Localization Of Insulinoma Research Articles

Accurate Combined Preoperative Localization of Insulinomas Aid the Choice for Enucleation: A Single Institution Experience over 25 Years

To assess the accuracy of combined preoperative localizations and analyze the change in management strategy of operation of insulinoma. One hundred and seventy-two patients with a diagnosis of insulinoma at a tertiary hospital between 1985 and 2010 were reviewed, where accurate combined preoperative localization before surgical exploration was the primary management policy of insulinoma. Operation details for 147 patients were checked. An average of 2.89 preoperative localization studies including 1.61 non-invasive studies and 1.28 invasive studies were utilized per patient. Contrast-enhanced ultrasonography (CEUS) was the most sensitive invasive modality (88.1%) whereas magnetic resonance imaging (MRI) was the most sensitive non-invasive modality (64.0%). All 147 patients underwent complete surgical resection which included 126 enucleations and 18 distal pancreatectomies with a cure rate of 95.2% (140/147) at a median follow-up of 45 months (range 1-248). The postoperative morbidity and long-term outcome of enucleation was similar to distal pancreatectomy despite a higher rate of microscopic margin involvement. Accurate combined preoperative localization of insulinomas is useful of the choice of enucleation, eliminates the need for blind distal pancreatectomy and avoids re-operation. Whenever possible, a pancreas-sparing approach such as enucleation should be adopted.

Glucagon-like peptide-1 receptor overexpression in cancer and its impact on clinical applications

Peptide hormones of the glucagon-like peptide (GLP) family play an increasing clinical role, such as GLP-1 in diabetes therapy. Moreover, GLP receptors are overexpressed in various human tumor types and therefore represent molecular targets for important clinical applications. In particular, virtually all benign insulinomas highly overexpress GLP-1 receptors (GLP-1R). Targeting GLP-1R with the stable GLP-1 analogs 111In-DOTA/DPTA-exendin-4 offers a new approach to successfully localize these small tumors. This non-invasive technique has the potential to replace the invasive localization of insulinomas by selective arterial stimulation and venous sampling. Malignant insulinomas, in contrast to their benign counterparts, express GLP-1R in only one-third of the cases, while they more often express the somatostatin type 2 receptors. Importantly, one of the two receptors appears to be always expressed in malignant insulinomas. The GLP-1R overexpression in selected cancers is worth to be kept in mind with regard to the increasing use of GLP-1 analogs for diabetes therapy. While the functional role of GLP-1R in neoplasia is not known yet, it may be safe to monitor patients undergoing GLP-1 therapy carefully.

18F-Labelled exendin to image GLP-1 receptor-expressing tissues: from niche to blockbuster?

18F-Labelled exendin to image GLP-1 receptor-expressing tissues: from niche to blockbuster?

Preoperative Tumor Studies Using MRI or CT in Patients with Clinically Suspected Insulinoma

Purpose: Insulinomas are rare tumors that originate from the islet cells of the pancreas. The aims of this study were to localize insulinomas preoperatively using CTand/or MRI in correlation with postoperative pathological results. Patients and Methods: Between December 2001 and June 2010, 27 consecutive patients with clinically suspected insulinoma were surgically treated in our university hospital. Preoperative CT (14 of 27 patients) and MRI studies (14 of 27 patients, one patient had both MRI and CT), operation reports, intraoperative ultrasonography reports, and pathological diagnoses were analyzed retrospectively. For each lesion, images were analyzed based on the presence of enhancement or the characteristics of signal intensities. Pathologic correlation was available for all the lesions. Results: The female: male ratio was 2.9, with a mean age of 47.5 years (range 12–82). Preoperative tumor localization was achieved by means of MRI and CT. A focal pancreatic lesion, which was hypointense on T1-weighted sequences, was detected on all the MR images (14 of 27 patients; 100%). These lesions were isointense (4 cases) to slightly hyperintense (10 of 14 cases) on T2-weighted sequences. In T1-weighted fat-suppressed contrast-enhanced sequences, there were two types of enhancement: homogeneously hyperintense lesions (in 10 of 14 cases) or peripherally hyper-, centrally isointense (in 4 of 14 cases). On all the CT images (14 of 27 patients), there was no detectable lesion on precontrast series; on arterial series in 13 of 14 patients (arterial series has not been done in one patient), lesions enhanced hypervascular in contrast to the rest of the pancreas with a mean enhancement of 147 HU (range 113–248) and 95 HU (range 65–141), respectively. On venous series in 13 of 14 patients (venous series has not been done in one patient), there was an enhanced lesion in contrast to the rest of the pancreas with a mean enhancement of 110 HU (range 91–151) and 86 HU (range 65–137), respectively. Intraoperative ultrasonography was performed in 11 of 27 patients to localize the tumor, which correlated with the results of the mentioned preoperative studies. Tumor size ranged from 9 × 11 to 31 × 37 mm. Enucleation was carried out in 14 patients, Whipple in 5, segmental resection in 3 and left distal pancreatectomy in 5 patients. The mortality rate was 0. Pathological findings were insulinoma or neuroendocrine tumors in 26 of 27 cases. One patient had a pathological finding of chronic pancreatic disease with intraepithelial neoplasia (grade 1A). Conclusion: We conclude that the preoperative localization of insulinoma in clinically suspected patients can be made on the basis of MRI and/or CT studies. A hallmark lesion is hypointense in T1-weighted sequences, homogeneously or peripherally hyperintense in T1-weighted fat-suppressed contrast-enhanced sequence using MRI (100% of cases) or/and a hypervascular enhanced lesion on arterial (100% of CT studies) and on venous series using CT (66.7% of CT studies).

