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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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Gujarathi R, Peshin S, Zhang X, Bachini M, Meeks MN, Shroff RT, Pillai A. Intrahepatic cholangiocarcinoma: Insights on molecular testing, targeted therapies, and future directions from a multidisciplinary panel. Hepatol Commun 2025; 9:e0743. [PMID: 40489757 DOI: 10.1097/hc9.0000000000000743] [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: 03/17/2025] [Accepted: 05/07/2025] [Indexed: 06/11/2025] Open
Abstract
Biliary tract cancers (BTCs) are a histologically and molecularly diverse group of malignancies arising from the gallbladder and the ductal epithelium of the biliary tree. Intrahepatic cholangiocarcinoma (iCCA) is the second most common primary liver malignancy in the United States. Surgical resection with negative margins is the only recognized curative treatment option for iCCA; however, most patients will present with advanced or unresectable disease. The clinical presentation is largely non-specific, with the characteristic symptoms of biliary malignancies being less frequent than extrahepatic cholangiocarcinoma. Clinical management in iCCA is heavily influenced by the molecular profile of individual tumors. Hence, pathologists must exercise caution to prevent tissue exhaustion during the diagnostic workup of iCCA and ensure the availability of tissue samples for molecular testing. Establishing standardized procedures for obtaining adequate tissue and using molecular testing is vital. Circulating tumor DNA (ctDNA) offers a potential alternative to tissue-based analysis, especially in cases with insufficient tissue samples. Drugs targeting alterations in NTRK, IDH1, BRAF, FGFR2, and HER2 are commonly utilized. Targeting the MDM2-p53 pathway represents an avenue for future investigations in advanced BTCs. Liver transplantation and locoregional therapies are treatment modalities that may represent curative intent treatments for patients with unresectable disease, and larger explorations are warranted. Akin to HCC, a multidisciplinary team-based approach is essential for patients with BTCs. Through this narrative review of literature, we provide an overview of the current management of iCCA with perspectives regarding future directions in the clinical management of iCCA. We also present patient perspectives regarding the importance of patient advocacy and access to advances in clinical research for patients with BTCs.
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Affiliation(s)
- Rushabh Gujarathi
- Department of Medicine, University of Chicago Medicine, Chicago, Illinois, USA
| | - Supriya Peshin
- Department of Internal Medicine, Norton Community Hospital, Norton, Virginia, USA
| | - Xuchen Zhang
- Department of Pathology, Yale School of Medicine, New Haven, Connecticut, USA
| | | | - Molly N Meeks
- Department of Medicine, University of Arizona Cancer Center, Tucson, Arizona, USA
| | - Rachna T Shroff
- Department of Medicine, University of Arizona Cancer Center, Tucson, Arizona, USA
| | - Anjana Pillai
- Department of Medicine, University of Chicago Medicine, Chicago, Illinois, USA
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Zhou T, Han X, Xiao C, Lei X, Lan X, Wei X, Liang Y, Wu H. Diagnostic accuracy of preoperative MRI in assessing macrotrabecular-massive subtype of hepatocellular carcinoma: a systematic review and meta-analysis. Eur Radiol 2025; 35:4111-4120. [PMID: 39836200 DOI: 10.1007/s00330-024-11344-9] [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: 07/18/2024] [Revised: 10/23/2024] [Accepted: 12/08/2024] [Indexed: 01/22/2025]
Abstract
OBJECTIVES To determine the value of preoperative magnetic resonance imaging (MRI) in predicting macrotrabecular-massive hepatocellular carcinoma (MTM-HCC). MATERIALS AND METHODS A search was conducted on PubMed, Web of Science, Cochrane Library databases, and Embase for studies evaluating the performance of MRI in assessing MTM-HCC. The quality assessment of diagnostic studies (QUADAS-2) tool was used to assess the risk of bias. Diagnostic accuracy measures, including sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR), were pooled. Summary receiver operating characteristic (SROC) curves with the area under the curve (AUC) were generated. Meta-regression analysis was performed to explore potential sources of heterogeneity. RESULTS A total of ten eligible studies including 2074 lesions in 2053 patients were analyzed. The pooled sensitivity, specificity, PLR, NLR, DOR, and AUC were 0.65 (0.52, 0.76), 0.88 (0.80, 0.94), 5.6 (3.70, 8.60), 0.40 (0.30, 0.53), 14 (10, 20), and 0.84 (0.81, 0.87), respectively. High heterogeneity was observed (I2 was 78.61% and 90.95% for sensitivity and specificity, respectively) along with a threshold effect (Spearman's correlation coefficient = 0.927, p < 0.001). Meta-regression analysis demonstrated that the MRI method (radiomics or non-radiomics) affected the heterogeneity. CONCLUSION MRI has diagnostic value for MTM-HCC due to its higher specificity and moderate sensitivity, but its clinical application remains suboptimal due to significant heterogeneity. Thus, further prospective studies with large sample sizes are needed to confirm these results. KEY POINTS Question What is the value of MRI for preoperatively predicting MTM-HCC? Findings Meta-regression analyses revealed that the MRI method (radiomics or non-radiomics) is a significant factor contributing to heterogeneity. Clinical relevance This study demonstrates the high diagnostic accuracy of MRI for early detection of MTM-HCC, which can assist in guiding individualized management.
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Affiliation(s)
- Tingwen Zhou
- Guangdong Medical University, Zhanjiang, China
- Department of Radiology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, China
| | - Xiaorui Han
- Department of Radiology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, China
| | - Chuyin Xiao
- Department of Radiology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, China
| | - Xiaoxiao Lei
- Department of Radiology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, China
| | - Xinxin Lan
- Department of Radiology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, China
| | - Xinhua Wei
- Guangdong Medical University, Zhanjiang, China
- Department of Radiology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, China
| | - Yingying Liang
- Guangdong Medical University, Zhanjiang, China
- Department of Radiology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, China
| | - Hongzhen Wu
- Guangdong Medical University, Zhanjiang, China.
- Department of Radiology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, China.
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Jiang H, Zhang W, Xu X, Yu X, Ji S. Decoding the genetic puzzle: Mutations in key driver genes of pancreatic neuroendocrine tumors. Biochim Biophys Acta Rev Cancer 2025; 1880:189305. [PMID: 40158667 DOI: 10.1016/j.bbcan.2025.189305] [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: 10/29/2024] [Revised: 03/23/2025] [Accepted: 03/24/2025] [Indexed: 04/02/2025]
Abstract
Although pancreatic neuroendocrine tumors (PanNETs) are less common than other pancreatic tumors, they show significant differences in clinical behavior, genetics, and treatment responses. The understanding of the molecular pathways of PanNETs has gradually improved with advances in sequencing technology. Mutations in MEN1 (the most frequently varied gene) may result in the deletion of the tumor suppressor menin, affecting gene regulation, DNA repair, and chromatin modification. Changes in ATRX and DAXX involve chromatin remodeling, telomere stability and are associated with the alternative lengthening of telomeres (ALT) pathway and aggressive tumors. VHL mutations emphasize the roles of hypoxia and angiogenesis. Mutations in PTEN, TSC1/TSC2, and AKT1-3 often disrupt the mTOR pathway, complicating the genetic landscape of PanNETs. Understanding these genetic alterations and their impact on the PI3K/AKT/mTOR axis help to investigate new targeted therapies, which in turn can improve patient prognosis. This review aims to clarify PanNET pathogenesis through key mutations and their clinical relevance.
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Affiliation(s)
- Huanchang Jiang
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China; Center for Neuroendocrine Tumors, Fudan University Shanghai Cancer Center, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China; Shanghai Pancreatic Cancer Institute, Shanghai 200032, China; Shanghai Key Laboratory of Precision Medicine for Pancreatic Cancer, Shanghai 200032, China; Pancreatic Cancer Institute, Fudan University, Shanghai 200032, China
| | - Wuhu Zhang
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China; Center for Neuroendocrine Tumors, Fudan University Shanghai Cancer Center, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China; Shanghai Pancreatic Cancer Institute, Shanghai 200032, China; Shanghai Key Laboratory of Precision Medicine for Pancreatic Cancer, Shanghai 200032, China; Pancreatic Cancer Institute, Fudan University, Shanghai 200032, China
| | - Xiaowu Xu
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China; Center for Neuroendocrine Tumors, Fudan University Shanghai Cancer Center, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China; Shanghai Pancreatic Cancer Institute, Shanghai 200032, China; Shanghai Key Laboratory of Precision Medicine for Pancreatic Cancer, Shanghai 200032, China; Pancreatic Cancer Institute, Fudan University, Shanghai 200032, China.
| | - Xianjun Yu
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China; Center for Neuroendocrine Tumors, Fudan University Shanghai Cancer Center, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China; Shanghai Pancreatic Cancer Institute, Shanghai 200032, China; Shanghai Key Laboratory of Precision Medicine for Pancreatic Cancer, Shanghai 200032, China; Pancreatic Cancer Institute, Fudan University, Shanghai 200032, China.
| | - Shunrong Ji
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China; Center for Neuroendocrine Tumors, Fudan University Shanghai Cancer Center, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China; Shanghai Pancreatic Cancer Institute, Shanghai 200032, China; Shanghai Key Laboratory of Precision Medicine for Pancreatic Cancer, Shanghai 200032, China; Pancreatic Cancer Institute, Fudan University, Shanghai 200032, 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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Okamoto K, Fujisawa K, Kono K, Ogawa Y, Shimoyama H, Haruta S, Takazawa Y, Ueno M, Udagawa H. Long-term survival with multimodal treatment including conversion surgery for locally advanced esophageal neuroendocrine carcinoma: A case report. World J Gastrointest Surg 2025; 17:107086. [DOI: 10.4240/wjgs.v17.i6.107086] [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: 03/18/2025] [Revised: 04/04/2025] [Accepted: 05/14/2025] [Indexed: 05/30/2025] Open
Abstract
BACKGROUND Esophageal neuroendocrine carcinoma (NEC), a rare and aggressive malignancy with a poor prognosis, is often diagnosed at an advanced stage. The optimal treatment strategy for locally advanced and recurrent esophageal NEC remains unclear, and conversion surgery has only been reported for a few cases. Herein, we present the case of a 66-year-old male with locally advanced esophageal NEC initially diagnosed as squamous cell carcinoma.
CASE SUMMARY The patient underwent induction chemotherapy with docetaxel, cisplatin, and 5-fluorouracil, followed by conversion surgery, including subtotal esophagectomy, three-field lymph node dissection, and distal pancreatectomy with splenectomy, due to infiltration of the pancreas by the No. 11p lymph node. Postoperative pathological findings revealed a large cell-type NEC without a squamous cell carcinoma component, suspected to be a mixed neuroendocrine/non-neuroendocrine neoplasm. Hepatic metastasis was diagnosed within one month of surgery. Despite the administration of four courses of irinotecan + cisplatin chemotherapy, the treatment effect was considered a ‘progressive disease’. After a multidisciplinary discussion, the patient underwent partial liver resection, followed by second-line chemotherapy with amrubicin. The patient achieved three-year survival with no new recurrence.
CONCLUSION This case highlights the potential of multimodal treatment for long-term survival in advanced esophageal NEC.
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Affiliation(s)
- Kazuya Okamoto
- Department of Gastroenterological Surgery, Toranomon Hospital, Tokyo 105-8470, Tōkyō, Japan
| | - Kentoku Fujisawa
- Department of Gastroenterological Surgery, Toranomon Hospital, Tokyo 105-8470, Tōkyō, Japan
| | - Kei Kono
- Department of Pathology, Toranomon Hospital, Tokyo 105-8470, Tōkyō, Japan
| | - Yusuke Ogawa
- Department of Gastroenterological Surgery, Toranomon Hospital, Tokyo 105-8470, Tōkyō, Japan
| | - Hayato Shimoyama
- Department of Gastroenterological Surgery, Toranomon Hospital, Tokyo 105-8470, Tōkyō, Japan
| | - Shusuke Haruta
- Department of Gastroenterological Surgery, Toranomon Hospital, Tokyo 105-8470, Tōkyō, Japan
| | - Yutaka Takazawa
- Department of Pathology, Toranomon Hospital, Tokyo 105-8470, Tōkyō, Japan
| | - Masaki Ueno
- Department of Gastroenterological Surgery, Toranomon Hospital, Tokyo 105-8470, Tōkyō, Japan
| | - Harushi Udagawa
- Department of Gastroenterological Surgery, Toranomon Hospital, Tokyo 105-8470, Tōkyō, Japan
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Le QD, Le NQ, Quach DT. Underwater vs conventional endoscopic mucosal resection for nonpedunculated colorectal neoplasms: A randomized controlled trial. World J Gastrointest Surg 2025; 17:103635. [DOI: 10.4240/wjgs.v17.i6.103635] [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: 11/25/2024] [Revised: 03/23/2025] [Accepted: 04/21/2025] [Indexed: 05/30/2025] Open
Abstract
BACKGROUND Underwater endoscopic mucosal resection (UEMR) has been shown to be a good treatment option for the management of nonpedunculated polyps ≥ 10 mm since its introduction. However, there is a paucity of randomized controlled trials (RCTs) in Asia.
AIM To compare the efficacy and safety of UEMR with those of conventional EMR (CEMR) in treating nonpedunculated colorectal lesions.
METHODS We carried out this RCT at a tertiary hospital from October 2022 to July 2024. Patients with nonpedunculated colorectal neoplasms ranging from 10 mm to 30 mm in size were randomly assigned to either the UEMR or CEMR group. The primary outcome was the curative resection (R0) rate. The secondary outcomes included en bloc resection, procedure time, adverse events, and the number of clips used for defect closure.
RESULTS A total of 260 patients with 260 lesions (130 in each UEMR and CEMR group) were recruited. The median age was 58 (27-85) years, the male/female ratio was 1.74, and the median lesion size was 20 (10-30 mm) mm. Compared with CEMR, UEMR was associated with a significantly greater curative resection (R0) rate (98.4% vs 90.3%; P = 0.007), greater en bloc resection rate (100% vs 94.6%; P = 0.014), shorter procedure time (65 vs 185 seconds; P < 0.001), lower rate of bleeding complications (1.5% vs 10%; P = 0.003), and fewer clips used (2 vs 3; P < 0.001). No perforations were observed in either group.
CONCLUSION Compared with CEMR, UEMR has a higher R0 rate, greater en bloc resection rate, shorter procedure time, fewer bleeding complications, and clips used in the management of nonpedunculated colorectal neoplasms.
