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19 pages, 8166 KB  
Article
TMAO Supplementation to High-Carbohydrate Diet Reprogrammed Hepatic Metabolism and Intestinal Microbiota to Improve Liver Health and Disease Resistance of Micropterus salmoides
by Weijun Tang, Yan Lei, Linyuan Jiang, Huijuan Ren, Shambel Boki, Xinyue Du, Kexin Xiong, Shihao Liu, Yaoqiang Yue and Qingchao Wang
Microorganisms 2026, 14(2), 284; https://doi.org/10.3390/microorganisms14020284 - 26 Jan 2026
Viewed by 161
Abstract
This study aimed to evaluate the effects of trimethylamine oxide (TMAO) supplementation (0.5% and 1%) to a high-carbohydrate diet on the growth performance, liver health, hepatic metabolome, intestinal microbiota and disease resistance of largemouth bass (Micropterus salmoides). After an eight-week feeding [...] Read more.
This study aimed to evaluate the effects of trimethylamine oxide (TMAO) supplementation (0.5% and 1%) to a high-carbohydrate diet on the growth performance, liver health, hepatic metabolome, intestinal microbiota and disease resistance of largemouth bass (Micropterus salmoides). After an eight-week feeding trial with three replicates, fish fed with TMAO-supplemented diets showed growth-promoting potential with increased difference with a prolonged rearing period. Importantly, TMAO supplementation significantly improved liver structure and function, with reduced intrahepatic glycogen accumulation due to reprogrammed glycogen metabolism, including down-regulated gys2 and ugp2b but up-regulated pygl expression levels. Targeted liver metabolomics analysis indicated the enhanced synthesis of long-chain fatty acid and amino acid in the 1% TMAO group, accompanied by decreased cortisol, indicating the attenuation of the stress response. Furthermore, TMAO supplementation changed the structure of the intestinal microbiota and particularly the intestinal content of Romboutsia, an important probiotic that can effectively utilize different kinds of dietary carbohydrate, showed an increasing trend with the increased TMAO supplementation levels. Finally, after sampling, all remaining fish were challenged with Nocardia seriolae. TMAO supplementation significantly enhanced the immune clearance function of largemouth bass against invading N. seriolae, with alleviated granulomatous nodules within liver but enhanced hepatic expression levels of nlrp3, caspase1, il-1β and il-18. These results collectively underscore the finding that TMAO may promote intestinal Romboutsia growth and reprogram hepatic metabolism to improve liver health, giving TMAO potential as a feed additive for growth and health promotion in largemouth bass. Full article
(This article belongs to the Special Issue Microbiome in Fish and Their Living Environment, Second Edition)
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14 pages, 817 KB  
Review
Non-Transplantable Recurrence After Initial Liver Resection of Hepatocellular Carcinoma: A Narrative Review
by Dima Malkawi, Ioannis A. Ziogas, Ana L. Gleisner, Richard D. Schulick and Dimitrios P. Moris
Cancers 2026, 18(2), 317; https://doi.org/10.3390/cancers18020317 - 20 Jan 2026
Viewed by 139
Abstract
Background/Objectives: Hepatocellular carcinoma (HCC) constitutes a leading cause of mortality worldwide. Liver transplantation (LT) and liver resection (LR) represent the main curative-intent treatment modalities for early-stage HCC. LT can offer the advantage of both removing the HCC and alleviating the potential underlying [...] Read more.
