Search Results (79)

Hepatobiliary diseases, which include disorders of the liver, gallbladder, and bile ducts, remain a major global health concern. A significant proportion of deaths worldwide are attributed to hepatic diseases, accounting for 4% of the total global mortality in 2023. Among benign hepatobiliary diseases, metabolic dysfunction-associated steatotic liver disease is the most prevalent liver pathology, with a concerning rise in incidence, while it is recognized as the leading cause of liver transplantation in the United States. However, there is a notable rise over time in cases of autoimmune hepatobiliary disorders, including autoimmune hepatitis, primary biliary cholangitis, and primary sclerosing cholangitis. Meanwhile, hepatocellular carcinoma still remains the most frequently diagnosed hepatobiliary malignancy, constituting the third leading cause of malignancy-related mortality globally. Meanwhile, cholangiocarcinoma and gallbladder cancer are the second and third most common hepatobiliary malignancies, respectively, both exhibiting highly aggressive malignant behavior. Despite the notable advances in biomarkers and the development of therapeutic tools, early diagnosis and monitoring are considered pivotal for the management of the aforementioned pathologies. The development of new non-invasive biomarkers that can effectively identify, monitor these pathologies, and guide their management is considered a necessity. Extracellular vesicles (EVs) constitute nanoparticles with several embedded cargoes, with a significant role in intercellular communication, which are considered promising biomarkers in several diseases, including viral, metabolic, autoimmune, and malignant diseases. In this review, we will shed light on the role of EVs as novel frontiers in hepatobiliary diseases. Full article

Background: Single-port laparoscopic hepatectomy is a minimally invasive modality for the treatment of benign and malignant liver lesions. Due to the method’s technical challenges, it is suitable for experienced hepatobiliary surgeons and selected groups of patients. The aim of this study was to evaluate the results of a single Slovenian center performing single-port laparoscopic hepatectomy with a literature overview. Methods: A single-center retrospective consecutive case series of the twenty-six patients with liver disease operated with the single-port technique from January 2018 to July 2024 at the Department of Abdominal Surgery at the University Medical Centre, Ljubljana, was performed. Lesions were located in easy-to-treat segments. Operative time, conversion rate, length of hospital stay, and surgical complications were recorded and evaluated. Results: We performed twenty-six single-port laparoscopic liver resections (median age 63.5, range 31 to 79 years). The mean operative time was 92 ± 31 min. None of the cases were converted to multi-port laparoscopic or open surgery. Safe resection margins were obtained in cases of malignant disease. The mean hospital stay was 4 days. The post-operative complication rate involving intervention was 7% (2/26). The incisional hernia rate was 11.5% (3/26). No life-threatening surgical complications or morbidity were noted. Conclusions: Single-port laparoscopic hepatectomy is a safe and feasible technique for the resection of benign and malignant liver lesions in the hands of skilled and well-trained hepatobiliary surgeons. Full article

Transplant oncology is a rapidly evolving discipline that incorporates oncology, transplant medicine, and surgery. As the field continues to grow, there remains an opportunity to enhance patient selection, detect recurrence after liver transplantation, and optimize treatment after recurrence. Liquid biopsies are an emerging resource to improve patient care. In this review, we evaluate the most recent available data on circulating tumor DNA and how it pertains to primary and metastatic hepatobiliary malignancies. We discuss the opportunities and current limitations to clinical practice, especially in relation to total hepatectomy and liver transplantation. We conclude that as both transplant oncology and our understanding of circulating tumor DNA continue to evolve, rigorous, prospective study is required to integrate this technology into a clinical paradigm. Full article

Radiological assessment following pancreaticoduodenectomy is critical for the prompt diagnosis and management of postoperative complications, significantly influencing patient outcomes. Pancreaticoduodenectomy, or the Whipple procedure, is the standard surgical intervention for pancreatic and periampullary malignancies, but it involves notable risks, especially from complications like fistulas, bleeding, or leakage. Cross-sectional imaging, particularly contrast-enhanced computed tomography, serves as the primary diagnostic tool due to its rapid acquisition, high resolution, and effective delineation of postoperative anatomy and complications. Magnetic resonance imaging (with cholangiopancreatography and hepatobiliary contrast agents) complements CT by providing superior contrast resolution for specific complications, notably in the biliary system and pancreatic duct. This narrative review discusses various imaging techniques and their applications, highlighting characteristic radiological features of common postoperative complications. It underscores the importance of a multidisciplinary approach, emphasizing close collaboration between radiologists and surgeons to optimize surgical decision-making and improve patient management post-pancreatic surgery. Full article

