Nonfunctioning Tumors Research Articles

Neoadjuvant 177Lu-DOTATATE for non-functioning pancreatic neuroendocrine tumours (NEOLUPANET): multicentre phase II study.

Resection of non-functioning pancreatic neuroendocrine tumours (NF-PanNETs) is curative in most patients. The potential benefits of neoadjuvant treatments have, however, never been explored. The primary aim of this study was to evaluate the safety of neoadjuvant 177Lu-labelled DOTA0-octreotate (177Lu-DOTATATE) followed by surgery in patients with NF-PanNETs. NEOLUPANET was a multicentre, single-arm, phase II trial of patients with sporadic, resectable or potentially resectable NF-PanNETs at high-risk of recurrence; those with positive 68Ga-labelled DOTA PET were eligible. All patients were candidates for neoadjuvant 177Lu-DOTATATE followed by surgery. A sample size of 30 patients was calculated to test postoperative complication rates against predefined cut-offs. The primary endpoint was safety, reflected by postoperative morbidity and mortality within 90 days. Secondary endpoints included rate of objective radiological response and quality of life. From March 2020 to February 2023, 31 patients were enrolled, of whom 26 completed 4 cycles of 177Lu-DOTATATE. A partial radiological response was observed in 18 of 31 patients, and 13 patients had stable disease. Disease progression was not observed. Twenty-four R0 resections and 4 R1 resections were performed in 29 patients who underwent surgery. One tumour was unresectable owing to vascular involvement. There was no postoperative death. Postoperative complications occurred in 21 of 29 patients. Severe complications were observed in seven patients. Quality of life remained stable after 177Lu-DOTATATE and decreased after surgery. Neoadjuvant treatment with 177Lu-DOTATATE is safe and effective for patients with NF-PanNETs.

The Incidence of Cancers in Patients With Nonfunctional Adrenal Tumors: A Swedish Population-Based National Cohort Study.

It is unclear if nonfunctional adrenal tumors (NFAT) are associated with higher cancer incidence. To analyze the cancer incidence in patients with NFAT. In this national register-based retrospective cohort study, consecutive patients with NFAT identified in Sweden 2005-2019 and matched control individuals without adrenal tumors were followed up to 15 years. Outcome data were collected from national registers and adjusted for confounders. Both cases and controls were followed until newly diagnosed malignancy, death, or until 2019. Individuals with adrenal hormonal excess or prior malignancy were excluded. Among 17 726 cases, 10 777 (60.8%) were women, and the median age was 65 (IQR, 57-73) years. Among 124 366 controls, 69 514 (55.9%) were women, and the median age was 66 (IQR, 58-73) years. The incidence of any cancer was higher in patients with NFAT compared to controls (hazard ratio [HR] 1.35 95% CI 1.29-1.40; adjusted HR 1.31, 95% CI 1.26-1.37). NFAT was associated with a higher incidence of adrenal, thyroid, lung, stomach and small intestine, kidney, pancreatic, breast, and colorectal cancer. Sensitivity analyses did not change the overall results, but associations were not significantly increased after adjustment in patients with NFAT and appendicitis or gallbladder/biliary tract/pancreas disorders. Cancer incidence may have been underestimated by adjusting for unclear and benign tumors. The incidence of cancer was increased in patients with NFAT. Long-term follow-up may be indicated.

Trends in the Use of Observation for Small Nonfunctional Pancreatic Neuroendocrine Tumors

This study assesses nationwide trends in the use of observation for pancreatic neuroendocrine tumors 2 cm or smaller and to evaluate factors associated with resection.

The Clinicopathological Characteristics and Surgical Treatment of Gastrointestinal Neuroendocrine Neoplasm-A 10-Year Single-Center Experience.

