Pancreatic Neuroendocrine Tumors

11/7/2005

Question:  How are pancreatic neuroendocrine tumors diagnosed?

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<1>

Unique Identifier [PMID]: 15763697

Authors: Jackson JE.

Institution: Department of Imaging, Hammersmith Hospital, Du Cane Road, London W12 0HS, UK. jejackson@hhnt.org

Title: Angiography and arterial stimulation venous sampling in the localization of pancreatic neuroendocrine tumours. [Review] [37 refs]

Source: Best Practice & Research Clinical Endocrinology & Metabolism. 19(2):229-39, 2005 Jun.

Abstract: Insulin- and gastrin-secreting neuroendocrine tumours of the pancreas are often very small at presentation because of the potent effects of their hormonal outputs, and they may therefore prove difficult to localize preoperatively. This is despite the advances made in recent years in cross-sectional imaging techniques, especially multidetector-row computed tomography and endoscopic ultrasound. In this chapter the techniques of angiography and arterial stimulation venous sampling used for the localization of these neoplasms are described; a combination of these two modalities provides both anatomical and functional data that are not available with other localization techniques, thereby improving operative outcome. [References: 37]

Publication Type: Journal Article. Review. Review, Tutorial.

<2>

Unique Identifier [PMID]: 15763694

Authors: McLean AM. Fairclough PD.

Institution: Departments of Diagnostic Imaging and Gastroenterology, St Bartholomew' Hospital, QE2 X-ray, West Smithfield, London EC1A 7BE, UK. alison.mclean@bartsandthelondon.nhs.uk

Title: Endoscopic ultrasound in the localisation of pancreatic islet cell tumours. [Review] [34 refs]

Source: Best Practice & Research Clinical Endocrinology & Metabolism. 19(2):177-93, 2005 Jun.

Abstract: The role of endoscopic ultrasound (EUS) in the evaluation of entero-pancreatic endocrine tumours has evolved in conjunction with advances in other imaging methods. The high spatial resolution of this technique allows the detection of very small lesions and their precise anatomical localisation. In patients with biochemically proven insulinoma, EUS can be effectively used as a first line investigation, with a sensitivity of 94%. Combined with thin section CT, the sensitivity rises to 100%. There is also high sensitivity in diagnosing intrapancreatic gastrinomas but lower for those arising in the duodenal wall which require detailed duodenal evaluation at surgery. EUS in conjunction with Somatostatin Receptor Scanning (SRS) has a combined sensitivity of 93% for gastrinomas. EUS is recommended for screening of asymptomatic patients with genetically proven MEN1. There is a limited role for EUS guided biopsy in pancreatic endocrine tumours. [References: 34]

Publication Type: Journal Article. Review. Review, Tutorial.

<3>

Unique Identifier [PMID]: 12732942

Authors: Pereira PL. Wiskirchen J.

Institution: Department of Diagnostic Radiology, Eberhard Karls University, Hoppe-Seyler-Strasse, 372076 Tubingen, Germany. philippe.pereira@med.uni-tuebingen.de

Title: Morphological and functional investigations of neuroendocrine tumors of the pancreas. [Review] [88 refs]

Source: European Radiology. 13(9):2133-46, 2003 Sep.

Abstract: 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. [References: 88]

Publication Type: Journal Article. Review. Review, Tutorial.

<4>

Unique Identifier [PMID]: 11472032

Authors: Fernandez-Cruz L. Herrera M. Saenz A. Pantoja JP. Astudillo E. Sierra M.

Institution: Department of Surgery, Institute of Digestive Diseases IMD, Hospital Clinic, University of Barcelona, Spain.

Title: Laparoscopic pancreatic surgery in patients with neuroendocrine tumours: indications and limits. [Review] [37 refs]

Source: Best Practice & Research Clinical Endocrinology & Metabolism. 15(2):161-75, 2001 Jun.

Abstract: Laparoscopic pancreatic procedures are still at an evaluation stage with regard to their indications and techniques. Between January 1998 and December 2000, 13 patients with endocrine pancreatic tumours - 11 insulinomas and 2 non-functioning tumours-underwent laparoscopic surgery, laparoscopic ultrasonography being used in all the patients. Enucleation was performed in five patients. The operative time was 2-3 hours. Distal pancreatectomy was performed in six patients with insulinomas, and spleen preservation with intact splenic vessels was feasible in five. Splenectomy was necessary in one patient for technical reasons. Laparoscopic distal pancreatectomy with splenic vessel preservation was performed in two patients with a large (6 and 8 cm) non-functioning tumour. The mean operative time for all the patients undergoing distal pancreatectomy was 4 hours, ranging from 3 to 5 hours. A pancreatic fistula occurred in three patients after tumour enucleation and in two patients after distal pancreatectomy; the mean hospital stay for all patients was 5 days. Enucleation guided by laparoscopic ultrasonography thus allows safe tumour dissection and excision, laparoscopic distal pancreatectomy also being feasible and safe. Splenic salvage with splenic vessel preservation is technically possible. The laparoscopic approach allows a shorter hospital stay and an earlier return to normal activities. Copyright 2001 Harcourt Publishers Ltd. [References: 37]

Publication Type: Journal Article. Review.

<5>

Unique Identifier [PMID]: 9866368

Authors: Hall RS. Hanley JF. Georgitis W. McNally PR.

Institution: Department of Medicine, Fitzsimons Army Medical Center, Aurora, CO 80045, USA.

Title: Endoscopic ultrasound localization of a pancreatic insulinoma: case report and review of the localization techniques. [Review] [34 refs]

Source: Military Medicine. 163(12):853-6, 1998 Dec.

Abstract: A 23-year-old male was referred to our hospital for evaluation of new-onset seizures. Signs and symptoms of neuroglycopenia, including weakness, dizziness, and confusion, appeared during fasting and resolved promptly with intravenous dextrose administration. Insulin, proinsulin, and C-peptide levels were consistent with a diagnosis of insulinoma. Screening tests for multiple endocrine neoplasia type 1 and surreptitious sulfonylurea uses were negative. Preoperative localization of the insulinoma by transabdominal ultrasonography, computed tomography, and indium-111 octreoscanning were unsuccessful. Endoscopic ultrasonography (EUS) identified a 6- to 7-mm tumor at the juncture of the head and body of the pancreas. Surgical exploration confirmed the preoperative localization, and an 8-mm tumor was simply enucleated. The patient has been free of symptoms for 18 months since surgery. This report describes the utility of EUS to localize a solitary pancreatic insulinoma and provides a comparison of EUS and other preoperative localization techniques. [References: 34]

Publication Type: Case Reports. Journal Article. Review. Review of Reported Cases.

