Ondrej Uher (Postdoctoral Fellow) , Katerina Hadrava Vanova (Postdoctoral Fellow) , Katerina Petrlakova (PhD Candidate) , Rachael Labitt (Attending Veterinarian) , Radka Lencova (PhD Candidate) , Andrea Frejlachova (PhD Candidate) , Juan Ye (Postdoctoral Fellow) , Herui Wang (Staff Scientist) , Michal Masarik (Senior Investigator) , Jan Zenka (Senior Investigator) , Zhengping Zhuang (Senior Investigator) , Karel Pacak (Senior Investigator)
{"title":"Role of B cells in intratumoral MBTA immunotherapy of murine pheochromocytoma model","authors":"Ondrej Uher (Postdoctoral Fellow) , Katerina Hadrava Vanova (Postdoctoral Fellow) , Katerina Petrlakova (PhD Candidate) , Rachael Labitt (Attending Veterinarian) , Radka Lencova (PhD Candidate) , Andrea Frejlachova (PhD Candidate) , Juan Ye (Postdoctoral Fellow) , Herui Wang (Staff Scientist) , Michal Masarik (Senior Investigator) , Jan Zenka (Senior Investigator) , Zhengping Zhuang (Senior Investigator) , Karel Pacak (Senior Investigator)","doi":"10.1016/j.beem.2024.101941","DOIUrl":"10.1016/j.beem.2024.101941","url":null,"abstract":"<div><div>Immunotherapy represents a revolutionary advancement in cancer treatment, which has traditionally focused on T cells; however, the role of B cells in cancer immunotherapy has gained interest because of their role in antigen presentation, antibody production, and cytokine release. In this study, we examined the role of B cells in previously developed intratumoral MBTA therapy (mannan-BAM, TLR ligands, and anti-CD40 antibody) in murine models of MTT pheochromocytoma. The results indicated that B cells significantly enhance the success of MBTA therapy, with wild-type mice exhibiting a lower tumor incidence and smaller tumors compared with B cell-deficient mice. Increased IL-6 and TNF-alpha levels indicated severe inflammation and a potential cytokine storm in B cell-deficient mice. Neutralization of TNF-alpha ameliorated these complications but resulted in increased tumor recurrence. The results highlight the important role of B cells in enhancing the immune response and maintaining immune homeostasis during MBTA therapy. Our findings offer new insights into improving therapeutic outcomes.</div></div>","PeriodicalId":8810,"journal":{"name":"Best practice & research. Clinical endocrinology & metabolism","volume":"39 1","pages":"Article 101941"},"PeriodicalIF":6.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142267228","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Christina Pamporaki (Endocrinologist) , Ruth T. Casey (Endocrinologist)
{"title":"Current views on paediatric phaeochromocytoma and paraganglioma with a focus on newest guidelines","authors":"Christina Pamporaki (Endocrinologist) , Ruth T. Casey (Endocrinologist)","doi":"10.1016/j.beem.2024.101957","DOIUrl":"10.1016/j.beem.2024.101957","url":null,"abstract":"<div><div>Phaeochromocytoma and paraganglioma (PPGL) are rare neuroendocrine tumours which arise from chromaffin cells of the adrenal medulla or extra-adrenal autonomic ganglia. PPGL most commonly present in adulthood but can arise in childhood and adolescence with an estimated annual incidence of 0.5 cases per million children per year. There have been significant advances in the diagnosis and management of PPGL over the past 2–3 decades based largely on the study of adult patients. These advances in clinical knowledge can be applied to paediatric patients but like other cancers, paediatric PPGL must be viewed as a distinct subset with their own specific challenges and opportunities for improved clinical care. This review article provides an overview on the diagnosis and management of PPGL in children focusing on recent international guidance.</div></div>","PeriodicalId":8810,"journal":{"name":"Best practice & research. Clinical endocrinology & metabolism","volume":"39 1","pages":"Article 101957"},"PeriodicalIF":6.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142649974","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Zbyněk Tüdös (Associate Professor in Radiology) , Lucia Veverková (Consultant in Radiology) , Jan Baxa (Professor in Radiology) , Igor Hartmann (Consultant in Urology) , Filip Čtvrtlík (Associate Professor in Radiology)