Background: Gastrointestinal neuroendocrine neoplasms (GI-NENs) represent a diverse group of tumors, with surgical resection being the gold standard for treatment. Materials and Methods: A retrospective analysis was conducted on 63 patients (32 women, 31 men) who underwent surgery for GI-NENs at the Department of Digestive Tract Surgery from January 2013 to June 2023. Tumors were classified by stage (localized, regionally advanced, metastatic). Results: Clinical symptoms were reported by 42 (66.7%) patients, with abdominal pain being the most common symptom, affecting 28 (44.4%) patients. The majority of tumors (44, 69.8%) originated in the midgut. The most frequently performed surgery was right hemicolectomy, carried out on 33 (52.4%) patients. Radical tumor resection was performed in 35 (55.6%) patients. Postoperative complications occurred in 12 (19%) patients, with male gender identified as an independent predictive factor for complications (p = 0.04). Non-functioning tumors were more common (33, 52.4%), and most tumors were classified as grade 1 histopathologically (49, 77.8%). Distant metastases were present in 29 (46%) patients. The overall two-year survival rate was 94.9%, with a five-year survival rate also estimated at 94.9%. Conclusions: GI-NENs are often diagnosed at advanced stages, frequently with distant or lymph node metastases, and predominantly arise in the midgut. Despite low postoperative morbidity and mortality, male gender may be a predictor of postoperative complications. Overall, the prognosis for GI-NENs is favorable, reflected in high overall survival rates.

Differential proteomic expression in non-functional pituitary neuroendocrine tumours and pituitary glands.

Pituitary neuroendocrine tumours (PitNETs) are common accounting for 10 to 25 % of all intracranial tumours. This project describes the feasibility of developing a novel membrane-based biomarker that could be used for fluorescent guided surgery. The aim was to catalogue the differential expression of membrane proteins between non-functional PitNETs and pituitary glands. Ten pituitary gland tissue specimens were obtained from the National Institute of Health (NIH) NeuroBio-Bank and twenty non-functional PitNETs were obtained from the Northwestern University Nervous System Tumour Bank. Mass spectrometry analysis using an Orbitrap Fusion Lumos Tribrid Mass Spectrometer linked to a Dionex Ultimate 3000 UPLC system was undertaken. Data Dependent Acquisition Mass Spectrometry and Data Independent Acquisition Mass Spectrometry was then completed. Pathway enrichment analysis was performed using clusterProfiler v4.6.0. Functional enrichment analysis was conducted using Gene Ontology terms and Reactome pathways. Differential expression analysis between the two groups revealed a total of 2110 significant differently expressed proteins (DEPs), with 1387 of these also having a Log2 fold change either greater than 1, or less than -1. Of the 2110 DEPs, 925 were upregulated in tumours compared to control, while 1185 were downregulated. We have demonstrated a proteomic comparison between non-functional PitNETs and normal pituitary glands. These results demonstrate differences consistent with contemporary literature but shows that NOTCH3 and PTPRJ are up-regulated in non-functional PitNETs compared to pituitary glands.

Large bilateral non-functional adrenal myelolipomas: A rare case report

Myelolipomas are rare, benign, and non-functional neuroendocrine tumors that are usually discovered incidentally. The widespread use of imaging modalities has increased the detection of incidental tumors over the last decades. Most myelolipomas are small, unilateral, and asymptomatic. Occasionally, tumors grow over time and become symptomatic due to the mass effect on adjacent structures. As a therapeutic approach, surgery is known as the standard treatment for symptomatic or large lesions. We report a patient presented with persisted abdominal pain which had been initiated two months ago. Ultrasonography examination showed large, bilateral, and well-defined hyperechoic lesions without calcification in both adrenal glands. Tumors were non-functional with hormone secretion-wise. After laparoscopic resection, on the macroscopic examination, two adrenal lesions with 60×50×40 mm and 35×30×10 mm size, respectively, were observed. The subsequent microscopic assessment also confirmed the diagnosis of bilateral adrenal myelolipomas.

