Localization Of Insulinoma Research Articles

Surgical management of insulinoma over three decades.

This paper reports our experience of the perioperative management of patients with sporadic, non-malignant, pancreatic insulinoma. A retrospective monocentric cohort study was performed from January 1989 to July 2019, including all the patients who had been operated on for pancreatic insulinoma. The preoperative work-up, surgical management, and postoperative outcome were analyzed. Eighty patients underwent surgery for sporadic pancreatic insulinoma, 50 of which were female (62%), with a median age of 50 (36-70) years. Preoperatively, the tumors were localized in 76 patients (95%). Computed tomography (CT) and magnetic resonance imaging allowed exact preoperative tumor localization in 76% of the patients (64-85 and 58-88 patients, respectively), increasing to 96% when endoscopic ultrasonography was performed. Forty-one parenchyma-sparing pancreatectomies (PSP) (including enucleation, caudal pancreatectomy, and uncinate process resection) and 39 pancreatic resections were performed. The mortality rate was 6% (n=5), with a morbidity rate of 72%, including 24 severe complications (30%) and 35 pancreatic fistulas (44%). No differences were found between formal pancreatectomy and PSP in terms of postoperative outcome procedures. The surgery was curative in all the patients. CT used in combination with endoscopic ultrasonography allows accurate localization of insulinomas in almost all patients. When possible, a parenchyma-sparing pancreatectomy should be proposed as the first-line surgical strategy.

The appearance of canine insulinoma on dual phase computed tomographic angiography.

To further evaluate the appearance of insulinoma in dogs on dual-phase CT angiography, given the disparity of findings in recent publications. To establish whether CT angiographic localisation of insulinoma correlates with surgical findings. Single centre study of dogs with a final diagnosis of insulinoma which underwent abdominal CT angiography. Scans were retrospectively re-evaluated for specific features by two board-certified veterinary radiologists. These findings were also subsequently compared to surgical and histopathological reports to determine the accuracy of lesion localisation on CT. Thirty-five cases were included in final analysis, with pancreatic nodules identified in 33. Twenty-one were confirmed as insulinoma with histopathology. Jack Russell Terriers were over-represented. Twenty of 21 cases with confirmed insulinoma and 27 of 33 overall showed hyperattenuation in the arterial phase. The mean size of pancreatic insulinoma on CT was 15.1 mm, and 18.2% were larger than 20 mm. Eighteen of 21 confirmed and eight of 12 suspected insulinomas caused a deformation of the pancreatic shape, with two only identified as a result of this feature as these lesions were isoattenuating throughout the study. Pancreatic insulinoma location at surgery matched that described on the CT images in 17 of 19 cases where location was described in the surgical report. In contrast to recent publications, this study suggests hyperattenuation of insulinomas in the arterial phase is a predominant feature, and that hypoattenuation or isoattenuation are much less common. CT angiography is accurate in prediction of lesion location before surgery in most cases.

Exendin‐4‐based imaging in insulinoma localization: Systematic review and meta‐analysis

Glucagon-like peptide-1 receptor (GLP-1 R) based imaging has shown higher sensitivity for insulinoma localization as compared to other anatomic/functional imaging. We reviewed the published English literature for GLP-1 R targeted imaging in insulinoma in PubMed until August 2020 in accordance with PRISMA guidelines using the MeSH terms "((Exendin-4 PET/CT) OR (Exendin-4 SPECT/CT) OR (GLP-1 R imaging)) AND (Insulinoma)". An individual patient data-metanalysis (IPD-MA) was performed, and performance parameters were calculated for the histopathological diagnosis of insulinoma. True-positive (TP), false-positive (FP), false-negative (FN), true-negative (TN), sensitivity (Sn), specificity (Sp), positive predictive value (PPV) and negative predictive value (NPV) for insulinoma localization. A total of 179 cases (316 lesions) from 16 publications were included for IPD-MA. For insulinoma localization, exendin-4-PET/CT (Sn & PPV: 94%) performed better than exendin-4-SPECT/CT (Sn: 63%, PPV: 94%). The Sn was lower in malignant insulinoma cases whereas the Sp was higher in cases with MEN-1 syndrome. With exendin-4-based imaging, FP uptakes in Brunner's gland, normal pancreas, and other β-cell pathologies and FN results in pancreatic tail lesions and malignancy were seen in a few patients. TN results suggested the correct diagnosis of other endogenous hyperinsulinemic hypoglycaemia (EHH) subtypes. For insulinoma localization, exendin-4 PET/CT should be preferred over exendin-4 SPECT/CT because of higher sensitivity and specificity. FP uptakes in Brunner's gland, normal pancreas, and other β-cell pathologies and FN results in tail lesions, and malignant insulinomas are limitations. Higher specificity for insulinoma localization is particularly useful in patients with MEN-1 syndrome.