Transplant oncology integrates a wide variety of fields, such as surgery, oncology, and transplant medicine, intending to increase the range of studies and treatments for hepatobiliary cancers and other liver-related malignant lesions. Liver transplantation (LT) has proven to be an effective treatment for hepatocellular carcinoma. While the Milan criteria are still the gold standard, several new, more inclusive criteria have been proposed, and hepatocellular carcinoma has become a major indication for liver transplantation. The continuous evolution of diagnostic technologies supported this with higher image quality and more accurate staging. This review describes the current applications of transplant oncology in hepatocellular carcinoma, cholangiocarcinoma, neuroendocrine tumors, and liver metastatic disease from colorectal cancer and discusses the path that led to the development of transplant oncology as an organized approach to managing gastrointestinal malignancies through transplantation. More importantly, the significance of a multidisciplinary approach and criteria in the selection of suitable candidates are discussed. In addition, newer aspects of transplant oncology, such as immunotherapy, circulating tumor DNA (ctDNA), novel surgical techniques, and the utilization of artificial intelligence, are presented. Finally, the opportunities and challenges involved in the field’s future, as well as the evolution of the criteria used over the years and insightful thoughts for the future of the criteria, are discussed. Full article

Background: Previously, we reported elevated levels of fucosylated α₁-acid glycoprotein (fAGP) in plasma samples from patients with diverse types of cancers. Accordingly, fAGP was assumed to be a potential biomarker for the early detection of cancers. Methods: The fAGP level was retrospectively measured in preoperative plasma samples from 213 patients with either hepatic, biliary tract, or pancreatic cancer and was analyzed together with levels of six existing tumor markers determined as reference standards. Results: When the cutoff value was set at 25.45 U/μg, elevated levels of fAGP were significantly observed in cancer patients. The sensitivity, specificity, and accuracy for the detection of malignancy in these diseases were determined to be 70.79, 51.72, and 68.12, respectively. In contrast, all the tumor markers exhibited low sensitivity and accuracy, even though they commonly had extremely high (≥80%) specificity. Further, a significant number of patients in both early and advanced clinical stages were found to be false negative in these tumor makers but were found to be positive in the fAGP level. A dramatic improvement in the diagnosis by tumor markers in such patients with all clinical stages was found by the determination of the fAGP level. This indicated that fAGP could serve to correct false-negative diagnosis with tumor markers. Conclusions: It is believed that fAGP could be a relevant, unique, and highly sensitive biomarker for early diagnosis of hepatobiliary and pancreatic cancers. Full article

Background: Advances in cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) and pressurized intraperitoneal aerosol chemotherapy (PIPAC) have improved outcomes for selected patients with peritoneal surface malignancies (PSMs). Methods: This retrospective study analyzed 743 PSM patients treated at Fondazione Policlinico Universitario Agostino Gemelli from January 2016 to February 2024. The primary aim was to assess median overall survival (mOS), median disease-free survival (mDFS), and median progression-free survival (mPFS) stratified by tumor origin. Secondary outcomes examined the role of diagnostic laparoscopy in the management of PSMs and intra- and postoperative complications’ rates. Results: A total of 1113 procedures were performed: 389 CRS, 370 PIPAC, and 354 diagnostic laparoscopies. Colorectal cancer was the predominant indication for CRS (52.4%), with a mOS of 52 months and mDFS of 22 months. Patients affected by gastric cancer undergoing CRS had a mOS of 18 months and a mDFS of 13 months, while PIPAC yielded a mOS of 9 months and a mPFS of 4 months. Among patients with pseudomyxoma peritonei undergoing CRS, the 5-year DFS rate was 64.1%, and OS rate was 89%. Patients affected by mesothelioma and treated with CRS exhibited a median OS of 43 months and a DFS of 26 months. Pancreatic and hepatobiliary cancers were treated with PIPAC, with a respective mOS of 12 and 8 months. Postoperative complications occurred in 12.6% of CRS, 3.2% of PIPAC, and 1.7% of diagnostic laparoscopies. High peritoneal cancer index (PCI), gastric resection, and blood loss over 500 mL were identified as risk factors for major complications in a multivariate analysis. Conclusions: Developing a highly experienced multidisciplinary team is crucial for delivering tailored treatment strategies which aim to achieve optimal oncological outcomes while preserving patients’ quality of life. Full article

