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In this paper, the solid-state interactions between metastable γ-UMo alloys (containing 5, 7 and 10 wt%Mo) and Al, at temperatures ranging from 440 to 600 °C and for ageing times up to 10 h, are studied using the diffusion couple technique and nuclear fuel plate annealing. The reaction product consists of three main zones, two of them presenting a periodic layered morphology. The growth kinetics is limited by solid-state diffusion and Al is the most mobile species. Both growth kinetics and its global energy of activation are similar to that found for the U/Al binary system. The diffusion path is determined and phase equilibrium relations are deduced for the Mo-poor part of the U–Mo–Al metastable ternary phase diagram.

La reseccion de los tumores endocrinos duodenopancreaticos se realiza despues de un proceso cuyos objetivos son la obtencion de un diagnostico lesional y secretor, asi como la determinacion de si el tumor es esporadico o se asocia a una poliendocrinopatia. El tumor secretor mas frecuente es el insulinoma, que se encuentra en el 8% de las poliendocrinopatias de tipo neoplasia endocrina multiple (MEN 1), pero el gastrinoma es el tumor presente con mas frecuencia (40%) en un contexto de MEN 1. El acceso quirurgico clasico en el insulinoma requiere una exploracion completa de todo el pancreas y en el gastrinoma, de la region duodenal y retro-duodeno-pancreatica. El rendimiento de las pruebas de imagen preoperatorias ha transformado el tratamiento de estos tumores, en especial el de los insulinomas. Estas neoplastias se pueden localizar en el pancreas en la practica totalidad de los casos antes de la intervencion, lo que deja obsoleto el dogma de la exploracion completa de la glandula en la mayoria de los casos. En pacientes con insulinoma, los tumores pequenos y habitualmente benignos deben tratarse mediante una reseccion caudal que respete el pancreas sano. Frente a la enucleacion o a la reseccion corta caudal o segmentaria usada en las formas esporadicas, en la MEN 1 se prefiere una pancreatectomia izquierda asociada a la enucleacion de las lesiones cefalicas. La laparoscopia se ha impuesto rapidamente como el acceso quirurgico de eleccion para el tratamiento del insulinoma esporadico. Esta tecnica aprovecha el rendimiento de las pruebas de imagen preoperatorias para localizar la lesion. El acceso laparoscopico sigue estando en entredicho para las cirugias mas extensas, en especial en el contexto de las poliendocrinopatias. La exploracion quirurgica debe constar de una ecografia intraoperatoria que confirme la localizacion y que precise las relaciones entre el tumor y el conducto de Wirsung. Esta especialmente indicada en caso de acceso laparoscopico que impida la palpacion. El control del caracter completo de la reseccion mediante un analisis rapido de la insulina al final de la intervencion no esta indicado de forma sistematica. En la cirugia del gastrinoma, que siempre se considera potencialmente maligno, hay que realizar una busqueda selectiva de los microtumores de localizacion duodenal, asi como las adenopatias metastasicas retropancreaticas y del pediculo hepatico. La hipoglucemia facticia, que es una causa de intervenciones inutiles, supone un problema destacado. Aunque el diagnostico es facil en caso de autoinyeccion de insulina, gracias a la determinacion del peptido C, es mas dificil en pacientes que toman sulfamidas hipoglucemiantes, que causan un perfil biologico similar al del insulinoma. Ante la minima duda, se debe solicitar una determinacion sanguinea de sulfamidas.

Resume L'hyperparathyroidisme (HPT) dans le cadre de la neoplasie endocrine multiple de type 1 (NEM 1) se manifeste de facon presque constante et souvent precoce. L'atteinte lesionnelle est presque constamment multiglandulaire du fait du stimulus genetique et en cas de parathyroidectomie moins que subtotale, le taux de recidives varie entre 20 et 40 %. La tactique operatoire consiste en la recherche et l'examen de toutes les glandes parathyroides y compris l'(les) eventuelle(s) et frequente(s) glande(s) surnumeraire(s) presente(s) chez 30 % des patients et en la realisation d’une parathyroidectomie subtotale. Une thymectomie transcervicale bilaterale doit toujours y etre associee. De plus l'HPT, parfois severe, stimule la secretion des gastrinomes associes et sa prise en charge chirurgicale peut permettre de reporter l’heure de la chirurgie duodenopancreatique. En cas de recidive de l’HPT, le bilan preoperatoire se focalise sur la recherche d’une hypertrophie du moignon residuel et sur l’existence de glandes surnumeraires. Le geste chirurgical vise a totaliser la parathyroidectomie. La cryopreservation d’une glande peut etre un secours utile en cas d’hypoparathyroidie definitive symptomatique invalidante.

Resume Propos. – Les neoplasies endocriniennes multiples (NEM) sont des affections hereditaires de transmission autosomique dominante caracterisees par la survenue chez plusieurs membres d’une meme famille de lesions endocriniennes diversement associees. La NEM 1 comporte 3 atteintes principales : hyperparathyroidie primaire, tumeur endocrine duodenopancreatique et adenome hypophysaire et de multiples autres lesions associees endocriniennes ou non endocriniennes. La NEM 2 est caracterisee par l’association d’un cancer medullaire de la thyroide et d’un pheochromytome et comporte 2 sous-types, la NEM 2A ou l’on trouve parfois une hyperparathyroidie primaire et la NEM 2B ou existe egalement une ganglioneuromatose. Des formes familiales de cancers thyroidiens medullaires isoles sont egalement decrites. Actualites et points forts. – Le gene NEM 1 est un gene suppresseur de tumeur codant pour une proteine interagissant avec differents facteurs de regulation de la transcription, la menine. Les NEM 2 et les formes familiales de cancer medullaire de la thyroide (CMT) sont liees a des mutations activatrices du proto-oncogene RET, codant pour un recepteur a activite tyrosine kinase. Le developpement des analyses genotypiques permet la reconnaissance des mutations de ces genes et ainsi l’identification des sujets a risque de presenter la maladie, le depistage precoce des differentes lesions et une prise en charge therapeutique adaptee. Perspectives et projets. – Le developpement des travaux de recherche fondamentale permet d’envisager une meilleure comprehension des mecanismes physiopathogeniques des NEM et une amelioration de leur prise en charge therapeutique.

