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Keywords = mucinous neoplasms

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12 pages, 1549 KiB  
Article
Differentiating Main-Duct IPMN from Chronic Pancreatitis Using Next-Generation Sequencing of Main Pancreatic Duct Fluid: A Pilot Study
by Daniel Schmitz, Stefan Prax, Martin Kliment, Felix Gocke, Daniel Kazdal, Michael Allgäuer, Roland Penzel, Martina Kirchner, Olaf Neumann, Holger Sültmann, Jan Budczies, Peter Schirmacher, Frank Bergmann, Jörg-Peter Ritz, Raoul Hinze, Felix Grassmann, Jochen Rudi, Albrecht Stenzinger and Anna-Lena Volckmar
Diagnostics 2025, 15(15), 1964; https://doi.org/10.3390/diagnostics15151964 - 5 Aug 2025
Abstract
Background: A dilated main pancreatic duct (MPD) ≥ 5 mm can be observed in main-duct IPMNs (MD-IPMN) and chronic pancreatitis (CP); however, distinguishing between the two differently treated diseases can be difficult. Cell-free (cf) DNA in MPD fluid obtained by EUS-guided FNA [...] Read more.
Background: A dilated main pancreatic duct (MPD) ≥ 5 mm can be observed in main-duct IPMNs (MD-IPMN) and chronic pancreatitis (CP); however, distinguishing between the two differently treated diseases can be difficult. Cell-free (cf) DNA in MPD fluid obtained by EUS-guided FNA might help to distinguish MD-IPMN from CP. Methods: All patients with a dilated MPD ≥ 5 mm on EUS during the period of 1 June 2017 to 30 April 2024 were prospectively analysed in this single-centre study, with EUS-guided MPD fluid aspiration performed for suspected MD-IPMN or CP in patients who were suitable for surgery. Twenty-two known gastrointestinal cancer genes, including GNAS and KRAS, were analysed by deep targeted (dt) NGS. The results were correlated with resected tissue, biopsy, and long-term follow-up. Results: A total of 164 patients with a dilated MPD were identified, of which 30 (18.3%) underwent EUS-guided FNA, with 1 patient having a minor complication (3.3%). Twenty-two patients (mean MPD diameter of 12.4 (7–31) mm) with a definitive, mostly surgically confirmed diagnosis were included in the analysis. Only a fish-mouth papilla, which was present in 3 of 12 (25%) MD-IPMNs, could reliably differentiate between the two diseases, with history, symptoms, diffuse or segmental MPD dilation, presence of calcifications on imaging, cytology, and CEA in the ductal fluid failing to achieve differentiation. However, GNAS mutations were found exclusively in 11 of the 12 (91.6%) patients with MD-IPMN (p < 0.01), whereas KRAS mutations were identified in both diseases. Conclusions: GNAS testing by dtNGS in aspirated fluid from dilated MPD obtained by EUS-guided FNA may help differentiate MD-IPMN from CP for surgical resection. Full article
(This article belongs to the Special Issue Advances in Endoscopy)
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7 pages, 1853 KiB  
Interesting Images
Mucinous Carcinoma, Mucinous Borderline Tumor and Pseudomyxoma Ovarii in a Cystic Teratoma: A Histological Conundrum
by Cinzia Giacometti, Mariateresa Mirandola, Camillo Aliberti, Filippo Molinari, Lisa Marcolini, Daniele Mautone and Guido Martignoni
Diagnostics 2025, 15(15), 1957; https://doi.org/10.3390/diagnostics15151957 - 4 Aug 2025
Abstract
Mature teratomas account for approximately 20% of all ovarian tumors identified in pathological studies. Benign or malignant somatic neoplasms developing within teratomas can arise from any tissue in up to 2% of mature cystic teratomas, including low-grade malignant mucinous neoplasms. This report presents [...] Read more.
Mature teratomas account for approximately 20% of all ovarian tumors identified in pathological studies. Benign or malignant somatic neoplasms developing within teratomas can arise from any tissue in up to 2% of mature cystic teratomas, including low-grade malignant mucinous neoplasms. This report presents the case of a 34-year-old woman with no previous gynecological or general health issues, who was admitted to our Hospital after an asymptomatic pelvic mass was detected during a routine exam. A transvaginal ultrasound revealed a unilateral pelvic mass in the left adnexal region, measuring 8 cm. The CT scan showed a cystic-appearing formation measuring nearly 12 cm, which indented the bladder dome. Final diagnosis indicated a mucinous carcinoma arising from a mucinous borderline lesion within the context of a mature ovarian teratoma. No other involvement or lymphadenopathies were detected on 18FDG-PET CT scan, and the patient is now well and free of recurrences. Full article
(This article belongs to the Special Issue Pathology and Diagnosis of Gynecologic Diseases, 3rd Edition)
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27 pages, 1326 KiB  
Systematic Review
Application of Artificial Intelligence in Pancreatic Cyst Management: A Systematic Review
by Donghyun Lee, Fadel Jesry, John J. Maliekkal, Lewis Goulder, Benjamin Huntly, Andrew M. Smith and Yazan S. Khaled
Cancers 2025, 17(15), 2558; https://doi.org/10.3390/cancers17152558 - 2 Aug 2025
Viewed by 188
Abstract
Background: Pancreatic cystic lesions (PCLs), including intraductal papillary mucinous neoplasms (IPMNs) and mucinous cystic neoplasms (MCNs), pose a diagnostic challenge due to their variable malignant potential. Current guidelines, such as Fukuoka and American Gastroenterological Association (AGA), have moderate predictive accuracy and may lead [...] Read more.
