Publications by authors named "Bernard Goichot"

97 Publications

What Is the Quality of Life in Patients Treated with Levothyroxine for Hypothyroidism and How Are We Measuring It? A Critical, Narrative Review.

J Clin Med 2021 Mar 30;10(7). Epub 2021 Mar 30.

Service d'Endocrinologie, Maladies Métaboliques et Nutrition, Pôle Cardio-Vasculaire et Métabolique, Hôpital Larrey, CHU de Toulouse, 31059 Toulouse, France.

Thyroid hormone replacement therapy (THRT, generally using oral levothyroxine (LT4)) is a safe, effective means of treating hypothyroidism. However, a proportion of LT4-treated patients with biochemically normal thyroid function tests complain of persistent symptoms that impact their health-related quality of life (QoL). The objectives of this critical, narrative review of the literature were to identify studies of QoL in LT4-treated patients with hypothyroidism, examine the instruments used to measure QoL, determine whether normal QoL is restored by THRT, and identify factors associated with QoL. The PubMed database was searched from 1 January 2000 to 31 December 2020. A total of 809 publications were screened, 129 full-text articles were retrieved, and 58 were analyzed. The studies of overt hypothyroidism evidenced an improvement in psychological and emotional well-being after three to six months of THRT with LT4, although contrasting results were found for patients with subclinical hypothyroidism. Combination treatment with LT4 and liothyronine was not generally associated with better QoL. In hypothyroidism, QoL appears to be influenced by a number of physiological, behavioral, cognitive and/or lifestyle factors that are not strictly related to thyroid hormone levels.
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http://dx.doi.org/10.3390/jcm10071386DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8037475PMC
March 2021

Plasmatic and Urinary 5-Hydroxyindolacetic Acid Measurements in Patients With Midgut Neuroendocrine Tumors: A GTE Study.

J Clin Endocrinol Metab 2021 Mar;106(4):e1673-e1682

Department of Hepato-Gastroenterology and Digestive Oncology, Hôpital Robert Debré and Université Reims-Champagne-Ardenne, Reims, France.

Context: Although 24-hour urinary 5-hydroxyindolacetic acid (24u5HIAA) is a key biomarker in midgut neuroendocrine tumors (NETs), it may be inaccurate and inconvenient.

Objective: We compared the diagnostic performances of 24u5HIAA, overnight urinary 5HIAA (Ou5HIAA), and plasmatic 5HIAA (p5HIAA) in midgut NETs.

Methods: This prospective, multicenter study included 80 patients with metastatic midgut NETs and 17 control patients with irritable bowel syndrome. 24u5HIAA, Ou5HIAA, and p5HIAA were measured in urine and plasma collected on 2 consecutive days following a specific recommended diet. Reproducibility of the biomarkers was evaluated by the Spearman test. Diagnostic performance was assessed by the area under the receiver operating characteristic curve (AUROC). Correlations with the main clinical features and declared observance to the specific diet were assessed using AUROC and logistic regression models.

Results: The reproducibility of 24u5HIAA, Ou5HIAA, and p5HIAA were excellent (ρ = 0.916; 0.897; 0.978, respectively, P < .001) with significant discrimination between patients and controls (AUROC = 0.795, P < .001; 0.757, P = .001; 0.717, P = .005, respectively). All 3 markers were correlated with the presence of carcinoid syndrome (AUROC = 0.702, P = .006; 0.701, P = .006; 0.697, P = .007, respectively), carcinoid heart disease (AUROC = 0.896; 0.887; 0.923, P < .001, respectively, P < .001), and liver metastatic involvement greater than 30% (AUROC = 0.827; 0.807; 0.849, P < .001, respectively, P < .001), independent from other traditional prognostic factors. Biomarker levels were similar between patients with optimal or suboptimal diet observance.

Conclusion: Ou5HIAA and p5HIAA could be used as more convenient alternatives to 24u5HIAA in patients with metastatic midgut NETs. Prospective long-term studies with repeated dosages are needed.
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http://dx.doi.org/10.1210/clinem/dgaa924DOI Listing
March 2021

A novel, automated, quantification of abnormal lung parenchyma in patients with COVID-19 infection: Initial description of feasibility and association with clinical outcome.

Anaesth Crit Care Pain Med 2021 Feb 13;40(1):100780. Epub 2020 Nov 13.

Department of Anesthesiology and Intensive Care, Hautepierre Hospital, Strasbourg University Hospital, France; Institut Hospitalo-Universitaire "Image-Guided Surgery", Strasbourg University Hospital, Strasbourg, France; Equipe d'Accueil 3072, Medical School, Strasbourg University, Strasbourg, France.

Objective: Ground-glass opacities are the most frequent radiologic features of COVID-19 patients. We aimed to determine the feasibility of automated lung volume measurements, including ground-glass volumes, on the CT of suspected COVID-19 patients. Our goal was to create an automated and quantitative measure of ground-glass opacities from lung CT images that could be used clinically for diagnosis, triage and research.

Design: Single centre, retrospective, observational study.

Measurements: Demographic data, respiratory support treatment (synthetised in the maximal respiratory severity score) and CT-images were collected. Volume of abnormal lung parenchyma was measured with conventional semi-automatic software and with a novel automated algorithm based on voxels X-Ray attenuation. We looked for the relationship between the automated and semi-automated evaluations. The association between the ground-glass opacities volume and the maximal respiratory severity score was assessed.