<6>

Unique Identifier [PMID]: 7710334

Authors: Modlin IM. Cornelius E. Lawton GP.

Institution: Department of Surgery, Yale University School of Medicine, New Haven, Conn, USA.

Title: Use of an isotopic somatostatin receptor probe to image gut endocrine tumors. [Review] [20 refs]

Source: Archives of Surgery. 130(4):367-73; discussion 373-4, 1995 Apr.

Abstract: OBJECTIVES: To evaluate the effectiveness of indium In 111 pentetate (diethylenetriaminepentaacetic acid [DTPA]-D-Phe-labeled octreotide scintigraphy in the localization of gastroenteropancreatic neuroendocrine lesions, and to identify covert lesions, determine multicentricity, define the distribution of metastases, confirm complete removal of tumor postoperatively, and evaluate the efficacy of therapeutic embolization. DESIGN: Unmasked comparison. SETTING: Tertiary care referral center. PATIENTS: We studied 28 patients over a 12-month period. Biochemical evidence of a gastroenteropancreatic tumor was present in 13 patients. Octreoscan 111 was employed in four patients with an ambiguous biochemical diagnosis of gastroenteropancreatic tumor. Postoperative examination to document complete tumor removal was undertaken in seven patients. In one patient, Octreoscan 111 was used to evaluate the efficacy of therapeutic embolization. INTERVENTION: [111In]DTPA-D-Phe-octreotide scintigraphy. MAIN OUTCOME MEASURE: Identification of somatostatin receptor-bearing neuroendocrine tumors. RESULTS: Intravenous administration of [111In]DTPA-D-Phe-octreotide followed by whole-body gamma camera scintigraphy resulted in the localization of gastroenteropancreatic neuroendocrine tumors with 75% sensitivity, 100% specificity, 100% positive predictive value, 63% negative predictive value, and 82% overall accuracy. CONCLUSIONS: While Octreoscan 111 has been shown to localize the majority of amine precursor uptake and decarboxylation system (APUD) cell tumors as well as various other somatostatin-positive tumors, this technique may also be useful in a number of other circumstances. These include prediction of tumors that will respond to octreotide therapy, identification of covert metastases, intraoperative identification of tumors, and postoperative surveillance. Use of an alternative isotope may provide a vehicle for the administration of local therapeutic radiation to tumor cells. The precise efficacy of Octreoscan 111 in the identification of lesions smaller than 3 cm with low-density somatostatin-2 receptor expression remains to be determined. [References: 20]

Publication Type: Clinical Trial. Journal Article. Review. Review, Tutorial.

<7>

Unique Identifier [PMID]: 7904550

Authors: Norton JA.

Institution: Washington University School of Medicine, St. Louis, Missouri.

Title: Neuroendocrine tumors of the pancreas and duodenum. [Review] [285 refs]

Source: Current Problems in Surgery. 31(2):77-156, 1994 Feb.

Publication Type: Journal Article. Review.

<8>

Unique Identifier [PMID]: 7583938

Authors: Leight GS Jr. Varhaug JE.

Institution: Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA.

Title: Preoperative endocrine tumor localization utilizing a cost-effective approach. [Review] [19 refs]

Source: Current Opinion in General Surgery. :108-14, 1993.

Abstract: Endocrine tumors commonly produce characteristic clinical signs, and laboratory tests lead to accurate diagnosis in a high percentage of cases. The successful management of these tumors usually requires complete surgical resection. A large number of preoperative localization procedures to facilitate the operative management of these tumors have been developed. This report reviews the recent contributions to this literature, with a particular emphasis on cost-effective use of these procedures. [References: 19]

Publication Type: Journal Article. Review. Review, Tutorial.

<9>

Unique Identifier [PMID]: 15043465

Authors: Diaz-Rubio JL. Duarte-Rojo A. Saqui-Salces M. Gamboa-Dominguez A. Robles-Diaz G.

Institution: Department of Gastroenterology, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Mexico City, Mexico.

Title: Cellular proliferative fraction measured with topoisomerase IIalpha predicts malignancy in endocrine pancreatic tumors.

Source: Archives of Pathology & Laboratory Medicine. 128(4):426-9, 2004 Apr.

Abstract: CONTEXT: Endocrine pancreatic tumors (EPTs) are rare lesions with varying biological behavior. Establishing malignancy is a challenge for clinicians and pathologists. OBJECTIVE: To establish the role of proliferative, apoptotic, angiogenic, and hormonal markers as predictors of malignancy in EPTs. DESIGN: Paraffin-embedded EPT samples were studied for prognostic markers. PATIENTS: Twenty-one consecutive patients with a diagnosis of EPT. MAIN OUTCOME MEASURES: The proliferative fraction (topoisomerase IIalpha), microvascular density (CD34), vascular endothelial growth factor expression, and estrogen receptor-beta (ERbeta) expression were studied by immunohistochemistry on all EPTs. Apoptosis was also assessed with terminal deoxynucleotidyl transferase nick-end labeling. RESULTS: We identified 13 benign and 8 malignant tumors. Topoisomerase IIalpha was significantly increased in malignant tumors (P =.001), while there were no differences in apoptosis, microvascular density, or vascular endothelial growth factor expression in association with malignancy. No correlation could be identified between microvascular density and vascular endothelial growth factor expression, and ERbeta was not detected. A receiver operating characteristic curve for topoisomerase IIalpha disclosed that above a labeling index of 13, the test had 88% sensitivity and 100% specificity for predicting malignancy. CONCLUSION: Cellular proliferation measured with topoisomerase IIalpha is a simple prognostic marker for malignancy in EPTs, unlike apoptosis, angiogenesis, or the presence of ERbeta, which were not associated with malignant behavior. These findings designate a defined field for future research on endocrine pancreatic carcinogenesis and a possible target for chemotherapeutic agents.

Publication Type: Evaluation Studies. Journal Article.

<10>

Unique Identifier [PMID]: 14602773

Authors: Bertherat J. Tenenbaum F. Perlemoine K. Videau C. Alberini JL. Richard B. Dousset B. Bertagna X. Epelbaum J.

Institution: Department of Endocrinology, Cochin Hospital, Paris, France. jerome.bertherat@cch.ap-hop-paris.fr

Title: Somatostatin receptors 2 and 5 are the major somatostatin receptors in insulinomas: an in vivo and in vitro study.

Source: Journal of Clinical Endocrinology & Metabolism. 88(11):5353-60, 2003 Nov.

