Reperfused human cadaver as a new simulation model for colonoscopy: a pilot study.

BACKGROUND: The reperfused human cadaver is a validated simulator for surgery. We aimed to use it as a colonoscopy simulator. METHODS: Novices, intermediates and skilled participants in gastrointestinal endoscopy were included. They performed one colonoscopy on a reperfused human cadaver and reaching rates, time, and length needed to reach anatomical landmarks were reported for construct validity analysis. We also assessed our model realism (SRS survey), educational content (CVS survey) and task load (NASA-TLX index). Score items were collected and defined as "favorable" when items were rated ≥ 5/7 with an inter-quartile range (IQR) overlapping four, and "very favorable" when rated ≥ 5/7 with an IQR excluding four (neutral). Primary endpoints were the rectosigmoid junction (RSJ) reaching rate and the descending colon (DC) reaching time. Secondary objectives were SRS, CVS and NASA-TLX questionnaire results. RESULTS: A total of 11 skilled participants, 5 intermediates and 8 novices were included. Skilled participants reached RSJ more often than novice and intermediary groups, respectively, 100%, 80% and 75% without differing significantly. They reached DC more frequently (100% for skilled, 80% for intermediates and 50% for novices, p = 0.018). The median time to reach RSJ (59, 272 and 686 s for skilled, intermediates and novices group, respectively) and DC (90, 534 and 1360 s for skilled, intermediates and novices) was significantly shorter for skilled participants (both p < .01). Nineteen out of the 22 items composing the realism survey obtained "very favorable" and "favorable" scores. Educational content was designated as "very favorable". Mental, physical, and technical demands were gradually higher the lower the initial level of experience. CONCLUSIONS: Reperfused human cadaver model has the potential to be valid simulation tool for diagnostic colonoscopy training.

Defining and Assessing the Reproducibility of Crohn's Disease Endoscopic Lesions: A Delphi-like Method from the GETAID.

BACKGROUND AND AIMS: Defining and assessing the reproducibility of Crohn's disease [CD] endoscopic lesions is essential in assessing endoscopic healing. METHODS: Twelve endoscopic CD experts from the GETAID defined aphthoid erosions [AE], superficial ulcerations [SU], deep ulcerations [DU], stenosis, and fistulas according to a Delphi-like method. Thirty different GETAID physicians declared if they found acceptable each definition. Intra- and inter-observer agreements were investigated using 100 videos with one tagged specific lesion [AE, SU, DU, or sham lesion] read by 15 independent endoscopists at baseline and 1 month later in a randomised order. Video quality was determined by an external reader. According to kappa estimate [κ ±standard error], intra or inter-observer agreement was qualified as 'moderate' [0.4-0.6], 'substantial' [0.6-0.8], or 'almost perfect' [0.8-1.0]. RESULTS: Among 30 different experts, 83% to 97% found acceptable the definitions retrieved from the Delphi-like method. Intra-observer κ was 0.717 [±0.019] for SU, 0.681 [±0.027] for AE, 0.856 [±0.014] for DU, showing 'substantial' agreement. It was 0.801 [±0.016] for any ulceration [DU or SU]. There was a high variability across readers from 'moderate' to 'almost perfect' agreement. Inter-observer κ was 0.548 [±0.042] for SU, 0.554 [±0.028] for AE 0.694 [±0.041] for DU, and 0.705 [±0.042] for any ulceration. Inter-observer agreement increased when reading the 53 high-quality videos: 0.787 [±0.064] [p = 0.001], 0.607 [±0.043] [p = 0.001], and 0.782 [±0.064][p = 0.001] for DU, AE, and any ulceration, respectively. CONCLUSIONS: Despite variable intra-agreement level across readers, the GETAID definitions for CD endoscopic lesions provided 'substantial' inter-observer agreements, especially in case of high-quality videos.

Measurement variability of liver metastases from neuroendocrine tumors on different magnetic resonance imaging sequences.