Background/Objectives: Hepatocellular carcinoma (HCC) constitutes a leading cause of mortality worldwide. Liver transplantation (LT) and liver resection (LR) represent the main curative-intent treatment modalities for early-stage HCC. LT can offer the advantage of both removing the HCC and alleviating the potential underlying liver disease, yet its application is limited by organ scarcity, waitlist dropout, and eligibility criteria. Hence, LR remains widely used due to greater accessibility but is associated with high recurrence rates. Salvage LT is a treatment option for patients with HCC recurrence post-LR, but up to 40% of patients develop non-transplantable recurrence (NTR), defined as recurrence beyond transplant criteria, which precludes LT and is associated in poor outcomes. Methods: The present review aims to summarize the current state of evidence on the comparison of LT and LR, the management of recurrent HCC, and the risk factors associated with NTR. Results: Clinical and histopathologic factors consistently associated with NTR across studies include larger tumor size, multiple tumors, elevated alpha-fetoprotein levels, underlying liver fibrosis or cirrhosis, microvascular invasion, and satellite nodules—features that reflect aggressive tumor biology and impaired hepatic reserve. Conclusions: Improved preoperative risk stratification and identification of patients at high risk for NTR is essential to inform optimal treatment selection. Full article
(This article belongs to the Collection Advances in the Management of Hepatocellular Carcinoma)
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12 pages, 3492 KB  
Case Report
Hepatic Vascular Involvement in Adenosine Deaminase 2 Deficiency (DADA2): Case Reports and Literature Review
by Mihaela Sparchez, Laura Damian, Mihai Adrian Socaciu, Otilia Fufezan and Zeno Sparchez
Diagnostics 2026, 16(2), 189; https://doi.org/10.3390/diagnostics16020189 - 7 Jan 2026
Viewed by 227
Abstract
Background and Clinical Significance: Deficiency of Adenosine Deaminase 2 (DADA2) is a rare monogenic vasculopathy characterised by systemic inflammatory and immunodeficiency features. Although neurological and haematological manifestations are well-documented, hepatic vascular involvement remains underappreciated. This report aims to describe the clinical and [...] Read more.
Background and Clinical Significance: Deficiency of Adenosine Deaminase 2 (DADA2) is a rare monogenic vasculopathy characterised by systemic inflammatory and immunodeficiency features. Although neurological and haematological manifestations are well-documented, hepatic vascular involvement remains underappreciated. This report aims to describe the clinical and imaging characteristics of hepatic vascular involvement in a patient with DADA2 and to illustrate the evolution of hepatic lesions during long-term Etanercept therapy. In addition, we provide a synthesis of the available evidence on hepatic manifestations in DADA2, emphasising vascular pathology, clinical presentation, and therapeutic implications. Case Presentation: We describe a girl with early-onset DADA2 presenting with recurrent systemic inflammation, hypogammaglobulinaemia, vasculopathy, and two childhood strokes, followed by the development of multiple FNH-like hepatic nodules on CEUS and MRI with persistently elevated GGT. Genetic testing confirmed biallelic ADA2 mutations, and treatment with Etanercept led to sustained clinical stabilisation and marked regression of liver lesions over a nine-year follow-up period. Her older sister, carrying the same mutations, showed a milder phenotype without hepatic involvement but experienced a mesenteric vascular event. Conclusions: Large regenerative nodules with an FNH-like appearance on CEUS or MRI have not been previously reported in this setting. In our patient, Etanercept therapy produced a favourable hepatic response, reflected by a significant reduction in both the number and size of the lesions. Our case contributes to the understanding of liver disease in DADA2 and the influence of imaging and treatment on the hepatic manifestations of the condition. Full article
(This article belongs to the Special Issue Advances in the Diagnosis and Management of Vasculitis)
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14 pages, 70161 KB  
Case Report
Unilateral Multifocal Follicular Thyroid Carcinoma with Vascular Invasion and Primary Hepatic Metastasis in a Dog: First Documented Case
by Yoobin Kim, Hyungsan Seo, Sang-kun Jang, Sangyul Lee and Hwi-Yool Kim
Vet. Sci. 2026, 13(1), 43; https://doi.org/10.3390/vetsci13010043 - 3 Jan 2026
Viewed by 324
Abstract
A 14-year-old spayed female Jindo dog presented with a firm, non-painful right-sided cervical mass. Computed tomography identified three distinct, separate masses thought to be arising from the right thyroid lobe; the largest measured 66.6 mm × 42.0 mm × 37.6 mm with an [...] Read more.