Abstract: Somatostatin (SRIF) receptors (sst) are present on normal pancreatic endocrine beta-cells. However, the use of SRIF analogs in the scintigraphic imaging of insulinomas and in the medical management of these tumors seems to be restricted to a subgroup of patients. The aim of this study was to determine the prevalence of sst expression in vitro and characterize sst subtype binding in insulinomas and its correlation with in vivo sst receptor scintigraphy (SRS). In vitro studies were performed on 27 insulinomas from 25 patients: 22 with benign and three with malignant tumors. Semiquantitative RT-PCR of sst mRNAs was performed for 20 of these insulinomas. Sst2 and sst5 were expressed in 70%, sst1 in 50%, and sst3 and sst4 subtypes only in 15-20% of the tumors. (125)I-Tyr(0)DTrp(8)SRIF(14) binding was assessed by quantitative autoradiography in 18 insulinomas, and competition experiments were performed with SRIF(14) and L797-591, L779-976, L796-778, L803-087, L817-818, selective agonists of the five sst subtypes, and BIM23244, a selective agonist of sst2 and sst5. Significant specific binding was observed in 72% of the insulinomas. Displacement experiments with ligands of higher affinity for each of the sst receptors revealed significant binding with the sst2 and sst5 ligands in 72%, sst3 in 44%, sst1 in 44%, and sst4 in 28% of cases. All insulinomas displaying sst2 binding were also sst5 sensitive. However, the ratio of sst5/sst2 displacement was variable and only equal to that for SRIF(14) in experiments with the sst2/sst5 agonist BIM23244. SRS was performed 10 times in nine patients; it detected 60% of the tumors, including metastases of a malignant insulinoma. All the tumors detected by SRS displayed high levels of (125)I-Tyr(0)DTrp(8)SRIF(14) binding. The mechanisms underlying the loss of expression of sst2/sst5 in a third of insulinomas remains to be determined, but this loss of expression may be involved in beta-cell dysfunction.

Publication Type: Journal Article.

<11>

Unique Identifier [PMID]: 12933480

Authors: Fidler JL. Fletcher JG. Reading CC. Andrews JC. Thompson GB. Grant CS. Service FJ.

Institution: Department of Radiology, Mayo Clinic and Mayo Foundation, 200 First St. S.W., Rochester, MN 55905, USA. fidler.jeff@mayo.edu

Title: Preoperative detection of pancreatic insulinomas on multiphasic helical CT.

Source: AJR. American Journal of Roentgenology. 181(3):775-80, 2003 Sep.

Abstract: OBJECTIVE: The objective was to analyze enhancement characteristics of insulinomas and to determine the ability of multiphase CT to localize these tumors. MATERIALS AND METHODS: Prospective interpretations of multiphase helical CT scans were reviewed in 30 patients who had insulinomas resected over a 5-year period. CT scans were retrospectively reviewed to determine enhancement characteristics, tumor conspicuity in each phase of enhancement, and potential causes for false-negative findings. RESULTS: Sixty-three percent (19/30) of tumors were identified on CT prospectively. An additional six tumors were visualized in retrospect, allowing characterization of 25 (83%) of 30 tumors. Most tumors were hyperdense on at least one phase (n = 19), three tumors were hypoattenuating, and three were isodense and pedunculated. Insulinomas were most conspicuous on the early phase in 15 patients and in the portal venous phase in three. All tumors that underwent pancreatic phase imaging were seen (13/13), whereas three of 18 arterial and six of 25 portal venous phase findings were inconclusive for tumor. In the six examinations with false-negative findings in which the tumor could be seen in retrospect, two tumors were isodense and pedunculated, three were in close proximity to vessels, and one had a cystic appearance. CONCLUSION: Multiphasic CT has a moderate sensitivity in the detection of insulinomas. Most tumors are more conspicuous on the earlier phases of enhancement. The pancreatic phase may be more useful than the arterial phase. Potential sources of false-negative results include tumors adjacent to vessels, pedunculated morphology, or nonhyperattenuating lesions.

Publication Type: Evaluation Studies. Journal Article.

<12>

Unique Identifier [PMID]: 12490839

Authors: Carneiro DM. Levi JU. Irvin GL 3rd.

Institution: Department of Surgery, University of Miami/Jackson Memorial, Miami, FL 33101-6310, USA.

Title: Rapid insulin assay for intraoperative confirmation of complete resection of insulinomas.

Source: Surgery. 132(6):937-42; discussion 942-3, 2002 Dec.

Abstract: BACKGROUND: Solitary insulinomas are usually the cause of organic hypoglycemia, whereas 13% to 24% of patients with hyperinsulinemia have multiple tumors or nesidioblastosis. Intraoperative glucose levels confirming complete excision have variable accuracy. Intraoperative insulin levels have been shown to predict operative outcome. The purpose of this study was to establish criteria for predicting operative success by using a new, rapid insulin assay as an intraoperative adjunct. METHODS: Eight consecutive patients with organic hypoglycemia underwent pancreatic exploration. With an 8-minute immunochemiluminescent insulin assay, peripheral blood levels were obtained preoperatively, during resection, and at 5-minute intervals after surgical excisions. Operative findings and outcome were compared with intraoperative insulin/glucose ratios (I/G), glucose, and insulin levels. RESULTS: By using the return of insulin levels to normal range and I/G ratios < or = 0.4 15 minutes after tumor(s) resection as criteria to predict operative success, 6 patients had their outcomes correctly predicted (5 true-positive and 1 true-negative). One patient with nesidioblastosis had a false-negative result. One could not be evaluated because of diazoxide medication. These criteria predicted postoperative absence of hypoglycemia with specificity of 100% and accuracy of 89%. CONCLUSIONS: These 8-minute insulin assay and criteria can be a useful adjunct for intraoperative assurance of complete insulinoma resection and prediction of postoperative outcome.

Publication Type: Clinical Trial. Journal Article.

<13>

Unique Identifier [PMID]: 11532420

Authors: O'Hanlon DM. Clarke E. Fenlon HM. O'Keane JC. McEntee GP.

Institution: Department of Surgery, Mater Misericordiae Hospital, Eccles St., 7, Dublin, Ireland. deirdreohanlon@hotmail.com

Title: Insulinoma of the pancreas.

Source: American Journal of Surgery. 182(1):73-4, 2001 Jul.

Publication Type: Case Reports. Journal Article.

<14>

Unique Identifier [PMID]: 11529824

Authors: Hiramoto JS. Feldstein VA. LaBerge JM. Norton JA.

Institution: Department of Surgery, San Francisco Veterans Affairs Medical Center, Surgical Service (112), 4150 Clement St, San Francisco, CA 94121, USA.

