Medullary thyroid cancer outcomes in patients with undetectable versus normalized postoperative calcitonin levels.

BACKGROUND: Calcitonin (Ct) is a sensitive diagnostic biomarker and one of the most important prognostic factors in medullary thyroid cancer (MTC). This study aimed to evaluate progression-free survival and recurrence rates of MTC associated with undetectable compared with normalized serum Ct levels after surgery. METHODS: This retrospective observational study included patients operated for MTC at the Digestive and Endocrine Surgery Department of Lyon Sud Hospital Centre between 2000 and 2019. Clinical and pathological factors were correlated with postoperative Ct concentrations. Undetectable and normalized Ct concentrations were defined as below 2 pg/ml and 2-10 pg/ml respectively. RESULTS: Overall, 176 patients were treated for MTC, and 127 were considered biochemically cured after surgery. Of these, 24 and 103 had normalized and undetectable Ct concentrations respectively. Patients with Ct level normalization had a 25 per cent risk of disease recurrence, compared with 3 per cent in patients with undetectable Ct levels after surgery. The presence of metastasis in two or more compartments was predictive of failure to achieve undetectable Ct concentrations after surgery and an increased risk of recurrence. CONCLUSION: Among patients with biochemically cured MTC, those with undetectable or normalized Ct concentrations after surgery had different risks of recurrence. Simply assessing postoperative Ct normalization can be falsely reassuring, and long-term follow-up is needed. LAY SUMMARY: Calcitonin (Ct) is a sensitive diagnostic biomarker and one of the most important prognostic factors for medullary thyroid cancer outcomes; however, the significance of postoperative Ct levels remains controversial. This study evaluated the differences between normal and undetectable postoperative Ct levels in patients who had undergone surgical treatment for medullary thyroid cancer. Patients who experienced postoperative Ct level normalization had a higher risk of disease recurrence than those with undetectable Ct levels after surgery.

Calcitonin (Ct) is a sensitive diagnostic biomarker and one of the most important prognostic factors for medullary thyroid cancer outcomes; however, the significance of postoperative Ct levels remains controversial. This study evaluated the differences between normal and undetectable postoperative Ct levels in patients who had undergone surgical treatment for medullary thyroid cancer. Patients who experienced postoperative Ct level normalization had a higher risk of disease recurrence than those with undetectable Ct levels after surgery.

[Endocrine surgery during and after the COVID-19 epidemic: Guidelines from AFCE]. / Chirurgie endocrinienne au cours et au décours de l'épidémie de COVID-19 : recommandations de l'AFCE.

The COVID-19 pandemic commands a major reorganization of the entire French healthcare system. In France, general rules have been issued nationally and implemented by each healthcare center, both public and private, throughout France. Guidelines drafted by an expert group led by the French-speaking Association of Endocrine Surgery (AFCE) propose specific surgical management principles for thyroid, parathyroid, endocrine pancreas and adrenal surgery during and after the COVID-19 epidemic.

Endocrine surgery during and after the COVID-19 epidemic: Expert guidelines from AFCE.

The COVID-19 pandemic commands a major reorganisation of the entire French healthcare system. In France, general rules have been issued nationally and implemented by each healthcare centre, both public and private, throughout France. Guidelines drafted by an expert group led by the French-speaking Association of Endocrine Surgery (AFCE) propose specific surgical management principles for thyroid, parathyroid, endocrine pancreas and adrenal surgery during and after the COVID-19 epidemic.

Preoperative Role of RAS or BRAF K601E in the Guidance of Surgery for Indeterminate Thyroid Nodules.

