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Papillary thyroid carcinoma (PTC), the most common malignancy of follicular cell derivation, is generally associated with good prognosis. Nevertheless, it is important to identify patients with aggressive PTCs and unfavorable outcome. Molecular markers such as BRAF V600E mutation and TERT promoter mutations have been proposed for risk stratification. While TERT promoter mutations have been frequently associated with aggressive PTCs, the association of BRAF V600E mutation with increased recurrence and mortality is less clear and has been controversially discussed. The aim of the present study was to analyze whether differentially expressed genes can predict BRAF V600E mutations as well as TERT promoter mutations in PTCs. RNA sequencing identified a large number of differentially expressed genes between BRAF V600E and BRAF wildtype PTCs. Of those, AHNAK2, DCSTAMP, and FN1 could be confirmed in a larger cohort (n = 91) to be significantly upregulated in BRAF V600E mutant PTCs using quantitative RT-PCR. Moreover, individual PTC expression values of DCSTAMP and FN1 were able to predict the BRAF V600E mutation status with high sensitivity and specificity. The expression of TERT was detected in all PTCs harboring TERT promoter mutations and in 19% of PTCs without TERT promoter mutations. Tumors with both TERT expression and TERT promoter mutations were particularly associated with aggressive clinicopathological features and a shorter recurrence-free survival. Altogether, it will be interesting to explore the biological function of AHNAK2, DCSTAMP, and FN1 in PTC in more detail. The analysis of their expression patterns could allow the characterization of PTC subtypes and thus enabling a more individualized surgical and medical treatment., (© 2024 The Author(s). Genes, Chromosomes and Cancer published by Wiley Periodicals LLC.)

Background: Angiosarcoma of the adrenal gland is a very rare malignant vascular neoplasm. The clinical symptoms are atypical or completely absent. Angiosarcomas of the adrenal gland are therefore often discovered incidentally, and the diagnosis is made histologically after resection., Case Presentation: A 46-year-old white Spanish male who was a previous smoker and nondrinker and was slightly overweight (92 kg, 176 cm, body mass index 29.7 kg/m 2 ) with no relevant medical history presented to the internal medicine emergency department of our hospital with an unclear 12 cm tumor of the right adrenal gland. Prior to the computed tomography scan, he had had persistent evening fevers for 4 months and unintentional weight loss of 5 kg. The laboratory results showed anemia and an elevated C-reactive protein, but no hormone production. We performed an open adrenalectomy of the right adrenal gland. Finally, the histologic findings revealed an angiosarcoma of the adrenal gland., Conclusion: Even though angiosarcomas of the adrenal gland are rare, the differential diagnosis of an angiosarcoma should be considered if a malignant tumor of the adrenal gland is suspected. Treatment decisions should be made on an interdisciplinary basis and preferably in a specialized center. Owing to the rarity of angiosarcomas of the adrenal gland, it is necessary to continue to share clinical experience to gain a better understanding of this particular tumor entity., (© 2024. The Author(s).)

Thyroid surgery is associated with a risk of injury to the recurrent laryngeal nerve, especially in the presence of anatomical variants such as a non-recurrent laryngeal nerve (NRLN). Injury to the nerve leads to transient or permanent vocal cord palsy (VCP). A novel method to prevent VCP is continuous intraoperative nerve monitoring (cIONM), but less is known about the applicability of this method in patients with NRLN. The aim of this study was to evaluate our own data regarding feasibility and detailed characteristics of cIONM in NRLN patients. We performed a monocentric retrospective cohort analysis including clinical data and intraoperative nerve monitoring data (measured by Inomed Medizintechnik GmbH, Emmendingen, 'C2' and 'C2 Xplore' device) of all thyroid surgery patients, showing NRLN between 2014 and 2022. Of 1406 patients who underwent thyroid surgery with cIONM between 2014 and 2022, 12 patients (0.9%) showed NRLN intraoperatively. Notably, cIONM was feasible in eight patients (67%). In all cases the onset latency of the right vagus nerve was shorter (<3.0 ms) than usually expected, suggesting that a short latency might be suitable to distinguish NRLN. None of the patients had a post-operative VCP. Overall, cIONM appears to be feasible and safe in NRLN patients and provides helpful information to prevent VCP.

