Correction to: Pheochromocytoma diagnosed during pregnancy: lessons learned from a series of ten patients.

The original article was updated to correct the listing of A. Hamy's name; it is correct as displayed above.

Pheochromocytoma diagnosed during pregnancy: lessons learned from a series of ten patients.

BACKGROUND: Pheochromocytoma (PHEO) in pregnancy is a life-threatening condition. Its management is challenging with regards to the timing and type of surgery. METHODS: A retrospective review of the management of ten patients diagnosed with pheochromocytoma during pregnancy was performed. Data were collected on the initial diagnostic workup, symptoms, treatment, and follow-up. RESULTS: PHEO was diagnosed in ten patients who were between the 10th and the 29th weeks of pregnancy. Six patients had none to mild symptoms, while four had complications of paroxysmal hypertension. Imaging investigations consisted of MRI, CT scan and ultrasounds. All had urinary metanephrines, measured as part of their workup. Three patients had MEN 2A, one VHL syndrome, one suspected SDH mutation. All patients were treated either with α/ß blockers or calcium channel blockers to stabilize their clinical conditions. Seven patients underwent a laparoscopic adrenalectomy before delivery. Three out of these seven patients had a bilateral PHEO and underwent a unilateral adrenalectomy of the larger tumor during pregnancy, followed by a planned cesarean section and a subsequent contralateral adrenalectomy within a few months after delivery. Three patients had emergency surgery for maternal or fetal complications, with C-section followed by concomitant or delayed adrenalectomy. All newborns from the group of planned surgery were healthy, while two out three newborns within the emergency surgery group died shortly after delivery secondary to cardiac and pulmonary complications. CONCLUSIONS: PHEO in pregnancy is a rare condition. Maternal and fetal prognosis improved over the last decades, but still lethal consequences may be present if misdiagnosed or mistreated. A thorough multidisciplinary team approach should be tailored on an individual basis to better manage the pathology. Unilateral adrenalectomy in a pregnant patient with bilateral PHEO may be an option to avoid the risk of adrenal insufficiency after bilateral adrenalectomy.

Thyroid Hürthle cell tumors: research of potential markers of malignancy.

INTRODUCTION: Hurthle cell tumors (HCTs) are rare thyroid neoplasia. To date, capsular and/or vascular invasion are the only findings predicting malignancy. Recently, mutation of 19p13, encoding two proteins involved in cell proliferation and apoptosis (GRIM-19 and p19), has been described. The aim of our study is to evaluate the cellular proliferation index (Ki67), GRIM-19 and p19 expression as diagnostic markers of malignancy in HCT. MATERIALS AND METHODS: Eighty patients with HCT (32 carcinomas, 48 adenomas) whom underwent surgery in our center were included. Samples of both neoplastic lesions and adjacent normal thyroid tissue were analyzed by means of tissue micro-arrays. Correlations between expressions of Ki67, GRIM-19 and p19 and final histology were analyzed. RESULTS: Mean size of the lesion was higher in carcinomas than in adenomas (p = 0.01). GRIM-19 and p19 were significantly underexpressed in Hurthle cells tumors compared to normal tissue (p = 0.0004 and p = 0.0001, respectively). Ki67 and GRIM-19 were, respectively, higher and down-expressed in carcinomas compared to adenomas (p = 0.0004 and p = 0.005, respectively). On multivariate analysis, size correlates with carcinoma diagnosis. Neither GRIM-19 nor Ki67 index was related to size. The expression of p19 was reduced in both adenoma and carcinoma but differences were not statistically significant (p = 0.13). CONCLUSIONS: Our study suggest that Ki67 and GRIM-19 correlate with malignancy in HCT. The expression of p19 is down-regulated in HCT, but it is not diagnostic of carcinoma. Ki67 and GRIM-19 may potentially help as cytological markers of malignancy in HCT.