Insulinoma of Pancreatic Head Localized by Intra-Arterial Calcium Stimulation with Hepatic Venous Sampling

Hypoglycemia is a common medical emergency. Insulinoma, a rare pancreatic endocrine tumour is the most common cause of hypoglycemia in patients without systemic illness. Most insulinomas are small, solitary and benign, which can be treated effectively by surgical removal of the tumour. Diagnosis is based on clinical features, laboratory tests and radiological investigation to localize the tumour. However, small size of this tumour leads to difficulty in localization of the disease, especially in occult insulinoma. Intra-arterial calcium stimulation with hepatic venous sampling can be utilised for preoperative localization of the tumour. We hereby present a case of a 33-year-old woman presenting with history of recurrent hypoglycemic symptoms and morbid obesity. A thorough history, clinical examination and laboratory investigation including prolonged fasting test were conducted and diagnosis of insulinoma was made. Intra-arterial calcium stimulation with hepatic venous sampling was carried out and revealed localization of insulinoma at pancreatic head.
 Bangladesh Journal of Medical Science Vol.20(1) 2021 p.216-219

Diagnosis value preoperative localization of insulinoma by diffusion-weighted imaging: A pilot study.

Insulinoma is the most common functional neuroendocrine tumor that originates from the islet of beta cells. Insulinoma is usually an isolated benign tumor and small in size (<2 cm). Due to the small size of the lesion, it often leads to difficulty in clinical preoperative localization diagnosis. However, we have unexpectedly discovered that the diffusion-weighted-imaging (DWI) adds great value in the preoperative localization diagnosis of insulinoma in non-invasive examination technique.We verified using operative pathology data and retrospectively analyzed the clinical and imageology findings of 5 cases who reported to have an insulinoma. All the 5 cases underwent DWI examination, among non-contrast enhanced magnetic resonance imaging (MRI) in 1 case, contrast-enhanced MRI in 4 cases.Five cases of DWI showed a nodular high signal <1.3 cm with pancreatic tail in 3 cases, pancreatic neck, and pancreatic head in 1 case each, respectively. Non-contrast enhanced MRI showed suspicious abnormal signals in the tail of the pancreas were detected in 1 case. MRI enhanced scans presented 2 cases with abnormal enhancement in the arterial phase and 2 cases without abnormal enhancement in arterial phase. Also, 3 cases showed mild persistence enhanced in the portal venous phase and delayed phase. However, 1 case remained normal in the portal venous phase and the delay period.DWI examination has high clinical value in the localization diagnosis of insulinoma and thus it can be used as a routine examination for preoperative localization diagnosis.

Essentials of Insulinoma Localization with Selective Arterial Calcium Stimulation and Hepatic Venous Sampling.

Insulinomas are the most common functional pancreatic neuroendocrine tumor. Most insulinomas can be localized non-invasively with cross-sectional and nuclear imaging. Selective arterial calcium stimulation and hepatic venous sampling is an effective and safe minimally-invasive procedure for insulinoma localization that may be utilized when non-invasive techniques are inconclusive. The procedure’s technical success and proper interpretation of its results is dependent on the interventional radiologist’s knowledge of normal and variant pancreatic arterial perfusion. Accurate pre-operative localization aids in successful surgical resection. Technical and anatomic considerations of insulinoma localization with selective arterial calcium stimulation and hepatic venous sampling are reviewed.

