Prevalence of DICER1 variants in large multinodular goiter: thyroid function, clinical and imaging characteristics.

Objective: Mutations in DICER1 are found in differentiated thyroid carcinoma (DTC) and in multinodular goiter (MNG) at a younger age with other tumors, which characterizes DICER1 syndrome. DICER1 is one driver to DTC; however, it is also found in benign nodules. We speculated that patients with mutations in DICER1 may present long-lasting MNG. Our aim was to investigate the frequency of DICER1 variants in patients with MNG. Subjects and methods: Patients who submitted to total thyroidectomy due to large MNG with symptoms were evaluated. DICER1 hotspots were sequenced from thyroid nodule samples. To confirm somatic mutation, DNA from peripheral blood was also analyzed. Results: Among 715 patients, 154 were evaluated with 56.2 ± 12.3 years old (28-79) and the thyroid volume was 115.7 ± 108 mL (16.2-730). We found 11% with six DICER1 variations in a homo or heterozygous state. Only rs12018992 was a somatic DICER1 variant. All remaining variants were synonymous and likely benign, according to the ClinVar database. The rs12018992 was previously described in an adolescent with DTC, measuring 13 mm. There were no significant differences according to gender, familial history of goiter, age, thyroid volume, TSH and TI-RADS classification between DICER1 carriers. Free T4 were lower in patients with DICER1 polymorphisms (13.77 ± 1.8 vs. 15.44 ± 2.4 pmol/L, p = 0.008), regardless of TSH levels. Conclusion: We conclude that germline DICER1 variants can be found in 11% of large goiters but no second-hit somatic mutation was found. DICER1 is one driver to thyroid lesion and a second-hit event seems unnecessary in the MNG development.

Prevalence of DICER1 variants in large multinodular goiter: thyroid function, clinical and imaging characteristics

ABSTRACT Objective: Mutations in DICER1 are found in differentiated thyroid carcinoma (DTC) and in multinodular goiter (MNG) at a younger age with other tumors, which characterizes DICER1 syndrome. DICER1 is one driver to DTC; however, it is also found in benign nodules. We speculated that patients with mutations in DICER1 may present long-lasting MNG. Our aim was to investigate the frequency of DICER1 variants in patients with MNG. Subjects and methods: Patients who submitted to total thyroidectomy due to large MNG with symptoms were evaluated. DICER1 hotspots were sequenced from thyroid nodule samples. To confirm somatic mutation, DNA from peripheral blood was also analyzed. Results: Among 715 patients, 154 were evaluated with 56.2 ± 12.3 years old (28-79) and the thyroid volume was 115.7 ± 108 mL (16.2-730). We found 11% with six DICER1 variations in a homo or heterozygous state. Only rs12018992 was a somatic DICER1 variant. All remaining variants were synonymous and likely benign, according to the ClinVar database. The rs12018992 was previously described in an adolescent with DTC, measuring 13 mm. There were no significant differences according to gender, familial history of goiter, age, thyroid volume, TSH and TI-RADS classification between DICER1 carriers. Free T4 were lower in patients with DICER1 polymorphisms (13.77 ± 1.8 vs. 15.44 ± 2.4 pmol/L, p = 0.008), regardless of TSH levels. Conclusions: We conclude that germline DICER1 variants can be found in 11% of large goiters but no second-hit somatic mutation was found. DICER1 is one driver to thyroid lesion and a second-hit event seems unnecessary in the MNG development.

Guidelines from the Brazilian society of surgical oncology regarding indications and technical aspects of neck dissection in papillary, follicular, and medullary thyroid cancers.

Objective: The purpose of these guidelines is to provide specific recommendations for the surgical treatment of neck metastases in patients with papillary, follicular, and medullary thyroid carcinomas. Materials and methods: Recommendations were developed based on research of scientific articles (preferentially meta-analyses) and guidelines issued by international medical specialty societies. The American College of Physicians' Guideline Grading System was used to determine the levels of evidence and grades of recommendations. The following questions were answered: A) Is elective neck dissection indicated in the treatment of papillary, follicular, and medullary thyroid carcinoma? B) When should central, lateral, and modified radical neck dissection be performed? C) Could molecular tests guide the extent of the neck dissection? Results and conclusion: Recommendation 1: Elective central neck dissection is not indicated in patients with cN0 well-differentiated thyroid carcinoma or in those with noninvasive T1 and T2 tumors but may be considered in T3-T4 tumors or in the presence of metastases in the lateral neck compartments. Recommendation 2: Elective central neck dissection is recommended in medullary thyroid carcinoma. Recommendation 3: Selective neck dissection of levels II-V should be indicated to treat neck metastases in papillary thyroid cancer, an approach that decreases the risk of recurrence and mortality. Recommendation 4: Compartmental neck dissection is indicated in the treatment of lymph node recurrence after elective or therapeutic neck dissection; "berry node picking" is not recommended. Recommendation 5: There are currently no recommendations regarding the use of molecular tests in guiding the extent of neck dissection in thyroid cancer.

