Endoscopic ultrasound-guided tissue acquisition for focal liver lesions in patients with a history of multiple primary malignant neoplasms.

Objective: This study aimed to investigate the usefulness of endoscopic ultrasound-guided tissue acquisition (EUS-TA) for diagnosing focal liver lesions in patients with a history of multiple primary malignant neoplasms. Methods: Among patients who underwent EUS-TA for focal liver lesions between 2016 and 2022, those with a history of multiple malignant neoplasms were included. A histologically confirmed malignant tumor within the past 5 years before EUS-TA was defined as a history of malignant neoplasm. The primary outcomes were diagnostic ability and adverse events of EUS-TA. Results: This study included 16 patients (median age, 73 [33-90] years), the median tumor size was 32 (6-51) mm, 14 had a history of double malignant neoplasms, whereas two had triple malignant neoplasms. Malignant neoplasms were detected histologically or cytologically in all cases. Immunohistochemistry was performed in 75% (12/16), and the final diagnosis of EUS-TA was metastatic liver tumor in 12 patients, and primary malignant liver tumor in four patients. The primary site could be identified in 11 of 12 metastatic tumor cases. The diagnostic yield of EUS-TA was 100% (16/16) for differentiating benign and malignant tumors and 94% (15/16) for confirming the histological type including the primary site of metastatic lesions. No adverse events were associated with the procedure. Conclusion: EUS-TA is a useful diagnostic modality for focal liver lesions in patients with a history of multiple malignant neoplasms, allowing for the differential diagnosis of primary and metastatic tumors and identification of the primary site of metastatic lesions.

The Paradox of Modern Technology in Standardizing Thermal Liver Ablation: Fostering Uniformity or Diversity?

PURPOSE: Currently, significant medical practice variation exists in thermal ablation (TA) of malignant liver tumors with associated differences in outcomes. The IMaging and Advanced Guidance for workflow optimization in Interventional Oncology (IMAGIO) consortium aims to integrate interventional oncology into the standard clinical pathway for cancer treatment in Europe by 2030, by development of a standardized low-complex-high-precision workflow for TA of malignant liver tumors. This study was conducted at the start of the IMAGIO project with the aim to explore the current state and future role of modern technology in TA of malignant liver tumors. MATERIALS AND METHODS: A cross-sectional questionnaire was conducted followed by an expert focus group discussion with core members and collaborating partners of the consortium. RESULTS: Of the 13 participants, 10 respondents filled in the questionnaire. During the focus group discussion, there was consensus on the need for international standardization in TA and several aspects of the procedure, such as planning based on cross-sectional images, the adoption of different techniques for needle placement and the importance of needle position- and post-ablative margin confirmation scans. Yet, also considerable heterogeneity was reported in the adoption of modern technology, particularly in navigational systems and computer-assisted margin assessment. CONCLUSION: This study mirrored the current diversity in workflow of thermal liver ablation. To obtain comparable outcomes worldwide, standardization is needed. While advancements in tools and software hold the potential to homogenize outcome measurement and minimize operator-dependent variability, the rapid increase in availability also contributes to enhanced workflow variation.

A Case of Spontaneous Regression of Adult Multi-system Langerhans Cell Histiocytosis Presenting as Liver Tumor Rupture.

Adult multisystem Langerhans cell histiocytosis (MS-LCH) is rare and has a poor prognosis. A 67-year-old man with MS-LCH presented with a hepatic tumor rupture and multiple masses in the lungs, liver, and pancreas. Despite the initial aggressive disease course and involvement of organs at risk, the patient experienced spontaneous regression and lesion disappearance following smoking cessation without chemotherapy. A literature review revealed a distinct subset of MS-LCH that can be managed by smoking cessation and careful observation through follow-up imaging. This suggests that careful observation through follow-up imaging may be a reasonable alternative to chemotherapy in select adult cases of MS-LCH.

Clinical Characteristics and Outcomes of Neonatal Hepatoblastoma: A Single Center Study.