Exendin-4-based imaging in endogenous hyperinsulinemic hypoglycaemia cohort: A tertiary Endocrine centre experience.

Insulinoma needs accurate preoperative localization for minimally invasive surgery. Exendin-4-based imaging has shown promising results. To evaluate performance parameters of exendin-4-based imaging in insulinoma localization and compare with other imaging modalities. Retrospective cross-sectional study. We report 14 patients with endogenous hyperinsulinemic hypoglycaemia (EHH) managed at our centre; in whom, the final diagnosis was insulinoma (n=11), Munchausen syndrome (MS) (n=2) and inconclusive (n=1). Retrospective reporting of CECT, 68 Ga-DOTATATE PET/CT and 68 Ga-NODAGA-exendin-4-PET/CT was done. With per-lesion analysis, performance parameters were calculated for the histopathological diagnosis of insulinoma. True positive (TP), false positive (FP), false negative (FN), true negative (TN), sensitivity (Sn), specificity (Sp), positive predictive value (PPV), negative predictive value (NPV) for insulinoma localization. In our cohort, 12 histopathologically proven insulinoma lesions [(TP): 11 primary lesions, 1 metastasis] were detected in 11 patients, whereas two patients had MS (TN). Sn and PPV were 75% and 100%, 33.3% and 80% and 83.3% and 71.4% for CECT, 68 Ga-DOTATATE PET/CT and 68 Ga-NODAGA-exendin-4-PET/CT, respectively. With exendin-4-based imaging, FP uptake in normal pancreatic tissue and FN results in the pancreatic tail lesion was seen. In one patient, TN result suggested the correct diagnosis of MS. 68 Ga-NODAGA-exendin-4-PET/CT has higher sensitivity than 68 Ga-DOTATATE PET/CT and CECT for insulinoma localization. FP uptake in normal pancreas and FN result in tail lesions are limitations of currently utilized exendin-4-based imaging.

Detection of Insulinomas Using Dual-Time-Point 68Ga-DOTA-Exendin 4 PET/CT.

Insulinomas are predominantly benign neuroendocrine tumors originating from beta cells within the islets of Langerhans of the endocrine pancreas. Because surgical resection represents the only curative therapy option, exact tumor localization and discrimination of insulinomas from focal or diffuse manifestations of congenital hyperinsulinism are crucial for optimal treatment strategies. We investigated the diagnostic value of glucagon-like peptide 1 receptor PET/CT using Ga-DOTA-exendin 4 for detecting insulinomas and compared the diagnostic value of PET scans performed at 2 time points. In 10 patients with clinically and biochemically suspected insulinoma, PET/CT was performed at 1 hour (PET1) and 2 hours (PET2) after injection of Ga-DOTA-exendin 4. In this retrospective analysis, tracer uptake was visually assessed in both scans by 2 independent readers. SUVmax and tumor-to-background ratio (TBR) of focal lesions were assessed. Imaging results were compared with histopathologic findings, if patients underwent resection. Increased focal Ga-DOTA-exendin 4 uptake was observed in 8 of 10 patients concordantly by both readers. Seven patients with focal uptake underwent surgery with tumor enucleation and histopathologic proof of insulinoma (7/8). Two of 10 patients without focal uptake were considered to suffer from diffuse form of congenital hyperinsulinism and consequently received medical treatment. A significant increase of tumoral SUVmax on PET2 (PET1: SUVmax 20.2 ± 8.2 g/mL; PET2: SUVmax 24.7 ± 7.9 g/mL; P = 0.0018) did not result in a significant improvement in TBR (PET1: TBR 4.9 ± 1.7; PET2: TBR 4.3 ± 1.2; P = 0.2892). Focal uptake of Ga-DOTA-exendin 4 reliably indicated insulinomas as histopathologically confirmed in all patients undergoing consecutive surgery. The diagnostic value of PET2 was not found to be superior to PET1, indicating that a single 1-hour Ga-DOTA-exendin 4 PET/CT scan is a sufficient and convenient approach for patient care.

