Hemicolectomy versus appendectomy for patients with appendiceal neuroendocrine tumours 1-2 cm in size: a retrospective, Europe-wide, pooled cohort study.

BACKGROUND: Awareness of the potential global overtreatment of patients with appendiceal neuroendocrine tumours (NETs) of 1-2 cm in size by performing oncological resections is increasing, but the rarity of this tumour has impeded clear recommendations to date. We aimed to assess the malignant potential of appendiceal NETs of 1-2 cm in size in patients with or without right-sided hemicolectomy. METHODS: In this retrospective cohort study, we pooled data from 40 hospitals in 15 European countries for patients of any age and Eastern Cooperative Oncology Group performance status with a histopathologically confirmed appendiceal NET of 1-2 cm in size who had a complete resection of the primary tumour between Jan 1, 2000, and Dec 31, 2010. Patients either had an appendectomy only or an appendectomy with oncological right-sided hemicolectomy or ileocecal resection. Predefined primary outcomes were the frequency of distant metastases and tumour-related mortality. Secondary outcomes included the frequency of regional lymph node metastases, the association between regional lymph node metastases and histopathological risk factors, and overall survival with or without right-sided hemicolectomy. Cox proportional hazards regression was used to estimate the relative all-cause mortality hazard associated with right-sided hemicolectomy compared with appendectomy alone. This study is registered with ClinicalTrials.gov, NCT03852693. FINDINGS: 282 patients with suspected appendiceal tumours were identified, of whom 278 with an appendiceal NET of 1-2 cm in size were included. 163 (59%) had an appendectomy and 115 (41%) had a right-sided hemicolectomy, 110 (40%) were men, 168 (60%) were women, and mean age at initial surgery was 36·0 years (SD 18·2). Median follow-up was 13·0 years (IQR 11·0-15·6). After centralised histopathological review, appendiceal NETs were classified as a possible or probable primary tumour in two (1%) of 278 patients with distant peritoneal metastases and in two (1%) 278 patients with distant metastases in the liver. All metastases were diagnosed synchronously with no tumour-related deaths during follow-up. Regional lymph node metastases were found in 22 (20%) of 112 patients with right-sided hemicolectomy with available data. On the basis of histopathological risk factors, we estimated that 12·8% (95% CI 6·5 -21·1) of patients undergoing appendectomy probably had residual regional lymph node metastases. Overall survival was similar between patients with appendectomy and right-sided hemicolectomy (adjusted hazard ratio 0·88 [95% CI 0·36-2·17]; p=0·71). INTERPRETATION: This study provides evidence that right-sided hemicolectomy is not indicated after complete resection of an appendiceal NET of 1-2 cm in size by appendectomy, that regional lymph node metastases of appendiceal NETs are clinically irrelevant, and that an additional postoperative exclusion of metastases and histopathological evaluation of risk factors is not supported by the presented results. These findings should inform consensus best practice guidelines for this patient cohort. FUNDING: Swiss Cancer Research foundation.

Thyroid surgery in children and adolescents: results from a multi-institutional German and Austrian database.

