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Xu JX, Su YX, Chen YY, Huang YY, Chen ZS, Peng YC, Qi LN. Immune infiltration landscape and potential drug-targeted implications for hepatocellular carcinoma with 'progression/hyper-progression' recurrence. Ann Med 2025; 57:2456113. [PMID: 39865865 PMCID: PMC11774162 DOI: 10.1080/07853890.2025.2456113] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/03/2024] [Revised: 12/20/2024] [Accepted: 01/08/2025] [Indexed: 01/30/2025] Open
Abstract
BACKGROUND AND AIMS Hepatocellular carcinoma (HCC) recurrence was previously characterized into four types, and patients with progression/hyper-progression recurrence (type III-IV) have an extremely poor prognosis. However, the immune background of resectable HCC, particularly in patients who experience recurrence, remains underexplored. Therefore, this study aimed to describe the immune landscape of resectable HCC, especially postoperative type III-IV recurrent HCC, and explore potential immune-targeted anti-relapse strategies for treated populations. METHODS The differences in gene expression in patients with recurrent HCC (type I-II (solitary or multi-intrahepatic oligo recurrence) vs. type III-IV) were investigated using bulk sequencing. Multiple immune infiltration methods (single-sample gene set enrichment analysis (GSEA), Microenvironment Cell Populations-counter and ESTIMATE) were used, and patients were divided into four groups to identify four distinct immune subtypes: immune-enrichment/matrix-poor (IE1), immune-enrichment/matrix-rich (IE2), immune intermediate/matrix-rich (ITM) and immune desert/matrix-poor (ID). Co-expression and protein interaction analyses were used to identify characteristic genes in ITM closely associated with type III-IV recurrence, which was matched with drug targets for Huaier granules (HG) and lenvatinib. Virtual docking was used to identify potential therapeutic targets, and the results were verified using single-nuclei RNA sequencing and histological analysis. RESULTS ITM was closely related to type III-IV recurrence and exhibited immunotherapy potential. The potential efficacy of inhibiting CCNA2, VEGFA, CXCL8, PLK2, TIMP1, ITGB2, ALDOA, ANXA5 and CSK in ITM reversal was determined. Molecular docking demonstrated that the proteins of these genes could bind to HG or lenvatinib. The immunohistochemical findings demonstrated differential VEGFA (p < .01) and PLK2 (p < .001) expression in ITM type and ID in type III-IV recurrent HCC. CONCLUSIONS Three primary immunotypes of resectable HCC (IE2, ITM and ID) were identified, and HG and lenvatinib could potentially overcome immune checkpoint blockade (ICB) resistance in ITM patients with HCC, particularly those classified as type III-IV.
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Affiliation(s)
- Jing-Xuan Xu
- Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning, China
- Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumour, Ministry of Education, Nanning, China
| | - Yue-Xiang Su
- Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning, China
- Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumour, Ministry of Education, Nanning, China
| | - Yuan-Yuan Chen
- Department of Ultrasound, First Affiliated Hospital of Guangxi Medical University, Nanning, China
| | - Yi-Yue Huang
- Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning, China
- Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumour, Ministry of Education, Nanning, China
| | - Zu-Shun Chen
- Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning, China
| | - Yu-Chong Peng
- Department of General Surgery, Chongqing Hospital of Traditional Chinese Medicine, Chongqing, China
| | - Lu-Nan Qi
- Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning, China
- Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumour, Ministry of Education, Nanning, China
- Guangxi Liver Cancer Diagnosis and Treatment Engineering and Technology Research Center, Nanning, China
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Möller L, Szentkirályi A, Eisfeld C, Wellmann I, Rees F, Claaßen K, Oesterling F, Kajüter H, Stang A. Incidence trends and relative survival of colorectal neuroendocrine neoplasms: A population-based study using German cancer registry data. Int J Cancer 2025; 157:116-125. [PMID: 39976321 PMCID: PMC12062926 DOI: 10.1002/ijc.35372] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2024] [Revised: 01/18/2025] [Accepted: 01/28/2025] [Indexed: 02/21/2025]
Abstract
Neuroendocrine neoplasms (NENs) of the colon and rectum are a heterogeneous group of epithelial neoplasms with neuroendocrine differentiation. They include well-differentiated neuroendocrine tumors (NETs), poorly differentiated neuroendocrine carcinomas (NECs) and mixed neuroendocrine-non-neuroendocrine neoplasms (MiNENs). Our aim was to calculate incidence, incidence trends and relative survival for colonic and rectal NETs, NECs, and MiNENs. We analyzed data covering the entire German population recorded between 2009 and 2021, calculating age-standardized incidence rates, annual percent changes, and the relative 5-year survival probability for the calendar period 2017-2021. Our comprehensive analyses included 12,602 NEN cases, with 59% located in the rectum. NECs, MiNENs and tumors with colonic location showed higher stages. We observed an increase in the incidence of NETs, particularly in patients aged <55 years, and in the incidence of MiNENs, and a constant incidence of NECs. The relative five-year survival was high for rectal NETs (95.9%, 95%-CI 94.6; 97.1) and colonic NETs (81.4%, 95%-CI 78.3; 84.5) and low for colonic NECs (20.5%, 95%-CI 17.6; 23.4) and rectal NECs (19.2%, 95%-CI 15.7; 22.6). The increase in the incidence of NETs might be partly due to colorectal cancer screening, improved diagnostics, and changes in classification of NETs. We attribute the increase in incidence of MiNENs to the recent introduction of this morphological category. Higher stages at diagnosis, a higher proportion of NECs and higher median age at diagnosis may contribute to the less favorable survival probabilities associated with colonic as opposed to rectal location.
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Affiliation(s)
- Lennart Möller
- Cancer Registry of North Rhine WestphaliaBochumGermany
- Faculty of MedicineUniversity of Duisburg‐EssenEssenGermany
| | | | | | - Ina Wellmann
- Cancer Registry of North Rhine WestphaliaBochumGermany
| | | | - Kevin Claaßen
- Cancer Registry of North Rhine WestphaliaBochumGermany
- Department of Medical Statistics and EpidemiologyMedical School HamburgHamburgGermany
| | | | | | - Andreas Stang
- Cancer Registry of North Rhine WestphaliaBochumGermany
- Institute of Medical Informatics, Biometry and EpidemiologyUniversity Hospital EssenEssenGermany
- School of Public Health, Department of EpidemiologyBoston UniversityBostonMassachusettsUSA
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Tacelli M, Gentiluomo M, Biamonte P, Castano JP, Berković MC, Cives M, Kapitanović S, Marinoni I, Marinovic S, Nikas I, Nosáková L, Pedraza-Arevalo S, Pellè E, Perren A, Strosberg J, Campa D, Capurso G. Pancreatic neuroendocrine neoplasms (pNENs): Genetic and environmental biomarkers for risk of occurrence and prognosis. Semin Cancer Biol 2025; 112:112-125. [PMID: 40158764 DOI: 10.1016/j.semcancer.2025.03.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2025] [Revised: 03/07/2025] [Accepted: 03/19/2025] [Indexed: 04/02/2025]
Abstract
Pancreatic neuroendocrine neoplasms (pNENs) are rare and heterogeneous tumors arising from neuroendocrine cells, representing approximately 10 % of all Gastro-Entero-Pancreatic neuroendocrine neoplasms. While most pNENs are sporadic, a subset is associated with genetic syndromes such as multiple endocrine neoplasia type 1 (MEN1) or von Hippel-Lindau disease (VHL). pNENs are further classified into functioning and non-functioning tumors, with distinct clinical behaviors, prognoses, and treatment approaches. This review explores genetic and environmental biomarkers that influence the risk, prognosis, and therapeutic responses in pNENs. The epidemiology of pNENs reveals an increasing incidence, primarily due to advancements in imaging techniques. Genetic factors play a pivotal role, with germline mutations in MEN1, VHL, and other genes contributing to familial pNENs. Somatic mutations, including alterations in the mTOR pathway and DNA maintenance genes such as DAXX and ATRX, are critical in sporadic pNENs. These mutations, along with epigenetic dysregulation and transcriptomic alterations, underpin the diverse clinical and molecular phenotypes of pNENs. Emerging evidence suggests that epigenetic changes, including DNA methylation profiles, can stratify pNEN subtypes and predict disease progression. Environmental and lifestyle factors, such as diabetes, smoking, and chronic pancreatitis, have been linked to an increased risk of sporadic pNENs. While the association between these factors and tumor progression is still under investigation, their potential role in influencing therapeutic outcomes warrants further study. Advances in systemic therapies, including somatostatin analogs, mTOR inhibitors, and tyrosine kinase inhibitors, have improved disease management. Biomarkers such as Ki-67, somatostatin receptor expression, and O6-methylguanine-DNA methyltransferase (MGMT) status are being evaluated for their predictive value. Novel approaches, including the use of circulating biomarkers (NETest, circulating tumor cells, and ctDNA) and polygenic risk scores, offer promising avenues for non-invasive diagnosis and monitoring. Despite these advancements, challenges remain, including the need for large, well-annotated datasets and validated biomarkers. Future research should integrate multi-omics approaches and leverage liquid biopsy technologies to refine diagnostic, prognostic, and therapeutic strategies. Interdisciplinary collaborations and global consortia are crucial for overcoming current limitations and translating research findings into clinical practice. These insights hold promise for improving prevention, early detection, and tailored treatments, ultimately enhancing patient outcomes.
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Affiliation(s)
- Matteo Tacelli
- Pancreato-Biliary Endoscopy and Endosonography Division, Pancreas Translational and Clinical Research Center, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | | | - Paolo Biamonte
- Pancreato-Biliary Endoscopy and Endosonography Division, Pancreas Translational and Clinical Research Center, IRCCS San Raffaele Scientific Institute, Milan, Italy; Vita-Salute San Raffaele University, IRCCS Ospedale San Raffaele, Milan, Italy
| | - Justo P Castano
- Maimonides Biomedical Research Institute of Cordoba (IMIBIC), Córdoba, Spain; Department of Cell Biology, Physiology, and Immunology, University of Córdoba, Córdoba, Spain; Reina Sofia University Hospital, Córdoba, Spain; CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Córdoba, Spain
| | - Maja Cigrovski Berković
- Department for Sport and Exercise Medicine, Faculty of Kinesiology University of Zagreb, Zagreb 10000, Croatia
| | - Mauro Cives
- Interdisciplinary Department of Medicine, University of Bari "Aldo Moro", Bari, Italy; Division of Medical Oncology, A.O.U. Consorziale Policlinico di Bari, Bari, Italy
| | - Sanja Kapitanović
- Laboratory for Personalized Medicine, Division of Molecular Medicine, Ruđer Bošković Institute, Zagreb 10000, Croatia
| | - Ilaria Marinoni
- Institute of Tissue Medicine and Pathology, University of Bern, Bern, Switzerland
| | - Sonja Marinovic
- Laboratory for Personalized Medicine, Division of Molecular Medicine, Ruđer Bošković Institute, Zagreb 10000, Croatia
| | - Ilias Nikas
- Medical School, University of Cyprus, Nicosia, Cyprus
| | - Lenka Nosáková
- Clinic of Internal Medicine - Gastroenterology, JFM CU, Jessenius Faculty of Medicine in Martin (JFM CU), Comenius University in Bratislava, Bratislava, Slovakia
| | - Sergio Pedraza-Arevalo
- Maimonides Biomedical Research Institute of Cordoba (IMIBIC), Córdoba, Spain; Department of Cell Biology, Physiology, and Immunology, University of Córdoba, Córdoba, Spain; Reina Sofia University Hospital, Córdoba, Spain; CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Córdoba, Spain
| | - Eleonora Pellè
- Department of GI Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA
| | - Aurel Perren
- Institute of Tissue Medicine and Pathology, University of Bern, Bern, Switzerland
| | - Jonathan Strosberg
- Department of GI Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA
| | - Daniele Campa
- Department of Biology, University of Pisa, Pisa, Italy
| | - Gabriele Capurso
- Pancreato-Biliary Endoscopy and Endosonography Division, Pancreas Translational and Clinical Research Center, IRCCS San Raffaele Scientific Institute, Milan, Italy; Vita-Salute San Raffaele University, IRCCS Ospedale San Raffaele, Milan, Italy.
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Zhang W, Li N, Li J, Zhao Y, Long Y, He C, Zhang C, Li B, Zhao Y, Lai S, Ding W, Gao M, Tan L, Wei X, Yang R, Jiang X. Noninvasive identification of proliferative hepatocellular carcinoma on multiphase dynamic CT: quantitative and LI-RADS lexicon-based evaluation. Eur Radiol 2025; 35:3460-3475. [PMID: 39665988 DOI: 10.1007/s00330-024-11247-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2024] [Revised: 10/20/2024] [Accepted: 11/24/2024] [Indexed: 12/13/2024]
Abstract
OBJECTIVE To identify proliferative hepatocellular carcinoma (HCC) preoperatively using quantitative measurements combined with the updated standard 2021 LI-RADS universal lexicon-based qualitative features on multiphase dynamic CT (MDCT). METHODS We retrospectively analyzed 273 patients (102 proliferative HCCs) who underwent preoperative MDCT with surgically confirmed HCC in two medical centers. Imaging features were evaluated according to the updated 2021 LI-RADS universal lexicon, and quantitative measurements were analyzed. All MDCT findings and clinical factors were compared. Four predictive models (clinical, CT quantitative-clinical, CT qualitative-clinical, and combinational models) were developed and validated in an external cohort for identifying proliferative HCC. ROC analysis was used to assess model performances. All models were tested in a subgroup of patients with a single lesion ≤ 5 cm (n = 124). RESULTS Both the CT quantitative-clinical and CT qualitative-clinical models effectively identified proliferative HCC in the training and external validation cohorts (all AUCs > 0.79). The combinational model, integrating one clinical (AFP ≥ 200 ng/mL), three qualitative (rim arterial phase hyperenhancement (APHE), non-smooth tumor margin, and incomplete or absent capsule), and one quantitative feature (standardized tumor-to-aorta density ratio in portal venous phase ≤ (- 0.13), showed significant improvement in the training cohort (AUC 0.871) and comparable performance in the validation cohort (AUC 0.870). Additionally, AFP ≥ 200 ng/mL and Rim APHE were significantly associated with HCC recurrence (p < 0.05). CONCLUSIONS The combinational model, integrating clinical, CT quantitative, and qualitative features, shows potential for the noninvasively preoperative prediction of proliferative HCC. Further validation is needed to establish its broader clinical utility. KEY POINTS Question Preoperative identification of proliferative HCC could influence patient treatment and prognosis, yet there is no CT-based universally applicable model to identify this subtype. Findings The updated standard 2021 LI-RADS universal lexicon-based features, in combination with quantitative MDCT measurements, could aid in the noninvasive detection of proliferative HCC. Clinical relevance The updated standard 2021 LI-RADS universal lexicon-based CT qualitative features and quantitative measurements may aid in identifying proliferative HCC and tumor recurrence, offering potential guidance for personalized treatment. Further studies are required to assess their generalizability to different clinical scenarios.
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Affiliation(s)
- Wanli Zhang
- Department of Radiology, The Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, China
- School of Medicine, South China University of Technology, Guangzhou, China
| | - Nan Li
- Department of Radiology, The Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, China
| | - Jiamin Li
- Department of Radiology, The Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, China
- School of Medicine, South China University of Technology, Guangzhou, China
| | - Yue Zhao
- Department of Radiology, Central People's Hospital of Zhanjiang, Zhanjiang, China
| | - Yi Long
- Department of Radiology, The Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, China
- School of Medicine, South China University of Technology, Guangzhou, China
| | - Chutong He
- Medical Imaging Center, Jinan University First Affiliated Hospital, Guangzhou, China
| | - Chuanxian Zhang
- Department of Radiology, The Zhaoqing Hospital of the Third Affiliated Hospital, Sun Yat-sen University, Zhaoqing, China
| | - Bo Li
- Department of Radiology, The First People's Hospital of Foshan, Foshan, China
| | - Yandong Zhao
- Department of Radiology, The Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, China
- School of Medicine, South China University of Technology, Guangzhou, China
| | - Shengsheng Lai
- School of Medical Equipment, Guangdong Food and Drug Vocational College, Guangzhou, China
| | - Wenshuang Ding
- Department of Pathology, Guangzhou First People's Hospital, Guangzhou, China
| | - Mingyong Gao
- Department of Radiology, The First People's Hospital of Foshan, Foshan, China
| | - Lilian Tan
- Department of Radiology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
| | - Xinhua Wei
- Department of Radiology, The Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, China
- School of Medicine, South China University of Technology, Guangzhou, China
| | - Ruimeng Yang
- Department of Radiology, The Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, China.
- School of Medicine, South China University of Technology, Guangzhou, China.
| | - Xinqing Jiang
- Department of Radiology, The Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, China.
- School of Medicine, South China University of Technology, Guangzhou, China.
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Zhang L, Mai X, Li B, Li H, Liu Q, Li Y, Zhu Y, Jiang X, Wang W, Qiao C, Chen J, Xu C, Chen J, Yu D. Fat fraction quantification by MRI predicts diagnosis and prognosis of HBV-related steatohepatitic hepatocellular carcinoma. Eur Radiol 2025; 35:3144-3157. [PMID: 39576331 DOI: 10.1007/s00330-024-11151-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2024] [Revised: 08/30/2024] [Accepted: 10/07/2024] [Indexed: 05/16/2025]
Abstract
OBJECTIVES This study explored the clinical prognosis and lipidomics of hepatitis B virus steatohepatitic hepatocellular carcinoma (HBV-SHHCC) and aimed to identify a noninvasive and convenient method to diagnose this phenotype and guide treatment using MRI. METHODS A total of 433 HBV-infected HCC patients were enrolled in this retrospective study. Survival data were analyzed using Cox regression analyses, and lipidomics was used to study HCC tissue composition. Logistic regression identified an independent predictor for HBV-SHHCC, and receiver-operating characteristic (ROC) analysis verified its discrimination. RESULTS HBV-SHHCC patients had longer disease-free survival (DFS, p < 0.0001) and overall survival (OS) time (p = 0.00097). Compared with common HCC (cHCC), SHHCC was associated with significantly higher mean triacylglyceride (p = 0.010) and diacylglyceride contents (p = 0.002) in tumor tissues. Fat fraction (FF) was linearly correlated with lipid composition and fatty acid degradation (FAD) subtype, which could help in treatment options for HCC. The univariate and multivariate logistic regression indicated FF (p < 0.001) as an independent predictor for diagnosing this phenotype. ROC analysis confirmed excellent discrimination (area under the curve (AUC), 0.914; sensitivity, 92.3%; specificity, 78.7.0%). After using the optimal cutoff point, the DFS time of patients with SHHCC stratified by FF was significantly higher than that of patients with cHCC. CONCLUSION The biological behavior and prognosis of HBV-SHHCC were better than those of other types. FF is a valuable tool for the clinical diagnosis of SHHCC, prognosis prediction, and treatment guidance in patients with HCC. KEY POINTS Question Can the diagnosis of steatohepatitic hepatocellular carcinoma (SHHCC) be made noninvasively? Findings Fat fraction (FF) correlated with lipid composition and could be used to diagnose SHHCC with an AUC of 0.914, sensitivity of 92.3%, and specificity of 78.7%. Clinical relevance MRI-based FF could be used to diagnose HBV-related SHHCC, indicate prognosis, and guide the clinical treatment of patients with HCC.