Changing Insulinoma Management Due to Incidentally Discovered Metastasis: A Case Report

Patient: Female, 46-year-oldFinal Diagnosis: Metastatic insulinomaSymptoms: Altered mental status • anxiety • hypoglycemia • unsteadinessMedication:—Clinical Procedure: EUS-guided ablation • EUS-guided FNASpecialty: Endocrinology and MetabolicObjective:Rare diseaseBackground:Hypoglycemia is rare in individuals without drug-treated diabetes mellitus. In a seemingly well individual, the differential diagnosis of hypoglycemia narrows to 2 major categories: 1) accidental, surreptitious, or intentional hypoglycemia, or 2) endogenous hyperinsulinism (EHH). Insulinomas are the most common cause of EHH. Localization of insulinomas can be challenging, as most tumors are less than 2 cm in size and may be present in any part of the pancreas. In fact, almost 30% of neuroendocrine tumors (NET) cannot be located preoperatively by traditional imaging techniques such as computerized tomography (CT) or magnetic resonance imaging (MRI).Case Report:This report describes a case of metastatic insulinoma in a patient with a complex medical history. CT with contrast of the abdomen identified 1 lesion located in the pancreas body. Endoscopic ultrasound (EUS) identified an additional 3 to 4 hypoechoic lesions in the pancreatic neck and body. 68-Gallium Dotatate scanning identified 3 distinct lesions within the pancreas and a right posterior rib sclerotic lesion.Conclusions:Reliance upon traditional imaging techniques (CT/MRI) for tumor localization would not have identified the multifocal pancreatic lesions and the metastatic bone lesion. Accurate identification of multifocal, metastatic insulinomas requires multiple imaging modalities, including first-line non-invasive imaging (CT or MRI) followed by second-line imaging (EUS or nuclear imaging).

Selective intra-arterial calcium stimulation test for the localization of insulinomas: an Australian hospital experience.

Insulinomas are rare tumours of the pancreas and the most common cause of hypoglycaemia in non-diabetic adults. They can be cured by surgery but require precise localization. The aim of this study was to assess the utility of the selective intra-arterial calcium stimulation test (SIACST) in patients with an insulinoma to correctly localize the tumour. Medical records of patients with a diagnosis of insulinoma or who underwent an SIACST were retrospectively reviewed. Localization of lesions by SIACST was compared to endoscopic ultrasound and radionuclide imaging studies and verified against findings at surgery. A total of 24 patients (mean age 58 years, 16 females, 20 with insulinoma) underwent SIACST. The SIACST correctly localized the insulinoma in 17 of 20 patients (85%). Localization rate for computed tomography was 55% and 75% for endoscopic ultrasound and glucagon-like peptide-1 receptor scan. SIACST provided incremental diagnostic information in patients with insulinoma who had equivocal non-invasive imaging preoperatively. This technique remains an essential diagnostic tool when a lesion is not localized by other methods.

Innovative imaging of insulinoma: the end of sampling? A review.

Receptors for the incretin glucagon-like peptide-1 (GLP-1R) have been found overexpressed in selected types of human tumors and may, therefore, play an increasingly important role in endocrine gastrointestinal tumor management. In particular, virtually all benign insulinomas express GLP-1R in high density. Targeting GLP-1R with indium-111, technetium-99m or gallium-68-labeled exendin-4 offers a new approach that permits the successful localization of small benign insulinomas. It is likely that this new non-invasive technique has the potential to replace the invasive localization of insulinomas by selective arterial stimulation and venous sampling. In contrast to benign insulinomas, malignant insulin-secreting neuroendocrine tumors express GLP-1R in only one-third of the cases, while they more often express the somatostatin subtype 2 receptors. Importantly, one of the two receptors appears to be always overexpressed. In special cases of endogenous hyperinsulinemic hypoglycemia (EHH), that is, in the context of MEN-1 or adult nesidioblastosis GLP-1R imaging is useful whereas in postprandial hypoglycemia in the context of bariatric surgery, GLP-1R imaging is probably not helpful. This review focuses on the potential use of GLP-1R imaging in the differential diagnosis of EHH.