BACKGROUND: Outcomes of paediatric thyroid surgery have only been reported in smaller series or over long intervals. The aim of this multicentre study was to describe the recent outcomes of paediatric thyroid surgery in Germany and Austria. METHODS: Patients aged less than or equal to 18 years who underwent thyroid surgery and were prospectively documented in the StuDoQ|Thyroid registry between March 2017 and August 2022 were studied. RESULTS: In total, 604 patients from 90 institutions were included. The mean age was 15.4 years and 75 per cent of patients were female. The most frequent benign pathologies were nodular goitre (35.6 per cent), follicular adenoma (30.1 per cent), and Graves' disease (28.5 per cent). Among 126 thyroid malignancies, papillary thyroid carcinoma was diagnosed in 77.8 per cent of patients, follicular thyroid carcinoma was diagnosed in 10.3 per cent of patients, and medullary thyroid carcinoma was diagnosed in 8.7 per cent of patients. Lymph node metastases were found in 45.9 per cent of patients with papillary thyroid carcinoma and in 36.4 per cent of patients with medullary thyroid carcinoma. Vascular invasion was found in 62.9 per cent of patients with follicular thyroid carcinoma. The mean tumour diameters were 18, 42, and 13 mm in patients with papillary thyroid carcinoma, follicular thyroid carcinoma, and medullary thyroid carcinoma respectively. Early postoperative recurrent laryngeal nerve injury was seen in 27 of 556 patients (4.9 per cent) (22 of 617 (3.6 per cent) nerves at risk with intermittent intraoperative nerve monitoring and 5 of 237 (2.1 per cent) nerves at risk with continuous intraoperative nerve monitoring). Persistent recurrent laryngeal nerve injury was documented in 4 of 556 patients (0.7 per cent). Early postoperative hypoparathyroidism correlated with Graves' disease, thyroid carcinoma, and lymph node dissection. CONCLUSION: Papillary thyroid carcinoma and follicular thyroid carcinoma in children were often advanced at presentation. Persistent or recurrent lymph node metastases were mainly seen in papillary thyroid carcinoma. Overall survival was excellent, but longer follow-up is needed.

Axillary Node Metastases of Medullary Thyroid Cancer: A Hallmark of Terminal Disease.

Little is known about axillary node metastasis of medullary thyroid cancer (MTC). To address this, a comparative study of patients with and without axillary node metastases of MTC was conducted. Among 1215 consecutive patients with MTC, 482 patients had node-negative MTC and 733 patients node-positive MTC. Among the 733 patients with node-positive MTC, 4 patients (0.5%) had axillary node metastases, all of which were ipsilateral. Patients with axillary node metastases had 5.7-6.9-fold more node metastases removed, both at the authors' institution (medians of 34.5 vs. 5 metastases; p=0.011) and in total (medians of 57 vs. 10 metastases; p=0.013), developed more frequently distant metastases (3 of 4 vs. 178 of 729 patients, or 75 vs. 24%; p=0.049), specifically to bone (2 of 4 vs. 67 of 729 patients, or 50 vs. 9%; p=0.046) and brain (1 of 4 vs. 4 of 729 patients, or 25 vs. 0.5%; p=0.027), and more often succumbed to cancer-specific death (3 of 4 vs. 52 of 729 patients, or 75 vs. 14%; p=0.005). Altogether, patients with axillary node metastases revealed 4-8-fold more node metastases in the ipsilateral lateral neck (medians of 11 vs. 3 metastases; p=0.021) and in the ipsilateral central neck (medians of 8 vs. 1 metastases; p=0.079) patients without axillary node metastases. Cancer-specific survival of patients with vs. patients without axillary node metastases of MTC was significantly shorter (means of 41 vs. 224 months; plog-rank<0.001). These findings show that patients with axillary node metastases of MTC have massive metastatic dissemination with poor survival.

Clinical Presentation, Treatment, and Outcome of Parathyroid Carcinoma: Results of the NEKAR Retrospective International Multicenter Study.

