-
Cancer Immunology, Immunotherapy : CII Jun 2024Alpha-fetoprotein elevated gastric cancer (AFPGC) got growing interests for its aggressive nature and unfavorable prognosis. Here, a phase 1 dose escalation study was...
BACKGROUND
Alpha-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.
METHODS
Histologically 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.
RESULTS
Nine 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.
CONCLUSIONS
GLS-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.
Topics: Humans; Quinolines; Male; Female; Middle Aged; Phenylurea Compounds; Antineoplastic Combined Chemotherapy Protocols; Stomach Neoplasms; Aged; alpha-Fetoproteins; Antibodies, Monoclonal, Humanized; Adult; Prognosis
PubMed: 38833154
DOI: 10.1007/s00262-024-03743-0 -
Annals of Surgical Oncology Jun 2024The management of Bismuth-Corlette type IV hilar cholangiocarcinoma typically necessitates extensive hepatectomy, resection of the extrahepatic bile ducts, regional...
BACKGROUND
The management of Bismuth-Corlette type IV hilar cholangiocarcinoma typically necessitates extensive hepatectomy, resection of the extrahepatic bile ducts, regional lymph node dissection, and reconstruction of the biliary tract; however, there is a high incidence of postoperative liver dysfunction and failure.
METHODS
A 64-year-old male patient was admitted to our department after 1 month of escalating jaundice and abdominal discomfort. Upon admission, his total bilirubin was 334 μmol/L and his direct bilirubin was 221 μmol/L. His carbohydrate antigen 19-9 was > 1200.00 U/mL, his carcinoembryonic antigen was 98.90 U/mL, and his α-fetoprotein was normal. Enhanced computed tomography (CT) and magnetic resonance imaging scans revealed a thickened and enlarged biliary tree extending from the common hepatic duct to the orifices of the left and right hepatic ducts.
RESULTS
The patient underwent total laparoscopic radical resection of S1 + S4, accompanied by radical lymphadenectomy with skeletonization and biliary reconstruction. The surgery was successfully conducted within 450 min, with a minimal blood loss of 200 mL. The histological grading was T2bN1M0 (stage III). CT on postoperative day 5 showed satisfactory postoperative recovery. The patient was discharged from the hospital on postoperative day 10 without complications, following which the patient underwent a regimen of single-agent capecitabine chemotherapy. Over a 20-month follow-up period, no recurrence was observed.
CONCLUSIONS
Resection of hepatic segments S1 + S4 is a viable surgical option for hilar carcinoma in cases with poor liver function or when the carcinoma is confined to both hepatic ducts without invasion of the hepatic artery and portal vein.
PubMed: 38833055
DOI: 10.1245/s10434-024-15531-2 -
PeerJ 2024Autoantibodies targeting tumor-associated antigens (TAAbs) have emerged as promising biomarkers for early cancer detection. This research aimed to assess the diagnostic...
BACKGROUND
Autoantibodies targeting tumor-associated antigens (TAAbs) have emerged as promising biomarkers for early cancer detection. This research aimed to assess the diagnostic capacity of anti-BIRC5 autoantibody in detecting AFP-negative hepatocellular carcinoma (ANHCC).
METHODS
This research was carried out in three stages (discovery phase, validation phase, and evaluation phase) and included a total of 744 participants. Firstly, the anti-BIRC5 autoantibody was discovered using protein microarray, exhibiting a higher positive rate in ANHCC samples (ANHCCs) compared to normal control samples (NCs). Secondly, the anti-BIRC5 autoantibody was validated through enzyme-linked immunosorbent assay (ELISA) in 85 ANHCCs and 85 NCs from two clinical centers (Zhengzhou and Nanchang). Lastly, the diagnostic usefulness of the anti-BIRC5 autoantibody for hepatocellular carcinoma (HCC) was evaluated by ELISA in a cohort consisting of an additional 149 AFP-positive hepatocellular carcinoma samples (APHCCs), 95 ANHCCs and 244 NCs. The association of elevated autoantibody to high expression of BIRC5 in HCC was further explored by the database from prognosis, immune infiltration, DNA methylation, and gene mutation level.
