Intraoperative neural monitoring (IONM) during thyroid and parathyroid surgery has gained widespread acceptance as an adjunct to the gold standard of visual nerve identification. Despite the ...increasing use of IONM, review of the literature and clinical experience confirms there is little uniformity in application of and results from nerve monitoring across different centers. We provide a review of the literature and cumulative experience of the multidisciplinary International Neural Monitoring Study Group with IONM spanning nearly 15 years. The study group focused its initial work on formulation of standards in IONM as it relates to important areas: 1) standards of equipment setup/endotracheal tube placement and 2) standards of loss of signal evaluation/intraoperative problem‐solving algorithm. The use of standardized methods and reporting will provide greater uniformity in application of IONM. In addition, this report clarifies the limitations of IONM and helps identify areas where additional research is necessary. This guideline is, at its forefront, quality driven; it is intended to improve the quality of neural monitoring, to translate the best available evidence into clinical practice to promote best practices. We hope this work will minimize inappropriate variations in monitoring rather than to dictate practice options. Laryngoscope, 121:S1–S16, 2011
Aim
To assess postoperative complications and control of hormone secretions following pancreatoduodenectomy (PD) performed on multiple endocrine neoplasia type 1 (MEN1) patients with ...duodenopancreatic neuroendocrine tumors (DP-NETs).
Background
The use of PD to treat MEN1 remains controversial, and evaluating the right place of PD in MEN1 disease makes sense.
Methods
Thirty-one MEN1 patients from the
Groupe d’étude des Tumeurs Endocrines
MEN1 cohort who underwent PD for DP-NETs between 1971 and 2013 were included. Early and late postoperative complications, secretory control and overall survival were analyzed.
Results
Indication for surgery was: Zollinger–Ellison syndrome (
n
= 18; 58%), nonfunctioning tumor (
n
= 9; 29%), insulinoma (
n
= 2; 7%), VIPoma (
n
= 1; 3%) and glucagonoma (
n
= 1; 3%). Mean follow-up was 141 months (range 0–433). Pancreatic fistulas occurred in 5 patients (16.1%), distant metastases in 6 (mean onset of 43 months; range 13–110 months), postoperative diabetes mellitus in 7 (22%), and pancreatic exocrine insufficiency in 6 (19%). Five-year overall survival was 93.3% CI 75.8–98.3 and ten-year overall survival was 89.1% CI 69.6–96.4. After a mean follow-up of 151 months (range 0–433), the biochemical cure rate for MEN-1 related gastrinomas was 61%.
Conclusion
In MEN1 patients, pancreatoduodenectomy can be used to control hormone secretions (gastrin, glucagon, VIP) and to remove large NETs. PD was found to control gastrin secretions in about 60% of cases.
Abstract Differentiated thyroid cancer is a cancer with a good prognosis but the presence of lymph node metastases is associated with increased rates of loco-regional recurrence and in some reports ...decreased survival. This has led to an increased interest in the lymph node status with guidelines calling for routine central node dissection and increased interest in lateral compartment node sampling and sentinel node biopsy. We know from studies in regions where routine central and ipsilateral node dissection is the preferred surgical management of differentiated thyroid cancer that lymph node metastases are present in the majority of cases and that many of these are micrometastatic deposits. However, where routine node dissection is not performed recurrence rates are relatively low suggesting that not all micrometastatic disease progresses to a loco-regional recurrence or that the majority of disease is mopped up by adjuvant radioactive iodine. This review examines the available evidence for the significance of micrometastatic disease in differentiated thyroid cancer and suggests that it is probably of little clinical significance and does not warrant further aggressive surgical intervention. We would expect a conservative surgical approach combined with adjuvant radioactive iodine to lead to durable disease control.
Aims
To investigate the performance of two proposed methods for assessing the prognosis of poorly differentiated thyroid carcinomas (PDTC): the Turin proposal and Hiltzik's histological grade (HHG). ...This was done using a series of 82 thyroid carcinomas of follicular origin.