Main Results: Thirty-seven patients were included in the main outcome analysis. The mean duration of automated and semi-automated volume measurement process were 15 (2) and 93 (41) min, respectively (p=8.05*10). The intraclass correlation coefficient between the semi-automated and automated measurement of ground-glass opacities and restricted normally aerated lung were both superior to 0.99. The association between the automated measured lung volume and the maximal clinical severity score was statistically significant for the restricted normally aerated (p=0.0097, effect-size: -385mL) volumes and for the ratio of ground-glass opacities/restricted normally aerated volumes (p=0.027, effect-size: 3.3).

Conclusion: The feasibility and preliminary validity of automated impaired lung volume measurements in a high-density COVID-19 cluster was confirmed by our results.
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http://dx.doi.org/10.1016/j.accpm.2020.10.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7664353PMC
February 2021

Middle-segment preserving pancreatectomy for multifocal neuroendocrine pancreatic tumors.

Surg Oncol 2020 Dec 14;35:466-467. Epub 2020 Oct 14.

Hepato-Pancreato-Biliary Surgery and Liver Transplantation, Pôle des Pathologies Digestives, Hépatiques et de la Transplantation, Hôpital de Hautepierre-Hôpitaux Universitaires de Strasbourg, Université de Strasbourg, Strasbourg, France.

Background: Multifocal neuroendocrine tumors (NET) usually occur in the context of a multiple neuroendocrine neoplasia type 1 (MEN1). When the proximal part of the pancreatic body is spared by NET, Miura et al. have proposed a "middle-segment preserving" pancreatectomy (MSP) as alternative to total pancreatectomy [1-3].

Video: A 28-year-old woman with MEN1 was referred for surgical resection of a multifocal pancreatic tumor with single metastasis located and a single liver metastasis in close contact with the left hepatic duct. The preoperative work-up by DOTATOC-PETSCAN revealed multifocal tumors sparing only the proximal part of the pancreatic body. Hormonal dosages were normal but Chromogranine A was elevated at 700 μg/l. At surgery pancreatic intraoperative ultrasonography confirmed the absence of tumor at the proximal part of the pancreas. A pancreaticoduodenectomy was performed first followed by a left pancreatectomy with partial splenectomy. A 3 × 5 cm remnant of the pancreatic body vascularized by a dorsal pancreatic artery was preserved (Fig. 1). A left hepatectomy was then performed (Fig. 2). Digestive reconstruction is performed by a pancreatojejunostomy with an externalized pancreatic stent (Fig. 3), hepaticojejunostomy and a gastrojejunal anastomosis.

Results: Surgery lasted 660 minutes. Postoperative course was uneventful but a late readmission was necessary because of pyelonephritis due to nephrolithiasis treated by ureteral stent insertion. At 11 months postoperative follow-up the patient was disease-free with no endocrine dysfunction under oral pancreatic enzyme supplementation. Total weight loss since surgery was 8 Kilograms.

Conclusions: A middle-segment-preserving pancreatectomy could be a valid surgical alternative to total pancreatectomy for multifocal pancreatic tumors sparing the proximal pancreatic body. This operation can achieve acceptable functional outcomes but large series with long-term follow up are needed to evaluate the advantages and results of MSP.
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http://dx.doi.org/10.1016/j.suronc.2020.10.004DOI Listing
December 2020

[36th Congress of the French Society of Endocrinology. SFE Marseille 2020].

Ann Endocrinol (Paris) 2020 09 31;81(4):127. Epub 2020 Jul 31.

Service de médecine interne, nutrition et endocrinologie, hôpitaux universitaires de Strasbourg, 1, avenue Molière, 67098 Strasbourg cedex, France. Electronic address:

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http://dx.doi.org/10.1016/j.ando.2020.07.001DOI Listing
September 2020

Intraindividual comparison of F-FDOPA and Ga-DOTATOC PET/CT detection rate for metastatic assessment in patients with ileal neuroendocrine tumours.

Clin Endocrinol (Oxf) 2021 Jan 15;94(1):66-73. Epub 2020 Sep 15.

Nuclear Medicine and Molecular Imaging, ICANS, University Hospitals of Strasbourg, Strasbourg, France.

Introduction: In patients with ileal neuroendocrine tumours (ileal NETs), head-to-head evaluation of diagnostic performances of Ga-DOTA-peptides and F-fluorodihydroxyphenylalanine ( F-FDOPA) positron emission tomography/computed tomography (PET/CT) has been performed in only few small patients' cohorts. The aim of this retrospective study was to compare Ga-DOTATOC and F-FDOPA PET/CT for metastatic disease assessment in a homogeneous large series of patients with well-differentiated ileal NETs.

Methods: All patients with ileal NETs who underwent both F-FDOPA and Ga-DOTATOC PET/CT within a 3-month period and no therapeutic change between the two studies were retrospectively included. The detection rates of both modalities were calculated using per-patient, per-region and per-lesion analyses.

Results: Forty one patients with ileal NETs were evaluated. F-FDOPA and Ga-DOTATOC showed similar detection rates according to per-patient (97% for both) and per-region analyses (94% for F-FDOPA vs 88% for Ga-DOTATOC, P = .35). For a total of 605 positive lesions, 458 (76%) were detected by both modalities, 122 (20%) exclusively by F-FDOPA PET/CT, and 25 (4%) by Ga-DOTATOC PET/CT only. In a per-lesion analysis, F-FDOPA PET/CT performed better than Ga-DOTATOC PET/CT (overall detection rates of 96% vs 80%; P < .001). F-FDOPA PET/CT detected significantly more metastases than Ga-DOTATOC PET/CT in the liver, peritoneum, abdominal and supra-diaphragmatic lymph nodes.

