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Insulinomas are rare neoplasms of the endocrine pancreas. Minimally invasive treatment options for insulinomas have gained prominence, replacing surgical resection due to its associated morbidity and mortality. Radiofrequency ablation (RFA) has emerged as a relevant treatment option. We present a case of a female patient with neuroglycopenic symptoms and severe hypoglycemic crises. The abdominal magnetic resonance imaging (MRI) showed a small nodular lesion in the pancreatic body. Laparotomy was performed, followed by RFA using a 15-mm active-tipped needle. No complications transpired, and no hypoglycemic episodes were observed during 12 months of follow-up.

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Surgery is the main treatment for insulinoma, and precise preoperative localization is important to determine the extent of resection and to rule out multiple lesions. The selective arterial calcium injection (SACI) test is instrumental in the localization of insulinoma. Here we report a patient in whom the exact location of pancreatic insulinoma could not be determined by the conventional SACI test, and thus surgery was replaced with oral diazoxide. The hyperselective SACI test subsequently localized the lesion accurately, allowing surgical resection of the pancreatic body and tail while preserving the pancreatic head. We recommend the use of the hyperselective SACI test when the conventional SACI test fails to accurately determine the location of insulinoma lesions within the pancreas.

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PURPOSE: This retrospective study evaluates the value of 68Ga-DOTATATE PET/CT in the diagnosis and localization of insulinomas, whether sporadic, malignant or MEN-1 associated insulinoma. METHOD: The study included 43 patients, having clinical (symptomatic hypoglycemia) and/or laboratory suspicion of having insulinoma (72 h fasting test with serum insulin ≥18 pmol/L), with available pre-operative 68Ga-DOTATATE PET/CT and CE-CT, and diagnosed with insulinoma confirmed by post-operative histopathology. Preoperative imaging was retrospectively analyzed by two radiologists who were blinded to the final diagnosis and to the results of other imaging modalities. Histopathology of specimen was considered the reference standard, and head-to-head comparison of preoperative CE-CT and PET imaging findings. Findings were classified as true positive (TP), true negative (TN), false positive (FP), and false negative (FN) for each modality. Based on these results, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of CE-CT, and 68Ga-DOTATATE PET/CT for the detection of insulinoma were calculated. RESULTS: 43 patients (N = 43 patients, L = 56 lesions), out of these, 37 patients had benign sporadic insulinoma (N = 37, L = 42), only 3 patients had malignant sporadic insulinoma (N = 2, L = 9), and 3 patients had MEN-1 syndrome associated insulinoma (N = 3, L = 5). There was no significant statistical difference in sensitivity (P = 0.3058) and PPV (P = 0.5533) for insulinoma localization in the overall cohort with 68Ga-DOTATATE PET/CT (87.5 %, 90.74 %) compared to CE-CT (80.36 %, 93.75 %). CONCLUSION: 68Ga-DOTATATE PET/CT is a non-invasive imaging modality that can identify most insulinomas. Still, it offers limited additional information when the tumor is localized by other anatomic imaging studies, so should be used as an adjunct when imaging studies fail to localize the tumor in insulinoma patients, especially when minimally invasive surgical is intended.

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Objectives: To develop and validate radiomics models utilizing endoscopic ultrasonography (EUS) images to distinguish insulinomas from non-functional pancreatic neuroendocrine tumors (NF-PNETs). Methods: 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. Results: 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. Conclusion: A novel and impactful radiomics model and nomogram were developed and validated for the accurate differentiation of NF-PNETs and insulinomas utilizing EUS images.

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ABSTRACT: Metastatic insulinomas can cause recurrent hypoglycemia requiring continuous IV glucose infusion. Various medical and chemotherapeutic treatment options are used to reduce the patient's risk of death due to hypoglycemia. Treatment-resistant hepatic metastatic insulinomas may benefit clinically from 90Y transarterial radioembolization therapy. In this case, we present a case of liver metastatic insulinoma that achieved clinical improvement after 2 cycles of 90Y microspheres transarterial radioembolization, and the presence of active metastases was demonstrated with 68Ga-NODAGA-exendin-4 PET/CT imaging.