Partial Thyroidectomy for Papillary Thyroid Microcarcinoma: Is Completion Total Thyroidectomy Indicated?

BACKGROUND: Total thyroidectomy is a well-established surgical approach for the management of papillary thyroid cancer (PTC). However, the best surgical approach for papillary microcarcinoma is nowadays still debated. Both total thyroidectomy and simple lobectomy are used. We report the experience of a single University center in the treatment of thyroid microcarcinoma. METHODS: A retrospective analysis on all patients who underwent thyroid surgery at our institution over a 24-year period (1991-2015) was performed. Patients were grouped according to whether they received total thyroidectomy (Group 1) or lobectomy (Group 2). Follow-up was made by routine clinical and ultrasound examination. Specific outcomes such as recurrence and need for reoperation as well as complications (transient vocal cord paralysis and hypocalcemia) were analyzed. RESULTS: During the study period 880 patients underwent surgery for PTC. Group 1 and 2 consisted, respectively, of 756 and 124 patients. A micro PTC (<10 mm) was present in 251 and 69 specimen of Group 1 and 2. No evidence of disease recurrence in the follow-up was reported in patients with microPTC in Group 1 and in 57 patients of Group 2. In the remaining 12 patients completion thyroidectomy was carried out due to ultrasound findings of contralateral nodules (10), lymphadenopathy (1), and capsular invasion (1). Five of these patients had a contralateral papillary carcinoma on final histopathologic examination. Thus recurrence rate for patients of Group 2 was 7.3%. Morbidity rates were, respectively, for Group 1 and 2: transient nerve palsy 81 and 5 (11 vs. 7.3%, p = ns), transient hypoparathyroidism (Calcium <2.00 mmol/L) 137 (18.6%) and 0 (p < 0.0001). Three of the 12 patients of Group 2 undergoing further surgery had a transient hypoparathyroidism. CONCLUSIONS: Thyroid lobectomy is an effective surgical strategy to manage papillary microcarcinomas with low complications. Routine completion thyroidectomy is not mandatory. Appropriate selection excluding high-risk patients is of paramount importance in order to achieve the best results.

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.

[Acute pancreatitis and primary hyperparathyroidism: a multicentric study by the Francophone Association of Endocrine Surgeons]. / Pancréatite aiguë et hyperparathyroïdie primaire: étude multicentrique de l'Association francophone de chirurgie endocrinienne.

BACKGROUND: Primary hyperparathyroidism is an unusual cause of acute pancreatitis. The aim of this study was to analyse data from multiple centers concerning patients with primary hyperparathyroidism and associated acute pancreatitis and to analyze potential predictive factors. METHODS: In this retrospective multicentric study, 19 patients were identified (Group A) with the associated diagnoses of acute pancreatitis and primary hyperparathyroidism. Their clinical data was compared to that of a control group of 65 patients (group B) with primary hyperparathyroidism without acute pancreatitis. RESULTS: Age, parathormone levels and pathology (uni/multiglandular disease) were similar between the two groups. The mean plasma calcium level was significantly higher in group A (12.64 mg/100ml) than in group B patients without pancreatitis (11.28 mg/100ml) (p<0.0001). CONCLUSION: This study confirms the causal relationship between primary hyperparathyroidism and acute pancreatitis. The degree of hypercalcemia may play an important role in this association. Calcium levels should be measured in all patients with acute pancreatitis.

[Virilizing ovarian tumors in the menopausal patient]. / Tumeurs virilisantes de l'ovaire chez la femme ménopausée.

Virilizing ovarian tumors are rare and can occur at any age. In postmenopausal women, they commonly present with signs of masculinization. These tumors should be suspected in any patient with virilization and high testosterone levels (>1ng/mL). Tumor localization is sometimes difficult. These tumors are usually benign; surgical resection is the accepted treatment. Masculinizing consequences of hormonal secretions may be managed by cosmetologic treatments which should not be overlooked.