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Affiliation(s)
- Laizhu Zhang
- Division of Hepatobiliary and Transplantation Surgery, Department of General Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China
| | - Xiaoli Mai
- Department of Radiology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China
| | - Binghua Li
- Division of Hepatobiliary and Transplantation Surgery, Department of General Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China
| | - Huan Li
- Division of Hepatobiliary and Transplantation Surgery, Department of General Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China
| | - Qi Liu
- Division of Hepatobiliary and Transplantation Surgery, Department of General Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China
| | - Yunzheng Li
- Division of Hepatobiliary and Transplantation Surgery, Department of General Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China
| | - Yican Zhu
- Division of Hepatobiliary and Transplantation Surgery, Department of General Surgery, Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, China
| | - Xiang Jiang
- Division of Hepatobiliary and Transplantation Surgery, Department of General Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China
| | - Weihong Wang
- Division of Hepatobiliary and Transplantation Surgery, Department of General Surgery, Nanjing Drum Tower Hospital Clinical College of Jiangsu University, Nanjing, China
| | - Chu Qiao
- Division of Hepatobiliary and Transplantation Surgery, Department of General Surgery, Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, China
| | - Jun Chen
- Department of Pathology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China
| | - Chun Xu
- Department of Pathology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China
| | - Jun Chen
- Department of Radiology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China.
| | - Decai Yu
- Division of Hepatobiliary and Transplantation Surgery, Department of General Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China.
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Bokhary RY. Prevalence of HER2 expression and its association with clinicopathological parameters in gastric and gastroesophageal junction adenocarcinoma: A 10?year experience of an academic center. Mol Clin Oncol 2025; 22:49. [PMID: 40242368 PMCID: PMC12001012 DOI: 10.3892/mco.2025.2844] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2024] [Accepted: 03/20/2025] [Indexed: 04/18/2025] Open
Abstract
HER2 overexpression is a marker for targeted therapy in adenocarcinoma of the gastroesophageal junction (GEJ) and stomach. The present study aimed to evaluate the frequency of HER2 overexpression with reference to clinicopathological characteristics in subjects from King Abdulaziz University Hospital, Jeddah, Saudi Arabia over a 10-year period. A retrospective cross-sectional study was conducted on all biopsy and resection specimens diagnosed with either gastric cancer (GC) or GEJ adenocarcinomas from patients between January 2014 and December 2023 that had a final pathology report. Demographic characteristics of 122 patients, including age and sex, were collected, along with pathological details such as tumor grade, histological subtype and HER2 status. χ2 test was used to analyze the association between collected clinicopathological characteristics and HER2 status of the tumor. Most patients were aged 40-60 years. Males constituted 66% of the patients, and the ethnic distribution between Saudi and non-Saudi was almost equal. The most common subtype of cancer was the intestinal type (49%), and the majority of cases were poorly differentiated (64%). HER2 status was assessed in only 61% of cases, with 13.5% showing gene amplification. There was no significant association found between HER2 status and clinicopathological features.
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Affiliation(s)
- Rana Y. Bokhary
- Department of Pathology, Faculty of Medicine, King Abdulaziz University & King Abdulaziz University Hospital, Jeddah 21589, Saudi Arabia
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Tang M, Chen X, Liu L, Chen B, Han W, Zhao X, Chen Y. Synchronous triple squamous cell carcinomas of the stomach, skin and gingiva with liver, lung, spleen, kidney, bone and brain metastases: A case report. Oncol Lett 2025; 29:278. [PMID: 40242269 PMCID: PMC12000799 DOI: 10.3892/ol.2025.15024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2024] [Accepted: 03/17/2025] [Indexed: 04/18/2025] Open
Abstract
Synchronous multiple squamous cell carcinomas (SCCs) of the stomach, skin and gingiva are very rare. A 67-year-old male patient was admitted to hospital with progressive chest tightness and fatigue, accompanied by melena. Gastric and dermal biopsies revealed SCCs, and it was considered that triple primary SCCs of the skin, stomach and gingiva had metastasized to the cerebrum, liver, lung, spleen, kidney, bone and subcutaneous tissue. The patient received one cycle of camrelizumab, carboplatin and nab-paclitaxel, followed by two cycles of camrelizumab monotherapy and best supporting care. However, his performance status deteriorated, and he had a very poor survival outcome, succumbing 3 months after diagnosis. Discriminating pathologically between synchronous SCCs in individual organs as metastases or primaries is challenging. In the present case, a diagnosis of triple primary SCCs of the skin, stomach and gingiva with multiple organ metastases was made based on epidemiologic features and clinical presentation. The results of the present case report suggested that anti-programmed death 1 antibodies combined with platinum-based chemotherapy may be a treatment option for metastatic SCC.
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Affiliation(s)
- Mengyao Tang
- Department of Internal Medicine, School of Medicine, Shaoxing University, Shaoxing, Zhejiang 312000, P.R. China
| | - Xiuxia Chen
- Department of Pathology, Zhuji People's Hospital of Zhejiang Province, Zhuji, Zhejiang 311800, P.R. China
| | - Linger Liu
- Department of Oncology, Zhuji People's Hospital of Zhejiang Province, Shaoxing University, Zhuji, Zhejiang 311800, P.R. China
| | - Baisong Chen
- Department of Oncology, Zhuji People's Hospital of Zhejiang Province, Shaoxing University, Zhuji, Zhejiang 311800, P.R. China
| | - Wenwen Han
- Department of Internal Medicine, School of Medicine, Shaoxing University, Shaoxing, Zhejiang 312000, P.R. China
| | - Xiaofeng Zhao
- Department of Internal Medicine, School of Medicine, Shaoxing University, Shaoxing, Zhejiang 312000, P.R. China
| | - Yao Chen
- Department of Oncology, Zhuji People's Hospital of Zhejiang Province, Shaoxing University, Zhuji, Zhejiang 311800, P.R. China
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Medawar E, Djinbachian R, Rex DK, Vieth M, Pohl H, Popescu Crainic I, Taghiakbari M, Marques P, Kaufman D, Huang F, von Renteln D. Clinical management of patients with colorectal intramucosal carcinoma compared to high-grade dysplasia and T1 colorectal cancer. Gastrointest Endosc 2025; 101:1211-1221.e5. [PMID: 39557202 DOI: 10.1016/j.gie.2024.11.021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/30/2024] [Revised: 11/07/2024] [Accepted: 11/10/2024] [Indexed: 11/20/2024]
Abstract
BACKGROUND AND AIMS In the colorectum, intramucosal carcinoma (IMC), like high-grade dysplasia (HGD), should be resected endoscopically. We were interested to understand how real-world treatment of IMC cases compares to management of HGD and T1 colorectal cancer (CRC). METHODS A multicenter cohort study was conducted. Through pathology databases, all patients diagnosed between 2010 and 2019 with HGD, IMC, or T1 CRC polyps at 3 hospitals in a regional Canadian center were identified. The primary outcome was the proportion of surgical management of IMC compared to HGD after complete endoscopic resection. Secondary outcomes were the proportion of synchronous advanced neoplasia (SAN) and the adjusted hazard ratios (aHRs) for metachronous advanced neoplasia (MAN) in the 3 groups among patients eligible for follow-up. RESULTS We identified 753 patients with IMC or HGD on a first pathology diagnosis, including 601 after complete endoscopic resection. Patients with IMC were more likely to undergo surgery after complete endoscopic resection compared to patients with HGD (10.5% [6 of 57] vs 0% [0 of 544], P < .001). A total of 455 patients had follow-up endoscopy and pathology (mean age, 67.1 years; 42.2% female; median follow-up, 3.4 years): 269 with HGD, 60 with IMC, and 126 with T1 CRC. Proportions of SAN were 24.2%, 26.7%, and 25.4% (P = .908). Compared to HGD, patients with IMC and T1 CRC had similar MAN risks (aHR, 0.82 [95% CI, 0.43-1.59] and aHR, 1.16 [95% CI, 0.66-2.05], respectively). No lymph node findings were positive (0 of 363), and no metastasis occurred among patients with IMC. CONCLUSIONS Patients diagnosed with colorectal IMC were more likely to undergo surgery after complete endoscopic resection than when HGD was diagnosed, although they were not at increased risk of SAN or MAN in this study, and the known risk of nodal metastasis with colorectal IMC is small (0%-2%). Unless a patient diagnosed with IMC is particularly concerned with this small risk, complete endoscopic resection should be considered the definitive treatment for IMC and should not be followed by surgery.
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Affiliation(s)
- Edgard Medawar
- Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada; University of Montreal Hospital Research Center, Montreal, Quebec, Canada
| | - Roupen Djinbachian
- University of Montreal Hospital Research Center, Montreal, Quebec, Canada; Division of Gastroenterology, University of Montreal Hospital Center, Montreal, Quebec, Canada
| | - Douglas K Rex
- Division of Gastroenterology/Hepatology, Indiana University School of Medicine, Indianapolis, Indiana, USA
| | - Michael Vieth
- Institute of Pathology, Friedrich-Alexander-Universitӓt Erlangen-Nürnberg, Klinikum Bayreuth, Bayreuth, Germany
| | - Heiko Pohl
- Gastroenterology and Hepatology, White River Junction Veterans Affairs Medical Center, White River Junction, Vermont, USA
| | | | - Mahsa Taghiakbari
- University of Montreal Hospital Research Center, Montreal, Quebec, Canada
| | - Paola Marques
- Department of Medicine, McMaster University, Hamilton, Ontario, Canada
| | - Daniel Kaufman
- University of Montreal Hospital Research Center, Montreal, Quebec, Canada
| | - Felix Huang
- University of Montreal Hospital Research Center, Montreal, Quebec, Canada
| | - Daniel von Renteln
- University of Montreal Hospital Research Center, Montreal, Quebec, Canada; Division of Gastroenterology, University of Montreal Hospital Center, Montreal, Quebec, Canada.
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9
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Abudalo R, Alqudah A, Alnajjar R, Abudalo R, Abuqamar A, Oqal M, Qnais E. KRAS/NRAS/BRAF mutational profile and association with clinicopathological characteristics in patients with metastatic colorectal cancer. Oncol Lett 2025; 29:312. [PMID: 40342724 PMCID: PMC12059616 DOI: 10.3892/ol.2025.15058] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2024] [Accepted: 03/26/2025] [Indexed: 05/11/2025] Open
Abstract
Colorectal cancer (CRC) is increasingly prevalent in Jordan and poses a significant public health challenge. The presence of Kirsten rat sarcoma viral oncogene homolog (KRAS), neuroblastoma RAS viral oncogene homolog (NRAS) and v-Raf Murine Sarcoma Viral Oncogene Homolog B (BRAF) mutations is key in CRC diagnostics, as these mutations are associated with resistance to monoclonal antibodies targeting the epidermal growth factor receptor. The present study aimed to identify these mutations in patients with CRC and assess their associations with clinicopathological characteristics. A retrospective analysis was conducted using data from 262 patients with metastatic CRC (mCRC) at the Jordanian Military Cancer Center-Royal Medical Services (Amman, Jordan). Variables such as age, sex, tumor differentiation and the mutational status of KRAS, NRAS and BRAF, along with tumor location, were analyzed statistically to explore associations between mutations and tumor characteristics. Among the included patients, 48.5% had KRAS mutations, 3.8% had NRAS mutations and 0.8% had BRAF mutations. The majority of KRAS mutations were in exon 2 at codons 12 and 13, with the highest mutational rate at 45.8%. In the univariate model, NRAS mutations were significantly associated with moderately differentiated tumors and the multivariate hierarchical regression analysis established that KRAS mutations were significantly associated with histological subtypes [mucinous adenocarcinoma, tubular adenocarcinoma, signet adenocarcinoma and adenocarcinoma (not specified)]. These results highlighted the molecular profiles and clinicopathological characteristics of patients with mCRC, which demonstrated the associations between mutational status and the varying clinicopathological aspects based on the type of RAS mutation. Thus, these specific traits (patient's age, sex, CRC site, histological subtypes and tumor grade) may be taken into account when evaluating the predictive significance of RAS and BRAF status in CRC and tailored treatment strategies.
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Affiliation(s)
- Rawan Abudalo
- Department of Clinical Pharmacy and Pharmacy Practice, Faculty of Pharmaceutical Sciences, The Hashemite University, Zarqa 13133, Jordan
| | - Abdelrahim Alqudah
- Department of Clinical Pharmacy and Pharmacy Practice, Faculty of Pharmaceutical Sciences, The Hashemite University, Zarqa 13133, Jordan
| | - Roaa Alnajjar
- Department of Biopharmaceutics and Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Jordan University, Amman 11942, Jordan
| | - Razan Abudalo
- Department of Radiology, Jordanian Royal Medical Services, Amman 855122, Jordan
| | - Ayman Abuqamar
- Department of Oncology and Hematology, Jordanian Royal Medical Services, Amman 855122, Jordan
| | - Muna Oqal
- Department of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, The Hashemite University, Zarqa 13133, Jordan
| | - Esam Qnais
- Department of Biology and Biotechnology, Faculty of Science, The Hashemite University, Zarqa 13133, Jordan
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10
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Lie JJ, Nabata K, Zhang JW, Rai S, Zhao D, Morad Hameed S, Dawe P, Hamilton TD. Rate of Neoplasia in Patients with Complicated Acute Appendicitis Managed Nonoperatively: A Prospective Study. Ann Surg Oncol 2025; 32:4272-4279. [PMID: 39971859 DOI: 10.1245/s10434-025-17031-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2024] [Accepted: 02/03/2025] [Indexed: 02/21/2025]
Abstract
BACKGROUND Recent studies suggest the rate of neoplasia in patients with complicated acute appendicitis initially managed nonoperatively is higher than previously reported. OBJECTIVE This study aimed to determine the incidence and predictors of neoplasia in patients with complicated appendicitis treated nonoperatively. METHODS We conducted a prospective cohort study of all patients who presented to a tertiary care center with acute appendicitis between 2019 and 2023. Patients with complicated appendicitis treated nonoperatively were included in the study cohort. Patient demographics, clinical course, radiological findings, and pathologic information were collected. The primary outcome was rate of neoplasia. Multivariable logistic regression analysis was performed to identify predictors of appendiceal neoplasia. RESULTS In total, we identified 1166 patients with acute appendicitis, of whom 75 patients had complicated appendicitis treated nonoperatively (median age 51 years [interquartile range 38-68]; 36 [48%] were female). Fifty-four (72%) patients had their appendix removed due to failure of nonoperative management, recurrent symptoms, suspicion of neoplasia, or elective surgery. The neoplasia rate among patients with complicated appendicitis initially treated nonoperatively was 16.0% (12/75). Two patients with neoplasia were younger than 40 years of age. Suspicion of malignancy on initial imaging was associated with an increased risk of appendiceal neoplasia (odds ratio 8.13, 95% confidence interval 1.20-55.15; p = 0.03). Age, sex, and appendiceal diameter were not significantly associated with appendiceal neoplasia. CONCLUSIONS The high rate of appendiceal neoplasia in patients with complicated appendicitis treated nonoperatively should be a factor in decision making for interval appendectomy for patients of all ages.
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Affiliation(s)
- Jessica J Lie
- Department of Surgery, University of British Columbia, Vancouver, BC, Canada
| | - Kylie Nabata
- Department of Surgery, University of British Columbia, Vancouver, BC, Canada
| | - Jenny W Zhang
- Faculty of Science, University of British Columbia, Vancouver, BC, Canada
| | - Sabrina Rai
- Faculty of Science, University of British Columbia, Vancouver, BC, Canada
| | - Darren Zhao
- Faculty of Science, University of British Columbia, Vancouver, BC, Canada
| | - S Morad Hameed
- Department of Surgery, University of British Columbia, Vancouver, BC, Canada
| | - Philip Dawe
- Department of Surgery, University of British Columbia, Vancouver, BC, Canada
| | - Trevor D Hamilton
- Department of Surgery, University of British Columbia, Vancouver, BC, Canada.
- Gordon and Leslie Diamond Health Care Centre, Vancouver, Canada.
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11
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Park E, Subasi NB, Wang X, Kmeid M, Chen A, Tooke-Barry C, Lee H. CXCR2 expression is associated with prostate-specific membrane antigen expression in hepatocellular carcinoma: reappraisal of tumor microenvironment and angiogenesis. Clin Transl Oncol 2025; 27:2544-2556. [PMID: 39636498 DOI: 10.1007/s12094-024-03789-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2024] [Accepted: 11/07/2024] [Indexed: 12/07/2024]
Abstract
PURPOSE Angiogenesis is a critical component of neoplastic progression, and inflammatory cells within the tumor microenvironment contribute to neoangiogenesis. Prostate-specific membrane antigen (PSMA) is expressed in the neovasculature of various solid tumors, including hepatocellular carcinoma (HCC). Also, CXCR2 + inflammatory cells, including CD15 + neutrophils, play crucial roles in HCC progression. We evaluated the associations between PSMA expression and CXCR2 + inflammatory cells in HCC by immunohistochemistry (IHC). METHODS CXCR2 expression and its correlation with PSMA, the PSMA/CD34 ratio, immune markers (CD3, CD15, CD68, and CD163), clinical parameters, and oncologic outcomes were evaluated in 76 HCC and background benign liver tissue. RESULTS PSMA and the PSMA/CD34 ratio showed a positive correlation with intratumoral CXCR2, but not with intratumoral CD15. Intratumoral CXCR2 + cell count was positively associated with intratumoral CD3, CD15, CD68, and CD163 expression levels. In the benign compartment, CXCR2 was significantly associated with CD15. Metabolic dysfunction-associated steatotic liver disease (MASLD) risk factors and cirrhosis had an opposite effect on CXCR2 + cell count in benign liver tissue. Higher CD15 + cell count in the benign liver was associated with decreased overall survival (OS) and recurrence-free survival (RFS). CONCLUSIONS In HCC, intratumoral CXCR2 + cell count is associated with PSMA expression. Intratumoral and benign compartments had different CXCR2 + inflammatory cell makeup. The immune microenvironment of HCC appears to differ depending on underlying risk factors. Further investigations are warranted to elucidate PSMA biology and assess the potential utility of CXCR2 IHC in PSMA-targeted theranostics.
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Affiliation(s)
- Eundong Park
- Pathology and Laboratory Medicine, Albany Medical Center, Mail Code 81, 47 New Scotland Avenue, Albany, NY, 12208, USA
| | - Nusret Bekir Subasi
- Pathology and Laboratory Medicine, Albany Medical Center, Mail Code 81, 47 New Scotland Avenue, Albany, NY, 12208, USA
| | - Xin Wang
- Pathology and Laboratory Medicine, Albany Medical Center, Mail Code 81, 47 New Scotland Avenue, Albany, NY, 12208, USA
| | - Michel Kmeid
- Pathology and Laboratory Medicine, Albany Medical Center, Mail Code 81, 47 New Scotland Avenue, Albany, NY, 12208, USA
- Pathology and Laboratory Medicine, Cleveland Clinic, Cleveland, OH, USA
| | - Anne Chen
- Pathology and Laboratory Medicine, Albany Medical Center, Mail Code 81, 47 New Scotland Avenue, Albany, NY, 12208, USA
- Pathology and Immunology, Washington University, St. Louis, MO, USA
| | - Chelsea Tooke-Barry
- Pathology and Laboratory Medicine, Albany Medical Center, Mail Code 81, 47 New Scotland Avenue, Albany, NY, 12208, USA
| | - Hwajeong Lee
- Pathology and Laboratory Medicine, Albany Medical Center, Mail Code 81, 47 New Scotland Avenue, Albany, NY, 12208, USA.
