenchymal tumor is an exceedingly rare sarcomatous overgrowth that can rarely progress to angiosarcoma.

S4323 Revealing Marginal Zone Lymphoma: Elevated AFP Levels as a Clue: A Case Report

S4323 Revealing Marginal Zone Lymphoma: Elevated AFP Levels as a Clue: A Case Report

S4173 Liver Transplantation After Successful Downstaging of Multifocal Hepatocellular Carcinoma With Marked AFP Elevation Using Interventional Immuno-oncology

S4173 Liver Transplantation After Successful Downstaging of Multifocal Hepatocellular Carcinoma With Marked AFP Elevation Using Interventional Immuno-oncology

Retrospective analysis of arginase 1 deficiency progression in adults over 5 years at a single metabolic centre.

The clinical presentation of ARG1-D is characterised by elevated arginine levels leading to neurological and mobility impairments. Information about long-term outcomes in adults is lacking, which prompted us to undertake a retrospective observational study. We extracted ARG1-D patient data spanning a 5-year period from electronic health records. Ethical approval was not required for the study. Informed consent was obtained. We identified nine ARG1-D patients from consanguineous backgrounds. Age of symptom onset ranged from infancy to age 7 years, age of diagnosis from infancy to 20 years. Patients had paraparesis or altered gait of varying degree and had experienced early ARG1-D onset. Over 5 years, mobility declined in six (6/9, 67%) patients. Three patients (3/9, 33%) were fully dependent and hoisted. Two (2/9, 22%) reached adulthood before experiencing hyperammonaemia, another one (1/9, 11%) first experienced hyperammonaemia at age 15 years. One patient (1/9, 11%) started on ammonia scavenger therapy in adulthood, one (1/9, 11%) required a second scavenger to be added to their treatment regimen. Two patients (2/9, 22%) had gastrostomy tubes inserted for nutrition and supplements at age 9 years and 15 years. Six patients (6/9, 67%) had raised levels of ALT; of these, four (4/9, 44%) also had elevated AFP. Heterogeneity of ARG1-D symptoms was evident, suggesting complex genetic and environmental interactions. ARG1-D presents significant lifelong challenges with deteriorating mobility and more frequent metabolic crises. Current management strategies are insufficient for preventing progression, highlighting the need for innovative treatments like enzyme replacement and gene therapy.

Intention-to-treat outcomes of patients with hepatocellular carcinoma receiving immunotherapy before liver transplant: the multicenter VITALITY study

The use of immune checkpoint inhibitors (ICI) in patients with advanced hepatocellular carcinoma (HCC) has become widespread with encouraging outcomes in the neoadjuvant setting. Safety and intention to treat (ITT) outcomes in the peri transplant setting are currently based on small and heterogenous single center reports. This first multiregional US study (2016-2023) included 117 consecutive HCC patients assessed for LT and treated preoperatively with ICIs. Intention to treat ITT and survival analyses were conducted with evaluation of post LT rejection rates. In total, 86 (73.5%) patients exceeded MC and 65 (75.6%) were successfully downstaged (DS) within a median of 5.6 months. 43 (36.7%) underwent transplantation, including 18 (15.4%) within MC and 23 (19.7%) initially beyond and DS. Overall, 94% of the cohort received concurrent ICIs and locoregional therapies. No grade 4-5 adverse events occurred on the waiting list. The 3-year cumulative probability of dropout was 28% for those within MC and 48% for those beyond. Independent predictors of dropout included: being beyond MC (p<0.001), AFP doubling from baseline (p=0.014) and radiographic responses (p<0.001). The 3-year ITT survival was 71.1% (73.5% within MC vs 69.7% beyond MC, p=0.329), with 3-year post LT survival rate of 85%. Post-LT rejection occurred in 7 patients, six received their last dose of ICI less than 3 months prior to LT, resulting in one graft loss. The first multicenter evaluation of HCC patients receiving ICI pre-LT demonstrates favorable survival and safety outcomes, justifying continued utilization and further evaluation of this strategy in clinical practice. High tumor burden, doubling of AFP levels, and radiographic response were identified as predictors of unfavorable oncologic outcomes. The first multicenter evaluation of pre-transplant immune-checkpoint-inhibitors in hepatocellular carcinoma to show promising intention-to-treat survival, safety and rejection rates. Immune-checkpoint-inhibitors, either alone or combined with LRT, demonstrate reliable efficacy. This preoperative strategy could be particularly beneficial for high-risk patients, including those requiring downstaging or with elevated AFP levels despite locoregional treatment. These findings fill current knowledge gaps and offer reassuring evidence for the feasibility of pre-transplant use of immune-checkpoint-inhibitors, pending results from ongoing trials.

