Liver Metastases Research Articles

Comparative analysis of clinical treatment outcomes: Breath-hold vs. free-breathing techniques in liver stereotactic body radiotherapy.

The aim of this study was to clarify the safety and efficacy of breath-hold irradiation in liver stereotactic body radiotherapy (SBRT). A retrospective analysis was conducted on 57 consecutive patients who received SBRT for hepatocellular carcinoma or liver metastases between 2013 and 2021. Breath-hold irradiation was implemented for patients treated after April 2020. The median follow-up period for all patients was 16.4 months (IQR: 7.36-20.9). The 2-year overall survival rate was 64.4% (95% CI: 47.4-77.2), and the local control rate was 84.3% (95% CI: 69.7-92.3) for all patients. The 1-year overall survival was 80.0% (95% CI: 60.8-90.5) versus 82.0% (95% CI: 53.5-93.9) in the free-respiratory (FR) group versus the breath-hold (BH) group, respectively (P = 0.60). The 1-year local control rates were 78.1% (95% CI: 57.5-89.5) in the FR group and 95.7% (95% CI: 72.9-99.4) in the BH group, respectively (P = 0.16). Radiation-induced liver injury, defined by an escalation of ≥2 in Child-Pugh score, was observed in four patients within each group (FR 13% vs. BH 15%). There were no gastrointestinal adverse events of Grade 3 or higher. Breath-hold irradiation can be safely administered and has demonstrated clinical potential in improving local control. Further research into dose escalation using breath-hold techniques is warranted.

Prospective single-arm multicenter interventional study of surgical resection for liver metastasis from gastric cancer; 3-year overall and recurrence-free survival

ObjectivePotential benefit of surgical resection for liver metastasis from gastric cancer (LMGC) remains controversial because most previous studies were retrospective. We evaluated the outcomes of surgical resection following chemotherapy for LMGC in a prospective single-arm multicenter interventional study. MethodsPatients with synchronous or metachronous LMGC received 2–4 cycles of standard chemotherapy and proceeded to surgical resection if restaging showed a non-progressive disease with a chance of R0 resection. The primary endpoint was 3-year OS of R0 patients, with RFS as secondary. Prognostic factors for R0 patients were evaluated by multivariable Cox regression analysis. ResultsSeventy patients were enrolled between 2011 and 2019. Two patients were ineligible, and 20 discontinued treatment before surgery. Of the 48 patients eventually undergoing surgery, 43 accomplished R0 resection of the primary and/or metastatic GC, while 1 ended in R2 resection and 4 were considered ineligible. Median and 3-year OS for R0 patients were 39.8 months (95 % confidence interval [CI], 26.9 to not reached) and 58.1 % (95 % CI, 43.1–71.8), respectively, while median and 3-year RFS were 14.9 months (95 % CI 7.9–34.0) and 34.9 % (95 % CI 22.2–50.1), respectively. On multivariable analysis, both multiple liver metastases and positive nodal status (pN1–3) were negatively associated with OS (multiple liver metastases: hazard ratio [HR] 2.71 (95 % CI, 1.16–6.35), P = 0.022; pN1–3: HR 9.11 (95 % CI, 1.22–68.2), P = 0.031). ConclusionR0 resection following chemotherapy for LMGC yielded promising survival, with multiple liver metastases and positive nodal status being significant indicators of poor prognosis. Clinical trial registration number: UMIN 000011445 (https://www.umin.ac.jp/ctr/).

Disrupting CENP-N mediated SEPT9 methylation as a strategy to inhibit aerobic glycolysis and liver metastasis in colorectal cancer.