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12
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Ren H, Niu P, Li Z, Zhang X, Sun C, Wen Z, Fei H, Li Z, Shi S, Chen Y, Zhao D. Survival and Metastatic Lymph Node Patterns in Gastric Carcinoma with Exocrine and Neuroendocrine Components. Ann Surg Oncol 2025; 32:4292-4303. [PMID: 40131626 DOI: 10.1245/s10434-024-16848-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2024] [Accepted: 12/25/2024] [Indexed: 03/27/2025]
Abstract
BACKGROUND Gastric carcinoma with coexisting exocrine and neuroendocrine components (GC-EN) is a rare and aggressive subtype of gastric cancer that presents unique challenges in diagnosis, treatment, and prognosis. The effect of lymph node metastasis with different components on survival in patients with GC-EN is unknown. PATIENTS AND METHODS This retrospective study included 98 patients diagnosed with GC-EN at the China National Cancer Center between January 2004 and December 2020. GC-EN was classified into NEC-dominant, mixed adenoneuroendocrine carcinoma (MANEC), and AC-dominant based on the proportion of adenocarcinoma (AC) and neuroendocrine (NEC) components. Additionally, lymph nodes were categorized into NEC, AC, and MANEC types based on cellular composition. RESULTS Of the 98 patients, 30 developed NEC-dominant type, 39 (39.8%) developed MANEC type, and 29 (29.6%) developed AC-dominant type. Additionally, 72.48% of the patients developed lymph node metastasis. The incidence rates of lymph node metastasis were significantly higher among patients with the NEC-dominant (76.6%, 23/30) and MANEC types (74.3%, 29/39) than among those with the ACC-dominant type (65.5%, 19/29; P < 0.05). Pathological T stage was a key factor influencing lymph node metastasis of NEC components in patients with GC-EN. Survival analysis revealed that lymph node metastasis significantly worsened the prognosis of patients with GC-EN (P < 0.05). Analysis of lymph node metastasis with different components on prognosis revealed that patients with GC-EN with lymph node metastasis of NEC components were associated with a significantly poorer prognosis than those without lymph node metastasis (hazard ratio 2.341, 95% confidence interval 1.125-4.871, P = 0.023), while patients with GC-EN with lymph node metastasis of MANEC and AC components exhibited no significant statistical differences. A new N staging system was developed on the basis of the number and different compositions of lymph node metastasis. The new N staging system demonstrated a higher C-index than the AJCC N staging system (0.739 vs. 0.719). CONCLUSIONS Lymph node metastasis of NEC components is significantly associated with a poorer prognosis in patients with GC-EN. This study proposes a new N staging system that integrates lymph node count and components, potentially facilitating prognostic stratification and personalized treatment for patients with GC-EN.
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Affiliation(s)
- Hu Ren
- Department of Pancreatic and Gastric Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Penghui Niu
- Department of Pancreatic and Gastric Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Zefeng Li
- Department of Pancreatic and Gastric Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Xiaojie Zhang
- Gastrointestinal Surgery Department, China-Japan Friendship Hospital, Beijing, China
| | - Chongyuan Sun
- Department of Pancreatic and Gastric Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Zelin Wen
- Department of Pancreatic and Gastric Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - He Fei
- Department of Pancreatic and Gastric Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Zheng Li
- Department of Pancreatic and Gastric Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Susheng Shi
- Department of Pathology, Department of Pancreatic and Gastric Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
| | - Yingtai Chen
- Department of Pancreatic and Gastric Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
| | - Dongbing Zhao
- Department of Pancreatic and Gastric Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
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13
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Zhang J, Tan Q, Fan Y, Xiao L, Zheng Z, Li K, Jing W, Song H, Liu X, Tan C, Wang X. Non-hypervascular pancreatic neuroendocrine neoplasms differentiation from CA19-9 negative pancreatic ductal adenocarcinomas based on contrast CT: A large sample series. Eur J Radiol 2025; 187:112095. [PMID: 40209484 DOI: 10.1016/j.ejrad.2025.112095] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2024] [Revised: 03/19/2025] [Accepted: 04/03/2025] [Indexed: 04/12/2025]
Abstract
PROPOSE This study aims to evaluate the effectiveness of contrast-enhanced computed tomography (CT) in distinguishing non-hypervascular pancreatic neuroendocrine neoplasms (PNENs) from pancreatic ductal adenocarcinomas (PDACs) with a normal serum level of carbohydrate antigen 19-9 (CA19-9) levels. METHODS This retrospective study included 134 patients with pathologically confirmed non-hypervascular PNENs and 128 patients with CA19-9-negative PDACs, all of whom underwent contrast-enhanced CT prior to surgery between January 2015 and March 2024. Following independent evaluation by two radiologists, qualitative features from both groups were extracted in the arterial and portal venous phase and subsequently compared using univariate and multivariate analysis. RESULTS Patients with CA19-9 negative PDACs were significantly older than those with non-hypervascular PNENs (p < 0.001), and the majority of PDACs were located in the head of the pancreas (p < 0.01).Univariate analysis showed that non-hypervascular PNENs exhibited a higher frequency of well-defined tumor margins (p < 0.001) and calcification (p = 0.032) and a lower frequency of local invasion (p < 0.001), peripancreatic vascular invasion (p = 0.001), intra- or extrahepatic bile duct dilatation (p < 0.001), distal main pancreatic duct dilatation (p < 0.001), regional lymphadenopathy (p < 0.001) and tumor homogeneity (p < 0.001) when compared to CA19-9 negative PDACs. Multivariate analysis identified the absence of local invasion (Odds Ratio (OR) = 0.233; 95 % Confidence Internals (95 % CI):0.114-0.476; p < 0.001), absence of peripancreatic vascular invasion (OR = 0.434; 95 % CI:0.217-0.870; p = 0.019), a normal distal main pancreatic duct diameter (OR = 0.398; 95 % CI:0.202-0.785; p = 0.008), absence of regional lymphadenopathy (OR = 0.455; 95 % CI:0.238-0.870; p = 0.017) and tumor heterogeneity (OR = 0.240; 95 % CI:0.126-0.456; p < 0.001) as significant predictors of non-hypervascular PNENs. The area under the receiver operating characteristic curve for the radiological feature model was 0.829 based on logistic regression. CONCLUSIONS Qualitative features in contrast-enhanced CT images could be beneficial in differentially diagnosing non-hypervascular PNENs and CA19-9 negative PDACs.
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Affiliation(s)
- Jinyin Zhang
- Division of Pancreatic Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
| | - Qingquan Tan
- Division of Pancreatic Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
| | - Yang Fan
- Department of Radiology, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
| | - Liu Xiao
- Department of Nuclear Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
| | - Zhenjiang Zheng
- Division of Pancreatic Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
| | - Keyu Li
- Division of Pancreatic Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
| | - Wenyi Jing
- Department of Pathology, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Haiyu Song
- Department of Hepatobiliary and Pancreatic Surgery, Chengdu Second People's Hospital, Chengdu, Sichuan Province, China
| | - Xubao Liu
- Division of Pancreatic Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China
| | - Chunlu Tan
- Division of Pancreatic Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China.
| | - Xing Wang
- Division of Pancreatic Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China.
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14
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Hu C, Chen L, Ding Y, Ye M, Tang Q. Metabolic changes in neuroendocrine neoplasms. Cell Mol Life Sci 2025; 82:205. [PMID: 40377669 DOI: 10.1007/s00018-025-05656-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2024] [Revised: 02/05/2025] [Accepted: 03/11/2025] [Indexed: 05/18/2025]
Abstract
Neuroendocrine neoplasms (NENs) are a group of highly heterogeneous neoplasms originating from neuroendocrine cells with a gradually increased incidence. Metabolic change is one of the recognized markers of tumor progression, which has been extensively and systematically studied in other malignant tumors. However, metabolic change in NENs has been relatively poorly studied, and systematic reviews are lacking. We reviewed the relationship between metabolic changes and NENs from the aspects of glucose metabolism, lipid metabolism, metabolic syndrome, amino acid metabolism and metabolomics, and discussed the potential therapeutic strategies of metabolic changes for NENs.
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Affiliation(s)
- Chunhua Hu
- Shanghai Key Laboratory of Gut Microecology and Associated Major Diseases Research, Digestive Disease Research and Clinical Translation Center, Department of Gastroenterology, Shanghai Ninth People's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
- Neuroendocrine Tumor Diagnosis and Treatment Center, Jiangsu Province Hospital, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China
| | - Lingyi Chen
- Neuroendocrine Tumor Diagnosis and Treatment Center, Jiangsu Province Hospital, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China
| | - Yi Ding
- Neuroendocrine Tumor Diagnosis and Treatment Center, Jiangsu Province Hospital, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China
| | - Mujie Ye
- Neuroendocrine Tumor Diagnosis and Treatment Center, Jiangsu Province Hospital, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China.
| | - Qiyun Tang
- Neuroendocrine Tumor Diagnosis and Treatment Center, Jiangsu Province Hospital, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China.
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15
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Bischoff H, Fattori A, Moinard-Butot F, Schneegans O, Diaz P, Reita D, Rimelen V, Voegeli AC, Bender L. First Report of SPECC1L::ALK Fusion in Medullary Thyroid Carcinoma with Remarkable Response to Alectinib. Thyroid 2025. [PMID: 40376737 DOI: 10.1089/thy.2025.0017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 05/18/2025]
Abstract
Background: Rearrangements of the ALK gene are rare in medullary thyroid carcinoma (MTC), with limited data on the efficacy of ALK inhibitors in this context. Novel fusions, such as SPECC1L::ALK, have not been extensively studied. Methods: We present a case of a 33-year-old woman with metastatic MTC, in whom molecular profiling using next-generation sequencing (Archer FusionPlex®) identified a SPECC1L::ALK gene fusion. Treatment with the ALK inhibitor alectinib was initiated at 600 mg twice daily. Results: The patient demonstrated a dramatic partial to near-complete response after 6 days of treatment, as shown by positron emission tomography-computed tomography. At 6 weeks, a complete response was confirmed. Treatment was generally well tolerated, aside from grade 3 myalgia with elevated creatine phosphokinase, managed with temporary cessation and dose adjustment. As of the latest follow-up (8 months), the patient remains on alectinib with sustained complete response. Conclusions: This is the first report of a SPECC1L::ALK fusion in MTC. The dramatic response to alectinib highlights the importance of molecular profiling and suggests that ALK inhibitors may benefit patients with rare ALK fusions in thyroid cancers.
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Affiliation(s)
- Hervé Bischoff
- Department of Medical Oncology, Institut de Cancérologie de Strasbourg Europe, Strasbourg, France
| | - Antonin Fattori
- Department of Pathology, Strasbourg University Hospital, Strasbourg, France
| | - Fabien Moinard-Butot
- Department of Medical Oncology, Institut de Cancérologie de Strasbourg Europe, Strasbourg, France
| | - Olivier Schneegans
- Department of Nuclear Medicine, Institut de Cancérologie de Strasbourg Europe, Strasbourg, France
| | - Pablo Diaz
- Department of Internal Medicine, Strasbourg University Hospital, Strasbourg, France
| | - Damien Reita
- Department of Cancer Molecular Genetics, Laboratory of Biochemistry and Molecular Biology, Strasbourg University Hospital, Strasbourg, France
| | - Valérie Rimelen
- Department of Cancer Molecular Genetics, Laboratory of Biochemistry and Molecular Biology, Strasbourg University Hospital, Strasbourg, France
| | - Anne-Claire Voegeli
- Department of Cancer Molecular Genetics, Laboratory of Biochemistry and Molecular Biology, Strasbourg University Hospital, Strasbourg, France
| | - Laura Bender
- Department of Medical Oncology, Institut de Cancérologie de Strasbourg Europe, Strasbourg, France
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16
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Hu HT, Wang P, Jiang YJ, Wang HK, Shao XX, Tian YT. Nomogram-based prognostic stratification for resectable gastric signet-ring cell carcinoma and adenocarcinoma: A retrospective cohort study. World J Gastrointest Oncol 2025; 17:106244. [DOI: 10.4251/wjgo.v17.i5.106244] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/19/2025] [Revised: 03/02/2025] [Accepted: 03/11/2025] [Indexed: 05/15/2025] Open
Abstract
BACKGROUND Gastric signet-ring cell carcinoma (GSRCC) is a more aggressive subtype of gastric cancer compared to gastric adenocarcinoma (GA), with an increasing incidence. However, the prognostic differences between these subtypes, particularly in resectable cases, remain unclear.
AIM To evaluate prognostic factors and develop a predictive model for GA and GSRCC patients undergoing curative resection.
METHODS This retrospective cohort study included patients with GA and GSRCC who underwent curative surgery at the National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences, from 2011 to 2018. Propensity score matching (PSM) (1:1) balanced the baseline characteristics. Prognostic factors were identified using univariate and multivariate Cox and least absolute shrinkage and selection operator (LASSO) regression analyses. Model performance was evaluated through calibration curves, decision curve analysis (DCA), and time-dependent receiver operating characteristic curves. Subgroup analysis and Kaplan-Meier survival curves were generated.
RESULTS In a cohort of 3027 patients, the GSRCC group was characterized by a significantly higher prevalence of individuals under 60 years of age, females, cases with poor differentiation, and early-stage (stage I) disease (all P < 0.001). After PSM, the baseline was balanced and 761 patients were retained in each group. Variables identified through univariate Cox regression were included in the LASSO regression analysis. Multivariate Cox regression analysis identified age, tumor differentiation, tumor size, vascular invasion, and post-treatment nodal margin staging as independent prognostic factors. Subgroup analysis indicated a notably poorer prognosis for GSRCC in patients aged 60 and above (hazard ratio = 1.36, P = 0.025). The nomogram (C-index = 0.755) exhibited greater predictive accuracy than tumor node metastasis (TNM) staging for 1-, 3-, and 5-year overall survival (all P < 0.001), and provided a higher clinical net benefit according to DCA.
CONCLUSION This study systematically compared resectable GA and GSRCC, revealing no overall survival difference. However, GSRCC demonstrated a significantly elevated mortality risk in subgroups stratified by age and tumor size. Multivariate analysis identified age, differentiation, tumor size, vascular invasion, and TNM stage as independent prognostic factors. The nomogram integrates clinicopathological features for precise risk stratification, surpassing traditional TNM staging.
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Affiliation(s)
- Hai-Tao Hu
- Department of Pancreatic and Gastric Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Peng Wang
- Department of Pancreatic and Gastric Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Yu-Juan Jiang
- Department of Pancreatic and Gastric Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Hai-Kuo Wang
- Department of Pancreatic and Gastric Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Xin-Xin Shao
- Department of Pancreatic and Gastric Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Yan-Tao Tian
- Department of Pancreatic and Gastric Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
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Liu D, Xing YL, Chen D. Low-grade appendiceal mucinous neoplasm at appendiceal orifice treated via appendectomy with double purse-string suture method: A case report. World J Gastrointest Oncol 2025; 17:104011. [DOI: 10.4251/wjgo.v17.i5.104011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/10/2024] [Revised: 02/23/2025] [Accepted: 03/25/2025] [Indexed: 05/15/2025] Open
Abstract
BACKGROUND Low-grade appendiceal mucinous neoplasms (LAMNs) are a class of histologically well-differentiated adenomas that can proliferate outside the appendix in the form of malignant tumours, resulting in the accumulation of external appendiceal mucus. They may present as an extra-appendiceal mass-like bulge, mucus or polypoid tissue at the appendiceal orifice, or even with abdominal dissemination. The surgical approach is usually appendectomy, ileocecal resection or right hemicolectomy. It is essential to raise awareness of LAMNs and choose an appropriate treatment.
CASE SUMMARY A 68-year-old man underwent a routine physical examination at our hospital on May 17, 2022. The patient had no symptoms of abdominal pain, bloating, or weight loss, and his tumour marker levels were normal. The faecal occult blood test was negative, and no abnormalities were identified on physical examination. Colonoscopy revealed a submucosal protrusion at the appendiceal orifice. During endoscopic ultrasound, uneven echoes were observed in the appendix cavity. A contrast-enhanced computed tomography scan of the abdomen revealed a nodular thickening at the base of the appendix, with a diameter of approximately 1 cm. When all the examination results were considered, we suspected the lesion to be an appendiceal mucinous tumour. Laparoscopic surgery was performed using the double purse-string suture method. Postoperative pathology suggested a low-grade mucinous cystadenoma of the appendix with no involvement of the margins. A repeat colonoscopy 18 months after surgery revealed no significant abnormality at the appendiceal orifice. A contrast-enhanced computed tomography scan of the abdomen suggested only postoperative changes.
CONCLUSION This study describes a case of LAMN that was treated by resecting the mass at the appendiceal orifice via the double purse-string suture technique and provides new insights on the diagnosis and treatment of LAMNs.
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Affiliation(s)
- Dong Liu
- Department of Hepatobiliary and Pancreatic Gastroenterology, Affiliated Jinhua Hospital of Wenzhou Medical University, Jinhua People’s Hospital, Jinhua 321000, Zhejiang Province, China
| | - Yue-Long Xing
- Department of Hepatobiliary and Pancreatic Gastroenterology, Affiliated Jinhua Hospital of Wenzhou Medical University, Jinhua People’s Hospital, Jinhua 321000, Zhejiang Province, China
| | - Dan Chen
- Department of Gastroenterology, Affiliated Jinhua Hospital of Wenzhou Medical University, Jinhua People’s Hospital, Jinhua 321000, Zhejiang Province, China
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Miao LF, Sun YY, Du XJ, Xu N, Shen JW, Hua H, Guo M, Yang HJ, Li JK, Zhu L. Combined detection of P53, Ki67, P504S, and IMP3: Diagnostic implications for gastric cancer and precursor lesions. World J Gastrointest Oncol 2025; 17:105604. [DOI: 10.4251/wjgo.v17.i5.105604] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2025] [Revised: 03/11/2025] [Accepted: 04/18/2025] [Indexed: 05/15/2025] Open
Abstract
BACKGROUND Differential diagnosis among atypical hyperplasia (AH) (including reparative hyperplasia and intestinal metaplasia), low-grade dysplasia (LGD), high-grade dysplasia (HGD), and adenocarcinoma (AC) in gastric mucosal biopsies is challenging due to histomorphological overlaps, variability in pathological diagnosis consistency, and limited reproducibility.
AIM To evaluate the diagnostic utility of P53, Ki67, P504S, and IMP3 in gastric cancer and its precancerous lesions, focusing on their effectiveness in distinguishing AH, LGD, HGD, and AC.
METHODS From January 2018 to September 2020, a total of 185 gastric mucosal biopsy specimens were analyzed according to the pathological diagnostic criteria outlined in the World Health Organization Classification of Digestive System Tumors (2019). The specimens were categorized into four groups: AH, LGD, HGD, and AC. Immunohistochemistry was employed to assess the expression status of P53, Ki67, P504S, and IMP3. Intergroup comparisons were performed using the χ2 test or Fisher's exact probability test to compare the differences in immunohistochemical markers across the distinct lesion groups.
RESULTS The expression rate of P504S was highest in the LGD group (53.3%, 16/30), while IMP3 expression was highest in the AC group (41.9%, 26/62), followed by the HGD group (33.3%). Significant differences in P504S and IMP3 expression levels were observed among the four lesion groups (P < 0.001). Pairwise comparisons revealed statistically significant differences in P504S expression between the AH group and the LGD, HGD, and AC groups (P < 0.001), as well as significant variations in IMP3 expression between the AH group and the HGD and AC groups, and between the LGD group and the HGD and AC groups (P < 0.001). Additionally, significant correlations were found between P504S and the polarity expression pattern of Ki67, and between IMP3 and the mutation expression pattern of P53 (P < 0.001). The combined detection of P504S with Ki67 and IMP3 with P53 increased the diagnostic sensitivity for LGD and HGD/AC, respectively.
CONCLUSION P504S is highly expressed in LGD and is associated with the Ki67 “polarity” expression pattern. IMP3 is highly expressed in HGD/AC and is correlated with the P53 mutation expression pattern. The combined detection of P504S with Ki67 and IMP3 with P53 increased the diagnostic sensitivity for LGD and HGD/AC, respectively. The rational use of P504S, Ki67, IMP3, and p53 can help distinguish gastric cancer and precancerous lesions, improving the early cancer diagnosis rate.
