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Hepatocellular carcinoma presenting as an extrahepatic mass: A case report and review of literature.World Journal of Gastrointestinal... May 2024Hepatocellular carcinoma (HCC) is a primary liver tumor generally diagnosed based on radiographic findings. Metastatic disease is typically associated with increased...
BACKGROUND
Hepatocellular carcinoma (HCC) is a primary liver tumor generally diagnosed based on radiographic findings. Metastatic disease is typically associated with increased tumor diameter, multifocality, and vascular invasion. We report a case of a patient who presented with extrahepatic HCC metastasis to a portocaval lymph node with occult hepatic primary on computed tomography (CT). We review the literature for cases of extrahepatic HCC presentation without known hepatic lesions and discuss strategies to differentiate between metastatic and ectopic HCC.
CASE SUMMARY
A 67-year-old male with remotely treated hepatis C was referred for evaluation of an enlarging portocaval, mixed cystic-solid mass. Serial CT evaluations demonstrated steatosis, but no cirrhosis or liver lesions. Endoscopic ultrasound demonstrated a normal-appearing pancreas, biliary tree, and liver. Fine needle aspiration yielded atypical cells. The differential diagnosis included duodenal or pancreatic cyst, lymphoproliferative cyst, stromal or mesenchymal lesions, nodal involvement from gastrointestinal or hematologic malignancy, or duodenal gastro-intestinal stromal tumor. After review by a multidisciplinary tumor board, the patient underwent open surgical resection of a 5.2 cm × 5.5 cm retroperitoneal mass with pathology consistent with moderately-differentiated HCC. Magnetic resonance imaging (MRI) subsequently demonstrated a 1.2 cm segment VIII hepatic lesion with late arterial enhancement, fatty sparing, and intrinsic T1 hyperintensity. Alpha fetoprotein was 23.3 ng/mL. The patient was diagnosed with HCC with portocaval nodal involvement. Review: We surveyed the literature for HCC presenting as extrahepatic masses without history of concurrent or prior intrahepatic HCC. We identified 18 cases of extrahepatic HCC ultimately found to represent metastatic lesions, and 30 cases of extrahepatic HCC found to be primary, ectopic HCC.
CONCLUSION
Hepatocellular carcinoma can seldomly present with extrahepatic metastasis in the setting of occult primary. In patients with risk factors for HCC and lesions suspicious for metastatic disease, MRI may be integral to identifying small hepatic lesions and differentiating from ectopic HCC. Tumor markers may also have utility in establishing the diagnosis.
PubMed: 38764834
DOI: 10.4251/wjgo.v16.i5.2241 -
World Journal of Gastrointestinal... May 2024The models for assessing liver function, mainly the Child-Pugh (CP), albuminbilirubin (ALBI), and platelet-ALBI (PALBI) classifications, have been validated for use in...
BACKGROUND
The models for assessing liver function, mainly the Child-Pugh (CP), albuminbilirubin (ALBI), and platelet-ALBI (PALBI) classifications, have been validated for use in estimating the prognosis of hepatocellular carcinoma (HCC) patients. However, thrombocytopenia is a common finding and may influence the prognostic value of the three models in HCC.
AIM
To investigate and compare the prognostic performance of the above three models in thrombocytopenic HCC patients.
METHODS
A total of 135 patients with thrombocytopenic HCC who underwent radical surgery were retrospectively analyzed. Preoperative scores on the CP, ALBI and PALBI classifications were estimated accordingly. Kaplan-Meier curves with log-rank tests and Cox regression models were used to explore the significant factors associated with overall survival (OS) and recurrence-free survival (RFS).
RESULTS
The preoperative platelet counts were significantly different among the CP, ALBI and PALBI groups. After a median follow-up of 28 mo, 39.3% (53/135) of the patients experienced postoperative recurrence, and 36.3% (49/135) died. Univariate analysis suggested that α-fetoprotein levels, tumor size, vascular invasion, and ALBI grade were significant predictors of OS and RFS. According to the multivariate Cox regression model, ALBI was identified as an independent prognostic factor. However, CP and PALBI grades were not statistically significant prognostic indicators.
CONCLUSION
The ALBI grade, rather than CP or PALBI grade, is a significant prognostic indicator for thrombocytopenic HCC patients.
PubMed: 38764822
DOI: 10.4251/wjgo.v16.i5.1763 -
World Journal of Gastrointestinal... May 2024Vessels encapsulating tumor clusters (VETC) represent a recently discovered vascular pattern associated with novel metastasis mechanisms in hepatocellular carcinoma...