OBJECTIVE: In this retrospective cohort study, we describe the clinical presentation and workup of parathyroid carcinoma (PC) and determine its clinical prognostic parameters. Primary outcome was recurrence free survival. SUMMARY BACKGROUND DATA: PC is an orphan malignancy for which diagnostic workup and treatment is not established. METHODS: Eighty-three patients were diagnosed with PC between 1986 and 2018. Disease-specific and recurrence-free survivals were estimated with the Kaplan-Meier method. Risk factors for recurrence were identified by binary logistic regression with adjustment for age and sex. Thirty-nine tumors underwent central histopathological review. RESULTS: Renal (39.8%), gastrointestinal (24.1%), bone (22.9%), and psychiatric (19.3%) symptoms were the most common symptoms. Surgical treatment was heterogeneous [parathyroidectomy [PTx)] alone: 22.9%; PTx and hemithyroidectomy: 24.1%; en bloc resection 15.7%; others 37.3%] and complications of surgery were frequent (recurrent laryngeal nerve palsy 25.3%; hypoparathyroidism 6%). Recurrence of PC was observed in 32 of 83 cases. In univariate analysis, rate of recurrence was reduced when extended initial surgery had been performed (P = 0.04). In multivariate analysis low T status [odds ratio (OR) = 2.65, 95% confidence interval (CI) 1.02-6.88, P = 0.045], N0 stage at initial diagnosis (OR = 6.32, 95% CI 1.33-30.01, P = 0.02), Ki-67 <10% (OR = 14.07, 95% CI 2.09-94.9, P = 0.007), and postoperative biochemical remission (OR = 0.023, 95% CI 0.001-0.52, P = 0.018) were beneficial prognostic parameters for recurrence-free survival. CONCLUSION: Despite a favorable overall prognosis, PC shows high rates of recurrence leading to repeated surgery and postoperative recurrent laryngeal nerve palsy and hypoparathyroidism. In view of the reduced recurrence rate in cases of extended surgery, ipsilateral completion surgery may be considered when PC is confirmed.

Risk Patterns of Distant Metastases in Follicular, Papillary and Medullary Thyroid Cancer.

This study of 542 patients with follicular thyroid cancer, 366 patients with the follicular variant and 1452 patients with the classical variant of papillary thyroid cancer, and 819 patients with sporadic medullary thyroid cancer operated at a tertiary referral center aimed to determine risk patterns of distant metastasis for each tumor entity, which are ill-defined. On multivariable logistic regression analyses, lymph node metastasis consistently emerged as an independent risk factor of distant metastasis, yielding odds ratios (ORs) of 2.4 and 2.8 for follicular thyroid cancer and the follicular variant of papillary thyroid cancer, and ORs of 5.9 and 6.4 for the classical variant of papillary thyroid cancer and sporadic medullary thyroid cancer. Another independent risk factor consistently associated with distant metastasis, most strongly in follicular thyroid cancer and the follicular variant of papillary thyroid cancer (OR 3.5 and 4.0), was patient age >60 years. Altogether, 2 distinct risk patterns of distant metastasis were identified, which were modulated by other cancer type-dependent risk factors: one with lymph node metastasis as leading component (classical variant of papillary thyroid cancer and sporadic medullary thyroid cancer), and another one with age as leading component (follicular thyroid cancer and the follicular variant of papillary thyroid cancer). Distant metastasis was exceptional in node-negative patients with sporadic medullary thyroid cancer (1.7%) and the classical variant of papillary thyroid cancer (1.4%), and infrequent in node-negative patients with the follicular variant of papillary thyroid cancer (4.4%). These findings delineate windows of opportunity for early surgical intervention before distant metastasis has occurred.

Metastatic risk profile of microscopic lymphatic and venous invasion in papillary thyroid cancer.

OBJECTIVES: The aim of this study was to define the suitability of microscopic lymphatic and venous invasion for prediction of lymph node and distant metastases in papillary thyroid cancer. DESIGN: Stratification by microscopic lymphatic and venous invasion, and multivariable analyses on lymph node and distant metastases including microscopic lymphatic and venous invasion as independent variables. SETTING: Tertiary referral centre. PARTICIPANTS: 422 patients who had ≥5 lymph nodes removed at initial thyroidectomy. MAIN OUTCOME MEASURES: Lymph node and distant metastases. RESULTS: Patients with microscopic lymphatic invasion had larger primary tumours than patients without and more often revealed microscopic venous invasion, multifocal tumour growth and lymph node metastases. Patients with microscopic venous invasion exhibited larger primary tumours than patients without and more commonly had microscopic lymphatic invasion, poor tumour differentiation, lymph node metastases and distant metastases. Prediction of lymph node metastases by microscopic lymphatic invasion was better than prediction of distant metastases by microscopic venous invasion regarding sensitivity (61.0 vs. 33.3%) and positive predictive value (92.6 vs. 20.9%), comparable regarding specificity (89.6 and 93.4%), and worse regarding negative predictive value (51.9 vs. 95.3%) and accuracy (70.1 vs. 87.7%). On multivariable logistic regression analysis, microscopic lymphatic invasion was associated with lymph node metastasis (odds ratio [OR] 11.1) and multifocal tumour growth (OR 2.4), whereas primary tumour size (OR 5.8 for tumours >40 mm relative to tumours ≤20 mm) and multifocal tumour growth (OR 3.1) were associated with distant metastasis. CONCLUSION: Stricter histopathological criteria are warranted to enhance the utility of microscopic vascular invasion for prediction of distant metastases in papillary thyroid cancer.