[Parathyroid carcinoma: multicenter study of 17 patients]. / Carcinome parathyroïdien.

PURPOSE OF THE STUDY: To evaluate clinical characteristics and survival of patients treated for parathyroid carcinoma. STUDY DESIGN: A retrospective multicenter chart review of patients treated for parathyroid carcinoma between January 1979 and January 2005. RESULTS: 17 patients (10 women, 7 men) presenting with parathyroid carcinoma underwent surgical resection. Symptoms were largely related to hypercalcemia. Mean postoperative follow-up was seven years. Local recurrence was noted in four patients (24%) and three patients had late distant metastasis (18%). At the end of the study, nine patients were alive without evidence of recurrence (53%) and one patient was alive with recurrence at 5 years. Seven patients had died, four of whom died as a result of their parathyroid disease. CONCLUSION: Even when symptoms and findings are suggestive, the diagnosis of parathyroid carcinoma is oftentimes difficult. An adequate resection at the first intervention (complete tumor resection including a homolateral thyroid lobectomy and parathyroidectomy with resection of central lymph nodes) is recommended.

The status of CDKN2A alpha (p16INK4A) and beta (p14ARF) transcripts in thyroid tumour progression.

CDKN2A locus on chromosome 9p21 encodes two tumour suppressor proteins pl6INK4A, which is a regulator of the retinoblastoma (RB) protein, and p14ARF, which is involved in the ARF-Mdm2-p53 pathway. The aim of this study was to determine if CDKN2A gene products are implicated in differentiated thyroid carcinogenesis and progression. We used real-time quantitative RT-PCR and immunohistochemistry to assess both transcripts and proteins levels in 60 tumours specimens. Overexpression of p14ARF and pl6INK4A was observed in follicular adenomas, follicular carcinomas and papillary carcinomas, while downregulation was found in oncocytic adenomas compared to nontumoral paired thyroid tissues. These deregulations were statistically significant for pl6INK4a (P=0.006) in follicular adenomas and close to statistical significance for p14ARF in follicular adenomas (P=0.06) and in papillary carcinomas (P=0.05). In all histological types, except papillary carcinomas, we observed a statistically significant relationship between p14ARF and E2F1 (r=0.64 to 1, P<0.05). Our data are consistent with involvement of CDKN2A transcript upregulation in thyroid follicular tumorigenesis as an early event. However, these deregulations do not appear to be correlated to the clinical outcome and they could not be used as potential prognostic markers.

Expression of TAp73 and DeltaNp73 isoform transcripts in thyroid tumours.

AIM: This study was aimed to determine p73 status in thyroid tumours. METHODS: Differential expression of the TAp73, DeltaTAp73 transcripts was measured in a panel of 60 thyroid malignancies by quantitative RT-PCR. RESULTS: By comparison to normal thyroid tissue surrounding the tumours, we observed significant downregulation of TP73 transcripts in adenomas and in differentiated carcinomas. Correlations were found in normal tissue specimens between the expression of TAp73 and DeltaNp73 transcripts and that of p53, p14ARF p16INK4a, but these correlations were lost in carcinomas (PTC or FTC). CONCLUSIONS: We have found significant variations of TAp73, DeltaNp73, p53, p14ARF p16INK4a, expressions and correlations between the expressions of those different genes in thyroid cancer.

Central neck dissection in the management of sporadic medullary thyroid microcarcinoma.