PURPOSE: To assess dimension measurement variability of liver metastases from neuroendocrine tumors (LMNET) on different magnetic resonance imaging (MRI) sequences. MATERIAL AND METHODS: In this institutional review board-approved retrospective study from January 2011 to December 2012, all liver MRI examinations performed at our department in patients with at least one measurable LMNET according to response evaluation criteria in solid tumors (RECIST1.1) were included. Up to two lesions were selected on T2-weighted MR images. Three reviewers independently measured long axes of 135 hepatic metastases in 30 patients (16 men, 14 women, mean age 61±11.4 (SD) years; range 28-78 years), during two separate reading sessions, on T2-weighted, diffusion-weighted MRI (DWI) (b; 50, 400, 800 s/mm2) and arterial, portal and late phases after intravenous administration of a gadolinium chelate. Intraclass-correlation coefficients and Bland-Altman plots were used to assess intra-and interobserver variability. RESULTS: Intra- and interobserver agreements ranged between 0.87-0.98, and 0.88-0.97, respectively. Intersequence agreements ranged between 0.92 [95%CI: 0.82-0.98] and 0.98 [95%CI: 0.93-0.99]. 95% limits of agreement for measurements were -10.2%,+8.9% for DWI (b=50s/mm2) versus -21.9%,+24.2% and -15.8,+17.2% for arterial and portal phases, respectively. CONCLUSION: An increase<9% in measurement and a decrease of -10% on DWI should not be considered as true changes, with 95% confidence, versus 24% and -22% on arterial and 17%, -16% on portal phases, respectively. DWI might thus be the most reliable MR sequence for monitoring size variations of LMNETs.

The future: surgical advances in MEN1 therapeutic approaches and management strategies.

Multiple endocrine neoplasia type 1 (MEN1) is a hereditary autosomal dominant disorder associated with numerous neuroendocrine tumors (NETs). Recent advances in the management of MEN1 have led to a decrease in mortality due to excess hormones; however, they have also led to an increase in mortality from malignancy, particularly NETs. The main challenges are to localize these tumors, to select those that need therapy because of the risk of aggressive behavior and to select the appropriate therapy associated with minimal morbidity. This must be applied to a hereditary disease with a high risk of recurrence. The overall aim of management in MEN1 is to ensure that the patient remains disease- and symptom-free for as long as possible and maintains a good quality of life. Herein, we review the changes that occurred in the last 20 years in the surgical management of MEN1-associated functional and non-functional pancreatico-duodenal NETs and thymic and bronchial NETs.

Poorly differentiated gastro-entero-pancreatic neuroendocrine carcinomas: Are they really heterogeneous? Insights from the FFCD-GTE national cohort.

BACKGROUND: Diagnosis and management of poorly differentiated gastro-entero-pancreatic (GEP) neuroendocrine carcinomas (NECs) remain challenging. Recent studies suggest prognostic heterogeneity. We designed within the French Group of Endocrine Tumours a prospective cohort to gain insight in the prognostic stratification and treatment of GEP-NEC. PATIENTS AND METHODS: All patients with a diagnosis of GEP-NEC between 1st January 2010 and 31st December 2013 could be included in this national cohort. Adenoneuroendocrine tumours were excluded. RESULTS: 253 patients from 49 centres were included. Median age was 66 years. Main primary locations were pancreas (21%), colorectal (27%), oesophagus-stomach (18%); primary location was unknown in 20%. Tumours were metastatic at diagnosis in 78% of cases. Performance status (PS) at diagnosis was 0-1 in 79% of patients. Among the 147 (58%) cases reviewed by an expert pathological network, 39% were classified as small cell NEC and 61% as large cell NEC. Median Ki67 index was 75% (range, 20-100). Median overall survival was 15.6 (13.6-17.0) months. Significant adverse prognostic factors in univariate analysis were PS > 1 (hazard ratio [HR] = 2.5), metastatic disease (HR = 1.6), NSE>2 upper limit of normal [ULN]; HR = 3.2), CgA>2 ULN (HR = 1.7) and lactate dehydrogenase >2 ULN (HR = 2.1). After first-line palliative chemotherapy (CT1) with platinum-etoposide (n = 152), objective response, progression-free survival and overall survival were 50%, 6.2 and 11.6 months; they were 24%, 2.9 and 5.9, respectively, after post-CT1 FOLFIRI regimen (n = 72). CONCLUSIONS: We report a large prospective series of GEP-NEC which show the predominance of large cell type and advanced stage at diagnosis. Prognosis was found more homogeneous than previously reported, mainly impacted by PS and tumour burden.

[Digestive neuroendocrine tumors]. / Tumeurs neuroendocrines digestives.

