Functioning Islet Cell Tumors Research Articles

SUN-129 Hipoinsulinemic Hipoglycemia Caused by Solitary Fibrous Tumor IGF-2 Producer: Case Report

BACKGROUND: Solitary Fibrous Tumor is a mesenchymal neoplasm composed of CD34+ fibroblastic cells that can produce spontaneous hypoglycemia by the overproduction of IGF-2. It closely resembles the hypoglycemia characteristic of functioning islet cell tumors. CLINICAL CASE A 77-year-old male was found unconscious and taken to an emergency department with evidence of hypoglycemia and clinical improvement following intravenous glucose administration. He did not have a history of diabetes mellitus and was not taking any glucose lowering medications. He was discharged with nutritional orientation and for control of capillary glycaemia to prevent hypoglycemia. He had 3 episodes of capillary hypoglycemia (50, 45 and 38) at home, that was predominant in the fasting morning and during its occurrence he presented mild sweating, speech difficulty, staring and diplopia, with complete improvement of symptoms after oral glucose replacement. Months earlier, he sought an otolaryngologist for intermittent mild dyspnea; denied cough, hemoptysis, chest pain and unintentional weight loss. He performed chest X-ray with evidence of large right hemithorax mass. Physical examination revealed diminished breath sounds in the right middle and lower lung fields and dullness to percussion. Despite marked hypoglycemia (31 mg/dl), the serum insulin level was less than 0.6 μIU/mL (less than 3 μIU/mL), the C-peptide level was 0.24 nmol/L (less than 0,6 nmol/L), had negative ketonemia and a positive response after glucagon administration (glycaemia increased in 50 mg/dl). Anti-insulin antibodies were negative. Serum cortisol secretion and adrenocorticotropic hormone were normal. The serum level of growth hormone (GH) was 0,03 (less than 0,97ng/ml). The serum IGF-2 level was 227 ng/ml (267 - 616 ng/ml), the IGF-I level was 72 ng/ml (37,1 - 172 ng/ml) and the IGF2/ IGF1 was 3,15 (equal or greater than 3). Computed tomographic (CT) scan revealed a large heterogeneous mass with dimensions of 17,4 × 15× 12.2 cm. It determines almost total atelectasis of the lower lobe on this side and maintains broad medial contact with the mediastinum, compressing the right atrium and the inferior pulmonary vein on this side. Preoperatively, was administered 40 mg oral prednisone with capillary glucose normalization. The tumor was completely resected and was a grayish-white solid, with dimensions of 17 x 16 x 12 cm. Immunohistochemical stains demonstrated positivity for CD34 and IGF2 expression. Postoperatively, serum glucose and insulin levels returned to normal, and episodes of hypoglycemia are resolved. CONCLUSION This case reinforce the importance of investigate IGF-2 tumor production as a cause of hypoinsulinemic hypoglycemia and reports the complete resolution of hypoglycemia after corticoid administration and/or tumor resection.

Efficacy of laparoscopic ultrasonography in laparoscopic resection of insulinoma.

Insulinoma is the most common functioning islet cell tumor of the pancreas, with an annual incidence of 4 cases/1 million individuals. It is treated by surgical methods. Open surgery was once considered the standard approach for the treatment of insulinoma. However, the procedure is traumatic and requires a large incision, which does not satisfy the growing expectations of minimally invasive management of small-sized tumors. Insulinomas are usually benign solitary tumors and mostly occur sporadically, which makes them suitable candidates for laparoscopic management. The potential advantages of laparoscopic management of insulinoma over open surgery include shorter duration of hospitalization, quicker recovery, and better cosmetic effect. However, because of the small tumor size as well as the depth and uncertainty of the location of the tumor, laparoscopic localization of the lesion without tactile sensation is difficult. Laparoscopic ultrasonography can detect about 90% of insulinomas, and its sensitivity is comparable to that of manual palpation along with intraoperative ultrasonography during open surgery; thus, it ensures the feasibility of laparoscopic management of insulinoma and reinforces its advantage as a minimally invasive procedure. Laparoscopic ultrasonography is vital for the localization of insulinomas and characterization of the surrounding pancreatic structure and should, therefore, be considered an integral part of the laparoscopic management of insulinoma.