(1) Background: Infiltration of the aerodigestive tract in advanced thyroid carcinoma determines the prognosis and quality of life. Different stages of tracheal tumor invasion require customization of the surgical concept. (2) Methods: In the period from January 2007 to January 2023, patients who underwent surgery for advanced thyroid carcinomas with trachea resections were included in a retrospective observational study. The surgical resection concepts and operation-associated complications were documented. The overall survival and post-resection survival were analyzed. (3) Results: From 2007 to 2023, at the single-center UMC Mainz, 33 patients (15 female and 18 male) underwent neck surgery with trachea resections for locally advanced thyroid carcinomas. Of these, 14 were treated with non-transmural (trachea shaving) and 19 transmural trachea resections (9 "window" resections, 6 near-circular resections, 3 sleeve resections and 1 total laryngectomy with extramucosal esophageal resection). The two-year postoperative survival rate was 82.0 percent. The two-year recurrence-free survival rate was 75.0 percent (mean follow-up period: 29.2 months). (4) Conclusions: Tracheal resections for locally advanced tumor infiltration are feasible as an element of highly individualized treatment concepts.

Background: Intraoperative neuromonitoring is widely used in thyroid and parathyroid surgery to prevent unilateral and especially bilateral recurrent nerve paresis. Reference values for amplitude and latency for the recurrent laryngeal nerve and vagus nerve have been published. However, data quality measures that exclude errors of the underlying intraoperative neuromonitoring (IONM) data (immanent software errors, false data labelling) before statistical analysis have not yet been implemented., Methods: The authors developed an easy-to-use application (the Mainz IONM Quality Assurance and Analysis tool) using the programming language R. This tool allows visualization, automated and manual correction, and statistical analysis of complete raw data sets (electromyogram signals of all stimulations) from intermittent and continuous neuromonitoring in thyroid and parathyroid surgery. The Mainz IONM Quality Assurance and Analysis tool was used to evaluate IONM data generated and exported from 'C2' and 'C2 Xplore' neuromonitoring devices (inomed Medizintechnik GmbH) after surgery. For the first time, reference values for latency and amplitude were calculated based on 'cleaned' IONM data., Results: Intraoperative neuromonitoring data files of 1935 patients consecutively operated on from June 2014 to May 2020 were included. Of 1921 readable files, 34 were excluded for missing data labelling. Automated plausibility checks revealed: less than 3 per cent device errors for electromyogram signal detection; 1138 files (approximately 60 per cent) contained potential labelling errors or inconsistencies necessitating manual review; and 915 files (48.5 per cent) were indeed erroneous. Mean(s.d.) reference onset latencies for the left vagus nerve, right vagus nerve, recurrent laryngeal nerve, and external branch of the superior laryngeal nerve were 6.8(1.1), 4.2(0.8), 2.5(1.1), and 2.1(0.5) ms, respectively., Conclusion: Due to high error frequencies, IONM data should undergo in-depth review and multi-step cleaning processes before analysis to standardize scientific reporting. Device software calculates latencies differently; therefore reference values are device-specific (latency) and/or set-up-specific (amplitude). Novel C2-specific reference values for latency and amplitude deviate considerably from published values., (© The Author(s) 2023. Published by Oxford University Press on behalf of BJS Society Ltd.)

Background: Renal hyperparathyroidism results from pathophysiologic changes induced and maintained by terminal renal failure. Surgical treatment is possible using various resection strategies., Aim of the Work (research Question): The aim of this work is to illustrate the indications, techniques and resection strategies for surgical treatment of renal hyperparathyroidism., Material and Methods: National and international guidelines regarding the surgical treatment of renal hyperparathyroidism were analyzed. Furthermore, our own practical experience was integrated into the article., Results: While the indications for surgery according to the Surgical Working Group Endocrinology (CAEK) guidelines are given in cases of clinical impairment and renal hyperparathyroidism that cannot be controlled by medication, international guidelines additionally refer to the absolute parathyroid hormone level for deciding for surgery., Discussion: Individual patient consultation is necessary in the case of renal hyperparathyroidism in order to determine the right time for surgical treatment as well as the most suitable surgical technique, taking into account the individual risk profile and other therapeutic perspectives, including renal transplantation., (© 2023. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Background: Currently, treatment recommendations for papillary thyroid carcinoma are not based on the genetic background causing tumourigenesis. The aim of the present study was to correlate the mutational profile of papillary thyroid carcinoma with clinical parameters of tumour aggressiveness, to establish recommendations for risk-stratified surgical treatment., Method: Papillary thyroid carcinoma tumour tissue of patients undergoing thyroid surgery at the University Medical Centre Mainz underwent analysis of BRAF, TERT promoter and RAS mutational status as well as potential RET and NTRK rearrangements. Mutation status was correlated with clinical course of disease., Results: One hundred and seventy-one patients operated for papillary thyroid carcinoma were included. The median age was 48 years (range 8-85) and 69 per cent (118/171) of patients were females. One hundred and nine papillary thyroid carcinomas were BRAF-V600E mutant, 16 TERT promotor mutant and 12 RAS mutant; 12 papillary thyroid carcinomas harboured RET rearrangements and two papillary thyroid carcinomas showed NTRK rearrangements. TERT promoter mutant papillary thyroid carcinomas had a higher risk of distant metastasis (OR 51.3, 7.0 to 1048.2, P < 0.001) and radioiodine-refractory disease (OR 37.8, 9.9 to 169.5, P < 0.001). Concomitant BRAF and TERT promoter mutations increased the risk of radioiodine-refractory disease in papillary thyroid carcinoma (OR 21.7, 5.6 to 88.9, P < 0.001). RET rearrangements were associated with a higher count of tumour-affected lymph nodes (OR 7950.9, 233.7 to 270495.7, P < 0.001) but did not influence distant metastasis or radioiodine-refractory disease., Conclusions: Papillary thyroid carcinoma with concomitant BRAF-V600E and TERT promoter mutations demonstrated an aggressive course of disease, suggesting the need for a more extensive surgical strategy. RET rearrangement-positive papillary thyroid carcinoma did not affect the clinical outcome, potentially obviating the need for prophylactic lymphadenectomy., (© The Author(s) 2023. Published by Oxford University Press on behalf of BJS Society Ltd.)