IGF2BP1 is the first positive marker for anaplastic thyroid carcinoma diagnosis.

Anaplastic thyroid carcinomas (ATC) are rare, but represent the most lethal malignancy of the thyroid. Selective molecular markers and drivers distinguishing ATC from other thyroid carcinomas of follicular origin remain largely unknown, limiting advances in diagnosis and treatment. In a retrospective study, we analyzed gene expression in 36 ATC, 18 poorly differentiated, 132 papillary, and 55 follicular thyroid carcinoma, as well as 124 paired and unpaired normal thyroid tissues in three independent cohorts by RNA-sequencing and immunohistochemistry. RNA-sequencing data in the test cohort suggested selective ATC protein biomarkers. Evaluation of these revealed that ATCs are characterized by the de novo expression of various testis antigens, including melanoma-associated antigen A3 (MAGEA3), but most importantly the oncofetal IGF2 mRNA binding protein 1 (IGF2BP1). Shallow whole genome sequencing essentially excluded that IGF2BP1 upregulation results from gene copy number alterations. Immunohistochemical analyses in all three tumor cohorts confirmed the selective de novo expression of IGF2BP1 protein in ATC. In sum, 75% (27/36) of all tested ATC and 0.5% (1/204) of poorly and well-differentiated thyroid carcinoma tissue samples were positive for IGF2BP1 protein. This indicates that IGF2BP1 protein expression identifies ATC with a diagnostic odds ratio of 612 (95% CI: 74.6-5021). In addition, we found that MAGEA3 is exclusively, although less consistently upregulated in ATC, presenting with an odds ratio of 411 (95% CI: 23.8-7098.7). Importantly, we provide confirmatory evidence that IGF2BP1 and MAGEA3 expression distinguishes ATC from poorly differentiated thyroid carcinoma. IGF2BP1 furthermore identified ATC foci within low-grade follicular thyroid carcinoma. In conclusion, IGF2BP1 represents the most promising single-gene marker available for ATC, followed by MAGEA3, improving on current techniques. Robust markers are essential to help distinguish this high-grade malignancy from other thyroid carcinomas, to guide surgical decision making, therapy and post-resection/therapy monitoring strategies.

Metastatic Risk Profile of Microscopic Lymphatic and Venous Invasion in Medullary Thyroid Cancer.

The metastatic risk profile of microscopic lymphatic and venous invasion in medullary thyroid cancer is ill-defined. This evidence gap calls for evaluation of the suitability of microscopic lymphatic and venous invasion at thyroidectomy for prediction of lymph node and distant metastases in medullary thyroid cancer. In this study of 484 patients with medullary thyroid cancer who had≥5 lymph nodes removed at initial thyroidectomy, microscopic lymphatic and venous invasion were significantly associated with greater primary tumor size (27.6 vs. 14.5 mm, and 30.8 vs. 16.2 mm) and more frequent lymph node metastasis (97.0 vs. 25.9%, and 85.2 vs. 39.5%) and distant metastasis (25.0 vs. 5.1%, and 32.8 vs. 7.3%). Prediction of lymph node metastases by microscopic lymphatic invasion was better than prediction of distant metastases by microscopic venous invasion regarding sensitivity (97.0 vs. 32.8%) and positive predictive value (58.4 vs. 39.2%); comparable regarding negative predictive value (98.5 vs. 90.5%) and accuracy (80.4 vs. 85.1%); and worse regarding specificity (74.1 vs. 92.7%). On multivariable logistic regression, microscopic lymphatic invasion predicted lymph node metastasis better (odds ratio [OR] 65.6) than primary tumor size (OR 4.6 for tumors>40 mm and OR 2.7 for tumors 21-40 mm, relative to tumors≤20 mm), whereas primary tumor size was better in predicting distant metastasis (OR 8.3 for tumors>40 mm and OR 3.9 for tumors 21-40 mm, relative to tumors≤20 mm) than microscopic venous invasion (OR 3.2). These data show that lymphatic invasion predicts lymph node metastases better in medullary thyroid cancer than venous invasion heralds distant metastases.