Background: Pancreatic cystic lesions (PCLs), including intraductal papillary mucinous neoplasms (IPMNs) and mucinous cystic neoplasms (MCNs), pose a diagnostic challenge due to their variable malignant potential. Current guidelines, such as Fukuoka and American Gastroenterological Association (AGA), have moderate predictive accuracy and may lead to overtreatment or missed malignancies. Artificial intelligence (AI), incorporating machine learning (ML) and deep learning (DL), offers the potential to improve risk stratification, diagnosis, and management of PCLs by integrating clinical, radiological, and molecular data. This is the first systematic review to evaluate the application, performance, and clinical utility of AI models in the diagnosis, classification, prognosis, and management of pancreatic cysts. Methods: A systematic review was conducted in accordance with PRISMA guidelines and registered on PROSPERO (CRD420251008593). Databases searched included PubMed, EMBASE, Scopus, and Cochrane Library up to March 2025. The inclusion criteria encompassed original studies employing AI, ML, or DL in human subjects with pancreatic cysts, evaluating diagnostic, classification, or prognostic outcomes. Data were extracted on the study design, imaging modality, model type, sample size, performance metrics (accuracy, sensitivity, specificity, and area under the curve (AUC)), and validation methods. Study quality and bias were assessed using the PROBAST and adherence to TRIPOD reporting guidelines. Results: From 847 records, 31 studies met the inclusion criteria. Most were retrospective observational (n = 27, 87%) and focused on preoperative diagnostic applications (n = 30, 97%), with only one addressing prognosis. Imaging modalities included Computed Tomography (CT) (48%), endoscopic ultrasound (EUS) (26%), and Magnetic Resonance Imaging (MRI) (9.7%). Neural networks, particularly convolutional neural networks (CNNs), were the most common AI models (n = 16), followed by logistic regression (n = 4) and support vector machines (n = 3). The median reported AUC across studies was 0.912, with 55% of models achieving AUC ≥ 0.80. The models outperformed clinicians or existing guidelines in 11 studies. IPMN stratification and subtype classification were common focuses, with CNN-based EUS models achieving accuracies of up to 99.6%. Only 10 studies (32%) performed external validation. The risk of bias was high in 93.5% of studies, and TRIPOD adherence averaged 48%. Conclusions: AI demonstrates strong potential in improving the diagnosis and risk stratification of pancreatic cysts, with several models outperforming current clinical guidelines and human readers. However, widespread clinical adoption is hindered by high risk of bias, lack of external validation, and limited interpretability of complex models. Future work should prioritise multicentre prospective studies, standardised model reporting, and development of interpretable, externally validated tools to support clinical integration. Full article
(This article belongs to the Section Methods and Technologies Development)
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17 pages, 5323 KiB  
Review
Contrast-Enhanced Harmonic Endoscopic Ultrasonography for Prediction of Aggressiveness and Treatment Response in Patients with Pancreatic Lesions
by Marco Spadaccini, Gianluca Franchellucci, Marta Andreozzi, Maria Terrin, Matteo Tacelli, Piera Zaccari, Maria Chiara Petrone, Gaetano Lauri, Matteo Colombo, Valeria Poletti, Giacomo Marcozzi, Antonella Durante, Roberto Leone, Maria Margherita Massaro, Antonio Facciorusso, Alessandro Fugazza, Alessandro Repici, Paolo Giorgio Arcidiacono and Silvia Carrara
Cancers 2025, 17(15), 2545; https://doi.org/10.3390/cancers17152545 - 1 Aug 2025
Viewed by 319
Abstract
Endoscopic ultrasonography represents a crucial aspect of the diagnosis of pancreatic lesions. The echo-endoscopic features of pancreatic lesions, particularly their contrast behavior with the advent of Contrast-Enhanced EUS (CE-EUS) and Contrast Enhanced Harmonic-EUS (CH-EUS), can predict a lesion’s aggressiveness, depending on its nature. [...] Read more.