Resume Devant une hypercalcitoninemie persistante apres cervicotomie pour cancer medullaire de la thyroide (CMT), les problemes sont radicalement differents suivant le fait que la cervicotomie initiale a ete adequate ou inadequate. Si elle a ete inadequate, il importe de reprendre la cervicotomie pour realiser le complement d’exerese chirurgicale aboutissant dans tous les cas a une thyroidectomie totale avec curage central et curage jugulocarotidien bilateral. Si la cervicotomie initiale a ete adequate, il faut suspecter un envahissement locoregional ou surtout une maladie systemique et les indications de reintervention doivent etre tres restrictives. Le probleme essentiel est celui de la stadification de la maladie residuelle. Dans cette eventualite, toute l’imagerie preoperatoire doit etre mise en œuvre, jusqu’a et y compris, la laparoscopie pour verifier l’absence de metastase miliaire hepatique. Il n’y a pas d’espoir de cure en cas de maladie systemique et il faut se rappeler que l’hypercalcitoninemie elle-meme peut etre longtemps tres bien toleree durant des decennies, le pronostic etant lie non pas a l’elevation de ce marqueur humoral mais a l’invasion locoregionale et a l’etendue de la maladie systemique. Il n’y a pas d’espoir de cure quand la calcitonine est superieure a 1000 pg/ml. Il n’y a pas d’espoir de possibilite de localisation de la maladie residuelle quand elle est inferieure a 50 pg/ml. Donc, il n’est licite d’envisager de mettre en œuvre les techniques de localisation de la maladie residuelle que pour les taux de calcitonine compris entre 50 et 1000 pg/ml. Un curage mediastinal par sternotomie n’est licite qu’en l’absence de metastase distale et en presence d’un envahissement des ganglions cervicaux les plus caudalement situes lors de la cervicotomie initiale, toujours apres exclusion des metastases hepatiques par laparoscopie. De grands espoirs sont fondes sur la chirurgie radio-immunoguidee en cas de maladie localement invasive et sur la radio-immunotherapie en cas de maladie systemique.

Resume But de l’etude : L’allogreffe intraportale d’ilots de Langerhans parait etre un des traitements prometteurs du diabete de type I, mais de nombreux facteurs limitant persistent. Une activation de la coagulation au contact des ilots, recemment mise en evidence in vitro, pourrait jouer un role decisif dans le declenchement d’une reaction inflammatoire non specifique et faire le lit du rejet immun specifique. L’objectif de cette etude experimentale etait de confirmer in vivo cette activation initiale de la coagulation. Materiel et methodes : Nous avons injecte par voie portale chez des porcs Large White ( n = 26) une preparation d’ilots allogeniques ou un materiel controle (microbilles inertes), associe ou non a un traitement anticoagulant (heparine). Des facteurs de l’hemostase standard et specifiques ont ete doses chez le porc durant les 72 heures suivant l’injection du materiel etudie. Resultats : Une hausse importante des complexes thrombine–antithrombine et une chute des plaquettes, en rapport avec une activation de la coagulation ont ete trouvees dans les groupes recevant des preparations d’ilots. Cette activation etait proportionnelle au volume injecte et a ete prevenue partiellement par l’administration d’heparine. Elle n’etait pas observee chez les porcs recevant le materiel controle. Conclusion : L’activation de la coagulation et la reaction inflammatoire non specifique pourraient donc etre un des obstacles au succes de la greffe d’ilots de Langerhans. L’emploi d’une therapeutique anticoagulante et anti-inflammatoire, utilisable en clinique, permettrait peut-etre en prevenant ces reactions, d’ameliorer les resultats actuels de cette greffe.

Hepatic metastases of gastroenteropancreatic tumors are observed in at least 10% of cases at presentation and in 85% of cases after 20 years of follow-up. They are slow-growing; and there is a 5-year life expectancy that varies between 13% and 60% depending of the degree of differentiation, with occasional survival of more than 20 years. Curative liver resection is the best treatment, with a 4-year survival rate of 73%, but this is possible in only 10% of cases. Chemoembolization is indicated for nonresectable multiple bilobar metastases: 87% of patients respond, half with tumor reduction and the other half with diminution of the symptoms of hypersecretion. The mean survival is 2 years; complete remission of more than 2 years is exceptional. The technique can be repeated but is not without risks, with a possible postembolization syndrome lasting up to 10 days and subsiding spontaneously, without indication for operation. Therefore one lobe only should be embolized at a session. It is not impossible that chemoembolization increases the occurrence of lung metastases. It is only a palliative method but with great functional benefit for patients with hypersecreting tumors.

Resume Nous avons realise une etude clinique d'un nouveau dosage serique de la chromogranine A. Notre etude prospective, sur deux ans, a porte sur un ensemble de 282 serums se repartissant comme suit : groupe Temoins (n = 98), Temoins hypertendus du groupe A (n = 39) et 145 tumeurs neuroendocrines composees de 32 pheochromocytomes, 21 cancers medullaires de la thyroide, 17 tumeurs des ilots pancreatiques, 30 hyperparathyroidies primaires, 15 gastrinomes et 30 carcinomes neuroendocrines. La chromogranine A (Cg A) serique est un marqueur sensible et specifique des tumeurs neuroendocrines. Les resultats les plus probants de notre etude ont ete obtenus pour les pheochromocytomes, les gastrinomes et les tumeurs carcinoides avec des sensibilites respectives de 87,5, 100 et 77 %. Lors du diagnostic de pheochromocytome, les taux de Cg A sont tres significativement correles a la masse tumorale et aux taux de metanephrines urinaires. Ce sont des index precoces pour la radicalisation de l'exerese. Ce dosage serique est peu sensible aux interferences medicamenteuses ou alimentaires. Une etude portant sur le suivi des patients dans le temps fournira des renseignements complementaires de ceux que nous avons obtenus.

Resume Objectif : Evaluer l'incidence des deces d'origine cardiaque en chirurgie generale non cardiovasculaire. Type d'etude : Enquete retrospective. Patients : Ensemble des patients operes dans un service universitaire de chirurgie generale, a orientation endocrinienne et digestive, entre 1991 et 1996. Methodes : Analyse des deces per- et postoperatoires, aussi longtemps que le patient reste hospitalise. Releve des donnees demographiques et medicales, en particulier des cardiopathies ischemiques averees et des facteurs de risque coronarien. Comparaison avec un groupe temoin constitue par l'ensemble des operes du service entre le 1er janvier et le 30 septembre 1996. Resultats : L'etude a porte sur 8 700 operes (66 % en chirurgie cervicale endocrinienne, 31 % en chirurgie abdominale). La mortalite (n = 96) a ete de 1,1 % (intervalle de confiance a 95 % [IC 95 %] = 0,9–1,3 %). La prevalence de l'insuffisance coronarienne ou d'au moins deux facteurs de risque d'atherosclerose coronarienne etait de 24 % en chirurgie cervicale, 31 % en chirurgie abdominale, et 60 % chez les patients decedes (P Conclusion : En chirurgie generale non cardiovasculaire, la mort d'origine cardiaque semble etre une cause rare de deces postoperatoire.