Results
The two methods were able to classify patients accurately into two different prognosis groups. Although the Turin proposal and HHG displayed discrepant cases, they provided similar prognostic information. The Turin proposal gave accurate numbers and thresholds of PTDC criteria (loss of follicular architecture and mitoses, necrosis or convoluted nuclei). One Turin criterion, convoluted nuclei, failed to provide any prognostic value. Hiltzik's histological grade was also a simple and reliable method, allowing detection of tumours with high‐grade features (mitosis and/or tumour necrosis), notably some papillary carcinomas that displayed an intermediate prognosis. We show that Ki67 labelling (≥ 4%) was an independent factor and predictor of cause‐specific survival.
Conclusion
With similar performances in predicting prognosis, the Turin proposal and HHG provided complementary results in identifying a larger group of ‘intermediate prognosis’ thyroid carcinomas, which require adequate treatment and follow‐up.
Lymph node involvement (LNI) is one of the most important prognostic factors for poor survival in medullary thyroid carcinoma (MTC). At diagnosis, LNI is found in over 50% of sporadic MTCs, and ...especially in large tumours. Cervical lymph node dissection is therefore mandatory during MTC surgery. However, some large tumours (responsible for high preoperative basal calcitonin levels) are found to lack LNI, and can be cured definitely. Preoperative detection of these particular tumours might spare patients from undergoing extensive cervical dissection. The objective of the present retrospective study of a series of large sporadic MTCs was to identify clinical, biological and pathological factors that were predictive of LNI. Consecutive cases of large, sporadic MTCs (measuring at least 1 cm in diameter) were retrieved and reviewed. The levels of several mature microRNAs (miRs) in paraffin-embedded samples were assessed using qPCR. Of the 54 MTCs, 26 had LNI and 28 were pN0. Relative to pN0 patients, patients with LNI had a significant higher preoperative basal calcitonin level (
p
= 0.0074) and a greater prevalence of infiltrative margins (
p
< 0.0001), lymphovascular invasion (
p
= 0.0004), extrathyroidal extension (
p
< 0.0001), a higher pT stage (
p
= 0.0003) and more abundant desmoplastic stroma (
p
= 0.0006). Tumour expression levels of miR-21 (
p
= 0.0008) and miR-183 (
p
= 0.0096) were higher in the LNI group. The abundance of desmoplastic stroma (
p
= 0.007) and the miR-21 expression level (
p
= 0.0026) were independent prognostic factors for LNI. The abundance of desmoplastic stroma and high levels of miR-21 expression were strong indicators of LNI, and may thus help the surgeon to choose the extent of cervical lymph node dissection for large, sporadic MTCs with no preoperatively obvious LNI.
Because of the rarity of adrenocortical carcinoma, survival rates and the prognosis for patients who have undergone operation are not well known. The purpose of the French Association of Endocrine ...Surgery was to evaluate these factors over an 18‐year period. A trend study was associated to assess changes in the clinical and biochemical presentations as well as the surgical evolution. A total of 253 patients (158 women, 95 men) with a mean age of 47 years were included. Cushing syndrome was the main clinical presentation (30%), and hormonal studies revealed secreting tumors in 66% of the cases. Altogether, 72% (n=182) of patients underwent resection for cure, and 41.5% (n=105) of them had an extensive resection because of metastatic cancer. A lymphadenectomy was performed in 32.5% (n=89) of the cases. The operative mortality was 5.5% (n=14). Patients were given mitotane as adjuvant therapy in 53.8% of the cases (n=135). The results of staging were stage I in 16 patients (6.3%), stage II (local disease) in 126 patients (49.8%), stage III (locoregional disease) in 57 patients (22.5%), and stage IV (metastases) in 54 patients (21.3%). Neither tumor staging nor the rate of curative surgery changed during the study period. More subcostal incisions were performed, and the use of mitotane increased significantly. The 5‐year actuarial survival rates were 38% overall, 50% in the curative group, 66% for stage I, 58% for stage II, 24% for stage III, and 0% for stage IV. Multivariate analysis showed that mitotane benefited only the group of patients not operated on for cure. A better prognosis was found in patients operated on after 1988 (p=0.04), in those with precursor‐secreting tumors (p=0.005), and in those at local stages of the disease (p=0.0003). Thus mitotane benefited only patients not operated on for cure. Curative resection, precursor secretion, recent diagnosis, and local stage were favorably associated with survival.