An Immunohistochemical Study of MAGE Proteins in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is one the most common primary malignancies with high mortality and morbidity. The melanoma-associated antigen (MAGE) gene family includes several genes that are highly expressed in numerous human cancers, making many of them part of the cancer-testis antigen (CTA) family. MAGE-C1 is expressed in various malignancies but is absent in normal cells, except for the male germ line. Its presence is associated with a worse prognosis, increased tumor aggressiveness, and lymph node invasion. Similarly, MAGE-C2 is linked to the development of various malignant tumors. Despite these associations, the roles and mechanisms of MAGE-C1/MAGE-C2 in HCC remain unclear. This study aimed to evaluate the expression of MAGE-C1 and MAGE-C2 in HCC and correlate it with clinicohistological characteristics. Our findings indicated that MAGE-C1 expression is associated with a higher number of nodules, elevated AFP levels, HBV or HCV positivity, older age, male sex, and lymph node invasion. MAGE-C2 expression was correlated with these characteristics and the presence of cirrhosis. These results align with the limited literature, which suggests a correlation between MAGE expression and older age and HBV infection. Consequently, our study suggests that MAGE-C1 and MAGE-C2 are promising novel biomarkers for prognosis and potential therapeutic targets in HCC.

Monocyte distribution width as a promising biomarker for differential diagnosis of chronic hepatitis, cirrhosis, and hepatocellular carcinoma.

We aimed to investigate the association and diagnostic value of monocyte distribution width (MDW) for chronic hepatitis B (CHB), liver cirrhosis (LC), and hepatocellular carcinoma (HCC). MDW levels were measured in 483 individuals (103 CHB, 77 LC, 153 HCC, and 150 controls). MDW was detected using UniCel Dx900 for specific cell volume parameters and the distribution of cell volumes. Our findings revealed a dynamic upward change in MDW levels across different stages of chronic liver disease, from CHB to LC and HCC. In CHB, MDW levels were highest among HBeAg-positive CHB patients and exhibited a negative correlation with HBV markers while positively correlating with ALT levels. In LC, MDW showed a positive association with the pathological progression of LC, demonstrating consistency with CP scores. MDW proved to be equally effective as traditional detection for diagnosing LC. In HCC, MDW was positively correlated with HCC occurrence and development, with higher levels observed in the high MDW group, which also exhibited elevated AFP levels, MELD scores, and 90-day mortality rates. MDW surpassed predictive models in its effectiveness for diagnosing HCC, as well as CHB and LC, with respective areas under the curve of 0.882, 0.978, and 0.973. Furthermore, MDW emerged as an independent predictor of HCC. MDW holds significant diagnostic efficacy in identifying CHB, LC, and HCC. These findings suggest that MDW could serve as a promising biomarker for predicting the severity of liver diseases and aid in rational clinical treatment strategies.

Relationship between increased maternal serum free human chorionic gonadotropin levels in the second trimester and adverse pregnancy outcomes: a retrospective cohort study

BackgroundA retrospective cohort study was conducted to collect the data of pregnant women who received hospital delivery in Hangzhou Women's Hospital from January 2018 to December 2020, and who participated in the second trimester (15–20+6 weeks) of free beta human chorionic gonadotropin (free β-hCG). And the study was conducted to explore the relationship between maternal serum free β-hCG and adverse pregnancy outcomes (APO).MethodsWe retrospectively analyzed the clinical data of 1,978 women in the elevated maternal serum free β-hCG group (free β-hCG ≥ 2.50 multiples of the median, MoM) and 20,767 women in the normal group (0.25 MoM ≤ free β-hCG < 2.50 MoM) from a total of 22,745 singleton pregnancies, and modified Poisson regression analysis was used to calculate risk ratios (RRs) and 95% confidence intervals (CI) of the two groups.ResultsThe gravidity and parity in the elevated free β-hCG group were lower, and the differences between the groups were statistically significant (all, P < 0.05). The risks of polyhydramnios, preeclampsia, and hyperlipidemia, were increased in women with elevated free β-hCG levels (RRs: 1.996, 95% CI: 1.322–3.014; 1.469, 95% CI: 1.130–1.911 and 1.257, 95% CI: 1.029–1.535, respectively, all P < 0.05), intrauterine growth restriction (IUGR) and female infants were also likely to happen (RRs = 1.641, 95% CI: 1.103–2.443 and 1.101, 95% CI: 1.011–1.198, both P < 0.05). Additionally, there was an association between elevated AFP and free β-hCG levels in second-trimester (RR = 1.211, 95% CI: 1.121–1.307, P < 0.001).ConclusionsAPOs, such as polyhydramnios, preeclampsia, and hyperlipidemia, were increased risks of elevated free β-hCG levels, IUGR and female infants were also likely to happen. Furthermore, there was an association between elevated AFP levels and elevated free β-hCG levels in second-trimester. We recommend prenatal monitoring according to the elevated maternal serum free β-hCG level and the occurrence of APO.