Endoscopic ultrasonography represents a crucial aspect of the diagnosis of pancreatic lesions. The echo-endoscopic features of pancreatic lesions, particularly their contrast behavior with the advent of Contrast-Enhanced EUS (CE-EUS) and Contrast Enhanced Harmonic-EUS (CH-EUS), can predict a lesion’s aggressiveness, depending on its nature. According to this, CH-EUS could be applied to structure an even more dedicated approach to patient care, for example, to ascertain eligibility for surgical intervention of a pancreatic ductal adenocarcinoma (PDAC) or the response to neoadjuvant chemotherapy in cases deemed borderline resectable. In addition to PDAC, other significant issues pertain to the management of small neuroendocrine tumors (NETs) and intraductal papillary mucinous neoplasms (IPMNs). In this context, CH-EUS can be crucial. The aim of this review is to underline the most recent evidence for EUS and CH-EUS applications in pancreatic lesion aggressiveness assessment and to focus on possible future research directions to further extend the application of CH-EUS in this field. Full article
(This article belongs to the Special Issue Clinical Applications of Ultrasound in Cancer Imaging and Treatment)
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27 pages, 2907 KiB  
Review
High-Grade Appendiceal Goblet Cell Adenocarcinoma—A Literature Review Starting from a Rare Case
by Mircea Gheorghe, Rodica Daniela Birla, Anca Evsei-Seceleanu, Luiza Bitina, Ioan Nicolae Mates and Dragos Valentin Predescu
Life 2025, 15(7), 1047; https://doi.org/10.3390/life15071047 - 30 Jun 2025
Viewed by 490
Abstract
Goblet cell adenocarcinomas (GCAs) are an exceedingly rare subtype of tumors, almost exclusively occurring in the appendix, and characterized by features overlapping both adenocarcinomas and neuroendocrine tumors (NETs), which has historically led to confusion and varied nomenclature. This study presents a comprehensive review [...] Read more.
Goblet cell adenocarcinomas (GCAs) are an exceedingly rare subtype of tumors, almost exclusively occurring in the appendix, and characterized by features overlapping both adenocarcinomas and neuroendocrine tumors (NETs), which has historically led to confusion and varied nomenclature. This study presents a comprehensive review of the literature highlighting particularities of this type of malignancy, starting from a rare case of a 54-year-old female operated on in our clinic for an appendiceal tumor, initially suspected to be a mucinous neoplasm based on colonoscopic biopsy, which was ultimately confirmed to be goblet cell adenocarcinoma on both intraoperative frozen section and definitive pathological examination. Exhibiting signs and symptoms associated with an abdominal mass, she underwent a right hemicolectomy with partial omentectomy for locally advanced, high-grade, invasive goblet cell adenocarcinoma of the appendix with lymphatic macro metastases and epiploic invasion, categorized as AJCC stage IVb carcinomatosis. The patient received FOLFOX adjuvant. Six months later, she required reoperation due to the progression of carcinomatosis, which was again confirmed histopathologically. A second-line oncological protocol comprising irinotecan, capecitabine, and bevacizumab was initiated. Given the rarity of GCAs and the absence of a consensus on nomenclature, classification, and diagnostic criteria, we conducted a comprehensive literature review to highlight current trends related to this entity, including its classification within different systems (Tang, Yozu, WHO, AJCC), as well as the therapeutic surgical approaches—ranging from simple appendectomy to extensive multiorgan resection, cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC), and the use of systemic therapy. Adhering to these recommendations will enhance communication among pathologists, surgeons, and oncologists regarding the natural history and prognosis of this rare malignancy. Full article
(This article belongs to the Special Issue Pathophysiology, Diagnosis, and Treatments of Intestinal Diseases)
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18 pages, 2465 KiB  
Case Report
Pancreatic Endometriosis Coexisting with a Splenic Mesothelial Cyst: A Rare Case Report and Review of the Literature
by Daniel Paramythiotis, Antonia Syrnioti, Dimitrios Tsavdaris, Aikaterini Smprini, Alexandros Mekras, Athanasios Apostolidis and Angeliki Cheva
Diseases 2025, 13(7), 203; https://doi.org/10.3390/diseases13070203 - 30 Jun 2025
Viewed by 351
Abstract
Endometriosis is a clinical entity affecting up to 10% of women of reproductive age, characterized by ectopic endometrial tissue outside the uterine cavity. While extrapelvic endometriosis has been documented, pancreatic endometriosis remains extremely rare and poses significant diagnostic challenges due to its similarity [...] Read more.
