Emanuel Christ

Consensus guidelines for the management of patients with liver metastases from digestive (neuro)endocrine tumors: Foregut, midgut, hindgut, and unknown primary

a DRK Kliniken Westend, Berlin , Germany; b UFR Bichat-Beaujon-Louis Mourier, Service de Chirurgie Digestive, Hopital Louis Mourier, Colombes , France; c Medicine and Surgery, General Surgery Section, MED/18 – General Surgery and d Department of Pathology, University of Verona, Verona , Italy; e Netherlands Cancer Centre, Amsterdam , and f Department of Nuclear Medicine, Erasmus University Medical Center, Rotterdam , The Netherlands;

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

CONTEXT 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. OBJECTIVE 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. DESIGN This was a prospective open-label investigation. SETTING The study was conducted at three tertiary referral centers in Switzerland. PATIENTS Patients included six consecutive patients with proven clinical and biochemical endogenous hyperinsulinemic hypoglycemia. INTERVENTION (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. MAIN OUTCOME MEASURE The detection rate of insulinomas was measured. RESULTS 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. CONCLUSION 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.

Glucagon-like peptide 1-receptor scans to localize occult insulinomas

The precise localization of some insulinomas with the use of conventional imaging techniques is a challenging clinical problem. These findings indicate that GLP-1–receptor scanning may offer a new ...

Consensus guidelines for the management of patients with digestive neuroendocrine tumours: Well-differentiated colon and rectum tumour/carcinoma

a Department of Gastroenterology, North Hampshire Hospital, Basingstoke , UK; b Stadtisches Klinikum Neuss, Lukaskrankenhaus, Chirurgische Klinik I, Neuss , Germany; c Istituto di Radiologia, Policlinco GB Rossi, Verona , Italy; d Institute for Pathology, Kantonsspital, Baden , Switzerland; e Departments of Internal Medicine and Endocrinological and Metabolic Sciences, University of Genoa, Genoa , Italy; f II. Internal Medical Department, University Hospital Martin, Martin , Slovakia; g G. Genimatas Hospital, Athens , Greece; h Erciyes University Medical School, Department of Endocrinology and Metabolism, Kayseri , Turkey; i H. Lee Moffitt Cancer Center/ University of South Florida, Tampa, Fla. , USA; j Anatomie Pathologique, Hopital Edouard Herriot, Lyon , France;

Consensus Guidelines for the Management of Patients with Digestive Neuroendocrine Tumours: Well-Differentiated Tumour/Carcinoma of the Appendix and Goblet Cell Carcinoma

Consensus guidelines for the management of patients with digestive neuroendocrine tumours : well-differentiated tumour/carcinoma of the appendix and goblet cell carcinoma

Glucagon-Like Peptide-1 Versus Somatostatin Receptor Targeting Reveals 2 Distinct Forms of Malignant Insulinomas

Glucagon-like peptide-1 (GLP-1) receptor imaging is superior to somatostatin receptor subtype 2 (sst2) imaging in localizing benign insulinomas. Here, the role of GLP-1 and sst2 receptor imaging in the management of malignant insulinoma patients was investigated. Methods: Eleven patients with malignant insulinoma were prospectively included. 111In-[Lys40(Ahx-diethylenetriaminepentaacetic acid [DTPA])NH2]-exendin-4 SPECT/CT, 68Ga- DOTATATE PET/CT, and in vitro receptor autoradiography were performed to assess the receptor status and to evaluate the detection rate. Results: GLP-1 receptor targeting was positive in 4 of 11 patients, and sst2 receptor expression was positive in 8 of 11. In only 1 patient were both receptors expressed. In 1 patient, GLP-1 receptor imaging was the only method that successfully localized the primary tumor in the pancreas. In 3 patients with sst2-expressing tumors, DOTATATE radiotherapy was effectively applied. Conclusion: As opposed to benign insulinomas, malignant insulinomas often lack GLP-1 receptors. Conversely, malignant insulinomas often express sst2, which can be targeted therapeutically.