{"title":"The current and upcoming era of radiomics in phaeochromocytoma and paraganglioma","authors":"Zbyněk Tüdös (Associate Professor in Radiology) , Lucia Veverková (Consultant in Radiology) , Jan Baxa (Professor in Radiology) , Igor Hartmann (Consultant in Urology) , Filip Čtvrtlík (Associate Professor in Radiology)","doi":"10.1016/j.beem.2024.101923","DOIUrl":"10.1016/j.beem.2024.101923","url":null,"abstract":"<div><div>The topic of the diagnosis of phaeochromocytomas remains highly relevant because of advances in laboratory diagnostics, genetics, and therapeutic options and also the development of imaging methods. Computed tomography still represents an essential tool in clinical practice, especially in incidentally discovered adrenal masses; it allows morphological evaluation, including size, shape, necrosis, and unenhanced attenuation. More advanced post-processing tools to analyse digital images, such as texture analysis and radiomics, are currently being studied. Radiomic features utilise digital image pixels to calculate parameters and relations undetectable by the human eye. On the other hand, the amount of radiomic data requires massive computer capacity. Radiomics, together with machine learning and artificial intelligence in general, has the potential to improve not only the differential diagnosis but also the prediction of complications and therapy outcomes of phaeochromocytomas in the future. Currently, the potential of radiomics and machine learning does not match expectations and awaits its fulfilment.</div></div>","PeriodicalId":8810,"journal":{"name":"Best practice & research. Clinical endocrinology & metabolism","volume":"39 1","pages":"Article 101923"},"PeriodicalIF":6.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142127599","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Emma Boehm , Anthony J. Gill , Roderick Clifton-Bligh , Richard W. Tothill
{"title":"Recent progress in molecular classification of phaeochromocytoma and paraganglioma","authors":"Emma Boehm , Anthony J. Gill , Roderick Clifton-Bligh , Richard W. Tothill","doi":"10.1016/j.beem.2024.101939","DOIUrl":"10.1016/j.beem.2024.101939","url":null,"abstract":"<div><div>Phaeochromocytomas (PC) and paragangliomas (PG) are neural crest cancers with high heritability. Recent advances in molecular profiling, including multi-omics and single cell genomics has identified up to seven distinct molecular subtypes. These subtypes are defined by mutations involving hypoxia-inducible factors (HIFs), Krebs cycle, kinase and WNT signalling, but are also defined by chromaffin differentiation states. PCPG have a dominant proangiogenic microenvironment linked to HIF pathway activity and are generally considered “immune cold” tumours with a high number of macrophages. PCPG subtypes can indicate increased metastatic risk but secondary mutations in telomere maintenance genes <em>TERT</em> or <em>ATRX</em> are required to drive the metastatic phenotype. Molecular profiling can identify molecular therapeutic (e.g. <em>RET</em> and <em>EPAS1</em>) and radiopharmaceutical targets while also helping to support variant pathogenicity and familial risk. Molecular profiling and subtyping of PCPG therefore confers the possibility of nuanced prognostication and individual treatment stratification but this still requires large-scale prospective validation.</div></div>","PeriodicalId":8810,"journal":{"name":"Best practice & research. Clinical endocrinology & metabolism","volume":"38 6","pages":"Article 101939"},"PeriodicalIF":6.1,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142267230","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xiao Guan (Urologist) , Minghao Li (Urologist) , Yingxian Pang (Urologist) , Yao He (Urologist) , Jing Wang (Pathologist) , Xiaowen Xu (Resident Urology) , Kai Cheng (Resident Urology) , Zhi Li (Resident Urology) , Longfei Liu (Urologist)