Laparoscopic Ultrasound Enhances Diagnosis and Localization of Insulinoma in Pancreatic Head and Neck for Laparoscopic Surgery With Satisfactory Postsurgical Outcomes

This study explored the value of laparoscopic ultrasonography (LUS) for tumor localization in laparoscopic pancreatic surgery of insulinomas, especially for tumors located at anatomically unfavorable positions. Twenty-eight patients with insulinomas were enrolled in this study between July 2007 and March 2009. Various image examinations were performed preoperatively. An iU22 ultrasound system equipped with a 5.0–9.0 MHz transducer was used for LUS. The tumor localization and postsurgical outcomes were evaluated. Intraoperative LUS precisely localized 33 insulinomas in 26 of 28 patients, whereas the preoperative imaging studies detected 27 of 33 (82%) tumors. No definite tumor in the pancreas and extra-pancreatic organs was identified in two patients by both preoperative and intraoperative imaging examinations. Of 33 tumors, 32 (97%) were localized in the pancreas (14 in the head and neck, 18 in the body and tail), whereas one (3%) was found in the duodenal ligament. Successful laparoscopic resection of insulinoma was performed in 21 of 26 patients, including resection of 11 tumors located in the head and neck of the pancreas. Five patients required conversion to open surgery. All insulinomas were benign with a mean size 13.8 mm. Four patients had pancreatic-related complications that spontaneously healed within 3 weeks after surgery. The median hospital stay was 8.5 days. Our study demonstrates that laparoscopic pancreatic resection under the guidance of advanced LUS is not only feasible and safe for tumors located at the body and tail but also for tumors located at the head and neck of the pancreas.

Preoperative Localisation and Surgical Management of Insulinoma: Single Centre Experience

Background: The majority of insulinomas are benign, small and intrapancreatic. Preoperative localisation is important to plan the surgical management. Methods: We retrospectively analysed our data on the preoperative imaging, type of surgery and histopathological features of the operated patients with an insulinoma from January 1993 to March 2010. Univariate and multivariate analyses were performed to detect the predictive factors for survival following surgery. Results: Forty patients were operated on for insulinoma, of which 33 were benign and 7 were malignant. The sensitivity of preoperative computed tomogram scan, magnetic resonance imaging and endoscopic ultrasound, for localising the lesions was 62, 82 and 94%, respectively. Enucleation was performed in 21 (52.5%) patients, and remaining had pancreatic resection. Hepatic resection was performed in 2 and liver transplantation in 1 patient. Morbidity and perioperative mortality was 17 (42.5%) and 1 (2.7%), respectively. The overall 5- and 10-year survival was 89 and 86.5%, respectively. The presence of metastases was found to be an independent predictor of poor survival on multivariate analysis. Conclusion: Preoperative computed tomogram/magnetic resonance imaging and endoscopic ultrasound are sensitive in localizing the majority of insulinomas. Surgery offers a good long-term survival, even in patients with malignant insulinoma.

Intraoperative Sonographic Localization of Insulinoma: Case Reports and Review of Literature

ABSTRACT Insulinomas, a rare clinical entity, are usually small, single, benign and intrapancreatic in location. Several modalities are available for preoperative localization of insulinomas. Intraoperative ultrasound is an important tool used for localization as well as to find anatomical relation of tumor to surrounding tissue. We are reporting three cases of insulinomas with brief discussion on modalities used for localization. After biochemical confirmation of hyperinsulinemia, preoperative localization was done initially by computed tomography followed by intraoperative ultrasonography. Preoperative localization by computed tomography was successful in all the cases but missed an additional lesion in one of the patients which was picked up by intraoperative ultrasonography (IOUS) that changed surgical management. Preoperative localization may not be successful in all the cases. Intraoperative direct inspection, palpation and ultrasound can be used to identify lesions in the cases where preoperative localization was unsuccessful.