Combinational zimberelimab plus lenvatinib and chemotherapy for alpha-fetoprotein elevated, advanced gastric cancer patients (AFPGC): a phase 1 dose-escalation study

BackgroundAlpha-fetoprotein elevated gastric cancer (AFPGC) got growing interests for its aggressive nature and unfavorable prognosis. Here, a phase 1 dose escalation study was conducted to evaluate safety and efficacy of zimberelimab (GLS-010, anti-PD-1) plus lenvatinib and chemotherapy (XELOX) as the first-line treatment for AFPGC.MethodsHistologically confirmed HER2-negative, advanced GC patients with elevated serum AFP level (≥ 20 ng/ml) were screened. Using a 3 + 3 dose escalation design, patients were administered varying doses of lenvatinib (12, 16, 20 mg) with GLS-010 and XELOX. The primary endpoints were safety and determination of recommended phase II dose (RP2D). Secondary endpoints included overall response rate (ORR), progression-free survival (PFS) and disease control rate.ResultsNine patients were enrolled with no dose-limiting toxicities observed. Most frequent treatment-related AEs were fatigue (55.6%), hand-foot syndrome (55.6%) and rash (55.6%), and no grade ≥ 4 AEs were reported. All patients exhibited disease control with ORR reaching 33.3%. The median PFS and OS reached 7.67 months (95% CI 4.07–11.27) and 13.17 months (95% CI 2.78–23.56), respectively. Serum AFP level was found correlated with therapeutic responses. Further 16s rRNA sequencing analysis demonstrated altered gut microbiota with elevated abundance of Lachnospiraceae bacterium-GAM79 and Roseburia hominis A2-183.ConclusionsGLS-010 plus lenvatinib and XELOX demonstrated a manageable safety profile with promising efficacy for AFPGC. With RP2D of lenvatinib determined as 16 mg, further expansion cohort is now ongoing. Translational investigation suggested that serum AFP can be indictive for therapeutic responses and certain microbiota species indicating favorable responses to immunotherapy was elevated after the combinational treatment.

Establishment and Validation of a Blood Test-based Nomogram to Diagnose Patients with AFP-negative HCC.

Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer death worldwide. Alpha-protein (AFP) is the most widely used blood biomarker for HCC. However, elevated serum AFP is only observed in part of HCC. This study aimed to develop an efficient nomogram model to distinguish patients with alpha- protein-negative HCC and liver cirrhosis. A total of 1130 patients (508 HCC patients + 622 cirrhosis patients) were enrolled in the training cohort. A total of 244 HCC patients and 246 cirrhosis patients were enrolled in the validation cohort. A total of 41 parameters about blood tests were analyzed with logistic regression. The nomogram was based on independent factors and validated both internally and externally. Independent factors were eosinophils %, hemoglobin concentration distribution width, fibrinogen, platelet counts, total bile acid, and mitochondria aspartate aminotransferase. The calibration curve for the probability of HCC showed good agreement between prediction by nomogram and actual observation. The concordance index was 0.851. In the validation cohort, the nomogram distinguished HCC from liver cirrhosis with an area under the curve of receiver operating characteristic of 0.754. This proposed nomogram was an accurate and useful method to distinguish patients with AFP-negative HCC from liver cirrhosis.

NR1H4 disease: rapidly progressing neonatal intrahepatic cholestasis and early death.