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Affiliation(s)
- Quang D Le
- Department of Internal Medicine, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City 70000, Viet Nam
| | - Nhan Q Le
- Department of Gastrointestinal Endoscopy, University Medical Center at Ho Chi Minh City, Ho Chi Minh City 70000, Viet Nam
| | - Duc T Quach
- Department of Internal Medicine, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City 70000, Viet Nam
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Guo LH, Hu KF, Miao M, Ding Y, Zhang XJ, Ye GL. Endoscopic resection of colorectal laterally spreading tumors: Clinicopathologic characteristics and risk factors for treatment outcomes. World J Gastrointest Endosc 2025; 17:106412. [DOI: 10.4253/wjge.v17.i6.106412] [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: 03/06/2025] [Revised: 04/09/2025] [Accepted: 05/08/2025] [Indexed: 06/11/2025] Open
Abstract
BACKGROUND Colorectal laterally spreading tumors (LSTs) are best treated with endoscopic submucosal dissection or endoscopic mucosal resection.
AIM To analyze the clinicopathological and endoscopic profiles of colorectal LSTs, determine predictive factors for high-grade dysplasia (HGD)/carcinoma (CA), submucosal invasion, and complications.
METHODS We retrospectively assessed the endoscopic and histological characteristics of 375 colorectal LSTs at our hospital between January 2016 and December 2023. We performed univariate and multivariate analysis to identify risk factors associated with HGD/CA, submucosal invasion and complications.
RESULTS The numbers of granular (LST-G) and non-granular LST (LST-NG) were 260 and 115, respectively. The rates of low-grade dysplasia and HGD/CA were 60.3% and 39.7%, respectively. Multivariate analysis indicated that a tumor size ≥ 30 mm [odds ratio (OR) = 1.934, P = 0.032], LST granular nodular mixed type (OR = 2.100, P = 0.005), and LST non-granular pseudo depressed type (NG-PD) (OR = 3.016, P = 0.015) were independent risk factors significantly associated with higher odds of HGD/CA. NG-PD (OR = 6.506, P = 0.001), tumor size (20-29 mm) (OR = 2.631, P = 0.036) and tumor size ≥ 30 mm (OR = 3.449, P = 0.016) were associated with increased odds of submucosal invasion. Tumor size ≥ 30 mm (OR = 4.888, P = 0.003) was a particularly important predictor of complications. A nomogram model demonstrated a satisfactory fit, with an area under the receiver operating characteristic curve of 0.716 (95% confidence interval: 0.653-0.780), indicating strong predictive performance.
CONCLUSION The novel nomogram incorporating tumor size, location, and morphology predicted HGD/CA during endoscopic resection for LSTs. NG-PD lesions larger than 20 mm were more likely to invade the submucosa. Tumor size ≥ 30 mm was an important predictor of complications.
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Affiliation(s)
- Li-Hua Guo
- Department of Gastroenterology, The First Affiliated Hospital of Ningbo University, Ningbo 315020, Zhejiang Province, China
| | - Ke-Feng Hu
- Department of Gastroenterology, The First Affiliated Hospital of Ningbo University, Ningbo 315020, Zhejiang Province, China
| | - Min Miao
- Department of Gastroenterology, The First Affiliated Hospital of Ningbo University, Ningbo 315020, Zhejiang Province, China
| | - Yong Ding
- Department of Gastroenterology, The First Affiliated Hospital of Ningbo University, Ningbo 315020, Zhejiang Province, China
| | - Xin-Jun Zhang
- Department of Gastroenterology, The First Affiliated Hospital of Ningbo University, Ningbo 315020, Zhejiang Province, China
| | - Guo-Liang Ye
- Department of Gastroenterology, The First Affiliated Hospital of Ningbo University, Ningbo 315020, Zhejiang Province, China
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10
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Yang ZY, Wan WN, Zhao L, Li SN, Liu Z, Sang L. Noninvasive prediction of Ki-67 expression in pancreatic cancer via contrast-enhanced ultrasound quantitative parameters: A diagnostic model study. World J Gastrointest Oncol 2025; 17:107919. [DOI: 10.4251/wjgo.v17.i6.107919] [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: 04/01/2025] [Revised: 04/27/2025] [Accepted: 05/21/2025] [Indexed: 06/13/2025] Open
Abstract
BACKGROUND The expression level of Ki-67 and the degree of differentiation in pancreatic cancer determine tumor aggressiveness and patient prognosis, which holds significant implications for clinical decision-making. A major challenge in preoperative pancreatic ductal adenocarcinoma management is predicting tumor malignancy. Contrast-enhanced ultrasound (CEUS), a dynamic imaging technique based on blood pool visualization, can reveal lesion vasculature and provide quantitative perfusion data reflecting angiogenesis. By tracking contrast agent kinetics, CEUS offers non-invasive insights into tumor vascularization, helping assess malignancy potential.
AIM To investigate the correlation between Ki-67 and pancreatic cancer differentiation using CEUS quantitative parameters and evaluated their diagnostic accuracy.
METHODS This retrospective study analyzed pancreatic cancer patients who underwent CEUS and pathological confirmation. Pathological differentiation, clinical data, and quantitative CEUS parameters [maximum intensity (IMAX), rise time (RT), rise slope 50% (Rs50), rise slope 10%-90% (Rs1090), etc.] were collected. Based on Ki-67 expression (< 50% vs ≥ 50%), patients were divided into low- and high-expression groups. The study evaluated correlations between Ki-67 expression, differentiation degree, and CEUS quantitative parameters to assess tumor aggressiveness.
RESULTS Among 54 patients (25 high Ki-67, 29 low Ki-67), significant differences (P < 0.05) were observed in Rs50, IMAX, wash-out area under the curve (WoutAUC), wash-in and out area under curve, and Rs1090 between high and low Ki-67 groups. High-expression patients showed elevated Rs50, IMAX, WoutAUC, and area under the curve (AUC), while RT and falling slope 50% (Fs50) were lower. Rs1090 demonstrated the highest diagnostic accuracy (AUC = 0.863, sensitivity = 0.92, specificity = 0.759). Fs50 was effective in low Ki-67 detection (AUC = 0.838). No correlation was found between enhancement patterns and Ki-67 or differentiation.
CONCLUSION CEUS parameters (Rs50, IMAX, WoutAUC, Rs1090) strongly correlate with Ki-67, aiding non-invasive pancreatic cancer assessment. Rs1090/IMAX predict high Ki-67; Fs50 identifies low Ki-67, supporting CEUS for tumor aggressiveness evaluation.
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Affiliation(s)
- Zi-Yi Yang
- Department of Ultrasonography, The First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning Province, China
| | - Wei-Na Wan
- Department of Ultrasonography, The First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning Province, China
| | - Lei Zhao
- Department of Ultrasonography, The First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning Province, China
| | - Si-Nong Li
- Department of Ultrasonography, The First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning Province, China
| | - Zhe Liu
- Department of Pancreatic-Biliary Surgery, The First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning Province, China
| | - Liang Sang
- Department of Ultrasonography, The First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning Province, China
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11
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Wang JC, Zhao L, Yu XY, Wu TP, Xia CF, Shi JF, He H, Chen ZQ, Shi D, Xue H, Ao Q, Liao SP, Zheng ZQ, Huang QF, Li L, Lin SL, Li YX, Hu WL, Peng J, Lei L, Cao MM, Yang F, Yan XX, He SY, Cao MD, Zhang SL, Teng Y, Li QR, Tan NP, Yu HY, Cheng HH, Wang XM, Wu WQ, Chen WQ. Diagnostic efficacy of fecal-based miR-92a for advanced colorectal neoplasia: a prospective multicenter screening trial. Mil Med Res 2025; 12:30. [PMID: 40506768 PMCID: PMC12164163 DOI: 10.1186/s40779-025-00613-3] [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] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/02/2025] [Accepted: 04/29/2025] [Indexed: 06/16/2025] Open
Abstract
BACKGROUND More efficacious, noninvasive screening methods are needed for advanced colorectal neoplasia. miR-92a is a reliable and reproducible biomarker for early colorectal cancer detection in stool samples. We compared the diagnostic efficacies of miR-92a, immunochemical fecal occult blood testing (FIT), and their combination (FIT + miR-92a) in a prospective multicenter screening trial. METHODS Overall, 16,240 participants aged 30-75 years were enrolled between April 1, 2021, and December 31, 2023. A total of 15,586 participants returned samples available for both FIT and miR-92a tests. All those with positive, and a random selection of those with negative screening tests were recommended to undergo colonoscopy. Follow-ups were performed until participants completed the colonoscopic examination. A total of 1401 screen-positive and 2079 randomly selected screen-negative individuals completed colonoscopies. Primary outcomes included sensitivity, number needed to screen (NNS), Youden index and receiver operating characteristic area under the curve (AUC) for advanced adenomas and colorectal cancer [advanced neoplasia (AN)] for each screening modality in the diagnostic performance analysis. RESULTS Colonoscopy was performed in 3480 individuals. The colonoscopy compliance rate was 47.8% for screen-positive individuals. The sensitivity of miR-92a versus FIT for AN was 70.9% versus 54.3% (P < 0.001), NNS was 24.7 versus 32.2 (P = 0.001), Youden index was 47.9% versus 35.0% (P < 0.001), AUC was 0.74 versus 0.67 (P = 0.010). FIT + miR-92a had a sensitivity of 85.4%, an NNS of 20.5, a Youden index of 47.9% and an AUC of 0.74 for AN. CONCLUSIONS For AN screening, miR-92a demonstrated better sensitivity, NNS, Youden index and AUC as compared with FIT. Compared with FIT, using miR-92a appears to be more efficient for population-based screening programs. Screening sensitivity for AN can be further enhanced if conditionally used in combination with FIT. TRIAL REGISTRATION Chinese Clinical Trial Registration Number: ChiCTR2200065415.
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Affiliation(s)
- Jia-Chen Wang
- Office of Cancer Screening, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Li Zhao
- Department of Health Management, Shenzhen People's Hospital, the Second Clinical Medical College of Jinan University/the First Affiliated Hospital of Southern University of Science and Technology, Shenzhen, 518053, Guangdong, China
| | - Xiang-Yang Yu
- Department of Gastrointestinal Surgery, Tianjin Nankai Hospital, Tianjin Medical University, Tianjin, 300000, China
| | - Ting-Ping Wu
- Department of Gastroenterology, Shenzhen Bao'an Traditional Chinese Medicine Hospital, Shenzhen, 518020, Guangdong, China
| | - Chang-Fa Xia
- Office of Cancer Screening, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Ju-Fang Shi
- Office of Cancer Screening, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Hui He
- Department of Health Management, Shenzhen People's Hospital, the Second Clinical Medical College of Jinan University/the First Affiliated Hospital of Southern University of Science and Technology, Shenzhen, 518053, Guangdong, China
| | - Zhi-Qi Chen
- Department of Nursing, Tianjin Nankai Hospital, Tianjin Medical University, Tianjin, 300000, China
| | - Dan Shi
- Department of Gastrointestinal Surgery, Tianjin Nankai Hospital, Tianjin Medical University, Tianjin, 300000, China
| | - Han Xue
- Department of Health Management, Shenzhen People's Hospital, the Second Clinical Medical College of Jinan University/the First Affiliated Hospital of Southern University of Science and Technology, Shenzhen, 518053, Guangdong, China
| | - Qi Ao
- Department of Gastrointestinal Surgery, Tianjin Nankai Hospital, Tianjin Medical University, Tianjin, 300000, China
| | - Shu-Ping Liao
- Department of Health Management, Shenzhen People's Hospital, the Second Clinical Medical College of Jinan University/the First Affiliated Hospital of Southern University of Science and Technology, Shenzhen, 518053, Guangdong, China
| | - Zhang-Qiang Zheng
- Department of Gastrointestinal Surgery, Tianjin Nankai Hospital, Tianjin Medical University, Tianjin, 300000, China
| | - Qiong-Fang Huang
- Department of Health Management, Shenzhen People's Hospital, the Second Clinical Medical College of Jinan University/the First Affiliated Hospital of Southern University of Science and Technology, Shenzhen, 518053, Guangdong, China
| | - Lin Li
- Department of Gastrointestinal Surgery, Tianjin Nankai Hospital, Tianjin Medical University, Tianjin, 300000, China
| | - Sui-Ling Lin
- Department of Gastroenterology, Shenzhen Bao'an Traditional Chinese Medicine Hospital, Shenzhen, 518020, Guangdong, China
| | - Ying-Xue Li
- Department of Gastroenterology, Shenzhen People's Hospital, the Second Clinical Medical College of Jinan University/the First Affiliated Hospital of Southern University of Science and Technology, Shenzhen, 518053, Guangdong, China
| | - Wen-Long Hu
- Clinical Medical Research Center, Shenzhen People's Hospital, the Second Clinical Medical College of Jinan University/the First Affiliated Hospital of Southern University of Science and Technology, Shenzhen, 518053, Guangdong, China
| | - Ji Peng
- Shenzhen Center for Chronic Disease Control, Shenzhen, 518081, Guangdong, China
| | - Lin Lei
- Shenzhen Center for Chronic Disease Control, Shenzhen, 518081, Guangdong, China
| | - Mao-Mao Cao
- Office of Cancer Screening, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Fan Yang
- Office of Cancer Screening, 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 Yan
- Office of Cancer Screening, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Si-Yi He
- Office of Cancer Screening, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Meng-Di Cao
- Office of Cancer Screening, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Shao-Li Zhang
- Office of Cancer Screening, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Yi Teng
- Office of Cancer Screening, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Qian-Ru Li
- Office of Cancer Screening, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Nuo-Pei Tan
- Office of Cancer Screening, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Hao-Yang Yu
- College of Life Sciences and Oceanography, Shenzhen University, Shenzhen, 518000, Guangdong, China
| | - Hong-Hui Cheng
- Department of Gastroenterology, Shenzhen Bao'an Traditional Chinese Medicine Hospital, Shenzhen, 518020, Guangdong, China.
| | - Xi-Mo Wang
- Tianjin Third Central Hospital, Tianjin Medical University, Tianjin, 300192, China.
- Tianjin Third Central Hospital, Nankai University, Tianjin, 300192, China.