Precise positioning and enucleation for the treatment of functional islet cell tumor

Objective To investigate the clinical value of intraoperative ultrasound guided precise positioning and enucleation of the functional islet cell tumor.Methods The clinical data of 20 patients with functional islet cell tumor who were admitted to the First Affiliated Hospital of Xinjiang Medical University from January 2005 to December 2011 were retrospectively analyzed.The method of precise positioning,surgical approach and prognosis of the patients were reviewed.Results The accurate rates of computed tomography (CT),magnetic resonance imaging (MRI) and transabdominal B ultrasound in detecting the position of the functional islet cell tumors were 12/18,2/6 and 7/13,respectively,and the diameters of the tumors were (1.7 ±0.8)cm,(1.3 ±0.2)cm and (1.9 ±0.9)cm,respectively.The accurate rates of arterial stimulation venous sampling and pancreatic perfusion CT imaging were 100％,and the diameters of the tumor detected were (0.7 ± 0.3) cm and (0.9 ± 0.4) cm.The accurate rate of intraoperative B ultrasound examination was 14/14,and the diameter of the tumor was (1.5 ± 0.6)cm.Routine surgery was carried out on 6 patients,and 2 patients were complicated with grade C pancreatic fistula,and 1 was complicated with grade A pancreatic fistula.Fourteen patients received precise enucleation of islet cell tumor,and 4 patients were complicated with grade A pancreatic fistula.Twenty patients were followed up.The general condition of the patients was good till April 2012,and no death,tumor recurrence and metastasis were detected.Conclusions Combination of pre-and intraoperative imaging positioning could precisely locate functional islet cell tumor.If the distance between the tumor and main pancreatic duct is above 3 mm,precise enucleation of the islet cell tumor should be considered. Key words: Functional islet cell tumor; Diagnosis; Treatment

533 Ultrasound Guided Ethanol Ablation of Insulinomas: A New Treatment Option

Insulinomas account for the majority of functioning islet cell tumors of the pancreas. Surgical enucleation or resection is the standard therapy when possible. We describe treatment by direct EUS and intraoperative ultrasound (IOUS) guided fine needle injection (FNI) of ethanol.

Sp694 Ultrasound Guided Ethanol Ablation of Insulinomas: A New Treatment Option

Insulinomas account for the majority of functioning islet cell tumors of the pancreas. Surgical enucleation or resection is the standard therapy. We describe treatment by direct EUS and intraoperative ultrasound (IOUS) guided fine needle injection (FNI) of ethanol. In this video we describe the methods and outcomes following EUS and IOUS-guided ethanol injection of insulinomas. To do so we identified patients with symptomatic insulinomas who underwent EUS or IOUS guided ethanol injection. Patients were contacted and charts reviewed to determine outcomes.

Spectrum of Functioning Islet Cell Tumor on Multislice Computed Tomography: Experience on 70 Patients

To review experience in preoperative detection of islet cell tumors using multislice computed tomography (MSCT) and summarize various imaging features of functioning islet cell tumors on enhanced MSCT. Seventy patients with clinical or pathological diagnosis of functioning pancreatic islet cell tumor between October 2003 and February 2007 were included in this retrospective study. Seventy-four enhanced MSCT scans in these patients were identified. All MSCT scans were interpreted by two experienced radiologists by consensus interpretation. Surgery and pathology reports were used to confirm the diagnosis, localization, and size of tumors. Totally, 73 functioning islet cell tumors including 65 benign insulinomas, 2 benign glucagonomas, 3 malignant insulinomas, and 3 malignant glucagonomas were pathologically diagnosed. Tumors in only two cases were not found by MSCT. In 67 benign lesions, 32 showed typical enhancement style, 21 showed prolonged enhancement in portal venous phase, 4 showed delayed enhancement, 4 had iso-dense enhancement with normal pancreatic parenchyma, 2 had no enhancement at all in arterial phase and portal venous phase, and 4 had inhomogeneous enhancement with necrosis or cyst-formation. Patchy or spotty calcifications were found in 3 of the 67 tumors. In 6 malignant islet cell tumors, vessel invasion (2/6) and bowel invasion (1/6) were seen. Different enhancement patterns were shown. All hepatic metastases showed hyper-enhancement during their arterial phase. Pancreatic islet cell tumor may display a wide spectrum of presentations in MSCT. Tumors with unusual appearances often present as diagnostic challenges. Non-contrast and post-contrast multiphase scans are recommended for the localization of functioning islet cell tumors.