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Insulinomas are the most common functional pancreatic neuroendocrine neoplasm; when treatment is delayed, they induce hyperinsulinemic hypoglycemia, which is life-threatening. As surgical resection is the only curative treatment for insulinoma, preoperative localization is crucial; however, localization based on conventional imaging modalities such as computed tomography (CT) and magnetic resonance imaging is often inconclusive. Somatostatin receptor-targeted imaging is another option for detecting pancreatic neuroendocrine neoplasms but has low sensitivity and is not specific for insulinoma. The clinical application of other localizing approaches such as selective arterial calcium stimulation and endoscopic ultrasonography-guided fine needle aspiration (EUS-FNA) is limited by their being invasive and/or technically complex. Moreover, an EUS-FNA specimen of an insulinoma may be negative on insulin immunostaining. Thus, a noninvasive and clinically practical insulinoma-specific diagnostic tool to discriminate insulinomas with high accuracy is anticipated. Glucagon-like peptide-1 receptor (GLP-1R)-targeted imaging has emerged in the effort to fulfill this need. We recently developed the novel fluorine-18-labeled exendin-4-based probe conjugated with polyethylene glycol, [18F]FB(ePEG12)12-exendin-4 (18F-exendin-4) for positron emission tomography (PET) imaging and reported its clinical benefit in a case of insulinoma in the pancreatic tail. We report here a case of insulinoma in the pancreatic head in which an EUS-FNA specimen was negative on insulin immunostaining while precise preoperative localization and conclusive evidence for curative enucleation was provided by 18F-exendin-4 PET/CT (Japan Registry of Clinical Trials; jRCTs051200156).

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When a neuroendocrine tumor with abundant blood flow is located in the pancreatic tail, it is difficult to distinguish it from accessory spleen. The patient was a 71-year-old woman who was admitted with impaired consciousness and hypoglycemia, raising suspicion of insulinoma. The selective arterial calcium injection test suggested a lesion in the pancreatic tail. Contrast-enhanced computed tomography and magnetic resonance imaging (MRI) showed a mass in the splenic hilum; however, its continuity with the pancreas was unclear. Contrast-enhanced MRI using super paramagnetic iron oxide (SPIO) showed no SPIO uptake in the splenic hilar mass. SPIO contrast-enhanced MRI is considered useful for differentiating pancreatic endocrine tumors from paraspleen tumors.

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Background and aims: Most pancreatic insulinomas can be treated by minimally invasive modalities. The aim of this meta-analysis was to assess the clinical outcomes of endoscopic ultrasound (EUS)-guided ablation and minimally invasive surgery (MIS) in the treatment of pancreatic insulinoma. Materials and methods: Online databases were searched for relevant studies. The primary aim was to compare the rates of adverse events (AEs) and the secondary aims were to compare the clinical and technical success rates, length of hospital stays, and symptom recurrence rates between EUS and MIS approaches. Results: Eight studies with 150 patients were identified that reported EUS-guided ablation outcomes, forming the EUS group, and 9 studies with 236 patients reported MIS outcomes, forming the MIS group. The pooled median age of the included patients in the EUS group was greater than that of the MIS group (64.06 vs. 44.98 years old, p < 0.001). Also, the technical success rate was significantly higher in the EUS group (100% vs. 96.6%, p = 0.025), while the clinical success was significantly higher (6%) in the MIS group (94% vs. 98.7%, p = 0.021). The AE rates (18.7% vs. 31.1%, p = 0.012) and severe AE rates (1.3% vs. 7.9%, p = 0.011) were significantly lower in the EUS group. The median length of hospital stay in the EUS group (2.68 days, 95% CI: 1.88-3.48, I2 = 60.3%) was significantly shorter than in the MIS group (7.40 days, 95% CI: 6.22-8.58, I2 = 42.2%, p < 0.001). The recurrence rate was significantly higher in the EUS group (15.3% vs. 1.3%, p < 0.001). Conclusions: EUS-guided ablation is associated with a lower AE rate and a shorter length of hospital stay, but a higher recurrence rate for the treatment of insulinoma compared with MIS. The EUS approach may be an alternative, even first-line, treatment for poor surgery candidates.