Résumé
Introduction: La survie et le pronostic des patients opérés d’un corticosurrénalome restent mal connus car il s’agit d’une tumeur rare. L’Association Française de Chirurgie Endocrinienne s’est fix pour but d’évaluer ces facteurs pendant une période de 18 ans. Les changements de présentation clinique, biochimique et l’évolution de la prise en charge chirurgicale ont également fait l’objet d’une analyse. Méthode: Deux cent cinquante trois patients (158 femmes, 95 hommes), d’une moyenne d’âge de 47 ans. ont été étudiés. Un syndrome de Cushing a été la situation clinique la plus fréquente (30%), et les études hormonales ont montré une tumeur sécrétante dans 66% des cas. Soixante‐douze pour cent (n=182) des patients ont bénéficié d’une chirurgie à visée curative et 41,5% (n=105) ont eu une résection étendue en raison des métastases. Un curage ganglionnaire a été réalisé dans 32,5% (n=89) des cas. La mortalité post‐opératoire a été de 5,5% (n=14). Du mitotane a été utilisé dans 53,8% des cas (n=135). La classification tumorale a montré : 16 stades I (6,3%): 126 stades II (maladie locale) (49,8%), 57 stades III (maladie loco‐régionale) (22,5%); et 54 stades IV (métastases) (21.3%). Résultats: Le stade des tumeurs et le pourcentage de chirurgie à visée curative n’ont pas évolué. II a été réalisé plus d’incisions sous‐costales et l’utilisation du mitotane n’a cessé de croître de façon significative. La survie actuarielle à 5 ans a été de 38% : 50% dans le groupe opéré à visée curative, 66% dans les stades I, 58% dans les stades II, 24% dans les stades III, et 0% dans les stades IV. L’analyse multivariée a montré que le mitotane a apporté un bénéfice de survie au groupe de patients opérés à visée palliative. Une amélioration du pronostic a été notée après 1988 (p=0.04), chez les patients sécrétant des précurseurs (p=0,005) et dans les stades locaux (p=0,0003). Conclusion: Le mitotane n’a été profitable qu’aux patients opérés à visée palliative. Le caractère curatif de la chirurgie, le type de sécrétion hormonale, la période récente de diagnostic et le stade local ont été des facteurs favorables de survie.