{"title":"Recent advances in algorithms predicting hemodynamic instability undergoing surgery for phaeochromocytoma and paraganglioma","authors":"Xiao Guan (Urologist) , Minghao Li (Urologist) , Yingxian Pang (Urologist) , Yao He (Urologist) , Jing Wang (Pathologist) , Xiaowen Xu (Resident Urology) , Kai Cheng (Resident Urology) , Zhi Li (Resident Urology) , Longfei Liu (Urologist)","doi":"10.1016/j.beem.2024.101956","DOIUrl":"10.1016/j.beem.2024.101956","url":null,"abstract":"<div><div>Abdominal pheochromocytomas and paragangliomas (PPGLs) are characterized by the overproduction of catecholamines, which are associated with hemodynamic instability (HDI) during surgery. Therefore, perioperative management to prevent intraoperative HDI is imperative for the surgical treatment of PPGLs. Owing to the rarity and heterogeneous nature of these tumors, pre-surgical prediction of HDI is a clinical dilemma. The reported risk factors for HDI include perioperative preparation, genetic background, tumor conditions, body composition, catecholamine levels, and surgical approach. Additionally, several personalized algorithms or models including these factors have been developed. The first part of this review outlines the prediction models that include clinical features such as tumor size and location, body mass index (BMI), blood glucose level, catecholamine levels, and preoperative management with α-adrenoceptor blockade and crystal/colloid fluid. We then summarize recently reported models that consider additional factors such as genetic background, radiomics, robotic-assisted surgical approach, three-dimensional visualization, and machine-learning models. These findings suggest that a comprehensive model including risk factors is the most likely approach for achieving effective perioperative management.</div></div>","PeriodicalId":8810,"journal":{"name":"Best practice & research. Clinical endocrinology & metabolism","volume":"38 6","pages":"Article 101956"},"PeriodicalIF":6.1,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142549515","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jingjing Jiang (Endocrinologist) , Yujun Liu (Urologist)
{"title":"Recent discoveries of Sino-Caucasian differences in the genetics of phaeochromocytomas and paragangliomas","authors":"Jingjing Jiang (Endocrinologist) , Yujun Liu (Urologist)","doi":"10.1016/j.beem.2024.101928","DOIUrl":"10.1016/j.beem.2024.101928","url":null,"abstract":"<div><div>Pheochromocytomas and paragangliomas (PPGLs) represent the highest degree of heritability of any known tumor types in humans. Previous studies have characterized a dramatic difference between Chinese and European Caucasians with regards to both genetics and clinical features of PPGLs. The proportion of PGLs in Chinese patients was higher than in Caucasians, and the prevalence of metastasis was much lower in Chinese patients. Compared with Caucasians, there were more pathogenic variants (PVs) found in <em>HRAS</em> and <em>FGFR1</em>, but less in <em>NF1</em> and <em>SDHB</em>. There were less germline PVs found in Chinese patients. Importantly, in Chinese patients, there was a large proportion of PGLs with PVs found in <em>HRAS</em> and <em>FGFR1</em>, mostly with epinephrine-producing capacity. This finding provided solid evidence that genetics (cluster 1 vs. 2), rather than location (PCC vs. PGL), determines the catecholamine-producing phenotype. Besides, the lower prevalence of <em>SDHB</em> partially explained lower occurrence of metastatic lesions in Chinese patients. These findings underscore the importance of considering ethnic differences when evaluating PPGLs and patient outcomes.</div></div>","PeriodicalId":8810,"journal":{"name":"Best practice & research. Clinical endocrinology & metabolism","volume":"38 6","pages":"Article 101928"},"PeriodicalIF":6.1,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142082831","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Katharina Wang (Resident Internal Medicine and Endocrinology) , Alessa Fischer (Resident Internal Medicine and Endocrinology) , Umberto Maccio (Consultant Pathologist and Molecular Pathologist) , Constanze Hantel (Head of Endocrine Research Lab) , Felix Beuschlein (Clinic Director Endocrinology, Diabetology and Clinical Nutrition) , Ashley B. Grossman (Emeritus Professor of Endocrinology, Green Templeton College, University of Oxford) , Karel Pacak (Professor, Chief, Section on Medical Neuroendocrinology, Head, Developmental Endocrinology, Metabolism, Genetics and Endocrine Oncology Affinity Group, NICHD/NIH) , Svenja Nölting (Assistant Professor Endocrine Tumours and Consultant Endocrinology, Diabetology and Clinical Nutrition)