A 14-year-old spayed female Jindo dog presented with a firm, non-painful right-sided cervical mass. Computed tomography identified three distinct, separate masses thought to be arising from the right thyroid lobe; the largest measured 66.6 mm × 42.0 mm × 37.6 mm with an estimated volume of 56 cm3 and showed invasion into the right internal jugular vein. Multiple hepatic nodules were detected without evidence of pulmonary metastasis and regional lymph node involvement. Right thyroidectomy with resection of the invaded vein and partial liver lobectomy were performed. The histologic results confirmed all three masses as follicular-compact thyroid carcinomas, and the hepatic lesion as metastatic thyroid carcinoma. The dog recovered uneventfully, remained euthyroid, and showed no local recurrence over a 5-month follow-up. In human medicine, multifocality is common in papillary thyroid carcinoma and is associated with a high rate of recurrence. This report documents the first canine case of multifocal thyroid carcinoma, featuring macroscopic vascular invasion and an uncommon metastatic pattern in which the liver was affected in the absence of detectable pulmonary lesion. The presence of multifocal disease within a single canine thyroid lobe necessitates comprehensive cross-sectional imaging, meticulous surgical planning with vascular considerations, and long-term monitoring to optimize the prognosis of this carcinoma. Full article
(This article belongs to the Section Veterinary Surgery)
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14 pages, 17952 KB  
Case Report
Primary Hepatic Squamous Cell Carcinoma
by Soo Ryang Kim, Soo Ki Kim, Hisato Kobayashi, Toyokazu Okuda, Yumi Fujii, Makiho Sakamoto, Yu-ichiro Koma, Osamu Nakashima, Motoko Sasaki, Akira Asai and Hiroki Nishikawa
Diagnostics 2026, 16(1), 120; https://doi.org/10.3390/diagnostics16010120 - 1 Jan 2026
Viewed by 300
Abstract
Background and Clinical Significance: We present an 85-year-old male case of primary hepatic SCC manifesting as multiple liver nodules with atypical imaging findings. Case Presentation: The patient was negative for hepatitis B surface antigen and hepatitis C virus antibody. Serum tumor markers were [...] Read more.
Background and Clinical Significance: We present an 85-year-old male case of primary hepatic SCC manifesting as multiple liver nodules with atypical imaging findings. Case Presentation: The patient was negative for hepatitis B surface antigen and hepatitis C virus antibody. Serum tumor markers were all within normal limits. Contrast-enhanced ultrasonography with perflubutane demonstrated hypervascular nodules in the early vascular phase, early washout in the portal phase, and a defect in the postvascular phase (10 mm in S5 and 25 mm in S6). Histopathological examination revealed irregularly shaped tumor cells with large hyperchromatic nuclei and basophilic cytoplasm, surrounded by dense fibrous stroma forming cords, solid nests, and sheet-like structures. Immunohistochemical analysis showed positivity for AE1/AE3, p40, CK5/6, c-kit, and NCAM. Conclusions: The lesions were diagnosed as primary hepatic squamous cell carcinoma and suggested the possible involvement of hepatic progenitor cells, supporting the hypothesis of de novo carcinogenesis. Full article
(This article belongs to the Section Clinical Diagnosis and Prognosis)
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18 pages, 5297 KB  
Review
HCC in the Era of Emerging MASH: The Role of Ultrasound in Surveillance and New Sonographic Features in Diagnosis
by Antonio Giorgio, Massimo De Luca, Anna Lombardi, Emanuela Ciracì, Valeria Cosima Rollo, Antonella Di Sarno, Luca Montesarchio, Giuseppe Stella and Valentina Giorgio
Cancers 2025, 17(24), 4037; https://doi.org/10.3390/cancers17244037 - 18 Dec 2025
Viewed by 579
Abstract
Conventional ultrasound (US) has long been central to hepatocellular carcinoma (HCC) surveillance in cirrhotic patients, due to its low cost, wide availability, non-invasiveness, and adequate sensitivity for detecting small nodules. However, its specificity in distinguishing HCC from other lesions is limited. Contrast-enhanced ultrasound [...] Read more.