BACKGROUND: RAS and K601E BRAF mutations are not a reliable indicator of malignancy in fine-needle aspirations (FNA) of thyroid indeterminate cytologic nodules. We aimed to evaluate the histologic characteristics, the risk of malignancy associated with such mutations in FNA and their potential interest for preoperative clinical management of nodules. METHODS: We evaluated 69 indeterminate thyroid nodules with RAS or K601E BRAF mutations with available histopathologic follow-up. All FNA specimens were indeterminate according to the thyroid Bethesda system. Diagnosis of malignant, benign or indolent neoplasms was classified according to 2017 WHO classification. Carcinoma, NIFTP (noninvasive follicular thyroid neoplasm with papillary-like features) and WDTUMP (well-differentiated tumor of uncertain malignant potential) were considered "surgical," as they require surgical excision. Adenoma was considered "non-surgical." The risk of malignancy and the risk of "surgical disease" were evaluated. RESULTS: Pathologic evaluation of the 69 mutated nodules demonstrated benign, indolent and malignant histology in 17 cases (25%), 21 cases (30%) and 31 cases (45%), respectively. The risk of malignancy was 45%, and the risk of surgical disease was 75%. The majority of carcinomas were a follicular variant of papillary thyroid carcinoma. On follow-up, there have been no recurrences to date. CONCLUSION: Preoperative RAS or BRAF K601E mutations detection in cytologic indeterminate thyroid nodules carries a high risk of surgical disease and may benefit from surgical management. Most surgical lesions harboring those mutations are low-risk tumors, which may be in favor of an initial lobectomy.

Poorly differentiated thyroid carcinoma with pleomorphic giant cells-a case report.

Poorly differentiated thyroid carcinoma (PDTC) refers to a malignant tumour that displays an intermediate prognosis between well-differentiated carcinomas and anaplastic thyroid carcinomas (ATC). In the thyroid, pleomorphic giant cells are observed in ATC or in some non-neoplastic thyroid diseases. We described the case of a 43-year-old woman with a 34-mm nodule in her thyroid right lobe. Microscopic examination revealed an encapsulated tumour with a main solid growth pattern and extensive capsular invasion. Multiple images of angioinvasion were observed. There was neither necrosis nor inflammation. Most of the tumour cells were medium-sized and intermingled with pleomorphic giant tumour cells with bizarre features. The immunoprofile (keratins +, TTF1+, Pax 8+) proved their thyroid origin. By NGS, no molecular alteration was identified. The patient was treated by surgery and radioiodine therapy and she has no recurrence after a follow-up of 24 months. Our case meets all the histological criteria of the Turin proposal for PDTC but with pleomorphic giant cells and is very different from ATC according to clinical, histological and immunohistochemical features. Pleomorphic tumour giant cells in thyroid carcinomas could be present in PDTC and do not always represent dedifferentiation and more aggressive carcinoma, thyroid neoplasm.

Impact of total thyroidectomy on quality of life at 6 months: the prospective ThyrQoL multicentre trial.

OBJECTIVE: This study is to determine the impact of complications after total thyroidectomy on health-related quality of life (HR-QoL) and to identify significant predictive factors of HR-QoL changes. HR-QoL is usually impaired in patients with thyroid diseases compared to the general population. Thyroidectomy is largely performed in the case of benign thyroid benign and can be associated with long-term complications (vocal cord palsy, hypoparathyroidism). DESIGN: The prospective ThyrQoL multicenter trial (NCT02167529) included 800 patients who underwent total thyroidectomy for benign or malignant non-extensive disease in seven French referral hospitals between 2014 and 2016. METHODS: HR-QoL was assessed using the MOS 36-item short form health survey (SF-36) self-questionnaire with a 6-month follow-up. RESULTS: We observed a significant improvement of HR-QoL 6 months after surgery (P < 0.0001). Postoperative complications were associated with a non-significant impairment of HR-QoL. In multivariable analysis, Graves' disease was associated with a significant improvement of HR-QoL (OR = 2.39 [1.49; 3.84]) and thyroid malignant disease with an impairment of HR-QoL (OR = 1.44 [0.99; 2.08]) after thyroidectomy. CONCLUSION: We observed a significant improvement of HR-QoL 6 months after total thyroid surgery for benign thyroid disease.

Molecular testing of BRAF, RAS and TERT on thyroid FNAs with indeterminate cytology improves diagnostic accuracy.

