Introduction Anaplastic thyroid carcinoma (ATC) is the most aggressive form of thyroid cancer with a bleak prognosis. Favorable outcomes are rare but help decipher molecular pathophysiology, ...investigate prognosis factors, and discover new therapeutic targets. Case presentation Two patients were diagnosed with locally advanced nonresectable ATC, one with metastatic extension. Each patient received chemotherapy and radiotherapy, allowing thyroid surgical resection. In both cases, the pathological examination was consistent with complete response with no viable tumor cells. After follow-ups of 48 and 70 months, both patients remain disease-free. Molecular explorations on thyroid biopsies revealed microsatellite instability (MSI) and alterations on mismatch repair–gene complex, also PTEN and ATM variants in both cases. Both also presented with non-classical immune infiltrate composed of equal parts T CD4+ lymphocytes and macrophages. Conclusion We report two cases of patients cured from advanced ATC and for the first time provide genetic and immunological explorations in this setting. It seems with these two cases that MSI-ATCs may indicate a better prognosis. Our study hypothesizes different responsible mechanisms including increased sensitivity to chemoradiotherapy and/or immune tumor infiltrate modulation.
Introduction
There are no randomised studies comparing open and laparoscopic approaches foradrenalectomy in patients with adrenal cortical carcinoma.
Methods
There is evidence of postoperative ...benefit for the patients undergoing laparoscopic adrenalectomy compared to open adrenalectomy (level B).
Results
Results from comparison of oncological outcomes in ACC between open and laparoscopic approaches are equivocal: increasedrisk of local recurrence and peritoneal carcinomatosis by the laparoscopic route (level D), and identical results between the two approaches in terms of survival, recurrence and peritoneal carcinomatosis (level C).
Conclusion
An open approach is recommended in case of local invasion, with a view to achieving an R0 resection (level D). Laparoscopic resection of ACC/potentially malignant tumours, which includes removal of surrounding periadrenal fat and results in an R0 resection without tumour capsule rupture, may be performed for preoperative and intraoperative stage 1–2 ACC and tumours with a diameter < 10 cm (level C).
ObjectiveThe objective of this study was to re-evaluate the adult CT reference values determined by five different immunoassays and by introducing criteria for selecting control subjects.DesignA ...prospective multicenter study.PatientsThree hundred and seventy-five clinically euthyroid subjects.MethodsWe used five different CT immunoassays. Sera were assayed for the concentration of TSH, gastrin, procalcitonin, urea, calcium, and anti-thyroperoxidase antibodies.ResultsScreening for the various potential causes of hypercalcitoninemia led to the exclusion of 23% of the sera. Our reference value analysis dealt with 287 subjects (142 men and 145 women). The proportion of samples in which no CT was detected varied from 56% (for assay D) to 88% (for assay C). We observed significant correlations (whose magnitude depended on the assay used) between CT levels and age or body mass index (BMI) (primarily in men). The distribution of CT levels showed that 4.7, 9.8, 2.5, 6.5, and 8.0% of the values were over 10 pg/ml respectively. These values corresponded essentially to samples from 11 male subjects (median age: 55 years), most of whom were smokers. The highest CT values were around twice as high in men than women, and were higher in smokers than non-smokers.ConclusionIn clinical practice (and after having excluded the usual causes of raised CT levels), the interpretation of CT assay results must take into account i) the method used; ii) the patient's gender, age, and weight; and iii) the potential influence of cigarette smoking.
Postoperative hypocalcemia is a common and most often transient event after extensive thyroid surgery. It may reveal iatrogenic injury to the parathyroid glands and permanent hypoparathyroidism. We ...prospectively evaluated the incidence of hypocalcemia and permanent hypoparathyroidism following total or subtotal thyroidectomy in 1071 consecutive patients operated during 1990–1991. We then determined in a cross‐sectional study which early clinical and biochemical characteristics of patients experiencing postoperative hypocalcemia correlated with the long‐term outcome. Postoperative calcemia under 2 mmol/l was observed in 58 patients (5.4%). In 40 patients hypocalcemia was considered severe (confirmed for more than 2 days, symptomatic or both). At 1 year after surgery five patients (0.5%) had persistent hypocalcemia. We found that patients carried a high risk for permanent hypoparathyroidism if fewer than three parathyroid glands were preserved in situ during surgery or the early serum parathyroid hormone level was ≤ 12 pg/ml, the delayed serum calcium levels ≤ 8 mg/dl, or the delayed serum phosphorus level ≥ 4 mg/dl under oral calcium therapy. When one or more of these criteria are present, long‐term follow‐up should be enforced to check for chronic hypocalcemia and to avoid its severe complications by appropriate supplement therapy.