The value of dehydroepiandrosterone sulfate in the differential diagnosis of primary bilateral adrenal macronodular hyperplasia

Objective: To investigate the value of serum dehydroepiandrosterone sulfate (DHEAS) in the differential diagnosis of primary bilateral macronodular adrenal hyperplasia (PBMAH) from nonfunctional adenoma tumors (NFA), adrenocortical adenoma (ADA) and Cushing's disease (CD). Methods: A cross-sectional study. The clinical data of 302 patients with PBMAH, NFA, ADA and CD diagnosed and treated in the First Medical Center of PLA General Hospital from January 2010 to June 2021 were retrospectively analyzed. Among them, 97 were males and 205 were females, aged (45.7±7.2) years. The area under receiver operating characteristic (ROC) curve was used to evaluate the DHEAS ratio (serum DHEAS value divided by the lower limit of normal reference range for the corresponding age and sex) and the 8∶00 adrenocorticotropic hormone (ACTH) level in the differential diagnosis of PBMAH from NFA, ADA and CD. The maximum value of Youden index was cut-off value. Results: Among the 302 patients, 33 were in PBMAH group, 125 were in NFA group, 67 were in ADA group, and 77 were in CD group. The DHEAS ratio in CD group, NFA group, PBMAH group and ADA group decreased successively, with values of 6.34(4.44, 9.93), 3.37(2.24, 4.79), 1.14(1.04, 2.40) and 0.58(0.27, 1.05), respectively. There was statistical significance among all groups (all P<0.01). The area under the ROC curve for distinguishing PBMAH from NFA, ADA and CD were 0.803, 0.741 and 0.930, and the cut-off value were 2.59, 0.99 and 2.92, respectively. The sensitivity was 66.1%, 64.2% and 87.9%, respectively. The specificity was 81.8%, 81.2% and 85.7%. According to the level of 8∶00 ACTH, PBMAH was divided into ACTH-inhibited group (ACTH<2.2 pmol/L,n=18) and ACTH-non-inhibited group (ACTH≥2.2 pmol/L, n=15).The DHEAS ratio in ACTH-non-inhibited PBMAH group was higher than that in ACTH-inhibited PBMAH group(P<0.01).The area under ROC curve of DHEAS ratio for identifying ACTH-non-inhibited PBMAH and CD was 0.877, the cut-off value was 4.55, the sensitivity was 93.3%, and the specificity was 75.3%. If the DHEAS ratio combined with 8∶00 ACTH was used as a differential diagnostic indicator, the area under the ROC curve for distinguishing ACTH-non-inhibitory PBMAH from CD can reach 0.967, with the sensitivity of 100.0% and the specificity of 81.8%. Conclusions: DHEAS ratios is different in PBMAH, NFA, ADA and CD patients, which can assist in the differential diagnosis of PBMAH from NFA、ADA and CD patients, especially in the differential diagnosis of ACTH-non-inhibited PBMAH patients and CD patients.

Anatomical Differences in Sphenoid Sinus During Endoscopic Transsphenoidal Surgery: Comparison Between Nonfunctioning Pituitary Neuroendocrine Tumor (PiTNET) and Growth Hormone-Secreting PiTNET

In surgical practice during endoscopic endonasal approach, growth hormone-secreting pituitary neuroendocrine tumor (GH-secreting PitNET) patients show morphologic differences in the nasal cavities and sinuses, leading to a narrower surgical field and a carotid prominence and potentially increasing the complexity of the surgical and the risk of complications. The aim of the study is to evaluate the anatomical differences of the sphenoid sinus between patients with GH-secreting PitNETs and patients with nonfunctioning pituitary neuroendocrine tumor (NF-PitNET) who underwent endoscopic endonasal approach. This is a monocentric retrospective study conducted at the author's institution. The minimum intercarotid distance, the largest diameter of the sphenoid sinus (DSS), and the distance between vomer and clivus (VCD) were collected and compared. Presence, localization, and course of intersphenoid sinus septum were also evaluated. One hundred consecutive patients were identified: 57 males (57%) and 43 females (43%), with a mean age of 55years. Sixty patients had NF-PitNET (60%) and 40 had GH-secreting PitNET (40%). GH-secreting PitNET group presented inferior values of intercarotid distance (16.8 ± 3.94mm vs. 20.4 ± 3.94mm, P < 0.001), DSS (32.5 ± 9.81mm vs. 38.6 ± 11.03mm, P= 0.006), and VCD (25.5 ± 6.96mm vs. 29.6 ± 8.47mm, P= 0.012) compared to NF-PitNET group. Intersphenoid sinus septum showed no differences between the 2 groups. Intercarotid distance, DSS, and VCD resulted smaller in acromegalic patients, confirming that patients with GH-secreting PitNETs have a narrower surgical field. A meticulous anatomical preoperative planning and neuronavigation are important to recognize the sphenoid anatomical landmarks in order to reduce the risk of complications, especially in acromegalic patients.