Conclusion: F-FDOPA PET/CT seems not inferior than Ga-DOTATOC PET/CT for the delineation of metastatic spread of ileal NETs. Therefore, according to local expertise and technical availability, F-FDOPA should be considered as a valid clinical diagnostic option for exhaustive metastatic assessment in patients with ileal NETs. Obviously, Ga-DOTATOC PET/CT remains mandatory for PRRT assessment. Further comparative studies are needed to determine the optimal approach in various clinical scenarios such as preoperative staging and primary tumour detection.
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http://dx.doi.org/10.1111/cen.14312DOI Listing
January 2021

Venous thromboembolism in non-critically ill patients with COVID-19 infection.

Thromb Res 2020 09 17;193:166-169. Epub 2020 Jul 17.

Division of Cardiovascular Medicine, Nouvel Hôpital Civil, Strasbourg University Hospital, Strasbourg, France; INSERM (French National Institute of Health and Medical Research), UMR 1260, Regenerative Nanomedicine, FMTS, Strasbourg, France. Electronic address:

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http://dx.doi.org/10.1016/j.thromres.2020.07.033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7367026PMC
September 2020

Laparoscopic resection of familial interaortocaval paraganglioma.

Surg Oncol 2020 06 17;33:143-144. Epub 2020 Feb 17.

Hepato-Pancreato-Biliary Surgery and Liver Transplantation, Pôle des Pathologies Digestives, Hépatiques et de La Transplantation, Hôpital de Hautepierre-Hôpitaux Universitaires de Strasbourg, Université de Strasbourg, Strasbourg, France.

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http://dx.doi.org/10.1016/j.suronc.2020.02.019DOI Listing
June 2020

Management of thyroid dysfunctions in the elderly. French Endocrine Society consensus 2019 guidelines. Short version.

Ann Endocrinol (Paris) 2020 10 21;81(5):511-515. Epub 2020 May 21.

Service d'endocrinologie et maladies métaboliques, CHU de Larrey, 31059 Toulouse, France. Electronic address:

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http://dx.doi.org/10.1016/j.ando.2020.05.002DOI Listing
October 2020

Solid pseudopapillary tumour should be part of differential diagnosis of focal pancreatic lesions with increased F-FDOPA uptake.

Clin Endocrinol (Oxf) 2020 07 5;93(1):78-81. Epub 2020 May 5.

Nuclear Medicine and Molecular Imaging, ICANS - University Hospitals of Strasbourg, Strasbourg, France.

Objective: To assess the specificity of increased F-dihydroxyphenylalanine ( F-FDOPA) uptake in patients who underwent PET/CT for suspicion of isolated pancreatic neuroendocrine tumour (pNET). False-positive results mimicking a pNET have been investigated.

Material And Methods: Carbidopa-assisted F-FDOPA PET/CT scans performed in patients with suspicion of localized pNET were retrieved. Only patients with a definitive diagnosis were retrospectively included. When available, the histopathological result after pancreatic surgery was the gold standard. In other cases, the diagnosis was based on endoscopic ultrasonography (EUS)/cytology and/or on concordant imaging results of at least two of the following: contrast-enhanced computed tomography (CE-CT), magnetic resonance imaging (MRI) and somatostatin receptor scintigraphy (SRS).

Results: Forty-four among 731 patients were selected. Among these, 36 patients (82%) were surgically treated, revealing pNET (n = 28), solid pseudopapillary tumour (SPT) (n = 4), adenocarcinoma (n = 2), serous cystadenomas (n = 1) and solitary fibrous tumour (n = 1) cases. An additional three cases of pNET were diagnosed by EUS/cytology. In the remaining five patients, a consensus was reached on follow-up imaging results: pNET (n = 1), serous cystadenoma (n = 2) and undetermined/no pNET (n = 2). Both specificity and negative predictive value of F-FDOPA PET/CT for localized pNET were 67%. Surprisingly, all four false-positive results were SPTs showing intense F-FDOPA uptake and negative SRS. There was no significant difference in F-FDOPA uptake intensity between PET-positive pNETs and SPTs.

Conclusion: F-FDOPA PET/CT is not specific for pNET in patients with localized pancreatic lesions. SPT could mimic pNET and should be part of differential diagnosis in such a clinical situation. If these results are confirmed in a broader population, the imaging pattern F-FDOPA PET-positive/SRS-negative lesions might be considered as the imaging phenotype of SPT.
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http://dx.doi.org/10.1111/cen.14202DOI Listing
July 2020

Severe Neutropenia and Agranulocytosis Related to Antithyroid Drugs: A Study of 30 Cases Managed in A Single Reference Center.

Medicines (Basel) 2020 Mar 19;7(3). Epub 2020 Mar 19.

Departments of Internal Medicine, Strasbourg University Hospitals, 67000 Strasbourg, France.

