18F-FDOPA PET Compared With 123I-Metaiodobenzylguanidine Scintigraphy and 18F-FDG PET in Secreting Sporadic Pheochromocytoma

International audienceWe report the case of a 23-year-old man presenting a right hypersecreting pheochromocytoma, falsely negative on 18 F-FDG PET/CT and on 123 I-metaiodobenzylguanidine (123 I-MIBG) scintigraphy but strongly positive on 18 F-FDOPA PET/CT. Functional imaging has a key role in diagnosis and prognosis of pheochromocytomas, but choosing the most relevant modality remains difficult. Despite its high specificity, 123 I-MIBG has a limited sensitivity. 18 F-FDG can be used, but it is an unspecific tracer, and 18 F-FDG uptake in brown adipose tissue can hinder the analysis. However, 18 F-FDOPA shows very high sensitivity and specificity in pheochromocyto-mas with fewer drug interferences than 123 I-MIBG

Carcinoembryonic Antigen Increase in a Patient with Colon Cancer Who Have Achieved Complete Remission and Negative 18F-FDG PET/CT: Don’t Forget the Thyroid!

International audienceSerum carcinoembryonic antigen (CEA) is a tumor marker especially used to follow a patient with colorectal cancer. However, it is non-specific and could be increased in several cancers and some benign conditions. We report the case of a 70-year-old man followed since 2014 for a left colon adenocarcinoma with the persistence of an increased CEA. There was no evidence of recurrence, but a right lobar thyroid nodule without a significantly increased uptake was incidentally discovered on the CT scan of 18F-fluorodeoxyglucose (18F-FDG) PET/CT. We suspected a medullary thyroid carcinoma (MTC) explaining the persistent elevation of CEA. Plasma calcitonin levels were 47 ng/L (N < 10). Fine needle aspiration cytology found atypia of undetermined significance and the patient was reluctant to undergo surgery without any further exploration. We performed a 18Ffluorodihydroxyphenylalanine (18F-FDOPA) PET/CT preoperatively which revealed a punctiform focus of the right thyroid lobe corresponding to a pT1aN1aMxR0 medullary thyroid carcinoma, histopathologically confirmed. This case highlights that despite the potential usefulness of 18F-FDG PET/CT in case of an unknown source of elevated CEA this imaging may be falsely negative as in the case of MTC and should lead to further explorations

Predictive value of preoperative DeMeester score on conversion to Roux-en-Y gastric bypass for gastroeosophageal reflux disease after sleeve gastrectomy

International audienceBackground: Obesity is well known to increase the risk of gastroesophageal reflux disease (GERD). The impact of sleeve gastrectomy (SG) on GERD is still discussed but seems to be associated with the development of de novo GERD or the exacerbation of preexisting GERD.Objective: The objective of this study was to evaluate the impact of preoperative pH monitoring, using the DeMeester score (DMS), on the risk of conversion to Roux-en-Y gastric bypass (RYGB) after SG.Setting: University Hospital in Nantes, France.Methods: This monocentric study reported the results of a retrospective chart review of 523 obese individuals treated between 2011 and 2018. All patients underwent primary bariatric surgery; 95% had undergone an SG. GERD diagnosis was established with preoperative DMS based on 24-hour esophageal pH monitoring.Results: Preoperative DMS was identified in 423 patients (86%). Sixty-seven patients (14%) underwent a second bariatric procedure; among them, 36 (54%) have been converted to RYGB because of GERD. There was no significant difference between preoperative DMS (16.1 ± 22 versus 13.7 ± 14, P = .37) in patients undergoing conversion for GERD and the nonconverted ones. The sensitivity, specificity, positive predictive, and negative predictive values of the preoperative DMS for predicting conversion to RYGB were 25%, 66%, 7%, and 4%, respectively. In patients who underwent a conversion for GERD, DMS (P < .002), rates of esophagitis (P = .035), and hiatal hernia (P = .039) significantly increased after SG.Conclusion: Preoperative DMS alone is not predictive of the risk of conversion of SG to RYGB for GERD

Comparison of Morbidity After Total Thyroidectomy Among Adult Patients With and Without Preoperative Hyperthyroidism.