OBJECTIVE: Hepatoblastoma (HB) diagnosed within one month following birth qualifies for a diagnosis of neonatal HB, whose prognosis is reportedly controversial, and its treatment is challenging. This study discussed the diagnosis, treatment, and outcomes of neonatal HB at a single center so as to enhance its overall management in the future. METHODS: The clinical information of babies diagnosed with neonatal HB at our center from August 2009 to September 2023 were retrospectively analyzed for demographics, clinical features, therapy, and outcomes. The outcomes were estimated by the Kaplan-Meier analysis method. RESULTS: The study comprised 79 patients aged less than one year old, among which 14 had neonatal HB whereas 65 were non-neonatal HB patients. No differences were found between groups regarding gender, birth weight, delivery details, parental age, clinical signs, or treatment strategies. Neonatal HB patients were more likely to have PRETEXT I-II, smaller tumor size, congenital diseases, and lower risk tumor grade (p < 0.05). Additionally, the AFP levels of all neonatal HB patients were greater than 10,000 ng/ml (p = 0.009) and they had higher levels of ferritin (p = 0.003) and hemoglobin (p = 0.021), but lower levels of serum total proteins (p = 0.001). The three-year survival rate (100% vs 90.8%) and three-year event-free survival rate (100% vs 86.2%) in the neonatal HB group were higher than the non-neonatal HB group. CONCLUSION: Neonatal HB patients have unique clinical features and can achieve an excellent prognosis following combined treatment with surgery and chemotherapy. Tumor resection, when carefully performed, was safe even in babies younger than one months old. Further and long-term studies are needed from a larger neonatal HB population. LEVEL OF EVIDENCE: Level III.

Ultrasomics in liver cancer: Developing a radiomics model for differentiating intrahepatic cholangiocarcinoma from hepatocellular carcinoma using contrast-enhanced ultrasound.

BACKGROUND: Hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) represent the predominant histological types of primary liver cancer, comprising over 99% of cases. Given their differing biological behaviors, prognoses, and treatment strategies, accurately differentiating between HCC and ICC is crucial for effective clinical management. Radiomics, an emerging image processing technology, can automatically extract various quantitative image features that may elude the human eye. Reports on the application of ultrasound (US)-based radiomics methods in distinguishing HCC from ICC are limited. AIM: To develop and validate an ultrasomics model to accurately differentiate between HCC and ICC. METHODS: In our retrospective study, we included a total of 280 patients who were diagnosed with ICC (n = 140) and HCC (n = 140) between 1999 and 2019. These patients were divided into training (n = 224) and testing (n = 56) groups for analysis. US images and relevant clinical characteristics were collected. We utilized the XGBoost method to extract and select radiomics features and further employed a random forest algorithm to establish ultrasomics models. We compared the diagnostic performances of these ultrasomics models with that of radiologists. RESULTS: Four distinct ultrasomics models were constructed, with the number of selected features varying between models: 13 features for the US model; 15 for the contrast-enhanced ultrasound (CEUS) model; 13 for the combined US + CEUS model; and 21 for the US + CEUS + clinical data model. The US + CEUS + clinical data model yielded the highest area under the receiver operating characteristic curve (AUC) among all models, achieving an AUC of 0.973 in the validation cohort and 0.971 in the test cohort. This performance exceeded even the most experienced radiologist (AUC = 0.964). The AUC for the US + CEUS model (training cohort AUC = 0.964, test cohort AUC = 0.955) was significantly higher than that of the US model alone (training cohort AUC = 0.822, test cohort AUC = 0.816). This finding underscored the significant benefit of incorporating CEUS information in accurately distinguishing ICC from HCC. CONCLUSION: We developed a radiomics diagnostic model based on CEUS images capable of quickly distinguishing HCC from ICC, which outperformed experienced radiologists.

Comparison of laparoscopic liver resection for the ventral versus the dorsal areas of segment 8.