Hepatobiliary cancers, such as hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA), are among the deadliest malignancies worldwide, leading to a significant number of cancer-related deaths. While bone metastases from these cancers are rare, they are highly aggressive and linked to poor prognosis. This review focuses on RNA-based molecular mechanisms that contribute to bone metastasis from hepatobiliary cancers. Specifically, the role of two key factors, microRNAs (miRNAs) and RNA-binding proteins (RBPs), which have not been extensively studied in the context of HCC and CCA, is discussed. These molecules often exhibit abnormal expression in hepatobiliary tumors, influencing cancer cell spread and metastasis by disrupting bone homeostasis, thereby aiding tumor cell migration and survival in the bone microenvironment. This review also discusses potential therapeutic strategies targeting these RNA-based pathways to reduce bone metastasis and improve patient outcomes. Further research is crucial for developing effective miRNA- and RBP-based diagnostic and prognostic biomarkers and treatments to prevent bone metastases in hepatobiliary cancers. Full article

There are several types of microvasculature supplying neoplasms: “newly formed blood vessels” (neoangiogenesis), which are a component of the tumor microenvironment (TME) of invasive carcinoma with wound healing-like reaction; and “pre-existing blood vessels”, which are used as tumor-supplying vessels by neoplasms (co-option vessels) and are likely to develop in hypervascularized organs. We herein review the microvasculature of neoplasms of biliary tract with reference to pre-existing vessels and vessel co-options. In the hepatobiliary system, intrahepatic large and extrahepatic bile ducts (large bile ducts) and the gallbladder as well as hepatic lobules are highly vascularized regions. In large bile ducts, the biliary lining epithelia and underlining capillaries (peribiliary capillary plexus [PCP]) form the biliary epithelia–PCP alignment, whereas the hepatocyte–sinusoid alignment composes hepatic lobules. Cholangiocarcinoma (CCA) and gallbladder carcinoma (GBC) are the main biliary tract carcinomas. CCA is subdivided into distal (d/CCA), perihilar (pCCA), and intrahepatic (iCCA), and iCCA is subdivided into small duct type (SD-iCCA) and large duct type (LD-iCCA). High-grade biliary intraepithelial neoplasm (BilIN), intraductal papillary neoplasm of the bile duct (IPNB), pyloric gland adenoma (PGA), and intracholecystic papillary neoplasm (ICPN) have recently been proposed as the precursors of LD-iCCA, p/dCCA, and GBC. In the large bile ducts and gallbladder, all cases of high-grade BilIN and PGA, about half of IPNB, and one-third of ICPN with less-complicated structure were found to have hijacked the PCP as their supporting vessels (vessel co-option), while p/dCCA, LD-iCCA, and GBC were supplied by neo-angiogenetic vessels associated with fibrous stroma. The intraluminal components of the remaining cases of ICPN and IPNB with complicated structure presented sparse capillaries without fibrous stroma, a unique microvasculature different from that of co-option or neoangiogenesis. Regarding iCCA showing invasion into the hepatic lobules, some SD-iCCAs replaced hepatocytic cords and used pre-existing sinusoids as co-opted vessels. Visualization of pre-existing vessels could be a new pathological tool for the evaluation of malignant progression and of vascular supply in CCAs and its precursors. Full article