OBJECTIVE: Liquid-based (LB)-FNA is widely recognized as a reliable diagnostic method to evaluate thyroid nodules. However, up to 30% of LB-FNA remain indeterminate according to the Bethesda system. Use of molecular biomarkers has been recommended to improve its pathological accuracy but implementation of these tests in clinical practice may be difficult. Here, we evaluated feasibility and performance of molecular profiling in routine practice by testing LB-FNA for BRAF, N/HRAS and TERT mutations. METHODS: We studied a large prospective cohort of 326 cases, including 61 atypia of undetermined significance, 124 follicular neoplasms, 72 suspicious for malignancy and 69 malignant cases. Diagnosis of malignancy was confirmed by histology on paired surgical specimen. RESULTS: Mutated LB-FNAs were significantly associated with malignancy regardless of the cytological classification. Overall sensitivity was 60% and specificity 89%. Importantly, in atypia of undetermined significance and follicular neoplasm patients undergoing surgery according to the Bethesda guidelines, negative predictive values were 85.4% and 90% respectively. TERT promoter mutation was rare but very specific for malignancy (5.5%) suggesting that it could be of interest in patients with indeterminate cytology. CONCLUSIONS: Mutation profiling can be successfully performed on thyroid LB-FNA without any dedicated sample in a pathology laboratory. It is an easy way to improve diagnostic accuracy of routine LB-FNA and may help to better select patients for surgery and to avoid unnecessary thyroidectomies.

Cluster randomized trial to evaluate the impact of team training on surgical outcomes.

BACKGROUND: The application of safety principles from the aviation industry to the operating room has offered hope in reducing surgical complications. This study aimed to assess the impact on major surgical complications of adding an aviation-based team training programme after checklist implementation. METHODS: A prospective parallel-group cluster trial was undertaken between September 2011 and March 2013. Operating room teams from 31 hospitals were assigned randomly to participate in a team training programme focused on major concepts of crew resource management and checklist utilization. The primary outcome measure was the occurrence of any major adverse event, including death, during the hospital stay within the first 30 days after surgery. Using a difference-in-difference approach, the ratio of the odds ratios (ROR) was estimated to compare changes in surgical outcomes between intervention and control hospitals. RESULTS: Some 22 779 patients were enrolled, including 5934 before and 16 845 after team training implementation. The risk of major adverse events fell from 8·8 to 5·5 per cent in 16 intervention hospitals (adjusted odds ratio 0·57, 95 per cent c.i. 0·48 to 0·68; P < 0·001) and from 7·9 to 5·4 per cent in 15 control hospitals (odds ratio 0·64, 0·50 to 0·81; P < 0·001), resulting in the absence of difference between arms (ROR 0·90, 95 per cent c.i. 0·67 to 1·21; P = 0·474). Outcome trends revealed significant improvements among ten institutions, equally distributed across intervention and control hospitals. CONCLUSION: Surgical outcomes improved substantially, with no difference between trial arms. Successful implementation of an aviation-based team training programme appears to require modification and adaptation of its principles in the context of the the surgical milieu. Registration number: NCT01384474 (http://www.clinicaltrials.gov).

Is it possible to limit the risks of thyroid surgery?

OBJECTIVE: Inferior laryngeal nerve (ILN) palsy and hypocalcemia remain the two most frequent major complications after thyroid surgery. Their occurrences may be explained by the influence of factors related to the patient, the surgical procedure, thyroid pathology, or the surgeon's technique. This study aims To assess whether systematically following a rigorous surgical technique during thyroidectomy affects postoperative complications and long-term patient recovery. METHODS: We conducted a multicenter, cross-sectional study of prospectively collected data in five high-volume referral centers enrolling all patients who underwent thyroid surgery between April 2008 and December 2009. Inferior laryngeal nerve (ILN) palsy and hypocalcemia were systematically assessed during hospitalization based on objective criteria. A six-month follow-up was conducted in cases of early complications. Multivariate regression models were computed to quantify their relationship with potential risk factors. RESULTS: A total of 3574 thyroid procedures were completed. Non-visualization of the ILN during dissection and a large thyroid mass were major risk factors for permanent ILN palsy (OR, 4.17 and 2.61, p<0.01) and persistent complications after initial injury (OR, 4.17 and 2.42, p<0.05). The presence of thyroiditis on the surgical specimen was an independent risk factor for permanent hypoparathyroidism and poor recovery after initial dysfunction (OR, 1.76 and 1.88, p<0.05). CONCLUSIONS: Thorough meticulous technique in thyroid surgery is a determinant of ILN function but fails to prevent persistent hypoparathyroidism.