Colorectal cancer (CRC) is a prevalent malignancy with a high mortality rate, primarily due to liver metastasis. This study explores the role of centromere protein N (CENP-N) in mediating the methylation of septin 9 (SEPT9) and its subsequent effects on aerobic glycolysis and liver metastasis in CRC. We employed in vitro and in vivo experiments, including single-cell RNA sequencing, methylation-specific PCR (MSP), ChIP assays, and various functional assays to assess the impact of CENP-N and SEPT9 on CRC cell proliferation, migration, invasion, and metabolic reprogramming. Our data reveal that CENP-N directly interacts with SEPT9, enhancing its methylation at specific lysine residues. This modification significantly upregulates key glycolytic enzymes, thereby promoting aerobic glycolysis, CRC cell proliferation, and migration. In vivo studies further demonstrate that the CENP-N/SEPT9 axis facilitates liver metastasis of CRC, as confirmed by fluorescence imaging and histological analysis. This study identifies a novel pathway where CENP-N-mediated methylation of SEPT9 drives metabolic reprogramming and metastasis in CRC. These findings suggest potential therapeutic targets for inhibiting CRC progression and liver metastasis, offering new insights into CRC pathogenesis.

Chemoembolization, Radioembolization, and Percutaneous Ablation: New Opportunities for Treating Ovarian Cancer Liver Metastasis.

Parenchymal liver metastases from ovarian cancer, occurring in 2-12.5% of cases, significantly worsen prognosis. While surgery and systemic treatments remain primary options, unresectable or chemotherapy-resistant multiple liver metastases pose a significant challenge. Recent advances in liver-directed therapies, including radiofrequency ablation, microwave ablation, cryoablation, transarterial chemoembolization (TACE), and radioembolization, offer potential treatment alternatives. However, the efficacy of these techniques is limited by factors such as tumor size, number, and location. The ideal candidate for tumor ablation is a patient with paucifocal disease, a single tumor up to 5cm or up to 3 tumors smaller than 3cm and tumors 1cm away from major bile ducts and high-flow vessels. Transarterial chemoembolization could be performed in patients with less than 70% tumor load. Differently, radioembolization is available with less limitation on the sites or number of liver cancers. Radioembolization techniques are also able to downsize liver metastases. However, there are limited data regarding the outcomes of loco-regional therapy in patients with hepatic metastases from ovarian cancer. Advancing liver-directed therapies through interventional oncology, combined with robust data on the oncological efficacy of these local treatments, will validate their potential as effective locoregional therapies for liver metastases. This could offer a promising treatment option for patients with ovarian cancer and unresectable hepatic metastases.

Preoperative identification of early extrahepatic recurrence after hepatectomy for colorectal liver metastases: A machine learning approach.

Machine learning (ML) may provide novel insights into data patterns and improve model prediction accuracy. The current study sought to develop and validate an ML model to predict early extra-hepatic recurrence (EEHR) among patients undergoing resection of colorectal liver metastasis (CRLM). Patients with CRLM who underwent curative-intent resection between 2000 and 2020 were identified from an international multi-institutional database. An eXtreme gradient boosting (XGBoost) model was developed to estimate the risk of EEHR, defined as extrahepatic recurrence within 12months after hepatectomy, using clinicopathological factors. The relative importance of factors was determined using Shapley additive explanations (SHAP) values. Among 1410 patients undergoing curative-intent resection, 131 (9.3%) patients experienced EEHR. Median OS among patients with and without EEHR was 35.4months (interquartile range [IQR] 29.9-46.7) versus 120.5months (IQR 97.2-134.0), respectively (p<0.001). The ML predictive model had c-index values of 0.77 (95% CI, 0.72-0.81) and 0.77 (95% CI, 0.73-0.80) in the entire dataset and the validation data set with bootstrapping resamples, respectively. The SHAP algorithm demonstrated that T and N primary tumor categories, as well as tumor burden score were the three most important predictors of EEHR. An easy-to-use risk calculator for EEHR was developed and made available online at: https://junkawashima.shinyapps.io/EEHR/. An easy-to-use online calculator was developed using ML to help clinicians predict the chance of EEHR after curative-intent resection for CRLM. This tool may help clinicians in decision-making related to treatment strategies for patients with CRLM.