Conventional ultrasound (US) has long been central to hepatocellular carcinoma (HCC) surveillance in cirrhotic patients, due to its low cost, wide availability, non-invasiveness, and adequate sensitivity for detecting small nodules. However, its specificity in distinguishing HCC from other lesions is limited. Contrast-enhanced ultrasound (CEUS) has significantly improved the characterization of nodules first identified on conventional US. Yet, when CEUS is performed using sulfur hexafluoride (SonoVue)—the only contrast agent available in Western countries—assessment remains restricted to a single nodule per examination, and enhanced CT or MRI is still required for full characterization and staging. In clinical settings, such as hepatology, internal medicine, infectious diseases, and surgery, CEUS offers the advantage of immediate availability, enabling rapid characterization of suspicious nodules in cirrhotic livers and facilitating timely therapeutic decisions. Although the introduction of direct-acting antivirals (DAAs) has substantially reduced HCV-related HCC, HCC incidence is increasingly driven by metabolic dysfunction-associated steatohepatitis (MASH). Evidence on surveillance strategies for MASH patients remains limited, and current EASL guidelines recommend monitoring only patients with >F2 fibrosis. Additionally, the effectiveness of US in obese or diabetic/obese populations is under ongoing investigation; abbreviated non-contrast MRI has been proposed as an alternative surveillance tool, but its adoption would entail significant economic implications for healthcare systems. HCC arising from MASH—sometimes even without cirrhosis—exhibits different sonographic and pathological features. Instead of small, hypoechoic nodules, typically seen in HCV-related cirrhosis, clinicians increasingly encounter larger or multiple lesions, often accompanied by macrovascular invasion, limiting access to curative treatments. Furthermore, typical CEUS LI-RADS patterns are less frequently observed. This review summarizes the evolving US findings in the era of MASH-related HCC and underscores the continued importance of US as the primary imaging tool in routine clinical practice. Full article
(This article belongs to the Section Cancer Causes, Screening and Diagnosis)
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33 pages, 5043 KB  
Review
Ultrasound Evaluation of Fontan-Associated Liver Disease: A State-of-the-Art Review
by Federica Di Natale, Andrea Boccatonda, Marco Musmeci, Alice Brighenti, Luciano Potena, Christoph Frank Dietrich and Carla Serra
Diagnostics 2025, 15(24), 3171; https://doi.org/10.3390/diagnostics15243171 - 12 Dec 2025
Viewed by 1373
Abstract
Background: Fontan-associated liver disease (FALD) is a progressive condition resulting from chronic hepatic venous congestion following the Fontan procedure for univentricular heart defects. As survival improves in these patients, recognition and management of FALD have become increasingly important. Objective: To describe [...] Read more.
Background: Fontan-associated liver disease (FALD) is a progressive condition resulting from chronic hepatic venous congestion following the Fontan procedure for univentricular heart defects. As survival improves in these patients, recognition and management of FALD have become increasingly important. Objective: To describe the pathophysiological mechanisms, imaging findings, and diagnostic approach to FALD, with a focus on the role of ultrasonography, including contrast-enhanced ultrasound (CEUS). Methods: This narrative review explores the evolution of FALD through a multidisciplinary lens, integrating cardiovascular and hepatic imaging data. Particular attention is paid to Doppler ultrasound and CEUS, both in early parenchymal changes and in the differential diagnosis of potential complications such as hepatic nodules. Results: FALD is characterized by progressive fibrosis due to long-standing passive congestion, resulting in a wide spectrum of imaging findings. B-mode ultrasound reveals hepatomegaly, heterogeneous parenchyma, and gallbladder wall thickening. Doppler studies show altered hepatic venous flow patterns, while CEUS provides dynamic vascular evaluation, highlighting areas of altered perfusion. In advanced stages, hypo-vascular areas in the late phase may simulate malignant lesions, emphasizing the need for careful interpretation. The role of liver biopsy, though limited by invasiveness, remains crucial in selected cases. Surveillance strategies are not standardized but require close multidisciplinary follow-up. Conclusions: FALD presents complex diagnostic challenges requiring integrated imaging and clinical assessment. CEUS emerges as a valuable, non-invasive tool in characterizing hepatic congestion and guiding management. Increased awareness and standardized protocols are essential for early detection and tailored care in this growing patient population. Full article
(This article belongs to the Special Issue Recent Progress in Abdominal Ultrasound)
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15 pages, 1621 KB  
Case Report
Triple Synchronous Primary Malignant Tumors of the Liver, Kidney, and Lung in a Male Patient: Case Report and Systematic Review
by Alexandru Vlad Oprița, Eduard Achim, Cornelia Nițipir, Nicolae Boleac, Alissia-Nicoleta Pilatec and Florin Andrei Grama
Diagnostics 2025, 15(24), 3172; https://doi.org/10.3390/diagnostics15243172 - 12 Dec 2025
Viewed by 540
Abstract
Background: Triple primary malignant tumors (TPMTs) are extremely rare and represent a major diagnostic and therapeutic challenge. Their frequency has increased with advances in cancer detection and longer patient survival. Case presentation: We report the case of a 76-year-old male diagnosed with three [...] Read more.