- Tianjin Third Central Hospital, Tianjin University, Tianjin, 300192, China.
| | - Wei-Qing Wu
- Department of Health Management, Shenzhen People's Hospital, the Second Clinical Medical College of Jinan University/the First Affiliated Hospital of Southern University of Science and Technology, Shenzhen, 518053, Guangdong, China.
| | - Wan-Qing Chen
- Office of Cancer Screening, 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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12
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Yu M, Chen X, Zheng Z. Comprehensive conditional survival analysis of pancreatic signet ring cell carcinoma: chemotherapy's role and predictive model development using the SEER database. Discov Oncol 2025; 16:1074. [PMID: 40504325 PMCID: PMC12162426 DOI: 10.1007/s12672-025-02946-w] [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: 01/12/2025] [Accepted: 06/09/2025] [Indexed: 06/16/2025] Open
Abstract
BACKGROUND Pancreatic signet ring cell carcinoma (PSRCC) is a rare and aggressive subtype of pancreatic cancer, with a poor prognosis and limited evidence on the survival benefit of chemotherapy. From the perspective of conditional survival (CS) prognosis, this study sought to assess the effect of chemotherapy on PSRCC survival and to construct a predictive model integrating CS analysis. METHODS Using the SEER database, 708 PSRCC patients diagnosed between 2000 and 2019 were analyzed. Propensity score matching (PSM) and Kaplan-Meier curves were employed to assess chemotherapy's impact on survival. The CS analysis was performed to evaluate dynamic survival probabilities. A nomogram was developed based on key prognostic factors identified through random survival forests (RSF), least absolute shrinkage and selection operator (LASSO) regression, and multivariate Cox analysis with a stepwise backward elimination procedure. And multiple evaluation methods were employed to assess the performance of the nomogram. RESULTS The CS analysis for all cohort showed a rapid decline in survival probability within the first few years, dropping to 18% by year 1, 5% by year 3 and 3% by year 5. Chemotherapy improved short-term survival, with a 30% one-year survival rate compared to 8% in the non-chemotherapy group. However, long-term survival probabilities converged after the first year. Key prognostic factors included age, tumor size, stage, site, surgery, and chemotherapy were identified to develop a CS-integrated nomogram. And the nomogram was found to have strong predictive accuracy and clinical utility, validated by calibration, ROC, and decision curve analyses. CONCLUSION Chemotherapy offered significant early survival benefits in PSRCC, although its long-term impact is limited. The developed nomogram provided a reliable tool for personalized survival prediction, with further validation needed in prospective studies.
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Affiliation(s)
- Mingxu Yu
- Department of Hepatobiliary and pancreatic surgery, The Third Affiliated Hospital of Wenzhou Medical University, Wenzhou city, 325000, China
| | - Xiaodong Chen
- Department of Emergency, The Third Affiliated Hospital of Wenzhou Medical University, Wenzhou city, China
| | - Zihao Zheng
- Department of Hepatobiliary and pancreatic surgery, The Third Affiliated Hospital of Wenzhou Medical University, Wenzhou city, 325000, China.
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13
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Holowatyj AN, Washington MK, Goldberg RM, Murphy CC. Birth Cohort Effects in Appendiceal Adenocarcinoma Incidence Across the United States. Ann Intern Med 2025. [PMID: 40489784 DOI: 10.7326/annals-24-02479] [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] [Indexed: 06/11/2025] Open
Abstract
BACKGROUND Incidence rates of appendiceal adenocarcinoma (AA) are increasing across all age groups in the United States. Birth cohort patterns of AA can provide new, etiologic clues into increasing rates but have not been examined. OBJECTIVE To estimate incidence rates of AA across birth cohorts in the United States. DESIGN Retrospective cohort study. SETTING The National Institutes of Health and National Cancer Institute SEER (Surveillance, Epidemiology, and End Results) Program of 8 population-based cancer registries. PATIENTS A total of 4858 persons aged 20 years or older when diagnosed with a pathologically confirmed primary AA (nonmucinous, mucinous, goblet cell, or signet ring cell carcinoma) from 1975 to 2019. MEASUREMENTS Five-year age groups and time periods were used to create 21 overlapping birth cohorts (1891-1899 to 1991-1999). The ratio of age-specific incidence rates was estimated in each birth cohort relative to the 1945 birth cohort (birth years 1941 to 1949) and reported as incidence rate ratios (IRRs) with 95% CIs. RESULTS Incidence rates of AA more than tripled among the 1980 birth cohort (IRR, 3.41 [95% CI, 2.54 to 4.56]) and quadrupled among the 1985 birth cohort (IRR, 4.62 [CI, 3.12 to 6.82]) compared with the 1945 birth cohort. Age-specific incidence rates of AA increased across successive birth cohorts after 1945-although to varying degrees-for all tumor histologic types. LIMITATION The rarity of AA precluded investigations specific to signet ring cell carcinomas of the appendix and across population groups (for example, sex and race). CONCLUSION There are strong yet distinct birth cohort effects for AAs across histologic subtypes that remain unexplained-particularly among persons born after 1945. Given these patterns, there is a timely need for etiologic research as well as increased AA awareness among providers and the public. Similar trends have been reported for other gastrointestinal cancers, suggestive of potential shared cause contributing to this increasing cancer burden across generations. PRIMARY FUNDING SOURCE Appendix Cancer Pseudomyxoma Peritonei Research Foundation, National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development, and National Cancer Institute.
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Affiliation(s)
- Andreana N Holowatyj
- Department of Medicine, Vanderbilt University Medical Center, Vanderbilt-Ingram Cancer Center, and Vanderbilt University School of Medicine, Nashville, Tennessee (A.N.H.)
| | - Mary K Washington
- Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee (M.K.W.)
| | - Richard M Goldberg
- West Virginia University Cancer Institute, Morgantown, West Virginia (R.M.G.)
| | - Caitlin C Murphy
- University of Texas Health Science Center at Houston School of Public Health, Houston, Texas (C.C.M.)
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14
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Guo C, Qu Y, Liu H. Low-grade appendiceal mucinous tumor complicated by intussusception. Medicine (Baltimore) 2025; 104:e42540. [PMID: 40489876 DOI: 10.1097/md.0000000000042540] [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: 06/11/2025] Open
Abstract
RATIONALE Appendiceal mucinous tumors with intussusception are extremely rare. As primary lesions, malignant tumors often present with atypical clinical symptoms, which increases the likelihood of misdiagnosis. PATIENT CONCERNS A 79-year-old female patient of Miao ethnicity in Guizhou Province, China, was admitted with intermittent paroxysmal abdominal pain for 20 days and abdominal distension for 3 days. DIAGNOSES Computed tomography revealed ileal intussusception in the lower abdomen, suspected to be associated with a tumor. INTERVENTIONS Laparoscopy-assisted right hemicolectomy was performed. OUTCOMES Postoperative histopathology showed a low-grade appendiceal mucinous tumor with mucinous components extending into the muscularis propria and localized calcification. Regular follow-up was recommended. LESSONS Low-grade appendiceal mucinous tumors are extremely rare and are even less common when complicated by intussusception. Their clinical presentation is nonspecific, which may result in missed diagnosis. Therefore, thorough preoperative evaluation and careful surgical planning are essential for improving prognosis and minimizing the risk of severe complications.
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Affiliation(s)
- Chunzhi Guo
- Department of Thyroid Surgery, Qingdao Central Hospital, University of Health and Rehabilitation Sciences (Qingdao Central Hospital), Qingdao, Shandong, China
| | - Yan Qu
- General Surgery/Department of Gastrointestinal Surgery, The Second Affiliated Hospital of ZunYi Medical University, Zunyi, Guizhou, China
| | - Hong Liu
- General Surgery/Department of Gastrointestinal Surgery, The Second Affiliated Hospital of ZunYi Medical University, Zunyi, Guizhou, China
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15
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Xu J, Shen L, Li J, Zhou Z, Bai C, Li Z, Chi Y, Li E, Yu X, Xu N, Bai Y, Wang X, Yuan X, Liu T, Yin Y, Chen J, Hu H, Li X, Xiu D, Zhang T, Lou W, Ying J, Qin S, Deng Y, Tao M, Cheng Y, Fan S, Luo X, Guo X, Shi MM, Su W. Surufatinib in advanced neuroendocrine tumours: Final overall survival from two randomised, double-blind, placebo-controlled phase 3 studies (SANET-ep and SANET-p). Eur J Cancer 2025; 222:115398. [PMID: 40306120 DOI: 10.1016/j.ejca.2025.115398] [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: 01/07/2025] [Revised: 03/19/2025] [Accepted: 03/22/2025] [Indexed: 05/02/2025]
Abstract
BACKGROUND SANET-ep (NCT02588170) and SANET-p (NCT02589821) demonstrated the efficacy and safety of surufatinib versus placebo in patients with advanced extra-pancreatic and pancreatic neuroendocrine tumours (NETs). Here, we present a pooled analysis of final overall survival (OS) from two randomised phase 3 studies. METHODS The SANET studies were randomised, placebo-controlled, double-blind, phase 3 studies in China, comparing the efficacy and safety of oral 300-mg surufatinib (n = 265) versus placebo (n = 133) in patients with unresectable/metastatic, well-differentiated NETs (grade 1/2). After progression of disease or study unblinding, patients receiving placebo crossed over/switched to open-label surufatinib. By pooling the data from the two studies, OS analysis was completed using Kaplan-Meier methodology and a Cox proportional hazards model in the intention-to-treat population. Exploratory analyses were performed using different models to correct the confounding effect introduced by crossover. Long-term safety was assessed. RESULTS At study termination, 69 % of the placebo group had crossed over/switched to surufatinib. Median OS was 50.1 versus 46.8 months for patients initially on surufatinib versus those initially on placebo (stratified hazard ratio [HR] 0.935, 95 % confidence interval [CI] 0.684-1.278; p = 0.6727). After correcting the confounding effect introduced by crossover/switching, the HR ranged from 0.558 to 0.825. Commonly (≥10 %) reported treatment-related adverse events (grade 3/4) included hypertension and proteinuria. CONCLUSION OS of patients initially on surufatinib was not significantly longer versus patients initially on placebo, likely due to the high amount of crossover from placebo to surufatinib. No new safety signals were observed. CLINICAL TRIALS REGISTRATION SANET-ep (NCT02588170) and SANET-p (NCT02589821).
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Affiliation(s)
- Jianming Xu
- Department of Gastrointestinal Oncology, The Fifth Medical Center, Chinese PLA General Hospital, Beijing, China.
| | - Lin Shen
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Beijing Key Laboratory of Carcinogenesis and Translational Research, Department of Gastrointestinal Oncology, Peking University Cancer Hospital & Institute, Beijing, China
| | - Jie Li
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Beijing Key Laboratory of Carcinogenesis and Translational Research, Department of Gastrointestinal Oncology, Peking University Cancer Hospital & Institute, Beijing, China
| | - Zhiwei Zhou
- Department of Gastric Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Chunmei Bai
- Department of Medical Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Zhiping Li
- Department of Abdominal Oncology, West China Hospital, Sichuan University, Chengdu, China
| | - Yihebali Chi
- National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Enxiao Li
- Department of Medical Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Xianjun Yu
- Department of Pancreatic and Hepatobiliary Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
| | - Nong Xu
- Department of Medical Oncology, The First Affiliated Hospital of Zhejiang University, Hangzhou, China
| | - Yuxian Bai
- Department of Gastrointestinal Oncology, Harbin Medical University Cancer Hospital, Harbin, China
| | - Xiuwen Wang
- Department of Medical Oncology, Qilu Hospital of Shandong University, Jinan, China
| | - Xianglin Yuan
- Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Tianshu Liu
- Department of Medical Oncology, Zhongshan Hospital of Fudan University, Shanghai, China
| | - Yongmei Yin
- Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Jia Chen
- Department of Oncology, Jiangsu Cancer Hospital, Nanjing, China
| | - Hanguang Hu
- Department of Medical Oncology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Xingya Li
- Department of Medical Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Dianrong Xiu
- Department of General Surgery, Peking University Third Hospital, Beijing, China
| | - Tao Zhang
- Department of Oncology, Xiehe Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Wenhui Lou
- Department of General Surgery, Zhongshan Hospital of Fudan University, Shanghai, China
| | - Jieer Ying
- Department of Abdominal Oncology, Zhejiang Cancer Hospital, Hangzhou, China
| | - Shukui Qin
- Cancer Center of Jinling Hospital, Nanjing University of Chinese Medicine, Nanjing, China
| | - Yanhong Deng
- Department of Medical Oncology, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangzhou, Guangdong, China
| | - Min Tao
- Department of Oncology, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Ying Cheng
- Department of Thoracic Oncology, Jilin Cancer Hospital, Changchun, China
| | - Songhua Fan
- Department of Clinical Development and Regulatory Affairs, HUTCHMED, Shanghai, China
| | - Xian Luo
- Department of Clinical Development and Regulatory Affairs, HUTCHMED, Shanghai, China
| | - Xiaojun Guo
- Department of Clinical Development and Regulatory Affairs, HUTCHMED, Shanghai, China
| | - Michael M Shi
- Department of Clinical Development and Regulatory Affairs, HUTCHMED, Shanghai, China
| | - Weiguo Su
- Department of Clinical Development and Regulatory Affairs, HUTCHMED, Shanghai, China
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16
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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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17
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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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19
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Hagen R, Srivastava A, Anderson JC. The serrated pathway and colorectal cancer: what the gastroenterologist should know. Expert Rev Gastroenterol Hepatol 2025; 19:593-606. [PMID: 40409278 DOI: 10.1080/17474124.2025.2509797] [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: 03/20/2025] [Revised: 04/28/2025] [Accepted: 05/19/2025] [Indexed: 05/25/2025]
Abstract
INTRODUCTION Serrated polyps can progress to colorectal cancer (CRC), through a pathway that is distinct from the conventional adenoma-carcinoma sequence. This pathway includes hyperplastic polyps (HPs), sessile serrated polyps (SSPs), and traditional serrated adenomas (TSAs). AREAS COVERED Our review includes the histology and pathological challenges, carcinogenesis, risk factors, detection, emerging technologies, resection, and surveillance. EXPERT OPINION Serrated polyp management presents many detection, diagnosis, resection, and surveillance challenges. Missed serrated polyps contribute to preventable CRCs. A new SSP detection rate benchmark will guide endoscopists with a goal when improving detection. Furthermore, new SSP-specific surveillance strategies may also aid in reducing CRC burden. Histologic differentiation remains a challenge, underscoring the need for standardized pathology practices and exploring novel ways to stratify risk independent of histology, given interobserver variation. Moreover, the clinical significance of proximal HPs requires further clarification. Which HPs < 1 cm require closer surveillance intervals? Molecular profiling may help identify markers that separate proximal low risk from high-risk HP. The best approach for resection of serrated polyps also needs to be clarified. There is also a lack of robust longitudinal outcome data to guide surveillance recommendations since current guidelines are based on low quality of evidence.