Background: The most important series devoted to antithyroid drug-induced severe neutropenia and agranulocytosis are Japanese studies, almost specifically in relation to the intake of methimazole. The clinical data of 30 Caucasian patients followed up for antithyroid drug-induced neutropenia at a third-level hospital are reported. The data of 30 patients with idiosyncratic antithyroid drug-induced neutropenia and agranulocytosis from a cohort study on drug-induced neutropenia and agranulocytosis conducted at the University Hospital of Strasbourg (France) were retrospectively reviewed. The mean patient age was 61.7 years old (range: 20-87), and the gender ratio (F/M) was 4. Several comorbidities were reported in 23 patients (76.7%), with the mean Charlson comorbidity index of 1. The causative drugs were carbimazole and benzylthiouracil, in 28 (93.3%) and 2 cases, respectively, prescribed primarily for multi-hetero-nodular goiter or thyroid nodule to 18 patients (60%). Sore throat and acute tonsillitis (40%), isolated fever (20%), septicemia (13.3%), documented pneumonia (6.7%), and septic shock (6.7%) were the main clinical features upon admission. The mean neutrophil count at nadir was 0.02 and 0 × 10/L (range: 0-0.3). Regarding the patients' hospital course: 13 cases (43.3%) worsened during hospitalization, severe sepsis was found in 26.7%, systemic inflammatory response syndrome-in 13.3%, and septic shock-in 3.3% of the cases, respectively. Broad-spectrum antibiotics were indicated for all the patients, and 21 (73.3%) of them received hematopoietic growth factors. Hematological recovery (neutrophil count ≥ 1.5 × 10/L) was seen at 8.3 days (range: 2-24), but faster in those receiving hematopoietic growth factors (4.9 days, = 0.046). Two patients died during hospitalization, and the rest had a favorable clinical outcome. Antithyroid drug-induced neutropenia represents a serious complication resulting from the rates of severe infections especially in those cases severe neutropenia. In this setting, an established procedure for the management of patients seems useful or even indispensable in view of potential mortality.
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http://dx.doi.org/10.3390/medicines7030015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7151575PMC
March 2020

Outcomes of Simultaneous Resection of Small Bowel Neuroendocrine Tumors with Synchronous Liver Metastases.

World J Surg 2020 07;44(7):2377-2384

Hepato-Pancreato-Biliary Surgery and Liver Transplantation, Pôle des Pathologies Digestives, Hépatiques et de la Transplantation, Hôpital de Hautepierre-Hôpitaux Universitaires de Strasbourg, Université de Strasbourg, 1, Avenue Molière, 67098, Strasbourg, France.

Background: This study evaluated the short- and long-term outcomes of synchronous resection of liver metastases (LM) from small bowel neuroendocrine tumors (SB-NET).

Methods: A retrospective review of patients undergoing resection for LMs from SB-NETs from January 1997 and December 2018 was performed.

Results: There were 44 patients with synchronous SB-NET and LMs. Perioperative and 90-day mortality values were zero, and the morbidity rate was 27%. The median overall survival (OS) was 128.4 months (CI 95% 74.0-161.5 months) with 1-, 3-, 5-, and 10-year survival rates of 100%, 83%, 79%, and 60%, respectively. Not achieving surgical treatment for LM was the unique independent factor for survival (HR 6.50; CI 95% 1.54-27.28; p = 0.01) in patients with unresected LMs having OS and 10-year survival rates (42 months, 33%) versus patients undergoing liver resection (152 months, 66%)(p = 0.0008). The recurrence rate was 81.8% and associated with longer OS and 5-year survival rates when limited to the liver [223 months (61%) vs 94 months (87%)].

Conclusions: Simultaneous resection of SB-NETs with synchronous LMs was safe and associated with considerable long-term survival even in the presence of bilobar disease. However, recurrence after resection was common (81%) but associated with longer survival rates when limited to the liver.
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http://dx.doi.org/10.1007/s00268-020-05467-5DOI Listing
July 2020

Identification of chloramphenicol in human hair leading to a diagnosis of factitious disorder.

Clin Toxicol (Phila) 2020 09 8;58(9):926-930. Epub 2020 Jan 8.

Institut de Médecine Légale, Strasbourg, France.

Chloramphenicol (2,2-dichloro-N-[1,3-dihydroxy-1-(4-nitrophenyl)porpan-2-yl]acetamide) is a bacteriostatic antibiotic of the phenicolated family, used in the past to treat meningitis, plague, cholera, or typhoid fever. Treatment with chloramphenicol can have life threatening side effects, the most serious of which is aplastic anemia, which may be fatal. For this reason, the antibiotic was removed from the French market in 2008. In this paper, the authors report the case of a woman consuming chloramphenicol possibly in the context of factitious disorder. After a capsule containing chloramphenicol was discovered in her hospital bed, a hair specimen (about 16 cm, brown, not oriented) was collected and sent to the toxicological laboratory in order to document exposure to chloramphenicol. The drug was identified in the hair specimen of the subject at 13.7 ng/mg. Identification of chloramphenicol in hair has not been reported in the literature. As consequence, the interpretation of the concentration, the dosage and the frequency of abuse are difficult to establish. Given the context, physicians considered the case as a possible factitious disorder, thus being a unique observation of using chloramphenicol in such a context.
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http://dx.doi.org/10.1080/15563650.2019.1708375DOI Listing
September 2020

Metabolomics of Small Intestine Neuroendocrine Tumors and Related Hepatic Metastases.

Metabolites 2019 Dec 11;9(12). Epub 2019 Dec 11.

Biophysics and Nuclear Medicine, University Hospitals of Strasbourg, 67098 Strasbourg, France.

To assess the metabolomic fingerprint of small intestine neuroendocrine tumors (SI-NETs) and related hepatic metastases, and to investigate the influence of the hepatic environment on SI-NETs metabolome. Ninety-four tissue samples, including 46 SI-NETs, 18 hepatic NET metastases and 30 normal SI and liver samples, were analyzed using 1H-magic angle spinning (HRMAS) NMR nuclear magnetic resonance (NMR) spectroscopy. Twenty-seven metabolites were identified and quantified. Differences between primary NETs vs. normal SI and primary NETs vs. hepatic metastases, were assessed. Network analysis was performed according to several clinical and pathological features. Succinate, glutathion, taurine, myoinositol and glycerophosphocholine characterized NETs. Normal SI specimens showed higher levels of alanine, creatine, ethanolamine and aspartate. PLS-DA revealed a continuum-like distribution among normal SI, G1-SI-NETs and G2-SI-NETs. The G2-SI-NET distribution was closer and clearly separated from normal SI tissue. Lower concentration of glucose, serine and glycine, and increased levels of choline-containing compounds, taurine, lactate and alanine, were found in SI-NETs with more aggressive tumors. Higher abundance of acetate, succinate, choline, phosphocholine, taurine, lactate and aspartate discriminated liver metastases from normal hepatic parenchyma. Higher levels of alanine, ethanolamine, glycerophosphocholine and glucose was found in hepatic metastases than in primary SI-NETs. The present work gives for the first time a snapshot of the metabolomic characteristics of SI-NETs, suggesting the existence of complex metabolic reality, maybe characteristic of different tumor evolution.
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http://dx.doi.org/10.3390/metabo9120300DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6950539PMC
December 2019

Prognostic and predictive value of nuclear imaging in endocrine oncology.