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INTRODUCTION: Insulinomas are the most common functional pancreatic neuroendocrine tumors (PNETs) that lead to incapacitating hypoglycemia. Guidelines recommend surgical resection as the mainstay of management. However, surgery is fraught with complications, causing significant peri/post-operative morbidity. Since insulinomas are usually benign, solitary, small (<2 cm), and do not need lymphadenectomy, hence, in this regard, endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) is now being increasingly performed, to circumvent these adverse events and impairment of pancreatic function. AREAS COVERED: A comprehensive literature search was undertaken across various databases (PubMed/MEDLINE, Embase, Scopus), with no language restriction, for relevant articles (case series, reviews, case reports) pertaining to EUS-RFA for insulinoma and PNETs, till October 2023. In this review, we have explicated the role of EUS-RFA for insulinoma management, detailing thoroughly its mechanism of action, EUS-RFA devices with data on its safety and efficacy, and an algorithmic approach for its management. EXPERT OPINION: EUS-RFA is being advocated as a 'mini-invasive' option with the potential to replace surgery as a first-line approach for benign, sporadic, solitary, and small (<2 cm) insulinomas. Under real-time guidance, EUS-RFA has immense precision, is safe, predictable, with acceptable safety profile. Presently, it is being frequently performed for high-risk or inoperable candidates. Current need-of-the-hour is a randomized controlled trial to substantiate its role in the therapeutic algorithm for insulinoma management.

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Introducción: La tomografía de emisión de positrones es una técnica diagnóstica no invasiva que permite tomar imágenes del organismo que muestra el metabolismo de los órganos del cuerpo. Objetivo: Destacar el valor de la PET/CT en el diagnóstico imagenológico prequirúrgico del enfermo. Presentación de caso: Se presentó un paciente masculino de 39 años sin antecedentes de importancia, con un cuadro de hipoglucemias severas de 5 años de evolución, a pesar de los múltiples estudios imagenológicos se incluyó la ecoendoscopía digestiva, lo que no fue posible evidenciar la lesión tumoral. Se le realiza PET/CT cuyo resultado fue crucial para localizar el tumor, se le dio al paciente la oportunidad de un tratamiento quirúrgico y la demostración anatomopatológica de insulinoma. Conclusiones: Los insulinomas son tumores pancreáticos poco frecuentes que provocan hiperinsulinismo endógeno y son difíciles de visualizar debido a su tamaño por las técnicas de imágenes convencionales, por lo que el PET/CT es un estudio bastante efectivo para localizar la lesión tumoral, y así realizar un procedimiento quirúrgico(AU)

Introduction: Positron emission tomography is a non-invasive diagnostic technique, allowing images of the body to be taken that show the metabolism of the body's organs. Objective: To highlight the value of PET/CT in the pre-surgical imaging diagnosis of the patient. Case presentation: We report the case of a 39-year-old male patient with no significant medical history, but a 5-year history of severe hypoglycemia. Despite multiple imaging studies, digestive ultrasound endoscopy was included, which was not possible to demonstrate the tumor lesion. PET/CT was performed, the result of which was crucial in locating the tumor. The patient was given the opportunity for surgical treatment and the pathological demonstration of insulinoma. Conclusions: Insulinomas are rare pancreatic tumors that cause endogenous hyperinsulinism and are difficult to visualize due to their size using conventional imaging techniques, therefore PET/CT is a fairly effective study to locate the tumor lesion, and thus perform a surgical procedure(AU)

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Insulinoma is a multifaceted disease that poses several challenges in terms of clinical presentation, diagnostic work-up, and surgical management. The aim of this study was to describe diagnostic work-up, surgical management, and postoperative outcomes of patients with insulinoma. All consecutive patients who underwent surgery for insulinoma at San Raffaele Hospital (Milan, Italy) between January 2008 and January 2022 were included. Overall, 98 patients were considered. The median delay between presenting symptoms and insulinoma diagnosis was 10 months (IQR, 4-21). Insulinoma diagnosis was made at our Institution in 45 patients, 20 of whom referred within 6 months from symptoms onset. In this subgroup, the median interval between symptoms presentation and insulinoma diagnosis was 4 months (IQR, 2-6), as compared to 14 months (IQR, 10-26) in patients (n = 25) who referred to our institution after 6 months from symptoms onset (p < .001). The insulinoma was localized preoperatively in all the cases. All patients underwent ≥1 high-quality imaging: computed tomography (CT: n = 87, sensitivity 84%), magnetic resonance imaging (MRI: n = 55, sensitivity 85%) and endoscopic ultrasound (EUS: n = 79, sensitivity 100%). MRI identified the tumor in eight patients with negative CT. EUS localized the insulinoma in three patients with negative CT and negative MRI. Parenchyma-sparing resections were performed in 41 patients. Contact with major vessels, lesion close to Wirsung duct and suspect of malignancy were the main reasons to perform a formal resection. An early referral to high-volume centers is important for reducing diagnostic delay in patients with insulinoma. The diagnostic work-up of insulinoma frequently requires several imaging modalities to be performed, with EUS being the most sensitive one. Parenchyma-sparing surgery for insulinoma should be performed whenever technically and oncologically feasible.