Title: Intraoperative ultrasound and preoperative localization detects all occult insulinomas; discussion 1025-6.

Source: Archives of Surgery. 136(9):1020-5, 2001 Sep.

Abstract: HYPOTHESIS: Preoperative invasive localization procedures with intraoperative ultrasound (IOUS) can result in successful surgical treatment of occult insulinomas when noninvasive imaging study results are equivocal or negative. DESIGN: Prospective study. SETTING: Tertiary care university hospital. PATIENTS: Thirty-seven consecutive patients with a biochemical diagnosis of insulinoma without multiple endocrine neoplasia (MEN). INTERVENTION: All patients underwent portal venous sampling (PVS) (n = 22) or calcium angiogram (n = 15) followed by surgery with palpation and IOUS (n = 37). MAIN OUTCOME MEASURE: Portal venous sampling, calcium angiogram, palpation, and IOUS were compared for accurate localization of insulinoma. RESULTS: All patients were cured of hypoglycemia after surgery. Portal venous sampling correctly localized tumors in 17 (77%) of 22 patients. Calcium angiogram was correct in 13 (87%) of 15 patients. Palpation identified 24 (65%) of 37 tumors, and IOUS found 35 (95%) of 37 tumors. The 2 tumors missed by IOUS were located in the tail of the pancreas and were resected based on regional localization alone. CONCLUSIONS: Intraoperative ultrasound is the single best localization study, but it will miss some tumors that regional localization can identify. Combining both modalities allowed surgical cure of all insulinomas in our study. Therefore, we recommend both IOUS and regional localization for insulinoma when preoperative imaging studies are equivocal.

Publication Type: Journal Article.

<15>

Unique Identifier [PMID]: 11147593

Authors: Tezel E. Nagasaka T. Nomoto S. Sugimoto H. Nakao A.

Institution: Department of Surgery II, Nagoya University, School of Medicine, Japan. etezel@tsuru.med.nagoya-u.ac.jp

Title: Neuroendocrine-like differentiation in patients with pancreatic carcinoma.

Source: Cancer. 89(11):2230-6, 2000 Dec 1.

Abstract: BACKGROUND: The accurate estimation of the rate and the clinicopathologic significance of neuroendocrine-like differentiation (NED) in patients with pancreatic carcinoma have not been studied in detail. METHODS: Forty-four patients with pancreatic carcinoma who underwent surgical resection at the Department of Surgery II, Nagoya University Hospital, were included in this study. For immunostaining, antibodies against neural cell adhesion molecule (NCAM), neuron-specific enolase (NSE), synaptophysin, CD57, and chromogranin A (CGA) were used at given dilutions. At least two positive results with antibodies were considered as NED. Statistical analysis was performed by chi-square and Spearman rank correlation tests for group differences. Survival rates were calculated by the Kaplan-Meier method, and statistical significance was examined using the log rank test. Prognostic factors were tested by univariate and multivariate analyses (proportional hazards regression model). P < 0.05 was considered statistically significant. RESULTS: Of 44 patients examined, 20 showed NED. The distribution of patients with positive or negative NED in terms of age, tumor differentiation, tumor size, and the extent of tumor or lymph node metastasis showed no significant difference. The cumulative survival rates of patient groups according to NED status were then calculated, and NED positive patients showed a significantly better survival rate (P < 0.05). Univariate and multivariate analyses of those factors showed that only NED status and TNM stage were significantly related to overall survival. CONCLUSIONS: The current study suggests the significance of NED status in determining the outcome of patients with pancreatic adenocarcinoma, giving solid evidence to encourage further studies on the differentiation and origin of tumor cells in the pancreas.

Publication Type: Journal Article.

<16>

Unique Identifier [PMID]: 11114622

Authors: Lo CY. Chan FL. Tam SC. Cheng PW. Fan ST. Lam KS.

Institution: Department of Surgery, University of Hong Kong Medical Centre, Queen Mary Hospital, Hong Kong.

Title: Value of intra-arterial calcium stimulated venous sampling for regionalization of pancreatic insulinomas.

Source: Surgery. 128(6):903-9, 2000 Dec.

Abstract: BACKGROUND: Intra-arterial calcium stimulation with hepatic venous sampling (ASVS) for insulin gradients has been reported to be the most sensitive preoperative localizing technique for insulinomas. We reviewed our experience with ASVS to localize and guide the treatment of insulinomas over the past decade. METHODS: Eighteen patients who underwent ASVS before surgical exploration for insulinoma were studied. The accuracy of ASVS was compared with intraoperative findings and other localizing studies. RESULTS: There were no complications arising from the procedures. A more than 2-fold step-up in insulin level 30 to 60 seconds after injection to at least 1 feeding artery was observed in 16 patients. Fourteen of the 16 solitary tumors (87.5%) were correctly located; 100% (6/6 tumors) at the head and 80% (8/10 tumors) at the body/tail. The overall accuracy of this test was 89%, compared with 11%, 33%, 38%, and 63% of ultrasonography, computed tomography, magnetic resonance imaging, and endoscopic ultrasonography, respectively. Six enucleations and 10 distal resections were performed, which included 2 laparoscopic procedures. The combination of intraoperative ultrasonography with preoperative ASVS identified all tumors. CONCLUSIONS: ASVS is the most accurate preoperative localization tool for the localization of insulinomas and, in combination with intraoperative ultrasonography, can enhance surgical success.

Publication Type: Journal Article.

<17>

Unique Identifier [PMID]: 10443803

Authors: Boukhman MP. Karam JM. Shaver J. Siperstein AE. DeLorimier AA. Clark OH.

Institution: Department of Surgery, University of California, San Francisco 94115, USA.

Title: Localization of insulinomas.

Source: Archives of Surgery. 134(8):818-22; discussion 822-3, 1999 Aug.

Abstract: HYPOTHESIS: Intraoperative ultrasonography is more sensitive than preoperative and other intraoperative techniques for localizing insulinoma. DESIGN: Retrospective review. SETTING: A tertiary referral center. PATIENTS: All patients with a biochemical diagnosis of organic hyperinsulinism who were referred to University of California, San Francisco, from 1975 to 1998. METHODS: Sensitivities of the localization techniques for insulinoma were evaluated. RESULTS: The sensitivities of tumor localization with arteriography, computed tomography, preoperative ultrasonography, magnetic resonance imaging, magnetic resonance imaging with gadolinium, transhepatic venous sampling, palpation, and intraoperative ultrasonography were 47%, 24%, 50%, 30%, 40%, 55%, 76%, and 91%, respectively. Nine of the 11 nonpalpable and nonvisible tumors at operation were localized by intraoperative ultrasonography. CONCLUSION: The currently available preoperative localization tests are not reliable enough to be recommended when intraoperative ultrasonography is available.