Endocrine 2020 01 16;67(1):9-19. Epub 2019 Nov 16.

Biophysics and Nuclear Medicine, Hautepierre Hospital, University Hospitals of Strasbourg, Strasbourg University/FMTS, Strasbourg, France.

In the last few years, the role and use of medical technologies in (neuro)endocrine oncology has greatly evolved allowing not only important diagnostic information but also prognostic stratification in different clinical situations. The terms "prognostic" and "predictive" are commonly used to describe the relationships between biomarkers and patients' clinical outcomes but have quite different meaning. The present work discusses the prognostic and predictive value of nuclear medicine imaging. It critically reviews the clinical significance and potential impact of molecular examinations on follow-up and therapeutic strategies in patients with neuroendocrine neoplasms, thyroid tumors, and adrenal malignancies.
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http://dx.doi.org/10.1007/s12020-019-02131-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7441826PMC
January 2020

Limited role of carbidopa-assisted F-FDOPA PET/CT in patients with sporadic non-functional gastroduodenal neuroendocrine neoplasms.

Ann Nucl Med 2019 Sep 15;33(9):697-707. Epub 2019 Jun 15.

Hepato-Pancreato-Biliary Surgery and Liver Transplantation, University Hospitals of Strasbourg, Strasbourg University, Strasbourg, France.

Objective: To evaluate F-fluorodihydroxyphenylalanine (F-FDOPA) positron emission tomography/computed tomography (PET/CT) after carbidopa premedication to localize sporadic, well-differentiated, nonfunctioning gastroduodenal neuroendocrine neoplasms (NENs).

Methods: Ten patients undergoing staging carbidopa-assisted F-FDOPA PET/CT before endoscopic or surgical resection of gastroduodenal NENs were retrospectively selected. Preoperative imaging work up also included CT, magnetic resonance imaging (MRI), and somatostatin receptor scintigraphy (SRS) single-photon emission computed tomography/computed tomography (SPECT/CT) in ten, six, and eight patients, respectively. Histopathological diagnosis of primary NEN was the diagnostic standard of truth. Metastatic spread was defined as the presence of histologically proven nodal, visceral, and/or bone metastases.

Results: Tumors were located in the duodenal bulb in five patients, in descending duodenum in three, and in the gastric fundus in two. Three patients presented with both lymph nodes and distant metastases, and two with exclusive lymphatic spread. CT and MRI detected primary tumor in one out of ten and three out of six patients, respectively. SRS failed to detect intestinal NEN in all cases. F-FDOPA PET/CT detected four primary NENs (one gastric and three duodenal tumors) and was false negative in six patients. NENs missed by F-FDOPA PET/CT were smaller than 10 mm in two cases and measured about 30 mm in three patients. The remaining tumor was detected only on blind endoscopic biopsy. Among patients who underwent both F-FDOPA PET/CT and SRS, three presented discordant results for primary tumor detection (PET/CT positive/SRS negative) and five showed concordant negative studies. F-FDOPA PET/CT correctly identified all three patients with both nodal and visceral metastatic disease and failed to detect lymph node metastases in both N+ M0 patients.

Conclusions: F-FDOPA PET/CT is not sufficiently accurate for localization of primary well-differentiated nonfunctioning sporadic gastroduodenal NENs. F-FDOPA PET/CT's value for the assessment of visceral and lymph node metastases needs to be clarified in multicenter trials including a larger number of patients.
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http://dx.doi.org/10.1007/s12149-019-01378-1DOI Listing
September 2019

Prognosis of Malignant Pheochromocytoma and Paraganglioma (MAPP-Prono Study): A European Network for the Study of Adrenal Tumors Retrospective Study.

J Clin Endocrinol Metab 2019 06;104(6):2367-2374

Department of Nuclear Medicine and Endocrine Tumors, Gustave Roussy, Villejuif, France.

Background: Malignant pheochromocytoma and paraganglioma (MPP) are characterized by prognostic heterogeneity. Our objective was to look for prognostic parameters of overall survival (OS) in MPP patients.

Patients And Methods: Retrospective multicenter study of MPP characterized by a neck-thoraco-abdomino-pelvic CT or MRI at the time of malignancy diagnosis in European centers between 1998 and 2010.

Results: One hundred sixty-nine patients from 18 European centers were included. Main characteristics of patients with MPP were: primary pheochromocytoma in 53% of patients; tumor- or hormone-related symptoms in 57% or 58% of cases; positive plasma or urine hormones in 81% of patients; identification of a mutation in SDHB in 42% of cases. Metastatic sites included bone (64%), lymph node (40%), lung (29%), and liver (26%); mean time between initial and malignancy diagnosis was 43 months (range, 0 to 614). Median follow-up was 68 months and median survival 6.7 years. Using univariate analysis, better survival was associated with head and neck paraganglioma, age <40 years, metanephrines less than fivefold the upper limits of the normal range, and low proliferative index. In multivariate analysis, hypersecretion [hazard ratio 3.02 (1.65 to 5.55); P = 0.0004] was identified as an independent significant prognostic factor of worst OS.