Volume, outcomes, and quality standards in thyroid surgery: an evidence-based analysis-European Society of Endocrine Surgeons (ESES) positional statement.

INTRODUCTION: Continuous efforts in surgical speciality aim to improve outcome. Therefore, correlation of volume and outcome, developing subspecialization, and identification of reliable parameters to identify and measure quality in surgery gain increasing attention in the surgical community as well as in public health care systems, and by health care providers. The need to investigate these correlations in the area of endocrine surgery was identified by ESES, and thyroid surgery was chosen for this analysis of the prevalent literature with regard to outcome and volume. MATERIALS AND METHODS: A literature search that is detailed below about correlation between volume and outcome in thyroid surgery was performed and assessed from an evidence-based perspective. Following presentation and live data discussion, a revised final positional statement was presented and consented by the ESES assembly. RESULTS: There is a lack of prospective randomized controlled studies for all items representing quality parameters of thyroid surgery using uniform definitions. Therefore, evidence levels are low and recommendation grades are based mainly on expert and peer evaluation of the prevalent data. CONCLUSION: In thyroid surgery a volume and outcome relationship exists with respect to the prevalence of complications. Besides volume, cumulative experience is expected to improve outcomes. In accordance with global data, a case load of < 25 thyroidectomies per surgeon per year appears to identify a low-volume surgeon, while > 50 thyroidectomies per surgeon per year identify a high-volume surgeon. A center with a case load of > 100 thyroidectomies per year is considered high-volume. Thyroid cancer and autoimmune thyroid disease predict an increased risk of surgical morbidity and should be operated by high-volume surgeons. Oncological results of thyroid cancer surgery are significantly better when performed by high-volume surgeons.

[Surgical aspects of multiple endocrine neoplasia type 2]. / Chirurgische Aspekte der Multiplen Endokrinen Neoplasie Typ 2.

Surgical aspects of multiple endocrine neoplasia type 2 Abstract. The multiple endocrine neoplasia type 2 (MEN 2) is an autosomal-dominant hereditary tumor-syndrome. The subtypes show clinically specific disease manifestations. In MEN 2a, medullary thyroid carcinoma, pheochromocytoma, and primary hyperparathyroidism occur, while in familial medullary thyroid carcinoma, the medullary thyroid carcinoma is the only clinical manifestation. In MEN 2b medullary thyroid carcinoma and pheochromocytoma are the clinically dominant manifestations. All MEN-2-specific disease is treated primarily surgically. It is of utmost importance to identify the individual gene carrier in order to enable timely intervention before malignancy develops (prophylactic surgery) or to reach surgical cure as well as to identify relatives that are MEN 2 gene-carriers. Typical MEN 2 manifestations and clinical signs important for surgery are outlined. In case MEN 2 is suspected, it may be vital to exclude underlying pheochromocytoma before diagnostic or surgical interventions are started to forego hyperadrenergic crisis unprepared.

Genotype-specific progression of hereditary medullary thyroid cancer.