Publication Type: Journal Article.

<18>

Unique Identifier [PMID]: 9854595

Authors: Proye C. Malvaux P. Pattou F. Filoche B. Godchaux JM. Maunoury V. Palazzo L. Huglo D. Lefebvre J. Paris JC.

Institution: Department of General and Endocrine Surgery, University Hospital, Lille, France.

Title: Noninvasive imaging of insulinomas and gastrinomas with endoscopic ultrasonography and somatostatin receptor scintigraphy.

Source: Surgery. 124(6):1134-43; discussion 1143-4, 1998 Dec.

Abstract: BACKGROUND: Classic morphological techniques are of limited value for imaging endocrine duodenopancreatic tumors, and invasive procedures such as intraarterial stimulation are often used. Two noninvasive procedures, endoscopic ultrasonography (EUS) and somatostatin receptor scintigraphy (SRS), were recently described with promising results. METHODS: In this study we correlated the results of preoperative EUS (n = 34) and SRS (n = 30) with operative findings in patients with histologically proven insulinoma (n = 20) or gastrinoma (n = 21). RESULTS: The sensitivity and positive predictive value (PPV) of EUS were respectively 77% and 94% for pancreatic tumors (insulinomas and gastrinomas), 40% and 100% for duodenal gastrinomas, and 58% and 78% for metastatic lymph nodes. The sensitivity and PPV of SRS for insulinoma were 60% and 100%, respectively. In patients with gastrinoma, the sensitivity and PPV of SRS were respectively 25% and 100% for pancreatic gastrinomas, 72% and 100% for duodenal gastrinomas or periduodenal metastatic lymph nodes, and 67% and 80% for liver metastasis. In patients with multiple endocrine neoplasia, neither one of the two techniques detected all tumors. Overall sensitivity of combined EUS and SRS was 89% for insulinoma (n = 9) and 93% for gastrinoma (n = 14). CONCLUSIONS: EUS and SRS for gastrinomas and insulinomas should be considered as the initial preoperative imaging procedures and may render invasive procedures unnecessary for most patients.

Publication Type: Journal Article.

<19>

Unique Identifier [PMID]: 9494488

Authors: Pereira PL. Roche AJ. Maier GW. Huppert PE. Dammann F. Farnsworth CT. Duda SH. Claussen CD.

Institution: Department of Diagnostic Radiology, Eberhard-Karls-University, Tubingen, Germany.

Title: Insulinoma and islet cell hyperplasia: value of the calcium intraarterial stimulation test when findings of other preoperative studies are negative.

Source: Radiology. 206(3):703-9, 1998 Mar.

Abstract: PURPOSE: To evaluate the efficacy of the intraarterial calcium test in localizing sources of hyperinsulinism that remain undetectable at preoperative morphologic studies. MATERIALS AND METHODS: Twenty-four patients with clinically proved endogenous hyperinsulinism due to tumorous insulin production were prospectively enrolled. They underwent ultrasound (US), computed tomography, magnetic resonance imaging, endoscopic US, abdominal arteriography, and a calcium test, in which insulin concentrations were measured in hepatic venous blood after selective intraarterial calcium stimulation. The results of the calcium test in seven patients (five women, two men; age range, 30-66 years; mean age, 47 years) with negative findings of morphologic studies are described. RESULTS: Six solitary insulinomas (mean diameter, 0.73 cm) and one nodular hyperplasia were diagnosed after surgery. In all seven cases, calcium test findings allowed accurate localization of the pathologic source of insulin secretion. In three of these seven cases, results of arterial calcium stimulation with hepatic venous sampling (ASVS) affected intraoperative management. An increase in insulin concentration after stimulation in the hepatic artery was not observed, making hepatic metastases unlikely. CONCLUSION: ASVS, which is procedurally simpler than transhepatic pancreatic venous sampling, is effective for localizing sources of hyperinsulinism not detected with preoperative morphologic studies.

Publication Type: Journal Article.

<20>

Unique Identifier [PMID]: 9445232

Authors: Huai JC. Zhang W. Niu HO. Su ZX. McNamara JJ. Machi J.

Institution: Department of Surgery, Second Affiliated Hospital, Henan Medical University, Zhengzhou, PR China.

Title: Localization and surgical treatment of pancreatic insulinomas guided by intraoperative ultrasound.

Source: American Journal of Surgery. 175(1):18-21, 1998 Jan.

Abstract: BACKGROUND: Approximately 20% to 60% of insulinomas cannot be localized preoperatively, and 10% to 20% cannot be found even during surgery. The operative complications associated with the blind surgical explorations are relatively high. METHODS: Between January 1987 and December 1995, intraoperative ultrasound was used to localize insulinomas and guide surgical procedures in 28 patients. RESULTS: Insulinomas were found by intraoperative systematic palpation in 24 patients (85.7%), while intraoperative ultrasound localized the tumors in 27 patients (96.4%). By the combination of these two techniques, all tumors were discovered. The surgical procedures were guided by intraoperative ultrasound. The operative complication rate was 14.3%. CONCLUSION: Intraoperative ultrasound can accurately localize insulinoma, and delineate the spatial relationship between tumor and vital structures, such as pancreatic duct, common bile duct, and critical blood vessels. It can thereby help to increase the successful rate of surgery and avoid unnecessary blind pancreatectomy.

Publication Type: Journal Article.

<21>

Unique Identifier [PMID]: 9267281

Authors: Lo CY. Lam KY. Kung AW. Lam KS. Tung PH. Fan ST.

Institution: Department of Surgery, University of Hong Kong, Queen Mary Hospital, People's Republic of China.

Title: Pancreatic insulinomas. A 15-year experience.

Source: Archives of Surgery. 132(8):926-30, 1997 Aug.