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Objective: Cognitive dysfunction is common in insulinoma patients, but the underlying neural mechanisms are less well understood. This study aimed to explore the alterations of intra- and inter-network connectivity patterns associated with patients with insulinoma. Methods: Resting-state fMRI were acquired from 13 insulinoma patients and 13 matched healthy controls (HCs). Group Independent component analysis (ICA) was employed to capture the resting-state networks (RSNs), then the intra- and inter-network connectivity patterns, were calculated and compared. Montreal Cognitive Assessment (MoCA) was used to assess the cognitive function. The relationship between connectivity patterns and MoCA scores was also examined. Results: Insulinoma patients performed significantly worse on MoCA compared to HCs. The intra-network connectivity analysis revealed that patients with insulinoma showed decreased connectivity in the left medial superior frontal gyrus within anterior default mode network (aDMN), and decreased connectivity in right lingual gyrus within the visual network (VN). The intra-network connectivity analysis showed that patients with insulinoma had an increased connectivity between the inferior-posterior default mode network (ipDMN) and right frontoparietal network (rFPN) and decreased connectivity between the ipDMN and auditory network (AUN). There was a significant negative correlation between the ipDMN-rFPN connectivity and MoCA score. Conclusion: This study demonstrated significant abnormalities in the intra- and inter-network connectivity in patients with insulinoma, which may represent the neural mechanisms underlying the cognitive impairment in insulinoma patients.

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Background: Insulinomas are the most common functioning pancreatic neuroendocrine neoplasms, and these tumors induce hypoglycemia due to hyperinsulinemia. Hypoglycemia caused by insulinomas can cause seizures, coma or death due to the delayed diagnosis. The only curative treatment is surgical resection. To perform curative surgical resection of insulinomas, preoperative localization is crucial. However, localization of insulinomas is often challenging using conventional imaging methods such as computed tomography (CT) and magnetic resonance imaging. Although endoscopic ultrasound (EUS) fine-needle aspiration and selective arterial calcium stimulation test, which can reflect the endocrine character of the tumor, are performed in such cases, these modalities are invasive and require operator-dependent techniques. Additionally, somatostatin receptor (SSTR)-targeted imaging has a relatively low sensitivity for detecting insulinomas due to its low SSTR type 2 expression. Thus, there is an urgent need for developing a noninvasive diagnostic technique which is specific for detecting insulinomas. Consequently, glucagon-like peptide-1 receptor-targeted imaging has recently emerged and gained a wide interest. Recently, we have developed a novel 18F-labeled exendin-4-based probe conjugated with polyethylene glycol, [18F]FB(ePEG12)12-exendin-4 (18F-exendin-4), for positron emission tomography (PET) imaging. Here we report a case of insulinoma in which 18F-exendin-4 PET/CT noninvasively provided critical information for localization. Case description: This is a case of a 58-year-old male with symptomatic hypoglycemia for 10 years; however, a preoperative diagnosis of insulinoma was not established due to the difficulty in differentiating it from an accessory spleen using conventional imaging. Moreover, the patient requested to avoid invasive diagnostic procedures including EUS. 18F-exendin-4 PET/CT revealed significant uptakes in the pancreatic tail whereas no apparent uptakes were observed in the spleen; thus, curative laparoscopic enucleation of the pancreatic tail was performed. The diagnosis of insulinoma was confirmed via histopathological examination. This is the first case report of insulinoma diagnosed using 18F-exendin-4 PET/CT. Conclusion: In this case, PET information led to curative resection through enucleation of the pancreas. 18F-exendin-4 PET/CT may serve as a useful noninvasive clinical tool for insulinoma localization.