RESULTS
In the validation phase, the area under the ROC curve (AUC) of anti-BIRC5 autoantibody to distinguish ANHCCs from NCs in Zhengzhou and Nanchang centers was 0.733 and 0.745, respectively. In the evaluation phase, the AUCs of anti-BIRC5 autoantibody for identifying ANHCCs and HCCs from NCs were 0.738 and 0.726, respectively. Furthermore, when combined with AFP, the AUC for identifying HCCs from NCs increased to 0.914 with a sensitivity of 77.5% and specificity of 91.8%. High expression of BIRC5 gene is not only correlated with poor prognosis of HCCs, but also significantly associated with infiltration of immune cells, DNA methylation, and gene mutation.
CONCLUSION
The findings suggest that the anti-BIRC5 autoantibody could serve as a potential biomarker for ANHCC, in addition to its supplementary role alongside AFP in the diagnosis of HCC. Next, we can carry out specific verification and explore the function of anti-BIRC5 autoantibody in the occurrence and development of HCC.
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; Autoantibodies; Biomarkers, Tumor; Male; Female; Middle Aged; Survivin; alpha-Fetoproteins; Enzyme-Linked Immunosorbent Assay; Adult
PubMed: 38832035
DOI: 10.7717/peerj.17494 -
Journal of Medical Case Reports Jun 2024Although the correlation between liver toxicity and vancomycin is generally considered low, it has been observed that the use of vancomycin can lead to abnormal liver...
BACKGROUND
Although the correlation between liver toxicity and vancomycin is generally considered low, it has been observed that the use of vancomycin can lead to abnormal liver function indicators, such as elevated aspartate aminotransferase, alanine aminotransferase, alpha fetoprotein, and jaundice. To further understand the clinical features associated with vancomycin-induced liver toxicity and to provide clinical guidance, we conducted an analysis of the characteristics and clinical manifestations of vancomycin-induced liver injury.
METHODS
Patients with liver function injury who received vancomycin treatment at the Third Xiangya Hospital of Central South University and Hunan Maternal and Child Health Hospital between 2016 and 2021 were selected for retrospective analysis of their general characteristics, vancomycin course, dose, liver function index, severity of liver injury, and concomitant medications.
RESULTS
Of the 4562 patients who received vancomycin, 17 patients were finally included, with an incidence rate of 0.37%. Of these patients, 12 were male (70.6%) and 5 were female (29.4%), ranging in age from 17 to 84 years with a mean average age of 45.41 ± 20.405 years. All patients were evaluated using Naranjo's score, with score ≥ 3. The dosage, time, and plasma concentration of vancomycin were analyzed and it was found that nine patients (52.94%) had abnormal liver function when initially given a dose of 1 g every 12 hours. In total, 14 patients (82.35%) with liver injury were taking vancomycin in combination with two to four drugs, and severe liver injury occurred in patients taking vancomycin in combination with two drugs. The occurrence time of liver injury was 2-12 days after starting vancomycin, with a mean of 4.53 ± 2.401 days. Of these patients, 16 patients (94.1%) showed liver function abnormalities within 7 days of taking the drug, and 2 patients with grade 3-4 liver injury both showed liver function abnormalities within 3 days of taking the drug. Only 4 of the 17 patients (23.53%) had vancomycin blood concentrations within the normal range, and there was no correlation found between blood concentration and severity of liver injury. Analysis of the correlation between the severity of liver injury and vancomycin showed that none of the patients had allergies such as rash, two patients (11.76%) had jaundice, and fatigue occurred in five patients (29.41%). The remaining ten patients (58.82%) had no symptoms related to liver injury. All 17 patients had abnormal aspartate aminotransferase/alanine aminotransferase levels and 9 patients also had abnormal bilirubin levels. In 15 patients (88.24%), the severity of liver injury was grade 1, indicating mild liver injury, and no correlation was observed between the severity of liver injury and creatinine. Of the 17 patients, 1 patient received no intervention, 4 patients stopped taking vancomycin after developing liver injury, 1 patient reduced the dose, and 11 patients (64.7%) were treated with hepatic protectant.
CONCLUSION
Although the study concluded that the incidence of liver injury was not high, the liver toxicity of vancomycin should still be considered and liver function indicators should be monitored during the clinical use of vancomycin.
Topics: Humans; Vancomycin; Female; Chemical and Drug Induced Liver Injury; Male; Middle Aged; Adult; Retrospective Studies; Anti-Bacterial Agents; Adolescent; Aged; Young Adult; Aged, 80 and over; Liver Function Tests
PubMed: 38831463
DOI: 10.1186/s13256-024-04574-4 -
Pediatric Radiology Jun 2024Multiple differentials exist for pediatric liver tumors under 2 years. Accurate imaging diagnosis may obviate the need for tissue sampling in most cases.