Clinical studies on progressive familial intrahepatic cholestasis (PFIC) type 5 caused by mutations in NR1H4 are limited. New patients with biallelic NR1H4 variants from our center and all patients from literature were retrospectively analyzed. Three new patients were identified to be carrying five new variants. Liver phenotypes of our patients manifests as low-γ-glutamyl transferase cholestasis, liver failure and related complications. One patient underwent liver transplantation (LT) and survived, and two other patients died without LT. Nine other patients were collected through literature review. Twelve out of 13 patients showed neonatal jaundice, with the median age of onset being 7 days after birth. Reported clinical manifestations included cholestasis (13/13, 100%), elevated AFP (11/11, 100%), coagulopathy (11/11, 100%), hypoglycemia (9/13, 69%), failure to thrive (8/13, 62%), splenomegaly (7/13, 54%), hyperammonemia (7/13, 54%), and hepatomegaly (6/13, 46%). Six of 13 patients received LT at a median age of 6.2 months, and only one patient died of acute infection at one year after LT. Other 7 patients had no LT and died with a median age of 5 months (range 1.2-8). There were 8 patients with homozygous genotype and 5 patients with compound heterozygous genotype. In total, 13 different variants were detected, and 5 out of 12 single or multiple nucleotides variants were located in exon 5. We identified three newly-diagnosed patients and five novel mutations. NR1H4-related PFIC typically cause progressive disease and early death. LT may be the only lifesaving therapy leading to cure.

Colorectal adenocarcinoma with enteroblastic differentiation: a clinicopathological analysis of eight cases

Objective: To investigate the clinicopathological features of colorectal adenocarcinoma with enteroblastic differentiation (CAED). Methods: Eight cases of CAED diagnosed at the Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China from January 2017 to August 2023 were collected. The histopathological, immunohistochemical, molecular and prognostic features of 8 CAED cases were analyzed. The relevant studies were also reviewed. Results: Among the eight patients, there were six males and two females, with an average age of 58 years (range: 29-77 years, median age: 61.5 years). Preoperative serum alpha-fetoprotein levels were elevated in five patients (14.0-286.6 μg/L). Four tumors were located in the colon, and four tumors in the rectum. Two patients were clinically staged as advanced stage (stage Ⅳ), and distant metastasis occurred at the initial diagnosis (one case had liver metastasis, and the other had lung, bone and multiple lymph nodes metastases). Six patients were clinically staged as locally-advanced stage (Stage Ⅱ-Ⅲ). Three of them developed distant metastases after surgery (one case had liver metastasis, one case had lung metastasis, and one case had peritoneal metastasis). Additionally, two patients died at 9 months and 24 months after surgery, respectively. The tumors were composed of various proportions of adenocarcinoma components with enteroblastic differentiation (30%-100%) and classical tubular adenocarcinoma components. The component with enteroblastic differentiation exhibited morphology similar to embryonic intestinal epithelium: cuboidal or columnar tumor cells arranged in tubular, papillary, cribriform, or solid nest patterns, with clear cytoplasm. Immunohistochemical studies showed that tumor cells expressed at least one oncofetal protein (SALL4, Glypican-3, and AFP). In addition, focal squamous differentiation was observed in 3 cases (3/8). Compared to the primary tumor, both CAED and squamous differentiation components were increased in the metastatic tumors. Based on the sequencing results of KRAS, NRAS and BRAF of the primary and/or metastatic tumors, 5 cases were wild-type, while KRAS exon 2 (G13D) mutations were identified in 2 cases. Conclusions: CAED is a rare colorectal malignancy with a dismal prognosis. Accurate pathological diagnosis is prognostically valuable. The histological features of enteroblastic differentiation, elevated serum AFP levels, and the expression of oncofetal proteins play an important role in the tumor diagnosis.

Clinical Characteristics of Non-B and Non-C Biopsy-Proven Primary Liver Cancers in an HBV- Endemic Area: A Retrospective Study.

To explore the distribution of probable causes and clinical characteristics of non-B and non-C (NBNC) primary liver cancer (PLC) patients in the HBV-endemic region. A total of 86 individuals with biopsy-proven NBNC-PLC were enrolled. NBNC-PLC patients were defined as negative for both anti-HCV antibodies and five serum hepatitis B markers. Patients' characteristics were collected from medical records. Among them, most of the NBNC-PLC patients had intrahepatic cholangiocarcinoma (ICC) (81.4%), and 12.8% had hepatocellular carcinoma (HCC). The NBNC ICC group had more platelet count, GGT, and CA199 levels; approximately two-thirds were female, and it was more often present in patients with biliary inflammatory diseases, especially intrahepatic biliary lithiasis. The NBNC HCC group was older and had a higher proportion of dyslipidemia, obesity, cirrhosis, and AFP levels. Our data revealed that most of the NBNC PLC patients were ICC. Female patients with biliary inflammatory diseases and higher CA199 levels had an increased risk of ICC, and patients with metabolic risk factors and elevated AFP levels were more likely to develop HCC. Additional research should be performed to verify this finding.