{"title":"Pre-clinical phaeochromocytoma and paraganglioma models: Cell lines, animal models, and a human primary culture model","authors":"Katharina Wang (Resident Internal Medicine and Endocrinology) , Alessa Fischer (Resident Internal Medicine and Endocrinology) , Umberto Maccio (Consultant Pathologist and Molecular Pathologist) , Constanze Hantel (Head of Endocrine Research Lab) , Felix Beuschlein (Clinic Director Endocrinology, Diabetology and Clinical Nutrition) , Ashley B. Grossman (Emeritus Professor of Endocrinology, Green Templeton College, University of Oxford) , Karel Pacak (Professor, Chief, Section on Medical Neuroendocrinology, Head, Developmental Endocrinology, Metabolism, Genetics and Endocrine Oncology Affinity Group, NICHD/NIH) , Svenja Nölting (Assistant Professor Endocrine Tumours and Consultant Endocrinology, Diabetology and Clinical Nutrition)","doi":"10.1016/j.beem.2024.101913","DOIUrl":"10.1016/j.beem.2024.101913","url":null,"abstract":"<div><div>While the establishment of human phaeochromocytoma and paraganglioma (PPGL) cell lines has proven to be particularly difficult over several decades of research, there are other reliable pre-clinical PPGL models currently available. This review provides a summary of these models, together with our recently established personalised drug screening platform using patient-derived PPGL primary cultures. Such currently available PPGL models include murine and rat PPGL cell lines, of which only one cell line (PC12) is publicly accessible through a cell repository, and PPGL animal models, of which the patient-derived xenograft models are promising but complex to establish. We have developed next-generation implementation of human PPGL primary cultures, enabling reliable and personalised drug screening and an individualised analysis of tumour drug responsivity based on the tumour’s unique genetic, biochemical, immunohistochemical and clinical profile. Overall, reliable PPGL models, including patient-derived primary culture models, are essential to advance pre-clinical research in the field of PPGLs.</div></div>","PeriodicalId":8810,"journal":{"name":"Best practice & research. Clinical endocrinology & metabolism","volume":"38 6","pages":"Article 101913"},"PeriodicalIF":6.1,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141556206","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
María Monteagudo , Bruna Calsina , Milton E. Salazar-Hidalgo , Ángel M. Martínez-Montes , Elena Piñeiro-Yáñez , Eduardo Caleiras , Maria Carmen Martín , Sandra Rodríguez-Perales , Rocío Letón , Eduardo Gil , Alexandre Buffet , Nelly Burnichon , Ángel Fernández-Sanromán , Alberto Díaz-Talavera , Sara Mellid , Ester Arroba , Clara Reglero , Natalia Martínez-Puente , Giovanna Roncador , Maria Isabel del Olmo , Mercedes Robledo
{"title":"MAML3-fusions modulate vascular and immune tumour microenvironment and confer high metastatic risk in pheochromocytoma and paraganglioma","authors":"María Monteagudo , Bruna Calsina , Milton E. Salazar-Hidalgo , Ángel M. Martínez-Montes , Elena Piñeiro-Yáñez , Eduardo Caleiras , Maria Carmen Martín , Sandra Rodríguez-Perales , Rocío Letón , Eduardo Gil , Alexandre Buffet , Nelly Burnichon , Ángel Fernández-Sanromán , Alberto Díaz-Talavera , Sara Mellid , Ester Arroba , Clara Reglero , Natalia Martínez-Puente , Giovanna Roncador , Maria Isabel del Olmo , Mercedes Robledo","doi":"10.1016/j.beem.2024.101931","DOIUrl":"10.1016/j.beem.2024.101931","url":null,"abstract":"<div><div>Pheochromocytomas