Abstract: OBJECTIVE: To describe our experience in the management of patients with pancreatic insulinomas, emphasizing the need for preoperative localization and the outcome of surgical treatment. DESIGN: A case series. SETTING: A university hospital in Hong Kong. PATIENTS: From 1981 to 1995, 27 patients with pancreatic insulinomas were surgically treated; the mean follow-up was 25.4 months. MAIN OUTCOME MEASURES: Postoperative morbidity and euglycemia during the follow-up period. RESULTS: The accuracy of tumor localization by ultrasonography, computed tomography, and angiography was 33%, 44%, and 52%, respectively. Venous sampling for an insulin assay regionalized 90% of the tumors. In 24 patients with solitary tumors, most lesions detected or missed by preoperative localization could be either seen (n = 14) or palpated (n = 22). Intraoperative ultrasonography (n = 17) has been routinely performed since 1987; nonpalpable tumors were imaged in 2 of 15 patients with solitary tumors. Eight solitary occult tumors were detected by palpation alone or a combination of palpation and intraoperative ultrasonography. Operative mortality occurred in 1 (3.7%) of the 27 patients, while major morbidity developed in 9 (33%) of the patients. Euglycemia was achieved in 25 patients. Surgery cured all patients with benign insulinomas, whereas the cure rate for patients with malignant neoplasms was only 33%. The type of surgical treatment or correct preoperative localization did not affect the outcome of surgery. CONCLUSIONS: Pancreatic insulinomas can be readily localized intraoperatively despite failed preoperative localization studies. Surgical treatment cured benign adenomas but was associated with notable morbidity.

Publication Type: Clinical Trial. Journal Article.

<22>

Unique Identifier [PMID]: 9145069

Authors: Kisker O. Bartsch D. Weinel RJ. Joseph K. Welcke UH. Zaraca F. Rothmund M.

Institution: Department of General Surgery, University Hospital, Philipps-University Marburg, Germany.

Title: The value of somatostatin-receptor scintigraphy in newly diagnosed endocrine gastroenteropancreatic tumors.

Source: Journal of the American College of Surgeons. 184(5):487-92, 1997 May.

Abstract: BACKGROUND: Conventional imaging techniques do not routinely detect endocrine gastroenteropancreatic tumors preoperatively. The purpose of this study was to determine whether the new technique of somatostatin-receptor scintigraphy would improve the detection rate of these tumors before initial treatment. STUDY DESIGN: In a prospective study, 55 patients with a recent diagnosis of endocrine gastroenteropancreatic tumors (22 intestinal carcinoids, 17 gastrinomas, 10 nonfunctioning pancreatic tumors, and 6 insulinomas), were examined with somatostatin-receptor scintigraphy, computed tomography, and ultrasonography. Results of the three imaging modalities were compared with findings at surgical exploration. RESULTS: None of the insulinomas were localized by somatostatin-receptor scintigraphy, but 4 of 6 insulinomas were detected by computed tomography and ultrasonography. Of 17 gastrinomas, 9 were detected by somatostatin-receptor scintigraphy; computed tomography and ultrasonography localized only 7. Metastases from the gastrinoma were localized by somatostatin-receptor scintigraphy in all cases; computed tomography and ultrasonography detected metastases in only 6 of 9 patients. Nonfunctioning tumors could be localized by somatostatin-receptor scintigraphy, computed tomography, and ultrasonography in 4, 7, and 8 of 10 cases, respectively. Detection rate for corresponding metastases was the same for all three imaging techniques. Primary carcinoids were identified by somatostatin-receptor scintigraphy, ultrasonography, and computed tomography in 7, 8, and 11 of 22 cases, respectively. Extra-abdominal metastases were detected by somatostatin-receptor scintigraphy in only 7 of 19 patients. CONCLUSIONS: In patients with insulinomas, somatostatin-receptor scintigraphy is not indicated because none of the six tumors was imaged. This holds true for nonfunctional pancreatic endocrine tumors and their metastases because no advantage for somatostatin-receptor scintigraphy was found over computed tomography and ultrasonography. In contrast, somatostatin-receptor scintigraphy is superior to computed tomography and ultrasonography for determining the extent of the disease in patients with gastrinomas or carcinoids. The problem of detecting primary tumors in these patients is not solved by somatostatin-receptor scintigraphy.

Publication Type: Journal Article.

<23>

Unique Identifier [PMID]: 8944566

Authors: Zimmer T. Stolzel U. Bader M. Koppenhagen K. Hamm B. Buhr H. Riecken EO. Wiedenmann B.

Institution: Departmnt of Internal Medicine/Gastroenterology, Klinikum Benjamin Franklin, Frele Universitat Berlin, Germany.

Title: Endoscopic ultrasonography and somatostatin receptor scintigraphy in the preoperative localisation of insulinomas and gastrinomas.

Source: Gut. 39(4):562-8, 1996 Oct.

Abstract: BACKGROUND: Endoscopic ultrasonography (EUS) and somatostatin receptor scintigraphy (SRS) can detect a high percentage of gastroenteropancreatic neuroendocrine tumours especially in the upper gastrointestinal tract. The ability of these procedures to localise primary tumour lesions and metastases of gastrinomas and insulinomas was evaluated in comparison with transabdominal ultrasonography (US), computed tomography (CT) and magnetic resonance imaging (MRI). PATIENTS AND METHODS: In a prospective trial, patients with gastrinomas (n = 10) and insulinomas (n = 10) diagnosed by clinical signs and laboratory tests were assessed by EUS, SRS, US, CT and MRI. RESULTS: In 10 patients with gastrinoma and 10 patients with insulinoma, a total of 14 separate primary tumour lesions were histologically confirmed for each of the tumour entities. The mean diameter was 2.1 cm for gastrinomas and 1.5 cm for insulinomas. All insulinomas and nine gastrinoma lesions were located in the pancreas. Three gastrinomas were found in the duodenal wall, one in a periduodenal lymph node, and one in the liver, For gastrinomas, sensitivities were 79% with EUS, 86% with SRS and 29% with CT, US, and MRI. For insulinomas, sensitivities were 93% with EUS, 14% with SRS, 21% with CT and 7% with US and MRI. CONCLUSIONS: EUS is of high value for localising primary lesions of both tumour entities. SRS is a very sensitive procedure for diagnosing of gastrinomas but not insulinomas. CT, US and MRI are primarily useful for visualising metastases.

Publication Type: Journal Article.

<24>

Unique Identifier [PMID]: 7559869

Authors: Gorden P. Skarulis MC. Roach P. Comi RJ. Fraker DL. Norton JA. Alexander HR. Doppman JL.

Institution: Diabetes Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.

Title: Plasma proinsulin-like component in insulinoma: a 25-year experience.

Source: Journal of Clinical Endocrinology & Metabolism. 80(10):2884-7, 1995 Oct.

Publication Type: Journal Article.

<25>

Unique Identifier [PMID]: 7611598

Authors: Axelrod L.

Title: Insulinoma: cost-effective care in patients with a rare disease.[comment].

Comments Comment on: Ann Intern Med. 1995 Aug 15;123(4):269-73; PMID: 7611592

Source: Annals of Internal Medicine. 123(4):311-2, 1995 Aug 15.

Publication Type: Comment. Editorial.

<26>

Unique Identifier [PMID]: 7611592

Authors: Doppman JL. Chang R. Fraker DL. Norton JA. Alexander HR. Miller DL. Collier E. Skarulis MC. Gorden P.