Endometriosis is a clinical entity affecting up to 10% of women of reproductive age, characterized by ectopic endometrial tissue outside the uterine cavity. While extrapelvic endometriosis has been documented, pancreatic endometriosis remains extremely rare and poses significant diagnostic challenges due to its similarity to other pancreatic diseases. At the same time, splenic mesothelial cysts are also rare and typically benign. This report presents a unique case of pancreatic endometriosis coexisting with a splenic mesothelial cyst in a 31-year-old woman. The patient presented to the emergency department with complaints of persistent epigastric and low back pain. She noted having similar symptoms approximately a year prior. Her past medical history was otherwise unremarkable, and there was no known family history of pancreatic disease or neoplasms. Initial imaging revealed a 3.8 cm cystic lesion in the pancreatic tail, with features suggestive of mucinous cystadenoma. Following clinical evaluation and confirmation of the cyst’s nature through endoscopic ultrasound-guided biopsy, the patient subsequently underwent laparoscopic distal pancreatectomy and splenectomy due to worsening symptoms. Gross examination revealed a multilocular pancreatic cyst with a smooth, hemorrhagic wall. Microscopic analysis showed the cyst to be lined by cuboidal to columnar epithelium, consistent with pancreatic endometriosis, confirmed by immunohistochemical staining. The spleen showed cystic formations, diagnosed as a multifaceted mesothelial cyst. In conclusion, this report is the first to document the coexistence of pancreatic endometriosis and splenic mesothelial cysts, highlighting the importance of accurate imaging and pathologic evaluation in the diagnosis of these rare conditions. Early diagnosis and surgical intervention lead to favorable outcomes, reinforcing the importance of comprehensive diagnostic strategies. Full article
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15 pages, 2147 KiB  
Article
Clinical Features of Intraductal Papillary Mucinous Neoplasm-Related Pancreatic Carcinomas in Long-Term Surveillance
by Kyohei Matsuura, Shinsaku Nagamatsu, Shoma Kikukawa, Yuya Nishio, Yusuke Komeda, Yuya Matsuo, Kohei Ohta, Chisa Yamamoto, Ayana Sueki and Kei Moriya
J. Clin. Med. 2025, 14(13), 4585; https://doi.org/10.3390/jcm14134585 - 27 Jun 2025
Viewed by 540
Abstract
Background and Aims: An appropriate surveillance system must be established to efficiently identify cases of intraductal papillary mucinous neoplasm (IPMN)-related malignant transformation. We analyzed the initial clinical background that affects long-term prognosis and narrowed the population for whom continued evaluation is inevitable. Methods: [...] Read more.
Background and Aims: An appropriate surveillance system must be established to efficiently identify cases of intraductal papillary mucinous neoplasm (IPMN)-related malignant transformation. We analyzed the initial clinical background that affects long-term prognosis and narrowed the population for whom continued evaluation is inevitable. Methods: We included 1645 patients with IPMN treated at our hospital since 2010. We examined the types and timing of malignant transformation in terms of the worrisome features (WFs). The chi-squared test, log-rank test, and Cox proportional hazards model were used for the analysis (statistical significance at α = 0.05). Results: In total, 123 (7.5%) and 41 patients (2.5%) had IPMN-derived carcinoma (IPMN-DC) and concomitant pancreatic ductal adenocarcinoma (c-PDAC), respectively. Compared with IPMN-DC, a significantly higher proportion of c-PDAC patients were diagnosed with an advanced disease stage that developed earlier. The factors with significantly shorter time for IPMN-DC development were maximum cyst diameter (MCD) ≥ 30 mm, nonbranched type, main pancreatic duct (MPD) diameter ≥ 5 mm, and septal nodal structure (SNS) for IPMN-DC, and MCD ≥ 30 mm, main duct type, MPD ≥ 5 mm, SNS, cyst enlargement (≥2.5 mm/year), and abnormal CA19-9 levels for c-PDAC. Both groups could be significantly stratified by the number of WFs. A relative risk analysis revealed that SNS, MCD ≥ 30 mm, and MPD ≥ 5 mm were significant factors for IPMN-DC, whereas abnormal CA19-9 and SNS were significant for c-PDAC. Conversely, significantly more patients exhibiting these factors initially later developed IPMN-DC or c-PDAC. Conclusions: Ten percent of IPMN cases will develop IPMN-DC or c-PDAC, thereby requiring careful follow-up, especially in cases with SNS, abnormal CA19-9, and MCD ≥ 30 mm. Full article
(This article belongs to the Section Oncology)
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10 pages, 1973 KiB  
Case Report
Mucinous Cystic Neoplasms in Male Patients: Histopathological and Molecular Diagnoses
by Lara Malaspina, Natale Calomino, Ludovico Carbone, Anastasia Batsikosta, Fabiola Rossi, Gianmario Edoardo Poto, Aurora Visani, Lucia Mundo, Bina Barbato, Ilaria Monteleone, Franco Roviello and Sergio Antonio Tripodi
Curr. Oncol. 2025, 32(6), 352; https://doi.org/10.3390/curroncol32060352 - 13 Jun 2025
Viewed by 407
Abstract
Cystic mucinous neoplasms (MCNs) of the pancreas are rare cystic tumors, accounting for approximately 2–5% of all pancreatic neoplasms. They predominantly occur in premenopausal women and are typically located in the body or tail of the pancreas. Due to their potential for malignant [...] Read more.