Background: Triple primary malignant tumors (TPMTs) are extremely rare and represent a major diagnostic and therapeutic challenge. Their frequency has increased with advances in cancer detection and longer patient survival. Case presentation: We report the case of a 76-year-old male diagnosed with three synchronous primary malignancies involving the liver, left kidney, and right lung. Imaging revealed a hepatic mass with arterial enhancement and portal washout, a large left renal mass, and a cavitated pulmonary nodule. Histopathological and immunohistochemical evaluation confirmed three distinct tumors: well-differentiated hepatocellular carcinoma, chromophobe renal cell carcinoma, and invasive non-mucinous lung adenocarcinoma. A multidisciplinary oncology board recommended surgical resection of the liver and kidney lesions and stereotactic body radiotherapy for the lung tumor. The patient underwent hepatectomy and nephrectomy but experienced severe postoperative complications leading to multi-organ failure and death. Results of the systematic review: A systematic search identified 83 relevant cases of triple primary malignancies after full-text eligibility assessment. None of the 159 articles included after primary screening described a synchronous association of primary liver, kidney, and lung cancers. Conclusions: This case highlights the importance of thorough diagnostic assessment and individualized, multidisciplinary management in patients with multiple synchronous malignancies. To our knowledge, this is the first reported case of synchronous hepatocellular carcinoma, chromophobe renal cell carcinoma, and lung adenocarcinoma. Full article
(This article belongs to the Section Clinical Diagnosis and Prognosis)
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16 pages, 4102 KB  
Article
Performance of Radiologists in Characterizing and Diagnosing Hepatic Lesions Using Dynamic Contrast-Enhanced CT With and Without Artificial Intelligence
by Daiki Nishigaki, Atsushi Nakamoto, Takahiro Tsuboyama, Hiromitsu Onishi, Yuki Suzuki, Tomohiro Wataya, Kosuke Kita, Junya Sato, Miyuki Tomiyama, Masahiro Yanagawa, Masatoshi Hori, Shoji Kido and Noriyuki Tomiyama
Appl. Biosci. 2025, 4(4), 56; https://doi.org/10.3390/applbiosci4040056 - 3 Dec 2025
Viewed by 542
Abstract
Background: To investigate the performance of radiologists in characterizing and diagnosing hepatic lesions with and without the assistance of deep learning-based artificial intelligence (AI). Methods: This retrospective study included 83 nodules/masses from 69 patients who underwent dynamic contrast-enhanced CT of the liver. Image [...] Read more.
Background: To investigate the performance of radiologists in characterizing and diagnosing hepatic lesions with and without the assistance of deep learning-based artificial intelligence (AI). Methods: This retrospective study included 83 nodules/masses from 69 patients who underwent dynamic contrast-enhanced CT of the liver. Image assessments were conducted by 20 radiologists. grouped according to their level of experience (10 senior and 10 junior). Each radiologist determined the probability of eight characteristics based on enhancement patterns and the diagnosis with and without AI attached to the SYNAPSE SAI viewer (FUJIFILM Corporation, Minato-ku, Japan). The reference standard for comparison was established as follows: final diagnoses were based on pathology for 39 lesions and expert imaging consensus for the remainder, while image characteristics for all lesions were determined by expert imaging consensus. Areas under the receiver operating characteristic curves (AUCs) were analyzed using the multireader multicase method. Results: Using AI significantly improved the overall AUCs for both the characterization and the diagnosis of liver lesions. Improvement was suggested for specific items, including the characterization of enhancement, nonperipheral washout, and delayed enhancement, and the diagnosis of hepatocellular carcinoma. The utilization of AI system also suggested potential improvements in the AUCs for image characterization in both the senior and junior groups. Conclusions: Using AI improved the radiologists’ performance in characterizing and diagnosing hepatic lesions. In terms of their capacity to assess imaging characteristics, improvements were observed regardless of their level of experience. Full article
(This article belongs to the Special Issue Neural Networks and Deep Learning for Biosciences)
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19 pages, 1657 KB  
Review
The Potential of Artificial Intelligence to Improve Selection Criteria for Liver Transplantation in HCC
by Jan-Paul Gundlach, Steffen M. Heckl, Patrick Langguth, Christian Oberkofler, Terbish Taivankhuu, Jan Henrik Beckmann, Thomas Becker, Felix Braun and Michael Linecker
Cancers 2025, 17(23), 3829; https://doi.org/10.3390/cancers17233829 - 29 Nov 2025
Viewed by 523
Abstract
Despite improved therapeutic concepts, the survival of patients with hepatocellular carcinoma (HCC) is limited. Liver transplantation (LT) is the best possible treatment for suitable patients. This therapy is of particular importance, because it not only removes the cancer but also cures the underlying [...] Read more.