Although already 25 years into the genomic era, age-related progression of hereditary medullary thyroid cancer (MTC), the prevalence of which is estimated at one in 80,000 inhabitants, remains to be delineated for most unique RET (REarranged during Transfection) mutations. Included in this study were 567 RET carriers. The age-related progression of MTC across histopathological groups (normal thyroid/C-cell hyperplasia; node-negative MTC; node-positive MTC) was statistically significant for 13 unique RET mutations (p.Cys611Phe/c.1832G > T; p.Cys611Tyr; p.Cys618Ser/c.1852T > A; p.Cys620Arg; p.Cys634Arg; p.Cys634Phe; p.Cys634Ser; p.Cys634Tyr; p.Glu768Asp; p.Leu790Phe/c.2370G > T; p.Val804Met; p.Ser891Ala; p.Met918Thr), whereas two unique RET mutations (p.Cys618Phe; p.Cys634Gly) trended toward statistical significance. When grouped by mutational risk (highest; high; moderate-high; low-moderate; polymorphism), the age-related progression of MTC was significant for all four categories of RET mutations, which differed significantly across and within the three histopathological groups. For high, for moderate-high, and for low-moderate risk RET mutations, the age-related progression of MTC by mutated codon was broadly comparable across and within the three histopathological groups, and essentially unaffected by the amino acid substitutions examined. These data argue in favor of splitting the American Thyroid Association's moderate-risk category into moderate-high and low-moderate risk categories, while emphasizing the need to contradistinguish the latter from rare nonpathogenic polymorphisms.

Chronic active Epstein-Barr virus infection of T-cell type, systemic form in an African migrant: case report and review of the literature on diagnostics standards and therapeutic options.

BACKGROUND: Chronic active Epstein-Barr virus (EBV) infection (CAEBV) of the T-/NK-cell type, systemic form is a rare and potentially life-threatening illness caused by persistent EBV infection. The highest incidence is found in children and adolescents with increased frequency among Asians and Native Americans, while the disease is uncommon in Western countries. Typically patients present with unspecific symptoms, like fever, lymphadenopathy, hepatosplenomegaly and liver dysfunction. Due to fatal complications including hemophagocytic syndrome, coagulopathy, multiple organ failure and development of EBV-positive lymphoproliferative disease (LPD) or lymphoma early diagnosis is critical for successful treatment. However, in consequence of the lack of experience due to the low incidence in Europe, a broad spectrum of clinical manifestations and a particularly unexpected group of patients, diagnosis can be challenging. Inhere we describe the clinicopathological findings of an African adult with CAEBV associated LPD with a brief review of the literature. CASE PRESENTATION: A 42-year-old African man with fever, enlargement of the spleen and a suspected epileptic seizure was referred to our hospital. Diagnostic testing repeatedly revealed a massive EBV-DNA load in peripheral blood. Whole-body PET-CT-scan presented a strong uptake at multiple bone marrow sites, the thyroid and the adrenal glands. Histopathological analysis of bone marrow and thyroid gland revealed a highly proliferating, atypical and predominantly intravascular cytotoxic T-cell population with intracellular EBV-encoded RNA. Clonality analysis revealed the presence of polyclonal T-cell-receptor. Based on these findings a CAEBV of the T-/NK-cell type, systemic form was diagnosed. Subsequent therapy including three cycles of chemotherapy with cyclophosphamide, doxorubicin, vincristine and prednisolone resulted in decreased EBV load, clinical improvement and ongoing complete remission. CONCLUSION: Adult-onset CAEBV of T/NK-cell type usually comprises a poor prognosis and is extremely rare in Western countries. Therefore, our case highlights the need for a clinical awareness of this disease in patients with systemic illness and for a comprehensive multidisciplinary diagnostic approach to facilitate diagnosis. Treatment options include antiviral drugs, immunosuppressive agents and systemic chemotherapy with or without allogeneic stem cell transplantation. Given the limited data these options need to be decided upon in each patient individually considering severity of the disease, comorbidities and response.

Parathyroid Hormone Levels Predict Long-Term Outcome After Operative Management of Parathyroid Cancer.