Neuropeptide Precursor VGF Promotes Liver Metastatic Colonization of Gαq Mutant Uveal Melanoma by Facilitating Tumor Microenvironment via Paracrine Loops.

Uveal melanoma (UM), the predominant primary ocular malignancy, often progresses to liver metastasis with limited therapeutic options. The interplay of the tumor microenvironment, encompassing secreted soluble factors, plays a crucial role in facilitating liver metastasis. In this study, the role is elucidated of the neural growth factor-inducible gene (VGF), a secreted neuropeptide precursor, in Gαq mutant UM. Employing a multiomics approach, encompassing transcriptomic and secretomic analyses, the intricate involvement of VGF in UM progression is unveiled. VGF is upregulated in Gαq mutant UM cells and associated with poor prognosis of UM patients. Targeting VGF significantly suppressed the growth of UM in vitro and in vivo. Further evidence shows that VGF is regulated by Gαq through MAPK/CREB pathway. Mechanistically, CREB modulates VGF expression by directly binding to consensus DNA response elements in the promoters of the VGF gene. Combined inhibition of Gαq and MEK remarkably reduces tumor burden in the UM xenograft model. Notably, VGF triggers liver metastatic colonization of UM and activates the fibrosis of hepatic stellate cells (HSCs), creating a favorable microenvironment, through an autocrine and paracrine loop. Furthermore, VGF directly binds to TGFBR2 and regulates TGF-β-SMAD signaling pathway, thereby regulating genes associated with endothelial-mesenchymal transition (EMT) to promote metastasis. Taken together, these findings identify VGF as a pivotal driver in the progression and metastasis of Gαq mutant UM and confers a promising therapeutic target and strategy for UM patients.

Risk stratification model for foreseeing overall survival in Chinese patients with initially metastatic small-cell lung cancer.

The study was outlined to develop and approve a nomogram and chance stratification demonstrate for foreseeing overall survival of Chinese patients with at first metastatic small-cell lung cancer (SCLC). We collected information from the Surveillance, Epidemiology, and End Results (SEER) database approximately Chinese SCLC patients with at first distant metastases between 2010 and 2015. Patients with incomplete data about the follow-up time or clinicopathological information were excluded. The included patients were randomized into the training and validation set. Univariate and multivariate Cox proportional hazard regression models were performed. By integrating the significant variables screened, a prescient nomogram and risk stratification model were developed. In addition, we collected 198 small-cell lung cancer patients with metastasis at diagnosis from the case database of the Affiliated Hospital of Shandong University of Traditional Chinese Medicine as an external validation cohort. In all, 421 patients were screened from the SEER database. Multivariate examination showed that age (P = .049), sex (P = .001), grade (P = .008), chemotherapy (P = .001), liver metastasis (P = .001), and pleural invasion (P = .012) were independent prognostic factors. The C-indicator of the nomogram to anticipate overall survival was higher than that of the eighth edition of the American Joint Committee on Cancer Tumor Node Metastasis classification system (0.75 vs 0.543; P < .001). A risk stratification model was encouraged to be created to precisely classify patients into 2 prognostic bunches. The survival rates anticipated by the nomogram appeared to have critical qualifications from the Kaplan-Meier curves in the entire SEER cohort. Calibration curves and survival predictions also showed strong accuracy and consistency in the external validation cohort. The nomogram provided a clear prognostic superiority over the traditional Tumor Node Metastasis system. It could help clinicians make individual risk predictions for initially metastatic Chinese SCLC cancer patients and give necessary treatment recommendations.