Background The aim of this manuscript is to describe the various possible clinical presentations of pheochromocytomas. Methods Retrospective review of unusual and sometimes fascinating case reports in both authors' experience. Results Catecholamine receptors are so ubiquitous, and the blend of catecholamines secreted by the pheochromocytomas so variable, that an astonishing array of clinical signs and symptoms should raise the suspicion and lead to the diagnosis of pheochromocytomas. Conclusions The clinician should be aware of the overwhelming diversity of clinical presentations of pheochromocytomas.

Resume Nous rapportons le cas d’un patient opere d’un pheochromocytome cardiaque chez qui est survenue une hypotension severe associee a une paraplegie par atteinte medullaire au niveau de la cinquieme vertebre thoracique. L’imagerie par resonance magnetique nucleaire realisee en urgence a mis en evidence un corps etranger (cire hemostatique) dans le canal medullaire et une lesion ischemique de la corne medullaire anterieure droite. L’ablation du corps etranger a ete suivie d’une amelioration rapide de l’etat hemodynamique et d’une limitation des troubles neurologiques (anesthesie en bande et monoparesie inferieure droite). L’association d'une atteinte medullaire et de la perte de la secretion catecholaminergique ectopique peut conduire a des situations hemodynamiques particulierement delicates apres l'exerese d'un pheochromocytome. En presence d’une lesion medullaire apres chirurgie thoracique, l’imagerie par resonance magnetique doit etre l’examen de choix.

In 1850 Sir Richard Owen discovered the parathyroid glands in rhinoceros. After they have been discovered in man in 1880 their history spread all along the 20th century. The history started from the descriptive anatomy and the clinical pictures of their illness to the trouble of their functioning. The hormone was studied while the surgeons began to cure adenoma, hyperplasia and cancers.

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The allograft of pancreatic islets represents a potential alternative to insulin therapy in patients suffering from the most severe forms of Type 1 diabetes. Here we report our experience of pancreatic procurement for isolation and islet allograft.Pancreata were procured in brain-dead donors. The islets were isolated using techniques developed and validated in pigs and men. Injection of a given preparation was decided after quantitative and qualitative controls. Islets were transplanted in Type 1 diabetic patients already grafted with a kidney or suffering from severe and/or unstable diabetes, after percutaneous or surgical settlement of an intra-portal catheter. Patients received an "Edmonton-like" immunosuppressive protocol. Grafts were repeated once or twice until a total quantity of 10,000 transplanted islet-equivalents was obtained.Twenty-nine pancreata were procured and 14 preparations were grafted to 7 patients. Eleven graftings were done percutaneously and three were surgical. The initial function of the 14 transplants was confirmed by secretion of C-peptide and decrease of insulin doses. Insulin therapy was completely interrupted in the 5 patients having received at least two grafts.These preliminary clinical results confirmed that the isolation technique of human islets and the technique of pancreas procurement are mastered by our team. If the results of this assay (assessment one year after graft) confirm our hopes, we will be able to offer islet allografts to an increasing number of patients with severe Type 1 diabetes.

Between 1971 and 2002, 80 patients underwent surgery for insulinoma at the Department of General and Endocrine Surgery of the Lille University Hospitals. The present report deals with 13 patients with proven multiple endocrine neoplasia type I (MEN I) or supposed genetic-related insulinomas. This entity differs from spontaneous insulinoma by the presence of multiple foci in the pancreas. Enucleation is not advised in this setting due to the strong likelihood of persistence or recurrence. Various studies suggest different strategies for preoperative localization and surgical approach. We analyzed retrospectively the surgical strategy proposed by the A.F.C.E. and G.E.N.E.M. The purpose of this study was to validate the strategy, integrate the contribution of genotypic diagnosis, simplify preoperative imaging studies, and re-evaluate the value of intraoperative baseline secretin-stimulated insulin measurements. We recommend preoperative endoscopic ultrasonography of the pancreatic head only and routine left pancreatectomy with enucleation of cephalic tumors under intraoperative hormone monitoring. Preoperative invasive localization studies are proposed only if the endoscopic ultrasonography is negative for the pancreatic head. Intraoperative secretin stimulation test can be useful in difficult cases, especially with concurrent nesidioblastosis or in case of secondary surgery. All but one of the 13 patients achieved long-term cure with this strategy.

To define a clinical and secretory profile of paragangliomas extra-adrenal chromaffin tumors.From 1971 throughout 2002, 39 paragangliomas have been observed in 38 patients (22 male, 16 female, average age 41,2 years).Four were located above the diaphragm, 35 were sub-phrenic (6 of the organ of Zuckerkandl), 32 secreted catecholamines, 23 were hypertensive (with only one without hypersecretion of catecholamines). Among 29 (131)I-metaiodobenzylguanidine scans (MIBG) reviewed, 20 tumors took up the radiopharmaceutical. The treatment was surgical in 35 cases with addition of external radiotherapy and MIBG in one case each; two patients died before any treatment. Two patients with persistent disease after surgery were successfully treated by surgery or MIBG. Histologically, 20 were malignant and 17 were seemingly benign. All exclusive dopamine secreting paragangliomas were malignant. Six patients relapsed two of which for a tumor initially classified as benign. The treatment of recurrences was surgical, by MIBG or by external radiotherapy. Nine patients had a family history of chromaffin tumor(s). The genetic survey made in five of these nine patients was positive in all cases.

In MEN1, HPT manifests precociously and it is almost constant. Whereas in MEN2 it seldom occurs and has been reported in 17 to 40% of the cases, in MEN1 HPT is much more severe, amplifying the secretion of associated gastrinomas. In MEN1, multiglandular involvement is almost constant, and in case of less than subtotal parathyroidectomy, recurrence rate varies from 20 to 40%. Practically, HPT is the first worry of the surgeon in a MEN1 setting, and the last in a MEN2 setting. It is rather important to think to the potential hypoparathyrodism at the time of the cervicotomy for MTC. The operative strategy is to examine all parathyroid glands. In MEN1, it is necessary to be aggressive and perform a subtotal parathyroidectomy, regardless of gland gross appearance. In the MEN2 only the enlarged glands should be removed. In both setting a bilateral cervical thymectomy should be done for removal of a possible supernumerary gland.