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Arterial enhancement is the commonly described characteristic of canine insulinomas in contrast-enhanced computed tomography (CECT). However, this finding is also reported as inconsistent. The main aim of this single-center retrospective observational study was to describe the contrast enhancement (CE) pattern of canine presumed and confirmed insulinomas and presumed metastases in three consecutive (early, mid, and late) arterial phases. Included dogs had a medical-record-based clinical or cytological/histopathological diagnosis of insulinoma and quadruple-phase CECT. The arterial phases were identified according to published literature. The arterial enhancement of confirmed and presumed lesions was assessed using a visual grading score. Twelve dogs with a total of 17 pancreatic nodules were analyzed. Three dogs had multiple pancreatic nodules and nine had solitary findings. Four insulinomas were histopathologically confirmed. Late arterial phase (LAP) images demonstrated the largest number of pancreatic nodules reaching the highest enhancement scores (n = 13, 76%). All analyzed dogs had CT evidence of arterially enhancing nodules in the liver (n = 12), seven in the hepatic, splenic, or colic lymph nodes, and three in the spleen. Three out of five sampled livers and three lymph nodes were metastatic. All sampled spleens were benign. Avid arterial enhancement was the most dominant feature of canine presumed and confirmed insulinomas and presumed metastases in quadruple-phase CECT. The highest enhancement scores were observed primarily in LAP, followed by MAP. Authors, therefore, recommend including LAP in the standard CT protocol for dogs with suspected pancreatic insulinomas.

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Knowledge of ectopic insulinomas comes from single cases. We performed a systematic review through PubMed, Web of Science, Embase, eLibrary and ScienceDirect of all cases reported in the last four decades. We also describe one unreported patient. From 28 patients with ectopic insulinoma, 78.6% were female and mean age was 55.7 ± 19.2 years. Hypoglycaemia was the first symptom in 85.7% while 14.3% complained of abdominal pain or genital symptoms. Median tumour diameter was 27.5 [15-52.5] mm and it was localised by CT (73.1%), MRI (88.9%), [68Ga]Ga-DOTA-exedin-4 PET/CT (100%), 68Ga-labelled-DOTA-conjugated somatostatin analogue PET/TC (100%), somatostatin receptor scintigraphy (40%) and endoscopic ultrasound (50%). Ectopic insulinomas were located at duodenum (n = 3), jejunum (n = 2), and one respectively at stomach, liver, appendix, rectum, mesentery, ligament of Treitz, gastrosplenic ligament, hepatoduodenal ligament and splenic hilum. Seven insulinomas were affecting the female reproductive organs: ovary (n = 5), cervix (n = 2) and remaining tumours were at retroperitoneum (n = 3), kidney (n = 2), spleen (n = 1) and pelvis (n = 1). 89.3% underwent surgery (66.7% surgery vs. 33.3% laparoscopy) and 16% underwent an ineffective pancreatectomy. 85.7% had localized disease at diagnosis and 14.3% developed distant metastasis. Median follow-up time was 14.5 [4.5-35.5] months and mortality was reported in 28.6% with median time until death of 60 [5-144] months. In conclusion, ectopic insulinomas are presented as hypoglycaemia with female preponderance. Functional imaging [68Ga]Ga-DOTA-exedin-4 PET/CT and 68Ga-labelled-DOTA-conjugated somatostatin analogue PET/TC have very high sensitivity. Clinicians should be alert to the possibility of extra-pancreatic insulinomas when classic diagnostic tests and intraoperative pancreas exploration failed to locate the tumour.

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Insulinoma is a rare neuroendocrine functional tumor of the pancreas of unknown etiology which manifests itself through hypoglycemic symptoms which resolve by administering glycose. Common autonomic symptoms of insulinoma include diaphroresis, tremor, and palpitations, whereas neuroglycopenenic symptoms include confusion, behavioural changes, personality changes, visual disturbances, seizure, and coma. In most cases, these are benign solitary tumors of the pancreas, and in 5% of the cases they are associated with MEN1 syndrome. A characteristic of the diagnosis is the presence of hypoglycemia, and increased levels of C-peptide and insulin. Further radiological verification (non-invasive imaging procedures: computed tomography and magnetic resonance imaging; and invasive modalities, such as endoscopic ultrasonography and arterial stimulation venous sampling) of the tumor are required as well as its surgical extraction. We present a case of a middle-aged male with history of recurrent hypoglycemic episodes with vertigo, sweating, tremors, anxiety, fatigue, and loss of consciousness, all of which resolved after eating food. The diagnoses were confirmed after we performed non-invasive imaging procedure, such as Computed Tomography and Magnetic Resonance Imaging. The patient underwent successful resection of the tumor, and his symptoms showed complete resolution. Despite the low incidence of these tumors, they should be suspected, in cases where the patient presents with repetitive hypoglycemic episodes, with symptoms, which resolve after eating a meal. Timely diagnosis and adequate treatment in most cases equals to complete withdrawal of symptoms.