PURPOSE: The technical difficulties of laparoscopic liver resection (LLR) are greatly associated with the location of liver tumors. Since segment 8 (S8) contains a wide area, the difficulty of LLR for S8 tumors may vary depending on the location within the segment, such as the ventral (S8v) and dorsal (S8d) area, but the difference is unclear. METHODS: We retrospectively investigated 30 patients who underwent primary laparoscopic partial liver resection for liver tumors in S8 at Kobe University Hospital between January 2018 and June 2023. RESULTS: Thirteen and 17 patients underwent LLR for S8v and S8d, respectively. The operation time was significantly longer (S8v 203[135-259] vs. S8d 261[186-415] min, P = 0.002) and the amount of blood loss was significantly higher (10[10-150] vs. 10[10-200] mL, P = 0.034) in the S8d group than in the S8v group. No significant differences were observed in postoperative complications or postoperative length of hospital stay. Additionally, intraoperative findings revealed that the rate at which the case performed partial liver mobilization in the S8d group was higher (2[15.4%] vs. 8[47.1%], P = 0.060) and the median parenchymal transection time of the S8d group was longer (102[27-148] vs. 129[37-175] min, P = 0.097) than those in the S8v group, but there were no significant differences. CONCLUSION: The safety of LLR for the S8d was comparable to that of LLR for S8v, although LLR for S8d resulted in longer operative time and more blood loss. THE TRIAL REGISTRATION NUMBER: B230165 (approved at December 26, 2023).

Pay attention to the application of indocyanine green fluorescence imaging technology in laparoscopic liver cancer resection.

Traditional laparoscopic liver cancer resection faces challenges, such as difficulties in tumor localization and accurate marking of liver segments, as well as the inability to provide real-time intraoperative navigation. This approach falls short of meeting the demands for precise and anatomical liver resection. The introduction of fluorescence imaging technology, particularly indocyanine green, has demonstrated significant advantages in visualizing bile ducts, tumor localization, segment staining, microscopic lesion display, margin examination, and lymph node visualization. This technology addresses the inherent limitations of traditional laparoscopy, which lacks direct tactile feedback, and is increasingly becoming the standard in laparoscopic procedures. Guided by fluorescence imaging technology, laparoscopic liver cancer resection is poised to become the predominant technique for liver tumor removal, enhancing the accuracy, safety and efficiency of the procedure.

Simultaneously Detected Liver and Lung Metastases from Colorectal Carcinoma: A Potential Treatment Strategy.

BACKGROUND/AIM: No clear treatment strategy for simultaneously detected liver and lung metastases (SLLM) of colorectal carcinoma has been established, to date. We aimed to identify the prognostic factors for SLLM and propose an appropriate treatment option. PATIENTS AND METHODS: This retrospective study included 64 patients with SLLM: 32 underwent pulmonary resection after hepatectomy in 32, while the other 32 underwent hepatectomy alone in 32. Poor prognostic factors and a suitable strategy for SLLM were assessed. RESULTS: Multivariate analysis showed that preoperative carcinoembryonic antigen (CEA) level ≥20 ng/ml (p=0.001) and unresected lung metastases (p=0.001) were independent prognostic factors for poor overall survival. Compared with the non-pulmonary resection group, the rate of R1 resection of liver tumors (46.8% vs. 15.6%; p=0.007), incidence of complications after hepatectomy (Clavien-Dindo grade ≥III: 21.8% vs. 0%; p=0.005) and having four or more metastatic lung nodules (40.6% vs. 3.2%; p=0.001) were significantly higher in the group that underwent hepatectomy only. CONCLUSION: Preoperative CEA ≥20 ng/ml and unresectable pulmonary nodules were prognostic factors for poor survival of patients with SLLM. Furthermore, the presence of more than four pulmonary nodules was a preoperative predictive factor for unresectable pulmonary nodules. R1 resection and the occurrence of complications after hepatectomy should be avoided; a smooth transition from hepatectomy to pulmonary resection is important.

Laparoscopic right upper transversal hepatectomy: Strategies for right hepatic vein resection and reconstruction.

OBJECTIVE: The right upper transversal hepatectomy (RUTH) is considered a complex technique of parenchymal-sparing hepatectomies. The intraoperative management of the right hepatic vein (RHV) is still controversial because it may cause obstruction of outflow in the remnant hepatic segment. The aim of this study is to present our experience of laparoscopic RUTH and the strategy of RHV resection and reconstruction in different settings. METHODS: Five patients who underwent laparoscopic RUTH for liver tumor were enrolled retrospectively. Clinical and pathological features of the patients, peri-operative treatment, as well as short- and long-term outcomes were collected for analysis. RESULTS: Laparoscopic RUTH was successfully performed in all five patients. Two individuals underwent RUTH while preserving RHV. Among the remaining patients who underwent RUTH with RHV resection, one patient underwent RHV reconstruction but the others did not. Immediate or long-term venous related complications did not occurred in a median follow-up period of nine months. CONCLUSIONS: Laparoscopic RUTH surgery for tumors in the right upper region of the liver is safe and feasible. The strategic workflow we proposed for the resection and reconstruction of the RHV offers a reliable method for preserving liver parenchyma and reducing the risk of postoperative liver failure.