Dynamics of Free Radical Oxidative Processes During the Latent Period of Experimental Metastasizing to the Liver

Purpose — to investigate the dynamics of the content of antioxidant enzymes superoxide dismutase 1 (SOD1), glutathione peroxidase 1 (GPO1), glutathione reductase (GR) and lipid peroxidation products diene conjugates (DC), malondialdehyde (MDA) in the spleen and liver during the latent period of growth and metastasis of experimental tumor.Materials and methods. Using 28 white male rats, a model of hematogenous liver metastasis was created by transplanting sarcoma 45 cells (S45) into the spleen, previously lead out under the skin 3 weeks before. Previously, was determined that a tumor visualized in the spleen at 5 weeks, and liver metastases at 7 weeks after transplantation S45. Levels of SOD1, GPO1, GR and MDA were determined using ELISA and DC by biochemical method in spleen and liver homogenates during the latent period of tumor growth and metastasis (1–2 weeks post-transplantation).Results. Significant changes (1.5–5.2 times, р &lt; 0.050–0.001) in studied factors levels were observed compared to intact rats and rats with the spleen lead out. Activation of lipid peroxidation and antioxidant system was noted in the spleen (tumor-carrying organ) during tumor growth and metastasis. At the same time, in the liver (the target organ of metastasis) observed also increased lipid peroxidation but simultaneously a pronounced decreased GR levels (5 times, p &lt; 0.001) without affecting SOD1 levels.Conclusion. Liver tissue exhibited the inferiority of antioxidant protection and the formation of pro-oxidant condition during the latent period of tumor growth, which may prepare the soil for metastasis.

Exploring the Frequency and Risk Factors of Hyperprogressive Disease in Patients with Advanced Melanoma Treated with Immune Checkpoint Inhibitors.

Hyperprogressive disease (HPD) is described as the unexpected rapid growth of a tumour accompanied by a decline in performance status. While immune checkpoint inhibitors (ICIs) have improved outcomes in advanced melanoma, HPD remains a significant challenge in a subset of patients. Although HPD has been extensively studied in various solid tumours, research specifically focusing on advanced melanoma remains limited. We analysed 158 advanced melanoma patients, with 66.5% (n = 105) receiving anti-PD-1 and 33.5% (n = 53) receiving nivolumab plus ipilimumab. The median overall survival was 4.9 months for patients with HPD compared to 8.9 months for those with progressive disease without HPD (p = 0.014). Factors associated with HPD included liver metastasis (p = 0.002), three or more metastatic sites (p < 0.001), elevated lactate dehydrogenase levels (p = 0.004), and Eastern cooperative oncology group performance status ≥2 (p = 0.023). Multivariate analysis identified the Royal Marsden Hospital score (HR 3.675, 95% CI: 1.166-11.580, p = 0.026) as an independent risk factor for HPD, with the MDA-ICI score also trending towards significance (HR 4.466, 95% CI: 0.947-21.061, p = 0.059). This study provides valuable insights into the frequency and factors associated with HPD in advanced melanoma patients treated with ICIs, highlighting the relevance of clinical markers and scoring systems in predicting HPD risk.

N-linked fucosylated glycans are biomarkers for prostate cancer with a neuroendocrine and metastatic phenotype.

Prostate cancer (PCa) is a heterogeneous disease with a spectrum of pathology and outcomes ranging from indolent to lethal. Although there have been recent advancements in prognostic tissue biomarkers, limitations still exist. We leveraged Matrix Assisted Laser Desorption Ionization (MALDI) imaging of formalin-fixed, paraffin embedded (FFPE) prostate cancer specimens to determine if N-linked glycans expressed in the extracellular matrix of lethal neuroendocrine prostate cancer were also expressed in conventional prostate adenocarcinomas that were associated with poor outcomes. We found that N-glycan fucosylation was abundant in neuroendocrine prostate cancer as well as adenocarcinomas at time of prostatectomy that eventually developed recurrent metastatic disease. Analysis of patient derived xenografts revealed that this fucosylation signature was enriched differently across metastatic disease organ sites, with the highest abundance in liver metastases. These data suggest that N-linked fucosylated glycans could be an early tissue biomarker for poor PCa outcomes. Implications: These studies identify that hyper-fucosylated N-linked glycans are enriched in neuroendocrine prostate cancer and conventional prostate adenocarcinomas that progress to metastatic disease, thus advancing biomarker discovery and providing insights into mechanisms underlying metastatic disease.