Silent Corticotroph Adenomas Demonstrate Predilection for Sphenoid Sinus, Cavernous Sinus, and Clival Invasion Compared with Other Subtypes

Nonfunctional pituitary neuroendocrine tumors (PitNETs) exhibit wide variability in growth pattern based on subtype. Silent corticotroph adenomas (SCAs) demonstrate aggressive growth compared with other nonfunctional pituitary adenomas (NFPAs), especially into the cavernous sinus. In this study, we sought to characterize other growth patterns of SCAs compared with NFPAs. We performed a retrospective analysis of all patients with nonfunctional PitNETs treated with surgical resection via endoscopic endonasal approach at a single institution from August 1, 2018, to May 11, 2024. Preoperative computed tomography and magnetic resonance imaging were reviewed to determine extension into the suprasellar space, sphenoid sinus, cavernous sinus, and clivus. The study comprised 91 patients, including 20 SCAs and 71 NFPAs. SCAs demonstrated significantly greater rates of growth into the sphenoid sinus (55.0% vs. 23.94%, P= 0.013), clivus (65.0% vs. 16.9%, P < 0.0001), and cavernous sinus (defined as Knosp grade 3 or 4; 55.0% vs. 23.35%, P= 0.016). Other NFPAs were more likely to grow into the suprasellar space (92.96% vs. 75.0%, P= 0.038). Tumor volume was similar between groups (11.93 cm3 vs. 9.06 cm3, P= 0.2). Silent corticotroph PitNETs demonstrate predilection for invasion of bony structures, with higher rates of growing through the sellar floor into the sphenoid sinus, growing posteroinferiorly into the clivus and laterally into the cavernous sinuses. Other nonfunctional PitNETs tended to follow the path of least resistance, growing superiorly into the suprasellar space. These differences in growth patterns may account for some of the clinical challenges of treating silent corticotroph PitNETs.

Pseudocapsular resection to prevent recurrence in nonfunctioning pituitary neuroendocrine tumors: a retrospective, single-center study with more than 5 years of follow-up.

Pseudocapsular resection is a well-recognized, useful approach to achieve endocrinological remission in functioning pituitary neuroendocrine tumors (PitNETs). However, its advantage in nonfunctioning PitNETs (NF-PitNETs) has not been established. This study aimed to clarify the contribution of pseudocapsular resection to the prevention of NF-PitNET recurrence in long-term follow-up. This retrospective study included 132 patients who underwent total tumor removal and were followed for more than 5 years after surgery. The patients were categorized into those who underwent total pseudocapsular resection (n = 67) and those who did not (n = 65). The nonpseudocapsule (nonpseudocap) resection group included patients who underwent partial pseudocapsular resection and those in whom the pseudocapsule was not resected, did not exist, or could not be identified during surgery. The main outcome measures were the tumor recurrence rate and site of recurrence. In the nonpseudocap resection group, 2 patients (3.1%) had tumor recurrence in the cavernous sinus and 5 (7.7%) had tumor recurrence in the pituitary fossa. In the pseudocapsule (pseudocap) resection group, only 2 patients (3.0%) had tumor recurrence in the cavernous sinus and 0 patients had tumor recurrence in the pituitary fossa. Tumor recurrence in the pituitary fossa was more likely to occur in the nonpseudocap resection group than in the pseudocap resection group (p = 0.0267). Multivariate regression analysis revealed that pseudocapsular resection was a significant factor for reducing the tumor recurrence rate in the pituitary fossa (p = 0.0107). Pseudocapsular resection may reduce the rate of tumor recurrence and improve the management of NF-PitNETs in long-term follow-up.