Glucagon-like peptide-1 receptor imaging for the localisation of insulinomas: a prospective multicentre imaging study

BACKGROUND Small benign insulinomas are hard to localise, leading to difficulties in planning of surgical interventions. We aimed to prospectively assess the insulinoma detection rate of single-photon emission CT in combination with CT (SPECT/CT) with a glucagon-like peptide-1 receptor avid radiotracer, and compare detection rates with conventional CT/MRI techniques. METHODS In our prospective imaging study, we enrolled adults aged 25-81 years at centres in Germany, Switzerland, and the UK. Eligible patients had proven clinical and biochemical endogenous hyperinsulinaemic hypoglycaemia and no evidence for metastatic disease on conventional imaging. CT/MRI imaging was done at referring centres according to standard protocols. At three tertiary nuclear medicine centres, we used whole body planar images and SPECT/CT of the abdomen up to 168 h after injection of (111)In-[Lys40(Ahx-DTPA-(111)In)NH2]-exendin-4 ((111)In-DTPA-exendin-4) to identify insulinomas. Consenting patients underwent surgery and imaging findings were confirmed histologically. FINDINGS Between Oct 1, 2008, and Dec 31, 2011, we recruited 30 patients. All patients underwent (111)In-DTPA-exendin-4 imaging, 25 patients underwent surgery (with histological analysis), and 27 patients were assessed with CT/MRI. (111)In-DTPA-exendin-4 SPECT/CT correctly detected 19 insulinomas and four additional positive lesions (two islet-cell hyperplasia and two uncharacterised lesions) resulting in a positive predictive value of 83% (95% CI 62-94). One true negative (islet-cell hyperplasia) and one false negative (malignant insulinoma) result was identified in separate patients by (111)In-DTPA-exendin-4 SPECT/CT. Seven patients (23%) were referred to surgery on the basis of (111)In-DTPA-exendin-4 imaging alone. For 23 assessable patients, (111)In-DTPA-exendin-4 SPECT/CT had a higher sensitivity (95% [95% CI 74-100]) than did CT/MRI (47% [27-68]; p=0.011). INTERPRETATION (111)In-DTPA-exendin-4 SPECT/CT could provide a good second-line imaging strategy for patients with negative results on initial imaging with CT/MRI. FUNDING Oncosuisse, the Swiss National Science Foundation, and UK Department of Health.

Assessment of quality of life in patients with uncontrolled vs. controlled acromegaly using the Acromegaly Quality of Life Questionnaire (AcroQoL)

Objective Acromegaly is a chronic disease with an important impact on quality of life. An acromegaly disease‐generated quality of life questionnaire (AcroQoL) has recently been developed. We aimed to confirm reliability, construct validity and disease‐specificity of the AcroQoL questionnaire. Second, we investigated the effect of remission status on health‐related quality of life (HRQoL) in patients with acromegaly.

Well-differentiated duodenal tumor/carcinoma (excluding gastrinomas)

a Digestive Diseases Branch, NIDDK, NIH, Bethesda, Md. , USA; b Dipartimento di Patologia e Medicina di Laboratorio, Universita di Parma, Parma , Italy; c Division of Gastroenterology and Endocrinology, Department of Internal Medicine, Philipps University, Marburg , Germany; d Department of Pathology, IPATIMUP Hospital, Porto , Portugal; e Dipartimento di Fisiopatologia Clinica, Universita di Firenze, Firenze , Italy; f Department of Surgery, Johann-Wolfgang-Goethe-Universitat, Frankfurt , Germany; g E. Christ, Department of Endocrinology, Inselspital, Bern , Switzerland; h Department of Oncology, Netherlands Cancer Centre, Amsterdam , The Netherlands; i Department of Surgery, Rigshospitalet Blegdamsvej Hospital, Copenhagen , Denmark; j Department of Surgery, Gothenburg University, Gothenburg , Sweden; k Department of Nuclear Medicine, Erasmus Medical Center, Rotterdam , The Netherlands; l Service de Gastroenterologie-Pancreatologie, Pole des Maladies de l’Appareil Digestif, Hopital Beaujon, Clichy , France

Association of 1,5-Anhydroglucitol and 2-h Postprandial Blood Glucose in Type 2 Diabetic Patients

OBJECTIVE—To assess the association of 1,5-anhydroglucitol (1,5-AG) with 2-h postprandial glucose values in type 2 diabetic patients followed over 12 months in an outpatient setting. RESEARCH DESIGN AND METHODS—In 55 patients, we examined self-measured postprandial blood glucose values for correlations with 1,5-AG values over prespecified preceding time periods (3 days, 1 week, and weekly up to 12 weeks). RESULTS—The correlation coefficients for postprandial glucose values were −0.34 (P < 0.05) for 3 days, −0.38 (P < 0.001) for 1 week, and −0.40 (P < 0.001) for 2 weeks preceding the measurement of 1,5-AG. Correlations declined for time periods >2 weeks before measurement of 1,5-AG. The correlation was lower with fasting/preprandial plasma glucose levels. There was no time dependency for the correlation between A1C and fasting or postprandial glucose. CONCLUSIONS—1,5-AG best reflected the 2-h postprandial glucose values of the 2 previous weeks.