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Affiliation(s)
- Rachael Hagen
- Department of Medicine, University of Connecticut, Farmington, CT, USA
| | - Amitabh Srivastava
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Joseph C Anderson
- Department of Medicine, University of Connecticut, Farmington, CT, USA
- Division of Gastroenterology and Hepatology, Department of Medicine, Geisel School of Medicine at Dartmouth, Hanover, NH, USA
- Division of Gastroenterology and Hepatology, Department of Medicine, White River Junction VAMC, White River Junction, VT, USA
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20
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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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21
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Abrantes AM, Caetano-Oliveira R, Oliveiros B, Cipriano MA, Tralhão JG. Association Between Colorectal Cancer Primary Features and Liver Metastases Histological Growth Patterns: Inflammation on the Primary Tumor is Associated with Desmoplastic Growth Pattern. Clin Colorectal Cancer 2025; 24:239-247. [PMID: 40021416 DOI: 10.1016/j.clcc.2025.01.004] [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: 06/03/2024] [Revised: 01/04/2025] [Accepted: 01/29/2025] [Indexed: 03/03/2025]
Abstract
BACKGROUND More than 50% of patients diagnosed with colorectal cancer (CRC) will develop liver metastases (CRCLM), which is the main cause of death for more than 60% of these patients. The aim of this study was to correlate the clinical and pathological characteristics of the primary CRC and CRCLM, with emphasis in predicting the histological growth pattern of the CRCLM. METHODS Cohort of 73 patients with CRC. Analysis of clinical data and blinded pathological review was performed related with primary tumor and CRCLM features. The analysis was performed in SPSS (version 27) with a significance level of 5%. RESULTS A statistically significant association was found between tumor size and metastasis growth pattern (P = .002), with larger tumors giving rise to metastases with a nondesmoplastic growth pattern. Lymphovascular invasion (LVI) was associated with metachronous CRCLM (P = .043). In the absence of LVI, the time required for CRCLM to appear was significantly longer (P = .011). The number of metastases was significantly higher (P = .049) in tumors without LVI when compared to tumors with LVI. There was a statistically significant association between CRC high-grade inflammation and the desmoplastic metastases growth pattern of the CRCLM (P = .017). CONCLUSION The possibility of predicting the CRCLM histological growth pattern resorting to primary CRC characteristics would be useful for proper patient selection for surgery and adapting biological therapies.
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Affiliation(s)
- Ana Margarida Abrantes
- Biophysics Institute, Faculty of Medicine, University of Coimbra, Coimbra, Portugal; Coimbra Institute for Clinical and Biomedical Research (iCBR) Area of Environment, Genetics and Oncobiology (CIMAGO), Faculty of Medicine, University of Coimbra, Coimbra, Portugal; Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, Coimbra, Portugal; Coimbra Centor Académico e Clínico (CACC), Coimbra, Portugal
| | - Rui Caetano-Oliveira
- Coimbra Institute for Clinical and Biomedical Research (iCBR) Area of Environment, Genetics and Oncobiology (CIMAGO), Faculty of Medicine, University of Coimbra, Coimbra, Portugal; Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, Coimbra, Portugal; Coimbra Centor Académico e Clínico (CACC), Coimbra, Portugal; Pathology Department, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal; Centro de Anatomia Patológica Germano de Sousa, Coimbra, Portugal; General Surgery Department, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal.
| | - Bárbara Oliveiros
- Coimbra Institute for Clinical and Biomedical Research (iCBR) Area of Environment, Genetics and Oncobiology (CIMAGO), Faculty of Medicine, University of Coimbra, Coimbra, Portugal; Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, Coimbra, Portugal; Coimbra Centor Académico e Clínico (CACC), Coimbra, Portugal
| | | | - José Guilherme Tralhão
- Biophysics Institute, Faculty of Medicine, University of Coimbra, Coimbra, Portugal; Coimbra Institute for Clinical and Biomedical Research (iCBR) Area of Environment, Genetics and Oncobiology (CIMAGO), Faculty of Medicine, University of Coimbra, Coimbra, Portugal; Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, Coimbra, Portugal; Coimbra Centor Académico e Clínico (CACC), Coimbra, Portugal; General Surgery Department, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal
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22
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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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23
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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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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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25
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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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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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Chai T, Tong Y, Yu Y, Hu B, Cui GB. Diagnostic Values of Magnetic Resonance Imaging and Computed Tomography for Predicting Macrotrabecular-Massive Hepatocellular Carcinoma Subtype: A Meta-analysis. Acad Radiol 2025; 32:3333-3341. [PMID: 39920007 DOI: 10.1016/j.acra.2025.01.029] [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: 11/09/2024] [Revised: 01/20/2025] [Accepted: 01/22/2025] [Indexed: 02/09/2025]
Abstract
BACKGROUND The diagnostic accuracy of magn\etic resonance imaging (MRI) vs. computed tomography (CT) for predicting macrotrabecular-massive hepatocellular carcinoma (MTM-HCC) is yet to be ascertained. Therefore, this meta-analysis aimed to summarise the diagnostic accuracies of MRI and CT for MTM-HCC. METHODS A comprehensive literature search of PubMed and Embase was conducted up to 20 August 2024, to evaluate the diagnostic performance of MRI and CT for the diagnosis of MTM-HCC. Pooled sensitivity and specificity were calculated for MRI and CT using a bivariate random-effects model. Subgroup analyses based on different covariates were conducted to compare the diagnostic performances of MRI and CT. RESULTS 15 studies involving 2299 patients, including 706 with MTM-HCC and 1593 with non-MTM-HCC were analysed. Comparative analysis revealed no significant differences between MRI and CT in pooled sensitivity (66% vs. 82%, respectively) and specificity (88% vs. 79%, respectively) for the diagnosis of MTM-HCC (P=0.53), with comparable areas under the summary receiver operating characteristic curves of 0.87 and 0.86, respectively. In the subgroup analysis of imaging methods within radiomics, CT had significantly higher sensitivity and specificity than MRI (98% vs. 85% [sensitivity], 83% vs. 79% [specificity], P=0.01). In the other subgroups, including age, the most common aetiology of liver disease, the proportion of patients with cirrhosis, and tumour size, there were no significant differences (all P>0.05). CONCLUSION CT and MRI had comparable predictive performances for the non-invasive diagnosis of MTM-HCC. In the subgroup of radiomics-based imaging methods, CT outperformed MRI. Nevertheless, multicenter prospective studies with uniform design are needed to confirm these findings.
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Affiliation(s)
- Tian Chai
- Department of Radiology, Functional and Molecular Imaging Key Lab of Shaanxi Province, Tangdu Hospital, Air Force Medical University (Fourth Military Medical University), Xi'an, Shaanxi Province, China
| | - Yao Tong
- Department of Radiology, Functional and Molecular Imaging Key Lab of Shaanxi Province, Tangdu Hospital, Air Force Medical University (Fourth Military Medical University), Xi'an, Shaanxi Province, China
| | - Ying Yu
- Department of Radiology, Functional and Molecular Imaging Key Lab of Shaanxi Province, Tangdu Hospital, Air Force Medical University (Fourth Military Medical University), Xi'an, Shaanxi Province, China
| | - Bo Hu
- Department of Radiology, Functional and Molecular Imaging Key Lab of Shaanxi Province, Tangdu Hospital, Air Force Medical University (Fourth Military Medical University), Xi'an, Shaanxi Province, China
| | - Guang-Bin Cui
- Department of Radiology, Functional and Molecular Imaging Key Lab of Shaanxi Province, Tangdu Hospital, Air Force Medical University (Fourth Military Medical University), Xi'an, Shaanxi Province, China.
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González IA, Pacheco MC. What is New in Pediatric Hepatic Neoplasms. Surg Pathol Clin 2025; 18:281-300. [PMID: 40412827 DOI: 10.1016/j.path.2024.12.002] [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: 05/27/2025]
Abstract
The goal of this review is to provide a practical update on hepatic lesions affecting the pediatric population and is not meant to be an exhaustive summary of each entity. Hepatoblastoma is purposely not discussed as recent comprehensive reviews on this topic are available; instead, a discussion on rhabdoid tumor and the evolving concept of small cell undifferentiated hepatoblastoma and blastemal hepatoblastoma is included.
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Affiliation(s)
- Iván A González
- Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, 350 W 11th St., Room 4068, Indianapolis, IN 46202, USA. https://twitter.com/IvanGonzalezMD
| | - Maria C Pacheco
- Department of Laboratory Medicine and Pathology, University of Washington, Seattle Children's Hospital, 4800 Sand Point Way NE, FB 4.521 - Pathology Lab, Seattle, WA 98105, USA.
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29
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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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30
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Zhang P, Shi G, Wang C, An L, Lu Y, Zhou H, Ma R. Clinical features and prognostic analysis of 14 cases of appendiceal mixed neuroendocrine-non-neuroendocrine tumors with peritoneal pseudomyxoma. World J Surg Oncol 2025; 23:209. [PMID: 40450323 DOI: 10.1186/s12957-025-03857-4] [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: 03/18/2025] [Accepted: 05/16/2025] [Indexed: 06/03/2025] Open
Abstract
BACKGROUND Appendiceal mixed neuroendocrine-non-neuroendocrine neoplasms (a-MiNENs) combined with peritoneal pseudomyxoma (PMP) represent an exceptionally rare and clinically challenging entity. This study aims to elucidate the clinical characteristics of this unique tumor subtype and identify critical prognostic factors, thereby providing insights into the management and outcomes of affected patients. METHODS We conducted a retrospective analysis of 14 patients diagnosed with a-MiNEN and PMP at the Department of Myxoma, Aerospace Center Hospital, between January 2014 and September 2022. Data included demographics, symptoms, tumor grading, treatments, and outcomes. RESULTS Pathological evaluation revealed a diverse spectrum of tumor grades and PMP subtypes: 5 cases were classified as G1 neuroendocrine tumors (NET), 4 as G2 NET, and 5 as G3 neuroendocrine carcinoma (NEC). Regarding PMP subtypes, 5 cases had disseminated peritoneal adenomucinosis (DPAM), 4 had peritoneal mucinous carcinomatosis (PMCA), and 5 had peritoneal mucinous carcinomatosis with signet ring cell carcinoma (PMCA-S). The median postoperative survival time was 28.55 months, with 1-year and 2-year survival rates of 80.0% and 66.7%, respectively. Patients aged < 60 years, male sex, absence of right hemicolectomy, postoperative peritoneal cancer index (PCI) ≥ 25, and perineural invasion demonstrated significantly lower 1-year and 2-year survival rates compared to their counterparts, with distinct separation observed in the Kaplan-Meier curves. These factors likely reflect biological differences in disease progression, inadequate surgical debulking, and aggressive tumor behavior. CONCLUSIONS a-MiNEN with PMP progresses rapidly. Young patients, male patients, those with absence of right hemicolectomy, postoperative PCI ≥ 25 and perineural invasion may face poorer outcomes. This study, one of the few to analyze this rare condition, underscores the need for targeted treatments and further validation in larger cohorts.
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Affiliation(s)
- Pu Zhang
- Department of Myxoma, Aerospace Center Hospital, Beijing, 100049, China
| | - Guanjun Shi
- Department of Myxoma, Aerospace Center Hospital, Beijing, 100049, China
| | - Chong Wang
- Department of Myxoma, Aerospace Center Hospital, Beijing, 100049, China
| | - Lubiao An
- Department of Myxoma, Aerospace Center Hospital, Beijing, 100049, China
| | - Yiyan Lu
- Department of Pathology, Aerospace Center Hospital, Beijing, 100049, China
| | - Haipeng Zhou
- Department of Myxoma, Aerospace Center Hospital, Beijing, 100049, China
| | - Ruiqing Ma
- Department of Myxoma, Aerospace Center Hospital, Beijing, 100049, China.
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Zhou E, Shi G, Shi H, Zhang K, Wei J, Tu M, Lu Z, Guo F, Chen J, Jiang K, Gao W. Outcome after spleen-preserving distal pancreatectomy by Warshaw technique for pancreatic body cancer. Ann Hepatobiliary Pancreat Surg 2025; 29:177-186. [PMID: 40122577 PMCID: PMC12093236 DOI: 10.14701/ahbps.24-202] [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: 10/15/2024] [Revised: 01/13/2025] [Accepted: 01/22/2025] [Indexed: 03/25/2025] Open
Abstract
Backgrounds/Aims Distal pancreatectomy with splenectomy (DPS) is a common surgical procedure for pancreatic body cancer. However, spleen-preserving distal pancreatectomy (SPDP) utilizing the Warshaw technique (WT) in malignancies is generally not favored due to concerns about inadequate resection. This study aims to assess the feasibility and oncologic outcomes of employing SPDP with WT in pancreatic body cancer. Methods We conducted a retrospective analysis comparing 21 SPDP patients with 63 DPS patients matched by propensity score from January 2018 to November 2022. Clinical outcomes and follow-up data were analyzed using R. Results Both groups exhibited similar demographic, intraoperative, and pathological characteristics, with the exception of a reduced number of total lymph nodes (p = 0.006) in the SPDP group. There were no significant differences in the rates of postoperative complications, recurrence, or metastasis. Local recurrence predominantly occurred in the central region as opposed to the spleen region. There were no cases of isolated recurrences in the splenic region. Median overall survival and recurrence-free survival times were 51.5 months for SPDP vs 30.5 months for DPS and 18.7 months vs 16.8 months, respectively (p > 0.05). The incidence of partial splenic infarction and left-side portal hypertension in the SPDP group was 28.6% (6/21) and 9.5% (2/21), respectively, without necessitating splenic abscess puncture, splenectomy, or causing bleeding from perigastric varices. Conclusions SPDP did not negatively impact local recurrence or survival rates in selected pancreatic body cancer patients. Further studies are necessary for validation.
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Affiliation(s)
- Endi Zhou
- Pancreas Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
- Pancreas Institute, Nanjing Medical University, Nanjing, China
- Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Guodong Shi
- Pancreas Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
- Pancreas Institute, Nanjing Medical University, Nanjing, China
- Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Hongyuan Shi
- Department of Radiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Kai Zhang
- Pancreas Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
- Pancreas Institute, Nanjing Medical University, Nanjing, China
- Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Jishu Wei
- Pancreas Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
- Pancreas Institute, Nanjing Medical University, Nanjing, China
- Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Min Tu
- Pancreas Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
- Pancreas Institute, Nanjing Medical University, Nanjing, China
- Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Zipeng Lu
- Pancreas Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
- Pancreas Institute, Nanjing Medical University, Nanjing, China
- Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Feng Guo
- Pancreas Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
- Pancreas Institute, Nanjing Medical University, Nanjing, China
- Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Jianmin Chen
- Pancreas Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
- Pancreas Institute, Nanjing Medical University, Nanjing, China
- Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Kuirong Jiang
- Pancreas Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
- Pancreas Institute, Nanjing Medical University, Nanjing, China
- Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Wentao Gao
- Pancreas Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
- Pancreas Institute, Nanjing Medical University, Nanjing, China
- Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
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Shang ZK, Zhang JH, Zhu JH, Deng CS, Chen XY, Ran-Xia, Sun CQ. Potential of neoadjuvant hepatic artery perfusion chemotherapy in improving surgical outcomes in hepatocellular carcinoma: a systematic review and meta-analysis. World J Surg Oncol 2025; 23:207. [PMID: 40442678 PMCID: PMC12123804 DOI: 10.1186/s12957-025-03859-2] [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: 03/16/2025] [Accepted: 05/17/2025] [Indexed: 06/02/2025] Open
Abstract
BACKGROUND The purpose of this study was to assess the effectiveness of adjuvant treatment with new hepatic arterial infusion chemotherapy (HAIC) prior to hepatic resection in patients with resectable hepatocellular carcinoma (HCC). METHODS A systematic review was conducted utilizing established databases and registries as of January 15, 2025, without imposing restrictions based on language, publication date, or status. The inclusion criteria were met by studies that examined the effects of HAlC, with or without surgical intervention, in comparison to surgical treatment alone. The primary outcomes encompassed overall survival (OS) and disease-free survival (DFS), while secondary outcomes included recurrence rate and adverse events. A random effects model was employed to analyze the data. RESULTS A total of 10 studies involving 1,014 patients were included. The results showed that preoperative HAlC improved patient survival (OS), disease-free survival (DFS), and recurrence rates compared with surgical treatment alone. The most common grade 3 and higher adverse reactions in patients treated with preoperative HAIC included vomiting, leukopenia, neutropenia, hypothyroidism, and diarrhea. CONCLUSION Preoperative HAIC has been demonstrated to enhance survival outcomes in patients with resectable HCC; however, the clinical efficacy of this approach requires further validation through large-scale design studies.