Morphological and functional investigations of neuroendocrine tumors of the pancreas.

Neuroendocrine tumors of the pancreas are rare neoplasms arising predominantly from the pancreatic islets of Langerhans and are thus known as islet cell tumors. More than the half of all neuroendocrine tumors are called functioning islet cell tumors because they secrete one or more biologically active peptides that may produce clinical symptoms. Clinical diagnosis of non-functioning, i.e., biologically inactive, tumors is often delayed and patients tend to present with advanced tumors (size greater than 5 cm) that are easily localized by using conventional imaging modalities. On the other hand, symptoms of functioning islet cell tumors usually appear early in the clinical course, rendering the preoperative localization of these small hormone-producing tumors (size less than 2 cm) difficult with non-invasive methods. Since functioning islet cell tumors can often be cured by surgical resection, invasive procedures are warranted when necessary for localization diagnosis. Failure to search for, detect, and resect these small tumors will invariably result in persistent symptoms. Regarding the unsatisfactory results of morphological imaging methods, functional studies, especially arterial stimulation with hepatic venous samplings, may provide a preoperative regionalization of the pancreatic adenoma, regardless of its size.

109: Non Functioning Islet Cell Tumors of the Pancreas: Case Report, Our Experience and Management (Oral Presentation)

109: Non Functioning Islet Cell Tumors of the Pancreas: Case Report, Our Experience and Management (Oral Presentation)

Duodenal carcinoid tumors: How aggressive should we be?

Duodenal carcinoid tumors are uncommon. It is not known whether they behave more like carcinoid tumors in the appendix (indolent course) or those in the ileum (often virulent)—crucial information for determining the need for radical resection. A retrospective review at our tertiary referral center (from 1976 to 1999) identified 27 patients with primary duodenal carcinoid lesions, excluding functional islet cell tumors. Endoscopic biopsy provided the diagnosis in 78% of patients. Treatment was by endoscopic excision (n = 11), transduodenal excision (n = 8), pancreaticoduodenectomy (n = 3), segmental distal duodenectomy (n = 2), or palliative operation (n = 2). One patient did not undergo operation because of comorbidity. Eighteen of 19 patients with tumors smaller than 2 cm remained disease free after local (endoscopic or transduodenal) excision. The exception was a patient with a small periampullary carcinoid lesion. In contrast, all four patients with carcinoid tumors 2 cm or larger who were resected for cure developed a recurrence (2 to 9 years postoperatively). We conclude that duodenal carcinoid tumors smaller than 2 cm may be excised locally; to ensure complete resection we recommend open transduodenal excision for tumors between 1 and 2 cm. Endoscopic follow-up is indicated. It is unclear whether patients with larger tumors benefit from more aggressive locoregional resection. Ampullary/periampullary carcinoid tumors should be considered separately, as their behavior is unpredictable.

Surgical Experience with Nonfunctioning Neuroendocrine Tumors of the Pancreas

Nonfunctioning neuroendocrine tumors of the pancreas are rare slow-growing tumors with a more indolent natural history compared with pancreatic adenocarcinoma. This retrospective report reviews the surgical experience with nonfunctioning neuroendocrine tumors in an academic referral center. Statistical analysis was performed using Student's t test and Kaplan-Meier method compared with log-rank tests. Thirty-eight patients (24 males and 14 females) underwent surgery for a neuroendocrine tumor of the pancreas from 1984 through 1999. Twenty-eight patients with a mean age of 59.9 years had nonfunctioning islet cell tumors and 10 patients with a mean age of 59.1 years had functioning islet cell tumors (four gastrinomas, three glucagonomas, two insulinomas, and one vipoma). The nonfunctioning islet cell tumors were located in the head, neck, or uncinate process in 14 patients (50%), the body in seven (25%), and the tail in seven (25%). Operative procedures for the nonfunctioning islet cell tumors included nine pancreaticoduodenectomies, 12 distal pancreatectomies, three palliative bypasses, and four exploratory laparotomies without a resection or bypass. Mean survival for the four patients explored and not resected or bypassed was 7 months. Median survival for node-negative patients was 124 months, for node-positive patients 75 months, and for patients with metastasis to the liver 9 months. Estimated 2-year actuarial survival for the node-negative patients was 77.8 per cent, for node-positive patients 71.4 per cent, and for patients with metastasis to the liver 36.4 per cent. Six patients (60%) with node-negative disease, three (43%) with node-positive disease, and one (9%) with metastasis to the liver are alive at a mean follow-up of 41.8 months (range 1-167). Significant differences in median survival and 2-year survival were demonstrated between the node-positive/node-negative patients and those with metastasis to the liver (P = 0.003). Patients with localized nonmetastatic disease should be considered for pancreatic resection as estimated median survival is 75 months or greater. Hepatic metastasis is a major predictor of survival.