How to differentiate between combined hepatocellular carcinoma-cholangiocarcinoma and intrahepatic cholangiocarcinoma with rim arterial phase hyperenhancement?

To analyze and compare the differences in MRI features between combined hepatocellular carcinoma-cholangiocarcinoma (cHCC-CCA) and intrahepatic cholangiocarcinoma (iCCA) with arterial phase peripheral enhancement, so as to provide valuable references for preoperative differential diagnosis. Seventy cHCC-CCA patients and 74 iCCA patients confirmed by pathology were included in this study. Their contrast-enhanced MRI showed rim arterial phase hyperenhancement (Rim APHE). The differences of clinicopathological data and MRI features between cHCC-CCA and iCCA were compared. Then, the sensitivity, specificity, and area under curve (AUC) were also analyzed and compared. Seventy cHCC-CCA patients (mean age, 55.7 ± 10.6years) and 74 iCCA patients (mean age, 61.1 ± 10.5years) were evaluated. In this study, univariable and multivariable regression analysis showed that AFP > 20ng/ml (OR = 5.824, p = 0.006), enhancing capsule (OR = 7.252, p = 0.001), and mosaic architecture (OR = 32.732, p < 0.001) were independent risk factors of cHCC-CCA with Rim APHE. However, only hepatic capsule retraction (OR = 0.091, p < 0.001) was an independent predictor of iCCA. In addition, combining AFP > 20ng/ml with enhancing capsule (96.7% vs. 79.2%, p < 0.001) and/or mosaic architecture (96.4% vs. 94.7%, p < 0.001) can improve the sensitivity of differentiating cHCC-CCA (vs. iCCA) with Rim APHE. The combination of elevated AFP and MRI features, such as enhancing capsule and mosaic architecture, will help in preoperative differential diagnosis of cHCC-CCA and iCCA with Rim APHE.

Modulation of the Tumor Microenvironment by Ellagic Acid in Rat Model for Hepatocellular Carcinoma: A Potential Target against Hepatic Cancer Stem Cells.

The resistance to therapy and relapse in hepatocellular carcinoma (HCC) is highly attributed to hepatic cancer stem cells (HCSCs). HCSCs are under microenvironment control. This work aimed to assess the systemic effect of ellagic acid (EA) on the HCC microenvironment to decline HCSCs. Fifty Wistar rats were divided into six groups: negative control (CON), groups 2 and 3 for solvents (DMSO), and (OVO). Group 4 was administered EA only. The (HCC-M) group, utilized as an HCC model, administered CCL4 (0.5 mL/kg in OVO) 1:1 v/v, i.p) for 16 weeks. HCC-M rats were treated orally with EA (EA + HCC) 50 mg/kg bw for five weeks. Biochemical, morphological, histopathological, and immunohistochemical studies, and gene analysis using qRT-PCR were applied. Results revealed elevated liver injury biomarkers ALT, AST, ALP, and tumor biomarkers AFP and GGT, and marked nodularity of livers of HCC-M. EA effectively reduced the biomarkers and restored the altered structure of the livers. At the mRNA level, EA downregulated the expression of TGF-α, TGF-β, and VEGF, and restored p53 expression. This induced an increase in apoptotic cells immunostained with caspase3 and decreased the CD44 immunostained HCSCs. EA could modulate the tumor microenvironment in the HCC rat model and ultimately target the HCSCs.

CfDNA and associated risk factors in the early diagnosis of cancers in Côte d’Ivoire: The case of primary liver cancer related to viral hepatitis B