The role of parathyroid hormone (PTH) serum levels for prediction of outcome is ill defined for parathyroid cancer, which is a very rare disease. This investigation of 17 consecutive patients with parathyroid cancer, (re-)operated on at a tertiary referral center between 1994 and July 2016, with a mean follow-up of 179.6 months (15 years) aimed to clarify the suitability of PTH serum levels for prediction of clinical outcome after comprehensive operative management of parathyroid cancer. Cancer-specific mortality occurred significantly more often with the performance of sternotomy before or at first operation at this institution (80 vs. 0%; p=0.002); mean PTH serum levels before first operation (1 105 vs. 357 pg/ml; p=0.008; r=0.77) and at most recent follow-up (3 167 vs. 101 pg/ml; p=0.019; r=0.60); and normalization of PTH serum levels at most recent follow-up (0 vs. 64%; p=0.034). For cancer-specific survival, receiver-operating characteristics analysis identified as optimum cut-off point an initial PTH serum level of 700 pg/ml. For local recurrence, no significant associations were found. Kaplan-Meier analysis confirmed that the patients with initial PTH serum levels >700 pg/ml (plog-rank=0.011) and sternotomy (plog-rank<0.001), but not node or lung metastases, had worse cancer-specific survival. Parathyroid cancer is much more an endocrine disease with oncological features than an oncological disease with endocrine features. Operative intervention(s) should be comprehensive and directed at clearing all metabolically active parathyroid tumor deposits early. If surgical cure cannot be reached, it is pivotal to achieve metabolic control, obviating the need for, or facilitating, medical therapy of hypercalcemia, and preserve renal function.

Surgical management of secondary hyperparathyroidism in chronic kidney disease--a consensus report of the European Society of Endocrine Surgeons.

BACKGROUND: Despite advances in the medical management of secondary hyperparathyroidism due to chronic renal failure and dialysis (renal hyperparathyroidism), parathyroid surgery remains an important treatment option in the spectrum of the disease. Patients with severe and complicated renal hyperparathyroidism (HPT), refractory or intolerant to medical therapy and patients with specific requirements in prospect of or excluded from renal transplantation may require parathyroidectomy for renal hyperparathyroidism. METHODS: Present standard and actual controversial issues regarding surgical treatment of patients with hyperparathyroidism due to chronic renal failure were identified, and pertinent literature was searched and reviewed. Whenever applicable, evaluation of the level of evidence concerning diagnosis and management of renal hyperparathyroidism according to standard criteria and recommendation grading were employed. Results were discussed at the 6th Workshop of the European Society of Endocrine Surgeons entitled Hyperparathyroidism due to multiple gland disease: An evidence-based perspective. RESULTS: Presently, literature reveals scant data, especially, no prospective randomized studies to provide sufficient levels of evidence to substantiate recommendations for surgery in renal hyperparathyroidism. Appropriate surgical management of renal hyperparathyroidism involves standard bilateral exploration with bilateral cervical thymectomy and a spectrum of four standardized types of parathyroid resection that reveal comparable outcome results with regard to levels of evidence and recommendation. Specific patient requirements may favour one over the other procedure according to individualized demands. CONCLUSIONS: Surgery for patients with renal hyperparathyroidism in the era of calcimimetics continues to play an important role in selected patients and achieves efficient control of hyperparathyroidism. The overall success rate and long-term control of renal hyperparathyroidism and optimal handling of postoperative metabolic effects also depend on the timely indication, individually suitable type of parathyroid resection and specialized endocrine surgery.

Surgical curability of medullary thyroid cancer in multiple endocrine neoplasia 2B: a changing perspective.

