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BMC Gastroenterology Jun 2024Type C hepatitis B-related acute-on-chronic liver failure (HBV-ACLF), which is based on decompensated cirrhosis, has different laboratory tests, precipitating events,...
BACKGROUND
Type C hepatitis B-related acute-on-chronic liver failure (HBV-ACLF), which is based on decompensated cirrhosis, has different laboratory tests, precipitating events, organ failure and clinical outcomes. The predictors of prognosis for type C HBV-ACLF patients are different from those for other subgroups. This study aimed to construct a novel, short-term prognostic score that applied serological indicators of hepatic regeneration and noninvasive assessment of liver fibrosis to predict outcomes in patients with type C HBV-ACLF.
METHOD
Patients with type C HBV-ACLF were observed for 90 days. Demographic information, clinical examination, and laboratory test results of the enrolled patients were collected. Univariate and multivariate logistic regression were performed to identify independent prognostic factors and develop a novel prognostic scoring system. A receiver operating characteristic (ROC) curve was used to analyse the performance of the model.
RESULTS
A total of 224 patients with type C HBV-ACLF were finally included. The overall survival rate within 90 days was 47.77%. Age, total bilirubin (TBil), international normalized ratio (INR), alpha-fetoprotein (AFP), white blood cell (WBC), serum sodium (Na), and aspartate aminotransferase/platelet ratio index (APRI) were found to be independent prognostic factors. According to the results of the logistic regression analysis, a new prognostic model (named the A3Twin score) was established. The area under the curve (AUC) of the receiver operating characteristic curve (ROC) was 0.851 [95% CI (0.801-0.901)], the sensitivity was 78.8%, and the specificity was 71.8%, which were significantly higher than those of the MELD, IMELD, MELD-Na, TACIA and COSSH-ACLF II scores (all P < 0.001). Patients with lower A3Twin scores (<-9.07) survived longer.
CONCLUSIONS
A new prognostic scoring system for patients with type C HBV-ACLF based on seven routine indices was established in our study and can accurately predict short-term mortality and might be used to guide clinical management.
Topics: Humans; Male; Female; alpha-Fetoproteins; Acute-On-Chronic Liver Failure; Retrospective Studies; Middle Aged; Prognosis; Adult; Biomarkers; Aspartate Aminotransferases; ROC Curve; Platelet Count; Hepatitis B, Chronic; Liver Cirrhosis; Survival Rate; Predictive Value of Tests; Logistic Models
PubMed: 38834942
DOI: 10.1186/s12876-024-03276-x -
Critical Reviews in Oncology/hematology Jun 2024The immune system plays a pivotal role in combating diseases, including cancer, with monocytes emerging as key regulators of immune response dynamics. This article... (Review)
Review
The immune system plays a pivotal role in combating diseases, including cancer, with monocytes emerging as key regulators of immune response dynamics. This article describes a novel strategy for cancer treatment centered on depleting myeloid-derived suppressor cells (MDSCs), to enhance the overall immune response while simultaneously targeting cancer cells directly. Alpha-fetoprotein (AFP) is an oncofetal protein that plays an important role in delivering nutrients to immature monocytes, embryonic, and cancer cells in a targeted manner. AFP can be repurposed, making it a vehicle for delivering toxins, rather than nutrients to kill cancer cells and deplete MDSCs in the tumor microenvironment (TME). Depleting monocytes not only stimulates the immune system but also improves the lymphocyte-to-monocyte ratio (LMR), often low in cancer patients. AFP combined with cytotoxic drugs, offers dual benefit-immune stimulation and targeted chemotherapy. Studies in xenograft models demonstrated high efficacy and safety of AFP-toxin conjugates, surpassing conventional targeted chemotherapy. Such conjugates have also been reported to provide superior efficacy and safety in cancer patients compared to chemotherapy. This approach, using AFP conjugated with toxins, either covalently or non-covalently, presents a safe and highly effective option for cancer immuno/chemotherapy.
PubMed: 38834093
DOI: 10.1016/j.critrevonc.2024.104407 -
International Journal of Surgery Case... Jul 2024Polyorchidism, or supernumerary testis, is a rare urogenital congenital disorder. Because of its rarity, there is no approved standard treatment protocol for preserving...
INTRODUCTION AND IMPORTANCE
Polyorchidism, or supernumerary testis, is a rare urogenital congenital disorder. Because of its rarity, there is no approved standard treatment protocol for preserving or removing the extra testicle, yet orchiopexy is frequently performed as a preferred treatment in most medical facilities.
CASE PRESENTATION
We present a 23-year-old single male with a bilaterally empty scrotum. He was unaware of his condition and had not seen a doctor before being admitted to our surgical unit. During his younger sibling's circumcision by a local circumcisionist (a medical staff member, idealy a nurse, whose duty is to perform circumcision, preferably at home), he saw something different (his emptey scrotum) and came to us with his problem. Laboratory findings revealed severe oligospermia, and tumor markers (Alpha fetoprotein, beta-human chorionic gonadotropin, and lactate dehydrogenase) were negative for malignancy. The patient underwent bilateral herniorrhaphy and orchiopexy of all six testicles (three in each inguinal canal) and had an uneventful recovery.
CLINICAL DISCUSSION
As polyorchidism is not a common problem, its management remains a contentious issue due to the lack of evidence-based consensus. However, with the introduction of new imaging modalities and on-table frozen section biopsy, the decision to continue with orchiopexy or orchiectomy can be easily justified; however, conservative treatment is preferable in cases of no coexisting anomalies, particularly cryptorchidism.
CONCLUSION
Polyorchidism could run unnoticed for years, especially if there is no direct and consistent access to a medical facility. In cases where polyorchidism is detected accidentally by imaging or during surgical exploration, the treatment must be justified accordingly.
PubMed: 38833904
DOI: 10.1016/j.ijscr.2024.109837 -
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