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BACKGROUND: Insulinoma is the most common functional pancreatic neuroendocrine tumor and treatment is required to address symptoms associated with insulin hypersecretion. Surgical resection is effective but burdened by high rate of adverse events (AEs). Endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) demonstrated encouraging results in terms of safety and efficacy for the management of these tumors. However, studies comparing surgery and EUS-RFA are lacking. AIMS: The primary aim is to compare EUS-RFA with surgery in term of safety (overall rate of AEs). Secondary endpoints include: (a) severe AEs rate; (b) clinical effectiveness; (c) patient's quality of life; (d) length of hospital stay; (e) rate of local/distance recurrence; (f) need of reintervention; (g) rate of endocrine and exocrine pancreatic insufficiency; (h) factors associated with EUS-RFA related AEs and clinical effectiveness. METHODS: ERASIN-RCT is an international randomized superiority ongoing trial in four countries. Sixty patients will be randomized in two arms (EUS-RFA vs surgery) and outcomes compared. Two EUS-RFA sessions will be allowed to achieve symptoms resolution. Randomization and data collection will be performed online. DISCUSSION: This study will ascertain if EUS-RFA can become the first-line therapy for management of small, sporadic, pancreatic insulinoma and be included in a step-up approach in case of clinical failure.

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Aims: This cross-sectional study compared the value of molecular imaging (Exendin-4 positron emission tomography/computed tomography [PET/CT], 68Ga-DOTATATE PET/CT, 18F- fluorodeoxyglucose [FDG] PET/CT) in insulinoma localization by stratified tumor size and grading, and explored the correlation of the related the maximum standardized uptake value (SUVmax) with insulinoma grading, Ki-67, maximum tumor diameter, and glucose metabolism. Methods: In 28 insulinoma patients, the sensitivity of three types of PET/CT for localizing insulinoma was calculated according to tumor size and grade. We compared the SUVmax for different insulinoma grades and analyzed the correlation of SUVmax with Ki-67, maximum tumor diameter, and glucose metabolism indicators. Results: The study included 12 grade (G) 1 and 16 G2 cases, with maximum tumor diameters ranging from 9 to 40 mm. Without differentiation by size and grade, the sensitivity of Exendin-4 PET/CT to localize insulinoma was 100%, which significantly exceeded that of 68Ga-DOTATATE PET/CT and 18F-FDG PET/CT (75% and 57%, respectively). In tumors with a maximum diameter ≤ 20 mm and ≤ 15 mm, the sensitivity of Exendin-4 (both 100%) significantly exceeded that of 68Ga-DOTATATE PET/CT (74% and 64%, respectively) and 18F-FDG PET/CT (54% and 50%, respectively). In G1 tumors, the sensitivity of Exendin-4 PET/CT was significantly higher than that of 18F-FDG PET/CT, but not that of 68Ga-DOTATATE PET/CT, while in G2 tumors, the sensitivity of Exendin-4 PET/CT was significantly higher than that of both other types. However, all three PET/CT types missed a metastatic lymph node in one patient. The 18F-FDG PET/CT SUVmax was significantly lower than that of the other PET/CT types and that of 68Ga-DOTATATE PET/CT was significantly lower in G2 than in G1. 68Ga-DOTATATE PET/CT SUVmax correlated negatively with Ki-67. A receiver operating characteristic (ROC) curve suggested that 68Ga-DOTATATE PET/CT SUVmax > 19.9 could predict G1 tumors. Conclusion: Exendin-4 PET/CT was superior to 68Ga-DOTATATE PET/CT and 18F-FDG PET/CT for insulinoma localization, particularly small and G2 tumors, but its diagnostic value in small metastatic lymph nodes requires further exploration. 68Ga-DOTATATE PET/CT SUVmax could be used as an adjunct to pathology, and a value > 19.9 could predict G1 tumors. No PET/CT SUVmax could predict tumor maximum diameter and glucose metabolism.

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