Management of adrenal incidentaloma.

Improvements in medical imaging have resulted in the incidental discovery of many silent and unrecognized adrenal tumors. The term "adrenal incidentaloma" (AI) is applied to any adrenal mass≥1cm in its longest axis that is discovered incidentally during abdominal imaging that was not performed to specifically evaluate adrenal pathology. These incidentalomas may be either secretory or non-secretory, benign or malignant. Distinctive characteristics of these lesions must be determined by the clinician to determine appropriate management. Such distinctions are based on laboratory findings and imaging, principally CT with and without contrast injection. Investigations must be carefully chosen to avoid ordering unnecessary and expensive tests for too many patients while, at the same time, avoiding the risk of failing to diagnose a secreting malignant or tumor. These examinations will determine patient care: surgery or surveillance. When simple surveillance is chosen, specific criteria must be met with regard to diagnostic modalities (clinical, imaging, laboratory testing) and its duration.

[Assessment of the check-list in the operating room: perceptions of caregivers and physicians (level II assessment)]. / Évaluation de la check-list au bloc opératoire : la perception des soignants et des médecins (évaluation du niveau II).

OBJECTIVE: To assess, a year after the deployment of the check-list in the centre hospitalier Lyon Sud (CHLS - HCL), the perception of medical and nursing staff regarding the advantages of the check-list and its level of integration within the overall organization of the operating room. TYPE OF STUDY: Descriptive study, questionnaires and audits. MATERIALS AND METHODS: Distribution of individual questionnaires to the entire operating room staff, and observational audits in the operating room, to objectively assess the quality of implementation of the check-list (level II of the HAS - French National Autority of Health). RESULTS: The medical and nursing staff participated equally in using the check-list. This was derived from the individual questionnaires and reinforced by the observational audit; they also revealed an uneven implementation of the three phases, with phase 3 almost never performed. In two-third of the cases, the time-out requirements did not comply with HAS instructions. Nurses and physicians perceived the check-list differently. Even though they agreed that the check-list should be a team effort and is useful, nurses noted a lack of investment and leadership from doctors, in addition to communication problems, which led to a feeling of disrespect towards them when they play the role of the check-list coordinator. CONCLUSION: The questionnaire and the audit of practice showed strong adherence to the concept in that the surgical check-list was considered useful by all staff. However, it was also considered to be an added formality and its full implementation was rare in practice. There was a problem of distribution and acceptance of roles with nurses often observing that they were the only ones strictly following the check-list due to a lack of medical investment.

(18)F-FDG uptake at initial staging of the adrenocortical cancers: a diagnostic tool but not of prognostic value.

BACKGROUND: Adrenocortical carcinoma (ACC) is a rare cancer for which little level evidence exists to guide management. (18)F-FDG PET ((18)F-fluorodeoxyglucose positron emission tomography) is an increasingly used diagnostic tool in patients with suspicious or indeterminate adrenal tumors. In some other solid tumors, (18)F-FDG PET may offer prognostic information that can guide optimal patient treatment. The aim of the present study was to evaluate whether preoperative (18)F-FDG PET based on SUVs assessments has a prognostic value in ACC patients. METHODS: A retrospective analysis was performed in patients who underwent (18)F-FDG PET/CT for the evaluation of ACC. Inclusion criteria were an unequivocal diagnosis of ACC; all data from primary diagnosis available; (18)F-FDG PET/CT performed prior to surgery or other treatment of the primary tumor; a minimum of 6-months follow-up for surviving patients. All (18)F-FDG PET/CT procedures were reinterpreted in a blind fashion. RESULTS: Thirty-seven patients (23 without metastasis [M0], 14 with metastasis [M1]) fulfilled the study criteria. Median uptake values were tumor standardized uptake values (SUV)(max) = 11 (range: 3-56) and a tumor/liver SUV(max) ratio = 4.2 (range: 1.3-15). Median follow-up was 20 months. Although classic risk factors (tumoral stage, Weiss score) were associated with poor outcome, there was no correlation between primary tumor FDG uptake with overall survival (OS) and disease free survival (DFS) in M0 patients and with overall survival in M1 patients. (18)F-FDG uptake correlated inconsistently with sinister histological features, such as atypical mitoses or necrosis. CONCLUSIONS: At initial staging, primary tumor FDG uptake in ACC patients does not correlate with OS and DFS at 2 years. Patient prognosis and treatment strategy should not be based on uptake values.