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Affiliation(s)
- Lan-Fang Miao
- Department of Pathology, Anyang Tumor Hospital, Anyang 455000, Henan Province, China
- Department of Pathology, The Affiliated Anyang Tumor Hospital of Henan University of Science and Technology, Anyang 455000, Henan Province, China
| | - Yuan-Yuan Sun
- Department of Pathology, Anyang Tumor Hospital, Anyang 455000, Henan Province, China
- Department of Pathology, The Affiliated Anyang Tumor Hospital of Henan University of Science and Technology, Anyang 455000, Henan Province, China
| | - Xian-Juan Du
- Department of Pathology, Anyang Tumor Hospital, Anyang 455000, Henan Province, China
- Department of Pathology, The Affiliated Anyang Tumor Hospital of Henan University of Science and Technology, Anyang 455000, Henan Province, China
| | - Nan Xu
- Department of Pathology, Anyang Tumor Hospital, Anyang 455000, Henan Province, China
- Department of Pathology, The Affiliated Anyang Tumor Hospital of Henan University of Science and Technology, Anyang 455000, Henan Province, China
| | - Jing-Wei Shen
- Department of Pathology, Anyang Tumor Hospital, Anyang 455000, Henan Province, China
- Department of Pathology, The Affiliated Anyang Tumor Hospital of Henan University of Science and Technology, Anyang 455000, Henan Province, China
| | - Hui Hua
- Department of Pathology, Anyang Tumor Hospital, Anyang 455000, Henan Province, China
- Department of Pathology, The Affiliated Anyang Tumor Hospital of Henan University of Science and Technology, Anyang 455000, Henan Province, China
| | - Mei Guo
- Department of Pathology, Anyang Tumor Hospital, Anyang 455000, Henan Province, China
- Department of Pathology, The Affiliated Anyang Tumor Hospital of Henan University of Science and Technology, Anyang 455000, Henan Province, China
| | - Hai-Jun Yang
- Department of Pathology, Anyang Tumor Hospital, Anyang 455000, Henan Province, China
- Department of Pathology, The Affiliated Anyang Tumor Hospital of Henan University of Science and Technology, Anyang 455000, Henan Province, China
| | - Jun-Kuo Li
- Department of Pathology, Anyang Tumor Hospital, Anyang 455000, Henan Province, China
- Department of Pathology, The Affiliated Anyang Tumor Hospital of Henan University of Science and Technology, Anyang 455000, Henan Province, China
| | - Lei Zhu
- Department of Pathology, Anyang Sixth People's Hospital, Anyang 455000, Henan Province, China
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Ben Rejeb S, Labadi A, Lakhal M, Bellil K, Chouchen A. Prognostic significance of B-Catenin and E-Cadherin expression in gastric carcinoma. J Immunoassay Immunochem 2025:1-14. [PMID: 40366977 DOI: 10.1080/15321819.2025.2505033] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/16/2025]
Abstract
INTRODUCTION Gastric cancer (GC) is a leading cause of cancer-related mortality worldwide. Dysregulation of molecular pathways, including β-Catenin-mediated Wnt signaling, epithelial-to-mesenchymal transition (EMT), and E-Cadherin-modulated cell adhesion, plays critical roles in gastric carcinogenesis. This study assesses the expression patterns of β-Catenin and E-Cadherin in GC and explores their prognostic significance. METHODS This retrospective, multi-center study analyzed GC cases diagnosed between 2009 and 2019 at the pathology departments of Security Forces and Rabta Hospitals. Tissue microarray (TMA) paraffin blocks from 48 GC cases were immunohistochemically stained using antibodies for β-Catenin (Leica, 17C2) and E-Cadherin (Leica, 36B5). β-Catenin expression was scored as membranous, cytoplasmic, or nuclear, with overexpression defined as ≥ 50% positive cells. E-Cadherin staining was categorized from absent (score 0) to marked membranous staining (score 3), with scores 0-2 considered aberrant. Statistical analysis was performed using SPSS version 23. RESULTS Of the 48 cases, β-Catenin overexpression was observed in 50% of cases, significantly associated with tumor differentiation (p = 0.033), age > 60 years (p = 0.042), and male sex (p = 0.028). Aberrant E-Cadherin expression was found in 65% of cases, linked to poorly cohesive and diffuse subtypes (p = 0.053), poor differentiation (p = 0.042), and recurrence (p = 0.043), with a trend toward reduced survival (p = 0.056). CONCLUSION β-Catenin overexpression and aberrant E-Cadherin expression are frequent in GC, reflecting their roles in tumor progression via Wnt signaling and EMT. These findings highlight their potential as prognostic biomarkers and therapeutic targets, particularly for Wnt pathway-directed therapies in personalized GC management.
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Affiliation(s)
- Sarra Ben Rejeb
- Pathology department, Security Forces Hospital, Marsa, Tunisia
- Research Unity UR17ES17 on Epithelial to Mesenchymal Transition, Faculty of Medicine of Tunis, Tunis, Tunisia
| | - Abir Labadi
- Pathology department, Security Forces Hospital, Marsa, Tunisia
| | - Marwa Lakhal
- Research Unity UR17ES17 on Epithelial to Mesenchymal Transition, Faculty of Medicine of Tunis, Tunis, Tunisia
| | - Khadija Bellil
- Research Unity UR17ES17 on Epithelial to Mesenchymal Transition, Faculty of Medicine of Tunis, Tunis, Tunisia
| | - Adnen Chouchen
- Surgery Department, Security Forces Hospital, Marsa, Tunisia
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20
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Zhuo L, Chen W, Xing L, Li X, Song Z, Dong J, Zhang Y, Li H, Cui J, Han Y, Hao J, Wang J, Yin X, Li C. MRI-based quantification of intratumoral heterogeneity for intrahepatic mass-forming cholangiocarcinoma grading: a multicenter study. Insights Imaging 2025; 16:101. [PMID: 40369381 PMCID: PMC12078897 DOI: 10.1186/s13244-025-01985-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2024] [Accepted: 04/27/2025] [Indexed: 05/16/2025] Open
Abstract
OBJECTIVE This study aimed to develop a quantitative approach to measure intratumor heterogeneity (ITH) using MRI scans and predict the pathological grading of intrahepatic mass-forming cholangiocarcinoma (IMCC). METHODS Preoperative MRI scans from IMCC patients were retrospectively obtained from five academic medical centers, covering the period from March 2018 to April 2024. Radiomic features were extracted from the whole tumor and its subregions, which were segmented using K-means clustering. An ITH index was derived from a habitat model integrating output probabilities of the subregions-based models. Significant variables from clinical laboratory-imaging features, radiomics, and the habitat model were integrated into a predictive model, and its performance was evaluated using the area under the receiver operating characteristic curve (AUC). RESULTS The final training and internal validation datasets included 197 patients (median age, 59 years [IQR, 52-65 years]); the external validation dataset included 43 patients (median age, 58.5 years [IQR, 52.25-69.75 years]). The habitat model achieved AUCs of 0.847 (95% CI: 0.783, 0.911) in the training set and 0.753 (95% CI: 0.595, 0.911) in the internal validation set. Furthermore, the combined model, integrating imaging variables, the habitat model, and radiomics model, demonstrated improved predictive performance, with AUCs of 0.895 (95% CI: 0.845, 0.944) in the training dataset, 0.790 (95% CI: 0.65, 0.931) in the internal validation dataset, and 0.815 (95% CI: 0.68, 0.951) in the external validation dataset. CONCLUSION The combined model based on MRI-derived quantification of ITH, along with clinical, laboratory, radiological, and radiomic features, showed good performance in predicting IMCC grading. CRITICAL RELEVANCE STATEMENT This model, integrating MRI-derived intrahepatic mass-forming cholangiocarcinoma (IMCC) classification metrics with quantitative radiomic analysis of intratumor heterogeneity (ITH), demonstrates enhanced accuracy in tumor grade prediction, advancing risk stratification for clinical decision-making in IMCC management. KEY POINTS Grading of intrahepatic mass-forming cholangiocarcinoma (IMCC) is important for risk stratification, clinical decision-making, and personalized therapeutic optimization. Quantitative intratumor heterogeneity can accurately predict the pathological grading of IMCC. This combined model provides higher diagnostic accuracy.
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Affiliation(s)
- Liyong Zhuo
- Department of Medical Imaging, The Second Hospital of Hebei Medical University, Shijiazhuang, People's Republic of China
- Department of Radiology, Affiliated Hospital of Hebei University, Baoding, People's Republic of China
| | - Wenjing Chen
- Department of Research and Development, United Imaging Intelligence (Beijing) Co., Ltd., Beijing, People's Republic of China
| | - Lihong Xing
- Department of Radiology, Affiliated Hospital of Hebei University, Baoding, People's Republic of China
| | - Xiaomeng Li
- Department of Radiology, Affiliated Hospital of Hebei University, Baoding, People's Republic of China
| | - Zijun Song
- Department of Critical Care Medicine, Baoding First Central Hospital, Baoding, People's Republic of China
| | - Jinghui Dong
- Department of Radiology, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, People's Republic of China
| | - Yanyan Zhang
- Department of Radiology, Beijing You'an Hospital, Beijing, People's Republic of China
| | - Hongjun Li
- Department of Radiology, Beijing You'an Hospital, Beijing, People's Republic of China
| | - Jingjing Cui
- Department of Research and Development, United Imaging Intelligence (Beijing) Co., Ltd., Beijing, People's Republic of China
| | - Yuxiao Han
- Department of Radiology, Affiliated Hospital of Hebei University, Baoding, People's Republic of China
| | - Jiawei Hao
- Department of Radiology, Affiliated Hospital of Hebei University, Baoding, People's Republic of China
| | - Jianing Wang
- Department of Radiology, Affiliated Hospital of Hebei University, Baoding, People's Republic of China
| | - Xiaoping Yin
- Department of Radiology, Affiliated Hospital of Hebei University, Baoding, People's Republic of China.
| | - Caiying Li
- Department of Medical Imaging, The Second Hospital of Hebei Medical University, Shijiazhuang, People's Republic of China.
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21
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Kim S, Seo J, Shin Y, Kim M. Expression of insulinoma-associated protein 1 (INSM1) in gastric neuroendocrine and non-neuroendocrine neoplasms. Discov Oncol 2025; 16:754. [PMID: 40358853 PMCID: PMC12075032 DOI: 10.1007/s12672-025-02576-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/04/2025] [Accepted: 05/05/2025] [Indexed: 05/15/2025] Open
Abstract
AIMS Insulinoma-associated protein 1 (INSM1) is a recently added nuclear marker for neuroendocrine differentiation. However, INSM1 expression in gastric neuroendocrine and non-neuroendocrine neoplasms has not been thoroughly investigated. METHODS We examined INSM1 expression in 72 gastric tumors, including 22 gastric neuroendocrine tumors and 50 gastric non-neuroendocrine neoplasms. Synaptophysin and chromogranin immunostaining were also performed for all cases. RESULTS For gastric neuroendocrine neoplasms, INSM1 immunostaining demonstrated excellent sensitivity (21/22, 95.5%), comparable to synaptophysin (22/22, 100.0%), but had lower specificity (32/50, 64.0%) compared with traditional neuroendocrine markers (synaptophysin (36/50, 72.0%) and chromogranin (42/50, 84.0%)). However, decreased expression of INSM1, measured by H-score, was frequently found among neuroendocrine carcinoma cases. Gastric non-neuroendocrine neoplasms frequently exhibited INSM1 positivity (18/50, 36.0%); however, in most cases (16/18, 88.9%), staining was focal (involving < 10% of tumor cells). Tumor histologic subtype and grade may be associated with INSM1 expression. CONCLUSIONS INSM1 nuclear positivity in gastric neoplasms should be interpreted with caution. INSM1 should not be used as a stand-alone marker for determining neuroendocrine differentiation in gastric tumors. Histologic evaluation with concurrent use of traditional neuroendocrine markers is warranted to accurately demonstrate neuroendocrine differentiation and minimize false positivity and false negativity.
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Affiliation(s)
- Sujeong Kim
- School of Medicine, Kyungpook National University, Daegu, Republic of Korea
| | - Jisu Seo
- School of Medicine, Kyungpook National University, Daegu, Republic of Korea
| | - Youjung Shin
- School of Medicine, Kyungpook National University, Daegu, Republic of Korea
| | - Moonsik Kim
- Department of Pathology, School of Medicine, Kyungpook National University, Kyungpook National University Chilgok Hospital, Kyungpook National University School of Medicine, Daegu, 41405, Republic of Korea.
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22
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Gu C, ChenLiu Z, Wu Q, Tang D. ncRNAs as Key Regulators in Gastric Cancer: From Molecular Subtyping to Therapeutic Targets. Ann Surg Oncol 2025:10.1245/s10434-025-17368-9. [PMID: 40358781 DOI: 10.1245/s10434-025-17368-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2025] [Accepted: 04/08/2025] [Indexed: 05/15/2025]
Abstract
Gastric cancer (GC) poses a major global health challenge, underscoring the need for advanced diagnostic and therapeutic approaches. Non-coding RNAs (ncRNAs), including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), have emerged as pivotal regulators in GC, with their dysregulated expression driving key processes such as tumorigenesis, metastasis, immune evasion, and chemoresistance. The functional diversity of ncRNAs across different GC molecular subtypes highlights their potential as biomarkers for improved subtype classification and patient stratification. Beyond their diagnostic value, ncRNAs demonstrate critical regulatory functions in tumor biology, establishing these RNA molecules as promising targets for therapeutic development. Strategies based on RNA hold considerable promise for addressing critical challenges such as immune escape and drug resistance by modulating key signaling pathways. These approaches can enhance immune responses, reprogram the tumor microenvironment, and reverse resistance mechanisms that compromise treatment efficacy, thereby improving clinical outcomes. Although ncRNAs represent a promising frontier in GC precision medicine, further research is required to fully harness their clinical potential.
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Affiliation(s)
- Chen Gu
- Clinical Medical College, Yangzhou University, Yangzhou, Jiangsu Province, China
| | - Zhenni ChenLiu
- Clinical Medical College, Yangzhou University, Yangzhou, Jiangsu Province, China
| | - Qihang Wu
- Clinical Medical College, Yangzhou University, Yangzhou, Jiangsu Province, China
| | - Dong Tang
- Department of General Surgery, Institute of General Surgery Northern Jiangsu People's Hospital Affiliated to Yangzhou University, Yangzhou, China.
- Northern Jiangsu People's Hospital, Yangzhou, China.
- The Yangzhou Clinical Medical College of Xuzhou Medical University, Xuzhou Medical University, Yangzhou, China.
- Northern Jiangsu People's Hospital, Clinical Teaching Hospital of Medical School, Nanjing University, Yangzhou, China.
- The Yangzhou School of Clinical Medicine of Dalian Medical University, Dalian Medical University, Yangzhou, China.
- The Yangzhou School of Clinical Medicine of Nanjing Medical University, Yangzhou, China.
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23
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Perez K, Del Rivero J, Kennedy EB, Basu S, Chauhan A, Connolly HM, Dasari AN, Gangi A, Clarke CN, Hallet J, Howe JR, Grady E, Ivanidze J, Mittra ES, White SB, Raj NP, Vijayvergia N, Lewis MA, Chan JA, Kunz PL, Mailman J, Arshad J, Soares HP, Singh S, Chandrasekharan C, Soulen MC, Janson ET, Halfdanarson TR, Strosberg JR, Bergsland EK. Symptom Management for Well-Differentiated Gastroenteropancreatic Neuroendocrine Tumors: ASCO Guideline. JCO Oncol Pract 2025:OP2500133. [PMID: 40344544 DOI: 10.1200/op-25-00133] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2025] [Revised: 03/07/2025] [Accepted: 03/24/2025] [Indexed: 05/11/2025] Open
Abstract
PURPOSE To develop a clinical practice guideline and recommendations for symptom management of patients with well-differentiated grade 1 to grade 3 metastatic gastroenteropancreatic neuroendocrine tumors. METHODS ASCO convened an Expert Panel to develop a clinical practice guideline by reviewing the literature for relevant guidelines, systematic reviews, randomized controlled trials (RCTs), and observational studies to develop recommendations for clinical practice. RESULTS The literature review identified eight guidelines, 19 systematic reviews, and three RCTs that informed the development of guideline recommendations. RECOMMENDATIONS Recommendations are included for carcinoid syndrome, carcinoid heart disease and carcinoid crisis, and functional pancreatic neuroendocrine tumor syndromes. Recommendations are provided for surgical management, liver-directed therapy, and systemic therapy options, as well as palliative care. Limited guidance is provided for sequencing of interventions.Additional information is available at www.asco.org/gastrointestinal-cancer-guidelines.
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Affiliation(s)
| | | | | | - Sandip Basu
- Radiation Medicine Centre, Bhabha Atomic Research Centre, Tata Memorial Hospital Parel, Mumbai, India
| | | | | | | | | | | | - Julie Hallet
- Odette Cancer Center, Sunnybrook Health Sciences Centre, Toronto, ON, Canada
| | | | | | | | | | | | - Nitya P Raj
- Memorial Sloan Kettering Cancer Center, New York, NY
| | | | | | | | | | | | | | | | - Simron Singh
- Odette Cancer Center, Sunnybrook Health Sciences Centre, Toronto, ON, Canada
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24
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Kitadai Y, Takigawa H, Shimizu D, Ariyoshi M, Tsuboi A, Tanaka H, Yamashita K, Hiyama Y, Kishida Y, Urabe Y, Ishikawa A, Kuwai T, Oka S. Endoscopic features differentiating non-Helicobacter pylori Helicobacter-induced gastric mucosa-associated lymphoid tissue lymphoma with a nodular gastritis-like appearance and H. pylori-induced conventional nodular gastritis. Dig Endosc 2025. [PMID: 40347029 DOI: 10.1111/den.15042] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/02/2024] [Accepted: 04/13/2025] [Indexed: 05/12/2025]
Abstract
OBJECTIVES Conventional nodular gastritis has been known to be caused by Helicobacter pylori infection. Several cases of gastric mucosa-associated lymphoid tissue (MALT) lymphoma with non-H. pylori Helicobacters (NHPH) exhibit endoscopic findings resembling nodular gastritis. Considering the differences in malignancy, distinguishing between these two conditions is crucial. This study aimed to identify the distinguishing endoscopic features of NHPH-induced gastric MALT lymphoma with nodular gastritis-like appearance (NHPHi-MNG) and H.-induced conventional nodular gastritis (HPi-NG). METHODS Between 2011 and 2022, we analyzed 17 patients with NHPHi-MNG and 50 patients with HPi-NG at Hiroshima University Hospital and evaluated nodule morphology and distribution patterns. RESULTS Compared with the HPi-NG group, the NHPHi-MNG group exhibited significantly larger nodules (2.5 vs. 2.0 mm, P < 0.05) with protruded morphology (protruded/superficial, elevated: 14/3 vs. 8/42, P < 0.05), most prominently in the gastric angulus. The variability in nodule size was significantly higher in the NHPHi-MNG group than in the HPi-NG group (0.85 vs. 0.37 mm, P < 0.05), reflecting nodule heterogeneity. The distance from the gastric angulus to the proximal end of the nodular lesions was significantly greater in the NHPHi-MNG group than in the HPi-NG group (4.4 vs. 1.7 cm, P < 0.05). The nodules in the HPi-NG group were smaller, superficial, elevated, and most prominent in the gastric antrum compared with those in the NHPHi-MNG group. They were predominantly distributed in the gastric antrum with a homogeneous morphology. CONCLUSION NHPHi-MNG and HPi-NG can be endoscopically differentiated according to nodule morphology and distribution. Recognizing these distinguishing features is essential for an accurate diagnosis.