Multiple endocrine neoplasias (MEN) are autosomal dominant inherited syndromes characterized by the association of different glandular lesions in several members of the same kindred. The main clinical features of MEN 1 include primary hyperparathyroidism, pancreatic islet cell tumors and pituitary adenomas; less common features are adrenal adenomas, thymic and bronchial carcinoid tumors, lipomas and various cutaneous lesions. The MEN 2 syndromes (MEN 2A, MEN 2B and familial medullary thyroid carcinomas) are characterized by high penetrance of medullary thyroid carcinoma and differ in their variable expression of pheochromocytoma, hyperparathyroidism and other clinical features.MEN 1 tumor suppressor gene encodes a nuclear protein, menin, which interacts with different regulation transcription factors. The MEN 2 syndromes are caused by germ-line mutations of the RET proto-oncogene, which encodes a transmembrane tyrosine kinase. Genetic testing for mutations in these 2 genes allows identification of individuals predisposed to the disease, early diagnosis, and clinical and therapeutic management.Fundamental approach will allow a best comprehension of physiopathogenic mechanisms of these disorders and the improvement of therapeutic management.

On July 2000, 127 gastrinomas (31.1%) were studied by the Endocrine Tumour Group (GTE) using a 408-patient cohort of Multiple Endocrine Neoplasia Type 1 patients. The aim of this study was to assess clinical, biological, surgical data as well as their trends over three periods (1980-1980/1989-1990). A Zollinger-Ellison syndrome (SZE) was present in 96% of the cases. Mean age at the onset of the disease was 39.4 years. There were 55.9% of men. Synchronous liver metastasis was present in 7.1%. Taken independently, the positivity of the four main diagnosis tests decreased over the time. The diagnosis of oesophagitis increased (4.5-29.7%), as well as the size of the resected tumours (9.9-16.8 mm). There was an increase in the familial background diagnosis (73.1-80%), an increasing use of Octreoscan scintigraphy and transduodenal ultrasound with positive detection of metastasis and tumours in 81.3% and 92.3%, respectively after 1991. Patients were operated on less frequently (96-52.5%), less frequently from the pancreas (87.5-37.5%), and from the gastro-intestinal tract (70.8-30%). The relative percentage of major pancreatic resections increased (with at least removal of the duodenum and the pancreatic head) (10-26.7%). The operative mortality disappeared. Six out of the seven patients (85.7%) who benefited from major pancreatic resections normalized their gastrine level postoperatively versus 15% in less radical techniques. Overall 5 years survival was 90 +/- 4.4%. Survival increased after 1985 (85 +/- 4.8% versus 95 +/- 3.6, P = 0.1).SZE in NEM1 were diagnosed at an earlier stage and were less frequently operated on. Nevertheless, the incidence of synchronous metastasis did not change significantly. Patients were mainly operated on for gastric emergencies and pancreatic tumours in order to prevent metastasis without mortality after 1991.

In the situation of persistent hypercalcaemia after cervicotomy for medullary carcinoma of the thyroid (CMT), the concerns are radically different depending on whether the initial operation has been adequate or not. If it has been inadequate, it is necessary to reoperate via cervicotomy and facilitate, in all cases, a total thyroidectomy and a bilateral and central neck dissection. If the cervicotomy has been adequate, it is necessary to have a high index of suspicion for a locoregional recurrence and systemic disease, but the indications for reintervention must be respected. The essential problem is the difficulty in staging residual or recurrent disease. In this situation all the imagery available should be utilised, including laparoscopy to rule out the possibility of miliary metastatic liver disease. There is no hope of cure in the setting of systemic disease, but it is necessary to recall that an extremely elevated calcitonin can be well tolerated and compatible with a survival for several decades. The overall prognosis lies not in the level of elevation of the tumoral marker but the extent of local invasion and systemic disease. There is no hope of cure when the calcitonin level is superior to 1000 pg/ml. There is also no chance of localising recurrent disease when the calcitonin level is inferior to 50 pg/ml. Therefore, one should only utilise the various available localisation techniques when the level of calcitonin is between 50 and 1000 pg/ml. A mediastinal dissection via sternotomy is only indicated in the absence of distal metastases and in the setting of nodal involvement just caudal to the initial cervicotomy, and only after a laparoscopy to exclude hepatic metastases. The future hopes lie with radio-immunoguided surgery in cases of local invasive disease and radiolabelled immunochemotherapy for systemic disease.

The postoperative pancreatitis was a classical complication in the historical series of primary hyperparathyroidism (HPT), but the causal association was never demonstrated and even recent studies denied it. The aim of this study was to determine the augmentation of postoperative amylasemia, and its possible clinical traduction in patients operated for primary HPT.Fifty consecutive patients operated for cure of a primary HPT were included in this study. Total amylase, as well as isoenzyme fractions P (pancreatic) and S (salivary), calcium, phosphorus and intact PTH serum concentrations were determined on the days prior and after parathyroidectomy. Fifteen normocalcemic patients operated for secondary HPT constituted the control group.The study deals with 42 female and eight male patients, their mean age was 58.5 years (range 19-89 years). All patients underwent parathyroidectomy for adenoma or hyperplasia. No patient had pancreatitis before parathyroidectomy. Postoperative amylasemia developed in four patients (8%), one with increased total amylase and P fraction, one with only increased total amylase, and two with increased total amylase and S fraction. No patients exhibited abdominal symptoms suggesting acute pancreatitis in the postoperative period. There was no correlation between pre- and post-operative calcium serum levels and pre- and post-operative amylasemia. In the secondary HPT group no significant diminution of the total amylasemia or of P and S fractions were observed.These results indicate that acute pancreatitis is an exceptional postoperative complication of primary HPT nowadays. The 8% incidence reported in the present study matches the incidence of hyperamylasemia reported postoperatively in non-abdominal or non-parathyroid surgery.

Chylous ascites is a rare case of peritonitis. We report here a case arising in a 21-year-old lady.