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Affiliation(s)
- Zi-Kui Shang
- Department of Hepatobiliary Surgery, The Third People's Hospital of Honghe Hani and Yi Autonomous Prefecture, Honghe, 661000, Yunnan Province, China
| | - Jian-Hua Zhang
- Department of Hepatobiliary Surgery, The Third People's Hospital of Honghe Hani and Yi Autonomous Prefecture, Honghe, 661000, Yunnan Province, China
| | - Jia-Hai Zhu
- Department of Hepatobiliary Surgery, The Third People's Hospital of Honghe Hani and Yi Autonomous Prefecture, Honghe, 661000, Yunnan Province, China
| | - Chuan-Sen Deng
- Department of Hepatobiliary Surgery, The Third People's Hospital of Honghe Hani and Yi Autonomous Prefecture, Honghe, 661000, Yunnan Province, China
| | - Xi-Yuan Chen
- Department of Hepatobiliary Surgery, The Third People's Hospital of Honghe Hani and Yi Autonomous Prefecture, Honghe, 661000, Yunnan Province, China
| | - Ran-Xia
- Department of Hepatobiliary Surgery, The Third People's Hospital of Honghe Hani and Yi Autonomous Prefecture, Honghe, 661000, Yunnan Province, China
| | - Chun-Quan Sun
- Department of Hepatobiliary Surgery, The Third People's Hospital of Honghe Hani and Yi Autonomous Prefecture, Honghe, 661000, Yunnan Province, China.
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Ma T, Wang H, Dai W, Shen P, Zhang J, Xie R. Historical trends in histological composition and cause specific mortality of small intestine tumors based on SEER database analysis. Sci Rep 2025; 15:18628. [PMID: 40436948 PMCID: PMC12120026 DOI: 10.1038/s41598-025-03046-z] [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: 07/07/2024] [Accepted: 05/19/2025] [Indexed: 06/01/2025] Open
Abstract
Small intestine tumors, though rare, have shown a concerning increase in incidence and mortality in recent years. This study aimed to investigate the historical trends in histological composition and causes of death among patients with small intestine tumors using the SEER database. A total of 18,234 patients diagnosed with primary small intestine cancer from 1992 to 2018 were included in this study. Demographic details, tumor characteristics, treatment modalities, and outcomes were collected. Cause-specific mortality was analyzed using Fine and Gray regression, with non-small intestine-specific deaths considered as competing risks. Small intestine-specific deaths were the leading cause of mortality, with adenocarcinoma and carcinoid tumors being the most common histological types. Heart disease emerged as a significant cause of death following diagnosis, surpassing small intestine-specific deaths after 5-6 years. The study revealed variations in mortality causes across histological subtypes and identified risk factors for small intestine-specific mortality, including age, tumor site, grade, and treatment modalities. The findings highlight the substantial impact of heart disease on the long-term survival of patients with small intestine tumors. This underscores the potential benefits of adopting comprehensive management strategies that integrate oncological and cardiological care to improve survival rates and quality of life. A multidisciplinary approach in oncocardiology may help address the complex needs of these patients and optimize clinical outcomes.
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Affiliation(s)
- Tianheng Ma
- Department of Gastroenterology, The Affiliated Huai'an No 1 People's Hospital of Nanjing Medical University, No.1 Huanghe West Road, Huai'an, 223300, Jiangsu, China
| | - Honggang Wang
- Department of Gastroenterology, The Affiliated Huai'an No 1 People's Hospital of Nanjing Medical University, No.1 Huanghe West Road, Huai'an, 223300, Jiangsu, China
| | - Weijie Dai
- Department of Gastroenterology, The Affiliated Huai'an No 1 People's Hospital of Nanjing Medical University, No.1 Huanghe West Road, Huai'an, 223300, Jiangsu, China
| | - Peng Shen
- Department of Gastroenterology, The Affiliated Huai'an No 1 People's Hospital of Nanjing Medical University, No.1 Huanghe West Road, Huai'an, 223300, Jiangsu, China
| | - Jialing Zhang
- Department of Gastroenterology, The Affiliated Huai'an No 1 People's Hospital of Nanjing Medical University, No.1 Huanghe West Road, Huai'an, 223300, Jiangsu, China.
| | - Rui Xie
- Department of Gastroenterology, The Affiliated Huai'an No 1 People's Hospital of Nanjing Medical University, No.1 Huanghe West Road, Huai'an, 223300, Jiangsu, China.
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Cai XH, Fan XF, Li S, Fang WL, Wang BM, Wang YF, Feng Y, Mu JB, Liu WT. Construction of a multimodal interpretable machine learning model based on radiomics and clinical features for distinguishing benign and malignant pancreatic lesions. Shijie Huaren Xiaohua Zazhi 2025; 33:361-372. [DOI: 10.11569/wcjd.v33.i5.361] [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: 03/31/2025] [Revised: 04/21/2025] [Accepted: 05/08/2025] [Indexed: 05/28/2025] Open
Abstract
BACKGROUND Machine learning (ML) has achieved good performance in predicting various clinical events due to its powerful data processing capabilities. This study aimed to develop ML models using clinical and endoscopic ultrasound data to accurately predict benign and malignant pancreatic lesions, and to interpret these models by applying the SHapley Additive exPlanations (SHAP) method.
AIM To develop an interpretable machine learning model based on endoscopic ultrasonography (EUS) radiomics features and clinical features to predict the benign and malignant nature of pancreatic lesions.
METHODS We collected EUS images and clinical information from 216 patients with pancreatic lesions who underwent EUS examination at Tianjin Medical University General Hospital from January 2014 to December 2024, including a training set of 150 patients and a validation set of 66 patients. We used t-tests and the least absolute shrinkage and selection operator logistic regression algorithm to select EUS radiomics features and constructed five radiomics-based machine learning models, ultimately selecting the extreme gradient boosting (XGBoost) model with the best performance for further analysis. Univariate and multivariate logistic regression analyses were used to identify statistically significant clinical indicators distinguishing benign and malignant pancreatic lesions in the training set, and a clinical feature-based XGBoost model was developed. Finally, a multimodal combined XGBoost model was constructed by integrating radiomics and clinical features. The SHAP method was used to explore the interpretability of the model.
RESULTS The radiomics-based XGBoost machine learning model was constructed with 15 radiomics features, achieving area under the curve (AUC) values of 0.8521 and 0.8761 for the training and validation sets, respectively. The clinical feature-based XGBoost machine learning model consisted of three clinical features, with AUC values of 0.9286 and 0.9200 for the training and validation sets, respectively. The multimodal machine learning model included the aforementioned 15 radiomics features and three clinical features, yielding AUC values of 0.9458 and 0.9357 for the training and validation sets, outperforming the other two models. SHAP analysis indicated that the top five contributing features or indicators in the machine learning model included three clinical laboratory indicators and two radiomics features.
CONCLUSION The multimodal machine learning model that combines EUS radiomics and clinical features can effectively predict the benign and malignant nature of pancreatic lesions, and the SHAP tool visualizes the prediction process for clinical application.
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Affiliation(s)
- Xiao-Han Cai
- Department of Gastroenterology, Tianjin Medical University General Hospital, Tianjin 300052, China
| | - Xiao-Fei Fan
- Department of Gastroenterology, Tianjin Medical University General Hospital, Tianjin 300052, China
| | - Shu Li
- Department of Gastroenterology, Tianjin Medical University General Hospital, Tianjin 300052, China
| | - Wei-Li Fang
- Department of Gastroenterology, Tianjin Medical University General Hospital, Tianjin 300052, China
| | - Bang-Mao Wang
- Department of Gastroenterology, Tianjin Medical University General Hospital, Tianjin 300052, China
| | - Yu-Feng Wang
- Tianjin Yujin Artificial Intelligence Medical Technology Co., Ltd., Tianjin 300392, China
| | - Yue Feng
- Tianjin Yujin Artificial Intelligence Medical Technology Co., Ltd., Tianjin 300392, China
| | - Jin-Bao Mu
- Tianjin Yujin Artificial Intelligence Medical Technology Co., Ltd., Tianjin 300392, China
| | - Wen-Tian Liu
- Department of Gastroenterology, Tianjin Medical University General Hospital, Tianjin 300052, China
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Zhou RQ, Yang PJ, Liu TT, Han DD, Liu XL, Liu LG, Si S, Yang SW, Xu SS, Guo YW, Tan HD. Liver transplantation for combined hepatocellular cholangiocarcinoma: Current evidence, selection criteria, and therapeutic controversies. World J Gastrointest Surg 2025; 17:105783. [DOI: 10.4240/wjgs.v17.i5.105783] [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: 02/07/2025] [Revised: 03/09/2025] [Accepted: 04/09/2025] [Indexed: 05/23/2025] Open
Abstract
Combined hepatocellular cholangiocarcinoma (cHCC-CCA) is a rare and aggressive primary liver malignancy characterized by features of both HCC and CCA. Preoperative diagnosis remains challenging because of overlapping imaging and histopathological features, which often lead to misclassification. Although liver resection is the primary curative therapy, the efficacy of liver transplantation (LT) remains controversial. Historically, LT has been considered contraindicated owing to the poor prognosis, high recurrence rate of cHCC-CCA, and the potential for organ wastage. Recent studies have suggested that LT may benefit carefully selected patients, particularly those with early-stage tumors or cirrhosis. However, there is no consensus on the criteria for LT in patients with cHCC-CCA. Lymphadenectomy and vascular resection strategies were discussed along with locoregional and systemic therapies. This review synthesized the current evidence on surgical strategies for cHCC-CCA, focusing on evolving LT criteria and outcomes.
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Affiliation(s)
- Rui-Quan Zhou
- Second Department of Hepatopancreatobiliary Surgery, China-Japan Friendship Hospital, Beijing 100029, China
| | - Pei-Jun Yang
- Second Department of Hepatopancreatobiliary Surgery, China-Japan Friendship Hospital, Beijing 100029, China
| | - Tian-Tong Liu
- Second Department of Hepatopancreatobiliary Surgery, China-Japan Friendship Hospital, Beijing 100029, China
| | - Dong-Dong Han
- Second Department of Hepatopancreatobiliary Surgery, China-Japan Friendship Hospital, Beijing 100029, China
| | - Xiao-Lei Liu
- Second Department of Hepatopancreatobiliary Surgery, China-Japan Friendship Hospital, Beijing 100029, China
| | - Li-Guo Liu
- Second Department of Hepatopancreatobiliary Surgery, China-Japan Friendship Hospital, Beijing 100029, China
| | - Shuang Si
- Second Department of Hepatopancreatobiliary Surgery, China-Japan Friendship Hospital, Beijing 100029, China
| | - Shi-Wei Yang
- Second Department of Hepatopancreatobiliary Surgery, China-Japan Friendship Hospital, Beijing 100029, China
| | - Shuai-Shuai Xu
- Second Department of Hepatopancreatobiliary Surgery, China-Japan Friendship Hospital, Beijing 100029, China
| | - Yi-Wen Guo
- Second Department of Hepatopancreatobiliary Surgery, China-Japan Friendship Hospital, Beijing 100029, China
| | - Hai-Dong Tan
- Second Department of Hepatopancreatobiliary Surgery, China-Japan Friendship Hospital, Beijing 100029, China
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Niu C, Song Y, Chen Y, Shi Y, Wang H, Wu X, Wang X, Zhao X, Bu Y, Li J, Tao T, Wu J, Xue C, Zhang F, Han C, Yuan J, Zhang Q. Epidemiology of Helicobacter pylori, gastric precancerous lesions and gastric cancer: a multicenter, population-based cross-sectional study in Nanjing. BMC Infect Dis 2025; 25:766. [PMID: 40426075 PMCID: PMC12117699 DOI: 10.1186/s12879-025-11147-3] [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: 09/05/2024] [Accepted: 05/20/2025] [Indexed: 05/29/2025] Open
Abstract
BACKGROUND Nanjing City has a high-incidence gastric cancer (GC), but the epidemiology of gastric precancerous lesions (GPLs) remains poorly understood. This study aimed to investigate the epidemiological characteristics of Helicobacter pylori (H. pylori) infection, GPLs, and GCs in patients undergoing endoscopic examination in Lishui District, Nanjing. METHODS This retrospective, population-based, cross-sectional study was conducted collaboratively by the Nanjing Lishui People's Hospital and six medical community units within the county between July 2022 and June 2023. Data on biopsies and 13C urea breath tests (13C-UBT) were collected. RESULTS A total of 15,668 individuals were included, among whom 259 had GPL (1.65%) and 218 had GC (1.39%). The H. pylori infection rate in total patients was 5014 (32.00%) (males: 2684 (34.06%); females: 2335 (29.92%)). The H. pylori infection rate is 31.45% in benign gastric lesions, 44.40% in GPLs, and 55.50% in GC, respectively. The multivariable logistic regression analysis showed that male (OR = 3.156, 95% CI: 2.865-3.376, P < 0.001), age (OR = 1.785, 95% CI: 1.703-1.876, P < 0.001), fresh vegetable, fruit, and white meat intake frequently (OR = 0.865, 95% CI: 0.506-2.061, P = 0.029), high-salt diet and high-fat diet intake frequently (OR = 1.906, 95% CI: 1.101-2.932, P = 0.014), rural residence (OR = 2.682, 95% CI: 1.010-4.754, P = 0.040), H. pylori infection (OR = 2.022, 95% CI: 1.155-2.865, P < 0.001) and atrophic gastritis and/or intestinal metaplasia (OR = 4.875, 95% CI: 2.229-10.663, P < 0.001) were associated with GPLs. Male (OR = 2.021, 95% CI: 1.080-3.780, P = 2.028), age (OR = 1.201, 95% CI: 1.174-1.238, P < 0.001), digestive symptoms (OR = 2.256, 95% CI: 1.548-3.289, P < 0.001), bachelor degree below (OR = 4.792, 95% CI: 3.439-6.837, P < 0.001), farmer (OR = 1.039, 95% CI: 1.026-1.159, P < 0.001), fresh vegetable, fruit, and white meat intake (OR = 0.231, 95% CI: 0.141-0.379, P < 0.001), fried/barbecue/pickled food intake (OR = 6.781, 95% CI: 3.783-12.153, P < 0.001), high-salt diet and high-fat diet intake (OR = 4.374, 95% CI: 2.363-8.097, P < 0.001), rural residence (OR = 1.230, 95% CI: 1.121-1.437, P < 0.001), H. pylori infection (OR = 3.248, 95% CI: 2.357-4.477, P < 0.001) and atrophic gastritis and/or intestinal metaplasia (OR = 4.875, 95% CI: 2.636-9.016, P < 0.001) were associated with GCs. CONCLUSIONS These findings underscore the importance of implementing targeted prevention strategies and early detection programs in high-risk populations to mitigate the burden of GPLs and GCs in Nanjing.