Institution: Diagnostic Radiology Department, Clinical Center, National Institutes of Health, Bethesda, MD 20892-1182, USA.

Title: Localization of insulinomas to regions of the pancreas by intra-arterial stimulation with calcium.[see comment][erratum appears in Ann Intern Med 1995 Nov 1;123(9):734].

Comments Comment in: Ann Intern Med. 1995 Aug 15;123(4):311-2; PMID: 7611598

Source: Annals of Internal Medicine. 123(4):269-73, 1995 Aug 15.

Abstract: OBJECTIVE: To determine the sensitivity of calcium injected into pancreatic arteries in localizing insulin-secreting tumors to regions of the pancreas. DESIGN AND PATIENTS: To stimulate the release of insulin, 25 patients with surgically proven insulinomas (average diameter, 15 mm) had calcium gluconate (0.025 mEq Ca++/kg body weight) injected before surgery into the arteries supplying the pancreatic head (gastroduodenal and superior mesenteric arteries) and the body and tail (splenic artery) of the pancreas. SETTING: Tertiary referral hospital. MEASUREMENTS: Insulin levels were measured in samples taken from the right and left hepatic veins before and 30, 60, and 120 seconds after calcium injection. A twofold increase in insulin level in the sample taken from the right hepatic vein 30 or 60 seconds after injection localized the insulinoma to the segment of the pancreas supplied by the selectively injected artery. Localization done using calcium stimulation was compared with localization done using transcutaneous ultrasonography (n = 22), computed tomography (n = 23), magnetic resonance imaging (n = 21), arteriography (n = 25), and portal venous sampling (n = 9). RESULTS: Calcium stimulation localized 22 of 25 insulinomas (sensitivity, 88% [95% CI, 68% to 97%]) to the correct region of the pancreas. The sensitivities of the other imaging methods were 9% for ultrasonography (CI, 1% to 23%), 17% for computed tomography (CI, 5% to 39%), 43% for magnetic resonance imaging (CI, 22% to 66%), 36% for arteriography (CI, 18% to 57%), and 67% for portal venous sampling (CI, 30% to 93%). Calcium stimulation added only a few minutes to the time needed for pancreatic arteriography and caused no morbid conditions. CONCLUSION: Intra-arterial calcium stimulation with right hepatic vein sampling for insulin gradients is the most sensitive preoperative test for localizing insulinomas.

Publication Type: Journal Article.

<27>

Unique Identifier [PMID]: 8175958

Authors: Kao PC. Taylor RL. Service FJ.

Institution: Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota 55905.

Title: Proinsulin by immunochemiluminometric assay for the diagnosis of insulinoma.

Source: Journal of Clinical Endocrinology & Metabolism. 78(5):1048-51, 1994 May.

Abstract: We used a newly developed immunochemiluminometric assay of proinsulin to determine its relative utility vis-a-vis C-peptide and insulin for the diagnosis of insulinoma. The evaluation was conducted in 20 consecutive patients with histologically confirmed insulinoma and 22 normal subjects who underwent a prolonged fast according to a standard protocol. Patients with insulinoma fasted to the point of demonstrating Whipple's triad; normal subjects fasted to 72 h. At the end of the prolonged fast, when the glucose value was 2.8 mmol/L or less (50 mg/dL), all three hormones had equal sensitivity (100%) in detecting insulinoma with no overlap with the values of normal subjects. When glucose levels were between 2.8 mmol/L (50 mg/dL) and 3.3 mmol/L (60 mg/dL) at the end of the prolonged fast, proinsulin was better than C-peptide and insulin in the diagnosis of insulinoma. The sensitivity was 90% for proinsulin and 85% for both C-peptide and insulin. Therefore, proinsulin not only is useful for the diagnosis of insulinoma, but it may have greater diagnostic accuracy than C-peptide and insulin.

Publication Type: Journal Article.

<28>

Unique Identifier [PMID]: 8345050

Authors: O'Brien T. O'Brien PC. Service FJ.

Institution: Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota 55905.

Title: Insulin surrogates in insulinoma.

Source: Journal of Clinical Endocrinology & Metabolism. 77(2):448-51, 1993 Aug.

Abstract: Universally accepted criteria for relative hyperinsulinemia have not been established for the diagnosis of insulinoma. Therefore, we sought measures of insulin action which might act as surrogates for insulin measurements and thereby contribute to the assessment of hyperinsulinemia. Since insulin is antilipolytic, antiketogenic, and glycogenic we measured plasma beta-hydroxybutyrate, FFA, and the response of plasma glucose to iv glucagon at the end of the prolonged fast in 40 patients, later confirmed histologically to have insulinoma and 25 normal persons. Plasma beta-hydroxybutyrate and FFA concentrations were significantly lower in the patients with insulinoma (median, range), (0.3, 0.1-2.7 vs. 4.5, 1.2-7.0 mmol, P < 0.0001, and 1.03, 0.17-1.75 vs. 1.79, 1.17-3.12 mmol, P < 0.001, respectively), whereas the responses of plasma glucose to glucagon were significantly greater (3.0, 1.4-5.4 vs. 0.7, 0.0-1.3 mmol, P < 0.001) than in the normals. For patients with insulinoma (20/40) and normal subjects (13/25) with plasma glucose less than or equal to 3.3 mmol and plasma insulin and C-peptide concentrations in the normal overnight fasting range, conditions in which hyperinsulinemia is most difficult to assess, a clear distinction was provided by plasma glucose response to glucagon and plasma beta-hydroxybutyrate but not by plasma FFA, plasma insulin, nor plasma C-peptide. We conclude that plasma glucose response to iv glucagon greater than or equal to 1.4 mmol and plasma beta-hydroxybutyrate less than or equal to 2.7 mmol, at the end of the prolonged fast are indicative of hyperinsulinemia of insulinoma when the plasma glucose is less than or equal to 3.3 mmol. In this plasma glucose range these insulin surrogates provide better diagnostic accuracy than plasma insulin and C-peptide.

Publication Type: Journal Article.

<29>

Unique Identifier [PMID]: 1558498

Authors: Pasieka JL. McLeod MK. Thompson NW. Burney RE.

Institution: Department of Surgery, University of Michigan, Ann Arbor 48109-0331.

Title: Surgical approach to insulinomas. Assessing the need for preoperative localization.

Source: Archives of Surgery. 127(4):442-7, 1992 Apr.

