Journal of Endocrinological Investigation最新文献

{"title":"Osteocalcin: may be a useful biomarker for early identification of rapidly progressive central precocious puberty in girls.","authors":"W Qin, T Xie, Y Chen, D Zeng, Q Meng, D Lan","doi":"10.1007/s40618-024-02478-0","DOIUrl":"10.1007/s40618-024-02478-0","url":null,"abstract":"<p><strong>Objective: </strong>To assess serum osteocalcin (OC) as a potential biomarker for the early detection of rapidly progressive central precocious puberty (RP-CPP) in girls.</p><p><strong>Methods: </strong>Serum OC levels were quantified using enzyme-linked immunosorbent assays (ELISAs). In the retrospective analysis, receiver operating characteristic (ROC) curve analysis was employed to evaluate the ability of OC to identify RP-CPP. A prospective study and screening tests were utilized to assess the potential of OC for use in the early prediction of RP-CPP. Variable selection in the multivariate analysis was conducted using the Bayesian Information Criterion (BIC) and binary logistic regression was employed to construct the diagnostic prediction model.</p><p><strong>Results: </strong>Girls with RP-CPP had significantly higher serum OC levels compared to girls with non-rapidly progressive central precocious puberty (NRP-CPP) (149.04±40.50 vs. 89.10±31.83 ng/mL, P < 0.001). The optimal OC cut-off point for differentiating RP-CPP from NRP-CPP was 107.05 ng/mL, the area under the ROC curve (AUC) was 0.90 (95%CI: 0.851-0.949; P < 0.001), with a sensitivity of 91.1% and specificity of 70.7%. The results of the prospective study indicated that changes in OC precede alterations in estradiol (E2) and bone age (BA). A diagnostic prediction model that includes duration of breast development, BA, OC, high-density lipoprotein cholesterol (HDL-C), and uterine length achieved an AUC of 0.961, with a sensitivity of 94.1% and specificity of 91.5% for the detection of RP-CPP. If OC is excluded from the model, the AUC decreases to 0.894, with sensitivity and specificity declining to 80.5% and 83.1%, respectively.</p><p><strong>Conclusions: </strong>Serum OC levels may serve as a promising biomarker for the early differentiation between RP-CPP and NRP-CPP in girls. The diagnostic prediction model that incorporates duration of breast development, BA, OC, HDL-C, and uterine length effectively identifies girls with RP-CPP.</p>","PeriodicalId":48802,"journal":{"name":"Journal of Endocrinological Investigation","volume":" ","pages":"721-730"},"PeriodicalIF":5.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142478394","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Improving the radiological prediction of surgical resection of nonfunctioning pituitary adenomas.","authors":"Eduardo Giardini, Monique Alvares Barbosa, Nina Ventura, Paulo José da Mata Pereira, André Guasti, Paulo Niemeyer, Felipe Andreiuolo, Leila Chimelli, Leandro Kasuki, Mônica R Gadelha","doi":"10.1007/s40618-024-02479-z","DOIUrl":"10.1007/s40618-024-02479-z","url":null,"abstract":"<p><strong>Purpose: </strong>Nonfunctioning pituitary adenomas (NFPAs) are benign tumors growing in the sellar region. Total surgical excision of the lesion is recommended as the preferred treatment choice with preservation of adjacent structures. The objective is to establish a radiological score to predict the feasibility of NFPA total surgical excision.</p><p><strong>Methods: </strong>Patients with treatment-naïve NFPA who underwent a transsphenoidal approach and sellar magnetic resonance imaging (MRI) in the preoperative period and 3 months after surgery were included. Data on age, sex, tumor diameter, extrasellar extension, postoperative cure rates, and hormone and transcription factor expression were collected. A combined score was proposed based on Knosp and SIPAP classifications. We proposed 3 classification groups depending on the tumoral extension to the suprasellar, infrasellar, anterior and posterior directions of the sellar region.</p><p><strong>Results: </strong>A total of 164 patients were included in the study, and 85 (52%) were female. Total excision was obtained in 46% (n = 75) of the patients. The majority of tumors were of gonadotrophic lineage (59%), followed by corticotrophic (17%) and other less common types. Largest tumor diameter was 6.8 cm [mean 3.8 cm (± 1.1 cm)]. From the established groups, 10 patients were classified in Group I, of whom 8 (80%) patients underwent total excision, 115 patients were classified in Group II, of whom 58 (50%) underwent complete excision and 39 patients in Group III, of whom 9 (23%) underwent complete excision (p value < 0.001).