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ENETS Consensus Guidelines for the Management of Patients with Liver and Other Distant Metastases from Neuroendocrine Neoplasms of Foregut, Midgut, Hindgut, and Unknown Primary

a Division of Hepatology and Gastroenterology, Department of Internal Medicine, Campus Virchow-Klinikum, Charite-Universitatsmedizin Berlin, Berlin , Germany; b Department of Pathology, Universitatsspital, Zurich , Switzerland; c Division of General Surgery, Department of Surgery, Medical University of Vienna, Vienna , Austria; d Department of Endocrinology and Metabolism, Hadassah University Hospital, Jerusalem , Israel; e Department of Internal Medicine, Philipps University, Marburg , Germany; f Hopital Sirio Libanes, Centro de Oncologia, Sao Paulo , Brazil; g Department of Radiology, Campus Virchow-Klinikum, Charite, University Medicine Berlin, Berlin , Germany; h Department of Oncology, Institut Catala d’Oncologia (IDIBELL), Barcelona , Spain; i Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, University of Oxford, Oxford , UK

a Department of Gastroenterology, Beaujon Hospital, Clichy , France; b Department of Oncology, Institut Catala d’Oncologia, Barcelona , Spain; c Department of Surgery, Verona University, Verona , Italy; d Department of Endocrinology and Metabolism, Genimatas Hospital, Athens , Greece; e Department of Gastroenterology, Beaujon Hospital, Clichy , France; f Department of Endocrinology, Erasmus MC University, Rotterdam , The Netherlands; g Department of Internal Medicine, Martin University, Martin , Slovakia; h Department of Propaedeutic Internal Medicine, Laiko Hospital, Athens , Greece; i Department of Nuclear Medicine, Erasmus MC University, Rotterdam , The Netherlands; j Department of Gastroenterology, Beaujon Hospital, Clichy , France; k Department of Gastroenterology, Royal Free Hospital, London , UK; l Department of Cell Biology, National Institute of Health, Bethesda, Md. , USA; m Department of Endocrinology, University Hospital, Uppsala , Sweden

A 45-year-old female had been suffering for about 6 months almost daily from paroxysmal neck swellings with occasional difficulties in swallowing and from non-specific abdominal complaints. Hormone analyses, performed because of the marked blood pressure increase up to 210/120 mm Hg during such an attack, revealed an increase in vanillyl mandelic acid and epinephrine concentrations in the 24-hour urine. CT demonstrated a tumour of 4 x 5 x 5 cm size in the region of the right adrenal. The paroxysmal neck swellings and blood pressure increase could be reproduced by means of pressure applied over the tumour range with the ultrasound transducer. The tumour was extirpated and histology revealed a phaeochromocytoma. For more than one year now the patient has been free from complaints. To date, recurrent neck swellings have not been reported in association with a phaeochromocytoma. Possible causes may be an enhanced congestion of the deep neck vessels during paroxysmal blood pressure increase or an enhanced response by the adrenoreceptors of these vessels to the released catecholamines.

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

Consensus guidelines for the management of patients with digestive neuroendocrine tumors : well-differentiated jejunal-ileal tumor/carcinoma

a Department of Pathology, Gothenburg University, Gothenburg , Sweden; b Department of Gastroenterology, Gasthuisberg University, Leuven , Belgium; c Department of Gastroenterology, Ospedale S. Andrea, Rome , Italy; d Department of Oncology, University of Texas, Houston, Tex. , USA; e Department of Endocrinology, Erlangen University, Erlangen , Germany; f Department of Oncology and Pathology, Royal Infirmary Hospital, Glasgow , UK; g Department of Oncology, Virgen de la Victoria Hospital, Malaga , Spain; h Department of Nuclear Medicine, Medizinische Hochschule Hannover, Hannover , Germany; i Department of Endocrinology, Erciyes University, Kayseri , Turkey; j Department of Surgery, Beaujon Hospital, Clichy , France; k Department of Nuclear Medicine, Catholique de Louvain University, Brussels , Belgium; l Department of Nuclear Medicine, Erasmus MC University, Rotterdam , The Netherlands; m Department of Gastroenterology, Royal Free Hospital, London , UK

PURPOSE The characterization of different liver tumors is of therapeutic and prognostic relevance and has been the purpose of several studies. Although ultrasound offers the opportunity to detect hepatic tumors without ionizing radiation, its previous techniques did not lead toward a definitive differentiation of different tumor entities. The purpose of this study was the clinical evaluation of contrast enhanced ultrasound followed by quantitative digital analysis in patients with focal hepatic tumors. MATERIALS AND METHODS In a prospective study, 50 patients (18 females, 32 males, age 28 to 83 years, mean age 59.4 years) with liver tumors previously detected by CT (n = 47) or MRI (n = 3) were examined by ultrasound of the upper abdomen using conventional technique and phase inversion technique after intravenous application of sulfur-based contrast enhancer SonoVue. At scheduled intervals after application of the contrast enhancer, a digital image was stored and the characteristic signal course of each lesion determined semiquantitatively. The gold standard was either resection (n = 17), percutaneous needle biopsy (n = 19) or the clinical course (n = 14). RESULTS While the percentage of tumors correctly characterized by CT/MRI amounted to 78 %, the percentage increased from 60 % using conventional ultrasound to 86 % using contrast enhanced ultrasound including grey-scale analysis. Typical graphs were achieved for different tumor entities on digital grey-scale analysis. The optimal intervals for the differentiation of particular entities were 20 and 100 seconds after injection. CONCLUSION Quantification of contrast enhanced ultrasound is an addition to the previous diagnostic procedure in hepatic tumors. It offers the possibility of an investigator-independent characterization of lesions and should be evaluated in further studies.