Comparison among different preclinical models derived from the same patient with a non-functional pancreatic neuroendocrine tumor.

Pancreatic neuroendocrine tumors are the second most common tumors of the pancreas, and approximately half of patients are diagnosed with liver metastases. Currently, the improvement in the efficacy of relevant treatment methods is still limited. Therefore, there is an urgent need for in-depth research on the molecular biological mechanism of pancreatic neuroendocrine tumors. However, due to their relatively inert biology, preclinical models are extremely scarce. Here, the patient-derived organoid, and patient-derived xenograft were successfully constructed. These two models and the previously constructed cell line named SPNE1 all derived from the same patient with a grade 3 non-functional pancreatic neuroendocrine tumor, providing new tumor modeling platforms, and characterized using immunohistochemistry, whole-exome sequencing, and single-cell transcriptome sequencing. Combined with a tumor formation experiment in immunodeficient mice, we selected the model that most closely recapitulated the parental tumor. Overall, the patient-derived xenograft model most closely resembled human tumor tissue.

KLHL14 and E-Cadherin Nuclear Co-Expression as Predicting Factor of Nonfunctioning PitNET Invasiveness: Preliminary Study.

Background/Objectives. Novel diagnostic and therapeutic approaches are needed to improve the clinical management of nonfunctioning pituitary neuroendocrine tumors (NF-PitNETs). Here, the expression of two proteins controlling the epithelial-mesenchymal transition (EMT)-an underlying NF-PitNET pathogenic mechanism-were analyzed as prognostic markers: E-cadherin (E-Cad) and KLHL14. Methods. The immunohistochemistry characterization of KLHL14 and E-Cad subcellular expression in surgical specimens of 12 NF-PitNET patients, with low and high invasiveness grades (respectively, Ki67+ < and ≥3%) was carried out. Results. The analysis of healthy vs. NF-PitNET tissues demonstrated an increased protein expression and nuclear translocation of KLHL14. Moreover, both E-Cad and KLHL14 shifted from a cytoplasmic (C) form in a low invasive NF-PitNET to a nuclear (N) localization in a high invasive NF-PitNET. A significant correlation was found between E-Cad/KLHL14 co-localization in the cytoplasm (p = 0.01) and nucleus (p = 0.01) and with NF-PitNET invasiveness grade. Conclusions. Nuclear buildup of both E-Cad and KLHL14 detected in high invasive NF-PitNET patients highlights a novel intracellular mechanism governing the tumor propensity to local invasion (Ki67+ ≥ 3%). The prolonged progression-free survival trend documented in patients with lower KLHL14 expression further supported such a hypothesis even if a larger cohort of NF-PitNET patients have to be analyzed to definitively recognize a key prognostic role for KLHL14.

Impact of adrenalectomy on hypertension in patients with nonfunctional adrenal tumors: a retrospective study.