The typical manifestations of severe hypercalcemia with osteitis fibrosa cystica have become exceedingly rare. We describe the case of a woman hospitalized for a tibial tumor with functional impotence, leading to a diagnosis of primary hyperparathyroidism (HPT I) associated with profound vitamin D deficiency. This 31-year-old woman was admitted, after two pregnancies complicated by the HELLP syndrome. Preoperative laboratory values were as follows: calcemia 4.05 mmol/l (2.2-2.6); urinary calcium 30 mmol/24 h (1.25-7.5); parathormone (PTH) 1 195 pg/ml (10-60); and 25 OH-vitamin D 13 nmol/l (22-120). Specific MIBI uptake by the tibial lesion oriented the diagnosis towards a brown tumor. After surgical excision of a parathyroid adenoma and the brown tumor (associated with tibial fracture), calcemia fell to 1.55 mmol/l and normalized after three months. Urinary calcium fell to 0.1 mmol/24 h and remained low during the 2 years following surgery. Vitamin D levels rapidly normalized on supplementation (87 nmol/l). PTH levels fell markedly after surgery but remained higher than normal till 2 years after surgery despite normalization of calcemia three months after. Bone repair, estimated by means of bone densitometry, improved from preoperative Z-score values of - 6.54, - 5.20 and - 3.50 in the left femoral neck, right femoral neck and lumbar spine, respectively, to - 0.20, - 1.55 and - 0.28, respectively, one year after surgery. In conclusion, this case illustrates: 1) the severe osseous expression of HPT probably related to vitamin D deficiency; 2) specific MIBI uptake by the bone lesion, orientating the diagnosis towards a brown tumor; 3) the consequences of vitamin D deficiency on postoperative outcome, with transient severe initial hypocalcemia related to bone calcium avidity; 4) a possible link between HPT and the HELLP syndrome.

The aim of this prospective cohort study was to identify the early criteria potentially predictive for outcome of permanent hypocalcemia after thyroidectomy.Serum calcium (Ca) et phosphorus (Ph) were measured daily until discharge in 2035 consecutive patients undergoing bilateral thyroidectomy. In all patients experiencing postoperative hypocalcemia, defined as a Ca8.0 mg/dl on two consecutive days, parathyroid hormone was measured prior initiation of calcium therapy et discharge (early PTH), et blood sample was also obtained 7 to 14 days after discharge for Ca et Ph measurements (delayed Ca et Ph). These patients were then followed up until complete resolution of hypocalcemia or at least one year. Those still needing substitutive therapy to maintain normocalcemia one year after surgery were considered to have permanent hypocalcemia. Correlation of outcome with clinical characteristics, postoperative Ca et Ph levels, early PTH, et delayed Ca et Ph were examined with univariate analysis et multivariate logistic regression.Postoperative hypocalcemia occurred in 153 patients (7.5%) and spontaneously recovered in all but 7 patients (0.3%). Delayed Ca, and delayed Ph were found to be predictive for outcome of hypocalcemia by univariate analysis (p0.01). Relative risk to develop permanent hypocalcemia was 15 for patients with early PTH12 pg/ml, 52 when delayed Ph was4.0 mg/dl, and 121 when delayed Ca was8.0 mg/dl. None of the 113 patients with delayed Caor = 8.0 mg/dl and delayed Phor = 4.0 mg/dl developed permanent hypocalcemia, in contrast to 1 out of 31 patients (3%) with delayed Ca8.0 mg/dl or delayed Ph4.0 mg/dl, and 6 out of 9 patients (66%) with delayed Ca8.0 mg/dl and delayed Ph4.0 mg/dl. Both delayed Ca and delayed Ph appeared as independent factors predicting outcome of hypocalcemia at one year with multivariate logistic regression analysis.Delayed serum calcium and phosphorus levels, when measured one week after starting calcium therapy but prior to administration of any vitamin D analogs, accurately predict outcome of hypocalcemia after thyroidectomy. Patients with delayed Ca under 8.0 mg/dl and/or delayed Ph above 4.0 mg/dl are at high risk to develop permanent hypocalcemia.

Multiple endocrine neoplasia type 1 (MEN1) is a rare but misleading disease. The diagnosis is evocated when two main lesions are present (parathyroid, endocrine pancreas, pituary gland) but also when a family tree shows recurrent lesions. Other lesions must be taken into account (adrenal glands, neuroendocrine thymic or bronchic lesions, cutaneous lesions, lipomas, nervous central system tumors). Any surgical cure without knowing the MEN1 background leads to failure. Specific treatment of each lesion is reviewed. Genetic diagnosis is possible but the mutation is not found in all cases. Nevertheless, when the mutation is known in a family, a negative genetic test allows to exclude the disease. Prognosis is related to hepatic metastases and to thymic neuroendocrine tumors which are rare (2.1%) but aggressive. As a general rule, any apparently isolated endocrine lesion such hyperparathyroidism must prompt the surgeon to look for another endocrine lesion and to look for an abnormal family tree with recurent monoglandular or pluriglandular lesions.

Malignant tumors have been associated with the development of nephrotic syndrome. We report a 73-year-old man with nephrotic syndrome who had a malignant stromal gastric tumor. Curative resection of the sarcoma resulted in remission of the nephrotic syndrome.

HPLC plasma methoxyamines measurements are the updated technique for the diagnosis of adrenergic hypersecretion. Their reliability meets that of urinary measurements. Significance of increased values is not yet fully established for the etiological diagnosis of hypertension in some situations, especially in case of renal insufficiency and in the peri-operative period. The aim of this study is to define the "normal" range of the values of plasma methoxyamines in both of those conditions.in a General and Endocrine Surgical Unit, 3 homogeneous group of 20 patients each have been studied: group 1, control (patients awaiting thyroidectomy); group 2, patients on maintenance hemodialysis submitted for hyperparathyroidism; group 3, patients submitted to digestive surgery. Measurements were done pre-operatively in group 1, pre and post-operatively in group 2, and post-operatively in group 3.in comparison to the control (11.8 nmol/l), we observed in group 2 a 18 fold increase preoperatively, and a 29 fold increase at post-operative day 1. In group 3, we observed a 2.3, 2.7 and 2 fold increase at post-operative days 1,2 and 3 respectively. All those results were statistically significant.Results of measurements of plama methoxyamines should always be matched to the serum creatinine levels. They are meaningful for the diagnosis of endocrine origin of hypertension only late after the early post-operative period.