BACKGROUND
Vessels encapsulating tumor clusters (VETC) represent a recently discovered vascular pattern associated with novel metastasis mechanisms in hepatocellular carcinoma (HCC). However, it seems that no one have focused on predicting VETC status in small HCC (sHCC). This study aimed to develop a new nomogram for predicting VETC positivity using preoperative clinical data and image features in sHCC (≤ 3 cm) patients.
AIM
To construct a nomogram that combines preoperative clinical parameters and image features to predict patterns of VETC and evaluate the prognosis of sHCC patients.
METHODS
A total of 309 patients with sHCC, who underwent segmental resection and had their VETC status confirmed, were included in the study. These patients were recruited from three different hospitals: Hospital 1 contributed 177 patients for the training set, Hospital 2 provided 78 patients for the test set, and Hospital 3 provided 54 patients for the validation set. Independent predictors of VETC were identified through univariate and multivariate logistic analyses. These independent predictors were then used to construct a VETC prediction model for sHCC. The model's performance was evaluated using the area under the curve (AUC), calibration curve, and clinical decision curve. Additionally, Kaplan-Meier survival analysis was performed to confirm whether the predicted VETC status by the model is associated with early recurrence, just as it is with the actual VETC status and early recurrence.
RESULTS
Alpha-fetoprotein_lg10, carbohydrate antigen 199, irregular shape, non-smooth margin, and arterial peritumoral enhancement were identified as independent predictors of VETC. The model incorporating these predictors demonstrated strong predictive performance. The AUC was 0.811 for the training set, 0.800 for the test set, and 0.791 for the validation set. The calibration curve indicated that the predicted probability was consistent with the actual VETC status in all three sets. Furthermore, the decision curve analysis demonstrated the clinical benefits of our model for patients with sHCC. Finally, early recurrence was more likely to occur in the VETC-positive group compared to the VETC-negative group, regardless of whether considering the actual or predicted VETC status.
CONCLUSION
Our novel prediction model demonstrates strong performance in predicting VETC positivity in sHCC (≤ 3 cm) patients, and it holds potential for predicting early recurrence. This model equips clinicians with valuable information to make informed clinical treatment decisions.
PubMed: 38764811
DOI: 10.4251/wjgo.v16.i5.1808 -
Journal of Molecular Medicine (Berlin,... Jul 2024Liver cirrhosis due to nonalcoholic steatohepatitis (NASH) is a life-threatening condition with increasing incidence world-wide. Although its symptoms are unspecific, it... (Review)
Review
Liver cirrhosis due to nonalcoholic steatohepatitis (NASH) is a life-threatening condition with increasing incidence world-wide. Although its symptoms are unspecific, it can lead to decompensation events such as ascites, hepatic encephalopathy, variceal hemorrhage, and hepatocellular carcinoma (HCC). In addition, an increased risk for cardiovascular events has been demonstrated in patients with NASH. Pharmacological treatments for NASH cirrhosis are not yet available, one of the reasons being the lack in surrogate endpoints available in clinical trials of NASH cirrhosis. The feasibility of non-invasive prognostic biomarkers makes them interesting candidates as possible surrogate endpoints if their change following treatment would result in better outcomes for patients in future clinical trials of NASH cirrhosis. In this systematic literature review, a summary of the available literature on the prognostic performance of non-invasive biomarkers in terms of cardiovascular events, liver-related events, and mortality is outlined. Due to the scarcity of data specific for NASH cirrhosis, this review includes studies on NAFLD whose evaluation focuses on cirrhosis. Our search strategy identified the following non-invasive biomarkers with prognostic value in studies of NASH patients: NAFLD fibrosis score (NFS), Fibrosis-4 (FIB-4), aspartate aminotransferase (AST) to platelet ratio index (APRI), enhanced liver fibrosis (ELF™), BARD (BMI, AST/ALT (alanine aminotransferase) ratio, diabetes), Hepamet Fibrosis Score (HFS), liver enzymes (AST + ALT), alpha-fetoprotein, platelet count, neutrophil to lymphocyte ratio (NLR), Lysyl oxidase-like (LOXL) 2, miR-122, liver stiffness, MEFIB (liver stiffness measured with magnetic resonance elastography (MRE) + FIB-4), and PNPLA3 GG genotype. The aim of the present systematic literature review is to provide the reader with a summary of the non-invasive biomarkers with prognostic value in NASH cirrhosis and give an evaluation of their utility as treatment monitoring biomarkers in future clinical trials.