International audienceHyperthyroidism is common, diagnosed in 2.0% of women and 0.2% of men worldwide. The main treatments for hyperthyroidism are antithyroid drugs, radioiodine, and surgery. Thyroidectomy has been reported to be an effective, safe, and cost-saving method and to have the lowest recurrence rate compared with radioiodine and antithyroid drugs.1 However, total thyroidectomy requires more careful and accurate hemostasis when performed in patients with hyperthyroidism vs patients with normal thyroid function (euthyroidism).2 The aim of this nonrandomized clinical trial was to compare the incidence of morbidity after total thyroidectomy among patients with preoperative hyperthyroidism vs patients with preoperative euthyroidism.MethodsWe performed an analysis of data collected in the FOThyr (Medico-Economic Evaluation Comparing the Use of Ultrasonic Scissors to the Conventional Techniques of Haemostasis in Thyroid Surgery by Cervicotomy; NCT01551914) study.3 The FOThyr study, conducted from March 2012 to June 2014, was a prospective randomized multicenter clinical trial comparing the use of a disposable hemostatic device with the use of conventional hemostasis for total thyroidectomy among adult patients. The study protocol was reviewed and approved by a regional ethics committee (Comité de Protection des Personnes Ouest IV) and by the national data protection authority in France (Commission Nationale de l’Informatique et des Libertés). The study was performed in accordance with the Guideline for Good Clinical Practice and the Declaration of Helsinki. All patients provided written informed consent before inclusion.All patients planning to undergo total thyroidectomy were eligible for inclusion if they had Graves disease, euthyroid or hyperthyroid goiter, or any thyroid nodule requiring total thyroidectomy via cervicotomy. In accordance with guidelines from the French Society of Endocrinology (http://www.sfendocrino.org), all patients with overt hyperthyroidism (ie, high triiodothyronine and/or thyroxine hormone levels) received preoperative antithyroid drugs to normalize thyroid hormone levels.An evaluation of recurrent laryngeal nerve function was systematically conducted after each surgery. A vocal cord examination with nasofibroscopy was performed before hospital discharge and 6 months after surgery to monitor potential postoperative recurrent laryngeal nerve abnormality.Postoperative hypocalcemia was defined as a serum calcium level lower than 8.0 mg/dL (corrected for albumin level; to convert to mmol/L, multiply by 0.172) at postoperative day 2, and definitive hypocalcemia was defined as a serum calcium level lower than 36.0 mg/dL at 6 months after surgery. Clinical observation was performed during hospitalization to diagnose potential hematomas. Data analysis was performed using SAS software, versions 9.2 and 9.3 (SAS Institute). Data were analyzed from September to December 2017.ResultsFrom March 2012 to June 2014, 1250 patients with usable data (mean [SD] age, 50.9 [13.3] years; 997 women [79.8%]) were enrolled at 14 sites in France. At the preoperative consultation, 255 patients (20.4%) had hyperthyroidism, and 995 patients (79.6%) had euthyroidism. All preoperative patient characteristics are shown in Table 1.Postoperative abnormal vocal cord mobility was diagnosed in 130 of 1250 patients (10.4%), representing 102 of 995 patients (10.3%) in the euthyroidism group and 28 of 255 patients (11.0%) in the hyperthyroidism group (difference, 0.70%; 95% CI, −0.05% to 0.04%) (Table 2). Definitive recurrent nerve palsy (RNP) was diagnosed in 12 patients (1.0%), representing 10 patients (1.0%) in the euthyroidism group and 2 patients (0.8%) in the hyperthyroidism group (difference, 0.22%; 95% CI, −0.01% to 0.02%). Postoperative hypocalcemia was diagnosed in 250 patients (20.0%), representing 196 patients (19.7%) in the euthyroidism group and 54 patients (21.2%) in the hyperthyroidism group (difference, 1.50%; 95% CI, −0.08% to 0.04%). Definitive hypocalcemia was diagnosed in 25 patients (2.0%), representing 19 patients (1.9%) in the euthyroidism group and 6 patients (2.4%) in the hyperthyroidism group (difference, 0.48%; 95% CI, −0.03% to 0.02%).DiscussionIn the present study, preoperative hyperthyroidism was not associated with substantial increases in the incidence of complications (neither postoperative nor definitive hypocalcemia, RNP, or hematoma) after total thyroidectomy among patients who received preoperative antithyroid drugs. These morbidity results may be surprising, given that one would expect a substantial difference between patients with preoperative hyperthyroidism and those with euthyroidism. However, our results are consistent with those of other studies.4,5This nonrandomized clinical trial was large (1250 patients), with minimal postoperative missing data. Data collection was thorough with regard to preoperative and immediate postoperative data but less thorough with regard to late postoperative data, especially for RNP incidence. Approximately 50% of postoperative patients with RNP chose not to undergo postoperative laryngoscopy at 6 months, which may have produced underestimation of definitive RNP. However, Lifante et al6 have reported an association between the incidence of definitive and immediate postoperative palsies.This study has 2 primary limitations. First, the FOThyr study, from which the sample for the present study was obtained, was not designed to assess morbidity but to evaluate the 6-month clinical efficacy and cost-effectiveness of using ultrasonic scissors (HARMONIC FOCUS; Johnson & Johnson) compared with conventional hemostasis for thyroidectomy.3 Second, data on thyroid-stimulating hormone levels were only collected at the first preoperative consultation; we did not collect data on thyroid-stimulating hormone, triiodothyronine hormone, or thyroxine hormone levels on the day of surgery. Because the study lacked data on thyroid hormone levels immediately before surgery, the effectiveness of preoperative treatments could not be assessed.Medical treatment should precede surgery. However, the results of this large nonrandomized clinical trial may encourage endocrine surgeons to reassure and motivate patients to undergo total thyroidectomy as a definitive treatment for hyperthyroidism