Intraportal islet allograft appears to be one of the promising treatments for type I diabetes. However, many limiting factors persist. An activation of the coagulation cascade upon contact with islets, has been reported recently in vitro and could play a crucial role in a non specific inflammatory reaction and favour the specific immune reaction. The aim of this experimental study was to confirm in vivo this activation of the coagulation cascade.An allogenic islets preparation or a material control (inert microbeads) was injected intraportally, in Large White pigs (n = 26), associated with or without an anticoagulant treatment (heparin). Systemic markers of haemostasis were measured in pigs for 72 hours following injection of the studied material.The thrombin-antithrombin complex increased and platelet count decreased in groups receiving preparation of islets, both indicators of an activation of the coagulation cascade. This activation was proportional to the injected volume and was partially attenuated by heparin. No activation was observed in pigs receiving the material control.The activation of the coagulation cascade and the non specific inflammatory reaction could be one of the obstacles to the success of the islet allografts. The use of anticoagulant and anti-inflammatory molecules could potentially allow an improvement of the present results of islet allograft.

To report feasibility and efficacy of radioguided mini invasive hyperparathyroidism surgery.From November 1998 to August 2000, 75 patients with primary hyperparathyroidism have been operated on by radioguided surgery within 90 to 180 minutes following i.v. injection of a diagnostic dose of MIBI and after parathyroid scanning with planar and oblique views. Exclusion criteria were thyroid pathology requiring surgery and suspicion of multiple endocrine neoplasia. A 20% step-up between the background noise and tissue uptake was the diagnostic threshold for parathyroid hyperfunctioning tissue.A 20% step-up was observed in only 17% of cases overall; all cured, but two. Various angles of application of the probe can result in significant discrepancies of recorded uptake for the same spot. These results demonstrate a physiological step-up between the ipsilateral unaffected upper and lower quadrants of the neck (range: -17 to -8%), because of the proximity of supraortic vessels (upper neck-upper mediastinal gradient: -44 to -30%). Therefore, significant ratios are meaningful only between either the symmetrical left and right controlateral quadrants respectively, and not between the upper and the lower ipsilateral quadrants. Eleven per cent (8/75) of preoperative scannings were non-contributory, and probe detection was contributory in 3/8 cases only.Benefit of the technique is limited in routine, but it can be helpful in redo cases if the offending gland is not located in close surroundings of tissues physiologically taking up the radiopharmaceutical (salivary glands, great vessels and heart).

We report the occurrence of a sustained hypotension (vasoplegia) following thoracic phaeochromocytoma surgery. Diagnosis of spinal cord injury was done by magnetic nuclear resonance (MNR) showing surgical "Horsley wax" inside the vertebral canal and ischaemic signal inside the anterior part of the spine cord. Removal of "Horsley wax" dramatically improved arterial blood pressure but did not correct all neurologic disorders. Haemodynamic disorders related to spinal cord injury are rare after thoracotomy, and may have been enhanced by the haemodynamic instability typically associated with phaeochromocytoma surgery. Early diagnosis has to be done by MNR.

Cell therapy offers today important perspectives for the treatment of type 1 diabetes. The current utilization of primary human islets of Langerhans nevertheless forbids all hope of developing this treatment on a large scale. The recent description of the persistence of stem cells capable of proliferating and differentiating in the adult pancreas offers an attractive alternative for the production in vitro of homologous insulin-secreting cells. We first reproduced in vitro from human islet preparations the proliferation of ductal epithelial structures and their progressive organization. Thereafter, we focused on the description of a reproducible source of human ductal cells by the transdifferentiation of exocrine preparations. More recently we described in these exocrine derived ductal cells the the expression the of insulin promoter factor-1 (IPF-1/otherwise known as PDX-1), a transcription factor essential for the differentiation of ductal cells into endocrine cells during both development and pancreatic regeneration. If the proliferation and differentiation of these cells is confirmed, this approach could lead to the description of an abundant source of human pancreatic stem cells for the production ex vivo of human insulin secreting cells and may even allow autologous cell therapy, in the absence of immunosuppression.

The paper gives a summary of the intraoperative findings in 38 patients who underwent a reoperation for persistent or recurrent primary hyperparathyroidism. The reasons for failure of the first intervention were inexperience of the surgeon, ectopic and supernumerary glands, parathyreomatosis and true recurrence. Careful localization studies are mandatory in the preoperative work-up of these patients.

Non-secreting pancreatic neuroendocrine tumors and diarrheogenic tumors are usually bulky and easy to recognize thanks to somatostatin-receptor scintigraphy and hormonal dosages. The real difficulty concerns insulinomas and particularly gastrinomas, which are found at the level of the duodenum and can be very small. Diagnosis is based on biological examinations, and the search for MEN I must be done systematically. Their localization is based on two essential and noninvasive exams: echoendoscopy and somatostatin-receptor imaging, though the surgeon's skill in the operative field, aided by an intraoperioperative echography, is indispensable. Surgical treatment of insulinomas gives excellent results. However, for sporadic gastrinomas, there was only a 34% recovery rate, and still less for MEN I gastrinomas.

CT scan performed for non-adrenal related symptoms detects an adrenal mass or 'incidentaloma' in 0.4 to 4.3% of cases, and most authors advocate a non-operative policy, after minimal but careful work-up aimed at excluding pheochromocytoma and aldosteronoma. The breakthrough of laparoscopic adrenalectomy has led some to challenge this attitude. This retrospective study focused on the outcome of non-operated adrenal masses.From 1986 through 1999, 126 patients (64 men and 62 women) presented with an incidental mass of the adrenal fossa, and a non-surgical attitude was elicited. Mean size was 36.5 mm in diameter. All patients underwent an in-depth clinical, biochemical and imaging work-up. They have been stratified into two groups: group I: no contraindication to surgery (n = 95); and group II: contraindication to surgery (frail patients, invasive adrenal or metastatic extra-adrenal cancer) (n = 31).With a mean follow-up of 4.3 years, 17 patients were lost to follow-up (13.5%), including 11/95 in group I; 36 were dead (28.5%), including 12/95 in group I (no adrenal-related death) and 24/31 in group II; 72 were alive and well without operation, including only one in group II; one patient was operated for a benign adrenal adenoma removed at the time of surgery for aortic aneurysm.Careful clinical, biochemical, imaging and nor-iodo-cholesterol scintigraphy with definite uptake by the adrenal mass, a strong indicator of benignancy, allows surgical indication to be postponed, and is likely to cancel it if, at one-year follow-up, imaging studies show no change in the mass.