AIM: Treatment of medullary thyroid carcinoma (MTC) includes total thyroidectomy with at least bilateral central neck dissection. Systematic measurement of thyrocalcitonin (CT) levels in thyroid nodules allows for early diagnosis of MTC. As central neck dissection (CND) is associated with high morbidity, the aim of this study was to investigate the necessity of this procedure in the treatment of sporadic medullary thyroid microcarcinoma (S-mMTC). METHODS: Prospective multicentric study including 43 patients with sporadic micro-MTC who underwent CND between January 1991 and August 2001. RESULTS: 26 women and 17 men with sporadic micro-MTC, aged 28-87 (mean age was 58 years), without family history of multiple endocrine neoplasia, underwent surgery. Total thyroidectomy was performed in all patients and combined with 'picking' (n=7) or CND (n=36). Size of tumours ranged from 0.2 to 9mm (mean size was 4.1mm). Solitary (32/43 patients) and multiple S-mMTC lesions (11/43 patients) were seen. 601 lymph nodes from the 41 subclinical patients were analysed. Mean follow-up period for these patients was 32 months. No mutations in the RET oncogene were seen. CONCLUSION: As lymph node involvement is uncommon in S-mMTC, systematic CND is of questionable value.

Increased calcitonin level in thyroid nodules without medullary carcinoma.

BACKGROUND: Basal calcitonin measurement is routinely performed in patients with a thyroid nodule to detect medullary carcinoma. However, increased calcitonin does not always correlate with medullary carcinoma. The aim of this study was to analyse increased calcitonin levels in patients without medullary carcinoma and to find out whether absence of this carcinoma can be predicted with certainty. METHODS: From 1992 to 2003, 5018 patients with thyroid nodules underwent thyroid surgery. A retrospective analysis of preoperative increased calcitonin levels in 67 of these patients was performed. RESULTS: Pathology revealed medullary carcinoma in 16 patients (group I), micromedullary carcinoma in 13 (group II) and no medullary carcinoma in 38 (group III). In group III, 30 patients had C-cell hyperplasia. The mean basal calcitonin level was 6250 pg/ml in group I (39-62 500), 109.6 pg/ml in group II (10-728) and 25.5 pg/ml in group III (10.5-145). The mean pentagastrin-stimulated calcitonin level was 1074.1 pg/ml in group II (26-5700) and 67.6 pg/ml in group III (10-205). CONCLUSION: There is an overlap of thyroid C-cell pathology for medullary carcinoma, micromedullary carcinoma and C-cell hyperplasia that occurs when basal calcitonin is between 10 and 145 pg/ml and pentagastrin-stimulated calcitonin between 10 and 205 pg/ml. In these patients, since medullary carcinoma cannot be completely excluded, total thyroidectomy should be recommended.

[Gastrinomas in multiple endocrine neoplasia type-1. A 127-case cohort study from the endocrine tumor group (ETG)]. / Les gastrinomes dans les néoplasies endocriniennes multiples de type 1. Une étude de cohorte de 127 cas du groupe des tumeurs endocrines (GTE).

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

[Management of thymic cysts]. / Prise en charge des kystes thymiques.

OBJECTIVE: The thymic cysts are rare tumors of the neck and anterior mediastinum. The management of these patients in our institution is reported. Minimally invasive procedures are discussed. PATIENTS AND METHODS: Six patients operated in our institution within ten years, with a follow-up of 7.1 +/-3.7 years are studied retrospectively. RESULTS: There were four women and two men with an average of 39.8 +/-16.5 years. The tumor was found on chest radiograph in four asymptomatic patients, one took medical advice for laryngeal discomfort and another for dysphagia and dyspnea. The tumor was localized in the anterior mediastinum in three cases, in the cervicomediastinal site in two cases and in the cervical site in one case. CT scan was practiced in three patients with a mediastinal tumor and MR imaging in one of them. In patients with cervical or cervicomediastinal tumor, a cervical echography was practiced. All patients were operated on: three by cervicotomy, one by sternotomy, one by partial upper mini-sternotomy and one by right lateral video-assisted mini-thoracotomy. Histology confirmed benign epithelial thymic cyst. CONCLUSION: There is no specific marker of thymic cysts. Only the surgical management, leads to precise the diagnosis and to treat these tumors. No mortality, no complications or recurrences are reported. The minimally invasive surgery takes an interesting place for thoracic location, to explore and treat these benign mediastinal lesions.