Cystic mucinous neoplasms (MCNs) of the pancreas are rare cystic tumors, accounting for approximately 2–5% of all pancreatic neoplasms. They predominantly occur in premenopausal women and are typically located in the body or tail of the pancreas. Due to their potential for malignant transformation, especially in cases associated with invasive carcinoma such as pancreatic ductal adenocarcinoma, early detection, complete surgical resection, and rigorous postoperative surveillance are essential. The occurrence of MCNs in male patients is exceedingly rare, comprising only about 2% of reported cases, and often resulting in preoperative diagnostic challenges. Molecular analyses have identified a strong association between KRAS mutations and disease progression in MCNs, underscoring their potential role as prognostic markers despite limited diagnostic utility. In this report, we present two additional cases of MCNs in male patients, highlighting their histopathological features and the ancillary investigations undertaken to support diagnosis. Full article
(This article belongs to the Section Surgical Oncology)
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11 pages, 1746 KiB  
Article
Safety and Efficacy of Radiofrequency Ablation in Management of Various Pancreatic Neoplasms
by Varshita Goduguchinta, Mohamed Ebrahim, Raahi Patel, Navkiran Randhawa, Ahamed Khalyfa, Mahnoor Inamullah, Rahil Desai and Kamran Ayub
J. Clin. Med. 2025, 14(11), 3958; https://doi.org/10.3390/jcm14113958 - 4 Jun 2025
Viewed by 654
Abstract
Background/Objectives: Pancreatic neoplasms, including adenocarcinoma, pancreatic neuroendocrine tumors (pNETs), intraductal papillary mucinous neoplasms (IPMNs), and high-grade cystic lesions, often require surgical resection as a form of curative treatment. However, comorbidities and high-risk features may preclude surgery. Endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) has emerged [...] Read more.
Background/Objectives: Pancreatic neoplasms, including adenocarcinoma, pancreatic neuroendocrine tumors (pNETs), intraductal papillary mucinous neoplasms (IPMNs), and high-grade cystic lesions, often require surgical resection as a form of curative treatment. However, comorbidities and high-risk features may preclude surgery. Endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) has emerged as a minimally invasive alternative with proven cytoreductive efficacy in solid tumors. This case series evaluates the safety and efficacy of EUS-RFA in patients with various unresectable, non-metastatic pancreatic neoplasms. Methods: A retrospective review was conducted on eight patients who underwent EUS-RFA at our institutions between July 2021 and February 2025. All patients were deemed unsuitable surgical candidates due to comorbidities such as advanced age, cardiovascular disease, renal insufficiency, and COPD or due to patient resistance to surgical intervention. EUS-RFA was performed using a 19-gauge RFA needle (Taewoong Corporation). Follow-up imaging was conducted 3 to 6 months after the completion of RFA treatment. Results: All eight patients demonstrated a good to excellent response in terms of tumor size reduction. The most notable response was observed in a patient with pNET, resulting in complete resolution from 15.6 × 12.0 mm to 0.0 × 0.0 mm after two RFA treatments. Other neoplasms, including pancreatic adenocarcinoma and intraductal papillary mucinous neoplasms (IPMNs), also demonstrated significant reductions. Mild post-procedure complications, including pancreatitis and abdominal pain, were noted in three cases. Conclusions: EUS-RFA is a promising alternative for managing unresectable pancreatic neoplasms in high-risk patients. Our findings support its use across various tumor types with favorable outcomes and minimal complications, reinforcing its role in expanding therapeutic options beyond surgery. Full article
(This article belongs to the Section Gastroenterology & Hepatopancreatobiliary Medicine)
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14 pages, 597 KiB  
Review
Endoscopic Ultrasound-Guided Pancreatic Cystic Fluid Biochemical and Genetic Analysis for the Differentiation Between Mucinous and Non-Mucinous Pancreatic Cystic Lesions
by Angelo Bruni, Luigi Tuccillo, Giuseppe Dell’Anna, Francesco Vito Mandarino, Andrea Lisotti, Marcello Maida, Claudio Ricci, Lorenzo Fuccio, Leonardo Henry Eusebi, Giovanni Marasco and Giovanni Barbara
J. Clin. Med. 2025, 14(11), 3825; https://doi.org/10.3390/jcm14113825 - 29 May 2025
Viewed by 780
Abstract
Pancreatic cystic lesions (PCLs) are increasingly identified via computerized tomography (CT) and magnetic resonance (MR), with a prevalence of 2–45%. Distinguishing mucinous PCLs (M-PCLs), which include intraductal papillary mucinous neoplasms (IPMNs) and mucinous cystic neoplasms (MCNs) that can progress to pancreatic ductal adenocarcinoma, [...] Read more.