Transcription factor ASCL1 targets SLC6A13 to inhibit the progression of hepatocellular carcinoma via the glycine-inflammasome signaling.

Hepatocellular carcinoma (HCC), the most common primary liver cancer, typically arises from chronic liver conditions such as hepatitis, cirrhosis, or other chronic liver diseases, and is characterized by its aggressive nature and poor prognosis. The purpose of this research was to clarify the function of achaete-scute family bHLH transcription factor 1 (ASCL1) and solute carrier family 6 member 13 (SLC6A13) in influencing tumor cell behavior, inflammatory responses, and the regulation of inflammasomes. We analyzed the differentially expressed genes (DEGs) in the Cancer Genome Atlas-Liver Hepatocellular Carcinoma (TCGA-LIHC) database, as well as in the GSE14520 and GSE67764 datasets, to identify the expression changes of SLC6A13 in liver cancer. The prognostic significance of SLC6A13 in LIHC was assessed through Kaplan-Meier survival curve analysis. Transcriptional regulation of SLC6A13 by ASCL1 was explored using the Joint Annotation of the Human Genome and other species by the Systematic Pipeline for the Annotation of Regulatory Regions (JASPAR) database and dual-luciferase assays. In vitro experiments investigated the impact of ASCL1 and SLC6A13 overexpression on HCC cell growth. Additionally, the effects of ethanol treatment and glycine modulation on the inflammatory response in HCC cell lines were evaluated. HCC samples showed reduced levels of SLC6A13, which correlates with a better prognosis for liver metastases. Elevated SLC6A13 expression correlated with improved overall survival (OS), progression-free survival (PFS), recurrence-free survival (RFS), and disease-specific survival (DSS). ASCL1 upregulated SLC6A13 and inhibited proliferation, migration, and invasion of HCC cells. Ethanol induced the production of inflammatory cytokines, which was enhanced by overexpression of SLC6A13 but counteracted by glycine. This study highlighted elevated expression of SLC6A13 in LIHC which has been correlated with improved OS, PFS, RFS, and DSS. Overexpression of SLC6A13 and ASCL1 in HCC cells enhanced inflammasome activation, which was exacerbated by ethanol and attenuated by glycine.

Ephrin A1 Stimulates CCL2 Secretion to Facilitate Pre-metastatic Niche Formation and Promote Gastric Cancer Liver Metastasis.

The liver is a primary target for distal metastasis of gastric cancer (GC). The hepatic pre-metastatic niche (PMN) facilitates crucial communications between primary tumor and liver, thereby playing an essential role in hepatic metastasis. Identification of the molecular mechanisms driving PMN formation in GC could facilitate development of strategies to prevent and treat liver metastasis. Here, we uncovered a role for ephrin A1 (EFNA1) signaling in development of the PMN. EFNA1 overexpression in GC cells significantly increased CCL2 secretion through the Hippo-YAP pathway. Secreted CCL2 activated hepatic stellate cells (HStCs) within the hepatic PMN via the WNT/β-catenin pathway. Inhibition of CCL2 significantly suppressed HStC activation and reduced liver metastasis triggered by EFNA1 signaling in GC cells. Moreover, high CCL2 expression correlated with poor survival in GC patients. Overall, these findings reveal that EFNA1 signaling in GC cells upregulates CCL2, which activates HStCs to engender establishment of a hepatic pre-metastatic niche that supports liver metastasis.

Effect of elevated CEA levels on the outcome of colorectal cancer patients with different histopathologic types: A SEER population-based study.