Background: In patients with neuroendocrine liver metastasis (NELM), liver transplantation (LT) is an alternative to liver resection (LR), although the choice of therapy remains controversial. In this multicenter study, we aim to provide novel insight in this dispute., Methods: Following a systematic literature search, 15 large international centers were contacted to provide comprehensive data on their patients after LR or LT for NELM. Survival analyses were performed with the Kaplan-Meier method, while multivariable Cox regression served to identify factors influencing survival after either transplantation or resection. Inverse probability weighting and propensity score matching was used for analyses with balanced and equalized baseline characteristics., Results: Overall, 455 patients were analyzed, including 230 after LR and 225 after LT, with a median follow-up of 97 months [95% confidence interval (CI): 85-110 months]. Multivariable analysis revealed G3 grading as a negative prognostic factor for LR [hazard ratio (HR)=2.22, 95% CI: 1.04-4.77, P =0.040], while G2 grading (HR=2.52, 95% CI: 1.15-5.52, P =0.021) and LT outside Milan criteria (HR=2.40, 95% CI: 1.16-4.92, P =0.018) were negative prognostic factors in transplanted patients. Inverse probability-weighted multivariate analyses revealed a distinct survival benefit after LT. Matched patients presented a median overall survival (OS) of 197 months (95% CI: 143-not reached) and a 73% 5-year OS after LT, and 119 months (95% CI: 74-133 months) and a 52.8% 5-year OS after LR (HR=0.59, 95% CI: 0.3-0.9, P =0.022). However, the survival benefit after LT was lost if patients were transplanted outside Milan criteria., Conclusions: This multicentric study in patients with NELM demonstrates a survival benefit of LT over LR. This benefit depends on adherence to selection criteria, in particular low-grade tumor biology and Milan criteria, and must be balanced against potential risks of LT., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.)

Purpose: EUROCRINE is an endocrine surgical register documenting diagnostic processes, indication for surgical treatment, surgical procedures, and outcomes. The purpose was to analyse data for PHPT in German speaking countries regarding differences in clinical presentation, diagnostic workup, and treatment., Methods: All operations for PHPT performed from 07/2015 to 12/2019 were analysed., Results: Three thousand two hundred ninety-one patients in Germany (9 centres; 1762 patients), Switzerland (16 centres; 971 patients) and Austria (5 centres; 558 patients) were analysed. Hereditary disease was seen in 36 patients in Germany, 16 patients in Switzerland and 8 patients in Austria. In sporadic disease before primary operation, PET-CT showed the highest sensitivity in all countries. In re-operations, CT and PET-CT achieved the highest sensitivities. The highest sensitivity of IOPTH was seen in Austria (98.1%), followed by Germany (96.4%) and Switzerland (91.3%). Operation methods and mean operative time reached statistical significance (p<0.05). Complication rates are low. Overall, 656 (19.9%) patients were asymptomatic; the remainder showed bone manifestations, kidney stones, fatigue and/or neuropsychiatric symptoms., Conclusion: Early postoperative normocalcaemia ranged between 96.8 and 97.1%. Complication rates are low. PET-CT had the highest sensitivity in all three countries in patients undergoing primary operation as well as in Switzerland and Austria in patients undergoing re-operation. PET-CT could be considered a first-line preoperative imaging modality in patients with inconclusive ultrasound examination. The EUROCRINE registry is a beneficial and comprehensive data source for outcome analysis of endocrine procedures on a supranational level., (© 2023. The Author(s).)