Digestive neuroendocrine tumors (NETs) are a group of rare tumors with increasing incidence. Pathological analysis is critical to establish the diagnosis and evaluate tumor grade that relies on differentiation and proliferation index. NETs are mostly diagnosed at an advanced stage because of late occurrence of nonspecific symptoms, and can be associated with hormone hypersecretion. Chromogranin A is the main biochemical marker of NETs. Extension workup relies on conventional imaging (CT-scan, MRI) and isotopic imaging including somatostatin-receptor scintigraphy, which should be soon replaced by positron-emitting scintigraphy. The main prognostic factors include tumor stage, metastatic volume, histological differentiation and grade. Hormonal syndromes and poorly differentiated tumors are the two therapeutic emergencies. The treatment of localized well-differentiated tumors relies on endoscopic or surgical resection depending on the location and aggressiveness. Surgical removal is the only potentially curative treatment of metastatic NETs but is rarely feasible and is associated with almost constant relapse. Other antitumor therapies include somatostatin analogs, systemic chemotherapy, liver trans-arterial chemo-embolization, targeted therapies and peptide-receptor radionuclide therapy. Management strategy relies on primary tumor location, tumor aggressiveness, metastatic volume and the presence of extra-hepatic metastases. It must take into account the risk of cumulated toxicity in patients whose survival is often prolonged.

MEN1 disease occurring before 21 years old: a 160-patient cohort study from the Groupe d'étude des Tumeurs Endocrines.

CONTEXT: Multiple endocrine neoplasia Type-1 (MEN1) in young patients is only described by case reports. OBJECTIVE: To improve the knowledge of MEN1 natural history before 21 years old. METHODS: Obtain a description of the first symptoms occurring before 21 years old (clinical symptoms, biological or imaging abnormalities), surgical outcomes related to MEN1 Neuro Endocrine Tumors (NETs) occurring in a group of 160 patients extracted from the "Groupe d'étude des Tumeurs Endocrines" MEN1 cohort. RESULTS: The first symptoms were related to hyperparathyroidism in 122 cases (75%), pituitary adenoma in 55 cases (34%), nonsecreting pancreatic tumor (NSPT) in 14 cases (9%), insulinoma in 20 cases (12%), gastrinoma in three cases (2%), malignant adrenal tumors in 2 cases (1%), and malignant thymic-NET in one case (1%). Hyperparathyrodism was the first lesion in 90 cases (56%). The first symptoms occurred before 10 years old in 22 cases (14%) and before 5 years old in five cases (3%). Surgery was performed before age 21 in 66 patients (41%) with a total of 74 operations: pituitary adenoma (n = 9, 16%), hyperparathyroidism (n = 38, 31%), gastrinoma (n = 1, 33%), NSPT (n = 5, 36%), and all cases of insulinoma, adrenal tumors, and thymic-NET. One patient died before age 21 due to a thymic-NET. Overall, lesions were malignant in four cases. CONCLUSIONS: Various MEN1 lesions occurred frequently before 21 years old, but mainly after 10 years of age. Rare, aggressive tumors may develop at any age. Hyperparathyroidism was the most frequently encountered lesion but was not always the first biological or clinical abnormality to appear during the course of MEN1.

Olmesartan-associated enteropathy: results of a national survey.

BACKGROUND: Recently, a new enteropathy has been described: olmesartan-associated enteropathy. However, the association has been questioned: a phase 3 trial and a cohort study found no association between gastrointestinal events and olmesartan. AIM: To collect French cases of sartan-associated enteropathy to describe further this entity, confirm or refute causality, and determine if the association exists with other sartans. METHODS: French gastroenterologists were invited to report cases of sartan-associated enteropathy and collect clinical, biological and histological data. Patients with diarrhoea and histological duodenal abnormalities were included. RESULTS: Thirty-six patients with olmesartan-associated enteropathy were reported, including 32 with villous atrophy and four without. There was only one patient with irbesartan-associated enteropathy. None of the patients died. Patients with villous atrophy had diarrhoea, vomiting, renal failure, hypokalaemia, body weight loss and hypoalbuminaemia. Thirty-one patients were hospitalised; four required intensive care. Anti-transglutaminase and anti-enterocyte antibodies were negative; anti-nuclear antibodies were positive (9/11). Endoscopic duodenal biopsies showed villous atrophy (32/32) and polyclonal intra-epithelial CD3+CD8+ lymphocytosis (11/11). Exactly, 14/15 patients responded to steroids and/or immunosuppressants, prescribed because of suspected autoimmune enteropathy. Ten olmesartan interruptions were followed by reintroductions before steroids or immunosuppressants. Interruptions were followed by remissions (9/10), but reintroductions were followed by relapses (9/9). Twenty-nine patients were in remission since olmesartan interruption, including 26 without immunosuppressants. Patients with normal villi had similar clinical characteristics, but mild histological abnormalities (intra-epithelial lymphocytosis and lamina propria lymphocytic infiltration). CONCLUSIONS: Olmesartan causes a severe and immune-mediated enteropathy, with or without villous atrophy. Enteropathy associated with other sartans seems to be very rare.