and paragangliomas are rare neuroendocrine tumours. Around 20–25 % of patients develop metastases, for which there is an urgent need of prognostic markers and therapeutic stratification strategies. The presence of a <em><u>MAML3</u></em>-fusion is associated with increased metastatic risk, but neither the processes underlying disease progression, nor targetable vulnerabilities have been addressed. We have compiled a cohort of 850 patients, which has shown a 3.65 % fusion prevalence and represents the largest <em><u>MAML3</u></em>-positive series reported to date. While <em><u>MAML3</u></em>-fusions mainly cause single pheochromocytomas, we also observed somatic post-zygotic events, resulting in multiple tumours in the same patient. <em><u>MAML3</u></em>-tumours show increased expression of neuroendocrine-to-mesenchymal transition markers, MYC-targets, and angiogenesis-related genes, leading to a distinct tumour microenvironment with unique vascular and immune profiles. Importantly, our findings have identified <em><u>MAML3</u></em>-tumours specific vulnerabilities beyond Wnt-pathway dysregulation, such as a rich vascular network, and overexpression of PD-L1 and CD40, suggesting potential therapeutic targets.</div></div>","PeriodicalId":8810,"journal":{"name":"Best practice & research. Clinical endocrinology & metabolism","volume":"38 6","pages":"Article 101931"},"PeriodicalIF":6.1,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142115912","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Best Practice and Research Clinical Endocrinology and Metabolism issue on Phaeochromocytomas and Paragangliomas","authors":"","doi":"10.1016/j.beem.2024.101959","DOIUrl":"10.1016/j.beem.2024.101959","url":null,"abstract":"","PeriodicalId":8810,"journal":{"name":"Best practice & research. Clinical endocrinology & metabolism","volume":"38 6","pages":"Article 101959"},"PeriodicalIF":6.1,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142792972","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Susan Richter , Georgiana Constantinescu , Giuseppe Fancello , Carlo T. Paties , Renato Mariani-Costantini , Mario Sanna
{"title":"Head and neck paragangliomas: Recent advances in translational and clinical research and guidelines for patient care","authors":"Susan Richter , Georgiana Constantinescu , Giuseppe Fancello , Carlo T. Paties , Renato Mariani-Costantini , Mario Sanna","doi":"10.1016/j.beem.2024.101951","DOIUrl":"10.1016/j.beem.2024.101951","url":null,"abstract":"<div><div>Head and neck paragangliomas (HNPGLs), rare neuroendocrine tumors that mainly arise from parasympathetic ganglia along the cranial nerves, are challenging due to anatomic origin, tendency to aggressive neurovascular and skull base infiltration, unpredictable metastatic potential, radio-chemoresistance, and risk of multiplicity. Symptoms range from mild to life threatening depending on location/size, but rarely relate to catecholamine excess. Risk factors include female sex and pathogenic germline variants in genes affecting hypoxia signaling (foremost succinate dehydrogenase genes). Diagnostic work-up relies on imaging, measurements of plasma free metanephrines/methoxytyramine, genetic testing, and pathology/immunohistochemistry. Management is tailored to patient/tumor characteristics and encompasses wait-scan, upfront surgery, debulking surgery, and radiotherapy. Presurgical embolization is recommended, except for small tympanic and tympanomastoid tumors. Presurgical stenting is required for internal carotid artery involvement, and two-stage surgery for intradural extension. Current treatments for metastatic/inoperable HNPGL are non-curative, and long-term follow-up should be recommended for all patients to monitor local recurrence and new tumors.</div></div>","PeriodicalId":8810,"journal":{"name":"Best practice & research. Clinical endocrinology & metabolism","volume":"38 6","pages":"Article 101951"},"PeriodicalIF":6.1,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142303283","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}