</p><p><strong>Conclusion: </strong>The newly proposed score helps to determine the feasibility of total NFPA excision, allowing for better surgical planning and predictions of postoperative outcomes.</p>","PeriodicalId":48802,"journal":{"name":"Journal of Endocrinological Investigation","volume":" ","pages":"701-709"},"PeriodicalIF":5.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142584520","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The assessment of urinary sexual hormones within minipuberty and correlations with anthropometrics in a cohort of healthy term children.","authors":"Viola Trevisani, Lucia Palandri, Beatrice Righi, Domenico Maione, Lisa De Pasquale, Enrico Tagliafico, Chiarina Grisolia, Mara Tagliazucchi, Barbara Predieri, Lorenzo Iughetti, Elena Righi, Laura Lucaccioni","doi":"10.1007/s40618-024-02493-1","DOIUrl":"10.1007/s40618-024-02493-1","url":null,"abstract":"<p><strong>Introduction: </strong>Minipuberty follows different trends in boys and girls. Aim of our study was to explore timing and dynamics of minipuberty in healthy infants, analyzing urinary levels of sexual hormones. Moreover, we analyzed the association among HPG axis activity and linear growth, ano-genital distances (AGDs) in both sexes, and penile length in males.</p><p><strong>Methods: </strong>Longitudinal cohort study in healthy term infants from birth to 6 months of life. Clinical evaluation (anthropometrics and AGDs) and urine sampling were performed at 0 (T0), 3 (T3), and 6 (T6) months. Urine samples were analyzed for gonadotropins and sex hormones.</p><p><strong>Results: </strong>165 participants were involved. The growth trend of our population was regular, as were the AGDs. Urinary hormones were correlated each other's. Specifically, in boys, the correlation coefficient between urinary FSH (uFSH) and urinary LH (uLH) decreased from T0 to T6, while between urinary Testosterone (uT) and uFSH increased. In girls, correlations between uFSH and urinary Estradiol (uE) were observed at each time point. Notably, several correlations between hormones and anthropometrics and AGDs were found; the most interesting correlation was found in males within uLH and PL (at T0 ρ: 0.323, p < 0.05 and at T3 ρ: 0.371, p < 0.01), whereas in females uFSH at T0 showed negative correlations with both length and body weight percentile at T3 (ρ: -0.505, p < 0.01 and ρ: -0.478, p < 0.01, respectively).</p><p><strong>Conclusion: </strong>Urinary matrix has proved to be a valuable, practical, non-invasive and cheaper method for sexual hormone assessment.</p>","PeriodicalId":48802,"journal":{"name":"Journal of Endocrinological Investigation","volume":" ","pages":"731-742"},"PeriodicalIF":5.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142569558","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Texture analysis can predict response to etoposide-doxorubicin-cisplatin in patients with adrenocortical carcinoma.","authors":"Filippo Crimì, Francesca Turatto, Carlo D'Alessandro, Giovanni Sussan, Maurizio Iacobone, Francesca Torresan, Irene Tizianel, Cristina Campi, Emilio Quaia, Mario Caccese, Filippo Ceccato","doi":"10.1007/s40618-024-02476-2","DOIUrl":"10.1007/s40618-024-02476-2","url":null,"abstract":"<p><strong>Background: </strong>The adrenocortical carcinoma (ACC) is a rare and highly aggressive malignancy originating from the adrenal cortex. These patients usually undergo chemotherapy with etoposide, doxorubicin, cisplatin and mitotane (EDP-M) in case of locally advanced or metastatic ACC. Computed tomography (CT) radiomics showed to be useful in adrenal pathologies. The study aimed to analyze the association between response to EDP-M treatment and CT textural features at diagnosis in patients with locally advanced or metastatic ACCs.</p><p><strong>Methods: </strong>We enrolled 17 patients with advanced or metastatic ACC who underwent CT before and after EDP-M therapy. The response to treatment was evaluated according to RECIST 1.1, Choi, and volumetric criteria. Based on the aforementioned criteria, the patients were classified as responders and not responders. Textural features were extracted from the biggest lesion in contrast-enhanced CT images with LifeX software. ROC curves were drawn for the variables that were significantly different (p < 0.05) between the two groups.