Topics: Humans; Non-alcoholic Fatty Liver Disease; Liver Cirrhosis; Biomarkers; Prognosis
PubMed: 38753041
DOI: 10.1007/s00109-024-02448-2 -
Frontiers in Oncology 2024The aim of this study was to evaluate tumor progression and recurrence patterns of radiofrequency ablation (RFA) with or without transarterial chemoembolization (TACE)...
Radiofrequency ablation with or without transarterial chemoembolization for hepatocellular carcinoma meeting Milan criteria: a focus on tumor progression and recurrence patterns.
BACKGROUND/OBJECTIVE
The aim of this study was to evaluate tumor progression and recurrence patterns of radiofrequency ablation (RFA) with or without transarterial chemoembolization (TACE) for treating hepatocellular carcinoma (HCC) that meets Milan criteria.
METHODS
This retrospective study included consecutive HCC patients meeting Milan criteria who underwent percutaneous RFA with or without TACE as initial treatment at a tertiary academic center between December 2017 and 2022. Technical success rate, local recurrence-free survival (LRFS), progression-free survival (PFS) and recurrence patterns were recorded.
RESULTS
A total of 135 HCC patients (109 male [80.7%]) with a mean age of 62 years and 147 target lesions were retrospectively enrolled. The technical success rate was 99.3%. The median LRFS was 60 months, and the cumulative 1-, 3-, and 5-year LRFS were 88.9%, 70.1%, and 30.0%, respectively. Additionally, the median PFS was 23 months, with cumulative 1-, 3-, and 5-year PFS of 74%, 30%, and 0%, respectively. Multivariate analysis confirmed that age > 60, alpha-fetoprotein (AFP) (> 10), and albumin were associated with PFS (2.34, p = 0.004; 1.96, p = 0.021; 0.94, p = 0.007, respectively). Six recurrence patterns were identified: local tumor progression (LTP) alone (n = 15, 25.0%), intrahepatic distant recurrence (IDR) alone (n = 34, 56.7%), extrahepatic recurrence (ER) alone (n = 2, 3.3%), IDR + ER (n = 2, 3.3%), LTP + IDR (n = 5, 8.8%), and LTP + IDR + ER (n = 2, 3.3%). IDR occurred most frequently as a sign of good local treatment.
CONCLUSIONS
RFA in combination with TACE does not appear to provide an advantage over RFA alone in improving tumor progression in patients with HCC meeting the Milan criteria. However, further prospective studies are needed to confirm these findings and to determine the optimal treatment approach for this patient population.
PubMed: 38751809
DOI: 10.3389/fonc.2024.1392495 -
Frontiers in Microbiology 2024Gastric and intestinal diseases possess distinct characteristics although they are interconnected. The primary objective of this study was to investigate the...
OBJECTIVE
Gastric and intestinal diseases possess distinct characteristics although they are interconnected. The primary objective of this study was to investigate the pathogenesis of gastrointestinal diseases through different analyses of clinical characteristics, serum immunology, and gut microbiota in patients with gastrointestinal diseases.
METHODS
We collected serum samples from 89 patients with gastrointestinal diseases and 9 healthy controls for immunological assessment, stool samples for DNA extraction, library construction, sequencing, as well as clinical data for subsequent analysis.
RESULTS
Regarding clinical characteristics, there were significant differences between the disease group and the healthy control (HC) group, particularly in terms of age, cancer antigen 125 (CA125), cancer antigen 199 (CA199), alpha-fetoprotein (AFP), total bilirubin (TBIL) and indirect bilirubin (IBIL). The intestinal disease (ID) group exhibited the highest IL-6 level, which significantly differed from the stomach disease (SD) group ( < 0.05). In comparing the HC with the ID groups, significant differences in abundance were detected across 46 species. The HC group displayed a greater abundance of and than other species. Similarly, when comparing the HC with the SD groups, significant differences in abundance were identified among 49 species, with only one species that the in the HC group exhibited a higher abundance than others. Furthermore, certain clinical characteristics, such as CA125, CA199, glucose (Glu), creatine kinase-MB (CKMB) and interleukin-22 (IL-22), displayed positive correlations with enriched gut species in the ID and SD groups, while exhibiting a negative correlation with the HC group.
CONCLUSION
The disturbance in human gut microbiota is intimately associated with the development and progression of gastrointestinal diseases. Moreover, the gut microbiota in the HC group was found more diverse than that in the ID and SD groups, and there were significant differences in microbial species among the three groups at different classification levels. Notably, a correlation was identified between specific clinical characteristics (e.g., CA125, CA199, Glu, CKMB and IL-22) and gut microbiota among patients with gastrointestinal diseases.