Introduction: In Côte d'Ivoire (CI), according to Globocan 2020 primary liver cancer (PLC) had an incidence of 10.1/1.0E+05 inhabitants in men (2nd rank) and 5.5/1.0E+05 inhabitants among women (4th rank). This situation has so far been favored by late diagnosis and ignorance of the risk factors responsible for the tumor in people at risk. Objective: To detect free circulating DNA (cfDNA) and evaluate its possible diagnostic role in order to contribute to the prevention of PLC in CI. Methodology: Prospective experimental study carried out at the Institut Pasteur in CI in patients coming for alfa-fetoprotein assay. Sociodemographic, clinical, paraclinical and epidemiological data were collected. A blood sample was taken for biological analysis. Data collected in Excel and processed with the GraphPad Prism 5. Results: 142 predominantly male patients with an average age of 45 were included. More than 50% had the same dietary habits including the consumption of tap water, rice, cassava, plantain, millet, maize and yam and 18% regularly consumed alcohol. 66.66% were carriers of chronic viral hepatitis B (HVB) including 2.81% at the cirrhosis stage and 0.70% at the PLC stage. 20% had a history of familial hepatitis and 9.6% a notion of familial cancer. The cfDNA concentration ranged from 38ng/ml to 10763ng/ml for an average of 571ng/ml. The elevation of AFP and transaminase levels was related to the presence of HBsAg (P˂0.001; P=0.02). In addition, the concentration of cDNA was strongly linked to HBsAg carriage as well as to other factors including the notion of familial cancer (P=0.03), and consumption of alcohol (p =0.04) and/or tobacco (p=0.02). Conclusion: HVB remains the predominant risk factor that can lead to PLC. The dosage of cfDNA and the monitoring of food and life hygiene in a chronic carrier of HVB could contribute to the prevention of PLC in the latter.

Retroperitoneal lymph node dissection for testicular cancer is a demanding procedure: detailed real-life data of complications and additional surgical procedures in 295 cases

PurposeRetroperitoneal lymph node dissection (RPLND) for germ cell tumours is a challenging procedure that may present relevant complications. The purpose was to analyse postoperative complications and identify risk factors for major complications.MethodsThis is a retrospective unicentric analysis of a large cohort of 295 RPLNDs from 1992 to 2020. Early complications (30 days) and late complications (31–180 days) were classified according to the Clavien‒Dindo classification. The influence of surgical, patient-specific, and tumour-specific parameters on grade III–V complications was analysed in univariate and multivariate logistic regression models.ResultsA total of 232 were postchemotherapy RPLNDs, and 63 were primary RPLNDs. Early postoperative complications were found to be grades I–II in 58.6% (173/295), grades III–IV in 9.8% (29/295), and grade V in 0.3% (1/295). In 20% (58/295), additional surgical procedures were needed. Grade III–V complications were associated with ≥ 4 cycles of preoperative chemotherapy (OR 3.7 (1.5–8.9); p = 0.004), RPLND specimen (nonseminoma or immature teratoma) (OR 3.1 (1.4–6.6); p = 0.005), transfusions (OR 2.4 (1.1–5.4); p = 0.03), salvage RPLND (OR 4.1 (1.8–9.3); p < 0.001), and preoperatively elevated AFP (OR 5 (2.2–11.7); p < 0.001). In multivariate analysis, the only independent predictor for grade III–V complications was preoperative AFP elevation (OR 3.3 (1.2–9.2); p = 0.02). Limitations include the retrospective study design.ConclusionsOur results demonstrate that RPLND is a demanding surgical procedure. Patients with a complex tumour history have a higher risk of complications. We recommend treatment of these complex cases in high-volume centres.

A single-arm, phase II study of durvalumab (D) and tremelimumab (T) for relapsed/refractory germ cell tumors (GCT).