Ultrasonography in the Assessment of Tumors of the Cheek: Water Mouth Distension Technique.

PURPOSE: To describe a new B-mode ultrasound examination technique to assess cheek tumors. MATERIALS AND METHODS: 30 cheek oral cavity lesions of different histological types (11 benign and 19 malignant) from 23 patients (11 women and 12 men, 7-82 years old, mean age of 49.5 years) were analyzed. Transcutaneous oral B-mode ultrasound (5-12 MHz transducer) was carried out in two stages. Initially it was performed conventionally with an empty mouth. Next, the patient was asked to keep their oral cavity filled with water (like when using a mouthwash) during imaging for the new test examination technique. The anatomical layers of this region and the characteristics of the tumors were evaluated. Lesions were classified as ill defined, partially defined, or defined. Conventional findings were compared to those of the new technique using the Wilcoxon signed-rank test. Ultrasound results were compared to histological findings analyzed by an independent team. RESULTS: The conventional empty mouth technique was able to confidently define lesion extension in only 6 of the 30 lesions, while the water-filled mouth technique was able to confidently define lesion extension in 29 of the 30 lesions (p<0.00001). CONCLUSION: We present a novel technique that dramatically improves ultrasound staging of cheek oral cavity tumors. In addition to the increase in ultrasound accuracy, this technique does not require any special equipment or extra cost, is very well tolerated by patients, and thus should be considered in the evaluation of every patient undergoing transcutaneous cheek ultrasound for oral cavity lesion characterization.

Guidelines from the Brazilian society of surgical oncology regarding indications and technical aspects of neck dissection in papillary, follicular, and medullary thyroid cancers

ABSTRACT Objective: The purpose of these guidelines is to provide specific recommendations for the surgical treatment of neck metastases in patients with papillary, follicular, and medullary thyroid carcinomas. Materials and methods: Recommendations were developed based on research of scientific articles (preferentially meta-analyses) and guidelines issued by international medical specialty societies. The American College of Physicians' Guideline Grading System was used to determine the levels of evidence and grades of recommendations. The following questions were answered: A) Is elective neck dissection indicated in the treatment of papillary, follicular, and medullary thyroid carcinoma? B) When should central, lateral, and modified radical neck dissection be performed? C) Could molecular tests guide the extent of the neck dissection? Results/conclusion: Recommendation 1: Elective central neck dissection is not indicated in patients with cN0 well-differentiated thyroid carcinoma or in those with noninvasive T1 and T2 tumors but may be considered in T3-T4 tumors or in the presence of metastases in the lateral neck compartments. Recommendation 2: Elective central neck dissection is recommended in medullary thyroid carcinoma. Recommendation 3: Selective neck dissection of levels II-V should be indicated to treat neck metastases in papillary thyroid cancer, an approach that decreases the risk of recurrence and mortality. Recommendation 4: Compartmental neck dissection is indicated in the treatment of lymph node recurrence after elective or therapeutic neck dissection; "berry node picking" is not recommended. Recommendation 5: There are currently no recommendations regarding the use of molecular tests in guiding the extent of neck dissection in thyroid cancer.

Characteristics and prevalence of orofacial pain as an initial symptom of oral and oropharyngeal cancer and its impact on the patient's functionality and quality of life.