Assessment of contrast-enhanced ultrasonography in diagnosis and preoperative localization of insulinoma

This study was to evaluate the value of contrast-enhanced ultrasonography (CEUS) in the diagnosis and preoperative localization of insulinoma and explore the enhancement patterns of the tumors. Unenhanced and contrast-enhanced ultrasonographic examinations of 31 patients who underwent resection of insulinomas were retrospectively reviewed. The diagnosis sensitivity and localization specificity of CEUS for insulinomas were determined. Results of unenhanced ultrasonography and CEUS were compared by Chi-square test. Unenhanced ultrasonography could display 9 of 37 (24.3%) surgically verified insulinomas in 31 patients, while the diagnosis sensitivity and localization specificity of preoperative CEUS was 33 (89.2%) and 32 (86.5%) of the 37 tumors, respectively. In contrast to the unenhanced ultrasonography, the improvement of CEUS in the diagnosis and preoperative localization of insulinomas was significant (p<0.0001). The enhancement pattern of insulinoma on CEUS was fast wash-in and slow wash-out. All the tumors were homogeneous hypervascularity in the earlier arterial phase, while the tumors still displayed hyperenhancing pattern in the late phase. Our study demonstrates the great potential of CEUS in the diagnosis and preoperative localization of insulinomas. Since CEUS is a convenient, inexpensive, effective and non-invasive modality, the study supports the use of CEUS as a primary tool in the evaluation of patients with insulinomas.

Diagnosis and localisation of insulinoma: the value of modern magnetic resonance imaging in conjunction with calcium stimulation catheterisation

The authors apologise for an error in the author list of the article titled above published in the journal, volume 162 on page 971. R H Reznek should be the penultimate author. The full list of authors and their affiliations for this article is as follows:Maralyn R Druce1, Vasantha M Muthuppalaniappan1, Benjamin O'Leary1, Shern L Chew1, William M Drake1, John P Monson1, Scott A Akker1, Michael Besser1, Anju Sahdev2, Andrea Rockall2, Soumil Vyas3, Satya Bhattacharya3, Matthew Matson2, Daniel Berney4, R H Reznek2 and Ashley B Grossman1Departments of 1Endocrinology, 2Radiology, 3Surgery and 4Histopathology, Barts and the London Medical School, St Bartholomew's Hospital, London EC1A 7BE, UK.

Glucagon-like peptide-1 receptor imaging for localization of insulinomas

Glucagon-like peptide-1 receptor imaging for localization of insulinomas

Diagnosis and localisation of insulinoma: the value of modern magnetic resonance imaging in conjunction with calcium stimulation catheterisation

Preoperative localisation of insulinoma improves cure rate and reduces complications, but may be challenging. To review diagnostic features and localisation accuracy for insulinomas. Cross-sectional, retrospective analysis. A single tertiary referral centre. Patients with insulinoma in the years 1990-2009, including sporadic tumours and those in patients with multiple endocrine neoplasia syndromes. Patients were identified from a database, and case notes and investigation results were reviewed. Tumour localisation by computed tomography (CT), magnetic resonance imaging (MRI), octreotide scanning, endoscopic ultrasound (EUS) and calcium stimulation was evaluated. Insulinoma localisation was compared to histologically confirmed location following surgical excision. Thirty-seven instances of biochemically and/or histologically proven insulinoma were identified in 36 patients, of which seven were managed medically. Of the 30 treated surgically, 25 had CT (83.3%) and 28 had MRI (90.3%), with successful localisation in 16 (64%) by CT and 21 (75%) by MRI respectively. Considered together, such imaging correctly localised 80% of lesions. Radiolabelled octreotide scanning was positive in 10 out of 20 cases (50%); EUS correctly identified 17 lesions in 26 patients (65.4%). Twenty-seven patients had calcium stimulation testing, of which 6 (22%) did not localise, 17 (63%) were correctly localised, and 4 (15%) gave discordant or confusing results. Preoperative localisation of insulinomas remains challenging. A pragmatic combination of CT and especially MRI predicts tumour localisation with high accuracy. Radionuclide imaging and EUS were less helpful but may be valuable in selected cases. Calcium stimulation currently remains useful in providing an additional functional perspective.