CT-Guided Fiducial Marker Implantation with Ultra-fine 25-Gauge Needle Prior to Proton Therapy for Liver Malignancies.

PURPOSE: Proton therapy is highly effective for liver malignancies, and to increase its accuracy, placement of fiducial markers in the liver is preferred. We retrospectively evaluated the safety and feasibility of CT-guided fiducial marker implantation using ultra-fine 25-gauge needles before proton therapy for liver malignancies. MATERIALS AND METHODS: Between May 2016 and April 2021, 334 cases were investigated. All of procedures were performed without anesthesia. Technical success was defined as the completion of implantation at the intended site. Tumor-marker distance and possibility of synchronization between tumors and markers were evaluated and compared with Mann-Whitney U test. Complications were evaluated using the Common Terminology Criteria for Adverse Events, version 4.0. RESULTS: Technical success rate was 97.3%. Tumor-marker distance was 19.1 mm (median, range 0-96) in the group in which the implanted marker was synchronized with tumor (n = 315), while it was 34.5 mm (median, range 6-94) in the group in which the implanted marker was not synchronized (n = 13) (p value = 0.011 < 0.05). The complication rate was 2.4%, 2 were classified as grade 4 and 5 as grade 1, and 1 as grade 2. There were no grade 3 or higher complications that seemed to be related to the procedure. CONCLUSION: CT-guided marker implantation using a 25-gauge needle achieved a satisfactory success rate with few complications and was useful for the image-guided and respiratory-synchronized proton therapy. LEVEL OF EVIDENCE 3: Local non-random sample.

Angiographic Aspects of Transarterial Radioembolization: A Comparison of Technical Options to Avoid Extrahepatic Microsphere Depositions.

The influence of the interventional treatment approach for transarterial radioembolization (TARE) on the incidence of extrahepatic microsphere depositions and to angiographic complications was evaluated. In total, 398 TARE cycles were analyzed. Interventional treatment approaches were classified as single treatment position (TP) with interventional occlusion (IO), multiple TPs without IO, and multiple TPs with IO. Correlations with extrahepatic microsphere depositions, angiographic complications, and periprocedural clinical events were performed. Alternative treatment strategies were evaluated. Applications from multiple TPs could have ensured the safe application of microspheres in 48.2% of cases that were originally performed from a single TP after IO. Extrahepatic microsphere accumulations were detected after 5.2%, 5.3%, and 1.5% of TARE procedures from a single TP without IO, a single TP with IO, and multiple TPs without IO, respectively. Applications from multiple TPs did not increase angiographic complications. During the 30-day follow-up, nausea/vomiting and upper abdominal discomfort were observed more frequently in the group with IO than in the group without IO (7.9%/4.6% and 9.2%/5.9%, respectively). In many TARE procedures, the same target liver can be treated from multiple TPs instead of a single TP, reducing the need for the interventional occlusion of aberrant arteries and potential extrahepatic microsphere depositions.

Hepatitis B virus X protein differentially regulates the angiogenesis of Hepatocellular Carcinoma through p53-VEGF axis according to glucose levels.