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Affiliation(s)
- Chunyan Niu
- Department of Gastroenterology, Nanjing Lishui People's Hospital (Zhongda Hospital Lishui Branch, Southeast University), Nanjing, 211200, China.
| | - Yongqiang Song
- Department of Gastroenterology, Nanjing Lishui People's Hospital (Zhongda Hospital Lishui Branch, Southeast University), Nanjing, 211200, China
| | - Yue Chen
- Department of Gastroenterology, Nanjing Lishui People's Hospital (Zhongda Hospital Lishui Branch, Southeast University), Nanjing, 211200, China
| | - Yongqiang Shi
- Department of Gastroenterology, Nanjing Lishui People's Hospital (Zhongda Hospital Lishui Branch, Southeast University), Nanjing, 211200, China
| | - Hui Wang
- Department of Gastroenterology, Nanjing Lishui People's Hospital (Zhongda Hospital Lishui Branch, Southeast University), Nanjing, 211200, China
| | - Xinguo Wu
- Department of Gastroenterology, Nanjing Lishui People's Hospital (Zhongda Hospital Lishui Branch, Southeast University), Nanjing, 211200, China
| | - Xiaoping Wang
- Department of Gastroenterology, Nanjing Lishui People's Hospital (Zhongda Hospital Lishui Branch, Southeast University), Nanjing, 211200, China
| | - Xiangyang Zhao
- Department of Gastroenterology, Nanjing Lishui People's Hospital (Zhongda Hospital Lishui Branch, Southeast University), Nanjing, 211200, China
| | - Yongdan Bu
- Dongping Street Health Center in Nanjing Lishui District, Nanjing, 211212, China
| | - Jijin Li
- Jingqiao Central Health Center in Nanjing Lishui District, Nanjing, 211224, China
| | - Tao Tao
- Honglan Street Health Center in Nanjing Lishui District, Nanjing, 211219, China
| | - Jinhua Wu
- Shiqiu Central Health Center in Nanjing Lishui District, Nanjing, 211222, China
| | - Changlin Xue
- Baima Central Health Center in Nanjing Lishui District, Nanjing, 211225, China
| | - Fuyu Zhang
- Yongyang Street Community Health Service Center in Nanjing Lishui District, Nanjing, 211299, China
| | - Chunrong Han
- Department of Pathology, Nanjing Lishui People's Hospital (Zhongda Hospital Lishui Branch, Southeast University), Nanjing, 211200, China
| | - Juan Yuan
- Department of Pathology, Nanjing Lishui People's Hospital (Zhongda Hospital Lishui Branch, Southeast University), Nanjing, 211200, China
| | - Qiang Zhang
- Department of Gastroenterology, Yancheng Third People's Hospital (The Yancheng School of Clinical Medicine of Nanjing Medical University), Yancheng, 224000, China.
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Wang Y, Jin RU, Xu J, Lin DC, Sun Z, Xu Y, Li QK, Zhang H. Harnessing technologies to unravel gastric cancer heterogeneity. Trends Cancer 2025:S2405-8033(25)00107-4. [PMID: 40425443 DOI: 10.1016/j.trecan.2025.04.011] [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: 10/24/2024] [Revised: 04/14/2025] [Accepted: 04/21/2025] [Indexed: 05/29/2025]
Abstract
Gastric cancer arises from complex carcinogenic factor interactions, with limited treatment options due to the lack of targetable driver gene mutations and significant tumor heterogeneity. Recent studies have provided promising novel approaches to improve our understanding of gastric cancer heterogeneity through integrated characterization, combining genomics with emerging technologies. Delineating the molecular changes and targeting specific molecular subtypes will enhance the efficacy of gastric cancer treatment and improve clinical outcomes. This review provides a comprehensive overview of current technologies used in gastric cancer research, highlighting key discoveries and treatment strategies driven by these innovations. Finally, we discuss the emerging technology-guided directions and potential breakthroughs that could enhance the understanding of gastric cancer tumor heterogeneity, ultimately improving clinical outcomes.
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Affiliation(s)
- Yuefan Wang
- Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
| | - Ramon U Jin
- Division of Oncology and Gastroenterology, Washington University School of Medicine, Saint Louis, MO 63110, USA
| | - Joanne Xu
- College of Engineering, The Ohio State University, Columbus, OH 43210, USA
| | - Ding Chiao Lin
- Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA
| | - Zhenyu Sun
- Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA
| | - Yuanwei Xu
- Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA
| | - Qing K Li
- Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA
| | - Hui Zhang
- Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA
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Christodoulidis G, Kouliou MN, Ragias D, Chatziisaak D, Agko ES, Schizas D, Zacharoulis D. Last decade of advances in gastric neuroendocrine tumors: Innovations, challenges, and future directions. World J Clin Oncol 2025; 16:104577. [DOI: 10.5306/wjco.v16.i5.104577] [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: 12/24/2024] [Revised: 02/27/2025] [Accepted: 03/10/2025] [Indexed: 05/19/2025] Open
Abstract
BACKGROUND Gastric neuroendocrine tumors (G-NETs) are rare tumors originating from enterochromaffin-like cells, with an incidence of 0.4 per 100000 annually. There are three main types: (1) Type I, linked to chronic atrophic gastritis and hypergastrinemia, makes up 75%–80% of G-NETs; (2) Type II, associated with Zollinger-Ellison syndrome (ZES) and multiple endocrine neoplasia, comprises 5%; and (3) Type III, sporadic tumors with a higher metastatic potential, accounting for 15%–25%. Diagnosis involves endoscopy, biopsy, and histological examination. Additional methods include serum gastrin testing, immunohistochemistry, and imaging techniques such as computer tomography or magnetic resonance imaging for detecting metastasis. Type I treatment usually involves endoscopic resection (ER), with surgical resection for recurrence. Somatostatin analogs (SSAs) can reduce tumor size, and the prognosis is generally excellent. Type II treatment centers on surgical removal of the gastrinoma, with ER for smaller lesions and SSAs for symptom management. Type III requires surgical resection (partial or total gastrectomy) with lymph node dissection, and possibly chemotherapy. This type has a worse prognosis due to its aggressive nature. Emerging treatments like Peptide Receptor Radionuclide Therapy are promising for advanced cases, and ongoing research into immunotherapies is expanding future treatment options. Regular endoscopic follow-up is crucial to monitor for recurrence or metastasis across all types. Our literature review explores the current perspectives on G-NETs and highlights the importance of further research to improve diagnostic precision and treatment, particularly for those associated with less favorable cases.
AIM To improve diagnostic precision and treatment, particularly for those associated with less favorable cases.
METHODS A systematic search was conducted in PubMed, Scopus, and Web of Science until September 2024. Two independent reviewers screened titles, abstracts, and full texts for eligibility based on G-NET treatment in adults. Eligible studies included cohort studies, clinical trials, case series, and case reports, while in vitro, pediatric, and non-English studies were excluded. Relevant data were extracted independently, and disagreements were resolved through discussion. Study quality was assessed using appropriate tools.
RESULTS G-NETs are rare, classified into three types: (1) Type I; (2) Type II; and (3) Type III. Type I G-NETs, often associated with chronic atrophic gastritis, are typically slow-growing and low-grade, with favorable outcomes following surgical resection. Type II G-NETs arise in hypergastrinemia conditions like multiple endocrine neoplasia and ZES, showing moderate malignancy risk. Type III G-NETs, the most aggressive and least common, present with distant metastases and poor prognosis. Diagnosis relies on endoscopy, imaging, and biomarkers like chromogranin A. Treatment varies by type, ranging from ER to aggressive surgery and chemotherapy for advanced cases. Regular follow-up is essential to monitor recurrence, particularly for type III G-NETs.
CONCLUSION G-NETs require tailored diagnosis and treatment based on type and stage. Types I and II generally have better prognosis, while types III and IV are linked to poorer outcomes due to invasion and metastasis. Treatment strategies vary from ER for type I to extensive surgery for type III. Emerging therapies, like somatostatin analogs and peptide-receptor radionuclide therapies, show promise in advanced cases. Further research is essential to improve early diagnosis and treatment, particularly for high-risk lesions.
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Affiliation(s)
| | - Marina Nektaria Kouliou
- Department of Internal Medicine, General Hospital of Argolida-Hospital Unit of Nafplio, Nafplio 21100, Pelopónnisos, Greece
| | - Dimitrios Ragias
- Department of Oncology, 251 Air Force General Hospital, Athens 11525, Greece
| | - Dimitrios Chatziisaak
- Department of Surgery, Kantonsspital St.Gallen, St.Gallen 9000, Switzerland
- Department of Surgery, Centre Hospitalier Universitaire Vaudois, Lausanne 1005, Switzerland
| | - Eirini Sara Agko
- Department of Intensive Care Unit, Asklepios Paulinen Clinic Wiesbaden, Wiesbaden 65197, Germany
| | - Dimitrios Schizas
- Department of Surgery, National and Kapodistrian University of Athens, Athens 11527, Greece
| | - Dimitrios Zacharoulis
- Department of General Surgery, University of Thessaly, Larisa 41110, Thessalia, Greece
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Zhang X, Huang XT, Xie JZ, Fu AQ, Chen W, Cai JP, Liang LJ, Yin XY. Prognostic significance of the number of hepatic lesions in multifocal intrahepatic cholangiocarcinoma after radical resection: an IPTW propensity-score analysis. BMC Cancer 2025; 25:930. [PMID: 40410740 PMCID: PMC12101014 DOI: 10.1186/s12885-025-13737-5] [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: 06/09/2024] [Accepted: 02/14/2025] [Indexed: 05/25/2025] Open
Abstract
BACKGROUND Multifocal hepatic lesions represent a distinctive subgroup within intrahepatic cholangiocarcinoma(iCCA), the management of these patients remains controversial. This study aimed to compare the survival of intrahepatic cholangiocarcinoma (iCCA) with different numbers of hepatic lesions and select patients benefiting most from surgery in multifocal iCCA. METHODS A cohort of 354 consecutive iCCA patients were included. Based on the number of hepatic lesions, patients were classified as follows: solitary tumors (type I), 2 or 3 hepatic lesions in the same-sided hepatic lobe (type II), and more than three hepatic lesions in the same-sided hepatic lobe (type III). Stabilized inverse probability treatment weighting (IPTW) was conducted for accurate prognosis comparisons. Furthermore, the long-term prognosis was compared between different American Joint Committee on Cancer. RESULTS Among all patients, multifocal iCCA presented significantly worse overall survival (OS) and recurrence-free survival (RFS) than solitary tumor (p < 0.001 and p < 0.001), 11.9% (n = 42), and 14.4% (n = 51) patients were classified into type II, and type III, respectively. After IPTW, type II exhibited similar while type III exhibited worse RFS and OS to type I cohort (solitary tumors) (p < 0.001and p < 0.001). Multivariable Cox analysis also identified type III tumors as an independent risk factor for OS (HR 1.95, 95% CI:1.33-2.87, p < 0.001). Among AJCC stage II (T2N0M0) patients, multifocal iCCA presented significantly worse OS than solitary tumors (vascular invasion) (p = 0.018), and type II exhibited similar while type III exhibited worse OS than solitary tumors (p = 0.500 and p = 0.040). Compared with stage III patients, type II exhibited better while type III exhibited similar OS (p < 0.001 and p = 0.300). CONCLUSIONS Multifocal iCCA presented a significantly worse prognosis, the number of hepatic lesions significantly influenced the prognosis of multifocal iCCA. Patients with type II tumors may derive comparable oncological benefits from surgery compared with solitary tumors, radical surgery still be strongly recommended as the preferred treatment.
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Affiliation(s)
- Xin Zhang
- Department of Pancreato-Biliary Surgery, The First Affiliated Hospital, Sun Yat-Sen University, 58 Zhongshan 2nd Rd, Guangzhou, Guangdong, 510080, People's Republic of China
| | - Xi-Tai Huang
- Department of Pancreato-Biliary Surgery, The First Affiliated Hospital, Sun Yat-Sen University, 58 Zhongshan 2nd Rd, Guangzhou, Guangdong, 510080, People's Republic of China
| | - Jin-Zhao Xie
- Department of Pancreato-Biliary Surgery, The First Affiliated Hospital, Sun Yat-Sen University, 58 Zhongshan 2nd Rd, Guangzhou, Guangdong, 510080, People's Republic of China
| | - Ai-Qing Fu
- Department of Pancreato-Biliary Surgery, The First Affiliated Hospital, Sun Yat-Sen University, 58 Zhongshan 2nd Rd, Guangzhou, Guangdong, 510080, People's Republic of China
| | - Wei Chen
- Department of Pancreato-Biliary Surgery, The First Affiliated Hospital, Sun Yat-Sen University, 58 Zhongshan 2nd Rd, Guangzhou, Guangdong, 510080, People's Republic of China
| | - Jian-Peng Cai
- Department of Pancreato-Biliary Surgery, The First Affiliated Hospital, Sun Yat-Sen University, 58 Zhongshan 2nd Rd, Guangzhou, Guangdong, 510080, People's Republic of China
| | - Li-Jian Liang
- Department of Pancreato-Biliary Surgery, The First Affiliated Hospital, Sun Yat-Sen University, 58 Zhongshan 2nd Rd, Guangzhou, Guangdong, 510080, People's Republic of China
| | - Xiao-Yu Yin
- Department of Pancreato-Biliary Surgery, The First Affiliated Hospital, Sun Yat-Sen University, 58 Zhongshan 2nd Rd, Guangzhou, Guangdong, 510080, People's Republic of China.