OBJECTIVE: To evaluate the prevalence and characteristics of orofacial pain in oral and oropharyngeal cancer (OOC), at diagnosis. MATERIAL AND METHODS: a) Study group (SG; n = 74) patients with cancer were divided into 2 subgroups: oral cancer (OC) and oropharyngeal cancer (OPC); b) control group (CG; n = 74) patients within dental care. STUDY DESIGN: An Orofacial Pain Assessment, verbal descriptive scale, Helkimo dysfunction index, Quality of Life questionnaire, and Karnofsky performance status (KPS) was used for evaluation. RESULTS: The mean age was 58.46 years (79.7% male) in SG, 58.61 years (20.3% male) in CG. The pain within the SG was indicated by the following: prevalence = 91.9% (21.6% in stages 0, I, or II; 70.3% in III or IV); reason for seeking care = 50.1%; main complaint = 55.4%; most important issue in the past 7 days = 74.3%; breakthrough-like pain = 64.9%; main features: chewing or swallowing as triggering factors, wake up patient, variable duration, independent of daytime, multiple descriptors, and earache. The following indexes were worse within the SG: clinical dysfunction, quality of life, and KPS. In addition, the OC subgroup reported toothache-like pain and burning; whereas the OPC subgroup reported heavy swallowing as triggering factor, throat as location, and a bilateral earache. CONCLUSION: At diagnosis, orofacial pain, including breakthrough-like pain, was prevalent in patients with OOC, and the pattern was heterogeneous. Predominantly, the pain was moderate to severe, related to stage of cancer, and already compromising the patients' quality of life and functionality.

Risk factors associated with disease-specific mortality in papillary thyroid cancer patients with distant metastases.

PURPOSE: Papillary thyroid carcinoma (PTC) is among the most curable cancer types. Even though uncommon, some patients present distant metastatic disease at diagnosis or during the follow-up and most of them have long-term survival. However, there continues to be controversies regarding what clinicopathological features are associated with mortality in these patients. This paper evaluates the factors related to poor disease-specific survival (DSS) in patients with metastatic PTC. METHODS: A retrospective cohort study included PTC patients with distant metastasis from a tertiary public oncological center. Clinicopathological features, treatment modalities, and outcome were reviewed. RESULTS: Between 1986 and 2014, 108 patients were diagnosed with metastatic PTC. In the multivariate analysis male sex (HR = 2.65; 95%CI: 1.08-6.53; P = 0.033), radioiodine refractory disease (HR = 9.50; 95%CI: 1.23-73.38; P = 0.031) and metastasis at multiple sites (HR = 5.91; 95%CI: 1.80-19.32; P = 0.003) were independent risk factors for death in patients with metastatic PTC. CONCLUSION: Male patients with metastatic PTC, with radioiodine refractory disease and metastasis at multiple sites have a high risk of death.

Multiparametric Ultrasound Evaluation of the Thyroid: Elastography as a Key Tool in the Risk Prediction of Undetermined Nodules (Bethesda III and IV)-Histopathological Correlation.

The purpose of this study was to select thyroid nodules most at risk for malignancy among those cytologically undetermined by fine-needle aspiration biopsy (FNAB), using B-mode, color duplex Doppler and 2-D shear wave shear wave elastography (2-D-SWE). This was a prospective diagnostic accuracy study with 62 Bethesda III/IV nodules according to FNAB (atypia/follicular lesion of undetermined significance or follicular neoplasia/Hürthle cell neoplasm). Ultrasonography (US) data were compared with resection histologic results, revealing 35 of 62 benign nodules (56.4%) and 27 of 62 carcinomas (43.6%). Conventional US was uses to evaluate nodule echogenicity, dimensions, contours, presence of halo and microcalcifications. Doppler US was used to assess the vascularization (exclusively or predominantly peripheral or central) and mean resistance index of three nodule arteries. Elastography was used to evaluate the nodule elastographic pattern; mean nodule deformation index; deformation ratio between nodule and adjacent thyroid parenchyma; and mean deformation ratio between nodule and pre-thyroid musculature (MDR). Statistical analysis included χ2, Fisher's exact, Student's t, Mann-Whitney tests and multivariable analysis by multiple logistic regression. Areas under the receiver operating characteristic curves (AUC-ROCs) were used for accuracy analysis. Fifty-eight participants (54.7 ± 14.0 y, 51 women) were studied. The parameters that were statistically significant to the univariate analysis were hypo-echogenicity, nodule diameter greater than width and all parameters analyzed from Doppler and elastography. Multivariate analysis revealed that the MDR (in kPa) was the best parameter for risk analysis of indeterminate nodules. Nodules with MDRs >1.53 exhibited a greater chance of malignancy (AUC-ROC = 0.98). We conclude that 2-D-SWE is able to select malignant nodules among those cytologically indeterminate, thus avoiding unnecessary surgery in these cytologic groups.

Comparison of 68Ga PET/CT to Other Imaging Studies in Medullary Thyroid Cancer: Superiority in Detecting Bone Metastases.