Despite improved therapeutic concepts, the survival of patients with hepatocellular carcinoma (HCC) is limited. Liver transplantation (LT) is the best possible treatment for suitable patients. This therapy is of particular importance, because it not only removes the cancer but also cures the underlying structural liver disease. Due to the persistent lack of donor organs, however, the oncological prognosis after LT is of particular importance for fair organ allocation. Bonus points on the organ waiting list are rewarded for tumors within a certain tumor extent. In general, macrovascular invasion and extrahepatic tumor manifestation are considered to be contraindications for LT, as survival in these patients is very low. In recent years, however, microvascular invasion and poorly differentiated tumors have also turned out to be unfavorable. Most selection criteria for LT in HCC are still based on very simple imaging criteria like size and number without utilizing additional imaging characteristics inherent to the tumor nodule, which could be processed in a “virtual biopsy”. Recently, diagnostic research has presented the clinical benefit of artificial intelligence (AI) in the use of deep-learning strategies for digital diagnosis of poorly differentiated or microvascular-infiltrated tumors. In addition, evaluation of TACE response is analyzed as a possibility to estimate LT survival. The aim of this review is to provide an overview of recent advances in HCC diagnosis and to classify the clinical relevance of these diagnostic and technical advances. Secondly, we discuss how these advances could affect the organ allocation process. Full article
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15 pages, 10213 KB  
Review
Synchronous Ileal Metastasis from Pancreatic Ductal Adenocarcinoma: Case Report and Narrative Review with Practical Diagnostic and Management Points
by Tiberiu Stefăniță Țenea Cojan, Valeriu Șurlin, Stelian-Stefaniță Mogoantă, Nicolae-Dragoș Mărgăritescu, Daniel-Cosmin Caragea, Ioana-Alexia Țenea Cojan, Valentina Căluianu, Marius Cristian Marinaș, Gabriel Florin Răzvan Mogoș, Liviu Vasile and Laurențiu Augustus Barbu
Life 2025, 15(11), 1684; https://doi.org/10.3390/life15111684 - 29 Oct 2025
Cited by 2 | Viewed by 776
Abstract
Background: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with poor prognosis, most frequently metastasizing to the liver, peritoneum, and lungs. Intestinal metastases are exceptionally rare and easily misinterpreted as primary small-bowel tumors, typically presenting with acute complications such as obstruction, perforation, [...] Read more.
Background: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with poor prognosis, most frequently metastasizing to the liver, peritoneum, and lungs. Intestinal metastases are exceptionally rare and easily misinterpreted as primary small-bowel tumors, typically presenting with acute complications such as obstruction, perforation, or bleeding. Methods: We combined a detailed case description with a narrative literature review. PubMed/MEDLINE and Embase (2000–2025) were searched for case reports and case series describing intestinal metastases from PDAC with histopathological and immunohistochemical confirmation. Case presentation: We report a female patient presenting with acute intestinal obstruction caused by a synchronous ileal metastasis from PDAC. Imaging revealed an ileal stenosing lesion and a pancreatic body mass. An exploratory laparotomy identified a 3 cm transmural ileal tumor with additional serosal nodules. Histopathology confirmed a moderately differentiated adenocarcinoma. Immunohistochemistry supported pancreatic origin (CK7+, CA19-9+, faint CDX2), with mutant-type p53 positivity, ultra-low HER2/Neu expression, and a Ki-67 index of ~50%. The patient underwent segmental enterectomy with terminal ileostomy, followed by systemic therapy. Conclusions: This represents an exceptional and rare clinical finding rather than a presentation from which broad conclusions can be drawn. Histopathological and immunohistochemical analysis supported pancreatic origin and helped avoid misclassification as a primary intestinal neoplasm. It underscores the importance of careful clinicopathological correlation and multidisciplinary evaluation in atypical metastatic scenarios, while illustrating how surgery can provide symptom control and enable systemic therapy. Given its rarity, these observations should be interpreted with caution and regarded as descriptive rather than generalizable. Full article
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13 pages, 3044 KB  
Case Report
Synchronous Pulmonary and Cecal High-Grade Neuroendocrine Carcinomas Presenting as Hepatic Metastases: A Diagnostic Challenges and Literature Review
by Georgiana Elena Sârbu, Alina Ecaterina Jucan, Claudiu Vasile Mihai, Carmen Atodiresei, Madalina Ene, Carmen Ungureanu, Ioana Ruxandra Mihai, Otilia Nedelciuc, Mihaela Dranga, Cristina Cijevschi Prelipcean and Catalina Mihai
Diagnostics 2025, 15(19), 2535; https://doi.org/10.3390/diagnostics15192535 - 8 Oct 2025
Viewed by 634
Abstract
Background and Clinical Significance: Neuroendocrine neoplasms (NENs) are a group of malignancies that may remain clinically silent for many years. The presence of hepatic metastases can be the first clue leading to diagnosis. Case Presentation: We report the case of a 67-year-old man [...] Read more.