Introduction: Gallbladder cancer (GBC) is a rare and aggressive hepatobiliary malignancy with poor prognosis. The symptoms of GBC are insidious and non-specific in its early stages, and most patients are diagnosed at advanced or late stages. Surgical resection is the only potentially curative treatment for GBC for select patients. There is a lack of robust data for patients with GBC, leading to heterogenous practices in management strategies and outcomes. In this study, we aimed to identify patient characteristics and cumulative overall survival (OS) in patients with GBC who underwent surgical resection with curative intent. Methods: All adult patients (age ≥18 years) with localized or locoregionally advanced GBC who underwent definitive surgery with curative intent at our tertiary institution between 1/2013 and 12/2023 were retrospectively identified. Clinical, laboratory, radiology, histopathology, treatment, and survival data were collected from electronic medical records. Postoperative data included the use of adjuvant chemotherapy or radiotherapy, and patient survival mortality at a cut-off date of 1 February, 2024, calculated from the date of curative surgery. Continuous variables are reported as median and quartile 1 (Q1) and quartile 3 (Q3), while categorical variables are reported as counts and percentages. Results: A total of 94 patients with GBC were included in the study. Median age was 71 (62–77) years and 58 (61.7%) patients were female. Median tumor size was 3.3 (1.9–5.0) cm. Perineural invasion was seen in 48.9% and vascular invasion in 38.3% of patients. A positive surgical margin was present in 50% of the patients, and incidental GBC (IGBC) was seen in 48.9% of patients. Tumor grade was well differentiated in 7.6%, moderately differentiated in 53.3%, and poorly differentiated in 39.1% of the patients. Patients with stage T1a (2.1%) and T1b (11.7%) tumors comprised the minority, and the majority of the tumors were stage T2 (55.3%), followed by T3 (31.9%). A total of 60.6% of patients with GBC underwent adjuvant chemotherapy, and 17% underwent adjuvant radiotherapy after surgical resection. Overall, 62 (66.0%) patients died, and the median OS was 1.88 years. The 1-year OS was 68.7%, 3-year OS was 37.4%, and 5-year OS was 32.2%. A higher absolute median OS was seen in patients who had adjuvant chemotherapy (2.1 years) compared to no chemotherapy (1.9 years); however, this finding was not statistically significant (p = 0.36). The median survival was 2.3 years in IGBC compared to 1.6 years in non-IGBC (p = 0.63). Conclusions: GBC is an aggressive hepatobiliary malignancy that is often diagnosed at advanced stages. Our study showed high rates of local and systemic involvement and high mortality, and the need for prospective and randomized studies on adjuvant therapies to assess their survival benefit. Real-world patient data remain important to identify patients at risk of worse outcomes and to stratify risks prior to surgery. Full article

Treatment options for intrahepatic cholangiocarcinoma (iCCA), a highly malignant tumor with poor prognosis, are limited. Recent developments in immunotherapy and immune checkpoint inhibitors (ICIs) have offered new hope for treating iCCA. However, several issues remain, including the identification of reliable biomarkers of response to ICIs and immune-based combinations. Tumor immune microenvironment (TIME) of these hepatobiliary tumors has been evaluated and is under assessment in this setting in order to boost the efficacy of ICIs and to convert these immunologically “cold” tumors to “hot” tumors. Herein, the review TIME of ICCA and its critical function in immunotherapy. Moreover, this paper also discusses potential avenues for future research, including novel targets for immunotherapy and emerging treatment plans aimed to increase the effectiveness of immunotherapy and survival rates for iCCA patients. Full article