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Affiliation(s)
- Yuki Kitadai
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Hidehiko Takigawa
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Daisuke Shimizu
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Misa Ariyoshi
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Akiyoshi Tsuboi
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Hidenori Tanaka
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Ken Yamashita
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Yuichi Hiyama
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Yoshihiro Kishida
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Yuji Urabe
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Akira Ishikawa
- Department of Molecular Pathology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Toshio Kuwai
- Gastrointestinal Endoscopy and Medicine, Hiroshima University Hospital, Hiroshima, Japan
| | - Shiro Oka
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
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25
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Zhang JY, Li D, Hu GJ. Development of a nomogram for predicting the risk of carcinoma in chronic atrophic gastritis. Discov Oncol 2025; 16:688. [PMID: 40338419 PMCID: PMC12062482 DOI: 10.1007/s12672-025-02453-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/30/2024] [Accepted: 04/21/2025] [Indexed: 05/09/2025] Open
Abstract
OBJECTIVE To construct a machine learning (ML) model to predict the progression of chronic atrophic gastritis (CAG) to gastric cancer (GC), given its precancerous significance. METHODS Using medical records from the Affiliated Hospital of Qingdao University, common laboratory indicators were extracted. LASSO regression identified 10 core risk factors, which were further analyzed using binary logistic regression to develop a nomogram model in R. The model's performance was evaluated using receiver operating characteristic (ROC) curves, the concordance index (C-index), calibration curves, and decision curve analysis (DCA). RESULTS The model showed excellent performance, with a C-index of 0.887. The key factors included sex, coagulation, blood cell indexes, and blood lipid levels. The ROC areas were 0.892 (quantitative) and 0.853 (qualitative), confirming model reliability. CONCLUSION A new nomogram model for assessing GC risk in CAG patients was successfully developed. However, due to data collection and time limitations, future studies should expand the sample size, perfect the validation process, and optimize the model to achieve more accurate risk prediction.
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Affiliation(s)
- Jia-Yi Zhang
- Institute of Integrated Medicine, Qingdao Medical College of Qingdao University, Qingdao University, Qingdao, Shandong, China
- Department of Traditional Chinese Medicine, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China
| | - Ding Li
- Department of Traditional Chinese Medicine, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China
| | - Guo-Jie Hu
- Department of Traditional Chinese Medicine, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China.
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26
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Hisaoka K, Matsuda S, Kawakubo H, Takeuchi M, Wada T, Sekine S, Takamoto T, Tsutsui M, Yura M, Ishida H, Ono Y, Kamiya S, Bando E, Nunobe S, Kinoshita T, Kitagawa Y. Distribution of Lymph Node Metastasis and Prognosis in Duodenal Bulb Tumors: A Multicenter Retrospective Study. Ann Surg Oncol 2025:10.1245/s10434-025-17388-5. [PMID: 40338425 DOI: 10.1245/s10434-025-17388-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2024] [Accepted: 04/13/2025] [Indexed: 05/09/2025]
Abstract
BACKGROUND The optimal surgical procedure for primary duodenal cancer has not been established because of its low incidence. The purpose of this study was to examine the distribution of lymph node (LN) metastasis in duodenal bulb tumors. Specifically, in tumors with submucosal invasion, we aimed to evaluate the feasibility of distal gastrectomy with duodenal bulb resection combined with lymphadenectomy of regional gastric LNs. METHODS Data from patients who underwent surgery for either adenocarcinoma or neuroendocrine tumors located in the duodenal bulb between 2000 and 2020 were retrospectively analyzed from five high-volume centers in Japan. Patient background, clinicopathological factors, type of surgery, distribution of LN metastasis, and long-term outcomes were evaluated. RESULTS The frequency of LN metastasis in tumors with submucosal invasion was 18%. Metastatic LNs were identified in T1b adenocarcinomas for #6, #8a, #8p, with similar results for neuroendocrine tumors. The 3-year overall survival rate for adenocarcinoma in stages T1a, T1b, and T2-4 was 100%, 81%, and 56%, respectively. Neuroendocrine tumors were 100% at all depths of invasion. Regarding LN tumors with submucosal invasion, while three patients had a recurrence, two cases were observed in distant organs without regional LNs, and one patient who underwent pancreaticoduodenectomy had metastasis in the gastric regional LNs. CONCLUSION For duodenal bulb tumors, based on the distribution of LN metastasis with tumors with submucosal invasion, distal gastrectomy with duodenal bulb resection and regional LN dissection is considered a curative treatment. Conversely, pancreaticoduodenectomy is recommended for tumors invading the muscularis propria and beyond.
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Affiliation(s)
- Kazuhiko Hisaoka
- Department of Surgery, Keio University School of Medicine, Tokyo, Japan
| | - Satoru Matsuda
- Department of Surgery, Keio University School of Medicine, Tokyo, Japan
| | - Hirofumi Kawakubo
- Department of Surgery, Keio University School of Medicine, Tokyo, Japan.
| | - Masashi Takeuchi
- Department of Surgery, Keio University School of Medicine, Tokyo, Japan
| | - Takeyuki Wada
- Department of Gastric Surgery, National Cancer Center Hospital, Tokyo, Japan
| | - Shigeki Sekine
- Department of Pathology, National Cancer Center Hospital, Tokyo, Japan
- Department of Pathology, Keio University School of Medicine, Tokyo, Japan
| | - Takeshi Takamoto
- Department of Hepatobiliary Surgery, National Cancer Center Hospital, Tokyo, Japan
| | - Mai Tsutsui
- Department of Gastric Surgery, National Cancer Center Hospital, Tokyo, Japan
| | - Masahiro Yura
- Department of Gastric Surgery, National Cancer Center Hospital East, Tokyo, Japan
| | - Hiroki Ishida
- Department of Gastroenterological Surgery, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Yoshihiro Ono
- Department of Gastroenterological Surgery, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Satoshi Kamiya
- Department of Gastric Surgery, Shizuoka Cancer Center, Nagaizumi, Japan
| | - Etsuro Bando
- Department of Gastric Surgery, Shizuoka Cancer Center, Nagaizumi, Japan
| | - Soya Nunobe
- Department of Gastroenterological Surgery, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Takahiro Kinoshita
- Department of Gastric Surgery, National Cancer Center Hospital East, Tokyo, Japan
| | - Yuko Kitagawa
- Department of Surgery, Keio University School of Medicine, Tokyo, Japan
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27
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Wee K, Yang KC, Schaeffer DF, Zhou C, Leung E, Feng X, Laskin J, Marra MA, Loree JM, Gorski SM. Genomic and transcriptomic landscapes of metastatic neuroendocrine neoplasms from distinct primary sites and their clinical implications. Sci Rep 2025; 15:15770. [PMID: 40328872 PMCID: PMC12056210 DOI: 10.1038/s41598-025-00549-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2024] [Accepted: 04/29/2025] [Indexed: 05/08/2025] Open
Abstract
Neuroendocrine neoplasms (NENs) encompass a highly heterogeneous group of neoplasms with varying prognoses and molecular alterations. Molecular profiling studies have furthered our understanding of NENs, but the majority of previous studies have focused on primary tumors and on mutational landscapes using DNA sequencing data. Here, we describe the genomic and transcriptomic landscapes of 28 metastatic NENs across different primary anatomical sites (PASs) and their potential clinical implications. Although our cohort is small, our analyses provide further insights on the molecular commonalities and distinctions between metastatic NENs of different PASs. Comparison to several reference transcriptome data sets revealed that despite considerable whole genome and transcriptome variability in NENs, the metastatic NENs are still more like each other than other cancer types. Our study also highlights the potential utility of NEN transcriptome data for molecular classification and clinical decision making.
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Affiliation(s)
- Kathleen Wee
- Canada's Michael Smith Genome Sciences Centre, BC Cancer, Vancouver, BC, Canada
| | - Kevin C Yang
- Canada's Michael Smith Genome Sciences Centre, BC Cancer, Vancouver, BC, Canada
| | - David F Schaeffer
- Division of Anatomic Pathology, Vancouver General Hospital, Vancouver, BC, Canada
- Pancreas Centre BC, Vancouver, BC, Canada
| | - Chen Zhou
- Department of Pathology and Laboratory Medicine, BC Cancer, Vancouver, BC, Canada
| | - Emily Leung
- Canada's Michael Smith Genome Sciences Centre, BC Cancer, Vancouver, BC, Canada
| | - Xiaolan Feng
- Vancouver Island Centre, BC Cancer, Victoria, BC, Canada
| | - Janessa Laskin
- Division of Medical Oncology, BC Cancer, Vancouver, BC, Canada
| | - Marco A Marra
- Canada's Michael Smith Genome Sciences Centre, BC Cancer, Vancouver, BC, Canada
- Department of Medical Genetics and Michael Smith Laboratories, University of British Columbia, Vancouver, BC, Canada
| | | | - Sharon M Gorski
- Canada's Michael Smith Genome Sciences Centre, BC Cancer, Vancouver, BC, Canada.
- Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, BC, Canada.
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28
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Tobias J, Clarke CN, Gangi A, Keutgen XM. The Landmark Series: Surgical Management of Functioning and Non-Functioning Pancreatic Neuroendocrine Tumors. Ann Surg Oncol 2025:10.1245/s10434-025-17390-x. [PMID: 40319207 DOI: 10.1245/s10434-025-17390-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2025] [Accepted: 04/13/2025] [Indexed: 05/07/2025]
Abstract
Pancreatic neuroendocrine tumors (PNETs) are comparatively rare pancreatic malignancies that exhibit diverse biologic behavior, ranging from indolent tumors to widely metastatic cancers, with up to 15 % secreting hormones that cause symptoms. As a consequence, the management of PNETs is highly individualized and can include active surveillance of small (1-2 cm) and very small (< 1 cm) nonfunctioning tumors without worrisome features, parenchymal-sparing resection of appropriately located tumors, anatomic pancreatectomy and, in select cases, debulking of metastatic disease, particularly in the liver. This review synthesizes society recommendations and contemporary evidence guiding the surgical management of PNETs. Innovations in molecular profiling and systemic therapies hold promise to refine surgical algorithms for this heterogeneous tumor.
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Affiliation(s)
- Joseph Tobias
- Division of Surgical Oncology, Section of Endocrine Surgery, University of Chicago, Chicago, IL, USA
| | - Callisia N Clarke
- Division of Surgical Oncology, Medical College of Wisconsin, Milwaukee, WI, USA
| | - Alexandra Gangi
- Division of Surgical Oncology, Cedars Sinai Medical Center, Los Angeles, CA, USA
| | - Xavier M Keutgen
- Division of Surgical Oncology, Section of Endocrine Surgery, University of Chicago, Chicago, IL, USA.
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29
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Salesse J, Chicaud M, Braham H, Taconet S. [Appendiceal goblet cell adenocarcinoma: Has the controversy come to an end?]. Ann Pathol 2025; 45:237-243. [PMID: 39304358 DOI: 10.1016/j.annpat.2024.08.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2024] [Revised: 08/29/2024] [Accepted: 08/30/2024] [Indexed: 09/22/2024]
Abstract
In 2019, the 5th edition of the WHO classification of digestive tumours has retained the terminology "goblet cell adenocarcinoma" (GCA) to designate a tumour whose amphicrine nature owed it more than ten denominations since its initial description among which the most tenacious "goblet cell carcinoid" is no longer recommended today. This rare tumour represents 15-19% of appendicular tumours. Its incidence is rising. The positive diagnosis is based on morphological examination and mandatory identification of a low-grade component of glands comprising goblet cells stained by PAS and Alcian blue. The appendix must be entirely examined. Global tumour grade (low, intermediate, high) is based on the proportions of low-grade and high-grade components. This tumour's immunohistochemical profile is particular because of expression of CK20 and often CK7 as well as neuroendocrine markers. It is often an incidental finding on a surgical specimen, among individuals aged 50 or more years, presenting with a locally advanced stage with vascular and perineural invasion. Lymph node metastases are present in a third of cases. Non-specific mutations of ARID1A and genes of the Wnt pathway may be identified. GCA is not associated with microsatellite instability or Lynch syndrome. Its prognosis is intermediate. Surgery is the reference therapy based on the stage. The main differential diagnoses are colorectal adenocarcinoma NOS, mucinous adenocarcinoma and signet ring cell adenocarcinoma. Patients are referred to the RENAPE expert network.
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Affiliation(s)
- Jeanne Salesse
- Service d'anatomie et cytologie pathologiques, hôpital Simone-Veil, 14, rue de Saint-Prix, 95600 Eaubonne, France; UFR de médecine, université Paris-Cité, 15, rue de l'École de Médecine, 75006 Paris, France
| | - Matthieu Chicaud
- Service d'anatomie et cytologie pathologiques, hôpital Simone-Veil, 14, rue de Saint-Prix, 95600 Eaubonne, France.
| | - Hamdi Braham
- Service de chirurgie générale et digestive, hôpital Simone-Veil, 14, rue de Saint-Prix, 95600 Eaubonne, France
| | - Sarah Taconet
- Service d'anatomie et cytologie pathologiques, hôpital Simone-Veil, 14, rue de Saint-Prix, 95600 Eaubonne, France
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30
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Huang S, Liu S, Tan F, Chen H, Chen G. Construction and validation of a risk nomogram model for colorectal sessile serrated lesions. J Int Med Res 2025; 53:3000605251337577. [PMID: 40357909 PMCID: PMC12075987 DOI: 10.1177/03000605251337577] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2024] [Accepted: 04/09/2025] [Indexed: 05/15/2025] Open
Abstract
ObjectiveThis study aimed to explore the risk factors for colorectal sessile serrated lesions and construct a risk nomogram model.MethodsPatients were enrolled retrospectively from the Affiliated Xuzhou Municipal Hospital of Xuzhou Medical University from January 2019 to September 2023 and randomized to the training and validation sets at a ratio of 7:3. The predictors for constructing the nomogram model were screened via univariate analysis and multivariate logistic regression analysis. Subsequently, the performance of the model was evaluated.ResultsMultivariate logistic regression analysis revealed that age, history of smoking, history of alcohol consumption, and triglyceride-glucose index were independent risk factors for colorectal sessile serrated lesions (p < 0.05). The area under the curve values of the nomogram model in the training and validation sets were 0.715 (95% confidence interval: 0.676-0.753) and 0.742 (95% confidence interval: 0.669-0.815), respectively. The calibration curves showed good homogeneity between the predicted and actual values. Decision curve analysis showed that this nomogram model can achieve positive clinical benefits.ConclusionsAge, history of smoking, history of alcohol consumption, and triglyceride-glucose index are independent predictors of colorectal sessile serrated lesions. This nomogram model may predict the risk of colorectal sessile serrated lesions.
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Affiliation(s)
| | | | - Fang Tan
- The Affiliated Xuzhou Municipal Hospital of Xuzhou Medical University, China
| | - Hu Chen
- The Affiliated Xuzhou Municipal Hospital of Xuzhou Medical University, China
| | - Guangxia Chen
- The Affiliated Xuzhou Municipal Hospital of Xuzhou Medical University, China
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31
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Kinoshita M, Kosaka H, Kaibori M, Ueno M, Yasuda S, Komeda K, Yamamoto Y, Tani M, Aihara T, Shinkawa H, Hayami S, Matsuo Y, Kawaguchi N, Morimura R, Mori H, Nakajima T, Kubo S, Ishizawa T. Favorable impact of hepatitis C virus infection control on recurrence after surgical resection for intrahepatic cholangiocarcinoma. Hepatol Res 2025; 55:707-717. [PMID: 40317596 DOI: 10.1111/hepr.14150] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/03/2024] [Revised: 11/24/2024] [Accepted: 11/25/2024] [Indexed: 05/07/2025]
Abstract
AIM Hepatitis C virus (HCV) infection is a risk factor of intrahepatic cholangiocarcinoma (ICC). However, the impact of HCV infection control status on prognosis after surgery for ICCs is still unclear. METHODS This multicenter retrospective study included patients who underwent curative resection for ICCs. The sera of 56 patients tested positive for anti-HCV antibody and negative for hepatitis B surface antigen (HCV group). Additionally, the sera of 358 patients tested negative for anti-HCV antibody and hepatitis B surface antigen (NBNC group). In the HCV group, 33 of 56 patients achieved sustained virologic response (SVR) for HCV (SVR group), whereas 23 patients did not (non-SVR group). To investigate the prognostic impact of HCV infection control status in the whole study cohort and in patients with solitary ICC without lymph node metastasis (StN0 study cohort), the postoperative prognosis of the SVR, non-SVR, and NBNC groups was compared. RESULTS In the whole study cohort, there were no significant differences in terms of recurrence-free survival (RFS) or overall survival among the three groups. Based on the multivariate Cox regression analysis, non-SVR was an independent unfavorable prognostic factor of RFS. In the StN0 study cohort, the non-SVR group had a significantly lower RFS than the NBNC and SVR groups. Based on the multivariate analysis, non-SVR was an independent unfavorable prognostic factor of RFS. CONCLUSIONS The achievement of SVR for HCV infection in patients with HCV infection-related ICCs is associated with a better RFS after surgery for HCV-related ICCs, particularly solitary ICC without lymph node metastasis.
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Affiliation(s)
- Masahiko Kinoshita
- Department of Hepatobiliary-Pancreatic Surgery, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan
| | - Hisashi Kosaka
- Department of Hepatobiliary Surgery, Kansai Medical University, Hirakata, Japan
| | - Masaki Kaibori
- Department of Hepatobiliary Surgery, Kansai Medical University, Hirakata, Japan
| | - Masaki Ueno
- Second Department of Surgery, Wakayama Medical University, Wakayama, Japan
| | - Satoshi Yasuda
- Department of Surgery, Nara Medical University, Kashihara, Japan
| | - Koji Komeda
- Department of General and Gastroenterological Surgery, Osaka Medical and Pharmaceutical University, Takatsuki, Japan
| | - Yusuke Yamamoto
- Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Masaji Tani
- Division of Gastrointestinal Surgery, Department of Surgery, Shiga University of Medical Science, Otsu, Japan
| | | | - Hiroji Shinkawa
- Department of Hepatobiliary-Pancreatic Surgery, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan
| | - Shinya Hayami
- Second Department of Surgery, Wakayama Medical University, Wakayama, Japan
| | - Yasuko Matsuo
- Department of Surgery, Nara Medical University, Kashihara, Japan
| | - Nao Kawaguchi
- Department of General and Gastroenterological Surgery, Osaka Medical and Pharmaceutical University, Takatsuki, Japan
| | - Ryo Morimura
- Division of Digestive Surgery, Department of Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Haruki Mori
- Division of Gastrointestinal Surgery, Department of Surgery, Shiga University of Medical Science, Otsu, Japan
| | | | - Shoji Kubo
- Department of Hepatobiliary-Pancreatic Surgery, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan
| | - Takeaki Ishizawa
- Department of Hepatobiliary-Pancreatic Surgery, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan
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32
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Elsayed B, Elshoeibi AM, Elhadary M, Al-Jubouri AM, Al-Qahtani N, Vranic S, Al-Saady R. Molecular and immunohistochemical markers in appendiceal mucinous neoplasms: A systematic review and comparative analysis with ovarian mucinous neoplasms and colorectal adenocarcinoma. Histol Histopathol 2025; 40:621-633. [PMID: 39743929 DOI: 10.14670/hh-18-830] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
Abstract
INTRODUCTION Appendiceal mucinous neoplasms (AMNs) represent a rare and diagnostically challenging group of tumors. This systematic review aims to summarize the reported molecular and immunohistochemical markers (IHC) associated with AMNs and compare them with ovarian mucinous neoplasms (OMNs) and colorectal adenocarcinoma (CRC). METHODS A comprehensive search was performed in PubMed/MEDLINE/PMC, Scopus, Embase, and Web of Science databases to identify studies looking at IHC and molecular markers in AMNs. Chi-squared and Fisher's exact tests were utilized to compare the marker expression across different tumor types. RESULTS We identified 27 articles reporting several potential biomarkers for distinguishing between different subtypes of AMNs. Mutations in KRAS, GNAS, and RNF43 emerged as notable biomarkers, with KRAS mutations being the most prevalent across all subtypes. Additionally, p53 IHC overexpression was associated with higher tumor grades. When comparing AMNs with OMNs, we observed a higher prevalence of CK20, CDX2, SATB2, and MUC2 IHC expression, as well as KRAS and GNAS mutations, in AMNs. Conversely, CK7 and PAX8 IHC expression were more prevalent in OMNs. Comparing AMNs with CRCs, we found a higher prevalence of TOPO1 and PTEN IHC expression, as well as KRAS and GNAS mutations, in AMNs. Conversely, nuclear β-catenin IHC expression, as well as TP53, APC, and PIK3CA mutations, were more prevalent in CRCs. CONCLUSION This systematic review identified possible markers for distinguishing AMNs and differentiating between AMNs, OMNs, or CRCs.