</p><p><strong>Results: </strong>Long-run high grey level emphasis (LRHGLE_GLRLM) and histogram kurtosis were significantly different between responder and not responder groups (p = 0.04) and the multivariate ROC curve combining the two features showed a very good AUC (0.900; 95%IC: 0.724-1.000) in discriminating responders from not responders. More heterogeneous tissue texture of initial staging CT in locally advanced or metastatic ACC could predict the positive response to EDP-M treatment.</p><p><strong>Conclusions: </strong>Adrenal texture is able to predict the response to EDP-M therapy in patients with advanced ACC.</p>","PeriodicalId":48802,"journal":{"name":"Journal of Endocrinological Investigation","volume":" ","pages":"711-720"},"PeriodicalIF":5.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11876227/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142394397","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Medical eyes on art: describing multinodular Goiter in Nicolini's Statue at the Aula Magna of University of Messina.","authors":"A Saturnino, P Pozzilli, F Trimarchi","doi":"10.1007/s40618-025-02553-0","DOIUrl":"https://doi.org/10.1007/s40618-025-02553-0","url":null,"abstract":"","PeriodicalId":48802,"journal":{"name":"Journal of Endocrinological Investigation","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143525010","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Causes of death in patients with malignant adrenal tumours: a population-based analysis.","authors":"Yang Zheng, Song Ren, Zeyi Yan, Ting Hu, Yunlin Feng, Dong Wang, Shida Fan, Shangqing Ren","doi":"10.1007/s40618-025-02555-y","DOIUrl":"https://doi.org/10.1007/s40618-025-02555-y","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to characterize the causes of death and compute the risk of mortality due to each cause among patients with malignant adrenal tumours.</p><p><strong>Methods: </strong>Data from malignant adrenal tumour patients were collected from the Surveillance, Epidemiology, and End Results (SEER) database (2004-2020). With reference data from the general population, the standardized mortality ratio (SMR) was calculated to assess all causes of death for malignant adrenal tumour patients.</p><p><strong>Results: </strong>A total of 1651 patients who died from primary malignant adrenal neoplasms were included; 854 cases of adrenocortical carcinoma (ACC)-related death, 118 cases of pheochromocytoma (PCC)-related death and 333 cases of neuroblastoma (NB)-related death were identified for further analysis. Approximately 56.78%~87.69% of patients died from primary malignant adrenal tumours, 7.21%~13.56% died from secondary malignant neoplasms (SMNs), and 5.11%~29.66% died from noncancer diseases. The main causes of death associated with SMNs included lung and bronchial cancer and soft tissue cancers, including heart, kidney and renal pelvis cancers; the noncancer causes of death included mainly heart disease, septicemia, and cerebrovascular disease. Compared with chemotherapy-naïve patients, chemotherapy-treated patients had higher SMRs of SMNs, including cancers of the colon (excluding the rectum), lung, bronchus, bones and joints; soft tissues, including the heart, kidney and renal pelvis; the brain and peripheral nervous system; and leukaemia, as well as nontumor diseases, including heart disease, septicemia, and cerebrovascular disease. Patients with NB were more likely to die from SMNs, including soft-tissue malignancies of the heart, bones and joints; brain; peripheral nervous system; the female genital system, including the ovary; leukaemia, including lymphocytic leukaemia; myeloid and monocytic leukaemia; and lymphoma, including non-Hodgkin lymphoma.</p><p><strong>Conclusion: </strong>In addition to primary cancer, SMNs and nontumor diseases were important causes of death in patients with malignant adrenal tumours. Neuroblastoma patients and chemotherapy- treated patients are more likely to die from SMNs and should monitored closely.