Conclusions: Our results do not confirm SDHB mutations as a major prognostic parameter in MPP and suggest additional key molecular events involved in MPP tumor progression. Aside from SDHB mutation, the biology of aggressive MPP remains to be understood.
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http://dx.doi.org/10.1210/jc.2018-01968DOI Listing
June 2019

Positive Impact of Genetic Test on the Management and Outcome of Patients With Paraganglioma and/or Pheochromocytoma.

J Clin Endocrinol Metab 2019 04;104(4):1109-1118

Équipe Labellisée par la Ligue Contre le Cancer, INSERM, UMR970, Paris-Centre de Recherche Cardiovasculaire, Paris, France.

Context: Pheochromocytomas and paragangliomas (PPGLs) are characterized by a strong genetic component, with up to 40% of patients carrying a germline mutation in a PPGL susceptibility gene. International guidelines recommend that genetic screening be proposed to all patients with PPGL.

Objective: Our objective was to evaluate how a positive genetic test impacts the management and outcome of patients with SDHx or VHL-related PPGL.

Design: We performed a multicentric retrospective study involving 221 propositi carrying an SDHB, SDHD, SDHC, or VHL germline mutation. Patients were divided into two groups: genetic patients, who were informed of their genetic status within the year following the first PPGL diagnosis, and historic patients, who only benefited from the genetic test several years after initial PPGL diagnosis.

Results: Genetic patients had better follow-up than historic patients, with a greater number of examinations and a reduced number of patients lost to follow-up (9.6% vs 72%, respectively). During follow-up, smaller (18.7 vs 27.6 mm; P = 0.0128) new PPGLs and metastases as well as lower metastatic spread were observed in genetic patients. Of note, these differences were reversed in the historic cohort after genetic testing. Genetic patients who developed metachronous metastases had a better 5-year survival rate than historic patients (P = 0.0127).

Conclusion: Altogether, our data suggest that early knowledge of genetic status had a positive impact on the management and clinical outcome of patients with a germline SDHx or VHL mutation.
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http://dx.doi.org/10.1210/jc.2018-02411DOI Listing
April 2019

F-FDOPA PET/CT Combined with MRI for Gross Tumor Volume Delineation in Patients with Skull Base Paraganglioma.

Cancers (Basel) 2019 Jan 8;11(1). Epub 2019 Jan 8.

Biophysics and Nuclear Medicine, University Hospitals of Strasbourg, 67098 Strasbourg, France.

In this simulation study, we assessed differences in gross tumor volume (GTV) in a series of skull base paragangliomas (SBPGLs) using magnetic resonance imaging (MRI), F-dihydroxyphenylalanine (F-FDOPA) combined positron emission tomography/computed tomography (PET/CT), and F-FDOPA PET/MRI images obtained by rigid alignment of PET and MRI. GTV was delineated in 16 patients with SBPGLs on MRI (GTV), F-FDOPA PET/CT (GTV), and combined PET/MRI (GTV). GTV was the union of GTV and GTV after visual adjustment. Three observers delineated GTV and GTV independently. Excellent interobserver reproducibility was found for both GTV and GTV. GTV and GTV were not significantly different. However, there was some spatial difference between the locations of GTV, GTV, and GTV. The Dice similarity coefficient median value was 0.4 between PET/CT and MRI, and 0.8 between MRI and PET/MRI. The combined use of PET/MRI produced a larger GTV than MRI alone. Nevertheless, both the target-delivered dose and organs-at-risk conservancy were respected when treatment was planned on the PET/MRI-matched data set. Future integration of F-FDOPA PET/CT into clinical practice will be necessary to evaluate the influence of this diagnostic modality on SBPGL therapeutic management. If the clinical utility of F-FDOPA PET/CT and/or PET/MRI is confirmed, GTV should be considered for tailored radiotherapy planning in patients with SBPGL.
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http://dx.doi.org/10.3390/cancers11010054DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6360018PMC
January 2019

Early F-FDOPA PET/CT imaging after carbidopa premedication as a valuable diagnostic option in patients with insulinoma.

Eur J Nucl Med Mol Imaging 2019 03 7;46(3):686-695. Epub 2019 Jan 7.

Biophysics and Nuclear Medicine, University Hospitals of Strasbourg, Strasbourg, France.

Purpose: Data on the diagnostic value of F-FDOPA PET/CT in patients with insulinoma are limited and are focused on small patient populations explored using different PET/CT protocols and the inconsistent use of carbidopa premedication. The aim of this study was to improve the current knowledge about the diagnostic value of F-FDOPA PET/CT combined with oral carbidopa premedication and early pancreatic imaging for tumour localization in patients with insulinoma-related hyperinsulinaemic hypoglycaemia (HH). The relationships among F-FDOPA quantitative uptake parameters, insulin secretion and tumour pathological features were also investigated.

Methods: Of 34 patients with suspicion of insulinoma-related HH examined by dual time-point carbidopa-assisted F-FDOPA PET/CT, 24 with histologically proven insulinoma were retrospectively included. One patient underwent two PET/CT examinations for relapsing insulinoma after surgical excision. Thus, 25 preoperative F-FDOPA PET/CT studies were finally retained and analysed. All studies were performed under carbidopa premedication (200 mg orally, 1-2 h prior to tracer injection). The PET/CT acquisition protocol included an early acquisition (5 min after F-FDOPA injection) over the upper abdomen and a delayed whole-body acquisition starting 20-30 min later. The cytological and/or histopathological diagnosis of insulinoma was the diagnostic standard of truth.