INTRODUCTION AND OBJECTIVES: Blood glucose fluctuates severely in the diabetes(DM) and tumor microenvironment. Our previous works have found Hepatitis B virus X protein (HBx) differentially regulated metastasis and apoptosis of hepatoma cells depending on glucose concentration. We here aimed to explore whether HBx played dual roles in the angiogenesis of hepatocellular carcinoma varying on different glucose levels. MATERIALS AND METHODS: We collected conditioned medium from HBx-overexpressing cells cultured with two solubilities of glucose, and then applied to EA.hy926 cells. Alternatively, a co-culture cell system was established with hepatoma cells and EA.hy926 cells. We analyzed the angiogenesis of EA.hy926 cells with CCK8, wound-healing, transwell-migartion and tube formation experiment. ELISA was conducted to detect the secretion levels of angiogenesis-related factors. siRNAs were used to detect the P53-VEGF axis. RESULTS: HBx expressed in hepatoma cells suppressed VEGF secretion, and subsequently inhibited the proliferation, migration and tube formation of EA.hy926 cells in a high glucose condition, while attenuating these in the lower glucose condition. Furthermore, the p53-VEGF axis was required for the dual role of HBx in angiogenesis. Additionally, HBx mainly regulated the nuclear p53. CONCLUSIONS: These data suggest that the dual roles of HBx confer hepatoma cells to remain in a glucose-rich environment and escape from the glucose-low milieu through tumor vessels, promoting liver tumor progression overall. We exclusively revealed the dual role of HBx on the angiogenesis of liver tumors, which may shed new light on the mechanism and management strategy of HBV- and DM-related hepatocellular carcinoma.

Malignant myopericytoma originating from the colon: A case report.

BACKGROUND: Myopericytoma is a benign tumor that typically occurs within subcutaneous tissue and most often involves the distal extremities, followed by the proximal extremities, neck, thoracic vertebrae and oral cavity. Complete resection is often curative. Malignant myopericytoma is extremely rare and has a poor prognosis. Here, we report for the first time a case of malignant myopericytoma originating from the colon. CASE SUMMARY: A 69-year-old male was admitted to our hospital with right upper quadrant pain for five days. Imaging suggested a liver mass with hemorrhage. A malignant hepatic tumor was the initial diagnosis. Surgical resection was performed after a complete preoperative work up. Initial postoperative pathology suggested that the mass was a malignant myoblastoma unrelated to the liver. Four months after the first surgery, an enhanced computed tomography (CT) scan revealed a recurrence of the tumor. The diagnosis of malignant myopericytoma derived from the colon was confirmed on histopathological examination of the specimen from the second surgery. The patient did not return to the hospital regularly for surveillance. The first postoperative abdominal CT examination six months after the second surgery demonstrated multiple liver metastases. Survival time between the diagnosis of the tumor to death was approximately one year. CONCLUSION: Malignant myopericytoma is a rare cancer. Preoperative diagnosis may be difficult. Due to a lack of treatment options, prognosis is poor.

Unmasking Carcinoid Syndrome in a Chronic Obstructive Pulmonary Disease (COPD) Patient: A Rare Presentation with Wheezing and Angioedema.

Carcinoid syndrome is a rare condition resulting from neuroendocrine tumors (NETs) that secrete vasoactive substances like serotonin. This report describes the case of a 61-year-old man with a history of chronic obstructive pulmonary disease (COPD) and hypertension who presented with new-onset angioedema, loss of consciousness, and a fall. He had been treated for COPD exacerbations during ER visits without improvement and was unaware of a prior mesenteric carcinoid tumor diagnosis from 2012. The next emergency evaluation revealed significant airway and facial edema necessitating intubation. Imaging and biopsy identified a well-differentiated grade 1 NET with extensive liver metastases. Laboratory tests showed elevated levels of serum serotonin, chromogranin A, and 24-hour urine 5-hydroxyindoleacetic acid (5-HIAA). Post-discharge, a PET scan confirmed metastatic lesions primarily in the liver and small bowel, with an unresectable mesenteric mass. The patient was treated with lanreotide and became symptom-free. This case underscores the need to consider carcinoid syndrome in patients with COPD presenting with unexplained respiratory symptoms, as timely diagnosis and treatment can significantly enhance patient outcomes.

Gaussian filter facilitated deep learning-based architecture for accurate and efficient liver tumor segmentation for radiation therapy.