Limited and contradictory evidence has been reported regarding the prognostic effects of carcinoembryonic antigen (CEA) on the prognosis and metastasis of classical adenocarcinoma (CA), mucinous adenocarcinoma (MA), and signet-ring cell carcinoma (SRCC) in colorectal cancer patients. We investigated the associations between histological subtypes and preoperative serum CEA levels in determining the oncologic outcomes of colorectal cancer (CRC) patients. A total of 47,692 patients with clearly diagnosed CRC were selected from the Surveillance, Epidemiology, and End Results (SEER) database and divided into two cohorts based on serum CEA levels: CEA-normal (C0) and CEA-elevated (C1). Chi-square analysis revealed a correlation between CEA levels and histological classification. We then included a newly defined interaction variable (H&CEA) in the Cox regression analysis, which demonstrated that this variable could serve as an independent prognostic factor (P<0.001). CA, in the context of elevated serum CEA levels, differed from the other two histopathological types, showing unexpectedly higher risks for both OS (HR = 1.70, 95% CI = 1.65-1.75, P<0.001) and CSS (HR = 1.78, 95% CI = 1.72-1.85, P<0.001). Furthermore, elevated CEA levels significantly increased the proportion of liver metastases in the CA group (25.43% vs. 3.95%, P<0.001). The interaction variable H&CEA can be used as an independent prognostic factor for CRC and should be considered in the diagnosis of CRC and the development of personalized treatment plans. Additionally, in the context of elevated CEA levels, CA is associated with poor prognosis and increased liver metastases. This CRC subgroup warrants special clinical attention from oncologists.

Initial Assessment of Resectability of Colorectal Cancer Liver Metastases Versus Clinical Outcome

BackgroundSurgery improves long-term survival for resectable, liver-only metastatic colorectal cancer (mCRC). With no consensus definition of “resectable” disease, decisions regarding resectability are reliant on the expertise and judgement of the treating clinician working in consultation with a multidisciplinary team (MDT). This study examines the clinical outcome versus initial assessment of resectability in an Australian population with mCRC. Patients and MethodsPatients with liver-only mCRC diagnosed January 2009 to December 2022 were identified from the Treatment of Recurrent and Advanced Colorectal Cancer (TRACC) registry. Patients were classified based on prospectively documented treatment assessment as “resectable,” “potentially resectable,” or “unresectable.” The correlation between initial assessment of resectability and clinical outcome, and any impact of clinicopathologic factors were examined. Kaplan-Meier analysis assessed overall survival based on initial resectability assessment and resection status. Results: Of 4437 patients with mCRC identified through TRACC, 1250 (28%) had liver-only disease at presentation, with 497 (43%), 277 (24%), and 374 (33%) classified as “unresectable,” “potentially resectable,” and “resectable,” respectively. In total, 516 (41%) ultimately underwent surgical resection, including 30 (6%) of the “initially unresectable,” 148 (53%) of the “potentially resectable,” and 338 (90%) of the “resectable” at a median of 9.5, 5.9, and 2.4 months from the diagnosis of liver metastases, respectively. Resection in the “unresectable” patient population was associated with younger age (mean age 63 vs. 69, P = .0006), better performance status (ECOG 0-1 100% vs. 74%, P = .0017), and fewer comorbidities (Charlson index 0-3 in 73% vs. 53%, P = .0296) compared with no resection. Median overall survival was longer for resected versus nonresected patients across all categories: “unresectable” (59.2 vs. 17.6 months, P < .0001), “potentially resectable” (57.2 vs. 22.8 months, P < .0001), and “resectable” (108 vs. 55 months, P < .0001). ConclusionsThis real-world study demonstrates the potential for “initially unresectable” patients to become surgical candidates following systemic therapy, more likely in younger and fitter patients, with overall excellent survival outcomes in resected patients. This highlights the value of routine, repeated MDT assessments for patients with liver-only disease who are continuing to respond to systemic therapy, even for those initially considered never to be surgical candidates.