Results: F-FDOPA PET/CT localized insulinoma in 21 of the 25 studies, leading to a primary lesion detection rate of 84%. Four lesions (19%) were detected only on early acquisitions. The false-negative tumour detection rates were, respectively, 22% and 12.5% in patients receiving and not receiving treatment for hypoglycaemic symptoms at the time of PET/CT. In benign insulinomas, the early maximum standardized uptake value (SUVmax) was significantly higher than the delayed SUVmax. Compared to the 21 benign lesions, four malignant insulinomas showed significantly higher F-FDOPA uptake. Lesion size, fasting-end insulin and C-peptide levels correlated with tumour F-FDOPA uptake, dopaminergic tumour volume and metabolic burden.

Conclusion: The present study showed that F-FDOPA PET/CT combined with carbidopa premedication and early pancreatic acquisitions is a valuable diagnostic option in patients with insulinoma when GLP1R-based imaging is not available. The results also provide new insights into the relationships between tumour secretion and imaging phenotype in insulinomas.
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http://dx.doi.org/10.1007/s00259-018-4245-3DOI Listing
March 2019

Macrovascular venous invasion of pancreatic neuroendocrine tumours: impact on surgical outcomes and survival.

HPB (Oxford) 2019 06 3;21(6):653-661. Epub 2018 Dec 3.

Hepato-Pancreato-Biliary Surgery and Liver Transplantation, Pôle des Pathologies Digestives, Hépatiques et de la Transplantation, Hôpital de Hautepierre-Hôpitaux Universitaires de Strasbourg, Université de Strasbourg, Strasbourg, France. Electronic address:

Background: This study evaluates the impact of macrovascular venous invasion (MVI) on surgical and survival outcomes of pancreatic neuroendocrine tumours (PNETs).

Methods: We retrospectively reviewed data of 125 patients operated for PNETs. Operative, pathological,and survival outcomes were compared between PNETs with and without MVI.

Results: Macrovascular venous invasion was detected in 25 of 125 PNETs (20%) presenting as tumour thrombi (n = 12) or venous wall invasion (n = 13). MVI was associated with larger tumours, a higher rate of lymph node involvement, less differentiated tumours, and a higher rate of perineural invasion. Resection of PNETS with MVI more often necessitated combined hepatic, venous and multivisceral resections, had a higher rate of intraoperative blood transfusion (p = 0.04) but similar morbidity (44% vs. 42%) and mortality (0 vs. 1%) as PNETs without MVI. PNETs with MVI had a lower median overall survival rate (60 vs. 149 months; p = 0.03). Multivariate analysis revealed that PNETs of the pancreatic head, synchronous liver metastases and higher tumour grade were prognostic factors for overall survival.

Conclusions: MVI is found in more advanced PNETs. Resection of PNETs with MVI is characterized by increased transfusion rate and reduced overall survival.
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http://dx.doi.org/10.1016/j.hpb.2018.10.010DOI Listing
June 2019

The Role of Endoscopic Endonasal Approach in the Multimodal Management of Giant Pituitary Adenoma: Case Report and Literature Review.

Asian J Neurosurg 2018 Jul-Sep;13(3):888-892

Department of Neurosurgery, Hautepierre University Hospital, Strasbourg, France.

Giant pituitary adenomas (GPAs) are defined as pituitary lesions larger than 40 mm of diameter. Surgical resection remains the gold standard to decompress the optic apparatus, reduce lesion load, and preserve hormonal function. The endoscopic endonasal approach (EEA) has been increasingly used for the treatment of pituitary adenomas and skull base tumors due to the wide angle of view and exposure. Through the description of an exemplificative case of EEA resection of a nonsecreting GPA in the setting of a multimodal treatment, the authors discuss the advantages and disadvantages of this management strategy and provide a detailed review of the literature.
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http://dx.doi.org/10.4103/ajns.AJNS_97_18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6159024PMC
October 2018

Diagnostic procedure in suspected Graves' disease.

Ann Endocrinol (Paris) 2018 Dec 18;79(6):608-617. Epub 2018 Aug 18.

Service d'endocrinologie, CHU de Rabat, Rabat, Morocco.

Diagnostic procedure in suspected Graves' disease has never been studied scientifically and actual practice seems quite variable, notably between countries. Recommendations are few and weak (expert opinion). This article presents the recommendations of an expert consensus meeting organized by the French Society of Endocrinology in 2016. In case of clinically suspected thyrotoxicosis, the first-line biological assessment is of thyroid-stimulating hormone (TSH). Free T4 and possibly free T3 assays assess biological severity and are necessary for treatment efficacy monitoring. Positive diagnosis of Graves' disease after biological confirmation of thyrotoxicosis does not always require complementary etiological examinations if clinical presentation is unambiguous, notably including extra-thyroid signs. Otherwise, first-line anti-TSH-receptor (TSH-R) antibody screening is recommended for its good intrinsic performance (sensitivity and specificity) and ease of access in France. Scintigraphy is reserved to rare cases of Graves' disease with negative antibody findings or when another etiology is suspected. Thyroid ultrasound scan may be contributive, but is not recommended in first line.
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http://dx.doi.org/10.1016/j.ando.2018.08.002DOI Listing
December 2018

18F-FDOPA Uptake Reflects the Efficacy of Dopamine Agonists Treatment in Pituitary Prolactinoma.

Clin Nucl Med 2018 Sep;43(9):e324-e325

Internal Medicine, University Hospitals of Strasbourg, University of Strasbourg, Strasbourg, France.