The tilt from open to laparoscopic surgery seems to be definite in most adrenal disorders. The aim of this study is to evaluate the current indications for laparoscopy and the persistent indications for open adrenalectomy, as seen in our experience and in the literature data. Between January 1985 and December 1999, 486 patients were operated on for adrenalectomy. Since January 1994, 91 laparoscopic adrenalectomies were performed in 84 patients. The Authors retrospectively evaluated the indications for laparoscopy in 55 patients (45.9%) and for open adrenalectomy in 65 others (54.1%) operated on in the last three years. Exclusion criteria for the laparoscopic approach included clinical suspicion of malignancy and tumour size greater than 6 cm, in the 38.5% and in the 23.0% of cases respectively. In Authors experience the laparoscopic adrenalectomy is the procedure of the choice for the surgical removal of non-malignant, unilateral or bilateral tumours under 6 or 7 cm. The laparoscopy is not a radical operation for cancer. Open surgery is always indicated for large and malignant tumours. The fascinating feature of laparoscopy has not to change the indications and the surgeon must plan the appropriate approach for every single patient.

To evaluate the incidence of cardiac deaths following noncardiac nonvascular surgery.Retrospective survey.All patients undergoing mainly endocrinous and digestive surgery in a University department of general surgery between 1991 and 1996.Analysis of all deaths occurring intra- and postoperatively, until discharge of the patients. Demographic and medical data, including patent myocardial ischaemia and risk factors for coronary artery disease, were recorded and compared with a control group including all patients undergoing surgery from January to September 1996.In the 8,700 patients who underwent mainly endocrine neck surgery (66%), or intra-abdominal surgery (31%), the mortality rate (n = 96) was 1.1% (95% confidence interval [95% CI] = 0.9-1.3%). Patent myocardial ischaemia or high risk factors for coronary artery disease were existing in 24% of patients with neck surgery, 31% of those with intra-abdominal surgery, and in 60% of the deceased patients (P0.01 vs control group). Those who died were older, were in a higher ASA physical class, and had undergone an emergency procedure more often than patients of the control group (P0.002 for each parameter). Two cardiac deaths, in patients with a patent cardiopathy, were recorded (cardiac mortality: 0.02%; 95% CI = 0.003-0.08%). The main cause of death was infection (n = 46), followed by haemorrhage (n = 12). Seven deaths remained unexplained.This study suggests that cardiac morbidity is a rare cause of death after noncardiac nonvascular surgery.

The aim of this retrospective study conducted by the "Groupe d'étude des néoplasies endocriniennes multiples type 1" (GENEM) was to report a series of insulinomas associated with multiple endocrine neoplasias type 1 (NEM 1) and to determine the most appropriate strategy for the topographical exploration and surgical management.From 1960 to 1996, 44 patients were included, 16 men and 28 women (mean age: 36.4 +/- 13.9 years). This study concerned morphological investigations, tumoral features, modalities and results of the treatment.Insulinomas were associated with other functional islet tumors in 15 patients: ZE syndrome (n = 8), glucagonoma (n = 6), vipoma (n = 1). Malignant lesions were present in 6 patients: isolated insulinomas (n = 2), insulinomas associated with ZE syndrome (n = 2) and vipoma (n = 1). The sensitivity of the preoperative imaging procedures was less than 70%. Fourty-one patients were operated on: subtotal pancreatectomy (n = 26 including cephalic enucleations in 8), enucleations (n = 8), total pancreatectomy (n = 3), pancreaticoduodenectomy with caudal enucleations (n = 1), and for 3 patients, no details were available. There was no postoperative mortality. Hyperinsulinism disappeared in 27 patients (including 2 after reoperation) with a mean follow-up of 9 years. Among 6 patients with malignant lesions, 3 were alive with a 3, 4 and 10 year-follow-up.Subtotal pancreatectomy with splenic conservation and enucleation of cephalic lesions is suggested as the procedure of choice in this group of patients. This procedure allows simplification of preoperative imaging investigations because lesions of the pancreatic head have only to be detected. Preoperative endoscopic ultrasonography and intraoperative ultrasonography are the best investigations.

Evaluation of the malignant potential of phaeochromocytomas in the absence of metastases presents a formidable challenge to both clinicians and pathologists. Until now, no widely accepted clinical, histological, immunohistochemical or molecular method has become available to discriminate malignant from benign phaeochromocytomas. In other endocrine tumours, estimation of proliferative activity by MIB-1 immunostaining has emerged as a promising approach for the determination of metastatic potential. In this study, the utility of MIB-1 immunostaining as a predictive marker for the occurrence of metastases in phaeochromocytomas was evaluated. In addition, the density of S100-positive sustentacular cells was studied, since their depletion has been identified as a negative predictive marker in smaller series. Furthermore, several clinicopathological parameters were evaluated. One hundred and ten patients operated on for a total of 99 benign and 37 malignant phaeochromocytomas were studied. All malignant tumours had documented metastases. The histopathological diagnosis of primary tumours and metastases was reviewed and graded for angioinvasion, capsular extension, and intra-tumoural necrosis. The proliferative index (percentage of MIB-1-positive cells) and the density of S100-positive cells were assessed. In addition, age at resection, associated familial tumour syndromes, tumour size, and tumour location were recorded. Univariate analysis revealed statistically significant correlations between malignancy and proliferative index (p0.0005) and depletion of S100-positive sustentacular cells (p0.0005). Fifty per cent of the malignant, but none of the benign phaeochromocytomas had a proliferative index greater than 2.5%. Higher age at resection (p=0. 03), sporadic occurrence (p0.0005), extra-adrenal location (p0. 0005), tumour size (p0.0005), and necrosis (p=0.03) were also significantly associated with malignancy. Logistic regression showed that proliferative index (p=0.0072), size (p=0.0022), and extra-adrenal location (p=0.0012) of the primary tumour were independently predictive for malignancy. In conclusion, this study indicates that assessing the proliferative activity of phaeochromocytomas by MIB-1 immunohistochemistry can predict the occurrence of metastases. The predictive value of S100 immunostaining, tumour size, and extra-adrenal location of the tumour was also confirmed.