Abstract: The purpose of this study was to examine our experience with the diagnosis, surgical approach, and outcomes of surgery for organic hyperinsulinemia in the era of transhepatic venous sampling. During the period from 1978 to 1991, 50 patients were evaluated and treated for hyperinsulinemia at the University of Michigan Medical Center, all of whom underwent preoperative localization. Forty-one patients (82%) had solitary, benign tumors; four (8%) had either multiple tumors or islet cell dysplasia; and five (10%) had metastatic disease. Forty-seven patients underwent laparotomy, and the source of the hyperinsulinemia was found in all patients. In three patients (6%) preoperative localization did not accurately locate the tumor due to technical difficulties with the completion of the studies. Overall, computed tomography localized nine (26%) of 35 tumors. Angiography accurately localized 18 (44%) of 41 tumors. Transhepatic venous sampling localized 34 (94%) of 36 tumors, and was essential to successful surgical treatment in 15 patients. Compared with angiography, transhepatic venous sampling was a more accurate method of localization and should be performed in all patients in whom computed tomography and visceral angiography do not clearly identify the site of disease. Preoperative localization plays a critical role in the surgical treatment of patients with organic hyperinsulinemia and eliminates the need for blind pancreatic resection.

Publication Type: Journal Article.

<30>

Unique Identifier [PMID]: 1745987

Authors: Doherty GM. Doppman JL. Shawker TH. Miller DL. Eastman RC. Gorden P. Norton JA.

Institution: Surgical Metabolism Section, National Cancer Institute, National Institutes of Health, Bethesda, Md 20892.

Title: Results of a prospective strategy to diagnose, localize, and resect insulinomas.

Source: Surgery. 110(6):989-96; discussion 996-7, 1991 Dec.

Abstract: Since 1982, 25 consecutive patients with benign sporadic (non-multiple endocrine neoplasia type I) insulinomas have been studied. Most were referred because either the tumor was not identified at the referring institution or the diagnosis was unclear. Each patient suffered severe neuroglycopenic symptoms for a median of 24 months before diagnosis of insulinoma, and 32% had hypoglycemic seizures. Eighteen patients (72%) had a confirmed weight gain. Each patient underwent a supervised fast until 72 hours or the onset of significant neuroglycopenic symptoms (median duration 16 hours), with serum levels of glucose (median 35 mg/dl; range 24 to 46 mg/dl), insulin (median 21 microU/ml; range 11 to 230 microU/ml), C-peptide (median 2.5 ng/ml; range 1.0 to 7.2 ng/ml), and proinsulin fraction (median 55%; range 14% to 86%) measured at the termination of the fast. Preoperative imaging with ultrasonography, computed tomography, magnetic resonance, and angiography visualized tumor in a minority of patients (26%, 17%, 25%, and 35%, respectively); in 48% of patients one or more imaging study results was positive. Selective portal venous sampling for insulin was the most informative localizing test (77% positive; no false-positive results). Tumor was resected for cure in 24 of 25 patients. Intraoperative ultrasonography identified nonpalpable tumor in seven patients and was crucial to the achievement of this high rate of surgical cure. We conclude that the diagnosis of insulinoma can be made by the results of a supervised fast, portal venous sampling is the most sensitive preoperative test for localizing insulinomas, and intraoperative ultrasonography is essential for intraoperative detection of insulinomas.

Publication Type: Journal Article.

<31>

Unique Identifier [PMID]: 1984627

Authors: Vinik AI. Delbridge L. Moattari R. Cho K. Thompson N.

Institution: Department of Surgery, University of Michigan Medical Center, Ann Arbor 48109-0331.

Title: Transhepatic portal vein catheterization for localization of insulinomas: a ten-year experience.[see comment].

Comments Comment in: Surgery. 1993 Apr;113(4):478; PMID: 8456408

Source: Surgery. 109(1):1-11; discussion 111, 1991 Jan.

Abstract: One of the most important factors in the management of insulinomas is the ability to localize the tumor accurately either before or during surgery. We prospectively carried out transhepatic portal venous sampling (THPVS) for tumor localization in 35 of 40 patients with organic hyperinsulinism during a 10-year period. In 32 patients who underwent THPVS and in whom a single tumor was subsequently identified surgically, the maximal insulin gradient was located in the vicinity of the tumor in 100% of cases. Specific regionalization of the tumor on the basis of the site of the maximal insulin gradient to one of three regions (the tail, the body/neck region, and the head/uncinate region) gave a sensitivity of 81% and a specificity of 91%. In contrast, the use of specific cutoff levels for the insulin gradient as a guide to the presence of a tumor in one of these three regions did not increase the accuracy, leading instead to a significant loss of sensitivity with no comparable increase in specificity. There were no major complications from the procedure in any patient. The initial use of computed tomographic/ultrasound scanning and selective angiography localized only 46% of tumors, whereas subsequent THPVS led to the accurate preoperative localization of 100% of all tumors submitted to surgery. Although the surgeon would have identified 81% of the tumors correctly at operation, in 19% (n = 6) he would have failed. Four tumors were in the uncinate and two were in the head. It seems that in patients with proved or established organic hyperinsulinism, THPVS may continue to be of value, if only to regionalize the tumor, especially those in the pancreatic head and uncinate process so as to preclude noncurative operations on the body and tail of the pancreas.

Publication Type: Journal Article.

<32>

Unique Identifier [PMID]: 1984311

Authors: Doppman JL. Miller DL. Chang R. Shawker TH. Gorden P. Norton JA.

Institution: Diagnostic Radiology Department, Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, MD 20892.

Title: Insulinomas: localization with selective intraarterial injection of calcium.[erratum appears in Radiology 1993 Jun;187(3):880].

Source: Radiology. 178(1):237-41, 1991 Jan.

Abstract: To facilitate the noninvasive preoperative localization of islet cell tumors less than 15 mm in diameter, the authors examined the use of calcium as an insulin secretagogue in an arterial stimulation venous sampling (ASVS) technique. In four patients with episodic hypoglycemia, calcium gluconate (0.01-0.025 mEq Ca2+/kg) was injected directly into branches of the celiac plexus (gastroduodenal, splenic, and hepatic arteries) and the superior mesenteric artery. In all patients, serum levels of insulin rose abruptly in blood samples taken from the right hepatic vein 30 and 60 seconds after the infusion of calcium into the artery supplying the tumor; injection into an artery not supplying the tumor did not result in a similar rise. Accurate localization of the insulinomas was verified at surgery in three patients. In the fourth patient, who did not undergo surgery, arteriographic results were positive for insulinoma at the predicted site. On the basis of these results, the authors believe noninvasive ASVS may replace invasive portal venous sampling as the most effective method for the localization of occult insulinomas.

Publication Type: Case Reports. Journal Article.