Factors associated with pregnancy outcome in anti-TNF treated women with inflammatory bowel disease.

BACKGROUND: The safety of anti-tumour necrosis factor (TNF) agents during pregnancy is a major concern for child-bearing women and physicians. AIM: To assess the impact of anti-TNF therapy on adverse pregnancy and foetal outcomes in women with inflammatory bowel disease (IBD). METHODS: Pregnancies occurring during anti-TNF treatment or less than 3 months after its cessation in IBD patients followed in GETAID centres were recorded from January 2009 to December 2010. Ninety-nine pregnancies in women without anti-TNF treatment were identified from the CESAME registry. We compared pregnancy and neonatal outcomes by a case-control study. RESULTS: In the 124 IBD patients followed, 133 pregnancies were reported. At the conception time, 23% of patients had active disease. Eighty-eight per cent (n = 117) of the 133 pregnancies followed until delivery resulted in 118 liveborns (one twin pregnancy). Complications were observed in 47 (35%) women and 24 (20%) newborns. In multivariate analysis, factors associated with pregnancy complications were: current smoking (P = 0.004), a B2 (stenotic) phenotype in CD women (P = 0.004), occurrence of a flare during pregnancy (P = 0.006) and a past history of complicated pregnancy (P = 0.007). Current smoking was the only factor associated with severe (i.e. potentially lethal) pregnancy complications (P = 0.02). Having IBD for more than 10 years prior to conception was associated with newborn complications (P = 0.007). No difference was found with the control group for any of the pregnancy and neonatal outcomes. CONCLUSION: In our series, the safety profile of anti-TNF therapy during pregnancy and the neonatal period appears similar to control group of IBD women not treated with anti-TNF therapy.

Gastroscopy-associated transmission of extended-spectrum beta-lactamase-producing Pseudomonas aeruginosa.

An unusual multi-drug-resistant Pseudomonas aeruginosa (MDR-PA) was isolated in four patients whilst hospitalized in a French teaching hospital between May and August 2011. All four patients had undergone an oesophago-gastro-duodenoscopy with the same gastroscope over a five-month period. This endoscope was associated with a culture positive for the MDR-PA. Observations of endoscope reprocessing identified deviations from the agreed processes: insufficient initial cleaning, shortening of the immersion time and brushing time, insufficient channel flushing, and inadequate drying prior to storage. Since withdrawing the gastroscope and institution of strict adherence to the agreed processes, no other MDR-PA cases have been isolated.

Gender-related differences in MEN1 lesion occurrence and diagnosis: a cohort study of 734 cases from the Groupe d'etude des Tumeurs Endocrines.

CONTEXT: Multiple endocrine neoplasia type 1 (MEN1) disease is an autosomal dominant syndrome that is believed to equally affect men and women. This assumption has never been confirmed. OBJECTIVE: The aims of this study were to evaluate the impact of gender on the prevalence of MEN1 lesions, on their lifetime probability of occurrence, and on the diagnosis of MEN1. DESIGN: Data regarding a study of 734 cases of MEN1 from the multicenter 'Groupe d'étude des Tumeurs Endocrines' were analyzed. RESULTS: There were 57.8% females. The prevalence and probability of pancreatic tumors were higher in males than in females (P=0.06, P=0.0004). This difference was due to gastrinomas. The prevalence and probability of developing pituitary tumors were significantly greater in females (P<0.001, P<0.0001). Thymic tumors were exclusively found in men. There were no significant gender differences in the prevalence and the probability of developing hyperparathyroidism, or adrenal and bronchial tumors, or in the proportion of positive genetic tests. A family history of MEN1 was more frequently found in men than in women at the time of diagnosis (P=0.02). In the case of pituitary tumor, the proportion of patients diagnosed with MEN1 at the time of the first lesion was lower in women (44.2%) than in men (67.3%). CONCLUSION: The phenotype expression of the MEN1 disease gene was different in males and females. In female patients, the possibility of MEN1 is not sufficiently taken into account. Any patient presenting a lesion that belongs to the MEN1 spectrum, such as a pituitary tumor, should be closely questioned about their family history and should be tested for hypercalcemia.