Resumen
Introducción: Dada la poca frecuencia del cáncer adreno‐cortical el pronóstico y la supervivencia de los pacientes intervenidos no es bien conocido. La Asociación Francesa de Cirugía Endocrina se ha marcado como objetivo valorar estos factores durante un periodo de tiempo de 18 años. Además, pretendemos analizar los cambios clínicos y bioquímicos, así como la evolución del tratamiento quirúrgico. Método: Se estudiaron 253 pacientes (158 hembras y 95 varones) cuya edad media fue de 47 años. El cuadro clínico más frecuente fue el del síndrome de Cushing (30%) y los análisis hormonales demostraron la existencia de un tumor secretor en el 66% de los casos. El 72% (n=182) de los pacientes fueron intervenidos quirúrgicamente con fines curativos y en el 41.5% (n=105) hubieron de efectuarse resecciones ampliadas por metástasis. Una linfadenectomia se realizó en el 32.5% (n=89) de los casos. La mortalidad operatoria fue del 5.5% (n=14). El 53.8% (n=135) de los pacientes recibieron como terapia adyuvante Mitotane. La clasificación tumoral registra: 16 estadios I (6.3%); 126 estadios II (enfermedad local) (49.8%). 57 estadios III (enfermedad loco‐regional) (22.5%) y 54 estadios IV (con metástasis) (21.3%). Resultados: El porcentaje de tumores en los diferentes estadios no se ha modificado, ni tampoco la cirugía con fines curativos. La vía de abordaje más frecuente ha sido la subcostal y el empleo, como terapia adyuvante, de Mitotane no ha cesado de aumentar significativamente. La supervivencia actuarial global a 5 años fue del 38%; 50% en el grupo operado con fines curativos: 66% en pacientes en estadio I, 58% en los del estadio II, 24% en los del estadio III y 0% en los del estadio IV. Un análisis multivariante ha demostrado los beneficiosos efectos del Mitotane, por lo que a la supervivencia se refiere, en el grupo de pacientes intervenidos con fines paliativos. El pronóstico ha mejorado desde 1988 (p=0.04), en los pacientes secretores de precursores (p=0.005) y en los pacientes con enfermedad local (p=0.0003). Conclusiones: El Mitotane sólo es útil en casos de cirugía paliativa. La cirugía radical, el tipo de secreción hormonal, el diagnóstico precoz y el estadio de enfermedad local, son los factores más favorables en cuanto a la supervivencia se refiere.
Background Adrenocortical carcinoma is a rare neoplasm with a high rate of recurrence. We studied the impact of surgery on the survival in recurrent adrenocortical carcinoma patients. Methods We ...performed a retrospective review of patients with recurrent adrenocortical carcinoma, managed in 5 French University Hospitals between 1980 and 2014. We compared surgery and medical management for ACC recurrence. Results Fifty-nine patients were included, 46 of whom had an initial R0 resection. Twenty-nine patients underwent reoperation for recurrence, while 30 had nonoperative treatments. Operated patients had a greater median overall survival after recurrence than nonoperated patients (91 vs 15 months; P < .001). Patients operated on for local or distant recurrence had similar overall survival (110 vs 91 months; P = .81). In nonoperated patients, types of medical managements did not impact survival. Surgery for recurrence ( P = .037) and a disease-free interval between initial resection and recurrence >12 months ( P = .059) were both prognostic factors for improved survival, whereas age, stage, and tumor size ( P ≥ .2 each) were not. A Ki67 <25% tended to be associated with better overall survival ( P = .051). Conclusion Both surgery for recurrence and disease-free interval between the initial resection of an adrenocortical carcinoma and recurrence >12 months are associated with better overall survival.
Background The functionality of cryopreserved parathyroid autotransplantation (CPAT) has been evaluated in few studies, mostly conducted by experienced single-institution centers that have reported ...different success rates ranging from 17% to 83%. In France, CPAT are rare and their functionality has never been evaluated. Moreover, French tissue banks are facing an accumulation of ungrafted samples. The aim of our work was to evaluate the implantation rate of cryopreserved parathyroid samples and the functionality of CPAT in a multicenter study. Methods Data from 9 French tissue banks were analyzed. CPAT functionality was defined as fully functional (normal parathyroid hormone PTH and calcium levels without treatment), partially functional (normal PTH levels but need for treatment to maintain normocalcemia), and nonfunctional (low PTH levels and need for treatment). For dialyzed patients, CPAT was considered nonfunctional if the PTH level in the nongrafted arm was less than 20 pg/mL, partially functional if the PTH level was between 20 and 50 pg/mL, and fully functional if the PTH level was between 50 and 300 pg/mL. Results The 9 centers had cryopreserved 1376 samples of parathyroid tissue and only 22 (1.6%) had been autografted in 20 patients (65% renal hyperparathyroidism, 20% multiple endocrine neoplasia type 1, 15% “other”) by 12 different surgical teams. The median duration of storage was 11.1 months (range, 0.4–28.5). Only 2 autografts (10%) were fully functional, 2 (10%) were partially functional, and 17 (80%) were nonfunctional at 26 months median follow-up. Conclusion The reimplantation rate is low, and the functionality of CPAT is less than those published by experienced centers. Logistical and technical problems occurring in less experienced centers are probably the main reasons for nonfunctioning implants. Considering the results of this study, we suggest that cryopreservation of parathyroid glands should be abandoned when not performed in very large experimented centers, that CPAT should be used only for patients with hyperplasic parathyroid tissue, and that tissue samples should be systematically destroyed when patients do not have hypoparathyroidism or after 1 year of storage.