We report the results of F-FDOPA PET/CT in an asymptomatic MEN-1 patient with secreting pituitary prolactinoma investigated before and during dopamine agonists treatment. PET/CT showed intense and focal F-FDOPA uptake in the right part of anterior pituitary corresponding to a microadenoma on MRI imaging. Six months after the beginning of cabergoline, prolactin secretion normalized, pituitary F-FDOPA uptake completely regressed, and tumor size reduced on follow-up PET/CT and MRI, respectively.
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http://dx.doi.org/10.1097/RLU.0000000000002202DOI Listing
September 2018

Metabolic Response to BRAF-MEK Combination Therapy in Cecal Neuroendocrine Carcinoma With BRAFV600E Mutation and Refractory Lactic Acidosis.

Clin Nucl Med 2018 Sep;43(9):701-702

Department of Internal Medicine, Diabetes and Metabolic Disorders, University Hospitals of Strasbourg, Strasbourg University, Strasbourg.

We report the results of serial F-FDG PET/CT investigations in a 49-year-old woman presenting with an advanced cecal high-grade neuroendocrine carcinoma harboring a somatic BRAF mutation. Patient was refractory to standard chemotherapy regimen showing life-threatening hyperlactatemia. Early after the beginning of BRAF-MEK therapy (dabrafenib and trametinib), impressive improvement in PET/CT imaging was achieved. The pathological F-FDG uptake in cecal primary tumor as well as in nodal, hepatic, and bone metastases drastically decreased. Moreover, the reduction of total lesion glycolysis on PET/CT images was strictly related to extraordinary patient clinical response and lactic acid level normalization.
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http://dx.doi.org/10.1097/RLU.0000000000002231DOI Listing
September 2018

18F-FDOPA PET/CT of Nonfunctioning Paraganglioma of the Gastroepiploic Pedicle.

Clin Nucl Med 2018 Sep;43(9):e326-e328

Hepato-Pancreato-Biliary Surgery and Liver Transplantation.

We report the case of a 54-year-old woman with a nonfunctioning paraganglioma arising from the gastroepiploic pedicle demonstrated by F-FDOPA PET/CT. Because gastroepiploic arcade can be assimilated to the gastric mesentery, this tumor has been classified as a mesenteric paraganglioma (PGL). Neural crest cells are a multipotent population of cells characterized by effective migratory properties potentially explaining PGL atypical localization as in the mesentery. Mesenteric PGLs are often nonfunctioning and can mimic gastric, colic, or pancreatic primary tumor because of their anatomical boundaries, making more difficult the diagnosis on preoperative imaging.
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http://dx.doi.org/10.1097/RLU.0000000000002185DOI Listing
September 2018

Current Management and Predictive Factors of Lymph Node Metastasis of Appendix Neuroendocrine Tumors: A National Study from the French Group of Endocrine Tumors (GTE).

Ann Surg 2019 07;270(1):165-171

Hospices Civils de Lyon, Hôpital Edouard Herriot, Service de Gastroentérologie et d'Oncologie Médicale, Lyon, France.

Objective: The primary endpoint was to analyze the predictive factors of lymph node involvement (LN+).

Background: Indications for additional right hemicolectomy (RHC) with lymph node (LN) resection after appendectomy for appendix neuroendocrine tumor (A-NET) remain controversial, especially for tumors between 1 and 2 cm in size.

Methods: National study including all patients with nonmetastatic A-NET diagnosed after January, 2010 in France.

Results: In all, 403 patients were included. A-NETs were: within tip (67%), body (24%) or base (9%) of the appendix; tumor size was < 1 cm (62%), 1 to 2 cm (30%), or >2 cm (8%); grade 1 (91%); mesoappendix involvement 3 mm (5%); lymphovascular (15%) or perineural (24%) invasion; and positive resection margin (8%). According to the European NeuroEndocrine Tumor Society (ENETS) recommendations, 85 patients (21%) should have undergone RHC. The agreement between ENETS guidelines and the multidisciplinary tumor board for complementary RHC was 89%. In all, 100 (25%) patients underwent RHC with LN resection, 26 of whom had LN+. Tumor size (best cut-off at 1.95 cm), lymphovascular and perineural invasion, and pT classifications were associated with LN+. Among the 44 patients who underwent RHC for a tumor of 1 to 2 cm in size, 8 (18%) had LN+. No predictive factor of LN+ (base, resection margins, grade, mesoappendix, lymphovascular, perineural involvement) was found in this subgroup of patients.

Conclusions: In the largest study using the latest pathological criteria for completion RHC in A-NET, a quarter of patients had residual tumor. Further studies are warranted to demonstrate the survival impact of RHC in this setting.
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http://dx.doi.org/10.1097/SLA.0000000000002736DOI Listing
July 2019

A Persistent Migrating Rash.

Gastroenterology 2018 Sep 13;155(3):e7-e8. Epub 2018 Mar 13.

Hepato-Pancreato-Biliary Surgery and Liver transplantation, Pôle des Pathologies Digestives, Hépatiques et de la Transplantation, Hôpital de Hautepierre, Strasbourg, France.

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http://dx.doi.org/10.1053/j.gastro.2018.02.039DOI Listing
September 2018

Preoperative Imaging with F-FDOPA PET/CT for Small Bowel Neuroendocrine Tumors.

J Gastrointest Surg 2018 11 12;22(11):1992-1994. Epub 2018 Mar 12.

Biophysics and Nuclear Medicine, Hôpital de Hautepierre-Hôpitaux Universitaires de Strasbourg, 1, Avenue Molière, 67098, Strasbourg Cedex 09, France.

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http://dx.doi.org/10.1007/s11605-018-3729-6DOI Listing
November 2018