Neuroendocrine tumors of the stomach (gastric carcinoids) are on the rise: small tumors, small problems?

Well differentiated neuroendocrine tumors (NETs) of the stomach (gastric carcinoid tumors) are observed more often, with a tenfold increase in the US in the last 30 - 35 years, and the prognosis has improved greatly in that time. Nowadays most carcinoids of the stomach are diagnosed at an early stage. Four types of gastric NETs have been proposed and recognition of the type is important for defining the diagnostic approach and treatment. Often gastric NETs (especially type 1) are found incidentally during a gastroscopy performed for other reasons; most of these NETs are smaller than 20 mm in size. Conservative management and endoscopic surveillance is adequate for well differentiated, multifocal gastric carcinoids (type 1 or type 2 gastric NETs) that are less than 10 - 20 mm in diameter, unless they show angioinvasion, infiltrate the muscular wall, or have a proliferation rate above 2 %. Endoscopic ultrasound is the method of choice to determine tumor size and depth of infiltration. It is essential to distinguish between multifocal (types 1 and 2) and unifocal type 3 or type 4 gastric NETs, since surgery is indicated for type 3 gastric NETs larger than 10 mm in diameter and for poorly differentiated (localized) neuroendocrine gastric carcinomas (type 4 gastric NET). For optimal management, the type, biology, and stage of the tumor as well as the individual situation of the patient must be considered. Most patients with well differentiated gastric NETs can be treated conservatively and be followed up with endoscopic surveillance.

Increased risk of colonic neoplasia in patients with sporadic duodenal adenoma.

BACKGROUND: Recent studies have shown an increased risk of colorectal neoplasia in patients with duodenal neoplasia. The aim of this retrospective case-control study was to confirm this risk. PATIENTS AND METHODS: Rate of colorectal neoplasia in 29 patients with one or more duodenal adenomas were compared with controls matched for gender and age, but without duodenal adenomas (one case to two controls). Patients with neoplasia of the ampulla, familial adenomatous polyposis or other known hereditary conditions of the digestive tract were excluded. Indications for upper and lower gastrointestinal endoscopy in controls were abdominal pain or changes in bowel habits. Controls with anemia or digestive bleeding were not included. Neoplastic lesions found at colonoscopy were classified as adenomas, advanced adenomas (size > or =10 mm, villous component, high-grade dysplasia), cancers and advanced neoplasia (cancers and advanced adenomas). Comparison between groups was by Fisher's exact test or Student's t test. Odds-ratios (OR) and 95% confidence intervals were calculated, if the difference was significant. RESULTS: Mean age of the 29 cases (seven women, 22 men) was 63.2 years and that of the 58 controls (14 women, 44 men) was 62.5 years. First-degree family history of colorectal cancer was present in four cases (13.8%) and eight controls (13.8%) (NS). Colonoscopy showed at least one adenoma in 15 cases (51.7%) and 11 controls (19%) (P=0.0027; OR 1.87, 1.0-3.49), advanced adenomas in four cases (13.8%) and three controls (5.2%) (NS), and colonic adenocarcinoma in three cases (10.3%) and no controls (0%) (P=0.03). Advanced neoplasia was present in seven cases (24.1%) and three controls (5.2%) (P=0.014; OR 2.86, 0.96-8.52). Results were not significantly modified after the exclusion of patients with a family history of colorectal cancer. CONCLUSION: Although lacking in statistical power, these results confirm that patients with sporadic duodenal adenoma are at high risk of colonic adenoma and advanced neoplasia, warranting systematic colonoscopy.

Thirteen-month registration of patients with gastroenteropancreatic endocrine tumours in France.