Pancreatic cystic lesions (PCLs) are increasingly identified via computerized tomography (CT) and magnetic resonance (MR), with a prevalence of 2–45%. Distinguishing mucinous PCLs (M-PCLs), which include intraductal papillary mucinous neoplasms (IPMNs) and mucinous cystic neoplasms (MCNs) that can progress to pancreatic ductal adenocarcinoma, from non-mucinous PCLs (NM-PCLs) is essential. Carcinoembryonic antigen (CEA) remains widely used but often demonstrates limited sensitivity and specificity. In contrast, endoscopic ultrasound-guided measurement of intracystic glucose more accurately differentiates PCL subtypes, as tumor-related metabolic changes lower cyst fluid glucose in mucinous lesions. Numerous prospective and retrospective studies suggest a glucose cut-off between 30 and 50 mg/dL, yielding a sensitivity of 88–95% and specificity of 76–91%, frequently outperforming CEA. Additional benefits include immediate point-of-care assessment via standard glucometers and minimal interference from blood contamination. DNA-based biomarkers, including KRAS and GNAS mutations, enhance specificity (up to 99%) but exhibit moderate sensitivity (61–71%) and necessitate specialized, expensive platforms. Molecular analyses can be crucial in high-risk lesions, yet their uptake is constrained by technical challenges. In practice, combining glucose assessment with targeted molecular assays refines risk stratification and informs the choice between surgical resection or active surveillance. Future investigations should establish standardized glucose thresholds, improve the cost-effectiveness of genetic testing, and integrate advanced biomarkers into routine protocols. Ultimately, these strategies aim to optimize patient management, limit unnecessary interventions for benign lesions, and ensure timely therapy for lesions at risk of malignant transformation. Full article
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22 pages, 1997 KiB  
Article
Bioadhesive Eudragit RL®100 Nanocapsules for Melanoma Therapy: A Repurposing Strategy for Propranolol
by Naomi Gerzvolf Mieres, Soraia de Oliveira Simião, Luiza Stolz Cruz, Rafaela Cirillo de Melo, Najeh Maissar Khalil, Juliana Sartori Bonini, Fabiane Gomes de Moraes Rego, Marcel Henrique Marcondes Sari, Roberto Pontarolo, Raul Edison Luna Lazo, Jéssica Brandão Reolon and Luana Mota Ferreira
Pharmaceutics 2025, 17(6), 718; https://doi.org/10.3390/pharmaceutics17060718 - 29 May 2025
Viewed by 700
Abstract
Background/Objectives: Cutaneous melanoma is a potent neoplasm whose advancement is linked to catecholamine-induced angiogenesis through β-adrenergic receptors. Propranolol (PROP), a non-selective β-blocker, holds potential in oncology, but its systemic side effects restrict its viability. This study aims to nanoencapsulate PROP in Eudragit RL [...] Read more.
Background/Objectives: Cutaneous melanoma is a potent neoplasm whose advancement is linked to catecholamine-induced angiogenesis through β-adrenergic receptors. Propranolol (PROP), a non-selective β-blocker, holds potential in oncology, but its systemic side effects restrict its viability. This study aims to nanoencapsulate PROP in Eudragit RL®100 polymeric nanocapsules for topical melanoma treatment. Methods: Nanocapsules were created through interfacial deposition of preformed polymer and characterized in terms of particle size, zeta potential, pH, drug content, and encapsulation efficiency. In vitro evaluations include release profile, antioxidant activity, bioadhesiveness, hemolysis, cytotoxicity, and antitumor effect on melanoma cells. Additionally, migration assays were conducted. Results: The nanocapsules displayed an acidic pH, an average size of 151 nm, and a positive zeta potential. An encapsulation efficiency of 81% was achieved, even with the hydrochloride form of the drug. The release profile exhibited sustained release of PROP, showcasing enhanced antioxidant activity in the nanoencapsulated form. The formulations also exhibited significant bioadhesion with mucin and an in vitro hemolysis rate over 50%, attributed to the cationic polymer and surfactants present. Moreover, in the cell viability assays, the NC-PROP formulations significantly reduced melanoma cell viability. In the migration assay, both the nanocapsules with and without the drug significantly inhibited cell migration, supporting the potential therapeutic benefits of these formulations. Conclusions: The nanoencapsulation of PROP in Eudragit RL®100 presents a viable strategy for topical treatment of cutaneous melanoma, enhancing release duration and reducing systemic effects. The assessments indicated distinct physical properties and substantial therapeutic potential. Full article
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10 pages, 206 KiB  
Article
Clinical Characteristics, Surgical Management, and Outcomes of Borderline Ovarian Tumours: A Retrospective Observational Study from North East London
by Kshitij Jamdade, Amal Hashi and Nandita Deo
J. Clin. Med. 2025, 14(7), 2383; https://doi.org/10.3390/jcm14072383 - 30 Mar 2025
Cited by 1 | Viewed by 847
Abstract
Background: Borderline ovarian tumours (BOTs) are a unique subset of epithelial ovarian neoplasms characterised by atypical epithelial proliferation without stromal invasion. BOTs are typically diagnosed at an early stage, primarily affect women of reproductive age, and have a favourable prognosis. This study aims [...] Read more.