PubMed: 38751718
DOI: 10.3389/fmicb.2024.1323842 -
World Journal of Oncology Jun 2024Hepatocellular carcinoma (HCC) is often diagnosed at a late stage and frequently recurs despite curative intervention, leading to poor survival outcomes. Frontline...
Complete Pathologic Response to Gemcitabine and Oxaliplatin Chemotherapy After Prior Therapies in a Patient With Hepatocellular Carcinoma and Peritoneal Metastases Undergoing Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy.
Hepatocellular carcinoma (HCC) is often diagnosed at a late stage and frequently recurs despite curative intervention, leading to poor survival outcomes. Frontline systemic therapies include combination immunotherapy regimens and tyrosine kinase inhibitors. We report a case of a 38-year-old woman with chronic hepatitis B and C coinfection-associated non-cirrhotic HCC, which recurred in the peritoneum after initial resection of her primary tumor. Disease progression occurred on both atezolizumab/bevacizumab and lenvatinib, and she was subsequently treated with gemcitabine and oxaliplatin (GEMOX) chemotherapy and exhibited a profound clinical response on imaging with normalization of alpha fetoprotein (AFP) after several months. Following extensive multidisciplinary discussion, she underwent cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) that removed all visible macroscopic tumor. Her pathology demonstrated a complete pathologic response. She received two additional months of postoperative chemotherapy, and then proceeded with close monitoring off therapy. To our knowledge, this is the first reported case of a complete pathologic response to GEMOX chemotherapy in the context of CRS/HIPEC for peritoneal metastases in HCC, after progression on standard immunotherapy and tyrosine kinase inhibitor treatments. In this report, we review the current systemic treatment landscape in HCC. We highlight potential consideration of cytotoxic chemotherapy, which is less frequently utilized in current practice, in selected patients with HCC, and discuss the role of CRS/HIPEC in the management of peritoneal metastases. Further investigation regarding predictors of response to systemic treatments is strongly needed. Multidisciplinary management may ultimately prolong survival in patients with advanced HCC.
PubMed: 38751709
DOI: 10.14740/wjon1840 -
Liver Cancer Apr 2024Microvascular invasion (MVI) is one of the most important prognostic factors for hepatocellular carcinoma (HCC) recurrence, but its application in preoperative clinical...
Preoperative Prediction of Microvascular Invasion with Gadoxetic Acid-Enhanced Magnetic Resonance Imaging in Patients with Single Hepatocellular Carcinoma: The Implication of Surgical Decision on the Extent of Liver Resection.
INTRODUCTION
Microvascular invasion (MVI) is one of the most important prognostic factors for hepatocellular carcinoma (HCC) recurrence, but its application in preoperative clinical decisions is limited. This study aimed to identify preoperative predictive factors for MVI in HCC and further evaluate oncologic outcomes of different types and extents of hepatectomy according to stratified risk of MVI.
METHODS
Patients with surgically resected single HCC (≤5 cm) who underwent preoperative gadoxetic acid-enhanced magnetic resonance imaging (MRI) were included in a single-center retrospective study. Two radiologists reviewed the images with no clinical, pathological, or prognostic information. Significant predictive factors for MVI were identified using logistic regression analysis against pathologic MVI and used to stratify patients. In the subgroup analysis, long-term outcomes of the stratified patients were analyzed using the Kaplan-Meier method with log-rank test and compared between anatomical and nonanatomical or major and minor resection.
RESULTS
A total of 408 patients, 318 men and 90 women, with a mean age of 56.7 years were included. Elevated levels of tumor markers (alpha-fetoprotein [α-FP] ≥25 ng/mL and PIVKA-II ≥40 mAU/mL) and three MRI features (tumor size ≥3 cm, non-smooth tumor margin, and arterial peritumoral enhancement) were independent predictive factors for MVI. As the MVI risk increased from low (no predictive factor) and intermediate (1-2 factors) to high-risk (3-4 factors), recurrence-free and overall survival of each group significantly decreased ( = 0.001). In the high MVI risk group, 5-year cumulative recurrence rate was significantly lower in patients who underwent major compared to minor hepatectomy (26.6 vs. 59.8%, = 0.027).
CONCLUSION
Tumor markers and MRI features can predict the risk of MVI and prognosis after hepatectomy. Patients with high MVI risk had the worst prognosis among the three groups, and major hepatectomy improved long-term outcomes in these high-risk patients.