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Ondu A, Herlea V, Botea F, Becheanu G, Diculescu MM. A peculiar mimicker of gastro-entero-pancreatic neuroendocrine tumors: Malignant Gastrointestinal Neuroectodermal Tumor - literature review and one case report. Arch Clin Cases 2025; 12:66-74. [PMID: 40416581 PMCID: PMC12096305 DOI: 10.22551/2025.47.1202.10316] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/27/2025] Open
Abstract
Malignant gastrointestinal neuroectodermal tumor (GNET) is a distinctive and relatively newly described neoplasm that is seldom encountered in routine clinical practice. It is characterized by a predominantly monomorphic population of polyhedral to epithelioid cells, exhibiting pale eosinophilic or clear cytoplasm, rounded nuclei with vesicular chromatin, and occasionally prominent eosinophilic nucleoli. These cells are arranged in a heterogeneous pattern, forming small nests, compact solid areas, and pseudo-papillary or pseudo-microcystic structures. Within the tumor, osteoclast-like giant cells may be a notable feature, although their presence is variable. This tumor consistently demonstrates positivity for S100, SOX10, and vimentin, while it is invariably negative for Melan-A, HMB45, desmin, CD117, and pan-cytokeratin. Additionally, it exhibits variable expression of the following immunohistochemical markers: synaptophysin, chromogranin, CD56, neuron-specific enolase (NSE), and neurofilament protein (NFP). A specific mutation in the Ewing's sarcoma breakpoint region 1 (EWSR1) gene has been described for GNET, characterized by EWSR1-CREB1 and EWSR1-ATF1 fusions. This article discusses the clinical, pathological, immunophenotypic, and genetic features of one clinical case of GNET, followed by a literature review of 127 cases published in the PubMed database, for which full-length articles were accessible. According to this review, approximately 10% of GNETs have been initially misdiagnosed, with about 6% being misclassified as neuroendocrine tumors or neuroendocrine carcinomas.
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Affiliation(s)
- Alexandra Ondu
- Faculty of Medicine, “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania
| | - Vlad Herlea
- Faculty of Medicine, “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania
- Fundeni Clinical Institute, Bucharest, Romania
| | | | - Gabriel Becheanu
- Faculty of Medicine, “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania
- Fundeni Clinical Institute, Bucharest, Romania
| | - Mihai-Mircea Diculescu
- Faculty of Medicine, “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania
- Fundeni Clinical Institute, Bucharest, Romania
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Nwoguh CA, Asmar ME, Mortagy M, Srirajaskanthan R, Russell B, White BE, Chandrakumaran K, Ramage JK. The geographical distribution of neuroendocrine neoplasms in England (2012-2018). J Neuroendocrinol 2025:e70038. [PMID: 40404336 DOI: 10.1111/jne.70038] [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: 01/16/2025] [Revised: 04/03/2025] [Accepted: 04/15/2025] [Indexed: 05/24/2025]
Abstract
Neuroendocrine Neoplasms (NEN) are increasing in incidence in England over the past two decades. Geographic and socio-economic disparities influence both incidence and survival rates. This study explores the relationship between environmental factors, access to specialised care in Centres of Excellence (CoE), and survival outcomes for NEN patients across England using Geographical Information Systems (GIS) to visualise disease distribution. Data on 19,958 NEN cases diagnosed between 2012 and 2018 were retrieved from the National Cancer Registry and Analysis Service (NCRAS) in England. GIS was used to analyse patient data, including spatial units, environmental factors, and travel times to CoE. Statistical analyses, including age-standardised rates, spatial autocorrelation, and survival analyses, were performed using QGIS, SPSS, R, and Stata software. Regional distribution showed the highest age-standardised rates (ASR) in the North-East, with lung NEN demonstrating significant spatial clustering. Environmental exposures, such as PM2.5 pollution, did not show a strong correlation with NEN distribution. Longer travel times to specialised centres were associated with worse overall survival, particularly in rural areas and among patients with higher socio-economic deprivation. Minor variations in survival rates were observed across different geographical regions when compared to London. This study highlights the uneven burden of disease across different regions in England. We have demonstrated variation in the country relating to anatomical sites and significant differences within rural or urban environments. Proximity to specialist centres was associated with better overall survival, highlighting the need for improved access to care.
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Affiliation(s)
| | | | | | | | - Beth Russell
- Centre for Cancer, Society and Public Health, Kings College London, London, UK
| | | | | | - John K Ramage
- Hampshire Hospitals NHS Foundation Trust, Basingstoke, UK
- Kings Health Partners NET Centre, Kings College Hospitals, Denmark Hill, UK
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Nagarajan KV, Yelsangikar A, Krishnamurthy AN, Bindu H, Patted A, Bhat V, Kaur T, Bhat N. Japanese narrow band imaging expert team classification of colorectal polyps: A validation study from India. Indian J Gastroenterol 2025:10.1007/s12664-025-01784-6. [PMID: 40392505 DOI: 10.1007/s12664-025-01784-6] [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: 10/25/2024] [Accepted: 04/07/2025] [Indexed: 05/22/2025]
Abstract
BACKGROUND Japanese narrow band imaging expert team (JNET) classification has a diagnostic accuracy above 90% in differentiating neoplastic from non-neoplastic colonic polyps as well as estimating the depth of invasion in colorectal cancer. However, its validation outside Japan is limited to expert centers and requires magnifying endoscopes. AIMS AND METHODS This study aimed at validating the JNET classification prospectively in a real-world setting in India using magnifying endoscopes with dual focus. We analyzed consecutive patients with colonic polyps detected via these endoscopes. The JNET classification was compared with histopathology, the gold standard and its diagnostic accuracy was assessed. RESULTS Total 203 consecutive patients with colonic polyps underwent examination using a magnifying endoscope with dual focus. In real time, 331 polyps were identified and classified based on the JNET classification. Among them, 15 polyps could not be retrieved, leaving 316 polyps for histopathological comparison in the study. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of each JNET classification type, along with their 95% confidence intervals, are as follows. For Type-1 JNET classification, the values are 78% (69-86), 97% (94-99), 92% (84-97), 92% (87-95) and 92% (88-94), respectively. Type-2 A JNET classification has corresponding values of 92% (86-96), 84% (78-89), 82% (75-88), 93% (88-97) and 88% (84-91). For Type-2B JNET classification, the values are 45% (24-68), 97% (95-99), 56% (31-78), 96% (93-98) and 93% (90-96). Lastly, Type-3 JNET classification has values of 95% (87-99), 98% (96-100), 94% (85-98), 99% (97-100) and 98% (96-99), respectively. CONCLUSIONS The JNET classification has good accuracy in characterizing colonic polyps using magnifying endoscopes with dual focus. Large-volume, multicentric data is necessary to validate the findings in our study.
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Affiliation(s)
- Kayal Vizhi Nagarajan
- Department of Gastroenterology, Hepatology and Clinical Nutrition, Aster CMI Hospital, Bengaluru, 560 092, India.
| | - Amit Yelsangikar
- Department of Gastroenterology, Hepatology and Clinical Nutrition, Aster CMI Hospital, Bengaluru, 560 092, India
| | - Anupama Nagar Krishnamurthy
- Department of Gastroenterology, Hepatology and Clinical Nutrition, Aster CMI Hospital, Bengaluru, 560 092, India
| | - Hima Bindu
- Department of Gastroenterology, Hepatology and Clinical Nutrition, Aster CMI Hospital, Bengaluru, 560 092, India
| | - Arun Patted
- Department of Gastroenterology, Hepatology and Clinical Nutrition, Aster CMI Hospital, Bengaluru, 560 092, India
| | - Vinay Bhat
- Department of Surgery and Allied Specialities, Aster CMI Hospital, Bengaluru, 560 092, India
| | - Tripti Kaur
- Department of Histopathology, Aster Labs, Bengaluru, 560 001, India
| | - Naresh Bhat
- Department of Gastroenterology, Hepatology and Clinical Nutrition, Aster CMI Hospital, Bengaluru, 560 092, India
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Zakeri N, Sundareyan R, Cain O, Good J, Shah T, Shetty S. Stereotactic ablative radiotherapy for patients with hepatocellular carcinoma: analysis of post-treatment radiology and explant histology. BJC REPORTS 2025; 3:36. [PMID: 40394138 PMCID: PMC12092826 DOI: 10.1038/s44276-025-00136-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/16/2024] [Revised: 03/11/2025] [Accepted: 03/23/2025] [Indexed: 05/22/2025]
Abstract
BACKGROUND Stereotactic ablative radiotherapy (SABR) has emerged as a new treatment modality for hepatocellular carcinoma (HCC). Evaluation of tumour responses following SABR are currently based on conventional radiological criteria used for locoregional therapies. Whether these criteria accurately reflect tumour responses following SABR remains unknown. In this study, we provide a direct comparison of post-SABR radiological evaluation and explant histology for patients with HCC who underwent bridging SABR prior to liver transplantation. METHODS Patients with HCC who received SABR as bridging therapy prior to liver transplantation (January 2016-December 2022) in a large UK liver transplant centre were included. Post-SABR imaging was reported by two specialist hepato-pancreato-biliary radiologists, and histological examination of the explanted liver was performed by experienced liver histopathologists. RESULTS Six patients with residual active HCC received SABR as bridging therapy prior to undergoing liver transplantation in our cohort. Of five patients with viable HCC detected on explant histology, recent radiological evaluation using LI-RADS treatment response criteria had suggested no evidence of residual active HCC for three patients, difficulty delineating residual disease from post-radiotherapy changes for one patient, and accurately identified viable tumour in one patient. CONCLUSION In our case series conventional radiological criteria underestimated HCC tumour viability following SABR compared to explant histology. As the role for SABR expands in the management of HCC, caution is needed with radiological interpretation of HCC responses to radiotherapy using standard LI-RADS criteria. Prospective study in a larger cohort is required to identify radiological criteria capable of more conclusively evaluating HCC responses to SABR.
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Affiliation(s)
- Nekisa Zakeri
- National Institute for Health and Care Research (NIHR) Birmingham Biomedical Research Centre, University of Birmingham, Birmingham, UK.
- Department of Hepatology and Liver Transplantation, Queen Elizabeth Hospital Birmingham, Birmingham, UK.
| | | | - Owen Cain
- Department of Cellular Pathology, Queen Elizabeth Hospital Birmingham, Birmingham, UK
| | - James Good
- Department of Oncology, Queen Elizabeth Hospital Birmingham, Birmingham, UK
| | - Tahir Shah
- Department of Hepatology and Liver Transplantation, Queen Elizabeth Hospital Birmingham, Birmingham, UK
| | - Shishir Shetty
- National Institute for Health and Care Research (NIHR) Birmingham Biomedical Research Centre, University of Birmingham, Birmingham, UK
- Department of Hepatology and Liver Transplantation, Queen Elizabeth Hospital Birmingham, Birmingham, UK
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Meyers M, Karfis I, Hendlisz A. Are epigenetic-targeting approaches ready for prime time in neuroendocrine neoplasms? Curr Opin Oncol 2025:00001622-990000000-00261. [PMID: 40422736 DOI: 10.1097/cco.0000000000001158] [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: 05/28/2025]
Abstract
PURPOSE OF REVIEW The purpose of this review is to evaluate the role of epigenetic-targeting approaches in the management of neuroendocrine neoplasms (NENs), particularly as a priming strategy for subsequent therapies. We explore the molecular basis of epigenetic modifications in NENs, and we review preclinical and clinical studies on DNA methyltransferase and histone deacetylase (HDAC) inhibitors. RECENT FINDINGS DNA methyltransferase and HDAC inhibitors can upregulate SSTR2 expression, thereby improving radioligand uptake and treatment response in NENs. The LANTana study investigates ASTX727 as a strategy to restore SSTR2 expression in metastatic NENs, allowing previously ineligible patients to receive PRRT. Preclinical studies demonstrate that combining epigenetic agents with radiotherapy, chemotherapy, or targeted inhibitors can enhance tumour sensitivity and overcome resistance. SUMMARY Epigenetic modifications play a crucial role in NENs, influencing tumour progression, therapy resistance, and SSTR2 expression. Epigenetic priming with DNA methyltransferase and HDAC inhibitors can enhance SSTR2 expression, improving the efficacy of PRRT in NENs. The LANTana study and other trials are investigating whether epigenetic-targeting approaches can be integrated into NEN treatment to optimize PRRT and overcome therapeutic limitations.
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Affiliation(s)
- Michel Meyers
- Université Libre de Bruxelles, Centre Hospitalier du Luxembourg, Luxembourg City, Luxembourg
- Institut Jules Bordet, Department of Medical Oncology
| | - Ioannis Karfis
- Université Libre de Bruxelles, Institut Jules Bordet, Department of Nuclear Medicine
| | - Alain Hendlisz
- Université Libre de Bruxelles, Institut Jules Bordet, Department of Digestive Oncology, ENETS Center of Excellence, Brussels, Belgium
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Sorbye H, Hjortland GO, Vestermark LW, Ladekarl M, Svensson J, Sundlöv A, Janson ET, Garresori H, Hofsli E, Kersten C, Elvebakken H, Pfeiffer P, Morken S, Assmus J, Lothe IMB, Tabaksblat E, Knigge U, Couvelard A, Perren A, Langer SW. Characteristics and treatment outcome in a prospective cohort of 639 advanced high-grade digestive neuroendocrine neoplasms (NET G3 and NEC). The NORDIC NEC 2 study. Br J Cancer 2025:10.1038/s41416-025-03054-w. [PMID: 40382522 DOI: 10.1038/s41416-025-03054-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2025] [Revised: 04/24/2025] [Accepted: 05/01/2025] [Indexed: 05/20/2025] Open
Abstract
BACKGROUND Digestive high-grade neuroendocrine neoplasms (HG-NEN) are rare and classified as neuroendocrine carcinomas (NEC) or neuroendocrine tumours G3 (NET G3), and differ in clinical and molecular characteristics, response to treatment and prognosis. METHODS Prospective multicenter study registering clinical data on patients with digestive HG-NEN. Treatment outcome in patients with advanced disease was compared after centralized pathological re-evaluation. RESULTS 427 NEC and 117 NET G3 received palliative chemotherapy. Immediate progression rate was 41% and 24%, progression-free survival (PFS) 3.4 m and 7.4 m, overall survival (OS) 7.4 m and 21.8 m for NEC and NET G3, respectively. Significant factors for OS in NEC were performance status (PS), Ki-67 > 55%, alkaline phosphatase (ALP), age, sex and for PFS colorectal primary and PS. NEC Ki-67 < 55% had similar OS comparing treatment. Significant factors for OS in NET G3 were platinum-based treatment, PS, age and ALP, and for PFS platinum-based treatment. CONCLUSIONS Survival was shorter than expected in this unique population-based cohort of advanced digestive HG-NEN, likely due to inclusion of elderly and patients with poor PS. Several novel prognostic factors were identified for NEC and NET G3. An initial sub-effective platinum-based treatment for NET G3 could not be compensated by later-line treatment.