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Affiliation(s)
- Basel Elsayed
- College of Medicine, QU Health, Qatar University, Doha, Qatar.
| | | | | | | | - Noof Al-Qahtani
- College of Medicine, QU Health, Qatar University, Doha, Qatar
| | - Semir Vranic
- Department of Pathology, College of Medicine, QU Health, Qatar University, Doha, Qatar
| | - Rafif Al-Saady
- Department of Pathology, College of Medicine, QU Health, Qatar University, Doha, Qatar
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Chen Y, Zhu X, Ding S, Chen M, Yang J, Deng K. Minimally invasive treatment strategies for submucosal tumors of the upper gastrointestinal tract: Advances in innovative endoscopy-based therapies. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2025; 51:109626. [PMID: 39874944 DOI: 10.1016/j.ejso.2025.109626] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2024] [Revised: 01/01/2025] [Accepted: 01/18/2025] [Indexed: 01/30/2025]
Abstract
The increasing detection of submucosal tumors (SMTs) in the upper gastrointestinal tract (UGI) is due to the increased clinical use of endoscopy and imaging technology. Some of these SMTs have malignant potential and may cause clinical symptoms. Thus, it is recommended in clinical guidelines to consider resection of these SMTs. Endoscopic techniques have become widely used in the diagnosis and treatment of SMT in the UGI as compared with traditional surgery due to their advantages of minimally invasive, quick recovery, and economical cost. Recently, new endoscopic techniques and instruments have been continuously implemented, leading to revolutionary innovation in endoscopic treatments. However, the safety and efficacy of these innovative techniques remain unclear. Therefore, we have comprehensively summarized the various techniques used in the treatment of UGI tumors in recent years, evaluated the indications and effects of each technique, and compared their benefits and disadvantages. We hope that this review will provide a more comprehensive reference for clinical and endoscopic practitioners, and help them develop more individualized treatment plans for different patients. This will ultimately expand the patient population that can benefit from these innovative technologies.
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Affiliation(s)
- Yuxiang Chen
- Department of Gastroenterology & Hepatology, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China; Sichuan University-Oxford University Huaxi Gastrointestinal Cancer Centre, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China
| | - Xinrui Zhu
- Department of Gastroenterology & Hepatology, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China; Sichuan University-Oxford University Huaxi Gastrointestinal Cancer Centre, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China
| | - Shasha Ding
- Department of Gastroenterology & Hepatology, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China; Sichuan University-Oxford University Huaxi Gastrointestinal Cancer Centre, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China
| | - Mo Chen
- Department of Gerontology, Tibetan Chengdu Branch Hospital of West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China; Department of Gerontology, Hospital of Chengdu Office of People's Government of Tibetan Autonomous Region, Chengdu, 610041, China
| | - Jinlin Yang
- Department of Gastroenterology & Hepatology, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China; Sichuan University-Oxford University Huaxi Gastrointestinal Cancer Centre, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China.
| | - Kai Deng
- Department of Gastroenterology & Hepatology, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China; Sichuan University-Oxford University Huaxi Gastrointestinal Cancer Centre, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China.
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López-Peña A, Herreros-Villanueva M, Olga A, Hermoso-Durán S, Ajay G, Sarasqueta C, Bujanda L. Long-term validation of intra-cystic biomarkers for pancreatic cysts. Dig Liver Dis 2025; 57:596-603. [PMID: 39933973 DOI: 10.1016/j.dld.2025.01.200] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/24/2024] [Revised: 01/08/2025] [Accepted: 01/24/2025] [Indexed: 02/13/2025]
Abstract
BACKGROUND Pancreatic Cyst Lesions (PCLs) are frequently diagnosed in radiologic imaging tests and can be classified as benign, premalignant and malignant. Their correct stratification is essential and has significant implications for the patient. The objective of the study was to determine the clinical and analytical characteristics that can help in their differential diagnosis. METHODS This observational retrospective study included patients with PCLs diagnosed by endoscopic ultrasound from 2011 to 2023. Data collected included age, sex, personal history, treatments, toxic habits, family history of cancer, body mass index, and radiological and serological findings. The following intra-cyst levels were gathered: glucose, amylase, lipase, CEA and CA19.9. RESULTS 271 patients with PCLs were included, 93 (35%) of them were benign, 55 (20%) were premalignant, and 123 (45%) malignant. Serous cystadenomas were the most common benign lesion in 71 (76%) patients. Within the premalignant group, intraductal papillary mucinous neoplasms (IPMNs) were the most common in 85% (47) patients. Cystic adenocarcinoma was the most prevalent malignant PCLs in 102 (83%) patients. Intra-cystic CEA value was the only parameter able to differentiate benign from malignant/premalignant lesions. Thirty (11%) patients underwent surgery with a final diagnosis of a malignant lesion in 13 (43%) patients, premalignant lesions in 5 (23%) (4 IPMNs and 1 mucinous cystadenoma) and benign cysts in 12 (40%). Five (38%) of the 13 malignant lesions were diagnosed at stages III/IV. CONCLUSION Intra-cyst CEA values can help us to classify premalignant PCNs. However, additional biomarkers and clinical parameters are required to better discriminate patients at the time of PCLs detection.
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Affiliation(s)
- Ana López-Peña
- Department of Liver and Gastrointestinal Diseases, Biogipuzkoa Health Research Institute - Donostia University Hospital, University of the Basque Country (UPV/EHU), 20014, CIBERedh, San Sebastian, Spain
| | - Marta Herreros-Villanueva
- Department of Liver and Gastrointestinal Diseases, Biogipuzkoa Health Research Institute - Donostia University Hospital, University of the Basque Country (UPV/EHU), 20014, CIBERedh, San Sebastian, Spain; Faculty of Life Sciences, Universidad Isabel I, Burgos, Spain
| | - Abian Olga
- Department of Biochemistry and Molecular and Cellular Biology, University of Zaragoza, Zaragoza, Spain; Institute of Biocomputation and Physics of Complex Systems (BIFI), Joint Units IQFR-CSIC-BIFI, and GBsC-CSIC-BIFI, Universidad de Zaragoza, Zaragoza, 50018, Spain; Instituto de Investigación Sanitaria Aragón (IIS Aragón), 50009, Zaragoza, Spain; Centro de Investigación Biomédica en Red en el Área Temática de Enfermedades Hepáticas y Digestivas (CIBERehd), 28029, Madrid, Spain
| | - Sonia Hermoso-Durán
- Institute of Biocomputation and Physics of Complex Systems (BIFI), Joint Units IQFR-CSIC-BIFI, and GBsC-CSIC-BIFI, Universidad de Zaragoza, Zaragoza, 50018, Spain; Centro de Investigación Biomédica en Red en el Área Temática de Enfermedades Hepáticas y Digestivas (CIBERehd), 28029, Madrid, Spain
| | - Goel Ajay
- Department of Molecular Diagnostics and Experimental Therapeutics, Beckman Research Institute of City of Hope Comprehensive Cancer Center, Duarte, California, USA
| | - Cristina Sarasqueta
- Donostia University Hospital, University of the Basque Country (UPV/EHU), 20014, San Sebastian, Spain
| | - Luis Bujanda
- Department of Liver and Gastrointestinal Diseases, Biogipuzkoa Health Research Institute - Donostia University Hospital, University of the Basque Country (UPV/EHU), 20014, CIBERedh, San Sebastian, Spain.
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Flicek KT, Nehra AK, Fidler JL, Sheedy SP. Imaging of the Small Bowel Tumors. Radiol Clin North Am 2025; 63:345-359. [PMID: 40221179 DOI: 10.1016/j.rcl.2024.11.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/14/2025]
Abstract
Small bowel tumors are rare gastrointestinal tumors. Neuroendocrine tumors are the most common and demonstrate unique subtypes depending on their location. Adenocarcinomas are most common in the duodenum demonstrating luminal narrowing and irregularity. Gastrointestinal stromal tumors are heterogeneously enhancing lesions with endophytic and/or exophytic growth patterns. Immunotherapy is a unique treatment of these tumors with tumoral response best assessed with both routine computed tomography (CT) and PET/CT. Primary small bowel lymphoma has many imaging patterns, most commonly being aneurysmal dilation and thickening of the small bowel. Metastases are common and may present as polypoid lesions, focal wall thickening, or serosal deposits.
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Affiliation(s)
- Kristina T Flicek
- Department of Radiology, Mayo Clinic, 200 First Street Southwest, Rochester, MN 55905, USA.
| | - Avinash K Nehra
- Department of Radiology, Mayo Clinic, 200 First Street Southwest, Rochester, MN 55905, USA
| | - Jeff L Fidler
- Department of Radiology, Mayo Clinic, 200 First Street Southwest, Rochester, MN 55905, USA
| | - Shannon P Sheedy
- Department of Radiology, Mayo Clinic, 200 First Street Southwest, Rochester, MN 55905, USA
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Fan W, Wang H, Hou L, Li S. A Case of Pancreatitis-Panniculitis-Polyarthritis Syndrome due to Primary Hepatic Neuroendocrine Tumor. Am J Dermatopathol 2025; 47:e57-e60. [PMID: 39983070 DOI: 10.1097/dad.0000000000002947] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/23/2025]
Abstract
ABSTRACT A 66-year-old male patient presented to our department with subcutaneous nodules in both lower extremities accompanied by pain. Skin pathology suggested pancreatic panniculitis. Subsequent imaging and histopathology identified a rare case of pancreatitis-panniculitis-polyarthritis syndrome secondary to a primary hepatic neuroendocrine tumor. This case highlights the rare association between nonpancreatic conditions and pancreatic panniculitis.
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Affiliation(s)
- Wenjin Fan
- Department of Dermatology and Venereology, 1st Hospital of Jilin University, Changchun, China
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Morita R, Sugeta S, Yoshida J, Ueda T, Hara T, Morimoto Y, Shibuya A, Ohno T, Nakajima T, Fuji N, Konishi E, Yoshida N. Primary Neuroendocrine Carcinoma of the Anal Canal with Cancer Genome Profiling. Intern Med 2025; 64:1350-1354. [PMID: 39401914 DOI: 10.2169/internalmedicine.4289-24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 05/02/2025] Open
Abstract
Primary neuroendocrine carcinoma (NEC) of the anal canal is a rare, highly malignant tumor with a poor prognosis. Despite the standard first-line treatment with etoposide or irinotecan combined with cisplatin, effective second-line therapies are lacking. In 2019, Japan approved cancer genome profiling (CGP) tests for solid tumors to enhance genomic understanding. We present the case of a 79-year-old woman with NEC of the anal canal, treated with etoposide, carboplatin, and amrubicin. As Post-standard therapy, CGP suggested pemigatinib, a tyrosine kinase inhibitor; however, the patient died before receiving it. This case highlights the potential of personalized medicine to improve outcomes in such cases.
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Affiliation(s)
- Ryuichi Morita
- Department of Gastroenterology and Hepatology, Kyoto Saiseikai Hospital, Japan
| | - Seiya Sugeta
- Department of Gastroenterology and Hepatology, Kyoto Saiseikai Hospital, Japan
| | - Juichiro Yoshida
- Department of Gastroenterology and Hepatology, Japanese Red Cross Society Kyoto Daiichi Hospital, Japan
| | - Tomohiro Ueda
- Department of Gastroenterology and Hepatology, Kyoto Saiseikai Hospital, Japan
| | - Tasuku Hara
- Department of Gastroenterology and Hepatology, Kyoto Saiseikai Hospital, Japan
| | - Yasutaka Morimoto
- Department of Gastroenterology and Hepatology, Kyoto Saiseikai Hospital, Japan
| | - Akiko Shibuya
- Department of Gastroenterology and Hepatology, Kyoto Saiseikai Hospital, Japan
| | - Tomoyuki Ohno
- Department of Gastroenterology and Hepatology, Kyoto Saiseikai Hospital, Japan
| | - Tomoki Nakajima
- Department of Gastroenterology and Hepatology, Kyoto Saiseikai Hospital, Japan
| | - Nobuaki Fuji
- Department of Digestive Surgery, Kyoto Saiseikai Hospital, Japan
| | - Eiichi Konishi
- Department of Surgical Pathology, Kyoto Prefectural University of Medicine, Japan
| | - Norimasa Yoshida
- Department of Gastroenterology and Hepatology, Kyoto Saiseikai Hospital, Japan
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Ushida Y, Sugawara G, Minami T, Yamashita Y, Inoue M. Cholangiolocarcinoma with Ductal Plate Malformation Pattern: A 6-Year Follow-Up. Surg Case Rep 2025; 11:25-0086. [PMID: 40330718 PMCID: PMC12055238 DOI: 10.70352/scrj.cr.25-0086] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2025] [Accepted: 04/16/2025] [Indexed: 05/08/2025] Open
Abstract
INTRODUCTION Cholangiolocarcinoma (CLC) with ductal plate malformation (DPM) is a rare primary liver cancer originating from the canals of Hering. It often exhibits intermediate behavior between hepatocellular carcinoma and intrahepatic cholangiocarcinoma. Diagnosing CLC with DPM is challenging due to overlapping imaging features with other liver malignancies. CASE PRESENTATION An 82-year-old man under surveillance for bladder cancer was incidentally found to have a liver nodule in segment 8. Over 6 years, the lesion grew from 10 mm to 41 mm and showed dynamic changes on imaging. Despite two inconclusive biopsies, a diagnosis of CLC with DPM was confirmed after a third biopsy and consultation with a specialized institution. The patient underwent a right hepatectomy, and pathological examination confirmed CLC with DPM. No evidence of recurrence was observed 19 months post-surgery. CONCLUSIONS This case underscores the importance of long-term follow-up and a multidisciplinary approach in managing rare hepatic malignancies. The clinical course provides valuable insights into the progression of CLC with DPM and may aid in diagnosing similar challenging cases.
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Affiliation(s)
- Yuta Ushida
- Department of Surgery, Toyota Kosei Hospital, Toyota, Aichi, Japan
| | - Gen Sugawara
- Department of Surgery, Toyota Kosei Hospital, Toyota, Aichi, Japan
| | - Takayuki Minami
- Department of Surgery, Toyota Kosei Hospital, Toyota, Aichi, Japan
| | - Yoriko Yamashita
- Department of Pathology, Toyota Kosei Hospital, Toyota, Aichi, Japan
| | - Masaya Inoue
- Department of Surgery, Toyota Kosei Hospital, Toyota, Aichi, Japan
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Toyoshima O, Nishizawa T, Yoshida S, Arano T, Watanabe H, Mizutani H, Yamada T, Takatori Y, Ebinuma H, Saito Y. Characteristics of Clinically Significant Hyperplastic Polyps: Distinctions Between Microvesicular and Goblet Cell-Rich Types. J Gastroenterol Hepatol 2025; 40:1182-1187. [PMID: 40025862 DOI: 10.1111/jgh.16921] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/23/2024] [Revised: 01/07/2025] [Accepted: 02/14/2025] [Indexed: 03/04/2025]
Abstract
BACKGROUND Clinically significant serrated polyps (CSSPs) are defined as sessile serrated lesions (SSLs), SSLs with dysplasia, traditional serrated adenomas (TSAs), hyperplastic polyps (HPs) ≥ 10 mm, and HPs ≥ 6 mm in the proximal colon. HPs are further classified as microvesicular HPs (MVHPs) and goblet cell-rich HPs (GCHPs). Among CSSPs, HPs were categorized into clinically significant MVHPs (CS-MVHPs) and clinically significant GCHPs (CS-GCHPs). This study compares the characteristics of CS-MVHPs, CS-GCHPs, and SSLs. METHODS This study included patients who underwent colonoscopy at the Toyoshima Endoscopy Clinic between March 2021 and April 2024. Lesions diagnosed as adenomas or CSSPs were removed. Age, sex, number of polyps, detection rate, and polyp size were compared among CS-MVHPs, CS-GCHPs, and SSLs. RESULTS In total, 14 065 patients were enrolled. The detection rates for CS-MVHPs, CS-GCHPs, and SSLs were 5.24%, 1.22%, and 6.36%, respectively. Patients with CS-MVHPs or SSLs were significantly younger and more often female than those with CS-GCHPs. The mean sizes of CS-MVHPs and SSLs were significantly larger than that of CS-GCHPs. The detection rate of CS-GCHPs increased with age, whereas the detection rates of CS-MVHPs and SSLs did not show a similar trend. CONCLUSIONS Compared with CS-GCHPs, CS-MVHPs were larger, more frequent, and more likely to be found in younger patients and females. The characteristics of CS-MVHPs are similar to those of SSLs, supporting the hypothesis that CS-MVHPs are precursors of SSLs.
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Affiliation(s)
| | - Toshihiro Nishizawa
- Gastroenterology, Toyoshima Endoscopy Clinic, Tokyo, Japan
- Department of Gastroenterology and Hepatology, International University of Health and Welfare Narita Hospital, Chiba, Japan
| | | | - Toru Arano
- Gastroenterology, Toyoshima Endoscopy Clinic, Tokyo, Japan
- Department of Gastroenterology, The University of Tokyo, Tokyo, Japan
| | | | - Hiroya Mizutani
- Gastroenterology, Toyoshima Endoscopy Clinic, Tokyo, Japan
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Tomoharu Yamada
- Gastroenterology, Toyoshima Endoscopy Clinic, Tokyo, Japan
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Yusaku Takatori
- Division of Research and Development for Minimally Invasive Treatment, Cancer Center, Keio University School of Medicine, Tokyo, Japan
| | - Hirotoshi Ebinuma
- Department of Gastroenterology and Hepatology, International University of Health and Welfare Narita Hospital, Chiba, Japan
| | - Yutaka Saito
- Endoscopy Division, National Cancer Center Hospital, Tokyo, Japan
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Sundar R, Nakayama I, Markar SR, Shitara K, van Laarhoven HWM, Janjigian YY, Smyth EC. Gastric cancer. Lancet 2025:S0140-6736(25)00052-2. [PMID: 40319897 DOI: 10.1016/s0140-6736(25)00052-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/20/2024] [Revised: 11/13/2024] [Accepted: 01/09/2025] [Indexed: 05/07/2025]
Abstract
Gastric cancer remains a major health challenge worldwide, with nearly 1 million new cases annually contributing to more than 650 000 deaths. Epidemiologically, gastric cancer shows substantial geographical variation in incidence, with higher rates in Asia, South America, and eastern Europe, and a rapid increase in early-onset cases among people younger than 50 years. Key risk factors for gastric cancer include Helicobacter pylori infection, diet, obesity, smoking, and genetic predisposition. Early detection through comprehensive diagnostic procedures is crucial for optimising treatment outcomes. Standard treatment approaches for locally advanced gastric cancer include surgical resection, particularly D2 lymphadenectomy, complemented by chemotherapy and radiotherapy. There is increasing implementation of minimally invasive surgical techniques for operable disease and integration of immune checkpoint inhibitors and targeted therapies for advanced stages. Emerging therapies, such as novel targeted treatments and next-generation immunotherapies, show promise in improving survival and quality of life. Future directions in the management of gastric cancer focus on precision medicine, continued advancement in immunotherapy, novel early detection methods, and a multidisciplinary approach to care. These strategies aim to enhance the overall effectiveness of treatment and prognosis worldwide.