Multifocal hepatic lesions in dogs arise from various benign and malignant liver diseases. Diagnosing these lesions is challenging because clinical signs, hematological data, and serum biochemistry are not definitive indicators. Ultrasound is utilized as a diagnostic imaging tool to evaluate liver parenchyma and detect hepatic lesions. This study aims to investigate the predictive factors that differentiate between benign and malignant multifocal hepatic lesions by examining ultrasound characteristics, blood tests, and serum biochemistry. In total, 43 dogs with multifocal hepatic lesions were included in this study. All dogs were classified into benign hepatic diseases (n = 32) and malignant haptic diseases (n = 11). For all dogs, their liver characteristics, lesion characteristics, and hepatobiliary ultrasound score by ultrasound were evaluated and we collected individual clinicopathological data for analysis. The findings of the univariate analysis revealed significant differences in four hematological and blood chemical parameters (hematocrit, white blood cell count, aspartate transaminase (AST), and alkaline phosphatase (ALP)) and six ultrasonographic parameters (liver parenchymal echogenicity, lesion homogeneity, lesion echogenicity, maximum lesion dimension, average lesion dimension, and hepatobiliary ultrasound score). Using multivariate analysis, only two parameters, hepatobiliary ultrasound score and lesion homogeneity, showed significant differences (p-value < 0.001 and p-value = 0.011, respectively). Additionally, these parameters demonstrated high accuracy in predicting malignant multifocal liver lesions, with accuracy rates of 97.67% and 93.02%, respectively. Therefore, the hepatobiliary ultrasound score and lesion homogeneity are considered effective parameters for screening malignant multifocal liver lesions in dogs. Full article

Hepatobiliary malignancies, which include hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA), are the sixth most common cancers and the third leading cause of cancer-related death worldwide. Hepatic carcinogenesis is highly stimulated by chronic inflammation, defined as fibrosis deposition, and an aberrant imbalance between liver necrosis and nodular regeneration. In this context, the gut–liver axis and gut microbiota have demonstrated a critical role in the pathogenesis of HCC, as dysbiosis and altered intestinal permeability promote bacterial translocation, leading to chronic liver inflammation and tumorigenesis through several pathways. A few data exist on the role of the gut microbiota or bacteria resident in the biliary tract in the pathogenesis of CCA, and some microbial metabolites, such as choline and bile acids, seem to show an association. In this review, we analyze the impact of the gut microbiota and its metabolites on HCC and CCA development and the role of gut dysbiosis as a biomarker of hepatobiliary cancer risk and of response during anti-tumor therapy. We also discuss the future application of gut microbiota in hepatobiliary cancer management. Full article

Primary hepatic angiosarcoma (PHA) is a rare liver malignancy with few studies describing its radiological characteristics. This article aims to assess the imaging features of each of the multiple delayed contrast-enhanced magnetic resonance imaging (MRI) scans, in addition to the conventional MRI protocol, in a patient with PHA. Standard MRI sequences and a liver protocol were used in the examination of a 71 year-old male with pathologically proven PHA after current imaging evaluation. In addition, the patient underwent transversal and coronal MRI T1-weighted scans at 10 min, 20 min and 90 min after intravenous (IV) administration of gadobenatedimeglumine (Gd-BOPTA). The PHA revealed a variable appearance on MRI, with classic imaging being insufficient in making a reliable diagnosis. Lesions have increased vascularity, which translates into increased IV contrast uptake in the MRI arterial phase, showing progressive and globular enhancement in the portal and parenchymatous phases. On delayed scans, at 10 min after IV administration, the lesions maintained no washout, but slightly began to washout at 20 min post-contrast. However, in the hepatobiliary phase (90 min post-contrast injection), on an MRI T1-weighted sequence, PHA lesions were hypointense, suggesting the absence of hepatocytes, thus indicating high-grade malignancy. This approach proved the conclusion that in a patient with PHA, an extra MRI T1-weighted scan at 90 min post-gadobenatedimeglumine injection can provide helpful information in differential diagnosis. Full article

The anterior gradient protein 2 (AGR2) plays a crucial role in facilitating the formation of protein disulfide bonds within the endoplasmic reticulum (ER). Research suggests that AGR2 can function as an oncogene, with its heightened expression linked to the advancement of hepatobiliary and pancreatic cancers through invasion and metastasis. Notably, AGR2 not only serves as a pro-oncogenic agent but also as a downstream targeting protein, indirectly fostering cancer progression. This comprehensive review delves into the established functions and expression patterns of AGR2, emphasizing its pivotal role in cancer progression, particularly in hepatobiliary and pancreatic malignancies. Furthermore, AGR2 emerges as a potential cancer prognostic marker and a promising target for immunotherapy, offering novel avenues for the treatment of hepatobiliary and pancreatic cancers and enhancing patient outcomes. Full article