In thyroid surgery, intra-operative neuromonitoring signals of the recurrent laryngeal nerve can be detected by surface electrodes on a tracheal tube positioned at the vocal fold level. The incidence of difficult tracheal intubation in patients undergoing thyroidectomy for nodular goitre ranges from 5.3% to 20.5%. The aim of this study was to compare videolaryngoscopy with conventional direct laryngoscopy as methods for proper placement of the surface electrode to prevent insufficient intra-operative nerve signal quality. In this prospective randomised trial, adult patients requiring tracheal intubation during thyroid surgery were randomly allocated to two groups of C-MAC ® (Macintosh style blade) videolaryngoscope or direct laryngoscopy using the Macintosh laryngoscope. Primary outcome was the incidence of insufficient signal electromyogram amplitude level (< 500 μV) after successful tracheal intubation. A total of 260 (130 per group) participants were analysed. An insufficient signal was more frequent with direct laryngoscopy (35/130, 27%), compared with C-MAC (12/130, 9%, p < 0.001). First-pass tracheal intubation success rate was lower with direct laryngoscopy (86/130 (66%)) compared with the C-MAC (125/130 (96%)) (p < 0.0001). Cormack and Lehane grade ≥ 3 was observed more frequently with direct laryngoscopy (16/130 (12%)), compared with the C-MAC (0/130, (0%)) (p < 0.0001). The results suggest that videolaryngoscopy has an impact on the quality of the initial intra-operative neuromonitoring signal in patients undergoing thyroid surgery, and this technique can provide optimised surface electrode positioning., (© 2022 The Authors. Anaesthesia published by John Wiley & Sons Ltd on behalf of Association of Anaesthetists.)

Competing Interests: Alexander Drzezga:Research support: Siemens Healthineers, Life Molecular Imaging, GE Healthcare, AVID Radiopharmaceuticals, SOFIE, EisaiSpeaker Honorary/Advisory Boards: Siemens Healthineers, Sanofi, GE Healthcare, Biogen, Novo Nordisk, Invicro, Novartis/AAAStock: Siemens Healthineers, Lantheus HoldingPatents: Patent pending for 18F-PSMA7 (PSMA PET imaging tracer).Ken Herrmann:Personal fees from Bayer, personal fees and other from Sofie Biosciences, personal fees from SIRTEX, non-financial support from ABX, personal fees from Adacap, personal fees from Curium, personal fees from Endocyte, grants and personal fees from BTG, personal fees from IPSEN, personal fees from Siemens Healthineers, personal fees from GE Healthcare, personal fees from Amgen, personal fees from Novartis, personal fees from ymabs, personal fees from Aktis Oncology, personal fees from Theragnostics, personal fees from Pharma15, outside the submitted work.Michael C Kreißl: Bayer Healthcare: advisory board, event sponsoring; Eisai: advisory board, event sponsoring, talks; Exelixis: advisory bord, talk; GE Healthcare: talks, event sponsoring, research funding; Ipsen: talks, event sponsoring, travel funding, advisory bord; Takeda: talks; SanofiGenzyme: talks, travel, research funding; Siemens: event sponsoring; Curium: event sponsoring.

A consensus statement about indications for post-surgical radioiodine therapy (RIT) in differentiated thyroid cancer patients (DTC) was recently published by the European Thyroid Association (ETA) 1. This publication discusses indications for RIT on the basis of an individual risk assessment. Many of the conclusions of this consensus statement are well founded and accepted across the disciplines involved. However, especially from the perspective of nuclear medicine, as the discipline responsible for indicating and executing RIT, some of the recommendations may require further clarification with regard to their compatibility with established best practice and national standards of care. Assessment of the indications for RIT is strongly dependent on the weighing up of benefits and risks. On the basis of longstanding clinical experience in nuclear medicine, RIT represents a highly specific precision medicine procedure of proven efficacy with a favorable side-effect profile. This distinguishes RIT significantly from other adjuvant oncological therapies and has resulted in the establishment of this procedure as a usually well-tolerated, standard safety measure. With regard to its favorable risk/benefit ratio, this procedure should not be unnecessarily restricted, in the interest of offering reassurance to the patients. Both patients' interests and regional/national differences need to be taken into account. We would therefore like to comment on the recent consensus from the perspective of authors and to provide recommendations based on the respective published data., Competing Interests: Alexander Drzezga:Research support: Siemens Healthineers, Life Molecular Imaging, GE Healthcare, AVID Radiopharmaceuticals, SOFIE, EisaiSpeaker Honorary/Advisory Boards: Siemens Healthineers, Sanofi, GE Healthcare, Biogen, Novo Nordisk, Invicro, Novartis/AAAStock: Siemens Healthineers, Lantheus HoldingPatents: Patent pending for 18F-PSMA7 (PSMA PET imaging tracer).Ken Herrmann:Personal fees from Bayer, personal fees and other from Sofie Biosciences, personal fees from SIRTEX, non-financial support from ABX, personal fees from Adacap, personal fees from Curium, personal fees from Endocyte, grants and personal fees from BTG, personal fees from IPSEN, personal fees from Siemens Healthineers, personal fees from GE Healthcare, personal fees from Amgen, personal fees from Novartis, personal fees from ymabs, personal fees from Aktis Oncology, personal fees from Theragnostics, personal fees from Pharma15, outside the submitted work., (Thieme. All rights reserved.)