Context: Persistent disease after surgery is common in medullary thyroid cancer (MTC), requiring lifelong radiological surveillance. Staging workup includes imaging of neck, chest, abdomen, and bones. A study integrating all sites would be ideal. Despite the established use of gallium-68 (68Ga) positron emission tomography (PET)/CT with somatostatin analogues in most neuroendocrine tumors, its efficacy is controversial in MTC. Objective: Evaluate the efficacy of 68Ga PET/CT in detecting MTC lesions and evaluate tumor expression of somatostatin receptors (SSTRs) associated with 68Ga PET/CT findings. Methods: Prospective study evaluating 30 patients with MTC [group 1 (n = 16), biochemical disease; group 2 (n = 14), metastatic disease]. Patients underwent 68Ga PET/CT, bone scan, CT and ultrasound of the neck, CT of the chest, CT/MRI of the abdomen, and MRI of the spine. 68Ga PET/CT findings were analyzed by disease site as positive or negative and as concordant or discordant with conventional studies. Sensitivity and specificity were calculated using pathological or cytological analysis or unequivocal identification by standard imaging studies. Immunohistochemical analysis of SSTRs was compared with 68Ga PET/CT findings. Results: In both groups, 68Ga PET/CT was inferior to currently used imaging studies except for bone scan. In group 2, 68Ga PET/CT sensitivities were 56%, 57%, and 9% for detecting neck lymph nodes, lung metastases, and liver metastases, respectively, and 100% for bone metastases, superior to the bone scan (44%). Expression of SSTRs, observed in 44% of tumors, was not associated with 68Ga-DOTATATE uptake. Conclusions: 68Ga PET/CT does not provide optimal whole-body imaging as a single procedure in patients with MTC. However, it is highly sensitive in detecting bone lesions and could be a substitute for a bone scan and MRI.

Ultrasonographic Evaluation of Cervical Lymph Nodes in Thyroid Cancer.

Objective To determine what ultrasonographic features can identify metastatic cervical lymph nodes, both preoperatively and in recurrences after complete thyroidectomy. Study Design Prospective. Setting Outpatient clinic, Department of Head and Neck Surgery, School of Medicine, University of São Paulo, Brazil. Subjects and Methods A total of 1976 lymph nodes were evaluated in 118 patients submitted to total thyroidectomy with or without cervical lymph node dissection. All the patients were examined by cervical ultrasonography, preoperatively and/or postoperatively. The following factors were assessed: number, size, shape, margins, presence of fatty hilum, cortex, echotexture, echogenicity, presence of microcalcification, presence of necrosis, and type of vascularity. The specificity, sensitivity, positive predictive value, and negative predictive value of each variable were calculated. Univariate and multivariate logistic regression analyses were conducted. A receiver operator characteristic (ROC) curve was plotted to determine the best cutoff value for the number of variables to discriminate malignant lymph nodes. Results Significant differences were found between metastatic and benign lymph nodes with regard to all of the variables evaluated ( P < .05). Logistic regression analysis revealed that size and echogenicity were the best combination of altered variables (odds ratio, 40.080 and 7.288, respectively) in discriminating malignancy. The ROC curve analysis showed that 4 was the best cutoff value for the number of altered variables to discriminate malignant lymph nodes, with a combined specificity of 85.7%, sensitivity of 96.4%, and efficiency of 91.0%. Conclusion Greater diagnostic accuracy was achieved by associating the ultrasonographic variables assessed rather than by considering them individually.

Sorafenib for the Treatment of Progressive Metastatic Medullary Thyroid Cancer: Efficacy and Safety Analysis.

BACKGROUND: Treatment of advanced medullary thyroid carcinoma (MTC) was recently improved with the approval of vandetanib and cabozantinib. However, there is still a need to explore sequential therapy with more than one tyrosine kinase inhibitor (TKI) and to explore alternative therapies when vandetanib and cabozantinib are not available. This study reports the authors' experience with sorafenib as a treatment for advanced MTC. METHODS: This is a retrospective longitudinal study of 13 patients with progressive metastatic MTC treated with sorafenib 400 mg twice daily between December 2011 and January 2015. The primary endpoints were to evaluate response and progression-free survival (PFS) in patients treated with sorafenib outside a clinical trial. The secondary endpoint was an assessment of the toxicity profile. One patient was excluded because of a serious allergic skin rash one week after starting sorafenib. RESULTS: The analysis included 12 patients with metastatic MTC (median age 48 years), 10 with sporadic and 2 with hereditary disease. The median duration of treatment was 11 months, and the median follow-up was 15.5 months. At data cutoff, 2/12 (16%) patients were still on treatment for 16 and 34 months. According to Response Evaluation Criteria in Solid Tumors analysis, 10 (83.3%) patients showed stable disease, and two (16.6%) had progression of disease; no partial response was observed. The median PFS was nine months. However, three patients with extensive and rapidly progressive disease died within three months of sorafenib treatment. The median PFS excluding these three patients was 12 months. Adverse events (AE) occurred in nine (75%) patients. The main AEs were skin toxicity, weight loss, and fatigue. Five (41.6%) patients needed dose reduction, and one patient discontinued treatment because of toxicity. CONCLUSIONS: Treatment with sorafenib in progressive metastatic MTC is well tolerated and resulted in disease control and durable clinical benefit in 75% of patients. Sorafenib treatment could be considered when vandetanib and cabozantinib are not available or after failing these drugs.