Since the histological expression of galectins is increased in thyroid carcinoma, determination of their serum levels may provide useful preoperative information. The goal of this study was to ...determine if a difference in galectin serum levels could be detected between benign and malignant nodular thyroid diseases.
Using validated ELISAs, the concentrations of several galectins were prospectively measured in serum samples from 30 healthy individuals and preoperatively in 90 patients with thyroid disease. Seventy-one patients had multiple thyroid nodules (MTN), 13 patients had a single thyroid nodule (STN), and 6 patients had Graves' disease. Nine of 71 patients with MTN had fine-needle aspiration biopsy (FNAB) of their nodules and in 7 patients a "benign" diagnosis was made, in 0 patient a "malignant" diagnosis was made, and in 2 patients a "suspicious" diagnosis was made. Six of 13 patients with STN had FNAB of their nodules and in 2 patients a "benign" diagnosis was made, in 3 patients a "malignant" diagnosis was made, and in 1 patient a "suspicious" diagnosis was made.
Thyroid disease was associated with higher levels of galectins-1 and -3 compared to normal subjects. Using a threshold value of 3.2 ng/mL as a cut-off point, the measurement of serum galectin-3 separated micro- and macropapillary thyroid carcinoma (PAP_CA) from patients with nonmalignant thyroid disease with 74% specificity, 73% sensitivity, 57% positive predictive value, and 85% negative predictive value. Elevated serum galectin-3 concentrations (>3.2 ng/mL) detected 87% of macropapillary thyroid carcinomas and 67% of micropapillary thyroid carcinomas.
Serum levels of galectins-1 and -3 are relatively high in patients with thyroid malignancy but there is considerable overlap in serum galectin-3 concentrations between those with benign and malignant nodular thyroid disease and, to a lesser extent, between those with and without nodular thyroid disease.
Background
Thymic neuroendocrine tumors (Th-NET) present a poor prognosis for patients with multiple endocrine neoplasia type 1 (MEN1). The purpose of this article was to study the clinical, ...biological, and pathological features of Th-NET in a large cohort of patients with MEN1.
Methods
The 761-patient MEN1 cohort from the GTE registry was used (Groupe des Tumeurs Endocrines).
Results
The actuarial probability of occurrence was 2.6% (range, 1.3–5.5%) at aged 40 years. All, except one, Th-NET patients were men. Four patients had no other associated lesions. The youngest patient was aged 16 years. Mean age at the time of diagnosis was 42.7 (range, 16.1–67.5) years. The 10-year probability of survival was 36.1% (range, 11.5–62%). Seven patients (33%) belonged to clustered MEN1 families. The spectrum of associated lesions in patients with Th-NET was not statistically different from the spectrum of the remainder of the cohort. Various endocrine markers were high, but none were sensitive or specific enough to be useful for Th-NET detection. CT-scan and MRI were always positive at the time of diagnosis. No particular mutation was found to be associated with Th-NET. Five cases underwent prophylactic thymectomy without success.
Conclusions
Several end points may be helpful for future guidelines: (1) earlier detection of Th-NET in MEN1 patients is required; (2) screening of both sexes is necessary; (3) a prospective study comparing MRI vs. CT scan in yearly screening for Th-NET is needed; (4) a reinforced screening program must be established for patients who belong to clustered families; and (5) thymectomies must be performed in specialized centers.
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