PubMed: 38751555
DOI: 10.1159/000531786 -
Journal of Translational Medicine May 2024Patients with alpha-fetoprotein (AFP)-positive hepatocellular carcinoma (HCC) have aggressive biological behavior and poor prognosis. Therefore, survival time is one of...
BACKGROUND
Patients with alpha-fetoprotein (AFP)-positive hepatocellular carcinoma (HCC) have aggressive biological behavior and poor prognosis. Therefore, survival time is one of the greatest concerns for patients with AFP-positive HCC. This study aimed to demonstrate the utilization of six machine learning (ML)-based prognostic models to predict overall survival of patients with AFP-positive HCC.
METHODS
Data on patients with AFP-positive HCC were extracted from the Surveillance, Epidemiology, and End Results database. Six ML algorithms (extreme gradient boosting [XGBoost], logistic regression [LR], support vector machine [SVM], random forest [RF], K-nearest neighbor [KNN], and decision tree [ID3]) were used to develop the prognostic models of patients with AFP-positive HCC at one year, three years, and five years. Area under the receiver operating characteristic curve (AUC), confusion matrix, calibration curves, and decision curve analysis (DCA) were used to evaluate the model.
RESULTS
A total of 2,038 patients with AFP-positive HCC were included for analysis. The 1-, 3-, and 5-year overall survival rates were 60.7%, 28.9%, and 14.3%, respectively. Seventeen features regarding demographics and clinicopathology were included in six ML algorithms to generate a prognostic model. The XGBoost model showed the best performance in predicting survival at 1-year (train set: AUC = 0.771; test set: AUC = 0.782), 3-year (train set: AUC = 0.763; test set: AUC = 0.749) and 5-year (train set: AUC = 0.807; test set: AUC = 0.740). Furthermore, for 1-, 3-, and 5-year survival prediction, the accuracy in the training and test sets was 0.709 and 0.726, 0.721 and 0.726, and 0.778 and 0.784 for the XGBoost model, respectively. Calibration curves and DCA exhibited good predictive performance as well.
CONCLUSIONS
The XGBoost model exhibited good predictive performance, which may provide physicians with an effective tool for early medical intervention and improve the survival of patients.
Topics: Carcinoma, Hepatocellular; Humans; alpha-Fetoproteins; Liver Neoplasms; Machine Learning; Female; Prognosis; Male; Middle Aged; ROC Curve; Aged; Area Under Curve; Calibration; Algorithms
PubMed: 38741163
DOI: 10.1186/s12967-024-05203-w -
Scientific Reports May 2024Lysyl oxidase-like 2 (LOXL2) mediates the crosslinking of extracellular collagen, reflecting qualitative changes in liver fibrosis. This study aimed to validate the...
Lysyl oxidase-like 2 (LOXL2) mediates the crosslinking of extracellular collagen, reflecting qualitative changes in liver fibrosis. This study aimed to validate the utility of serum LOXL2 levels as a predictive biomarker for the development of hepatocellular carcinoma (HCC) in patients with hepatitis C virus (HCV) infection who achieved a sustained virological response (SVR). This retrospective study included 137 patients with chronic HCV infection without history of HCC development and who achieved SVR via direct-acting antiviral therapy. Median LOXL2 levels decreased significantly after SVR achievement (pre-Tx, 2.33 ng/mL; post-Tx, 1.31 ng/mL, p < 0.001). Post-Tx LOXL2 levels, fibrosis-4 index, platelet counts, Wisteria floribunda agglutinin-positive human Mac-2 binding protein levels, and alpha-fetoprotein (AFP) levels were identified as independent predictive factors for post-SVR HCC development in the univariate analysis. The incidence of post-SVR HCC development was significantly higher in patients with post-Tx LOXL2 levels ≥ 2.08 ng/mL and AFP levels ≥ 5.0 ng/mL than in patients with elevated levels of either marker or with lower marker levels. Serum LOXL2 levels can serve as a predictive biomarker for HCC development after achieving SVR. The combination of serum LOXL2 and AFP levels provides robust risk stratification for HCC development after SVR, suggesting an enhanced surveillance strategy.
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; Male; Female; Middle Aged; Amino Acid Oxidoreductases; Sustained Virologic Response; Retrospective Studies; Hepatitis C, Chronic; Aged; Antiviral Agents; Hepacivirus; Biomarkers, Tumor; alpha-Fetoproteins; Adult
PubMed: 38740815
DOI: 10.1038/s41598-024-61366-y