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Affiliation(s)
- Raghav Sundar
- Department of Medicine, Section of Medical Oncology, Yale School of Medicine, New Haven, CT, USA; Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Department of Haematology-Oncology, National University Cancer Institute, Singapore
| | - Izuma Nakayama
- Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan
| | - Sheraz R Markar
- Surgical Intervention Trials Unit, Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK
| | - Kohei Shitara
- Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan
| | - Hanneke W M van Laarhoven
- Cancer Center Amsterdam, Imaging and Biomarkers, Amsterdam, Netherlands; Department of Medical Oncology, Amsterdam UMC Location University of Amsterdam, Amsterdam, Netherlands
| | - Yelena Y Janjigian
- Department of Medicine, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY, USA
| | - Elizabeth C Smyth
- Oxford NIHR Biomedical Research Centre, Churchill Hospital, Oxford, UK.
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Hanevelt J, Brohet RM, Moons LMG, Laclé MM, Vleggaar FP, van Westreenen HL, de Vos Tot Nederveen Cappel WH. Risk of Lymph Node Metastasis in T2 Colon Cancer: A Nationwide Population-Based Cohort Study. Ann Surg Oncol 2025; 32:3078-3088. [PMID: 39847281 DOI: 10.1245/s10434-025-16921-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2024] [Accepted: 01/04/2025] [Indexed: 01/24/2025]
Abstract
BACKGROUND Similar to T1 colon cancer (CC), risk stratification may guide T2 CC treatment and reduce unnecessary major surgery. In this study, prediction models were developed that could identify T2 CC patients with a lower risk of lymph node metastasis (LNM) for whom (intensive) follow-up after local treatment could be considered. METHODS A nationwide cohort study was performed involving pT2 CC patients who underwent surgery between 2012 and 2020, using data from the Dutch ColoRectal Audit, which were linked to the Nationwide Pathology Databank. Four machine learning models were evaluated to predict LNM. RESULTS LNMs were found in 1877/9803 patients (19.1%). Independent risk factors included (younger) age (odds ratio [OR] 0.98, 95% confidence interval [CI] 0.979-0.990), left-sided CC (OR 1.5, 95% CI 1.4-1.7), poor differentiation (OR 1.7, 95% CI 1.4-2.2), and lymphovascular invasion (LVI; OR 4.1, 95% CI 3.6-4.7). A deficient mismatch repair (MMR) status significantly lowered the risk of LNM (OR 0.3, 95% CI 0.2-0.5). The general linear model demonstrated the highest prediction accuracy, achieving area under the receiver operating characteristic curves of 0.67 and 0.68, with good calibration. In the absence of risk factors, elderly patients (≥74 years of age) had a predicted risk of LNM of 10.7%, yet up to 30% experienced postoperative complications, with mortality rates reaching up to 3.5%. Patients with a deficient MMR status had a predicted risk of LNM of 6.1% if LVI was absent and the tumor was well-differentiated. CONCLUSIONS The risk of LNM should be weighed against surgical risks. The findings of this study will enable clinicians to make more deliberate considerations about these competing risks before making a shared decision.
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Affiliation(s)
- Julia Hanevelt
- Department of Gastroenterology and Hepatology, Isala, Zwolle, The Netherlands.
| | - Richard M Brohet
- Department of Epidemiology and Statistics, Isala, Zwolle, The Netherlands
| | - Leon M G Moons
- Department of Gastroenterology and Hepatology, University Medical Center Utrecht (UMCU), Utrecht, The Netherlands
| | - Miangela M Laclé
- Department of Pathology, University Medical Center Utrecht (UMCU), Utrecht, The Netherlands
| | - Frank P Vleggaar
- Department of Gastroenterology and Hepatology, University Medical Center Utrecht (UMCU), Utrecht, The Netherlands
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Li Q, Chang X, Gu J, Yang Y, Ouyang J, Zhou Y, Zhao H, Zhou J. Adjuvant Transarterial Chemoembolization in Resected Macrotrabecular-massive Hepatocellular Carcinoma (ATAC-MACRO): A Multicenter Real-world Retrospective Study. Acad Radiol 2025; 32:2585-2595. [PMID: 39848885 DOI: 10.1016/j.acra.2024.12.053] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2024] [Revised: 12/08/2024] [Accepted: 12/22/2024] [Indexed: 01/25/2025]
Abstract
RATIONALE AND OBJECTIVES The purpose of this study was to demonstrate the impact of postoperative adjuvant transarterial chemoembolization (TACE) on the prognosis of patients with macrotrabecular-massive hepatocellular carcinoma (MTM-HCC). MATERIALS AND METHODS This retrospective study used the clinical records of patients with resected MTM-HCC with/without adjuvant TACE at three centers between January 2015 and December 2022. The primary end point was recurrence free survival (RFS). The secondary end points were overall survival (OS) and safety. RESULTS A total of 559 eligible patients were classified into the adjuvant TACE group and the observation group. After propensity score matching analysis, both RFS (HR 0.62 [95% CI, 0.48 to 0.80]; P < 0.001) and OS (HR 0.59 [95% CI, 0.42 to 0.84]; P = 0.013) in the adjuvant TACE group were significantly better than the observation group. By Cox regression models, mALBI grade, types of hepatectomy, number, satellite lesion, without adjuvant TACE were identified as independent risk factors for RFS, and mALBI grade, number, maximum tumor size, satellite lesion, microvascular invasion, high AFP level, without adjuvant TACE were identified as independent risk factors for OS. The incidence of surgery-related adverse events (AEs) had no significant difference between the two groups (P = 0.609). The majority of AEs associated with adjuvant TACE were grade I (84.4%), and no treatment-related deaths occurred in either group. CONCLUSIONS Adjuvant TACE significantly improved the RFS and OS of patients with resected MTM-HCC with acceptable toxicity.
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Affiliation(s)
- Qingjun Li
- Department of Hepatobiliary and Pancreatic Surgery, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, Henan, China (Q.L., J.O., Y.Z., J.Z.)
| | - Xu Chang
- Department of Interventional Therapy II, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China (X.C.)
| | - Jiaye Gu
- School of Ophthalmology & Optometry, Wenzhou Medical University, Wenzhou, Zhejiang, China (J.G.)
| | - Yi Yang
- Department of Liver Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China (Y.Y., H.Z.)
| | - Jingzhong Ouyang
- Department of Hepatobiliary and Pancreatic Surgery, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, Henan, China (Q.L., J.O., Y.Z., J.Z.)
| | - Yanzhao Zhou
- Department of Hepatobiliary and Pancreatic Surgery, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, Henan, China (Q.L., J.O., Y.Z., J.Z.)
| | - Hong Zhao
- Department of Liver Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China (Y.Y., H.Z.)
| | - Jinxue Zhou
- Department of Hepatobiliary and Pancreatic Surgery, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, Henan, China (Q.L., J.O., Y.Z., J.Z.).
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Ferrante ND, Hubbard RA, Weinfurtner K, Mezina AI, Newcomb CW, Furth EE, Bhattacharya D, Njei B, Taddei TH, Singal A, Hoteit MA, Park LS, Kaplan D, Lo Re V. Validity of Diagnostic Codes and Laboratory Tests to Identify Cholangiocarcinoma and Its Subtypes. Pharmacoepidemiol Drug Saf 2025; 34:e70154. [PMID: 40328444 PMCID: PMC12055315 DOI: 10.1002/pds.70154] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2025] [Revised: 03/13/2025] [Accepted: 04/04/2025] [Indexed: 05/08/2025]
Abstract
BACKGROUND The absence of validated methods to identify cholangiocarcinoma in real-world data has prevented the conduct of pharmacoepidemiologic studies to evaluate determinants of this malignancy and examine the effectiveness of cholangiocarcinoma treatments. OBJECTIVE To determine the accuracy of International Classification of Diseases for Oncology, Third Edition (ICD-O-3)-based algorithms to identify cholangiocarcinoma and its subtype (intrahepatic or extrahepatic) within US Veterans Health Administration (VA) data. METHODS We identified patients with cholangiocarcinoma ICD-O-3 diagnosis codes from January 2000-December 2019 in VA data. We developed eight algorithms utilizing ICD-O-3 histology codes for cholangiocarcinoma and further used ICD-O-3 topography codes for location (liver, intrahepatic bile duct, extrahepatic bile duct) plus maximum total bilirubin (≥ 3 mg/dL vs. < 3 mg/dL) within ± 45 days of diagnosis to identify cholangiocarcinoma subtype. Up to 80 patients were randomly selected for each algorithm, and their records were reviewed by two hepatologists. The positive predictive values (PPV) and 95% confidence interval (CI) for each algorithm were estimated. RESULTS Among 2934 unique patients who met inclusion criteria, 574 were randomly selected for validation. All eight algorithms had high PPV for definite or probable cholangiocarcinoma, ranging from 83.8% (95% CI, 73.8%-91.1%) to 100.0% (95% CI, 95.5%-100.0%). Among three algorithms to identify intrahepatic cholangiocarcinoma, two had PPV ≥ 80% (range: 88.8% [95% CI, 79.7%-94.7%]-91.3% [95% CI, 82.8%-96.4%]). Among five algorithms to identify extrahepatic cholangiocarcinoma, four had PPV ≥ 80% (range: 80.0% [95% CI, 69.6%-88.1%]-94.0% [83.5%-98.7%]). CONCLUSION These algorithms can be used in future pharmacoepidemiologic studies to evaluate medications associated with intrahepatic or extrahepatic cholangiocarcinoma.
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Affiliation(s)
- Nicole D. Ferrante
- Division of Gastroenterology and Hepatology, Perelman School of MedicineUniversity of PennsylvaniaPhiladelphiaPennsylvaniaUSA
- Center for Real‐World Effectiveness and Safety of Therapeutics, Center for Clinical Epidemiology and Biostatistics, Department of Biostatistics, Epidemiology, and Informatics, Perelman School of MedicineUniversity of PennsylvaniaPhiladelphiaPennsylvaniaUSA
| | - Rebecca A. Hubbard
- Center for Real‐World Effectiveness and Safety of Therapeutics, Center for Clinical Epidemiology and Biostatistics, Department of Biostatistics, Epidemiology, and Informatics, Perelman School of MedicineUniversity of PennsylvaniaPhiladelphiaPennsylvaniaUSA
| | - Kelley Weinfurtner
- Division of Gastroenterology and Hepatology, Perelman School of MedicineUniversity of PennsylvaniaPhiladelphiaPennsylvaniaUSA
| | - Anya I. Mezina
- Division of Gastroenterology and Hepatology, Perelman School of MedicineUniversity of PennsylvaniaPhiladelphiaPennsylvaniaUSA
| | - Craig W. Newcomb
- Center for Real‐World Effectiveness and Safety of Therapeutics, Center for Clinical Epidemiology and Biostatistics, Department of Biostatistics, Epidemiology, and Informatics, Perelman School of MedicineUniversity of PennsylvaniaPhiladelphiaPennsylvaniaUSA
| | - Emma E. Furth
- Division of Pathology, Department of Medicine, Perelman School of MedicineUniversity of PennsylvaniaPhiladelphiaPennsylvaniaUSA
| | - Debika Bhattacharya
- Department of Medicine, Division of Infectious Diseases, David Geffen School of MedicineUniversity of CaliforniaLos AngelesCaliforniaUSA
| | - Basile Njei
- Yale School of MedicineYale Center for Clinical InvestigationNew HavenConnecticutUSA
| | - Tamar H. Taddei
- VA Connecticut Health SystemWest HavenConnecticutUSA
- Department of MedicineYale University School of MedicineNew HavenConnecticutUSA
| | - Amit Singal
- Division of Digestive and Liver DiseasesUT Southwestern Medical CenterDallasTexasUSA
| | - Maarouf A. Hoteit
- Division of Gastroenterology and Hepatology, Perelman School of MedicineUniversity of PennsylvaniaPhiladelphiaPennsylvaniaUSA
| | - Lesley S. Park
- VA Connecticut Health SystemWest HavenConnecticutUSA
- Stanford Department of Epidemiology and Population HealthStanford University School of MedicinePalo AltoCaliforniaUSA
| | - David Kaplan
- Division of Gastroenterology and Hepatology, Perelman School of MedicineUniversity of PennsylvaniaPhiladelphiaPennsylvaniaUSA
- Department of MedicineCorporal Michael J. Crescenz VA Medical CenterPhiladelphiaPennsylvaniaUSA
| | - Vincent Lo Re
- Center for Real‐World Effectiveness and Safety of Therapeutics, Center for Clinical Epidemiology and Biostatistics, Department of Biostatistics, Epidemiology, and Informatics, Perelman School of MedicineUniversity of PennsylvaniaPhiladelphiaPennsylvaniaUSA
- Division of Infectious Diseases, Department of Medicine, Perelman School of MedicineUniversity of PennsylvaniaPhiladelphiaPennsylvaniaUSA
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Tran M, Wagner S, Weichert W, Matek C, Boxberg M, Peng T. Navigating Through Whole Slide Images With Hierarchy, Multi-Object, and Multi-Scale Data. IEEE TRANSACTIONS ON MEDICAL IMAGING 2025; 44:2002-2015. [PMID: 40031287 DOI: 10.1109/tmi.2025.3532728] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 03/05/2025]
Abstract
Building deep learning models that can rapidly segment whole slide images (WSIs) using only a handful of training samples remains an open challenge in computational pathology. The difficulty lies in the histological images themselves: many morphological structures within a slide are closely related and very similar in appearance, making it difficult to distinguish between them. However, a skilled pathologist can quickly identify the relevant phenotypes. Through years of training, they have learned to organize visual features into a hierarchical taxonomy (e.g., identifying carcinoma versus healthy tissue, or distinguishing regions within a tumor as cancer cells, the microenvironment, …). Thus, each region is associated with multiple labels representing different tissue types. Pathologists typically deal with this by analyzing the specimen at multiple scales and comparing visual features between different magnifications. Inspired by this multi-scale diagnostic workflow, we introduce the Navigator, a vision model that navigates through WSIs like a domain expert: it searches for the region of interest at a low scale, zooms in gradually, and localizes ever finer microanatomical classes. As a result, the Navigator can detect coarse-grained patterns at lower resolution and fine-grained features at higher resolution. In addition, to deal with sparsely annotated samples, we train the Navigator with a novel semi-supervised framework called S5CL v2. The proposed model improves the F1 score by up to 8% on various datasets including our challenging new TCGA-COAD-30CLS and Erlangen cohorts.
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Zhao W, Li T, Wang P, Zhang R, Gao F, Ma Z, Zhen S, Liu F, Chu Y. Development and validation of a relatively accurate gastric cancer high-risk group screening scoring system in urban residents. Clin Transl Oncol 2025; 27:2269-2280. [PMID: 39377973 DOI: 10.1007/s12094-024-03748-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2024] [Accepted: 09/25/2024] [Indexed: 11/29/2024]
Abstract
PURPOSE Our study aimed to develop a relatively accurate gastric cancer (GC) screening score system for urban residents and to validate the screening efficacy. METHODS The present study included a derivation cohort (n = 3406) and a validation cohort (n = 868) of urban residents. Applying the full-stack engineering intelligent system platform of Hualian Health Big Data of Shandong University, the clinical physical examination data of subjects were collected. Univariate and multivariate analyses were used to identify risk factors for GC, and subsequently, an optimal prediction rule was established to create three distinct scoring systems. RESULTS In the GC-risk scoring system I, age, plateletocrit (PCT), carcinoembryonic antigen (CEA), glucose, albumin, creatinine were independent risk factors of GC, with scores ranging from 0 to 28 and optimal cut-off was 15.5. The second scoring system consisted of age, PCT, RDW-CV, CEA, glucose, albumin, and creatinine, with scores ranging from 0 to 31. The optimal cut-off point was determined to be 15.5. The scoring system III comprise of age, sex, PCT, RDW CV, CEA, glucose, with scores ranging from 0 to 21 and optimal cut-off was 10.5. All three scoring systems demonstrated excellent discrimination for GC, achieving an AUC of 0.884, 0.89, and 0.876, respectively. In external validation, the AUC values were 0.654, 0.658, and 0.714. Notably, the GC-risk scoring system III exhibited the highest screening efficiency. CONCLUSIONS Urban residents benefited from the effective and verified GC-risk scoring systems, which demonstrated excellent performance in identifying individuals with an elevated risk of GC.
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Affiliation(s)
- Weipeng Zhao
- Department of Gastroenterology, Weihai Municipal Hospital, Cheeloo College of Medicine, Shandong University, Weihai, China
- Department of Gastroenterology, Heze Municipal Hospital, Heze, China
| | - Tian Li
- Department of Gastroenterology, Weihai Municipal Hospital, Cheeloo College of Medicine, Shandong University, Weihai, China
| | - Ping Wang
- Department of Gastroenterology, Weihai Municipal Hospital, Cheeloo College of Medicine, Shandong University, Weihai, China
| | - Rui Zhang
- Department of Gastroenterology, Weihai Municipal Hospital, Cheeloo College of Medicine, Shandong University, Weihai, China
| | - Fan Gao
- Department of Gastroenterology, Weihai Municipal Hospital, Cheeloo College of Medicine, Shandong University, Weihai, China
| | | | | | - Feng Liu
- Department of Gastroenterology, Weihai Municipal Hospital, Cheeloo College of Medicine, Shandong University, Weihai, China
| | - Yanliu Chu
- Department of Gastroenterology, Weihai Municipal Hospital, Cheeloo College of Medicine, Shandong University, Weihai, China.
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46
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Chen W, Lin G, Li X, Feng Y, Mao W, Kong C, Hu Y, Gao Y, Yang W, Chen M, Yan Z, Xia S, Lu C, Xu M, Ji J. Dual-energy computed tomography for predicting histological grading and survival in patients with pancreatic ductal adenocarcinoma. Eur Radiol 2025; 35:2818-2832. [PMID: 39414655 DOI: 10.1007/s00330-024-11109-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2024] [Revised: 08/07/2024] [Accepted: 09/24/2024] [Indexed: 10/18/2024]
Abstract
OBJECTIVES We evaluated the value of dual-energy computed tomography (DECT) parameters derived from pancreatic ductal adenocarcinoma (PDAC) to discriminate between high- and low-grade tumors and predict overall survival (OS) in patients. METHODS Data were retrospectively collected from 169 consecutive patients with pathologically confirmed PDAC who underwent third-generation dual-source DECT enhanced dual-phase scanning before surgery between January 2017 and March 2023. Patients with prior treatments, other malignancies, small tumors, or poor-quality scans were excluded. Two radiologists evaluated three clinical and seven radiological features and measured sixteen DECT-derived parameters. Univariate and multivariate analyses were applied to select independent predictors. A prediction model and a corresponding nomogram were developed, and the area under the curve (AUC), calibration, and clinical applicability were assessed. The correlations between factors and OS were evaluated using Kaplan-Meier survival and Cox regression analyses. RESULTS One hundred sixty-nine patients were randomly divided into training (n = 118) and validation (n = 51) cohorts, among which 43 (36.4%) and 19 (37.3%) had high-grade PDAC confirmed by pathology, respectively. The vascular invasion, normalized iodine concentration in the venous phase, and effective atomic number in the venous phase were independent predictors for histological grading. A nomogram was constructed to predict the risk of high-grade tumors in PDAC, with AUCs of 0.887 and 0.844 in the training and validation cohorts, respectively. The nomogram exhibited good calibration and was more beneficial than a single parameter in both cohorts. Pathological- and nomoscore-predicted high-grade PDACs were associated with poor OS (all p < 0.05). CONCLUSIONS The nomogram, which combines DECT parameters and radiological features, can predict the histological grade and OS in patients with PDAC before surgery. KEY POINTS Question Preoperative determination of histological grade in PDAC is crucial for guiding treatment, yet current methods are invasive and limited. Findings A DECT-based nomogram combining vascular invasion, normalized iodine concentration, and effective atomic number accurately predicts histological grade and OS in PDAC patients. Clinical relevance The DECT-based nomogram is a reliable, non-invasive tool for predicting histological grade and OS in PDAC. It provides essential information to guide personalized treatment strategies, potentially improving patient management and outcomes.