</p>","PeriodicalId":48802,"journal":{"name":"Journal of Endocrinological Investigation","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143484220","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"\"Who and how to screen for endogenous hypercortisolism among young women presenting with clinical hyperandrogenism and/or menstrual abnormalities \".","authors":"Francesco Ferraù, Ylenia Alessi, Federica Nista, Anna Roux, Diego Ferone, Emanuela Arvat","doi":"10.1007/s40618-025-02537-0","DOIUrl":"https://doi.org/10.1007/s40618-025-02537-0","url":null,"abstract":"<p><p>Endogenous Cushing's syndrome (CS) is rare, with an incidence of 0.7-2.4 per million population per year according to population-based studies. However, evaluation of patients presenting disorders potentially related to cortisol excess, and therefore with a 'high risk of clinical suspicion' profile, could bring out several unrecognized cases. CS represents one of the most challenging endocrine diseases, with clinical features overlapping with those of common conditions affecting general population, invariably resulting in potential mis- or delayed diagnosis with negative consequences in terms of morbidity and mortality. CS is remarkably prevalent among young females, variably presenting with menstrual irregularities and/or signs and symptoms of hyperandrogenism. Herein we briefly reviewed literature on prevalence and clinical impact of menses abnormalities, acne and hirsutism -also coexisting in the context of a polycystic ovary syndrome- in CS, aiming at clarifying if, when and how to screen for hypercortisolism young women with these disorders.</p>","PeriodicalId":48802,"journal":{"name":"Journal of Endocrinological Investigation","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143469717","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Artificial intelligence in the management of metabolic disorders: a comprehensive review.","authors":"Aamir Anwar, Simran Rana, Priya Pathak","doi":"10.1007/s40618-025-02548-x","DOIUrl":"https://doi.org/10.1007/s40618-025-02548-x","url":null,"abstract":"<p><p>This review explores the significant role of artificial intelligence (AI) in managing metabolic disorders like diabetes, obesity, metabolic dysfunction-associated fatty liver disease (MAFLD), and thyroid dysfunction. AI applications in this context encompass early diagnosis, personalized treatment plans, risk assessment, prevention, and biomarker discovery for early and accurate disease management. This review also delves into techniques involving machine learning (ML), deep learning (DL), natural language processing (NLP), computer vision, and reinforcement learning associated with AI and their application in metabolic disorders. The following study also enlightens the challenges and ethical considerations associated with AI implementation, such as data privacy, model interpretability, and bias mitigation. We have reviewed various AI-based tools utilized for the diagnosis and management of metabolic disorders, such as Idx, Guardian Connect system, and DreaMed for diabetes. Further, the paper emphasizes the potential of AI to revolutionize the management of metabolic disorders through collaborations among clinicians and AI experts, the integration of AI into clinical practice, and the necessity for long-term validation studies. The references provided in the paper cover a range of studies related to AI, ML, personalized medicine, metabolic disorders, and diagnostic tools in healthcare, including research on disease diagnostics, personalized therapy, chronic disease management, and the application of AI in diabetes care and nutrition.</p>","PeriodicalId":48802,"journal":{"name":"Journal of Endocrinological Investigation","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143450764","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Extending curve matching with flexible hyperparameter selection to predict response to long-acting PEGylated growth hormone treatment in growth hormone deficiency children: method development and validation.","authors":"Ling Hou, Junfen Fu, Haiyan Wei, Liyang Liang, Hongwei Du, Jianping Zhang, Yan Zhong, Ruimin Chen, Xinran Cheng, Jiayan Pan, Xiaoou Shan, Ting Zeng, Chunxiu Gong, Wei Liao, Deyun Liu, Shunye Zhu, Dan Lan, Zhiya Dong, Huamei Ma, Yu Yang, Min Zhu, Wen Sun, Xiaoping Luo","doi":"10.1007/s40618-025-02546-z","DOIUrl":"https://doi.org/10.1007/s40618-025-02546-z","url":null,"abstract":"<p><strong>Purpose: </strong>Curve matching can predict the height trajectories of children by analyzing longitudinal growth data. We extended the method to improve the prediction of response to long-acting growth hormone treatment in children with growth hormone deficiency (GHD).</p><p><strong>Methods: </strong>We analyzed data from a previous real-world study with a 36-month treatment of PEGylated recombinant human growth hormone (PEG-rhGH). The matching database comprises height measures imputed using the broken stick method. For curve matching, we proposed a flexible hyperparameter selection approach to determining the number of similar patients.