Evaluating glycocalyx morphology and composition in frozen and formalin-fixed liver tumor sections

BackgroundThe glycocalyx (GCX) is a glycan structure on the vascular endothelium and cancer cells. It is crucial for blood flow regulation, tumor invasion, and cancer drug resistance. Understanding the role of GCX in human tumors could help develop new cancer biomarkers and therapies. AimThis study aimed to demonstrate microstructural changes in human primary and metastatic liver tumors (henceforth termed liver tumors) by visualizing GCX using surgical specimens and comparing formalin-fixed paraffin-embedded sections (FFPEs) with frozen sections. The results of lectin staining were also compared between frozen and FFPE specimens to determine which was more useful for accurately assessing GCX structure and composition. MethodsLiver tumors and normal tissue samples from three patients were collected and processed into FFPEs and frozen sections, respectively. Lanthanum nitrate staining and scanning electron microscopy (SEM) were used to assess the GCX structures. Twenty lectins were analyzed for their glycan components in the samples. ResultsSEM revealed significant differences in GCX morphology among the cancer specimens. Frozen sections provided a more accurate GCX evaluation than FFPEs, showing distinct glycan compositions in hepatocellular carcinoma, colorectal carcinoma liver metastases, and melanoma liver metastases. Hepatocellular carcinoma samples exhibited a loss of N-acetylgalactosamine-related lectins. ConclusionThe results revealed that liver tumors have distinct and bulky GCX compared to normal liver tissue, while frozen sections are more reliable for GCX evaluation. These findings highlight glycan alterations in liver tumors and contribute to the development of new cancer therapies targeting GCX on tumor cell surfaces.

Retraction: Variable Inhibition of Thrombospondin 1 against Liver and Lung Metastases through Differential Activation of Metalloproteinase ADAMTS1.

Retraction: Variable Inhibition of Thrombospondin 1 against Liver and Lung Metastases through Differential Activation of Metalloproteinase ADAMTS1.

Unusual Presentation: Nephroblastoma/Wilms tumor in an Adult – A Case Report

Abstract Introduction/Objective Nephroblastoma/Wilms tumor is a common renal tumor primarily observed in children, and its occurrence in adults is exceedingly rare. This rarity contributes to the diagnostic challenges encountered in adults. Here, we present a case of a 32-year-old male diagnosed with biphasic nephroblastoma/Wilms tumor in the kidney, with liver and lung metastases. Methods/Case Report A 32-year-old male, without significant past medical history, presented with the chief complaint of abdominal pain for 2-3 weeks. Imaging studies revealed a substantial 17.5 cm kidney lesion accompanied by numerous lung and liver lesions. A liver biopsy indicated a small blue cell tumor, morphologically and immunophenotypically, (positive WT1) resembling nephroblastoma, with a strong suspicion of metastasis. Subsequent kidney biopsy confirmed a small blue cell malignant tumor demonstrating biphasic features, including blastema and epithelial components forming tubular structures similar to the liver biopsy, predominantly showing the blastemal component. The renal tumor biopsy supported the diagnosis of nephroblastoma. Despite chemotherapy, the patient passed away two months after the initial liver tumor biopsy. Results (if a Case Study enter NA) NA Conclusion Diagnosing nephroblastoma in adults poses significant challenges, particularly when initial presentations involve metastases. The occurrence of pediatric tumors in adulthood, though rare, should be considered in the diagnostic process after exhausting other possibilities. It is also important to note that the clinical presentation of pediatric tumors in adults may deviate from typical patterns. While Wilm’s tumor commonly presents as a painless, palpable abdominal mass in pediatric cases, adults may exhibit abdominal pain as the predominant symptom, as present in our case.