BACKGROUND
Multiple differentials exist for pediatric liver tumors under 2 years. Accurate imaging diagnosis may obviate the need for tissue sampling in most cases.
OBJECTIVE
To evaluate the imaging features and diagnostic accuracy of computed tomography (CT) in liver tumors in children under 2 years.
METHODS
Eighty-eight children under 2 years with treatment naive liver neoplasms and baseline contrast-enhanced CT were included in this institutional review board approved retrospective study. Two blinded onco-radiologists assessed these tumors in consensus. Findings assessed included enhancement pattern, lobulated appearance, cystic change, calcifications, central scar-like appearance, and metastases. The radiologists classified the lesion as hepatoblastoma, infantile hemangioma, mesenchymal hamartoma, rhabdoid tumor, or indeterminate, first based purely on imaging and then after alpha-fetoprotein (AFP) correlation. Multivariate analysis and methods of comparing means and frequencies were used for statistical analysis wherever applicable. Diagnostic accuracy, sensitivity, and positive predictive values were analyzed.
RESULTS
The mean age of the sample was 11.4 months (95% CI, 10.9-11.8) with 50/88 (57%) boys. The study included 72 hepatoblastomas, 6 hemangiomas, 4 mesenchymal hamartomas, and 6 rhabdoid tumors. Presence of calcifications, multilobular pattern of arterial enhancement, lobulated morphology, and central scar-like appearance was significantly associated with hepatoblastomas (P-value < 0.05). Fourteen out of eighty-eight lesions were called indeterminate based on imaging alone; six lesions remained indeterminate after AFP correlation. Pure radiology-based diagnostic accuracy was 81.8% (95% CI, 72.2-89.2%), which increased to 92.1% (95% CI, 84.3-96.7%) (P-value > 0.05) after AFP correlation, with one hepatoblastoma misdiagnosed as a rhabdoid tumor. If indeterminate lesions were excluded for biopsy, the accuracy would be 98.8% (95% CI, 93.4-99.9%).
CONCLUSION
CT had high accuracy for diagnosing liver neoplasms in the under 2-year age population after AFP correlation. Certain imaging features were significantly associated with the diagnosis of hepatoblastoma. A policy of biopsying only indeterminate lesions after CT and AFP correlation would avoid sampling in the majority of patients.
PubMed: 38831055
DOI: 10.1007/s00247-024-05958-w -
Journal of Pediatric Hematology/oncology Jul 2024The standard-risk hepatoblastoma has a good prognosis in children; however, refractory or relapsed (R/R) hepatoblastoma has a poor prognosis and high mortality rate....
BACKGROUND
The standard-risk hepatoblastoma has a good prognosis in children; however, refractory or relapsed (R/R) hepatoblastoma has a poor prognosis and high mortality rate. This study aimed to demonstrate the efficacy of high-dose chemotherapy and autologous hematopoietic stem cell transplantation (HSCT) rescue in pediatric patients with R/R hepatoblastoma.
METHODS
We retrospectively analyzed 6 pediatric patients with R/R hepatoblastoma who underwent autologous HSCT. The MEC conditioning regimen was used for all patients, comprising melphalan 140 mg/m 2 /day intravenously (IV) on day 7 and 70 mg/m 2 on day 6, etoposide 200 mg/m 2 IV on days 5 to 8, and carboplatin 400 mg/m 2 IV on days 5 to 8. One patient received a TopoThioCarbo regimen, comprising topotecan 2 mg/m 2 /day IV on days 4 to 8, thiotepa 300 mg/m 2 /day IV on days 6 to 8, and carboplatin 500 mg/m 2 /day IV on days 3 to 5, as the conditioning regimen for the first transplantation. This was followed by salvage chemotherapy for relapse, and the second transplantation was performed using MEC as the conditioning regimen.