[Surgical treatment of secondary hyperparathyroidism: a systematic review of the literature]. / Tratamento cirúrgico do hiperparatireoidismo secundário: revisão sistematizada da literatura.

Secondary hyperparathyroidism (HPT) has a high prevalence in renal patients. Secondary HPT results from disturbances in mineral homeostasis, particularly calcium, which stimulates the parathyroid glands, increasing the secretion of parathyroid hormone (PTH). Prolonged stimulation can lead to autonomy in parathyroid function. Initial treatment is clinical, but parathyroidectomy (PTx) may be required. PTx can be subtotal or total followed or not followed by parathyroid tissue autograft. We compared the indications and results of these strategies as shown in the literature through a systematic literature review on surgical treatment of secondary HPT presented in MedLine and LILACS from January 2008 to March 2014. The search terms were: hyperparathyroidism; secondary hyperparathyroidism; parathyroidectomy and parathyroid glands, restricted to research only in humans, articles available in electronic media, published in Portuguese, Spanish, English or French. We selected 49 articles. Subtotal and total PTx followed by parathyroid tissue autograft were the most used techniques, without consensus on the most effective surgical procedure, although there was a preference for the latter. The choice depends on surgeon's experience. There was consensus on the need to identify all parathyroid glands and cryopreservation of parathyroid tissue whenever possible to graft if hypoparathyroidism arise. Imaging studies may be useful, especially in recurrences. Alternative treatments of secondary HPT, both interventional and conservative, require further study.

Tratamento cirúrgico do hiperparatireoidismo secundário: revisão sistematizada da literatura / Surgical treatment of secondary hyperparathyroidism: a systematic review of the literature

O hiperparatireoidismo (HPT) secundário tem prevalência elevada em doentes renais crônicos. Decorre de alterações na homeostase mineral, principalmente do cálcio, que estimulam as glândulas paratireoides, com aumento na secreção de paratormônio (PTH). O estímulo prolongado pode levar à autonomia na função paratireóidea. Inicialmente, o tratamento é clínico, mas a paratireoidectomia (PTx) pode ser necessária. A PTx pode ser total, subtotal e total seguida de autoimplante de tecido paratireóideo. Este trabalho compara as indicações e resultados dessas técnicas na literatura. Foi realizada revisão sistematizada dos trabalhos publicados entre janeiro de 2008 e março de 2014 sobre tratamento cirúrgico do hiperparatireoidismo secundário nas bases de dados MedLine e LILACS. Foram utilizados os termos: hiperparatireoidismo; hiperparatireoidismo secundário; glândulas paratireoides e paratireoidectomia. Foram restritos a pesquisas apenas em humanos; artigos disponíveis em meio eletrônico; publicados em português, espanhol, inglês ou francês. A amostra final foi constituída de 49 artigos. A PTx subtotal e a total mais autoimplante foram as técnicas mais utilizadas, sem consenso sobre a técnica mais efetiva. Embora haja certa preferência pela última, a escolha depende da experiência do cirurgião. Há consenso sobre a necessidade de identificar todas as paratireoides e sobre a criopreservação de tecido paratireóideo, quando possível, para enxerto em caso de hipoparatireoidismo. Exames de imagem podem ser úteis, especialmente nas recidivas. Tratamentos alternativos do HPT secundário, tanto intervencionistas quanto conservadores, carecem de estudos mais aprofundados.