OBJECTIVE: This investigation aimed at exploring the suitability of nonendocrine manifestations preceding medullary thyroid cancer (MTC) for early diagnosis of multiple endocrine neoplasia type 2B (MEN 2B). BACKGROUND: MEN 2B patients, running a high risk of metastatic MTC, must be diagnosed early for biochemical cure. METHODS: Forty-four MEN 2B patients carrying inherited (3 patients) and de novo (41 patients) M918T RET mutations were examined for signs and symptoms prompting MEN 2B. RESULTS: All 3 patients with inherited mutations were diagnosed before the age of 1 year and cured of their C-cell disease. Among 41 patients with de novo mutations, MEN 2B was diagnosed in 12 patients after recognition of nonendocrine manifestations [intestinal ganglioneuromatosis (6 patients), oral symptoms (5 patients), ocular ("tearless crying") (4 patients), and skeletal stigmata (1 patient) alone or concomitantly]. In the remaining 29 patients with de novo mutations, the diagnosis of MEN 2B was triggered by symptomatic MTC (28 patients) or pheochromocytoma (1 patient). The former patients, being significantly (P < 0.001) younger (means of 5.3 vs 17.6 years) and having lower calcitonin levels (means of 115 vs 25,519 pg/mL), smaller tumors (67% vs 0% were ≤10 mm) and less often extrathyroidal extension (0% vs 81%), lymph node (42% vs 100%), and distant metastases (8% vs 79%), were biochemically cured more often (58% vs 0%). CONCLUSIONS: MTC is curable in patients with de novo mutations when nonendocrine MEN 2B components are quickly appreciated and surgical intervention is performed before patients turn 4 years old.

Results of intraoperative neuromonitoring in thyroid surgery and preoperative vocal cord paralysis.

BACKGROUND: Systematic studies of intermittent intraoperative neuromonitoring (IONM) have shown that IONM enhances recurrent laryngeal nerve (RLN) identification via functional assessment, but does not significantly reduce rates of vocal cord (VC) paralysis (VCP). The reliability of functional nerve assessment depends on the preoperative integrity of VC mobility. The present study was therefore performed to analyze the validity of IONM in patients with pre-existing VC paralysis. METHODS: Of 8,128 patients, 285 (3.5 %) with preoperative VCP underwent thyroid surgery using standardized IONM of the RLN and vagus nerves (VNs). VC function was assessed by pre- and postoperative direct videolaryngoscopy. Quantitative parameters of IONM in patients with VCP were compared with IONM in patients with intact VC function. Clinical symptoms and surgical outcomes of patients with pre-existing VCP were analyzed. RESULTS: A total of 244 patients revealed negative, and 41 revealed positive IONM on the side of the VCP. VCP with positive IONM revealed significantly lower amplitudes of VN and RLN than intact VN (p = 0.010) and RLN (p = 0.011). Symptoms of patients with VCP included hoarseness (25 %), dyspnea (29 %), stridor (13 %), and dysphagia (13 %); 13 % were asymptomatic. New VCP occurred in five patients, ten needed tracheostomy for various reasons, and one patient died. CONCLUSIONS: Patients with pre-existing VCP revealed significantly reduced amplitude of ipsilateral VN and RLN, indicating retained nerve conductivity despite VC immobility. Preoperative laryngoscopy is therefore indispensable for reliable IONM and risk assessment, even in patients without voice abnormalities.

Surgical strategy for primary hyperparathyreoidism with thyroid hemiagenesis.

BACKGROUND: Thyroid hemiagenesis is a rare congenital anomaly, and still more rarely associated with primary hyperparathyroidism (pHPT). Due to the embryologic pathways of the thyroid and parathyroid glands, it remains unclear whether or not thyroid hemiagenesis may be linked to ipsilateral parathyroid agenesis, and consequently, surgical strategy for thyroid hemiagenesis associated pHPT (THAP) does not only depend on preoperative localization but also on the thyroid anomaly. METHODS: Including the present case report, a total of nine cases with THAP retrieved from the literature were reviewed. Seven of nine cases had thyroid hemiagenesis on the left side, three out of nine showed a parathyroid adenoma on the contralateral side to the thyroid hemiagenesis. CONCLUSIONS: Based on these cases, it can be concluded that the embryologic pathways of the thyroid and parathyroid glands are different, and in cases of THAP, parathyroid exploration should follow standard recommendations for pHPT surgery.