Diagnostic value of ASVS for insulinoma localization: A systematic review and meta-analysis

Previous studies on the diagnostic value of arterial calcium stimulation with hepatic venous sampling (ASVS) for the localization of insulinoma have reported inconsistent results. Here, we performed a meta-analysis of the relevant published studies. PubMed, Embase, Web of Science, the Cochrane Library, and Wanfang Data were searched for studies on the diagnostic value of ASVS in insulinoma localization published up to May 2019. We calculated the sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and receiver operating characteristic (ROC) curve of ASVS in the localization of insulinoma. We included ten studies involving 337 patients in the study. The pooled sensitivity, specificity, PLR, and NLR were 0.93 (95% confidence interval [CI]: 0.83-0.97), 0.86 (95%CI: 0.75-0.93), 6.8(95%CI: 3.7-12.7), and 0.08 (95%CI: 0.03-0.19), respectively. The DOR was 84 (95%CI: 30-233), and the area under the ROC curve was 0.96 (95%CI: 0.94-0.97).The results of the heterogeneity of the studies (P = 0.00, I2 = 80.17) were calculated using forest plots of the DOR. ASVS is of significant value in localization of insulinoma. If a qualitative diagnosis of insulinoma is definite and the imaging examination results are negative, ASVS should be performed to confirm the localization of insulinoma.

Importance of localization of insulinomas: a systematic analysis.

Procedures suitable for preoperative localization of insulinomas are widely used but it is unclear whether they determine surgical success. We wanted to clarify whether preoperative localization or intraoperative ultrasound determines the success of surgically identifying and removing insulinomas. We performed a systematic literature search (PubMed) yielding 100 publications with patient-level data on preoperative localization procedures, intraoperative ultrasound, success of surgical identification and removal or single, benign insulinomas (published until 31 December 2016). The consequences of successful preoperative localization and intraoperative ultrasound for surgical identification and removal of an insulinoma could be analyzed for 863 and 529 patients with single benign insulinomas, respectively. Sensitivities of commonly employed methods to localize biochemically proven insulinomas were calculated for single benign (1,153 patients), multiple benign, and malignant insulinomas, also in relation to diameter and intra-pancreatic location. The success of surgery (identification and removal of single benign insulinomas) in patients with a biochemically proven insulinoma was high (approximately 98%) even in the absence of preoperative localization. However, successful preoperative localization or intraoperative ultrasonography slightly, but significantly, increased the probability of surgically identifying/removing single benign insulinomas (by 1.4% and 2.0%, P=0.012 and 0.0032, respectively). Diagnostic sensitivities of localization procedures varied widely, with GLP-1 receptor scintigraphy achieving the highest sensitivity despite its non-invasive nature. The probability of surgically identifying and removing a single, benign insulinoma is high even in the absence of successful preoperative localization or intraoperative ultrasound. However, both approaches slightly, but significantly, improve the outcome to near 100%.

Superior Diagnostic Performance of the GLP-1 Receptor Agonist [Lys40(AhxHYNIC-[99mTc]/EDDA)NH2]-Exendin-4 over Conventional Imaging Modalities for Localization of Insulinoma.