Pheochromocytoma revealed by acute heart failure. When should we operate? Presented at the ESES Congress, Gothenburg May 25-26, 2012.

PURPOSE: The aim of this study was to assess the safety and efficacy of adrenalectomy on patients with pheochromocytoma diagnosed at the time of an acute heart failure (AHF). METHODS: We reported cases of patients who presented an AHF secondary to a pheochromocytoma during a period of 10 years. The diagnosis of AHF was defined by a left ventricular ejection fraction of less than 30 % or the use of circulatory assistance. They had adrenalectomy as emergency surgery or later. Morbidity and mortality of surgery were studied. RESULTS: Thirteen patients required an adrenalectomy for AHF secondary to pheochromocytoma. Four patients (31 %) had an adrenalectomy in emergency. Nine patients (69 %) had a delayed surgery with a median delay of 25 days (7-180). Eight patients had circulatory assistance (61 %). Five of them had a circulatory assistance and a delayed surgery (38 %), two of them had a circulatory assistance followed by emergency surgery (at 1.5 and 3 days) and one had emergency surgery immediately followed by circulatory assistance. Emergency surgery was performed by laparotomy in all cases and delayed surgery by laparoscopy for seven patients (54 %). Perioperative complications consisted in: one circulatory arrest, two bleedings requiring transfusion, one intestinal ischaemia, one haemoperitoneum with re-operation (day 8). One patient died on day 5. Post-operative course of patients with delayed surgery was uneventful. CONCLUSIONS: AHF revealing a pheochromocytoma is a rare and serious event. Patients with emergency surgery have more complications than those with delayed surgery.

Hospital volume influences the choice of operation for thyroid cancer.

BACKGROUND: Many authors advocate total or near-total thyroidectomy for thyroid carcinoma. This study examined the relationship between hospital volume of thyroidectomies and choice of bilateral thyroidectomy for thyroid carcinoma. METHODS: Data were extracted from the administrative databases of all hospital discharge abstracts in the Rhône-Alpes area of France. The study population included inpatient stays from 1999 to 2004 with a diagnosis of thyroid disease (benign or malignant) and a procedural code for thyroid surgery. Multivariable logistic regression analyses were performed to determine factors associated with the extent of surgery (unilateral versus bilateral) for thyroid carcinoma. RESULTS: A total of 20 140 thyroidectomies were identified, including 4006 procedures for cancer. Compared with hospitals performing a high volume of procedures for all thyroid diseases (at least 100 annually), the risk of a unilateral procedure for thyroid cancer increased by 2.46 (95 per cent confidence interval 1.63 to 3.71) in low-volume hospitals (fewer than ten operations per year) and by 1.56 (1.27 to 1.92) in medium-volume centres (ten to 99 per year). CONCLUSION: There is a significant relationship between hospital volume and the decision to perform bilateral surgery for thyroid carcinoma. Thyroid cancer surgery should be performed by experienced surgical teams in high-volume centres.

Quality monitoring in thyroid surgery using the Shewhart control chart.