The prevalence, clinical profiles and management of gastroenteropancreatic endocrine tumours (GEP) in France are not known. From August 1, 2001 to September 1, 2002, standardized records on patients with GEP were prospectively completed in 87 participating centres. The total group amounted to 668 patients (median age: 56 years, range: 12-89). WHO performance status was 0/1 for 80.2% of patients. The primary sites were the small bowel and colon (288), pancreas (211), unknown (77), stomach (33), non-digestive primary sites (24), appendix (20), rectum-anus (12), and oesophagus or cardia (3). GEP were functional in 260 patients (39%). Most pancreatic tumours were non-functional (72%). Metastatic disease was observed in 73.4% of cases. Most tumours (85.8%) were well or moderately differentiated. Somatostatin receptor scintigraphy was performed in only 55% of patients. The following treatment modalities were employed: resection of primary tumour: 66%; systemic chemotherapy: 41%; somatostatin analogues: 44 and 26% for GEP of small intestine and pancreas, respectively; interferon: 12%, and intra-arterial hepatic (chemo)embolization in 23 and 15% of GEP arising from the midgut and pancreas, respectively. Despite their low prevalence, well-differentiated GEP represent a significant and heterogeneous clinical group, which warrants improved medical education, referral to expert centres at an early stage, and the design of prospective therapeutic trials.

Clinical trial: Radiofrequency energy delivery in proton pump inhibitor-dependent gastro-oesophageal reflux disease patients.

BACKGROUND: Radiofrequency (RF) energy delivery is an endoscopic procedure developed for the treatment of gastro-oesophageal reflux disease. AIM: To compare RF and a proton pump inhibitor strategy (PPI) in PPI-dependent patients by carrying out a prospective, randomized trial. METHODS: Patients with PPI-dependent typical reflux symptoms were randomly allocated to either RF or PPI regimen alone. The primary endpoint, evaluated at 6-month, was defined as the possibility for the patient to stop or to decrease PPI use to <50% of the effective dose required at baseline. RESULTS: In the RF group, 18/20 patients stopped (n = 3) or decreased (n = 15) PPI use as compared to eight of 16 in the PPI group (P = 0.01). None of the control patients could stop PPI. Health-related quality of life scores were not different between groups. No significant change in oesophageal acid exposure (OAE) was noted between baseline and 6-months after RF. No severe complication was reported. CONCLUSIONS: Radiofrequency energy delivery is a safe and effective therapeutic option, allowing reduction in or discontinuation of PPI therapy in patients with PPI-dependent symptoms, without loss of quality of life. However, in a majority of patients, PPI therapy cannot be completely stopped. The efficacy of RF does not seem to be related to a decrease in OAE.

Nodular regenerative hyperplasia in patients with inflammatory bowel disease treated with azathioprine.

AIM: To assess the characteristics and clinical course of nodular regenerative hyperplasia (NRH) in patients with inflammatory bowel disease treated with azathioprine, so as to estimate the frequency of this complication and search for risk factors. METHODS: Cases were identified through a systematic survey of patients followed at 11 centres. At one centre, the cumulative risk of NRH was estimated and a case-control study was undertaken to identify risk factors. RESULTS: 37 cases of NRH (30 male, 7 female) were identified between 1994 and 2005. The median dose of azathioprine was 2 mg/kg/d (range 1.5 to 3.0). The median time between the start of azathioprine and the diagnosis of NRH was 48 months (range 6 to 187). After a median follow up period of 16 months (range 1 to 138), 14 patients developed complications of portal hypertension. Using multivariate analysis, male sex and stricturing behaviour were the two risk factors associated with NRH in patients treated with azathioprine. The cumulative risk calculated from the database (one centre) was 0.5% at 5 years (95% confidence interval, 0.11 to 0.89) and 1.25% at 10 years (0.29 to 2.21). CONCLUSIONS: NRH is a rare but potentially severe complication of azathioprine in patients with inflammatory bowel disease. Clinicians should be aware of this complication, and should monitor liver function tests and platelet counts closely in their patients.

[A Multiple endocrine neoplasia type-1 observatory in a French-speaking area. A tool from the Endocrine Tumor study Group (GTE)]. / Observatoire francophone des néoplasies endocriniennes multiples de type 1. Un outil du Groupe d'étude des Tumeurs Endocrines (GTE).

Wermer's syndrome or Multiple Endocrine Neoplasia Type-1 (MEN1) is an autosomal dominant inherited disease, related to mutations in MEN1, an approximately 10-kb gene encoding menin, localized on chromosome 11q13. The Endocrine Tumor Group (GTE) has set up a MEN1 observatory of 1001 regularly followed MEN1 cases. This observatory aims at registering and evaluating MEN1 cases in a large cohort. Any new study on a particular unexplored aspect of the disease may be proposed by a physician to the GTE. This article describes the way to diagnose a new MEN1 case and to register it. Procedures for participating in a new study are presented. Some original results are quoted.