Insulinomas are the most common functioning neuroendocrine neoplasms of the pancreas, typically diagnosed due to characteristic symptoms. In the vast majority, the treatment is surgical and curative, requiring accurate localization of the tumour; conventional imaging, including somatostatin receptor molecular imaging, is negative in up to 10% of cases. Recently, labelled glucagon-like peptide receptor (GLP-1R) analogues were introduced as a sensitive diagnostic method for localization of insulinomas. The aim of this study was to assess the diagnostic accuracy of a Tc-99m-labelled GLP-1R agonist [Lys40(AhxHYNIC-[99mTc]EDDA)NH2]-exendin-4 for localization of occult insulinoma. Eight patients (all females; age range 35-75years) with biochemically proven insulinoma and with negative or inconclusive conventional imaging (consisting of somatostatin receptor scintigraphy, computed tomography, endoscopic ultrasound and magnetic resonance imaging) were enrolled. Whole-body single-photon emission tomography/computed tomography (SPECT/CT) imaging was performed 4h post-injection of 740MBq of [Lys40(AhxHYNIC-[99mTc]EDDA)NH2]-exendin-4. Surgical treatment was performed based on imaging findings. Histology of the removed lesions and biochemical and clinical symptom resolution was considered as the gold standard for analysis of the imaging results. Focal uptake of [Lys40(AhxHYNIC-[99mTc]EDDA)NH2]-exendin-4 was found in all patients, leading to successful removal of the offending lesion and complete biochemical and symptomatic resolution. Histological analysis confirmed insulinoma in all included patients. [Lys40(AhxHYNIC-[99mTc]EDDA)NH2]-exendin-4 SPECT/CT appears to be an excellent molecular imaging method for preoperative localization of an occult insulinoma, surpassing conventional imaging methods. If routinely available, it could be considered as a method of choice due to its favorable combination of imaging characteristics.

SUN-314 Gallium-68 DOTATATE PET/CT for Preoperative Localization of Metastatic Insulinoma

Introduction Metastatic insulinoma is a rare clinical entity. Preoperative localization of metastatic insulinoma in the setting of multiple hepatic lesions represents a challenge, as it can coexist with noninsulinoma hepatic lesions1. Gallium-68 DOTATATE was first FDA-approved for the localization of neuroendocrine tumors in mid-2016 and has demonstrated effectiveness for insulinoma2. We present a case where multiple lesions were present in the setting of metastatic insulinoma and Ga-68 DOTATATE PET/CT was utilized in localizaton. Case Report A 37-year-old female with a history of pancreatic insulinoma s/p resection via Whipple procedure in 2007 presented to the ED with a five-day history of visual changes and lightheadedness concerning for hypoglycemia. Abdominal CT obtained in the ED demonstrated a low-attenuation lesion in the hepatic dome. TFTs were normal and cosyntropin stimulation testing was unemarkable. A subsequent 72-hour fast ended after < 12 hours due to symptomatic hypoglycemia; BGL was 55mg/dl and insulin level was 31.5 mU/L, confirming a hyperinsulinemic etiology. Sulfonylurea screen was negative. Abdominal MRI demonstrated a 1.1 cm mass within hepatic segment VIII, as well as additional lesions in segment VIII and at the junction between VIII and VII. Due to uncertainty regarding which of the hepatic lesions represented recurrent metastatic insulinoma, Ga-68 DOTATATE PET/CT scan was pursued; this demonstrated a 1.3 cm focus of increased activity consistent with neuroendocrine tumor metastasis in hepatic segment VIII. The other lesions were not DOTATATE-avid. Resection of the 1.3 cm lesion demonstrated a 1.1 cm tumor with cells positive for chromogranin, synaptophysin, and scattered weak positivity for insulin. While one episode of hypoglycemia did occur shortly after surgery, there was no further symptomatic hypoglycemia on outpatient follow-up. Present plan includes repeat Ga-68 DOTATATE PET/CT six months postoperatively. Conclusion Localization of metastatic insulinoma in the setting of multiple hepatic lesions on traditional imaging modalities represents a challenge. While Ga-68 DOTATATE PET/CT has been shown to be an effective tool in insulinoma localization, there is a paucity of literature regarding its utility in the setting of suspected recurrent metastatic insulinoma. We present a case where Ga-68 DOTATATE PET/CT was effectively utilized in preoperative localization of metastasis in the setting of multiple hepatic lesions. Further research into this area with prospective data regarding clinical recurrence is warranted.

Molecular Imaging to the Surgeons Rescue: Gallium-68 DOTA-Exendin-4 Positron Emission Tomography-Computed Tomography in Pre-operative Localization of Insulinomas.