Liver Metastasis Masking as Neuroendocrine Carcinoma (NEC) Predates Discovery of Intra/Peri-Thyroid Thymic Carcinoma (ITTC)

Abstract Introduction/Objective Intrathyroidal thymic carcinoma (ITTC) also known as Carcinoma showing Thymus-Like differentiation (CASTLE) is a rare malignancy comprising 0.1 to 0.15% of thyroid cancers. The WHO 5th Edition emphasizes that these tumors may also occur outside the thyroid typically at the lower pole Methods/Case Report Our aim is to show that NEC is a mimic of ITTC; that CD5, c-KIT (CD 117), p40, CK5/6 expression distinguishes ITTC from NEC, and that ITTC may at times express NE markers. Briefly, a 51-year-old man presented with hoarseness left neck mass and a PET avid liver lesion in 2016. Biopsy of the neck and liver masses revealed an infiltrating poorly differentiated “NEC” with similar morphology; positive for p53, chromogranin, and synaptophysin; negative for cam5.2, thyroglobulin, TTF-1, CD20, Pax5, CD3, CD5, S-100, calcitonin, CD56, p16, p63, c-KIT (CD117), AE1/3; and 100% staining for Ki-67. The patient underwent chemotherapy, responded well, remained under surveillance, and was symptom-free in the interim. A new 2.1 x 2.0 cm nodule appeared at the left thyroid lower pole after 6 years. The tumor was positive for CD5, CD117, p40, CK5/6, with &amp;gt; 95% Ki67 expression. Chromogranin, synaptophysin, CD56, thyroglobulin, calponin, TTF1, and Epstein Barr virus were negative and was overall diagnostic of ITTC Results (if a Case Study enter NA) NA Conclusion This shows the diagnostic dilemma of distinguishing ITTC from NEC which may share expression of neuroendocrine (NEC) markers and that positivity for CD5, c-KIT (CD117), p40, and CK5/6 are key diagnostic features of ITTC.

Evaluation of colorectal liver metastases using virtual monoenergetic images obtained from dual-layer spectral computed tomography.

To assess the potential of virtual monoenergetic images in assessing colorectal liver metastasis (CRLM) compared with conventional CT images. This single-center, retrospective study included 173 consecutive patients (mean age, 65.5 ± 10.6years; 106 men) who underwent dual-layer spectral CT (DLSCT) between November 2016 and April 2021. Portal venous phase images were reconstructed using hybrid iterative reconstruction (iDose) and virtual monoenergetic imaging at 50keV. Four radiologists independently and randomly reviewed the de-identified iDose and 50keV images. Lesion detection, CRLM conspicuity, and CRLM diagnosis were compared between these images using a generalized estimating equation analysis. The reference standards used were histopathology and follow-up imaging findings. The study included 797 focal liver lesions, including 463 CRLMs (median size, 18.1mm [interquartile range, 10.9-37.7mm]). Lesion detection was better with 50keV images than with iDose images (45.0% [95% confidence interval [CI]: 39-50] vs 40.0% [95% CI: 34-46], P = 0.003). CRLM conspicuity was higher in the 50keV images than in the iDose images (3.27 [95% CI: 3.09-3.46] vs 3.09 [95% CI: 2.90-3.28], P < 0.001). However, the specificity for diagnosing CRLM was lower with 50keV images than with iDose images (94.5% [95% CI: 91.6-96.4] vs 96.0% [95% CI: 93.2-98.1], P = 0.022), whereas sensitivity did not differ significantly (77.6% [95% CI: 70.3-83.5] vs 76.9% [95% CI: 70.0-82.7], P = 0.736). Indeterminate lesions were more frequently noted in 50keV images than in iDose images (13% [445/3188] vs 9% [313/3188], P = 0.005), and 56% (247/445) of the indeterminate lesions at 50keV were not CRLMs. The 50keV images obtained from DLSCT were better than the iDose images in terms of CRLM conspicuity and lesion detection. However, 50keV images did not improve CRLM diagnosis but slightly increased the reporting of indeterminate focal liver lesions associated with CRLMs.

Liver transplantation plus chemotherapy improved survival in patients with colorectal liver metastasis.

Liver transplantation plus chemotherapy improved survival in patients with colorectal liver metastasis.