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Affiliation(s)
- Weiyue Chen
- Zhejiang Key Laboratory of Imaging and Interventional Medicine, Zhejiang Engineering Research Center of Interventional Medicine Engineering and Biotechnology, Key Laboratory of Precision Medicine of Lishui City, The Fifth Affiliated Hospital of Wenzhou Medical University, Lishui, China
- Clinical College of The Affiliated Central Hospital, School of Medicine, Lishui University, Lishui, China
| | - Guihan Lin
- Zhejiang Key Laboratory of Imaging and Interventional Medicine, Zhejiang Engineering Research Center of Interventional Medicine Engineering and Biotechnology, Key Laboratory of Precision Medicine of Lishui City, The Fifth Affiliated Hospital of Wenzhou Medical University, Lishui, China
- Clinical College of The Affiliated Central Hospital, School of Medicine, Lishui University, Lishui, China
| | - Xia Li
- Zhejiang Key Laboratory of Imaging and Interventional Medicine, Zhejiang Engineering Research Center of Interventional Medicine Engineering and Biotechnology, Key Laboratory of Precision Medicine of Lishui City, The Fifth Affiliated Hospital of Wenzhou Medical University, Lishui, China
- Clinical College of The Affiliated Central Hospital, School of Medicine, Lishui University, Lishui, China
| | - Ye Feng
- Zhejiang Key Laboratory of Imaging and Interventional Medicine, Zhejiang Engineering Research Center of Interventional Medicine Engineering and Biotechnology, Key Laboratory of Precision Medicine of Lishui City, The Fifth Affiliated Hospital of Wenzhou Medical University, Lishui, China
- Clinical College of The Affiliated Central Hospital, School of Medicine, Lishui University, Lishui, China
| | - Weibo Mao
- Department of Pathology, The Fifth Affiliated Hospital of Wenzhou Medical University, Lishui, China
| | - Chunli Kong
- Zhejiang Key Laboratory of Imaging and Interventional Medicine, Zhejiang Engineering Research Center of Interventional Medicine Engineering and Biotechnology, Key Laboratory of Precision Medicine of Lishui City, The Fifth Affiliated Hospital of Wenzhou Medical University, Lishui, China
- Clinical College of The Affiliated Central Hospital, School of Medicine, Lishui University, Lishui, China
| | - Yumin Hu
- Zhejiang Key Laboratory of Imaging and Interventional Medicine, Zhejiang Engineering Research Center of Interventional Medicine Engineering and Biotechnology, Key Laboratory of Precision Medicine of Lishui City, The Fifth Affiliated Hospital of Wenzhou Medical University, Lishui, China
- Clinical College of The Affiliated Central Hospital, School of Medicine, Lishui University, Lishui, China
| | - Yang Gao
- Zhejiang Key Laboratory of Imaging and Interventional Medicine, Zhejiang Engineering Research Center of Interventional Medicine Engineering and Biotechnology, Key Laboratory of Precision Medicine of Lishui City, The Fifth Affiliated Hospital of Wenzhou Medical University, Lishui, China
- Clinical College of The Affiliated Central Hospital, School of Medicine, Lishui University, Lishui, China
| | - Weibin Yang
- Zhejiang Key Laboratory of Imaging and Interventional Medicine, Zhejiang Engineering Research Center of Interventional Medicine Engineering and Biotechnology, Key Laboratory of Precision Medicine of Lishui City, The Fifth Affiliated Hospital of Wenzhou Medical University, Lishui, China
- Clinical College of The Affiliated Central Hospital, School of Medicine, Lishui University, Lishui, China
| | - Minjiang Chen
- Zhejiang Key Laboratory of Imaging and Interventional Medicine, Zhejiang Engineering Research Center of Interventional Medicine Engineering and Biotechnology, Key Laboratory of Precision Medicine of Lishui City, The Fifth Affiliated Hospital of Wenzhou Medical University, Lishui, China
- Clinical College of The Affiliated Central Hospital, School of Medicine, Lishui University, Lishui, China
| | - Zhihan Yan
- Wenzhou Key Laboratory of Structural and Functional Imaging, Wenzhou, China
| | - Shuiwei Xia
- Zhejiang Key Laboratory of Imaging and Interventional Medicine, Zhejiang Engineering Research Center of Interventional Medicine Engineering and Biotechnology, Key Laboratory of Precision Medicine of Lishui City, The Fifth Affiliated Hospital of Wenzhou Medical University, Lishui, China
- Clinical College of The Affiliated Central Hospital, School of Medicine, Lishui University, Lishui, China
| | - Chenying Lu
- Zhejiang Key Laboratory of Imaging and Interventional Medicine, Zhejiang Engineering Research Center of Interventional Medicine Engineering and Biotechnology, Key Laboratory of Precision Medicine of Lishui City, The Fifth Affiliated Hospital of Wenzhou Medical University, Lishui, China
- Clinical College of The Affiliated Central Hospital, School of Medicine, Lishui University, Lishui, China
| | - Min Xu
- Zhejiang Key Laboratory of Imaging and Interventional Medicine, Zhejiang Engineering Research Center of Interventional Medicine Engineering and Biotechnology, Key Laboratory of Precision Medicine of Lishui City, The Fifth Affiliated Hospital of Wenzhou Medical University, Lishui, China
- Clinical College of The Affiliated Central Hospital, School of Medicine, Lishui University, Lishui, China
| | - Jiansong Ji
- Zhejiang Key Laboratory of Imaging and Interventional Medicine, Zhejiang Engineering Research Center of Interventional Medicine Engineering and Biotechnology, Key Laboratory of Precision Medicine of Lishui City, The Fifth Affiliated Hospital of Wenzhou Medical University, Lishui, China.
- Clinical College of The Affiliated Central Hospital, School of Medicine, Lishui University, Lishui, China.
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Huang C, Liu J. Well-differentiated Adenocarcinoma Arising from Gastric Cystica Profunda Treated by Endoscopic Submucosal Dissection: A case report and literature review. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2025; 63:497-501. [PMID: 39965649 DOI: 10.1055/a-1920-4161] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/20/2025]
Abstract
Gastritis cystica profunda (GCP) is a rare disease that is often observed at the stoma site of patients undergoing gastric surgery. Specific symptoms are often lacking, making it difficult to diagnose. GCP may develop into cancer. Endoscopic resection is a good method to reduce surgical injury, and the therapeutic effect depends on the status of the primary disease.The patient was a 77-year-old male who was admitted to the hospital for repeated epigastric distention. The man had never undergone gastric surgery and did not have Helicobacter pylori infection. Physical and laboratory tests showed no abnormality. Computed tomography showed no significant abnormality. Endoscopy revealed multiple ulcers on the posterior wall of the gastric body, but biopsy showed no evidence of malignancy. The patient subsequently underwent ESD surgery with a lesion of 1.5 cm×2.3 cm. Pathological results showed the cystic dilatation of gastric glands in the submucosa, with some well-differentiated adenocarcinoma. The final diagnosis was GCP with well-differentiated gastric adenocarcinoma.Herein, we describe a case of ESD therapy for GCP with well-differentiated gastric adenocarcinoma. When gastric mucosal lesions are difficult to diagnose, further treatment and diagnosis with EMR or ESD can be considered. For patients with early gastric cancer, long-term postoperative monitoring should be carried out.
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Affiliation(s)
- Cao Huang
- Gastroenterology, Huzhou Central Hospital, Huzhou, China
| | - Jiang Liu
- Huzhou Central Hospital, Huzhou, China
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48
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Fujiki Y, Ishikawa A, Katsuya N, Shiwa Y, Fukui T, Kuraoka K, Sudo T, Tazuma S, Ishii Y, Oka S, Yasui W, Mii S. Minichromosome maintenance 4 is associated with poor survival and stemness of patients with pancreatic cancer. Med Mol Morphol 2025:10.1007/s00795-025-00438-y. [PMID: 40293517 DOI: 10.1007/s00795-025-00438-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2025] [Accepted: 04/16/2025] [Indexed: 04/30/2025]
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is one of the most well-known cancer types, with a persistently poor 5-year survival rate. We previously reported MCM4 as a molecule associated with cancer stem cells; however, its role in PDAC has not been reported. Therefore, in this study, we aimed to fill this gap in the literature. We analyzed MCM4 expression in 81 PDAC samples using immunohistochemistry (IHC). The functional role of MCM4 in PDAC was investigated using RNA interference in PDAC cell lines. Additionally, a single-cell analysis was conducted by downloading data from six PDAC cases. On IHC, high MCM4 expression was observed in 42 out of 81 (51.9%) PDAC cases. MCM4-positive PDAC was significantly associated with a higher pN grade. Furthermore, high MCM4 expression was linked to a significantly poorer prognosis and was identified as an independent prognostic factor in multivariate analysis. In PDAC cell lines, MCM4 knockdown impairs cell growth and spheroid formation. Single-cell analysis also revealed that MCM4-expressing cells were located upstream of the trajectory, with a cluster showing a correlation with KIFC1, which has been reported to be associated with cancer stemness. These results indicated the significance of MCM4 expression in PDAC and its association with cancer stemness.
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Affiliation(s)
- Yuto Fujiki
- Department of Molecular Pathology, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
| | - Akira Ishikawa
- Department of Molecular Pathology, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.
| | - Narutaka Katsuya
- Department of Molecular Pathology, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
| | - Yuki Shiwa
- Department of Molecular Pathology, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
| | - Takafumi Fukui
- Department of Molecular Pathology, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
| | - Kazuya Kuraoka
- Department of Diagnostic Pathology, National Hospital Organization (NHO), Kure Medical Center, and Chugoku Cancer Center, 3-1 Aoyama, Kure, 737-0023, Japan
| | - Takeshi Sudo
- Department of Surgery, National Hospital Organization (NHO), Kure Medical Center, and Chugoku Cancer Center, 3-1 Aoyama, Kure, 737-0023, Japan
| | - Sho Tazuma
- Department of Surgery, National Hospital Organization (NHO), Kure Medical Center, and Chugoku Cancer Center, 3-1 Aoyama, Kure, 737-0023, Japan
| | - Yasutaka Ishii
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
| | - Shiro Oka
- Department of Gastroenterology, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
| | - Wataru Yasui
- Department of Molecular Pathology, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
- Division of Pathology, Hiroshima City Medical Association Clinical Laboratory, 3 Chome-8-6 Sendamachi, Naka-ku, Hiroshima, 730-8611, Japan
| | - Shinji Mii
- Department of Molecular Pathology, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
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49
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Wu GZ, Lu LN, Lin HP, Wang XY, Yu SA, Yu M. Laparoscopic management of intraductal oncocytic papillary neoplasm of the pancreas: Two case reports and review of literature. World J Gastrointest Surg 2025; 17:105096. [PMID: 40291896 PMCID: PMC12019044 DOI: 10.4240/wjgs.v17.i4.105096] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/13/2025] [Revised: 02/04/2025] [Accepted: 03/03/2025] [Indexed: 03/29/2025] Open
Abstract
BACKGROUND Intraductal oncocytic papillary neoplasm (IOPN) of the pancreas is an extremely rare pancreatic tumor, with only sporadic cases reported in the literature. IOPN is difficult to diagnose and highly prone to misdiagnosis. IOPN carries a certain risk of progressing to invasive cancer. Surgical resection is the primary treatment for IOPN. According to the existing literature reports, the vast majority of patients with IOPN of the pancreas undergo open surgery, while only one case of laparoscopic surgery have been reported. CASE SUMMARY This report presents two cases of IOPN in elderly female patients, aged 60 and 61. Both patients were asymptomatic, and their pancreatic masses were discovered incidentally. Preoperative diagnosis of IOPN is challenging and prone to misdiagnosis. In the first case, the patient underwent a laparoscopic distal pancreatectomy and splenectomy. The surgical procedure spanned 342 minutes, with an estimated intraoperative blood loss of around 100 mL. The patient experienced an uneventful postoperative recovery and was discharged on the 8th postoperative day. For the second case, a laparoscopic pancreaticoduodenectomy was performed. The operation lasted for 431 minutes with an intraoperative blood loss of approximately 50 mL. The patient also demonstrated a favorable postoperative course and was discharged on the 24th postoperative day. Postoperative pathology and immunohistochemistry confirmed the diagnosis of IOPN. No recurrence was observed in either patient after follow-up periods of 8 and 10 months, respectively. CONCLUSION These cases demonstrate that laparoscopic surgery can be considered as one of the treatment options for IOPN of the pancreas.
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Affiliation(s)
- Guo-Zhen Wu
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua 321000, Zhejiang Province, China
| | - Li-Na Lu
- Department of Gastroenterology, Wenrong Hospital of Jinhua City, Jinhua 321000, Zhejiang Province, China
| | - Hai-Ping Lin
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua 321000, Zhejiang Province, China
| | - Xin-Yu Wang
- Department of Radiology, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua 321000, Zhejiang Province, China
| | - Shi-An Yu
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua 321000, Zhejiang Province, China
| | - Min Yu
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua 321000, Zhejiang Province, China
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50
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Watanabe H, Fujishima F, Yamazaki Y, Imamura M, Hijioka S, Hara K, Kuwahara T, Yatabe Y, Sakamoto K, Shiga H, Kawaguchi T, Suzuki H, Kanbayashi Y, Ohkoshi A, Shimada M, Niikawa H, Sato M, Fujio A, Masui T, Kasai Y, Ota H, Ozawa H, Endo H, Unno M, Sasano H, Suzuki T. GLP- 1R status using validated monoclonal antibody in 689 cases of neuroendocrine neoplasm and its correlation with somatostatin receptor scintigraphy, insulin production, and histological grades. Virchows Arch 2025:10.1007/s00428-025-04098-2. [PMID: 40281248 DOI: 10.1007/s00428-025-04098-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2025] [Revised: 03/19/2025] [Accepted: 03/31/2025] [Indexed: 04/29/2025]
Abstract
Radiolabeled glucagon-like peptide 1 (GLP- 1) analog scintigraphy is a new, high-sensitivity imaging method for detecting small insulinomas. Somatostatin receptor scintigraphy (SRS) is an established method for detecting gastroenteropancreatic neuroendocrine tumors. However, small benign insulinomas are difficult to detect using SRS. Furthermore, GLP- 1 receptor (GLP- 1R) expression and SRS results may be inversely correlated. We identified 689 neuroendocrine neoplasms, including pancreatic neuroendocrine tumors (PanNETs) and neuroendocrine neoplasms originating from non-pancreatic sites, and performed GLP- 1R immunostaining. Among the non-insulinoma PanNETs, immunohistochemical insulin or proinsulin positive cases were categorized as Inspos, and both negative cases as Insneg. High prevalence of GLP- 1R expression was detected in PanNETs and duodenal NETs (34% and 53%, respectively). Some pulmonary NETs were GLP- 1R positive (9%). In contrast, neither GI-NEC excluding one case nor pulmonary NEC exhibited GLP- 1R expression. The percentage of GLP- 1R positive cases for Inspos, Insneg, and insulinoma was 31%, 0%, and 84%, respectively. Among PanNETs, GLP- 1R positive cases showed higher expression of insulin and proinsulin than negative cases. SRS-positive patients showed lower expression levels of insulin, proinsulin, and GLP- 1R than SRS-negative patients. The expression in PanNETs and duodenal NETs may be derived from the expression in their normal counterparts. Insulinoma and Inspos cases showed GLP- 1R expression. Furthermore, as GLP- 1R-positive patients showed significantly higher expression of insulin and proinsulin than GLP- 1R negative patients, GLP- 1R may also be associated with neoplastic insulin production and GLP- 1 analog scintigraphy may detect subclinical insulinomas. In addition, SRS-negative cases showed significantly higher GLP- 1R expression than SRS-positive cases. These results suggest the application potential of GLP- 1 analog scintigraphy in combination with SRS as a detection tool.
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Affiliation(s)
- Hirofumi Watanabe
- Department of Pathology, Tohoku University Hospital, 1 - 1 Seiryo-Machi, Aoba-Ku, Sendai, Miyagi, 980 - 8574, Japan
| | - Fumiyoshi Fujishima
- Department of Pathology, Tohoku University Hospital, 1 - 1 Seiryo-Machi, Aoba-Ku, Sendai, Miyagi, 980 - 8574, Japan.
| | - Yuto Yamazaki
- Department of Pathology, Tohoku University Hospital, 1 - 1 Seiryo-Machi, Aoba-Ku, Sendai, Miyagi, 980 - 8574, Japan
| | - Masayuki Imamura
- Department of Surgery, Kansai Electric Power Hospital, Osaka, Japan
| | - Susumu Hijioka
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center, Tokyo, Japan
| | - Kazuo Hara
- Department of Gastroenterology, Aichi Cancer Center Hospital, Aichi, Japan
| | - Takamichi Kuwahara
- Department of Gastroenterology, Aichi Cancer Center Hospital, Aichi, Japan
| | - Yasushi Yatabe
- Department of Pathology and Clinical Laboratories, National Cancer Center, Tokyo, Japan
| | | | - Hisashi Shiga
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Miyagi, Japan
| | | | - Hiroyoshi Suzuki
- Department of Diagnostic Pathology, South Miyagi Medical Center, Miyagi, Japan
| | - Yumi Kanbayashi
- Department of Dermatology, Tohoku University Graduate School of Medicine, Miyagi, Japan
| | - Akira Ohkoshi
- Department of Otorhinolaryngology, Head and Neck Surgery, Tohoku University Graduate School of Medicine, Miyagi, Japan
| | - Muneaki Shimada
- Department of Gynecology, Tohoku University Graduate School of Medicine, Miyagi, Japan
| | - Hiromichi Niikawa
- Department of Thoracic Surgery, Institute of Development, Aging and Cancer, Tohoku University, Miyagi, Japan
| | - Mami Sato
- Department of Breast and Endocrine Surgery, Tohoku University Hospital, Miyagi, Japan
| | - Atsushi Fujio
- Department of Surgery, Graduate School of Medicine, Tohoku University, Miyagi, Japan
| | - Toshihiko Masui
- Department of Surgery, Kyoto University Graduate School of Medicine, Kyoto, Japan
| | - Yosuke Kasai
- Department of Surgery, Kyoto University Graduate School of Medicine, Kyoto, Japan
| | - Hideki Ota
- Department of Diagnostic Radiology, Tohoku University Hospital, Miyagi, Japan
| | - Hiroshi Ozawa
- Department of Orthopaedic Surgery, Tohoku Medical and Pharmaceutical University, Miyagi, Japan
| | - Hidenori Endo
- Department of Neurosurgery, Tohoku University Graduate School of Medicine, Miyagi, Japan
| | - Michiaki Unno
- Department of Surgery, Graduate School of Medicine, Tohoku University, Miyagi, Japan
| | - Hironobu Sasano
- Department of Pathology, Tohoku University Hospital, 1 - 1 Seiryo-Machi, Aoba-Ku, Sendai, Miyagi, 980 - 8574, Japan
| | - Takashi Suzuki
- Department of Pathology, Tohoku University Hospital, 1 - 1 Seiryo-Machi, Aoba-Ku, Sendai, Miyagi, 980 - 8574, Japan
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