Background
Ectopic hormone-secreting pheochromocytomas are rare; only case reports exist in the literature. This condition has been linked with increased malignancy, familial syndromes, and ACTH ...secretion. We wanted to test these hypotheses and shed light on the nature of ectopic hormone-secreting pheochromocytomas.
Methods
This is a multicenter (francophone) observational study. Inclusion was based upon abnormal preoperative hormone tests in patients with pheochromocytoma that normalized after removal of the tumor. Where possible, immunohistochemistry was performed to confirm that ectopic secretion came from the tumor.
Results
Sixteen cases were found: nine female and seven male patients. Median age was 50.5 (range 31–89) years. Most presented with hypertension, diabetes, or cushingoid features. Ten patients had specific symptoms from the ectopic hormone secretion. Two had a familial syndrome. Of eight patients with excess cortisol secretion, three died as a result of the tumor resection: two had pheochromocytomas >15 cm and their associated cortisol hypersecretion complicated their postoperative course. The other died from a torn subhepatic vein. The 13 survivors did not develop any evidence of malignancy during follow-up (median 50 months). Symptoms from the ectopic secretion resolved after removal of the tumor. Immunohistochemistry was performed and was positive in eight tumors: five ACTH, three calcitonins, and one VIP.
Conclusions
Most pheochromocytomas with ectopic secretion are neither malignant nor familial. Most ectopic hormone-secreting pheochromocytoma cause hypercortisolemia. Patients with a pheochromocytoma should be worked up for ectopic hormones, because removal of the pheochromocytoma resolves those symptoms. Associated cortisol secretion needs careful attention.
Objective We previously described a family in which predisposition to pheochromocytoma (PCC) segregates with a germline heterozygous KIF1B nucleotide variant (c.4442G>A, p.Ser1481Asn) in three ...generations. During the clinical follow-up, one proband’s brother, negative for the KIF1B nucleotide variant, developed a bilateral PCC at 31 years. This prompted us to reconsider the genetic analysis. Design and methods Germline DNA was analyzed by next-generation sequencing (NGS) using a multi-gene panel plus MLPA or by whole exome sequencing (WES). Tumor-derived DNA was analyzed by SnapShot, Sanger sequencing or NGS to identify loss-of-heterozygosity (LOH) or additional somatic mutations. Results A germline heterozygous variant of unknown significance in MAX (c.145T>C, p.Ser49Pro) was identified in the proband’s brother. Loss of the wild-type MAX allele occurred in his PCCs thus demonstrating that this variant was responsible for the bilateral PCC in this patient. The proband and her affected grandfather also carried the MAX variant but no second hit could be found at the somatic level. No other pathogenic mutations were detected in 36 genes predisposing to familial PCC/PGL or familial cancers by WES of the proband germline. Germline variants detected in other genes, TFAP2E and TMEM214, may contribute to the multiple tumors of the proband. Conclusion In this family, the heritability of PCC is linked to the MAX germline variant and not to the KIF1B germline variant which, however, may have contributed to the occurrence of neuroblastoma (NB) in the proband.
Background
Clinical guidelines edited in 2006 by the American Thyroid Association (ATA) and stated in the European Thyroid Association Consensus (ETA) recommend routine central lymph node dissection ...(level VI neck dissection) in addition to thyroidectomy for the surgical treatment of differentiated thyroid cancer. This central dissection increases the incidence of postoperative hypocalcemia, which is related to the resection or devascularization of the inferior parathyroids together with bilateral thymectomy. Some authors perform unilateral thymectomy in order to minimize this complication. Our aim was to study the benefit/risk (incidence of thymic lymph node metastases versus postoperative hypocalcemia) of both procedures.
Methods
We retrospectively reviewed the records of 138 patients who underwent total thyroidectomy with central neck lymph node dissection for differentiated thyroid cancer between 2004 and 2007. Bilateral thymectomy was performed in 45 patients (group 1, 15 males and 30 females) and unilateral thymectomy was performed in 93 patients (group 2, 27 males and 66 females). Forty-two papillary and 3 medullary cancers were found in group 1, and 75 papillary, 2 follicular, and 17 medullary cancers were found in group 2. The presence of thymic metastases at pathology and the occurrence of postoperative hypocalcemia were reviewed.