Hepatic neuroendocrine metastases: does intervention alter outcomes?

Background: In most instances, advanced neuroendocrine tumors follow an indolent course. Hepatic metastases are common, and although they can cause significant pain, incapacitating endocrinopathy, and even death, they are usually asymptomatic. The appropriate timing and efficacy of interventions, such as hepatic artery emobolization (HAE) and operation, remain controversial. Study Design: The records of 85 selected patients referred for treatment of hepatic neuroendocrine tumor metastases between 1992 and 1998 were reviewed from a prospective database. A multidisciplinary group of surgeons, radiologists, and oncologists managed all patients. Overall survival among this cohort is reported and prognostic variables, which may be predictive of survival, are analyzed. Results: There were 37 men and 48 women, with a median age of 52 years. There were 41 carcinoid tumors, 26 nonfunctional islet cell tumors, and 18 functional islet cell tumors. Thirty-eight patients had extrahepatic metastases, and in 84% of patients, the liver metastases were bilobar. Eighteen patients were treated with medical therapy or best supportive care, 33 patients underwent HAE, and 34 patients underwent hepatic resection. Both the HAE-related mortality and the 30-day operative mortality rates were 6%. By univariate analysis, earlier resection of the primary tumor, curative intent of treatment, and initial surgical treatment were associated with prolonged survival (p < 0.05). On multivariate analysis, only curative intent to treat remained significant (p < 0.04). Patients with bilobar or more than 75% liver involvement by tumor were least likely to benefit from surgical resection. One-, 3-, and 5-year survival rates for the entire group were 83%, 61%, and 53%, respectively. The 1-, 3-, and 5-year survivals for patients treated with medical therapy, HAE, and operation were 76%, 39%, and not available; 94%, 83%, and 50%; and 94%, 83%, and 76%, respectively. Conclusions: Hepatic metastases from neuroendocrine tumors are best managed with a multidisciplinary approach. Both HAE and surgical resection provide excellent palliation of hormonal and pain symptoms. In select patients, surgical resection of hepatic metastases may prolong survival, but is rarely curative.

Detection of small, functional islet cell tumors in the pancreas: selection of MR imaging sequences for optimal sensitivity.

To determine the sensitivity and specificity of magnetic resonance (MR) imaging for depicting pancreatic small, functional islet cell tumors and the minimum number of sequences for expedient diagnosis. Twenty-eight patients clinically suspected to have functional islet cell tumors underwent T1- and T2-weighted spin-echo (SE) MR imaging with and without fat suppression, T2-weighted fast SE imaging, and spoiled gradient-echo (GRE) imaging before and after injection of gadopentetate dimeglumine. Sensitivity, specificity, and the best and minimum number of sequences for definitive diagnosis were determined. MR images depicted proved islet cell tumors in 17 of 20 patients (sensitivity, 85%). Images were true-negative in eight patients with negative follow-up examination results for more than 1 year. Specificity was 100%; positive predictive value, 100%; and negative predictive value, 73%. Among 20 patients with tumor, T1-weighted SE images with fat suppression and nonenhanced spoiled GRE images each showed lesions in 15 (75%); T2-weighted conventional SE with fat suppression, in 13 (65%); gadolinium-enhanced spoiled GRE, in 12 (60%); and T2-weighted fast SE, in seven of 10 patients (70%). MR imaging accurately depicts small islet cell tumors. T2-weighted fast SE and spoiled GRE sequences usually suffice. Gadolinium-enhanced sequences are needed only if MR imaging results are equivocal or negative.