To investigate the impact of adrenalectomy on hypertension in patients with nonfunctional adrenal tumors. Between January 2020 and October 2022, patients with adrenal lesions were retrospectively screened for nonfunctional adrenal tumors at the Zhongnan Hospital of Wuhan University. All patients underwent detailed endocrinological examination and computed tomography to characterize the lesions. One year after discharge, follow-up blood pressure (BP) was assessed and compared to the blood pressure on admission. Univariate analysis and multivariate regression analysis were performed to determine factors predicting favorable hypertension outcomes after adrenalectomy. A total of 309 patients were found to be eligible, including 123 who underwent adrenalectomy. Patients who underwent adrenalectomy were stratified into two groups: (Bancos I (2022) Adrenal Incidentalomas: Insights Into Prevalence. Ann Intern Med 175:1481-1482. https://doi.org/10.7326/M22-2600 ) those with improved hypertension (n = 71), and (Fassnacht M, Tsagarakis S, Terzolo M, Tabarin A, Sahdev A, Newell-Price J et al. (2023) European Society of Endocrinology clinical practice guidelines on the management of adrenal incidentalomas, in collaboration with the European Network for the Study of Adrenal Tumors. Eur J Endocrinol 189:G1-42. https://doi.org/10.1093/ejendo/lvad066 ) those without improved hypertension (n = 52). In contrast, the blood pressure levels of conservatively treated patients remained relatively stable 1 year after discharge. Univariate analysis and multivariate regression analysis showed that body mass index (BMI) and duration of hypertension were significantly different between the hypertension improvement group and the non-improvement group (p < 0.05). Adrenalectomy has been shown to be effective in improving hypertension in certain patients with nonfunctional adrenal tumors. BMI and duration of hypertension were independent factors associated with favorable hypertension outcomes after adrenalectomy.

Suspected silent pituitary somatotroph neuroendocrine tumor associated with acromegaly-like bone disorders: a case report

BackgroundGrowth hormone (GH) positive pituitary neuroendocrine tumors do not always cause acromegaly. Approximately one-third of GH-positive pituitary tumors are classified as non-functioning pituitary tumors in clinical practice. They typically have GH and serum insulin-like growth factor 1 (IGF-1) levels in the reference range and no acromegaly-like symptoms. However, normal hormone levels might not exclude the underlying hypersecretion of GH. This is a rare and paradoxical case of pituitary tumor causing acromegaly-associated symptoms despite normal GH and IGF-1 levels.Case presentationWe report a case of a 35-year-old woman with suspicious acromegaly-associated presentations, including facial changes, headache, oligomenorrhea, and new-onset diabetes mellitus and dyslipidemia. Imaging found a 19 × 12 × 8 mm pituitary tumor, but her serum IGF-1 was within the reference, and nadir GH was 0.7ng/ml after glucose load at diagnosis. A thickened skull base, increased uptake in cranial bones in bone scan, and elevated bone turnover markers indicated abnormal bone metabolism. We considered the pituitary tumor, possibly a rare subtype in subtle or clinically silent GH pituitary tumor, likely contributed to her discomforts. After the transsphenoidal surgery, the IGF-1 and nadir GH decreased immediately. A GH and prolactin-positive pituitary neuroendocrine tumor was confirmed in the histopathologic study. No tumor remnant was observed three months after the operation, and her discomforts, glucose, and bone metabolism were partially relieved.ConclusionsGH-positive pituitary neuroendocrine tumors with hormonal tests that do not meet the diagnostic criteria for acromegaly may also cause GH hypersecretion presentations. Patients with pituitary tumors and suspicious acromegaly symptoms may require more proactive treatment than non-functioning tumors of similar size and invasiveness.

Outcome of non-functioning ACTH pituitary tumors: silent does not mean indolent.

Silent corticotroph tumors (siACTH) represent a rare entity of pituitary tumors (PT), usually more aggressive than other PT. Few predictor factors of recurrence in the post-operative period have been proposed until now. This study aimed (1) to evaluate the clinical outcome of siACTH after surgery according to a five-tiered clinicopathological classification (2) to compare siACTH characteristics to ACTH-secreting macroadenomas (macroCD), and silent gonadotropinomas (siLH/FSH). Between 2008 and 2022, 29 siACTH out of 865 PT cases operated in one tertiary center were included. Clinical, paraclinical, histological, and surgical data were collected and compared to 25 macroCD and 143 siLH/FSH cases, respectively. The tumor grading was established according to both invasion (no = 1; yes = 2) and proliferation (no = a; yes = b). Progression-free survival was estimated using Kaplan-Meier method and log-rank test. We identified 15 (51.7%) grade 1a, 11 (37.9%) grade 2a and 3 (10.3%) grade 2b siACTH with a trend for a 7-fold-time higher risk of progression/recurrence in grade 2b as compared to 1a (p = 0.06). The repartition of tumor grades was similar between the three subgroups, however a 5.7-fold-higher risk of progression was observed in grade 1a siACTH than in grade 1a siLH/FSH (p = 0.02). Compared to siLH/FSH, higher ACTH levels may help to preoperatively identify siACTH. The five-tiered clinicopathological classification contribute to predict the risk of recurrence of operated siACTH tumors. Noteworthy, non-invasive and non-proliferative siACTH exhibit a less favorable outcomes than their siLH/FSH counterparts, which should prompt for a personalized follow up.