High-flow Nasal Cannulae Versus Non-invasive Ventilation for Preoxygenation of Obese Patients: The PREOPTIPOP Randomized Trial

International audienceIn obese patients, preoxygenation with non-invasive ventilation (NIV) was reported to improve outcomes compared with facemask. In this setting, high-flow nasal cannulae (HFNC) used before and during intubation has never been studied against NIV

Effect of parathyroidectomy on quality of life and non-specific symptoms in normocalcaemic primary hyperparathyroidism

International audienceBACKGROUND: Normocalcaemic primary hyperparathyroidism (NcPHPT) is a new clinical entity being diagnosed increasingly among patients with mild primary hyperparathyroidism (PHPT). The aim of this study was to evaluate quality of life and non-specific symptoms before and after parathyroidectomy in patients with NcPHPT compared with those with hypercalcaemic mild PHPT (Hc-m-PHPT).METHODS: This was a prospective multicentre study of patients with mild PHPT from four university hospitals. Patients were evaluated before operation, and 3, 6 and 12 months after surgery for quality of life using the SF-36-v2® questionnaire, as well as for 25 non-specific symptoms.RESULTS: Before operation, the only statistically significant difference between the NcPHPT and Hc-m-PHPT groups was in the mean(s.d.) blood calcium level (2·54 versus 2·73 mmol; P &lt; 0·001). At 1 year after surgery, the blood calcium level had improved significantly in both groups, with no significant difference between them. Quality of life improved significantly in each group compared with its preoperative score, with regard to the physical component summary (P = 0·040 and P = 0·016 respectively), whereas the mental component summary improved significantly in the Hc-m-PHPT group only (P = 0·043). Only two non-specific symptoms improved significantly in the NcPHPT group compared with nine in the Hc-m-PHPT group.CONCLUSION: Parathyroidectomy mildly improves quality of life and some non-specific symptoms in patients with NcPHPT.</p

Mild sporadic primary hyperparathyroidism: high rate of multiglandular disease is associated with lower surgical cure rate

International audienceBACKGROUND:Mild primary hyperparathyroidism (serum calcium ≤ 2.85 mmol/L) is the most representative form of pHPT nowadays. The aim of this study was to evaluate its subtypes and the multiglandular disease (MGD) rate as it may lower the sensitivity of preoperative parathyroid scintigraphy and the surgical cure rate.METHODS:We retrospectively included patients with mild pHPT who underwent parathyroid dual-tracer scintigraphy with 99mTc-MIBI SPECT/CT and surgery between January 2013 and December 2015. Cure was defined as normalization of serum calcium (or PTH in the normocalcemic form) at 6 months. MGD was defined by either two abnormal resected glands or persistent disease after resection of at least one abnormal gland.RESULTS:We included 121 patients. Median preoperative serum calcium was 2.68 mmol/L and median PTH was 83.4 pg/mL. A total of 141 glands were resected (95 adenomas, 33 hyperplasias). The subtypes were 57% classic, 32.2% normohormonal, and 10.7% normocalcemic. MGD occurred in 23.5% of patients divided as 13%, 30%, and 64% respectively (p = 0.0011). The surgical cure rate was 85.2%. The normocalcemic form had lower cure rate than the normohormonal (45% vs 84%, p = 0.018) and classic forms (45% vs 93%, p = 0.0006). MIBI scintigraphy identified at least one abnormal lesion, later confirmed by the pathologist in 90/98 patients, making the sensitivity per patient 91.8% (95% CI 84.1-96.2%).CONCLUSIONS:MGD is strongly associated with mild pHPT, especially the normocalcemic form where it accounts for 64% of cases. Bilateral neck exploration should be performed in this population to improve the cure rate, even if the scintigraphy shows a single focus

Pretargeted radioimmunotherapy (pRAIT) in medullary thyroid cancer (MTC).