RESULTS
We report the retrospective results of 6 patients with a median age of 1.8 (range 0.4 to 10.2) years who had R/R hepatoblastoma and underwent autologous HSCT. The median follow-up period was 58 (range 28 to 113) months after diagnosis. The median stage at diagnosis was 2.0 (range 2 to 4). Two patients had lung metastases during diagnosis. The median initial alpha-fetoprotein level was 292,888 (range 28,831 to 2,406,942) ng/mL, and the median number of chemotherapy lines before autologous HSCT was 3.5 (range 2 to 7). The disease status before HSCT was complete remission (CR) for all patients. The engraftment rate was 100%. No treatment-related mortality was reported. The 3-year event-free survival and overall survival rates were 83.3% and 100%, respectively. One patient relapsed after the second HSCT and achieved CR after salvage chemotherapy.
CONCLUSION
This study suggests autologous HSCT as an effective treatment in pediatric patients with R/R hepatoblastoma. Nevertheless, future large-scale prospective studies are warranted.
Topics: Humans; Hepatoblastoma; Hematopoietic Stem Cell Transplantation; Retrospective Studies; Male; Female; Child, Preschool; Liver Neoplasms; Neoplasm Recurrence, Local; Transplantation, Autologous; Child; Infant; Antineoplastic Combined Chemotherapy Protocols; Survival Rate; Salvage Therapy; Transplantation Conditioning; Carboplatin; Prognosis
PubMed: 38830616
DOI: 10.1097/MPH.0000000000002888 -
Talanta May 2024A label-free optical sandwich immunoassay sensor, utilizing weak value amplification and total internal reflection, was devised for real-time, high-sensitivity analysis...
A label-free optical sandwich immunoassay sensor, utilizing weak value amplification and total internal reflection, was devised for real-time, high-sensitivity analysis and detection of low-concentration targets. 3D printed channels and sodium chloride solution were employed to ensure reproducibility, reliability, and stability of the measurements for calibration. The sandwich structure demonstrated enhanced responsiveness in the proposed optical biosensor through a comparative analysis of the direct assay and sandwich assay for detecting alpha-fetoprotein (AFP) at the same concentration. By optimizing the binding sequences of the coating antibody, target, and detection antibody in the sandwich method, a more suitable sandwich sensing approach based on weak value amplification was achieved. With this approach, the limit of detection (LOD) of 6.29 ng/mL (pM level) for AFP in PBS solution was achieved. AFP testing and regeneration experiments in human serum have proved the feasibility of our methods in detecting complex samples and the reusability of sensing chips. Additionally, the method demonstrated excellent selectivity for unpaired antigens. The efficacy of this methodology was evaluated by simultaneously detecting AFP, carcinoembryonic antigen (CEA), and CA15-3 on a singular sensor chip. In conclusion, the label-free sandwich immunoassay sensing scheme holds promise for advancing the proposed optical sensors based on weak value amplification in early diagnosis and prevention applications. Compared to other biomarker detection methods, it will be easier to promote in practical applications.
PubMed: 38830277
DOI: 10.1016/j.talanta.2024.126302 -
Zhonghua Bing Li Xue Za Zhi = Chinese... Jun 2024
Topics: Humans; Female; Ovarian Neoplasms; beta Catenin; Carcinoma, Hepatocellular; Adenocarcinoma; Telomerase; alpha-Fetoproteins; Diagnosis, Differential; Mutation; Middle Aged; Glypicans; Liver Neoplasms
PubMed: 38825912
DOI: 10.3760/cma.j.cn112151-20231020-00278 -
Zhonghua Bing Li Xue Za Zhi = Chinese... Jun 2024
Topics: Humans; Endodermal Sinus Tumor; Male; Mediastinal Neoplasms; Adult; Retrospective Studies; Pleural Effusion, Malignant; Young Adult; alpha-Fetoproteins; Keratins; Diagnosis, Differential; Transcription Factors; Glypicans; Alkaline Phosphatase; Proto-Oncogene Proteins c-kit; Diagnostic Errors; Immunophenotyping; Isoenzymes; GPI-Linked Proteins
PubMed: 38825911
DOI: 10.3760/cma.j.cn112151-20231010-00245 -
Zhonghua Bing Li Xue Za Zhi = Chinese... Jun 2024
Topics: Humans; Male; Endodermal Sinus Tumor; Transcription Factors; DNA Helicases; Adult; Aged; Paranasal Sinus Neoplasms; Nuclear Proteins; Diagnosis, Differential; alpha-Fetoproteins; Cell Differentiation; Neoplasm Recurrence, Local; Glypicans
PubMed: 38825909
DOI: 10.3760/cma.j.cn112151-20231025-00306