Medullary thyroid carcinoma (MTC) is a calcitonin (CT)-secreting endocrine tumor. Although plasma CT level is a specific and sensitive marker of MTC, its preoperative usefulness in predicting tumor size and postoperative CT normalization has not been documented. From a nationwide database set up by the French CT Tumor Study Group, 226 MTC patients were selected according to the following criteria: preoperative CT level determination by an immunoradiometric assay (normal value,10 pg/mL) within the 6 months prior to surgery, total thyroidectomy and diagnosis of MTC ascertained by histological report including tumor size. Patients were 129 females and 97 males (female/male ratio, 1.3). One hundred and twelve patients (49.6%) had the sporadic variety of the disease, 74 (32.7%) had multiple endocrine neoplasia 2A, three (1.3%) had multiple endocrine neoplasia 2B, and 37 (16.4%) had familial MTC. Median age at diagnosis was 44.8 yr (range, 4.9-80.1 yr). Complete neck dissection was performed in 159 patients (70.4%). Postoperative CT normalization was ascertained by negative response of CT to pentagastrin stimulation (10 pg/mL) in 94 patients. Seventy-one patients were considered as not cured because of residual tumor tissue and/or elevated CT levels. Median tumor size was 11.0 mm (range, 0.2-80.0 mm), significantly larger in females (15.0 vs. 8.0 mm, P0.05), and in sporadic forms (15.0 vs. 7.0 mm, P0.05). Tumor size was significantly correlated (r2 = 0.52, P0.01) with preoperative CT levels, the relationship being more straight in familial (r2 = 0.71) than in sporadic (r2 = 0.36) forms. Furthermore, preoperative CT levels under 50 pg/mL appeared to be predictive of postoperative CT normalization (44 of 45 patients). However, higher CT levels did not mean absence of postoperative CT normalization (50 of 120 patients). We conclude that low preoperative CT levels are predictive of tumor size and postoperative CT normalization.

BACKGROUND: Once genetic testing accurately identifies MEN 2 gene carriers, affected children are given the opportunity to undergo thyroidectomy at the earliest stages of the C-cell disease. OBJECTIVE: To define reliable parameters by which to identify the best moment for thyroidectomy in patients who are carriers of the MEN 2 gene. PATIENTS AND METHODS: Seventy-one MEN 2/FMTC gene carriers, collected through the national register of the French Calcitonin Tumours Study Group, were evaluated. All the patients included were younger than 20 years of age and underwent total thyroidectomy. Basal and pentagastrin-stimulated calcitonin were assayed using an immunoradiometric method (sensitivity less than 2pg/ml). Calcitonin measurement was evaluated on the basis of histopathological findings in surgical thyroid specimens. RESULTS: We found C-cell hyperplasia or medullary thyroid carcinoma in all the 71 gene carriers - even for the youngest patients - and nodal metastases were present in four cases. Calcitonin measurement (basal or pentagastrin-stimulated) detected C-cell disease preoperatively in all patients. Six of the 71 patients were not surgically cured: one had nodal metastases, one had an advanced staged disease and four had an incomplete nodal dissection or had not undergone lymph node surgery. CONCLUSIONS: Determination of calcitonin forms an integral part of the management of MEN 2 gene carriers. Thyroidectomy is undisputably indicated when basal calcitonin is abnormal. When basal calcitonin is undetectable, a pentagastrin-stimulated increase in calcitonin to more than 10 pg/ml indicates an early thyroidectomy to cure the patient.

The aim of this prospective study conducted by the AFCE was to analyze the indications, approach and results of all adrenalectomies performed during the year 1997 in 17 centers, active or specialized in endocrine surgery.During 1997, adrenalectomy was performed in 247 patients, 149 men and 98 women (mean age: 51 years). The lesion was located in the right side in 166 patients, in the left side in 99, in both sides in 28 patients and ectopic in four patients. Pheochromocytomas (n = 61), Conn adenomas (n = 50) and Cushing syndrome lesions (n = 48) were the most frequent in this series. Laparoscopic adrenalectomy was performed in 172 patients (70%) through a transperitoneal approach in all cases except one, and by 'open' surgery in 75 patients (30%).In patients operated on by the laparoscopic approach, the mean duration of surgery was 132 min, and there were peroperative complications in 15 patients (8.7%), mainly hemorrhages. Conversion rate into laparotomy was 7%. In the postoperative course, there were three reoperations and two deaths, an early one in a patient reoperated for bleeding and a very late one in relation with necrotising acute pancreatitis. Mean duration of hospitalization was 5.8 d. Mean tumoral size was 49 mm. In patients operated on by 'open' surgery, the mean duration of surgery was 148 min. There was a postoperative complication in eight patients (10.6%), mostly hemorrhages, and two intraoperative deaths in relation with uncontrollable bleeding. Mean duration of hospitalization was 11 d. Mean tumoral size was 72 mm.Laparoscopic adrenalectomy is now indicated for the majority of adrenal tumors. Several complications observed in this series were related to the learning curve in several centers. Laparoscopic adrenalectomy is the 'gold standard' in uni- or bilateral benign tumors no larger than 6 or 7 cm. 'Open' surgery is indicated in malignant tumors, especially in adreno-cortical carcinomas, and in all large tumors.

Intraoperative hormonal measurement has been successfully used to guide the surgical treatment of various endocrine diseases. In this study, we report the results of intraoperative insulin measurement in patients with organic hypoglycemia (n = 52 operations in 51 patients) and the results of intraoperative gastrin measurement in patients with gastrinoma (n = 20). Measurements were done in the systemic and portal blood at the beginning of the operation, and 20 min after removal of the lesion(s), with intra-operative secretin stimulation test for gastrinoma in some cases. Results accurately predicted cure (insulinomas) or non-cure (half of gastrinomas) of the disease. Limitations of the method are the possibility of normal hormone base line levels at the time of surgery and the importance of secretion of pro-insulin products by insulinomas not taken in account by the assay with monoclonal antibodies.

Risk factors of metachronous liver metastases and death are not well known in patients with the Zollinger-Ellison syndrome and multiple endocrine neoplasia type 1. These factors were retrospectively determined in 77 patients.Data chart review was performed.Median follow-up was 102 months (range, 12-366). Surgery was performed on 48 patients, including 9 of the 10 patients with large pancreatic tumors (/=3 cm). Liver metastases developed in 4 patients (40%) with large pancreatic tumors, in 3 (4.8%) without, and in 1 of the 4 patients with pancreatic tumors of unknown size; all had previously undergone surgery. The only independent factor associated with development of liver metastases identified by multivariate analysis was large pancreatic tumors (risk ratio, 29.0; 95% confidence interval [CI], 3. 2-260.7). Surgery was not selected. The probability of being free of liver metastases in the 63 patients without large pancreatic tumors was 96% (95% CI, 88-100) at 10 and 15 years. Thirteen (16.9%) patients died. The only independent factors of death selected by multivariate analysis were Zollinger-Ellison syndrome diagnosis before 1980 (risk ratio, 8.2; 95% CI, 1.7-40.6) and age at diagnosis (risk ratio/year, 1.08; 95% CI, 1.03-1.14).Large pancreatic tumors are predictive of the development of metachronous liver metastases, and surgery does not seem to prevent them.