Prospective study of provocative angiograms to localize functional islet cell tumors of the pancreas

Background. Controversy exists concerning the use of preoperative imaging studies in patients with islet cell tumors. Since 1993 we have evaluated the use of provocative angiography in patients with insulinoma or Zollinger-Ellison syndrome (ZES). Methods. Twelve patients with a working diagnosis of insulinoma (n = 4) or ZES (n = 8) were studied. Of the eight patients with ZES, four were known to have multiple endocrine neoplasia type 1. All patients underwent conventional imaging studies followed by provocative angiography. Angiograms were graded based on the ability to detect tumor and regionalize it within the pancreas. Results. Of the three patients with a working diagnosis of ZES but equivocal results of biochemical studies, none had arteriographic imaging of an islet cell tumor or a positive provocative study result (true negative result). Of the nine patients with documented islet cell tumor, seven (78%) underwent arteriographic imaging of the tumor and eight (89%) had correct regional localization by provocative angiography. Sensitivity and specificity for imaging were 78% and 100%, respectively, and for regional localization 89% and 100%, respectively. Conclusions. Provocative angiography is the localization study of choice for both gastrinoma and insulinoma. Having few false-negative results, it can be used to corroborate the diagnosis and, having few false-positive results, it detects tumor and biochemically confirms localization in nearly every patient.

Islet cell tumors of the pancreas: clinical, radiologic, and pathologic correlation in diagnosis and localization.

Islet cell tumors are rare pancreatic or peripancreatic neoplasms that produce and secrete hormones to a variable degree. These tumors are best divided on clinical grounds into those that produce a recognizable, clinically evident endocrine syndrome (ie, functioning) and those that exhibit no clinical evidence of hormone production (ie, clinically silent). Clinically silent tumors produce symptoms due to mass effect because of their large size. They are often partially cystic or necrotic. Functioning islet cell tumors usually manifest earlier in the course of the disease because of the distinctive signs and symptoms of the associated endocrine syndrome. Clinically silent and functioning tumors cannot be histologically distinguished reliably even with the use of immunohistochemical stains. Insulinoma and gastrinoma, the two most common functioning lesions, are typically small homogeneous masses. Other functioning islet cell tumors include glucagonoma, somatostatinoma, vipoma, and adrenocorticotropic hormone-producing tumor. Larger tumors are associated with calcification, cystic degeneration and necrosis, and a more aggressive behavior (local and vascular invasion as well as distant metastases). There are many different techniques for detection and characterization of these lesions that are usually chosen according to the radiologist's experience and preference. Treatment and prognosis of these lesions depend on the hormone produced, their size, and their behavior.

Functioning islet cell tumor of the pancreas

Purpose: The purpose of this study was to evaluate the usefulness of dynamic spiral CT, including multidimensional reformation, in the detection and localization of islet cell tumors of the pancreas.Material and Methods: Seven patients with histopathologically proven functioning islet cell tumors of the pancreas were studied with 2-phase contrast-enhanced spiral CT. Scanning of the arterial phase and late phase was started 30 s and 180 s, respectively, after injection of 100 ml of contrast medium at a rate of 3 ml/s.Results: Axial images in the arterial phase depicted the lesions in 5 patients, but in the late phase in only one patient. Multiplanar reformatted images of the arterial phase depicted the lesions in all 7 patients. Maximal intensity projection images demonstrated all lesions with information of their relationship to the vascular structure.Conclusion: Dynamic spiral CT with scanning during the arterial phase and retrospective multidimensional reformation is useful for preoperative detection an...

Functioning islet cell tumor of the pancreas. Localization with dynamic spiral CT.