</p><p><strong>Results: </strong>The matching database included 681 patients, with an average of 12.20 ± 2.09 height measurements per patient. Our approach demonstrated significantly improved prediction accuracy compared with the previous approach using a fixed number of similar patients (mean squared errors of 0.0412 ± 0.1156 vs. 0.564 ± 0.1639, 0.851 ± 0.2627, and 0.1077 ± 0.2960 for 5, 10, and 15 similar patients, respectively, all P < 0.05). The optimal prediction scenario was having four height measurements within the first six months and predicting height trajectories from there on.</p><p><strong>Conclusion: </strong>By extending curve matching with flexible hyperparameter selection, we accurately predicted the response to long-acting PEG-rhGH in the GHD children included in this study.</p>","PeriodicalId":48802,"journal":{"name":"Journal of Endocrinological Investigation","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143450688","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical and biological heterogeneity of Grade 2 digestive neuroendocrine neoplasms: prognostic significance of the 10% Ki-67 index cutoff and implications for treatment strategies. A longitudinal study.","authors":"Sara Massironi, Camilla Gallo, Lorenzo Coltro, Giuseppe Dell'Anna, Paoletta Preatoni, Silvio Danese","doi":"10.1007/s40618-025-02552-1","DOIUrl":"https://doi.org/10.1007/s40618-025-02552-1","url":null,"abstract":"<p><strong>Background: </strong>Digestive neuroendocrine neoplasms (NENs) encompass a heterogeneous group of tumors with varying prognoses and clinical behaviors. Grade 2 (G2) tumors, defined by a Ki-67 index between 3% and 20%, are particularly challenging to manage due to their intermediate and variable biological behavior. Evidence suggests a distinct prognosis between G2 digestive NENs with a Ki-67 index < 10% and those with a Ki-67 index ≥ 10%.</p><p><strong>Aim: </strong>To investigate the clinical and biological heterogeneity between Grade 1 (G1) and G2 digestive NENs, and within G2 tumors, with a focus on the prognostic significance of a 10% Ki-67 index cutoff.</p><p><strong>Methods: </strong>This study involved a combined retrospective and prospective analysis of patients with low-grade G1 and G2 digestive NENs managed at IRCCS San Gerardo Hospital in Monza, Italy, between January 2000 and May 2024. Data on patient demographics, tumor characteristics, treatment modalities, and survival outcomes were collected and potential differences were analyzed between G1, G2 with Ki-67 index < 10% and G2 with Ki-67 index ≥ 10%.</p><p><strong>Results: </strong>Out of a total of 113 enrolled patients, 69 (61%) had G1 tumors, and 44 (39%) had G2 tumors. Median tumor size at diagnosis was 19 mm (IQR: 12-25 mm), with primary lesions mainly localized in the pancreas (57% among G1 and 45% among G2). Most G1 tumors were diagnosed at stage I (29 patients, 42%), while the majority of G2 tumors were metastatic at diagnosis (24 patients, 54.5%). Patients with G1 tumors exhibited a slightly higher 5-year OS rate compared to G2 tumors (98.1% vs. 92.8% respectively, though not statistically significant), and a significantly longer median PFS (141 vs. 22 months, p = 0.0003). Within the G2 group, 31 patients (70%) had a Ki-67 index < 10%, while 13 (30%) had a Ki-67 index ≥ 10%, with comparable baseline characteristics. A Ki-67 index < 10% was associated with a significantly better median PFS (38 vs. 8 months for tumors with Ki-67 index ≥ 10% G2 tumors, p = 0.002). PFS after first-line medical therapy was significantly longer in patients with a Ki-67 index < 10%, compared to those with ≥ 10% (undefined vs. 16 months, p = 0.0085), as well as median post-surgical PFS (84 vs. 10.5 months, p < 0.0001). Multivariate analysis identified higher tumor grade, advanced stage at diagnosis, and absence of PRRT as independent predictors of worse outcomes.</p><p><strong>Conclusions: </strong>The findings highlight the significant clinical heterogeneity within G2 digestive NENs. A Ki-67 index cutoff of 10% within G2 tumors may serve as a critical prognostic marker, with patients with a Ki-67 index < 10% exhibiting significantly better outcomes in terms of PFS. These results suggest that the Ki-67 index could play an essential role in guiding treatment strategies, emphasizing the need for personalized approaches in managing G2 digestive NENs.</p>","PeriodicalId":48802,"journal":{"name":"Journal of Endocrinological Investigation","volume":" ","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143450687","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}