Background: Borderline ovarian tumours (BOTs) are a unique subset of epithelial ovarian neoplasms characterised by atypical epithelial proliferation without stromal invasion. BOTs are typically diagnosed at an early stage, primarily affect women of reproductive age, and have a favourable prognosis. This study aims to evaluate the clinical characteristics, surgical management, and outcomes of BOTs in a North East London cohort. Methods: A retrospective, multicentric analysis was conducted on 69 patients with histologically confirmed BOTs managed between January 2018 and December 2022 across the Barts Health NHS Trust hospitals. Clinical and demographic data, surgical details, histopathological findings, and recurrence rates were analysed. We used descriptive and exploratory statistical methods. Results: The mean age at diagnosis was 44 years, with 46.37% under 40, including 18 nulliparous women. Most tumours (91.3%) were FIGO stage I, with mucinous histology predominating (56.52%), followed by serous BOTs (27.53%). Ultrasound and MRI demonstrated 65.45% and 81.5% sensitivities for borderline or malignant features, respectively. Surgical approaches included open surgery (75.4%), laparoscopy (17.4%), and robotic-assisted procedures (2.9%). Fertility-sparing surgery (FSS) was performed in all nulliparous women under 40 years of age. Recurrence occurred in 2 cases, both in patients with prior FSS performed over a decade earlier. Conclusions: FSS is a viable option for young women, especially if nulliparous and under the age of 40, with recurrence rates comparable to radical procedures. Most patients were diagnosed early (FIGO I) with excellent prognoses. MRI proved most sensitive for diagnosis, while long-term follow-up with transvaginal ultrasound and CA-125 monitoring is crucial for detecting recurrences. Full article
(This article belongs to the Section Oncology)
11 pages, 806 KiB  
Article
Evaluating the Usefulness of the Blood Apolipoprotein A2 Isoform Index for Pancreatic Cancer Diagnosis
by Kento Shionoya, Atsushi Sofuni, Shuntaro Mukai, Takayoshi Tsuchiya, Reina Tanaka, Ryosuke Tonozuka, Kenjiro Yamamoto, Kazumasa Nagai, Yukitoshi Matsunami, Hiroyuki Kojima, Hirohito Minami, Noriyuki Hirakawa, Kyoko Asano, Yuma Yamaguchi, Kazuki Hama and Takao Itoi
Cancers 2025, 17(7), 1071; https://doi.org/10.3390/cancers17071071 - 22 Mar 2025
Viewed by 677
Abstract
Background: Early detection of pancreatic cancer using existing tumor markers is challenging, and novel biomarkers are needed. Apolipoprotein A2 (APOA2), which is not directly produced by tumors, may help detect pancreatic cancer through mechanisms distinct from carbohydrate antigen 19-9 (CA 19-9). This [...] Read more.
Background: Early detection of pancreatic cancer using existing tumor markers is challenging, and novel biomarkers are needed. Apolipoprotein A2 (APOA2), which is not directly produced by tumors, may help detect pancreatic cancer through mechanisms distinct from carbohydrate antigen 19-9 (CA 19-9). This study aimed to evaluate the diagnostic performance of the APOA2-isoform (APOA2-i) Index in patients with pancreatic cancer. Methods: Serum levels of the APOA2-i Index and CA 19-9 were measured in 76 patients with pancreatic cancer (Stage 0, n = 5; I, n = 4; II, n = 15; III, n = 19; and IV, n = 33) and 98 patients with non-pancreatic cancer (intraductal papillary mucinous neoplasm, n = 36; chronic pancreatitis, n = 33; pancreatic neuroendocrine neoplasm, n = 8; autoimmune pancreatitis, n = 9; and others, n = 12) to evaluate diagnostic performance. Results: APOA2 showed lower accuracy for advanced (stages II–IV) pancreatic cancer compared to CA 19-9 (sensitivity, 50.7% vs. 83.6%; sensitivity, 77.6% vs. 87.9%), but it provided superior accuracy for early-stage (stages 0 and I) detection (sensitivity, 33.3% vs. 22.2%; specificity, 66.7% vs. 59.4%). Three early-stage pancreatic cancer cases negative for CA 19-9 were detected with the APOA2-i Index, demonstrating high diagnostic accuracy for early-stage pancreatic cancer when both biomarkers are combined (sensitivity, 44.4%; specificity, 46.7%). The multivariate analysis revealed pancreatic cancer to be an independent risk factor for APOA2-i Index positivity (odds ratio [OR]: 3.48, p < 0.001), CA 19-9 positivity (OR: 25.5, p < 0.001), and positivity for either marker (OR: 13.3, p < 0.001). Conclusions: The APOA2-i Index, combined with CA 19-9, may improve early-stage pancreatic cancer detection, especially in challenging cases and for high-risk patient surveillance. Full article
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13 pages, 965 KiB  
Systematic Review
Primary Adenocarcinoma of the Upper Urinary Tract: A Systematic Review of the Literature on a Rare Entity
by Ilias Giannakodimos, Evripidis Bekiaris, Afroditi Ziogou, Alexios Giannakodimos, Evangelia Mitakidi, Konstantina Psalla, Evangelos Fragkiadis, Aris Kaltsas, Zisis Kratiras and Michael Chrisofos
J. Clin. Med. 2025, 14(6), 2010; https://doi.org/10.3390/jcm14062010 - 16 Mar 2025
Viewed by 585
Abstract
Background: Only a few published cases of primary adenocarcinoma of the upper urinary tract have been described in the literature. The aim of this systematic review was to collect all published cases of primary adenocarcinoma of the upper UT and identify prognostic [...] Read more.