5040 Background: Patients (pts) with GCT and progressive disease (PD) after salvage high-dose chemotherapy (HDCT) have dismal outcomes with median progression free survival (PFS) and overall survival (OS) of 1.0 and 4.7 months (mo), respectively (Feldman et al. Cancer 2012). Immune checkpoint blockade (ICB) has resulted in durable benefit in multiple tumor types. We tested D (anti-PD-L1) + T (anti-CTLA-4) for pts with relapsed/refractory GCTs in a phase II trial (NCT03158064). Methods: Eligible pts were ≥ 18 years old with GCT of any primary site who had PD after first-line chemotherapy and HDCT or were not candidates for HDCT or other curative options. Pts received D (1500 mg) and T (75 mg) every 4 weeks (wks) for 4 cycles followed by D (1500 mg) every 4 wks for up to 1 year (schedule 1). The study was later amended to one cycle of D (1500 mg) and T (300 mg) followed by D (1500 mg) every 4 wks for up to 1 year (schedule 2). The primary endpoint was initially overall response rate (ORR) in a Simon’s two-stage design with null and alternate rates of 5% and 20%, respectively. The study was then amended to use a primary endpoint of 16-wk PFS in a new Simon’s two-stage design with null and alternate rates of 5% and 25%. The regimen would be considered promising if 16-wk PFS was achieved in ≥ 3 of 20 pts. Secondary endpoints included PFS, OS, safety, and association of PD-L1 staining with outcome. Results: Between July 2017 and Jan 2022, 29 pts were treated, the last 7 (24%) on schedule 2. Median age was 37 (range, 21-70). Histology was non-seminoma in 25 pts (86%), and primary sites were testis in 20 (69%), mediastinum in 7 (24%), ovary in 1 (3%), and unknown in 1 (3%). Six (21%) pts had late relapse and 21 (72%) received prior HDCT. Median AFP was 310 ng/mL (range, 1–18,087) and HCG 471 mIU/mL (range, 3.3-62,302). Ten pts were treated with the ORR primary endpoint with no responses in stage 1, but 2 pts had tumor reductions of 20% and 22% with PFS of 9.9 and 10.4 mo, respectively, and 1 patient with elevated AFP but no RECIST measurable disease had a PFS of 5.7 mo. Of 19 pts treated with the 16-wk PFS primary endpoint, one had an ongoing partial response (59% tumor reduction) with 33 months follow-up; all others had PD in &lt;16 wks (17 with PD and 1 with stable disease). Thus, the study did not meet its primary endpoint. Among 29 treated pts, the 16-wk PFS was 13.8% (range, 4.3-28.6), and median PFS and OS were 1.4 (95% CI: 4.1, 7.1) and 7.3 mo (95% CI: 3.2, 10.9), respectively. PD-L1 expression data was available for 20/29 pts - 3/13 (23%) with low/negative and 1/7 (14%) with high expression achieved PFS &gt;16 wks. Six (21%) pts had grade 3-4 treatment-related adverse events, 3 (10%) of whom required high-dose steroids. Conclusions: D+T had limited antitumor activity in pts with relapsed/refractory GCT, failing to meet protocol-defined success. However, some pts did appear to benefit, including one exceptional responder. Additional correlative studies are ongoing. Clinical trial information: NCT03158064 .

Doxorubicin, paclitaxel, and cisplatin (ATP) for refractory germ cell tumors.

e17028 Background: Patients with refractory germ cell tumor (GCT) have limited treatment options and poor prognosis. We describe our institutional experience with doxorubicin, paclitaxel, and cisplatin (ATP) as an outpatient chemotherapy regimen for patients with refractory GCT. Methods: We performed a retrospective chart review of all patients who received ATP at our institution between August 2017 and August 2022. ATP consisted of doxorubicin 30 mg/m2, paclitaxel 100 mg/m2 over one hour, and cisplatin 30 mg/m2 every 2-3 weeks. We reviewed patient and disease characteristics including staging, histology, prior therapies, tumor marker and imaging responses. Progression free survival (PFS) and overall survival (OS) were respectively calculated from the first ATP dose date to disease progression/death and to death/last follow up. Results: A total of 39 patients with refractory GCT received ATP. Patients were 95% male, 54% white, with a mean age of 30 years (range 18-63). Prior to ATP administration, 92% of GCTs had elevated tumor markers, including 54% with elevated AFP, 56% with elevated HCG, and 18% with elevated both tumor markers. 8% of GCTs did not have elevated tumor markers at baseline. Further disease characteristics are described in table 1. Patients received a median of 2 lines of prior systemic therapies (range 1-6), including 97% with prior cisplatin-based regimens and 21% with prior high dose chemotherapy with stem cell rescue transplant. Patients received a median of 3 doses of ATP (range 1-8) with 31% for palliative intent and the rest as a bridge to transplant or other therapies. After ATP administration, 77% patients had decreased tumor markers, including 18% with tumor marker normalization. Of the 19 patients with imaging post-ATP, 53% had complete or partial response, 16% had stable disease, and 32% had disease progression. By December 2022, 79% patients had progression or death, with a median PFS of 3.8 months (95% CI: 1.94, 7.16) and median OS of 10.7 months (95% CI: 6.37, 32.69). 18% of patients experienced toxicities requiring admissions. Conclusions: Based on our retrospective single institution experience, ATP has clinical activity in refractory GCT and is associated with decreased tumor markers and imaging response in most patients. ATP is a convenient and feasible outpatient regimen and can be used in the salvage setting and as a bridge to other therapies. [Table: see text]