Objectives: Fine-needle aspiration cytology (FNAC) is recommended by international guidelines for the preoperative evaluation of suspicious thyroid nodules >1 cm. Despite robust evidence from endocrine centers demonstrating the key role of FNAC results for the indication of surgery, the method is not routinely used in European clinics. The database EUROCRINE ® , which was introduced in 2015 with the scope of registering operations of the endocrine system, allows for a large-scale analysis of the current service reality in Europe concerning FNAC use and associated accuracy., Methods: Operations performed to "exclude malignancy", registered from January 2015 to December 2018 in EUROCRINE ® , were analyzed. Parameters of accuracy were calculated for FNAC. FNAC results were considered "test positive" in the case of Bethesda category IV, V, and VI, since these categories usually prompt surgical interventions in European centers for thyroid surgery. Bethesda category II and III were considered "test negative"., Results: Of 8,791 operations, 5,780 had preoperative FNAC (65.7%). The overall malignancy rate was 28.3% (2,488/8,791). Malignancy rates were 68.8% for Bethesda VI, 69.9% for Bethesda V, 32.6% for Bethesda IV, 28.2% for III, 20.2% for Bethesda II, and 24.5% for Bethesda I. After exclusion of papillary microcarcinomas (PTMCs), the sensitivity of FNAC was 71.7% and specificity 43.5%, the positive predictive value was 29.1% and the negative predictive value 82.7%., Conclusions: Although the indication to "exclude malignancy" was the predominant reason that prompted thyroid resection in the present cohort, FNAC was only used in about 65.7% of cases. When performed, FNAC was associated with unexpectedly low accuracy. Interestingly, in Bethesda II, 20.2% of malignant entities were present (13.3% after the exclusion of PTMCs)., Competing Interests: Competing interests: Authors state no conflict of interest., (© 2021 Julia I. Staubitz et al., published by De Gruyter, Berlin/Boston.)