Background: Only a few published cases of primary adenocarcinoma of the upper urinary tract have been described in the literature. The aim of this systematic review was to collect all published cases of primary adenocarcinoma of the upper UT and identify prognostic factors and useful diagnostic modalities for their optimal treatment. Methods: Systematic research in the PubMed/Medline and Scopus databases concerning primary adenocarcinoma of the upper urinary tract was performed by two independent investigators. A total of 85 studies were included in the review. Results: In total, 84 patients were included, consisting of 54 males (64.29%) and 30 females (35.71%). Out of the available data, 24.71% reported a history of lithiasis, 16.47% episodes of pyelonephritis and 10.59% a history of hydronephrosis. Concerning histologic findings on excised tumors, 52.44% of neoplasms were mucinous, 19.51% tubulovilous, 18.29% papillary, 4.88% mixed mucinous–papillary and 4.88% poorly differentiated. Concerning anatomical origin, 62.34% of tumors were found in the renal pelvis, 22.08% in the ureter and 12.99% in both the renal pelvis and the ureter. Surgical treatment was the preferred therapeutic option and was performed in 96.39% of the included patients. In multivariable analysis, a statistically significant relationship was found between a clinical cure and ureter origin of the lesion (OR: 0.17, 95% CI: 0.00–0.22, p = 0.002), the presence of an abdominal mass (OR: 0.08, 95% CI: 0.01–0.63, p: 0.034) and a poorly differentiated histological type (OR: 0.02, 95% CI: 0.00–0.91). In multivariable time-to-event analysis, the male sex (HR: 0.12, 95% CI: 0.02–1.01, p: 0.019) and poorly differentiated histological type (HR: 91.06, 95% CI: 7.31–1134.32, p: 0.002) had statistically significant impacts on overall survival. Conclusions: Selection of the optimal surgical management, via either nephrectomy or nephroureterectomy, depends on the origin of the primary lesion and represents the mainstay of treatment. A suspicion from the urologist is needed for the identification and optimal treatment of these rare tumors. Full article
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Systematic Review
Acute Appendicitis or Appendiceal Diverticulitis? A Case Report and Systematic Literature Review
by Stipe Vidović, Nenad Čekić, Ivica Šuvak, Mladen Ugljarević and Zenon Pogorelić
Clin. Pract. 2025, 15(3), 60; https://doi.org/10.3390/clinpract15030060 - 13 Mar 2025
Viewed by 1291
Abstract
Background: Appendiceal diverticulitis is a rare and poorly understood condition of the appendix. The diagnosis of appendiceal diverticulitis is challenging due to its rarity and a clinical presentation that often mimics other ileocecal disorders. Unlike acute appendicitis, appendiceal diverticulitis may be associated [...] Read more.
Background: Appendiceal diverticulitis is a rare and poorly understood condition of the appendix. The diagnosis of appendiceal diverticulitis is challenging due to its rarity and a clinical presentation that often mimics other ileocecal disorders. Unlike acute appendicitis, appendiceal diverticulitis may be associated with a higher risk of perforation, increased mortality, and a potential link to neoplasms. However, further research is necessary to enhance our understanding of its epidemiology, risk factors, clinical presentation, and outcomes. Case Report: A 53-year-old male presented to the emergency department with right lower abdominal pain. On physical examination, tenderness was noted in the right lower quadrant, without rebound tenderness or muscle guarding. Laboratory tests revealed leukocytosis and elevated C-reactive protein (CRP) levels. Ultrasonographic imaging of the ileocecal region suggested acute appendicitis, leading to a decision for surgical intervention. Laparoscopic exploration revealed multiple cylindrical, red, and edematous herniations, up to 4 mm in size, on the surface of the vermiform appendix. An appendectomy was performed. Histopathological examination confirmed appendiceal diverticulitis with surrounding peridiverticulitis. The surgery and early postoperative course were uneventful. Literature review: The study included 5 retrospective studies and 30 case reports, analyzing a total of 112 patients with appendiceal diverticulitis. Of these, 65.5% were male and 34.5% were female, with a median age of 49 years (IQR: 39–59). The most commonly reported clinical findings included pain in the right iliac fossa or right lower abdominal quadrant (56.5%), nausea (18.9%), vomiting (9.8%), rebound tenderness (24.6%), fever (15.6%), leukocytosis (25.4%), and elevated C-reactive protein levels (16.4%). Diagnosis was confirmed histopathologically in 86.9% of the cases via computed tomography imaging in 4.1% and ultrasonography in 1.6%. A histopathological analysis identified five neoplasms (4.1%), including two sessile serrated adenomas, two neuroendocrine carcinoids, and one mucinous tumor. Appendectomy was the treatment of choice, with no intraoperative or postoperative complications recorded and no mortality reported. The median hospital stay was 6.8 days (IQR: 3.0–6.8). Conclusions: Appendiceal diverticulitis should be considered as a differential diagnosis in patients presenting with symptoms resembling acute appendicitis. Early diagnosis and treatment are essential to reduce morbidity and mortality. Appendectomy is a safe and effective treatment approach for appendiceal diverticulitis. Full article
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