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Affiliation(s)
- Halfdan Sorbye
- Cancer Clinic, Haukeland University Hospital, Bergen, Norway.
- Department of Clinical Science, University of Bergen, Bergen, Norway.
| | | | | | - Morten Ladekarl
- Department of Oncology, Aarhus University Hospital, Aarhus, Denmark
- Department of Oncology, Clinical Cancer Research Center, Aalborg University Hospital, and Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
| | - Johanna Svensson
- Department of Oncology, Sahlgrenska University Hospital, Gothenburg, Sweden
| | - Anna Sundlöv
- Department of Oncology, Skåne University Hospital, Lund, Sweden
| | - Eva Tiensuu Janson
- Department of Medical Sciences, Section of Endocrine Oncology, Uppsala University, Uppsala, Sweden
| | - Herish Garresori
- Department of Oncology, Stavanger University Hospital, Stavanger, Norway
| | - Eva Hofsli
- Department of Oncology, St.Olavs Hospital, Trondheim, Norway
| | - Christian Kersten
- Department of Research, Hospital of Southern Norway, Kristiansand, Norway
| | - Hege Elvebakken
- Department of Oncology, Ålesund Hospital, Møre og Romsdal Hospital Trust, Ålesund, Norway
| | - Per Pfeiffer
- Department of Oncology, Odense University Hospital, Odense, Denmark
| | - Siren Morken
- Cancer Clinic, Haukeland University Hospital, Bergen, Norway
- Department of Clinical Science, University of Bergen, Bergen, Norway
| | - Jorg Assmus
- Centre for Clinical Research, Haukeland University Hospital, Bergen, Norway
| | | | | | - Ulrich Knigge
- Department of Surgery C and Endocrinology PE, Rigshospitalet, Faculty of Health Science, University of Copenhagen, Copenhagen, Denmark
| | | | - Aurel Perren
- Institute of Tissue Medicine and Pathology, University of Bern, Bern, Switzerland
| | - Seppo W Langer
- Department of Oncology, Rigshospitalet, Copenhagen, Denmark
- Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
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Yoshida M, Kinoshita M, Nonomiya Y, Kawai R, Shintani A, Sato Y, Kawaguchi T, Tanaka R, Kurihara S, Nishio K, Shinkawa H, Kimura K, Yamamoto A, Kubo S, Ishizawa T. A Preoperative Diagnostic Nomogram to Predict Tumor Subclassifications of Intrahepatic Cholangiocarcinoma. Cancers (Basel) 2025; 17:1690. [PMID: 40427187 PMCID: PMC12110386 DOI: 10.3390/cancers17101690] [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: 04/02/2025] [Revised: 05/13/2025] [Accepted: 05/15/2025] [Indexed: 05/29/2025] Open
Abstract
BACKGROUND/OBJECTIVES Intrahepatic cholangiocarcinoma (ICC) is subclassified into small and large duct types. Although these subclassifications may help determine the appropriate treatment strategy, subclassification diagnosis currently depends on postoperative pathological examinations. This study aimed to establish a nomogram to predict ICC subclassifications. METHODS This study included 126 patients with ICC who underwent liver resection. The participants were divided into small and large duct-type ICC groups. A nomogram to predict large duct-type ICC was developed using four diagnostic imaging findings: rim-type enhancement in the early phase, an absence of tumor enhancement in the early phase, the presence of peripheral biliary dilatation due to tumor invasion, the presence of penetrating Glisson's vessels in the tumor, and two laboratory test results: serum gamma-glutamyl transpeptidase and carbohydrate antigen 19-9 levels. Nomogram performance was also assessed. Moreover, the bootstrap method and calibration plots were used to assess nomogram validity. RESULTS Seventy and fifty-six patients were pathologically diagnosed with small and large duct-type ICCs, respectively. The area under the curve of the established nomogram was 0.93 and remained 0.91 after Harrell's bias correction. The sensitivity and specificity of the nomogram developed using the Youden index were higher than those of any of the characteristic imaging findings. Calibration plots demonstrated a strong association between the nomogram and the actual data. CONCLUSIONS We developed a novel preoperative nomogram to predict large duct-type ICC. This nomogram can be clinically useful for predicting the subclassifications of ICCs and may contribute to the establishment of a more appropriate treatment strategy for ICC.
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Affiliation(s)
- Mizuki Yoshida
- Department of Hepato-Biliary-Pancreatic Surgery, Osaka Metropolitan University Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585, Japan; (M.Y.); (T.K.); (R.T.); (S.K.); (K.N.); (H.S.); (K.K.); (S.K.); (T.I.)
| | - Masahiko Kinoshita
- Department of Hepato-Biliary-Pancreatic Surgery, Osaka Metropolitan University Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585, Japan; (M.Y.); (T.K.); (R.T.); (S.K.); (K.N.); (H.S.); (K.K.); (S.K.); (T.I.)
| | - Yuta Nonomiya
- Department of Medical Statistics, Osaka Metropolitan University Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585, Japan; (Y.N.); (R.K.); (A.S.)
- Smart Data & Knowledge Services, Deutsches Forschungszentrum für Künstliche Intelligenz (DFKI), Trippstadter Straße 122, 67663 Kaiserslautern, Germany
| | - Ryota Kawai
- Department of Medical Statistics, Osaka Metropolitan University Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585, Japan; (Y.N.); (R.K.); (A.S.)
| | - Ayumi Shintani
- Department of Medical Statistics, Osaka Metropolitan University Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585, Japan; (Y.N.); (R.K.); (A.S.)
| | - Yasunori Sato
- Department of Human Pathology, Kanazawa University Graduate School of Medical Sciences, 13-1 Takaramachi, Kanazawa, Ishikawa 920-8640, Japan;
| | - Takahito Kawaguchi
- Department of Hepato-Biliary-Pancreatic Surgery, Osaka Metropolitan University Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585, Japan; (M.Y.); (T.K.); (R.T.); (S.K.); (K.N.); (H.S.); (K.K.); (S.K.); (T.I.)
| | - Ryota Tanaka
- Department of Hepato-Biliary-Pancreatic Surgery, Osaka Metropolitan University Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585, Japan; (M.Y.); (T.K.); (R.T.); (S.K.); (K.N.); (H.S.); (K.K.); (S.K.); (T.I.)
| | - Shigeaki Kurihara
- Department of Hepato-Biliary-Pancreatic Surgery, Osaka Metropolitan University Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585, Japan; (M.Y.); (T.K.); (R.T.); (S.K.); (K.N.); (H.S.); (K.K.); (S.K.); (T.I.)
| | - Kohei Nishio
- Department of Hepato-Biliary-Pancreatic Surgery, Osaka Metropolitan University Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585, Japan; (M.Y.); (T.K.); (R.T.); (S.K.); (K.N.); (H.S.); (K.K.); (S.K.); (T.I.)
| | - Hiroji Shinkawa
- Department of Hepato-Biliary-Pancreatic Surgery, Osaka Metropolitan University Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585, Japan; (M.Y.); (T.K.); (R.T.); (S.K.); (K.N.); (H.S.); (K.K.); (S.K.); (T.I.)
| | - Kenjiro Kimura
- Department of Hepato-Biliary-Pancreatic Surgery, Osaka Metropolitan University Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585, Japan; (M.Y.); (T.K.); (R.T.); (S.K.); (K.N.); (H.S.); (K.K.); (S.K.); (T.I.)
| | - Akira Yamamoto
- Department of Radiology, Osaka Metropolitan University Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585, Japan;
| | - Shoji Kubo
- Department of Hepato-Biliary-Pancreatic Surgery, Osaka Metropolitan University Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585, Japan; (M.Y.); (T.K.); (R.T.); (S.K.); (K.N.); (H.S.); (K.K.); (S.K.); (T.I.)
- Health Education Course, Department of Education, Faculty of Education, Shitennoji University, 3-2-1 Gakuenmae, Habikino, Osaka 583-8501, Japan
| | - Takeaki Ishizawa
- Department of Hepato-Biliary-Pancreatic Surgery, Osaka Metropolitan University Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585, Japan; (M.Y.); (T.K.); (R.T.); (S.K.); (K.N.); (H.S.); (K.K.); (S.K.); (T.I.)
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Goto N, Agudo J, Yilmaz ÖH. Early immune evasion in colorectal cancer: interplay between stem cells and the tumor microenvironment. Trends Cancer 2025:S2405-8033(25)00112-8. [PMID: 40382216 DOI: 10.1016/j.trecan.2025.04.016] [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: 01/27/2025] [Revised: 04/23/2025] [Accepted: 04/24/2025] [Indexed: 05/20/2025]
Abstract
Most colorectal cancers (CRCs) are characterized by a low mutational burden and an immune-cold microenvironment, limiting the efficacy of immune checkpoint blockade (ICB) therapies. While advanced tumors exhibit diverse immune evasion mechanisms, emerging evidence suggests that aspects of immune escape arise much earlier, within precancerous lesions. In this review, we discuss how early driver mutations and epigenetic alterations contribute to the establishment of an immunosuppressive microenvironment in CRC. We also highlight the dynamic crosstalk between cancer cells, stromal niche cells, and immune cells driving immune evasion and liver metastasis. A deeper understanding of these early events may guide the development of more effective preventive and therapeutic strategies for CRC.
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Affiliation(s)
- Norihiro Goto
- Joan and Sanford I. Weill Department of Medicine, Division of Gastroenterology & Hepatology, Weill Cornell Medicine, Cornell University, New York, NY 10021, USA; Jill Roberts Institute for Research in Inflammatory Bowel Disease, Weill Cornell Medicine, Cornell University, New York, NY 10021, USA.
| | - Judith Agudo
- Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Immunology, Harvard Medical School, Boston, MA 02215, USA; Ludwig Center at Harvard, Boston, MA 02215, USA; Parker Institute for Cancer Immunotherapy at Dana-Farber Cancer Institute, Boston, MA 02215, USA; New York Stem Cell Foundation, New York, NY 10019, USA
| | - Ömer H Yilmaz
- Department of Biology, The David H. Koch Institute for Integrative Cancer Research at MIT, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA 02142, USA; Department of Pathology, Beth Israel Deaconess Hospital and Harvard Medical School, Boston, MA 02114, USA; Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
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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 PMCID: PMC12084448 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] [Download PDF] [Figures] [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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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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Levy V, Jreige M, Haefliger L, Du Pasquier C, Noirot C, Dorothea Wagner A, Mantziari S, Schäfer M, Vietti-Violi N, Dromain C. Evaluation of MRI for initial staging of esophageal cancer: the STIRMCO study. Eur Radiol 2025:10.1007/s00330-025-11549-6. [PMID: 40379940 DOI: 10.1007/s00330-025-11549-6] [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: 10/31/2024] [Revised: 01/08/2025] [Accepted: 02/21/2025] [Indexed: 05/19/2025]
Abstract
OBJECTIVES To compare the diagnostic accuracy of MRI and PET/CT combined versus standard staging methods (CT, endoscopic ultrasound [EUS], and PET/CT) for initial staging of esophageal cancer (EC). MATERIALS AND METHODS This study included patients newly diagnosed with histologically proven EC between 2017 and 2021. Patients underwent a 3-T esophageal MRI alongside standard staging (CT, EUS, PET/CT) prior to treatment. TNM-stages were assessed by two independent reviewers for MRI, CT, and PET/CT, with EUS evaluated by one operator. Discrepancies were resolved by a third reviewer. Patients were categorized based on treatment management: surgery (T1-T2N0M0), neoadjuvant (radio)chemotherapy (T3-T4a and/or N1-N2-N3M0), and palliative chemotherapy (T4b and/or M1). The reference standard was histopathology from surgical specimens or TNM staging from tumor board discussions. The area under the curve (AUC) was calculated for each imaging combination. RESULTS 60 patients newly diagnosed with EC (50M/10F; mean age 66.5 years) were prospectively enrolled. MRI + PET/CT combination exhibited the highest AUC (0.92, 95% CI: 0.79-1) for differentiating curative versus palliative patients, without statistically significant difference compared to CT + EUS (0.80, 95% CI: 0.56-1, p = 0.34), CT + PET/CT (0.77, 95% CI: 0.53-1, p = 0.42), and CT + EUS + PET/CT (0.78, 95% CI: 0.58-0.97, p = 0.26). In term of differentiating patients eligible for upfront surgery from those with indication for neoadjuvant (radio)chemotherapy, the combination of CT + EUS + PET/CT demonstrated the highest AUC (0.90, 95% CI: 0.75-1) without statistically significant difference compared to CT + EUS (0.82, 95% CI: 0.56-1, p = 0.49), CT + PET/CT (0.79, 95% CI: 0.46-1, p = 0.36), and MRI + PET/CT (0.83, 95% CI: 0.65-1, p = 0.59). CONCLUSION MRI + PET/CT combination is highly accurate for initial EC staging and non-inferior to standard methods, offering less invasiveness and reduced radiation exposure. KEY POINTS Question Can MRI help improve the TNM staging of esophageal cancer? Findings MRI + PET/CT showed no statistically significant difference compared to endoscopic ultrasound (EUS) + CT + PET/CT in identifying curative vs palliative patients but with a tendency for improved staging. Clinical relevance Thoraco-abdominal MRI can provide added value (as a replacement of CT and EUS) in initial staging of esophagus cancer, particularly in cases of stenotic or advanced tumors.
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Affiliation(s)
- Vincent Levy
- Department of Radiodiagnostic and Interventional Radiology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland
| | - Mario Jreige
- Department of Nuclear Medicine, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland
| | - Laura Haefliger
- Department of Radiodiagnostic and Interventional Radiology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland
| | - Celine Du Pasquier
- Department of Radiodiagnostic and Interventional Radiology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland
| | - Camille Noirot
- Department of Radiodiagnostic and Interventional Radiology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland
| | - Anna Dorothea Wagner
- Department of Oncology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland
| | - Styliani Mantziari
- Department of Visceral Surgery, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland
| | - Markus Schäfer
- Department of Visceral Surgery, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland
| | - Naik Vietti-Violi
- Department of Radiodiagnostic and Interventional Radiology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland
| | - Clarisse Dromain
- Department of Radiodiagnostic and Interventional Radiology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
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