Background: Surgery is the curative therapy for patients with medullary thyroid carcinoma (MTC). In determining the extent of surgery, the risk of complications should be considered. The aim of this study was to assess procedure-specific outcomes and risk factors for complications after surgery for MTC., Methods: Patients who underwent thyroid surgery for MTC were identified in two European prospective quality databases. Hypoparathyroidism was defined by treatment with calcium/active vitamin D. Recurrent laryngeal nerve (RLN) palsy was diagnosed on laryngoscopy. Complications were considered at least transient if present at last follow-up. Risk factors for at-least transient hypoparathyroidism and RLN palsy were identified by logistic regression analysis., Results: A total of 650 patients underwent surgery in 69 centres at a median age of 56 years. Hypoparathyroidism, RLN palsy and bleeding requiring reoperation occurred in 170 (26·2 per cent), 62 (13·7 per cent) and 17 (2·6 per cent) respectively. Factors associated with hypoparathyroidism were central lymph node dissection (CLND) (odds ratio (OR) 2·20, 95 per cent c.i. 1·04 to 4·67), CLND plus unilateral lateral lymph node dissection (LLND) (OR 2·78, 1·20 to 6·43), CLND plus bilateral LLND (OR 2·83, 1·13 to 7·05) and four or more parathyroid glands observed (OR 4·18, 1·46 to 12·00). RLN palsy was associated with CLND plus LLND (OR 4·04, 1·12 to 14·58) and T4 tumours (OR 12·16, 4·46 to 33·18). After compartment-oriented lymph node dissection, N0 status was achieved in 248 of 537 patients (46·2 per cent)., Conclusion: Complications after surgery for MTC are procedure-specific and may relate to the unavoidable consequences of radical dissection needed in some patients., (© The Author(s) 2021. Published by Oxford University Press on behalf of BJS Society Ltd. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Since 2015 operations performed in the field of endocrine surgery have been entered into the European registry EUROCRINE®. The aim of this analysis was a description of the current healthcare situation for adrenal surgery in a homogeneous healthcare environment corresponding to the German-speaking countries-or to the presence of the working group on surgical endocrinology (CAEK) of the German society for general and visceral surgery (DGAV)-and to assess the adherence to current international treatment guidelines., Methods: An analysis of the preoperative diagnostics, the applied operative techniques and the underlying histological entities was carried out for all operations on adrenal glands in Germany, Switzerland and Austria, which were registered in EUROCRINE® from 2015 to 2019., Results: In the total of 21 participating hospitals from the German-speaking EUROCRINE® countries, 658 operations on adrenal glands were performed. In 90% of cases unilateral adrenalectomy was performed, in 3% bilateral adrenalectomy and in 7% other resection procedures. In 41% the main histological diagnosis was an adrenocortical adenoma. In 15% malignant entities were detected on final histology, including 6% adrenocortical carcinoma (ACC) and 8% metastases to the adrenal glands. 23% of the operations were performed for pheochromocytoma. This entity was primarily resected using minimally invasive approaches (82%), whereas minimally invasive techniques were applied in 28% for ACC and in 66% for metastases to the adrenal glands., Conclusion: Surprisingly, following adrenocortical adenoma and pheochromocytoma, the third most common histological entity was metastasis of different extra-adrenal primary tumors to the adrenal gland. Of the operations for ACC 28% were scheduled for minimally invasive techniques, but conversion to open surgery was necessary in 20%. The analysis revealed discrepancies between treatment reality and international guideline recommendations that raise questions, which will be addressed by an updated version of the EUROCRINE® module for the documentation of adrenal surgery.

Background: The impact of intraoperative frozen section (iFS) analysis on the frequency of completion thyroidectomy for the management of thyroid carcinoma is controversial. Although specialized endocrine centres have published their respective results, there are insufficient data from primary and secondary healthcare levels. The aim of this study was to analyse the utility of iFS analysis., Methods: In the Prospective Evaluation Study Thyroid Surgery (PETS) 2 study, 22 011 operations for benign and malignant thyroid disease were registered prospectively in 68 European hospitals from 1 July 2010 to 31 December 2012. Group 1 consisted of 569 patients from University Medical Centre (UMC) Mainz, and group 2 comprised 21 442 patients from other PETS 2 participating hospitals. UMC Mainz exercised targeted but liberal use of iFS analysis for suspected malignant nodules. iFS analysis was compared with standard histological examination regarding the correct distinction between benign and malignant disease. The percentage of completion thyroidectomies was assessed for the participating hospitals., Results: iFS analysis was performed in 35.70 per cent of patients in group 1 versus 21.80 per cent of those in group 2 (risk ratio (RR) 1.6, 95 per cent c.i. 1.5 to 1.8; P < 0.001). Sensitivity of iFS analysis was 75.0 per cent in group 1 versus 63.50 per cent in group 2 (RR 1.2, 1.2 to 1.3; P = 0.040). Completion surgery was necessary in 8.10 per cent of patients in group 1 versus 20.8 per cent of those in group 2 (RR 0.4, 0.2 to 0.7; P = 0.001)., Conclusion: iFS analysis is a useful tool in determining the appropriate surgical management of thyroid disease. Targeted use of iFS was associated with a significantly higher sensitivity for the detection of malignancy, and with a significantly reduced necessity for completion surgery., (© The Author(s) 2021. Published by Oxford University Press on behalf of BJS Society Ltd.)

Purpose: The robot-assisted approach for Ivor Lewis esophagectomy offers an enlarged, three-dimensional overview of the intraoperative situs. The vagal nerve (VN) can easily be detected, preserved, and intentionally resected below the separation point of the recurrent laryngeal nerve (RLN). However, postoperative vocal cord paresis can result from vagal or RLN injury during radical lymph node dissection, presenting a challenge to the operating surgeon., Methods: From May to August 2019, 10 cases of robot-assisted minimally invasive esophagectomy (RAMIE) with extended 2-field lymphadenectomy, performed at the University Medical Center Mainz, were included in a prospective cohort study. Bilateral intermittent intraoperative nerve monitoring (IONM) of the RLN and VN was performed, including pre- and postoperative laryngoscopy assessment., Results: Reliable mean signals of the right VN (2.57 mV/4.50 ms) and the RLN (left 1.24 mV/3.71 ms, right 0.85 mV/3.56 ms) were obtained. IONM facilitated the identification of the exact height of separation of the right RLN from the VN. There were no cases of permanent postoperative vocal paresis. Median lymph node count from the paratracheal stations was 5 lymph nodes., Conclusion: IONM was feasible during RAMIE. The intraoperative identification of the RLN location contributed to the accuracy of lymph node dissection of the paratracheal lymph node stations. RLN damage and subsequent postoperative vocal cord paresis can potentially be prevented by IONM.