The purpose of this study was to evaluate the usefulness of dynamic spiral CT, including multidimensional reformation, in the detection and localization of islet cell tumors of the pancreas. Seven patients with histopathologically proven functioning islet cell tumors of the pancreas were studied with 2-phase contrast-enhanced spiral CT. Scanning of the arterial phase and late phase was started 30 s and 180 s, respectively, after injection of 100 ml of contrast medium at a rate of 3 ml/s. Axial images in the arterial phase depicted the lesions in 5 patients, but in the late phase in only one patient. Multiplanar reformatted images of the arterial phase depicted the lesions in all 7 patients. Maximal intensity projection images demonstrated all lesions with information of their relationship to the vascular structure. Dynamic spiral CT with scanning during the arterial phase and retrospective multidimensional reformation is useful for preoperative detection and localization of small islet cell tumors of the pancreas.

Clinical review 72: diagnosis and management of functioning islet cell tumors.

Functional islet cell tumors cause recognizable clinical syndromes based on the peptide products they secrete (Table 1). Frequently, the diagnosis of these tumors is delayed. A high index of suspicion coupled with the use of appropriate biochemical and provocative tests should lead to earlier diagnosis. A suggested management plan for patients suspected of having an islet cell tumor is shown in Fig. 1. Earlier diagnosis coupled with advances in preoperative and intraoperative localization techniques have resulted in an increased number of patients being cured.

Clinical review 72: diagnosis and management of functioning islet cell tumors

Clinical review 72: diagnosis and management of functioning islet cell tumors

Malignant islet cell tumor associated with hypercalcemia

Three cases of islet cell tumors of the pancreas with hypercalcemia were studied, and 16 similar cases have been found in a 25-year review of the English-language literature. The purpose of the study was to review the cause of the hypercalcemia and the clinical characteristics of the tumors. Tumor tissue retrieved from paraffin-embedded blocks was studied immunohistochemically for both parathyroid hormone (PTH) and PTH-related protein (PTHrP). PTH was measured in the serum in each patient and the serum PTHrP was measured by immunoassay in one patient. One of our patients had a fatal serum calcium level of 26.4 mg/dl. PTHrP stains were positive in two of our tumors, and one patient had an elevated PTHrP serum level. Serum PTH levels were normal or low in each patient. All three tumors were malignant and extremely vascular. The total group of 19 patients have in common hypercalcemia associated with a normal or low serum PTH level. Although the cause of hypercalcemia has not been proved, the tumors apparently produce PTHrP, because seven of eight tumors stained positive for PTHrP and each of the four patients tested had an elevated PTHrP serum titer. The tumors are extremely vascular, are usually malignant (17 of 18), and become large, but they are compatible with a relatively long patient survival time. These neuroendocrine tumors associated with hypercalcemia share several characteristics, but a claim that they represent another type of "functioning islet cell tumor" should await a clearer delineation of the cause of the hypercalcemia.

Is there a prognostic difference between functional and nonfunctional islet cell tumors?

Pancreatic islet cell tumors are categorized as either functioning or nonfunctioning. Functioning islet cell tumors (FIT) elaborate a variety of hormones, producing dramatic symptoms, while the initial presentation of non-functioning islet cell tumors (NIT) is commonly an abdominal mass or symptom complex related to invasion of adjacent structures. As a result, NIT are purported to present at a later stage, with lower resectability rates, and an overall poorer prognosis, when compared to FIT. In addition, a number of reports have indicated that the incidence of NIT has increased significantly in recent years. Twenty-eight patients were studied retrospectively. All had islet cell tumors of the pancreas and were seen at the University of Nebraska Medical Center and affiliated Nebraska Methodist Hospital during a 19-year period. There were 9 patients (32%) in the NIT group and 19 (68%) in the FIT group. The mean ages at presentation were 61 years for the NIT and 52 years for the FIT group. In the NIT group, all presented with either abdominal pain (n = 7) or jaundice (n = 2). In contrast, over 90% of the patients with FIT had symptoms referable to the specific hormone elaborated by the tumor. Primary tumor size for NIT was 4.1 +/- 0.7 cm versus 5.0 +/- 0.6 cm for the FIT group. No significant difference was found for NIT versus FIT with respect to the incidence of metastatic disease at presentation (44% versus 53%), resectability rate with curative intent (44% versus 53%), or disease-free survival at 2 years (67% versus 40%). This series, in contrast to earlier reports, suggests that nonfunctioning islet cell tumors do not present at a more advanced stage, have lower resectability rates, or an overall poorer long-term prognosis when compared to functioning tumors.