European Neuroendocrine Tumor Society (ENETS) 2024 guidance paper for the management of well-differentiated small intestine neuroendocrine tumours.

Both the incidence and prevalence of well-differentiated neuroendocrine tumours from the small intestine (Si-NET) are gradually increasing. Most patients have non-functioning tumours with subtle GI symptoms and tumours are often discovered incidentally by endoscopy or at advanced disease stages by imaging depicting mesenteric lymph node and /or liver metastases while around 30% of the patients present with symptoms of the carcinoid syndrome. Adequate biochemical assessment and staging including functional imaging is crucial for treatment-related decision-making that should take place in an expert multidisciplinary team setting. Preferably, patients should be referred to specialised ENETS Centres of Excellence or centres of high expertise in the field. This guidance paper provides the current evidence and best knowledge for the management of Si-NET grade (G) 1-3 following 10 key questions of practical relevance for the diagnostic and therapeutic decision making.

Critical appraisal of the adequacy of surgical indications for non-functioning pancreatic neuroendocrine tumours.

The lack of preoperative prognostic factors to accurately predict tumour aggressiveness in non-functioning pancreatic neuroendocrine tumours may result in inappropriate management decisions. This study aimed to critically evaluate the adequacy of surgical treatment in patients with resectable non-functioning pancreatic neuroendocrine tumours and investigate preoperative features of surgical appropriateness. A retrospective study was conducted on patients who underwent curative surgery for non-functioning pancreatic neuroendocrine tumours at San Raffaele Hospital (2002-2022). The appropriateness of surgical treatment was categorized as appropriate, potential overtreatment and potential undertreatment based on histologic features of aggressiveness and disease relapse within 1 year from surgery (early relapse). A total of 384 patients were included. Among them, 230 (60%) received appropriate surgical treatment, whereas the remaining 154 (40%) underwent potentially inadequate treatment: 129 (34%) experienced potential overtreatment and 25 (6%) received potential undertreatment. The appropriateness of surgical treatment was significantly associated with radiological tumour size (P < 0.001), tumour site (P = 0.012), surgical technique (P < 0.001) and year of surgical resection (P < 0.001). Surgery performed before 2015 (OR 2.580, 95% c.i. 1.570 to 4.242; P < 0.001), radiological tumour diameter < 25.5 mm (OR 6.566, 95% c.i. 4.010 to 10.751; P < 0.001) and pancreatic body/tail localization (OR 1.908, 95% c.i. 1.119 to 3.253; P = 0.018) were identified as independent predictors of potential overtreatment. Radiological tumour size was the only independent determinant of potential undertreatment (OR 0.291, 95% c.i. 0.107 to 0.791; P = 0.016). Patients subjected to potential undertreatment exhibited significantly poorer disease-free survival (P < 0.001), overall survival (P < 0.001) and disease-specific survival (P < 0.001). Potential overtreatment occurs in nearly one-third of patients undergoing surgery for non-functioning pancreatic neuroendocrine tumours. Tumour diameter emerges as the sole variable capable of predicting the risk of both potential surgical overtreatment and undertreatment.