Advanced thyroid carcinomas with infiltration of the aerodigestive tract are rare but are responsible for approximately 50% of the tumor-specific mortality. Due to impending and frequently life-threatening local complications and in the absence of promising therapeutic alternatives, a resection in curative or palliative intention is indicated if the local tumor is resectable. The resection and especially reconstruction of the trachea represent an extraordinary surgical challenge, require an individualized approach as well as exact knowledge of tracheal resection techniques. The decision for surgery in general, the selection of adequate resection and reconstruction strategies as well as the perioperative management should be accompanied by a particularly experienced interdisciplinary team.

Background: Intraoperative nerve monitoring (IONM) of the recurrent laryngeal nerve (RLN) predicts the risk of vocal cord palsy (VCP). IONM can be used to adapt the surgical strategy in order to prevent bilateral VCP and associated morbidity. Controversial results have been reported in the literature for the effect of IONM on rates of VCP, and large multicentre studies are required for elucidation., Methods: Patients undergoing first-time thyroidectomy for benign thyroid disease between May 2015 and January 2019, documented prospectively in the European registry EUROCRINE®, were included in a cohort study. The influence of IONM and other factors on the development of postoperative VCP was analysed using multivariable regression analysis., Results: Of 4598 operations from 82 hospitals, 3542 (77·0 per cent) were performed in female patients. IONM was used in 4182 (91·0 per cent) of 4598 operations, independent of hospital volume. Postoperative VCP was diagnosed in 50 (1·1 per cent) of the 4598 patients. The use of IONM was associated with a lower risk of postoperative VCP in multivariable analysis (odds ratio (OR) 0·34, 95 per cent c.i. 0·16 to 0·73). Damage to the RLN noted during surgery (OR 24·77, 12·91 to 48·07) and thyroiditis (OR 2·03, 1·10 to 3·76) were associated with an increased risk of VCP. Higher hospital volume correlated with a lower rate of VCP (OR 0·05, 0·01 to 0·13)., Conclusion: Use of IONM was associated with a low rate of postoperative VCP., (© 2020 The Authors. BJS Open published by John Wiley & Sons Ltd on behalf of British Journal of Surgery Society.)

Purpose: Thyroid nodules in the pediatric population are more frequently associated with malignant thyroid disease than in adult cohorts. Yet, there is a potential risk of surgical overtreatment. With this single center study, an analysis of potential overtreatment for suspected malignant thyroid disease in children and young adults was aimed for., Methods: In a period from 2005 to 2018, 155 thyroid operations in children and young adults performed at the University Medical Center Mainz, Germany, were analyzed (patient age 3-20 years, 117 female). Cases were categorized for preoperative diagnosis: non-malignant (group I, n = 45) and malignant thyroid disease (group II, n = 110). Postoperative parameters (histology, complication rates) were assessed and compared between groups., Results: 91.1% of group I were histologically benign. 44.5% of group II harbored malignancy. Permanent hypoparathyroidism was documented in group I (2.7%) and in group II (1.4%, p = 1.000). Wound infections were absent in group I but observed in group II (0.9%, p = 1.000). Transient vocal cord palsy was recorded only in group I (2.3%, 2/85 vs. 0/177 nerves at risk, p = 0.104). Permanent vocal cord palsies were absent., Conclusion: Preoperative diagnoses were correct in over 90% of group I and in nearly 45% of group II. The high proportion of carcinomas in group II ruled out the issue of potential overtreatment. The risk of severe postoperative complications was equally low in both patient groups.

Purpose: Patients with thyroid cancer are often assumed to have no quality of life (QOL) impairments after treatment because of thyroid cancer's good prognosis. However, the QOL implications of surgical complications and the necessity to take lifelong medication are seldom assessed., Methods: Patients who had surgery due to thyroid cancer at the University Medical Center Mainz between 2010 and 2015 and who had calcium or parathyroid hormone levels below the reference values immediately following surgery were eligible for this study. QOL was assessed using the EORTC QLQ-C30 and the thyroid cancer module EORTC QLQ-THY34. Multiple logistic regression was used to determine factors associated with a worse QOL compared with a general population., Results: A total of 75 (56%) of 134 eligible patients participated in the study. Patients with persistent/prolonged calcium or vitamin D intake reported worse QOL in the domains of global health, physical functioning, role functioning, emotional functioning, and insomnia than patients without current intake. Current calcium and vitamin D intake, higher education, living with a partner, and age had an effect on the odds of having worse QOL than the age- and sex-adjusted general population., Conclusion: Prolonged calcium and/or vitamin D intake are negatively associated with certain domains of QOL in thyroid cancer patients who are at least 1 year post surgery. Assessment of calcium and vitamin D and diagnosis of hypoparathyroidism are therefore important for the follow-up of thyroid cancer survivors since it may affect their QOL.