BACKGROUND: A control chart can help to interpret and reduce sources of variability in patient safety by continuously monitoring indicators. The aim of this study was to monitor the outcome of thyroid surgery using control charts. METHODS: Patients who had thyroid surgery during 2006-2007 were included in the study. Safety was monitored based on postoperative complications of recurrent laryngeal nerve palsy and hypocalcaemia. Indicators were extracted prospectively from the hospital information system and plotted each month on a P-control chart. Performance of the surgical team was also measured retrospectively for 2004-2005 (baseline period) to compare surgical outcomes before and after control chart implementation. Electromyographic monitoring of recurrent laryngeal nerves was not used, nor was calcium or vitamin D given routinely. RESULTS: The outcomes of 1114 thyroid procedures were monitored. Although the proportion of patients with recurrent laryngeal nerve palsy was similar for baseline and monitored periods (6.4 and 7.2 per cent respectively), there was a 35.3 per cent decrease in hypocalcaemia after implementation of control charts (P < 0.001). Complications almost doubled during a period when one surgeon was away and operating room renovations took place. CONCLUSION: Outcome monitoring in thyroid surgery using control charts is useful for identifying potential issues in patient safety.

[Early improvement in Type 2 diabetes in obese patients following gastric bypass and bilio-pancreatic diversion: the role of the entero-insular axis]. / Traitement précoce du diabète de type 2 chez l'obèse après gastric bypass et diversion bilio-pancréatique: rôle de l'axe entéro-insulinique.

Improvement in Type 2 diabetes is seen in 80-98% of obese diabetic patients who undergo gastric bypass or bilio-pancreatic diversion. This improvement is evident early after the operation before significant weight loss has occurred. Although numerous teams have extensively studied the physiology of this early post-bypass amelioration of type 2 diabetes, the exact mechanism of diabetes remission remains unclear. Studies have focused on changes in the entero-insular axis, which is mediated in part by the interaction of insulinotropic hormones GIP and GIP 1 on the beta islet cells of the pancreas. Other mechanisms which have been postulated focus on the adipo-insular axis; the actions of adiponectin and leptin seem to have an important role in insulin resistance but their action is weight-loss dependent. Post-operative caloric restriction may also contribute to the early resolution of type 2 diabetes observed after gastric bypass and bilio- pancreatic diversion.

[Indications for sternotomy in thyroid surgery. Evolution over 20 years' experience]. / Evolution des indications de la sternotomie en chirurgie thyroïdienne. A propos d'une expérience de 20 ans.

From October 1984 to August 2005, 11,452 thyroidectomies were performed; 52 (0.45%) required a sternotomy. The patients included 32 women and 20 men. Sternotomy was total in 27 patients (52%) and partial in 25 (48%). Thirty patients (58%) had a benign goitre with intrathoracic extension, and 22 patients (42%) had thyroid malignancy. In 8 cases, the procedure was a reintervention. There were no post-operative deaths. Complications directly related to the sternotomy occurred in four patients (10%) and included one subcutaneous abscess, two cases of chylothorax (one requiring re-operation), and one pneumothorax. One patient developed a tight pseudoarthrosis of the sternotomy at eighteen months which caused neither pain nor functional disability. In comparing the first with the second decade of this study, we find that the incidence of sternotomy has not changed but that the indications have evolved. Initially sternotomy was indicated for benign intrathoracic goitres. More recently, thyroidectomy for malignancy, particularly in cases of re-operation, has been the major indication. Sternotomy is only rarely indicated in thyroid surgery. It adds moderately to hospital stay but does not increase morbidity when compared to the cervical approach.

Hürthle cell thyroid carcinoma metastatic to the sigmoid colon.

Prognosis of differentiated thyroid cancer is favorable in the majority of cases. However, distant metastases occur in 10-15% of cases, predominantly in lungs and bones, especially in older patients exhibiting poorly differentiated forms or advanced stages. We report a case history of Hürthle cell thyroid carcinoma metastasized to the sigmoid colon. To the best of our knowledge, this location has never been described before. This case history illustrates the difficulties of diagnosis and treatment in patients whose metastases do not concentrate radioiodine. The interest of different imaging modalities, including fluoro-deoxy-glucose positron emission tomography scan and somatostatin receptor scintigraphy, is discussed.