Background:Insulinoma is an islet-cell neoplasm that secretes insulin. It is usually localized to the pancreas and is often the most common cause of endogenous hyperinsulinemic hypoglycaemia in non-diabetic adult patients. Surgical excision with a curative intent is the standard modality of treatment, and it requires precise localization of tumor tissue. Ga-68 DOTA-exendin-4 PET/CT scan is a clinically reasonable and sensitive scan for the identification of insulinoma. The aim of this prospective cohort study was to determine the overall accuracy of Ga-68 DOTA-exendin-4 PET/CT scan in the detection of insulinoma.Materials and Methods:Eight patients with fasting hyperinsulinemic hypoglycaemia with neuroglycopenic symptoms were enrolled in this study which was conducted during October 2016 to October 2017. Whole body PET/CT scan was performed on a Philips time of flight PET/CT scanner, 60 minutes after injection of Ga-68 DOTA-exendin-4 (and also Ga-68 DOTANOC). The imaging findings were compared to the histopathological diagnosis in six out of eight patients and to subsequent follow up in the remaining two patients who did not undergo surgery.Results:The sensitivity of Ga-68 DOTA-Exendin-4 PET/CT scan in insulinoma detection was found to be 75%.Conclusion:Ga-68 DOTA-Exendin-4 PET/CT scan is highly sensitive for identification and exact localization of insulinoma which can guide better surgical exploration. However, randomised controlled trials are needed to assess the accuracy of Ga-68 DOTA-Exendin PET/CT scan in localization of insulinoma.

(68)Ga-exendin-4 PET-CT for the localization of occult insulinomas: a prospective cohort study

Objective: To explore the accuracy in localizing occult insulinomas with Glucagon-like peptide-1 receptor(GLP-1R) PET-CT with (68)Ga-exendin-4. Methods: In this prospective cohort study, patients with biochemically proven endogenous hyperinsulinemic hypoglycemia and negative contrast-enhanced CT with pancreatic perfusion scans were enrolled consecutively at Department of Nuclear Medicine, Peking Union Medical College Hospital from February 2014 to June 2018.There were 37 males and 32 females, with age of (43.2±17.9)years. (68)Ga-exendin-4 PET-CT, MRI and endoscopic ultrasound(EUS) were done before elective surgery. Sensitivity, specificity, accuracy, positive predictive value(PPV) and negative predictive value(NPV) of the above imaging modalities were calculated. Results: A total of 69 patients were recruited. Thirty-two patients were diagnosed with insulinomas at histology. Four patients with positive (68)Ga-exendin-4 PET-CT findings did not undergo surgery so far. Twenty-eight patients were proven to be noninsulinoma induced hyperinsulinemic hypoglycemia. Five patients were unknown of etiology of hypoglycemia. The sensitivity, specificity, accuracy, PPV and NPV of (68)Ga-exendin-4 in localizing occult insulinomas were 96.9%(31/32), 100%(30/30), 98.3%(59/60), 100%(29/29), 96.8%(30/31), respectively.The sensitivity, specificity, accuracy, PPV and NPV of MRI were 74.1%(20/27), 9/11, 76.3%(29/38), 90.9%(20/22), 9/16, respectively. The sensitivity, specificity, accuracy, PPV and NPV of EUS were 75.0% (15/20), 2/2, 77.3%(17/22), 15/15, and 2/7. Conclusion: (68)Ga-exendin-4 PET-CT has a high sensitivity, specificity and accuracy for detection of occult insulinoma, which shows superiority to MRI and EUS.

Diagnostic value of endoscopic ultrasound for insulinoma localization: A systematic review and meta-analysis.