Background and Clinical Significance: Neuroendocrine neoplasms (NENs) are a group of malignancies that may remain clinically silent for many years. The presence of hepatic metastases can be the first clue leading to diagnosis. Case Presentation: We report the case of a 67-year-old man with intermittent tiredness and suspicious hepatic nodules detected on routine abdominal ultrasound. Contrast-enhanced ultrasonography showed arterial hyperenhancement with early washout, suggestive of metastases. Synchronous high-grade neuroendocrine carcinomas (NECs) of the lung and cecum were identified. Although the liver lesions were initially presumed to arise from the cecal tumor, liver biopsy immunohistochemistry was TTF-1 positive/CDX2 negative, whereas the cecal lesion was TTF-1 negative/CDX2 positive. This mutually exclusive immunophenotype confirmed two separate primary carcinomas. Given the high-grade histology, the patient received platinum-based chemotherapy and achieved a partial response. Conclusions: This case illustrates the diagnostic complexity of synchronous lesions and highlights the “mirage of the first lesion” phenomenon, in which the initially detected tumor may not represent the true primary site. A comprehensive, multidisciplinary strategy is crucial for establishing the correct diagnosis and guiding optimal management. Full article
(This article belongs to the Special Issue Diagnosis and Management of Neuroendocrine Tumors)
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12 pages, 714 KB  
Article
Assessment of Preprocedural Factors Associated with 5-Year Complete Response After Transarterial Radioembolization in Patients with Hepatocellular Carcinoma
by June Park, Dong Kyu Kim, Seungsoo Lee and Shin Hye Hwang
Diagnostics 2025, 15(18), 2297; https://doi.org/10.3390/diagnostics15182297 - 10 Sep 2025
Viewed by 713
Abstract
Background: There is little evidence available regarding the long-term tumor response after transarterial radioembolization (TARE) for hepatocellular carcinoma (HCC). Aim: To identify preprocedural predictive factors for achieving a 5-year complete response (CR) following TARE in patients with HCC. Methods: This [...] Read more.
Background: There is little evidence available regarding the long-term tumor response after transarterial radioembolization (TARE) for hepatocellular carcinoma (HCC). Aim: To identify preprocedural predictive factors for achieving a 5-year complete response (CR) following TARE in patients with HCC. Methods: This retrospective study included 37 patients with treatment-naïve HCC who underwent TARE between January 2016 and December 2019 and were followed for at least 5 years. Tumor characteristics—including maximum diameter, number of main lesions, presence of satellite nodules, and portal vein thrombosis—were evaluated using preprocedural liver dynamic magnetic resonance imaging. Treatment response was assessed according to the modified Response Evaluation Criteria in Solid Tumors. Multivariate logistic regression analyses were performed to identify factors associated with tumor response following TARE. Results: Thirty-seven patients (median age, 64 years) were categorized into two groups: (1) the CR group (n = 9), consisting of patients without tumor recurrence for 5 years and without additional treatment; and (2) the non-CR group (n = 28), consisting of patients who required additional treatment because of residual or recurrent viable tumors. Tumors in the non-CR group had significantly larger diameters compared with those in the CR group (9.8 cm vs. 5.9 cm, p = 0.006). In multivariable analysis, a tumor diameter > 7 cm was the only factor significantly associated with tumor recurrence (odds ratio = 21.277, p = 0.010). Portal vein thrombosis did not reach statistical significance (odds ratio = 9.779, p = 0.063). Conclusions: Tumor diameter > 7 cm is a significant predictor of tumor recurrence within 5 years after TARE for HCC. This finding may support a more individualized post-TARE management approach, potentially allowing clinicians to avoid overtreatment and adopt a watchful waiting strategy for selected patients. Full article
(This article belongs to the Section Medical Imaging and Theranostics)
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12 pages, 2904 KB  
Article
Enhancing LI-RADS Through Semi-Automated Quantification of HCC Lesions
by Anna Jöbstl, Piera Maria Tierno, Anna-Katharina Gerstner, Gudrun Maria Feuchtner, Benedikt Schaefer, Herbert Tilg and Gerlig Widmann
J. Pers. Med. 2025, 15(9), 400; https://doi.org/10.3390/jpm15090400 - 29 Aug 2025
Viewed by 1276
Abstract
Background/Objectives: Hepatocellular carcinoma (HCC) is the most common primary malignant tumour of the liver. In a cirrhotic liver, each nodule larger than 10 mm demands further work-up using CT or MRI. The Liver Imaging Reporting and Data System (LI-RADS) is still based on [...] Read more.