Current peri-operative and surgical management of bladder paraganglioma

Introduction: In this article, we provide a narrative review of current peri-operative and surgical management of paraganglioma of the urinary bladder (PUB). Methods: Key articles relating to peri-operative optimisation, intra-operative considerations and post-operative follow-up of patients with PUB were identified for review. Discussion: Although the majority of PUBs are functionally active with potential for catecholamine release, typical catecholaminergic symptoms are often overshadowed by the presence of lower urinary tract symptoms such as painless visible haematuria. Consequently, many cases are diagnosed based on post-operative histopathology, resulting in inferior short- and long-term outcomes. Accurate pre-operative diagnosis is crucial as this informs pre-operative optimisation and choice of surgical approach. Partial cystectomy is the mainstay of treatment, but transurethral resection may be appropriate for non-functional tumours &lt;3 cm. The presence of succinate dehydrogenase ( SDH) subunit B (SDHB) pathogenic variants may prompt upfront radical cystectomy. Long-term outcomes of surgical patients remain incompletely characterised and lifelong follow-up is recommended to exclude tumour recurrence. Conclusion: Patients with PUBs require meticulous peri-operative optimisation under the care of an experienced multidisciplinary team. A pre-operative diagnosis is crucial to ensure optimal outcomes and guide surgical decision-making. Level of evidence: 4

Endoscopic ultrasonography-based intratumoral and peritumoral machine learning radiomics analyses for distinguishing insulinomas from non-functional pancreatic neuroendocrine tumors.

To develop and validate radiomics models utilizing endoscopic ultrasonography (EUS) images to distinguish insulinomas from non-functional pancreatic neuroendocrine tumors (NF-PNETs). A total of 106 patients, comprising 61 with insulinomas and 45 with NF-PNETs, were included in this study. The patients were randomly assigned to either the training or test cohort. Radiomics features were extracted from both the intratumoral and peritumoral regions, respectively. Six machine learning algorithms were utilized to train intratumoral prediction models, using only the nonzero coefficient features. The researchers identified the most effective intratumoral radiomics model and subsequently employed it to develop peritumoral and combined radiomics models. Finally, a predictive nomogram for insulinomas was constructed and assessed. A total of 107 radiomics features were extracted based on EUS, and only features with nonzero coefficients were retained. Among the six intratumoral radiomics models, the light gradient boosting machine (LightGBM) model demonstrated superior performance. Furthermore, a peritumoral radiomics model was established and evaluated. The combined model, integrating both the intratumoral and peritumoral radiomics features, exhibited a comparable performance in the training cohort (AUC=0.876) and achieved the highest accuracy in predicting outcomes in the test cohorts (AUC=0.835). The Delong test, calibration curves, and decision curve analysis (DCA) were employed to validate these findings. Insulinomas exhibited a significantly smaller diameter compared to NF-PNETs. Finally, the nomogram, incorporating diameter and radiomics signature, was constructed and assessed, which owned superior performance in both the training (AUC=0.929) and test (AUC=0.913) cohorts. A novel and impactful radiomics model and nomogram were developed and validated for the accurate differentiation of NF-PNETs and insulinomas utilizing EUS images.

INTERESTING CLINICAL CASE: ROLE OF ULTRASOUND DIAGNOSTICS IN DETECTING NEUROENDOCRINE TUMOR OF THE PANCREAS

Neuroendocrine tumors of the pancreas today occupy the second place in the prevalence of malignant epithelial tumors of the pancreas [1, p. 132]. Neuroendocrine tumors are divided according to activity into functioning and non-functioning tumors, the latter in turn have the second name “non-secreting” and are more common than functioning tumors. Non-functioning tumors are unfavorable because their growth is slow and a person does not feel symptoms for a long time, but the tumor grows to large sizes, thereby causing symptoms of compression of adjacent anatomical structures [3, p.458]. Neuroendocrine tumors are often diagnosed when they have already metastasized or reached a large size. In view of this, assessment of the tumor load requires the use of several methods of radiation diagnostics: ultrasound, computed tomography, magnetic resonance imaging [2, p.30]. This article will review clinical cases of neuroendocrine tumors using different diagnostic methods.