Insulin secretion and insulin-producing tumors

Insulinomas are rare neuroendocrine tumors of pancreatic islet cells that retain the ability to produce and secrete insulin. In contrast to normally differentiated β-cells, insulinoma cells continue to secrete insulin and proinsulin at low blood glucose. This deregulated insulin secretion manifests clinically as fasting hypoglycemia. The molecular pathways that characterize normal insulin secretion and β-cell growth are reviewed and contrasted to the biology of insulinomas. The second half of this review summarizes the clinical approach to the disorder. The diagnosis of insulinoma is established by demonstrating inappropriately high insulin levels with coincident hypoglycemia at the time of a supervised fast. Localization of insulinomas is challenging owing to their small size but should be attempted to maximize the chance for successful surgical resection and avoid risks associated with reoperation. In the majority of cases, successful surgical resection leads to lifelong cure.

Insulinoma: pathophysiology, localization and management.

Insulinoma is a rare neuroendocrine tumor that causes oversecretion of insulin and, as a result, patients present with symptoms of hypoglycemia. Fortunately, insulinomas are usually benign and solitary, and surgical cure rates are highly favorable. Most of these tumors occur sporadically, but they can also be associated with multiple endocrine neoplasia type-1 syndrome. The diagnosis is confirmed by a supervised fast, and early detection is important. Several preoperative and intraoperative techniques with various success rates have been employed in order to localize the lesion. When technically feasible, tumor enucleation is the procedure of choice; however, a more formal resection may be necessary for certain tumors. In the age of laparoscopy, the role of laparoscopic surgery in the management of insulinomas is continuing to attract attention. This review will discuss the historical background, pathogenesis, diagnosis, localization and management of insulinomas.

The Usefulness of Super-Selective Computed Tomography Angiography (CTA) for Diagnosing and Localizing a Small Insulinoma

Localization of insulinomas by preoperative imaging is critical for successful surgical resection. However, the visualization and localization of small insulinomas by recent imaging modalities still remains a challenge. Here, we report a 77-year-old woman with a small insulinoma successfully localized by performing arterial stimulation and venous sampling (ASVS), and subsequent super-selective CTA (SSCTA). It was not visualized by routine non-invasive imaging tests such as digital subtraction angiography (DSA). The small size (1.0 cm) of the surgically removed tumor supports the usefulness of SSCTA for localizing very small insulinomas.

Giant Malignant Insulinoma Which Developed from a Non-Functioning Pancreatic Tumor Over a Long Period of Time

Insulinomas are the most common hormone-producing pancreatic neuroendocrine tumors (NETs), which are usually benign, solitary and small. We describe herein a patient with a giant insulinoma (>10 cm in diameter) with concomitant thyroid tumor as detected by Somatostatin receptor scintigraphy (SRS). A 50-year-old man presented hypoglycemic symptoms 20 years after the first detection of a pancreatic tumor, which was ameliorated by administration of a somatostatin analogue, octreotide. SRS showed abnormal uptake by the insulinoma as well as by the thyroid tumor. RT-PCR and immunohistochemical study revealed abundant expression of somatostatin receptor (SSTR)-1, -2, and -5 in his insulinoma and SSTR-1 and -2 in his thyroid follicular neoplasm. This is a rare case of a slow-growing pancreatic well-differentiated neuroendocrine carcinoma over a long period of time to become a symptomatic giant insulinoma. Furthermore, SRS proves to be a useful tool for localization of insulinoma as well as concomitant thyroid neoplasm with predominant expression of SSTRs.

Intraoperative Localization of Insulinoma and Normal Pancreas Using Invisible Near-Infrared Fluorescent Light

Neuroendocrine tumors of the pancreas, such as insulinoma, are difficult to localize, and complete resection is essential for cure. Our hypothesis is that a near-infrared (NIR) fluorophore exhibiting uptake in insulinoma could provide high-sensitivity detection intraoperatively. The optical properties of methylene blue (MB) were measured in vitro in 100% serum at 37 degrees C and in vivo after tissue uptake. MB was injected as a rapid intravenous bolus at doses ranging from 0.25 to 2 mg/kg into wildtype rats and pigs, and into insulinoma-bearing transgenic mice. The FLARE imaging system was used to acquire color video and NIR fluorescence images simultaneously and in real-time. The signal-to-background ratios (SBR) of tissues and tumors were quantified using FLARE software. When appropriately diluted, MB exhibits moderate NIR fluorescence emission peaking at 688 nm. At doses > or =1 mg/kg, certain normal tissues, such as pancreas, accumulate MB and remain NIR fluorescent for up to 1 h with an SBR > or = 1.6. MB spectral properties are maintained after uptake into tissue. Interestingly, insulinoma exhibits even higher MB signal than normal pancreas, resulting in insulinoma-to-pancreas ratios of 3.7 and insulinoma-to-muscle ratios of 16.2. MB permitted high-sensitivity, real-time localization of primary, multicentric, and metastatic insulinoma and permitted differentiation among tumor, normal pancreas, and other abdominal structures. A single intravenous injection of a clinically available, commonly used NIR fluorophore provides prolonged intraoperative localization of normal pancreas and insulinoma using invisible NIR fluorescent light.