Die Indikationsstellung zur operativen Therapie hepatisch metastasierter neuroendokriner Tumoren (NET) sollte in ein multidisziplinares Therapiekonzept eingebettet sein. Eine klare Indikation liegt bei Patienten vor, bei denen ein radikales Vorgehen im Rahmen der chirurgisch-technischen Moglichkeiten zur Tumorfreiheit fuhrt. Trotz hoher Rezidivraten im Langzeitverlauf legitimiert sich die Indikation zum leberchirurgische Eingriff durch Symptompalliation und Hinweise auf ein verbessertes Patientenuberleben bei gleichzeitig niedriger perioperativer Mortalitat in spezialisierten Zentren. Auf dem Boden des Evidenzgrads der vorliegenden Studien ist der Indikationsbereich der palliativen Resektionen zur Tumormassenreduktion und Symptompalliation nicht abschliesend bewertbar. Ahnliches gilt fur Patienten mit hepatisch metastasierten asymptomatischen NET. Jedoch besteht ein Konsens, dass die Tumormassenreduktion um mehr als 90% sinnvoll ist, wenn mit der konservativen Behandlung nur eine unzureichende Palliation erzielt werden kann. Die Indikation zur Lebertransplantation muss restriktiv gehandhabt werden und beschrankt sich auf Einzelfalle.

PURPOSE Due to the shortage of cadaver donors, living related liver donation (LRLD) has emerged as an alternative to cadaver donation. The expected graft weight is one of the main determinants for donor selection. This study investigates the accuracy of preoperatively performed CT-volumetry to predict the actual weight of the right liver lobe graft. MATERIALS AND METHODS In a prospective study the weight of the right hepatic lobe was calculated by volumetric analysis based on CT in 33 patients (21 females, 12 males, mean age 42.1 years, median age 41 years) prior to living related liver donation. Graft weight was calculated as the product of CT-based graft volume and 1.00 g/ml (the approximated density of healthy liver parenchyma). The calculated weight was compared with the intraoperatively measured weight of the harvested right hepatic lobe. The difference was used to determine a correction factor for estimating the actual graft weight. RESULTS Based on the assumption of a parenchymal density of 1.00 g/ml, the preoperatively estimated graft weight (mean 980 g +/- 168 g) deviated +33 % from the intraoperatively measured right hepatic lobe weight (mean 749 g +/- 170 g). By reducing the preoperatively predicted weight of the right hepatic lobe with a correction factor of 0.75, the actual graft weight can be calculated. CONCLUSION Preoperative estimation of the weight of the right hepatic lobe based on CT of living related liver donors predicts the weight of the right lobe graft with sufficient accuracy by applying a single correction factor. Intraoperative fluid loss (i.e., blood, bile) from the harvested liver as well as variations in parenchymal density may contribute to the observed preoperative overestimation of the actual graft volume by CT-based volumetry.

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

We investigated the factors regulating glucose homeostasis in 10 healthy (control) subjects, as well as in stable, long-term, liver-grafted patients receiving monotherapy in the form of either cyclosporin A (n=10) or tacrolimus (n=10).We measured insulin sensitivity, first- and second-phase insulin secretion, with a minimal modeling technique based on the analysis of glucose, insulin, and C-peptide profiles during frequently sampled intravenous glucose tolerance tests (FSIGTT). Proinsulin levels, as a marker of beta-cell dysfunction, were measured in the fasting state and during FSIGTT.Glucose and insulin concentrations before and after glucose loading did not differ in liver transplant patients and in control subjects. Fasting C-peptide levels in both liver-grafted groups were higher than in healthy subjects and remained elevated during FSIGTT (P0.05). Intravenous glucose tolerance [(K(G)), i.e. the slope of the regression of logarithm of the blood glucose concentrations vs. time], insulin sensitivity, and first-phase insulin secretion did not differ in liver-grafted groups and healthy subjects. Second-phase insulin secretion was about 56% higher in liver-grafted patients than in controls (P0.05). Body mass index was the overall determinant of insulin sensitivity in all groups.Long-term monotherapy with cyclosporin A or tacrolimus has no deleterious effects on insulin sensitivity, first-phase insulin secretion, and insulin synthesis in liver transplant patients. Normal insulin sensitivity (posthepatic insulin effect) and enhanced second-phase insulin secretion (prehepatic insulin) point to an accelerated hepatic insulin clearance rate in liver transplant patients. Increased hepatic insulin clearance is compensated by enhanced insulin secretion, indicating that insulin clearance is the major determinant of pancreatic function in liver-grafted patients.