Papillary thyroid cancer (PTC) is the most common type of endocrine malignancy. By RNA-seq analysis, we identify a RET rearrangement in the tumour material of a patient who does not harbour any known RAS or BRAF mutations. This new gene fusion involves exons 1-4 from the 5' end of the Trk fused Gene (TFG) fused to the 3' end of RET tyrosine kinase leading to a TFG-RET fusion which transforms immortalized human thyroid cells in a kinase-dependent manner. TFG-RET oligomerises in a PB1 domain-dependent manner and oligomerisation of TFG-RET is required for oncogenic transformation. Quantitative proteomic analysis reveals the upregulation of E3 Ubiquitin ligase HUWE1 and DUBs like USP9X and UBP7 in both tumor and metastatic lesions, which is further confirmed in additional patients. Expression of TFG-RET leads to the upregulation of HUWE1 and inhibition of HUWE1 significantly reduces RET-mediated oncogenesis.

Background: Neuroendocrine neoplasia (NEN) are rare and heterogenous tumours. Few data exist on the impact of surgical therapy., Materials and Methods: This is a retrospective analysis of prospectively collected data of gastroenteropancreatic NEN in the German NET-Registry (1999-2012). It focuses on patients without distant metastases (limited disease, LD, stage I-IIIB)., Results: Data of 2239 patients with NEN were recorded. Median age was 59 years, the gender ratio was 1:1.3 (f:m). A total of 986 patients (44%) had LD, and the 5-year survival rate (5 years) was 77% for all and 90% for patients with LD. A total of 1635 patients (73%) received a surgical therapy (1st to 6th line); the 5 and 10 ysr were 83/65% after and 59/35% without surgery for all patients (p < .001). The resection margins in the LD patients were 76%, 16%, and 3% for R0, R1 and R2, respectively. The 10 ysr was 84%, 59% and 42% for R0, R1 and R2 resections, respectively (p = .021 R0/R1, p < .001 R0/R2). The R0 resection rate was 75% for G1/G2 NET and 67% for G3 NEC., Conclusion: The rate of complete tumour resection (R0) in LD is independent of tumour grading, and R0 resection is the key determinant of long-term survival, as demonstrated by the 10 ysr. of 84%. All NEN patients with limited disease should be considered for operation, if possible, as the best 10-year survival is shown after an R0 resection.

Background: In contrast to exocrine pancreatic carcinomas, prognosis and treatment of pancreatic neuroendocrine neoplasms (PNEN) are significantly different. The variable growth pattern and associated clinical situation of functioning and non-functioning PNEN demand an individualized surgical approach. However, due to the scarce evidence associated with the rare disease, guidelines lack detailed recommendations for indication and for the required extent of surgical resection., Methods: In a retrospective single-center study from 1990 to 2018, 239 patients with PNEN were identified. Clinical data were collected in the MaDoc database of the University Medical Center Mainz. A total of 155 non-functional PNEN were selected for further analysis., Results: According to the classification of NET by the WHO in 2017, 28.8% (n = 40) of the tumors were G1, 61.9% (n = 86) G2, and 9.4% (n = 13) G3. In 73 patients, hepatic metastases were present. Sixty patients had lymph node metastasis. An R0 resection was achieved in 98 cases, an R1 situation in 10 cases. Five times, a tumor debulking was carried out (R2) and 5 times the operation was aborted without any resection because of the advanced tumor stage. A relapse occurred in 29 patients. Different prognostic factors (grade, tumor size, age) were analyzed. Grade-dependent 10-year overall survival rates were 79.5% (grade 1) and 60.1% (grade 2), respectively. The survival rate of grade 3 patients was limited to 66.7% after 13 months., Conclusion: In our study, patients with non-functioning PNEN had a longer overall survival after successful R0 resection. The risk analysis confirmed a Ki-67 cutoff value of 5%, which divided a high- and low-risk group. Patients with a PNEC G3 (Ki-67 index > 50%) had a very poor prognosis.