International audiencePrognosis of medullary thyroid carcinoma (MTC) varies from long- to short-term survival, based on prognostic factors, such as serum calcitonin doubling time (Ct DT). Pretargeted radioimmunotherapy (pRAIT) is a novel targeted radionuclide therapy, using a bispecific monoclonal antibody (BsMAb) and a radiolabeled bivalent hapten, designed to improve the therapeutic index and to deliver increased tumor-absorbed doses to relatively radioresistant solid tumors. Pretargeting has demonstrated a more favorable therapeutic index and clinical efficacy than directly labeled anti-carcinoembryonic antigen (CEA) MAb in preclinical MTC models. Moreover, two phase I/II clinical trials assessing anti-CEA × anti-DTPA-indium BsMAb (murine F6x734 and chimeric hMN14x734) with (131)I-di-DTPA-indium showed encouraging therapeutic results in progressive, metastatic, MTC patients, with an improved survival in intermediate- and high-risk (pre-pRAIT Ct DT, <2 years) patients, as compared to contemporaneous untreated patients (median overall survival, 110 months vs 61 months; P < 0.030). pRAIT efficacy has been recently confirmed in a prospective multicenter phase II study assessing hMN14x734 and (131)I-di-DTPA-indium in rapidly progressive MTC patients. New pRAIT compounds are now available with fully humanized, recombinant, trivalent BsMAb (anti-CEA TF2) and histamine-succinyl-glutamine (HSG) peptides. The HSG peptide allows easy and stable labeling with different radiometals, such as (177)Lu or (90)Y beta-emitters having favorable physical features for pRAIT or (68)Ga and (18)F positron-emitters, allowing the development of a highly sensitive and specific immuno-positron emission tomography method in MTC or other CEA-positive tumors

Stable Isotope Abundance and Fractionation in Human Diseases

International audienceThe natural abundance of heavy stable isotopes (13C, 15N, 18O, etc.) is now of considerable importance in many research fields, including human physiology. In fact, it varies between tissues and metabolites due to isotope effects in biological processes, that is, isotope discriminations between heavy and light isotopic forms during enzyme or transporter activity. The metabolic deregulation associated with many diseases leads to alterations in metabolic fluxes, resulting in changes in isotope abundance that can be identified easily with current isotope ratio technologies. In this review, we summarize the current knowledge on changes in natural isotope composition in samples (including various tissues, hair, plasma, saliva) found in patients compared to controls, caused by human diseases. We discuss the metabolic origin of such isotope fractionations and highlight the potential of using isotopes at natural abundance for medical diagnosis and/or prognostic

In vivo evidence for transintestinal cholesterol efflux in patients with complete common bile duct obstruction

International audienceBackground: Beyond the hepatobiliary pathway, studies have demonstrated that direct TransIntestinal Cholesterol Efflux (TICE) of plasma-derived cholesterol may contribute to reverse cholesterol transport. The clinical evidence of TICE in human remains challenged due to the difficulty to discriminate the hepatobiliary and transintestinal routes in vivo. Objective: To provide the first proof of concept that TICE exists in vivo in humans by demonstrating that plasma labeled cholesterol can be excreted in the feces of patients with complete bile duct obstruction. Methods: Plasma, bile and fecal cholesterol excretion was measured by mass spectrometry 24, 48 and 72h after intravenous injection of D7-cholesterol in two patients presenting cholangiocarcinomas with a total obstruction of their primary bile duct. Results: No trace of bile acids was detected in the feces of the two patients. Despite this, a significant amount of plasma D7-cholesterol was quantified in the feces of the two patients 48h and 72h after the intravenous injection. Conclusion: our data bring a direct proof that TICE is an active pathway in humans. ClinicalTrials.gov Registration number: NCT01958216 Highlights: The transintestinal (TICE) route is crucial for plasma cholesterol excretion in rodent To date, the physiological relevance of TICE in humans remains questioned Patients with obstructed biliary route can excrete plasma cholesterol in their feces TICE is an active pathway in human