BackgroundPrevious studies reported varies parameters of endoscopic ultrasound (EUS) for the localization of insulinomas, the purpose of this meta-analysis based on published studies to accuracy the diagnostic value of EUS.MethodsPubMed, Embase, Web of science, Cochrane library and Wanfang digital database were searched to identify published studies up to April 2018, which diagnostic insulinoma by using EUS. Retrieved sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR) and receiver operating characteristic (ROC) curves data were summarized for meta-analysis.ResultsA total of 9 studies involved a total of 350 patients were included in final analysis. The summary sensitivity, specificity, PLR, and NLR were 0.81 (95%CI: 0.75–0.86), 0.90 (95%CI: 0.84–0.94), 7.90 (95%CI: 4.9–12.8), and 0.21 (95%CI: 0.16–0.29), respectively. Further, the pooled DOR was 37.00 (95%CI:19.55–70.04) and area under the ROC was 0.92 (95%CI: 0.90–0.84).ConclusionThe findings of this study demonstrate that EUS should be a routine diagnosis approach for the preoperative localization of insulinomas.

New Diagnostic Criteria for the Localization of Insulinomas with the Selective Arterial Calcium Injection Test: Decision Tree Analysis

PurposeTo explore optimal diagnostic criteria for localizing insulinomas with the selective arterial calcium injection (SACI) test using decision tree analysis. Materials and MethodsA retrospective study included 86 vessels of 18 patients (5 men, 13 women; mean age 67 y; range, 49–73 y) with insulinomas who underwent SACI test between June 2007 and May 2016. Of 27 insulinomas, 7 were found in the head, 13 in the body, and 7 in the tail of the pancreas. Two patients had multiple tumors. To identify optimal diagnostic criteria, decision tree analysis was performed, and sensitivity, specificity, and accuracy of the conventional and the proposed new diagnostic criteria (plasma insulin concentration after calcium injection [ICpost] > 2.0 × plasma insulin concentration before calcium injection [ICpre]) were compared. ResultsThe proposed new diagnostic criteria for insulinoma obtained by decision tree analysis were (i) ICpost > 2.7 × ICpre and maximum insulin concentration > 60.3 μIU/mL or (ii) ICpost > 2.7 × ICpre and maximum insulin concentration < 60.3 μIU/mL with ICpre being ≥ 7.5 μIU/mL. Sensitivity, specificity, and accuracy of the new criteria for the SACI test were 100%, 91.4%, and 94.2; sensitivity, specificity, and accuracy of conventional criteria were 100%, 69.0%, and 79.1%. ConclusionsNew diagnostic criteria for localization of insulinomas with the SACI test yielded higher diagnostic performance than conventional criteria.

Insulinoma presenting with post-prandial hypoglycaemia following fundoplication.

SummaryInsulinomas are rare neuroendocrine tumours that classically present with fasting hypoglycaemia. This case report discusses an uncommon and challenging case of insulinoma soon after upper gastrointestinal surgery. A 63-year-old man presented with 6 months of post-prandial hypoglycaemia beginning after a laparoscopic revision of Toupet fundoplication. Hyperinsulinaemic hypoglycaemia was confirmed during a spontaneous episode and in a mixed-meal test. Localisation studies including magnetic resonance imaging (MRI), endoscopic ultrasound (EUS) and gallium dotatate positron emission tomography (68Ga Dotatate PET) were consistent with a small insulinoma in the mid-body of the pancreas. The lesion was excised and histopathology was confirmed a localised well-differentiated neuroendocrine pancreatic neoplasm. There have been no significant episodes of hypoglycaemia since. This case highlights several key points. Insulinoma should be sought in proven post-prandial hyperinsulinaemic hypoglycaemia – even in the absence of fasting hypoglycaemia. The use of nuclear imaging targeting somatostatin and GLP1 receptors has improved accuracy of localisation. Despite these advances, accurate surgical resection can remain challenging.Learning points:Hypoglycaemia is defined by Whipple’s triad and can be provoked by fasting or mixed-meal tests.Although uncommon, insulinomas can present with post-prandial hypoglycaemia.In hypoglycaemia following gastrointestinal surgery (i.e. bariatric surgery or less commonly Nissen fundoplication) dumping syndrome or non-insulinoma pancreatogenous hypoglycaemia syndrome (NIPHS) should be considered.Improved imaging techniques including MRI, endoscopic ultrasound and functional nuclear medicine scans aid localisation of insulinomas.Despite advances in imaging and surgical techniques, accurate resection of insulinomas remains challenging.