Results
Two cases of papillary thymic metastases were found in group 1. These were lymph node micrometastases localized in the ipsilateral side of the primary tumor in both cases. Transient hypocalcemia was significantly more frequent (
P
< 0.001) in group 1 than in group 2: 16 patients (35.5%) versus 10 (10.7%). There was one case of permanent hypocalcemia in group 1 after the follow-up period.
Conclusions
Bilateral thymectomy risk outweighs any likely carcinologic benefit. We do not recommend routine bilateral thymectomy during central neck dissection for differentiated thyroid cancer.
Pheochromocytoma is a catecholamine-secreting tumor associated with clinical presentations ranging from paroxysmal hypertension to intractable cardiogenic shock. We report the use of central ...extracorporeal life support (ECLS) in a young woman admitted to the intensive care unit with cardiogenic shock. Her medical history included neurofibromatosis type I and pheochromocytoma. ECLS was needed because of severe left ventricular failure and inotropic therapy unresponsiveness. ECLS permitted full recovery of left ventricular function. Right adrenelectomy was performed 4 months later. In this case, central ECLS was used to treat pheochromocytoma-induced cardiogenic shock complicated by pulmonary edema.
Background Operative excision of abdominal extra-adrenal paragangliomas (EAPs) does not preclude the late development of local-regional recurrence. We describe the incidence, characteristics, and ...outcome of this rarely reported feature. Methods Retrospective analysis of local-regional recurrence that occurred during follow-up of 51 consecutive patients operated for a sporadic ( n = 26) or hereditary ( n = 25) EAP. Results Seven patients with a sporadic or syndromic EAP ( n = 4: von Hippel-Lindau syndrome and SDHB, SDHC, and SDHD gene mutations) underwent reoperation for a local-regional recurrence after a median time of 46 months (interquartile range IQR, 16–100). The Kaplan-Meier estimated incidence of local-regional recurrence (± standard error of the mean) reached 15% ± 7% at 5 years and 23% ± 9% after 10 years. Recurrent EAPs were all secreting and 38% provoked clinical symptoms. New lesions were smaller than the primary EAP ( P = .01) and more often associated with lymph node metastases (43% vs 4%, P = .01). Operative excision seemed complete in 5 patients. Clinical remission was maintained in 4 patients after a median follow-up of 57 months (IQR, 22–102). Conclusion Local-regional recurrence of sporadic and syndromic EAPs is frequent and may be delayed beyond 10 years, requiring lifelong follow-up after the initial operation. When technically feasible, operative excision can lead to prolonged remission.
Background
Ectopic abnormal parathyroid glands are relatively common in the superior mediastinum but are rarely situated in the aortopulmonary window (APW). The embryological origin of these abnormal ...parathyroid glands is controversial. The purpose of this investigation was to investigate the embryological origin and the surgical management of abnormal parathyroid glands situated in the APW.
Methods
The databases of patients operated on for primary, secondary, and tertiary hyperparathyroidism at eight European medical centers with a special interest in endocrine surgery were reviewed to identify those with APW adenomas. Demographic features, localization procedures, and perioperative and pathology findings were documented. The embryological origin was determined based on the number and position of identified parathyroid glands.
Results
Nineteen (0.24%) APW parathyroid tumors were identified in 7,869 patients who underwent an operation for hyperparathyroidism (HPT) and 181 patients (2.3%) with mediastinal abnormal parathyroid glands. Ten patients had primary, eight had secondary, and one had tertiary HPT. Sixteen patients had undergone previous unsuccessful cervical exploration. In three patients, an APW adenoma was suspected by preoperative localization studies and was cured at the initial operation. Sixteen patients had persistent HPT of whom 15 were reoperated, resulting in 6 failures. Evaluation of 17 patients who had bilateral neck exploration allowed us to determine the most probable origin of the APW parathyroid tumors: 12 were supernumerary, 4 appeared to originate from a superior, and 1 from an inferior gland.
Conclusions
Abnormal parathyroid glands situated in the APW are rare and usually identified after an unsuccessful cervical exploration. Preoperative imaging of the mediastinum and neck are essential. The origin of these ectopically situated tumors is probably, as suggested by our data, from a supernumerary fifth parathyroid gland or from abnormal migration of a superior parathyroid gland during the embryologic development.
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