Secondary hyperparathyroidism (HPT) has a high prevalence in renal patients. Secondary HPT results from disturbances in mineral homeostasis, particularly calcium, which stimulates the parathyroid glands, increasing the secretion of parathyroid hormone (PTH). Prolonged stimulation can lead to autonomy in parathyroid function. Initial treatment is clinical, but parathyroidectomy (PTx) may be required. PTx can be subtotal or total followed or not followed by parathyroid tissue autograft. We compared the indications and results of these strategies as shown in the literature through a systematic literature review on surgical treatment of secondary HPT presented in MedLine and LILACS from January 2008 to March 2014. The search terms were: hyperparathyroidism; secondary hyperparathyroidism; parathyroidectomy and parathyroid glands, restricted to research only in humans, articles available in electronic media, published in Portuguese, Spanish, English or French. We selected 49 articles. Subtotal and total PTx followed by parathyroid tissue autograft were the most used techniques, without consensus on the most effective surgical procedure, although there was a preference for the latter. The choice depends on surgeon’s experience. There was consensus on the need to identify all parathyroid glands and cryopreservation of parathyroid tissue whenever possible to graft if hypoparathyroidism arise. Imaging studies may be useful, especially in recurrences. Alternative treatments of secondary HPT, both interventional and conservative, require further study.

Lymph node distribution in the central compartment of the neck: an anatomic study.

BACKGROUND: Dissection of the central compartment of the neck (CCN) is performed for proven or suspected lymph node metastases of thyroid carcinoma. During this procedure, the recurrent laryngeal nerves and the parathyroid glands are at risk. The purpose of this study was to determine the anatomic distribution of the lymph nodes in the CCN. METHODS: The anatomic distribution of the lymph nodes in the CCN was studied by dissection of 30 fresh cadavers. The soft tissue between the cricoid cartilage and the innominate vein, carotid arteries, and prevertebral fascia was removed and divided according to CCN sublevels. Nodules were identified by palpation in the specimen and sent for pathological examination. RESULTS: Three to 44 (18.5 ± 10.29) nodules were identified macroscopically. Two to 42 nodules were confirmed as lymph nodes after microscopic examination. The lymph node distribution was as follows: precricoid: 0 to 2 (0.9 ± 0.72); pretracheal: 1 of 35 (12.4 ± 8.19); lateral to the right recurrent laryngeal nerve (RLN): 0 to 11 (3.4 ± 2.34); and lateral to the left: 0 to 4 (1.7 ± 1.30). Twenty-six parathyroid glands were removed by 14 dissections. The innominate vein was found at 15 mm above the superior border of the clavicles to 35 mm below on the left side of the neck and 5 to 45 mm on the right side. CONCLUSION: The number of confirmed lymph nodes in the central neck varied from 2 to 42. Sixty-seven percent of the lymph nodes were in the pretracheal sublevel. There was no division between level VI and VII lymph nodes. Additionally, the innominate vein was found to be from 15 mm above the superior border of the clavicles to 35 mm below on the left side of the neck and 5 to 45 mm on the right side. Parathyroid glands were identified to be far away from the thyroid gland.

Total parathyroidectomy in a large cohort of cases with hyperparathyroidism associated with multiple endocrine neoplasia type 1: experience from a single academic center.

Most cases of sporadic primary hyperparathyroidism present disturbances in a single parathyroid gland and the surgery of choice is adenomectomy. Conversely, hyperparathyroidism associated with multiple endocrine neoplasia type 1 (hyperparathyroidism/multiple endocrine neoplasia type 1) is an asynchronic, asymmetrical multiglandular disease and it is surgically approached by either subtotal parathyroidectomy or total parathyroidectomy followed by parathyroid auto-implant to the forearm. In skilful hands, the efficacy of both approaches is similar and both should be complemented by prophylactic thymectomy. In a single academic center, 83 cases of hyperparathyroidism/ multiple endocrine neoplasia type 1 were operated on from 1987 to 2010 and our first surgical choice was total parathyroidectomy followed by parathyroid auto-implant to the non-dominant forearm and, since 1997, associated transcervical thymectomy to prevent thymic carcinoid. Overall, 40% of patients were given calcium replacement (mean intake 1.6 g/day) during the first months after surgery, and this fell to 28% in patients with longer follow-up. These findings indicate that several months may be needed in order to achieve a proper secretion by the parathyroid auto-implant. Hyperparathyroidism recurrence was observed in up to 15% of cases several years after the initial surgery. Thus, long-term follow-up is recommended for such cases. We conclude that, despite a tendency to subtotal parathyroidectomy worldwide, total parathyroidectomy followed by parathyroid auto-implant is a valid surgical option to treat hyperparathyroidism/multiple endocrine neoplasia type 1. Larger comparative systematic studies are needed to define the best surgical approach to hyperparathyroidism/multiple endocrine neoplasia type 1.