Purpose: Addressing the challenges of unclear tumor boundaries and the confusion between cysts and tumors in liver tumor segmentation, this study aims to develop an auto-segmentation method utilizing Gaussian filter with the nnUNet architecture to effectively distinguish between tumors and cysts, enhancing the accuracy of liver tumor auto-segmentation. Methods: Firstly, 130 cases of liver tumorsegmentation challenge 2017 (LiTS2017) were used for training and validating nnU-Net-based auto-segmentation model. Then, 14 cases of 3D-IRCADb dataset and 25 liver cancer cases retrospectively collected in our hospital were used for testing. The dice similarity coefficient (DSC) was used to evaluate the accuracy of auto-segmentation model by comparing with manual contours. Results: The nnU-Net achieved an average DSC value of 0.86 for validation set (20 LiTS cases) and 0.82 for public testing set (14 3D-IRCADb cases). For clinical testing set, the standalone nnU-Net model achieved an average DSC value of 0.75, which increased to 0.81 after post-processing with the Gaussian filter (P<0.05), demonstrating its effectiveness in mitigating the influence of liver cysts on liver tumor segmentation. Conclusion: Experiments show that Gaussian filter is beneficial to improve the accuracy of liver tumor segmentation in clinic.

Mode of action of dieldrin-induced liver tumors: application to human risk assessment.

Dieldrin is an organochlorine insecticide that was widely used until 1970 when its use was banned because of its liver carcinogenicity in mice. Several long-term rodent bioassays have reported dieldrin to induce liver tumors in in several strains of mice, but not in rats. This article reviews the available information on dieldrin liver effects and performs an analysis of mode of action (MOA) and human relevance of these liver findings. Scientific evidence strongly supports a MOA based on CAR activation, leading to alterations in gene expression, which result in increased hepatocellular proliferation, clonal expansion leading to altered hepatic foci, and ultimately the formation of hepatocellular adenomas and carcinomas. Associative events include increased liver weight, centrilobular hypertrophy, increased expression of Cyp2b10 and its resulting increased enzymatic activity. Other associative events include alterations of intercellular gap junction communication and oxidative stress. Alternative MOAs are evaluated and shown not to be related to dieldrin administration. Weight of evidence shows that dieldrin is not DNA reactive, it is not mutagenic, and it is not genotoxic in general. Furthermore, activation of other pertinent nuclear receptors, including PXR, PPARα, AhR, and estrogen are not related to dieldrin-induced liver tumors nor is there liver cytotoxicity. In previous studies, rats, dogs, and non-human primates did not show increased cell proliferation or production of pre-neoplastic or neoplastic lesions following dieldrin treatment. Thus, the evidence strongly indicates that dieldrin-induced mouse liver tumors are due to CAR activation and are specific to the mouse, which are qualitatively not relevant to human hepatocarcinogenesis. Thus, there is no carcinogenic risk to humans. This conclusion is also supported by a lack of positive epidemiologic findings for evidence of liver carcinogenicity. Based on current understanding of the mode of action of dieldrin-induced liver tumors in mice, the appropriate conclusion is that dieldrin is a mouse specific liver carcinogen and it does not pose a cancer risk to humans.

Changes in Mutations of Cell-Free DNA and Liver Tumor Tissue in Patients with Advanced Hepatocellular Carcinoma before and after Introduction of Lenvatinib.

INTRODUCTION: Cell-free DNA (cfDNA) is expected to contribute to the decision for treatment and prediction of effects with minimally invasion. We investigated the correlation between gene mutations before and after lenvatinib (LEN) treatment and its effectiveness, in order to find advanced hepatocellular carcinoma (HCC) patients who would benefit greatly from the therapy. METHODS: We analyzed cfDNA before and 6-8 weeks after the start of treatment in 20 advanced HCC patients who started LEN. A next-generation sequencer was used for CTNNB1 and TP53. Concerning TERT promoter, -124C>T and -146C>T mutations are researched using digital PCR. In addition, we examined liver tumor biopsy tissues by the same method. Computerized tomography evaluation was performed at 6-8 weeks and 3-4 months to assess the efficacy. RESULTS: Frequencies of TERT promoter, CTNNB1, and TP53 mutations in pretreatment cfDNA were 45%, 65%, and 65%, but 53%, 41%, and 47% in HCC tissues, respectively. There were no clear correlations between these gene mutations and the disease-suppressing effect or progression-free survival. Overall, there were many cases showing a decrease in mutations after LEN treatment. Integrating the reduction of CTNNB1 and TP53 genetic mutations increased the potential for disease suppression. CONCLUSION: This study suggests that analysis of cfDNA in advanced HCC patients may be useful for identifying LEN responders and determining therapeutic efficacy. Furthermore, it has potential for selecting responders for other molecular-targeted drugs.