Background/Objectives: Hepatocellular carcinoma (HCC) is the most common primary malignant tumour of the liver. In a cirrhotic liver, each nodule larger than 10 mm demands further work-up using CT or MRI. The Liver Imaging Reporting and Data System (LI-RADS) is still based on visual assessment and measurements. The purpose of this study was to evaluate whether semi-automated quantification of visual LR-5 lesions is appropriate and can objectify HCC classification for personalized radiomic research. Methods: A total of 52 HCC patients (median age 67 years, 17% females, 83% males) from a retrospective data collection were evaluated visually and compared by the results using an oncology software with features of LI-RADS-based structured tumour evaluation and documentation, semi-automated tumour segmentation, and texture analysis. Results: Software-based evaluation of non-rim arterial-phase hyperenhancement (APHE) and non-peripheral washout, as well as the LI-RADS-score, showed no statistically significant differences compared with visual assessment (p = 0.2, 0.7, 0.17), with a consensus between a human reader and the software approach in 98% (APHE), 89% (washout), and 93% (threshold growth) of cases, respectively. The software provided automated LI-RADS classification, structured reporting, and quantitative features for HCC registries and radiomic research. Conclusions: The presented work may serve as an outlook for LI-RADS-based automated qualitative and quantitative evaluation. Future research may show if texture analysis can be used to foster personalized medical approaches in HCC. Full article
(This article belongs to the Section Methodology, Drug and Device Discovery)
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9 pages, 3584 KB  
Case Report
Gallbladder Carcinoma in a Eurasian Otter (Lutra lutra)
by Lorenzo Domenis, Marzia Pezzolato, Elena Biasibetti, Raffaella Spedicato and Serena Robetto
Animals 2025, 15(17), 2484; https://doi.org/10.3390/ani15172484 - 24 Aug 2025
Viewed by 843
Abstract
An adult female Eurasian otter (Lutra lutra), introduced with another subject in the National Park of Gran Paradiso (Aosta Valley Region, Italy), was found dead. The necropsy found a mass involving mainly the gallbladder walls with other multicentric masses in the [...] Read more.
An adult female Eurasian otter (Lutra lutra), introduced with another subject in the National Park of Gran Paradiso (Aosta Valley Region, Italy), was found dead. The necropsy found a mass involving mainly the gallbladder walls with other multicentric masses in the liver and pancreas. In addition to these, through the histological examination, other nodules were detected in the pancreas, with structure similar to gallbladder neoplasm. Histopathology diagnosed it as neoplasia composed of epithelioid cells, forming lobules of tubules and pseudoacini, with a very low mitotic count, discrete cellular pleomorphism, and prominent fibrous stroma. Neoplastic cells demonstrated positive immunoreactivity for cytokeratin and negative immunoreactivity for S100. Gross and histologic lesions and immunohistochemical findings were consistent with a primary gallbladder carcinoma (GBC) of metastatic type. GBC is a rare neoplasm in both humans and animals, sometimes associated with cholelithiasis and cholecystitis, with few reports in the veterinary literature especially in cattle, pigs, dogs and cats. To the best of our knowledge, this is the first report of GBC in a Eurasian otter. Full article
(This article belongs to the Special Issue Wildlife Diseases: Pathology and Diagnostic Investigation)
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