Localization of insulinomas to regions of the pancreas by intraarterial calcium stimulation: the NIH experience

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Glucagon-Like Peptide-1 Receptor Imaging for Localization of Insulinomas

The surgical removal of insulinomas is hampered by difficulties to localize it using conventional radiological procedures. Recently these tumors were shown to exhibit a very high density of glucagon-like peptide-1 receptors (GLP-1R) in vitro that may be used as specific targets for in vivo receptor radiolabeling. The objective of the study was to test the 111In-labeled GLP-1R agonist 111In-DOTA-exendin-4 in localizing insulinomas using single photon emission computed tomography in combination with computed tomography images. This was a prospective open-label investigation. The study was conducted at three tertiary referral centers in Switzerland. Patients included six consecutive patients with proven clinical and biochemical endogenous hyperinsulinemic hypoglycemia. (111)In-DOTA-exendin-4 was administered iv at a dose of about 90 MBq (30 microg peptide) over 5 min. Whole-body planar images of the abdomen were performed at 20 min, 4 h, 23 h, 96 h, and up to 168 h after injection. After surgical removal of the insulinomas, GLP-1R expression was assessed in the tumor tissue in vitro by GLP-1R autoradiography. The detection rate of insulinomas was measured. In all six cases, the GLP-1R scans successfully detected the insulinomas identified using conventional methods in four cases. By using a gamma-probe intraoperatively, GLP-1R detection permitted a successful surgical removal of the tumors in all patients, diagnosed histopathologically as five pancreatic and one extrapancreatic insulinomas. In vitro GLP-1R autoradiography showed a high density of GLP-1R in all tested insulinomas. In vivo GLP-1R imaging is an innovative, noninvasive diagnostic approach that successfully localizes small insulinomas pre- and intraoperatively and that may in the future affect the strategy of insulinoma localization.

Noninvasive examinations for localization of insulinoma

To investigate the value of the noninvasive examinations for localization of insulinoma. The clinical materials of 88 cases of insulinoma treated in Peking Union Medical College Hospital between January 2005 and November 2008 were analyzed retrospectively. There were 40 males and 48 females aged from 15 to 74 years old (averaged, 46.5 years old). The positive rates for localization were 19.3% (17/88), 52.4% (11/21), 95.5% (64/67), 1/6, 30.0% (6/20), 83.9% (26/31), 8/8 and 5/5 respectively in transabdominal ultrasound, enhanced CT, multislice spiral CT pancreatic perfusion, MRI, somatostatin receptor scintigraphy, endoscopic ultrasound, laparoscopic ultrasound and intraoperative ultrasound. Thirty-one multiple tumors in 8 patients were resected. The positive rates of locating the multiple insulinomas of multislice spiral CT pancreatic perfusion and Intraoperative Ultrasound were 48.4% (15/31) and 100% (14/14) respectively. The locating diagnosis of insulinoma has came to noninvasive examination era. Multislice spiral CT pancreatic perfusion is the first choice for localization. Intraoperative ultrasound might play an important role in locating tumors for patients with multiple insulinomas.

The role of arterial stimulation and simultaneous venous sampling in addition to cross-sectional imaging for localisation of biochemically proven insulinoma

Insulinomas, although rare, cause considerable morbidity but are frequently amenable to surgical cure. Laparoscopic surgery can now be considered if the tumour is localised pre-operatively, but the optimal imaging approach has not been determined. The objective of this study was to evaluate the ability of different imaging investigations, including CT, MRI, endoscopic ultrasound, octreotide scintigraphy and arterial stimulation with simultaneous venous sampling (ASVS), to localise insulinomas. All patients with biochemically proven insulinoma at our institution underwent ASVS along with other imaging investigations as part of their routine investigation. The results of these investigations were compared with histological findings. Twenty-eight patients with biochemically proven insulinoma confirmed by histology were identified. Ultimately ASVS localised a lesion in all patients. Seventeen patients (61%) had laparoscopic surgery. Tumor-detection rates for other imaging investigations included 43.5% of cases using CT, 71% using MRI, 86% using endoscopic ultrasound and 33% using octreotide scintigraphy. In four patients, the ASVS was the only test to correctly localise the lesion. ASVS should be considered routinely before surgery to ensure accurate localisation of insulinomas.