Publications by authors named "Katrin Brauckhoff"

28 Publications

  • Page 1 of 1

An experimental study on intraoperative recovery of recurrent laryngeal nerve function.

Laryngoscope Investig Otolaryngol 2020 Oct 4;5(5):954-960. Epub 2020 Sep 4.

Department of Breast and Endocrine Surgery Haukeland University Hospital Bergen Norway.

Objective: If bilateral thyroid surgery is planned and staged thyroidectomy considered in case of loss of neuromonitoring signal (LOS), a waiting time of 20 minutes is suggested for evaluation of early nerve recovery. This recommendation is based on clinical observations and has not been thoroughly validated experimentally.

Methods: Sixteen pigs were randomly studied, and electromyogram (EMG) was continuously recorded during traction injury until an amplitude decrease of 70% from baseline (BL) (16 nerves) or LOS (16 nerves), and further during 40-minute recovery time. At the end of the experiments, vocal cord twitch was evaluated by video-laryngoscopy.

Results: In the 70% group, 8 of 16 nerves recovered to or above an amplitude of 50% of baseline after 20 minutes and finally one more after 40 minutes. In the LOS group, only one nerve showed recovery after 20 minutes and one more after 40 minutes. Video-laryngoscopy revealed good or strong vocal cord twitches, in 10 of 14 nerves in the 70% group and in only 2 of 14 nerves in the LOS group.

Conclusions: The overall intraoperative recovery was low after LOS. Even after 70% amplitude depression, only half of the nerves showed recovery to amplitudes ≥50% of BL. Nerve recovery is dynamic, and a waiting time of 20 minutes seems appropriate for the identification of early nerve recovery before decisions are taken to continue or terminate surgery. The final EMG amplitude was not always well correlated with estimated vocal cord twitch, evaluated by video-laryngoscopy. This observation needs further investigation.
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http://dx.doi.org/10.1002/lio2.456DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7585241PMC
October 2020

Multimodal imaging of thyroid cancer.

Curr Opin Endocrinol Diabetes Obes 2020 10;27(5):335-344

Nuclear Medicine/PET-center, Department of Radiology, Haukeland University Hospital.

Purpose Of Review: Thyroid cancer is the most common endocrine cancer in adults with rising incidence. Challenges in imaging thyroid cancer are twofold: distinguishing thyroid cancer from benign thyroid nodules, which occur in 50% of the population over 50 years; and correct staging of thyroid cancer to facilitate appropriate radical surgery in a single session. The clinical management of thyroid cancer patients has been covered in detail by the 2015 guidelines of the American Thyroid Association (ATA). The purpose of this review is to state the principles underlying optimal multimodal imaging of thyroid cancer and aid clinicians in avoiding important pitfalls.

Recent Findings: Recent additions to the literature include assessment of ultrasound-based scoring systems to improve selection of nodules for fine needle biopsy (FNB) and the evaluation of new radioactive tracers for imaging thyroid cancer.

Summary: The mainstay of diagnosing thyroid cancer is thyroid ultrasound with ultrasound-guided FNB. Contrast-enhanced computed tomography and PET with [F]-fluorodeoxyglucose (FDG) and MRI are reserved for advanced and/or recurrent cases of differentiated thyroid cancer and anaplastic thyroid cancer, while [F]FDOPA and [Ga]DOTATOC are the preferred tracers for medullary thyroid cancer.
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http://dx.doi.org/10.1097/MED.0000000000000574DOI Listing
October 2020

Vocal cord function during recurrent laryngeal nerve injury assessed by accelerometry and EMG.

Laryngoscope 2020 04 2;130(4):1090-1096. Epub 2019 Aug 2.

Department of Breast and Endocrine Surgery, Haukeland University Hospital, Bergen, Norway.

Objective: Gradual impairment of nerve conduction is expected to be tightly associated with simultaneous gradual loss of vocal cord contractility, related to the fact that injured axons are connected to a defined number of muscle cells. In clinical studies, there is a time gap between observed adverse electromyographic (EMG) changes and examination of vocal cord function. This study evaluates the impact of intraoperative EMG changes on synchronous vocal cord contractility by simultaneous use of continuous intraoperative neuromonitoring (C-IONM) and accelerometry for registration of actual vocal cord function at a given change of EMG amplitude.

Methods: EMG was obtained following vagus nerve stimulation by use of C-IONM. A vocal cord accelerometer probe that could be attached to the vocal cords was developed based on a LIS3DH ultra low-power high performance three axis linear accelerometer (STMicroelectronics, Geneva, Switzerland). Accelerometer data were registered continuously together with EMG data during traction injury of the recurrent laryngeal nerve (RLN) until an amplitude depression ≤100 μV.

Results: Six RLN from four immature domestic pigs were studied. Vocal cord contractility assessed by vocal cord accelerometry decreased in parallel with EMG amplitude, with significant correlations ranging from 0.707 to 0.968.

Conclusion: Decrease of EMG amplitude during traction injury to the RLN injury is closely associated with a parallel drop in vocal cord contractility.

Level Of Evidence: NA Laryngoscope, 130:1090-1096, 2020.
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http://dx.doi.org/10.1002/lary.28215DOI Listing
April 2020

The Role of Calcitonin in Predicting the Extent of Surgery in Medullary Thyroid Carcinoma: A Nationwide Population-Based Study in Norway.

Eur Thyroid J 2019 Jun 29;8(3):159-166. Epub 2019 Apr 29.

Institute of Clinical Medicine, University of Oslo, Oslo, Norway.

Background: Preoperative predictors for the need of prophylactic lymph node dissection in the lateral neck have been studied in patients with medullary thyroid carcinoma (MTC).

Objectives: To evaluate the ability of serum calcitonin to predict the extent of surgery needed in the lateral neck.

Methods: This retrospective population-based cohort study includes data from 94 of 139 patients with MTC surgically treated in Norway from 2003 to 2016. Patients were identified in the 4 regional centers treating MTC and by the Cancer Registry of Norway, and grouped according to calcitonin levels. In 58 patients without distant metastases or disease progression to the next tumor level (NPNL), data were compared in prognostic groups (N0-NPNL), (N1a-NPNL), and (N1b-NPNL).

Results: At calcitonin levels ≤500, 501-1,000, and >1,000 pmol/L, metastatic lymph nodes in the lateral neck were found in 16, 50, and 71% of the patients, respectively. In the prognostic groups, 19% of N0-NPNL patients had calcitonin >500 pmol/L and 17% of N1b-NPNL patients had calcitonin ≤500 pmol/L. In multivariate analysis, factors predicting biochemical cure and calcitonin level ≤500 pmol/L were no metastatic lymph nodes in the lateral neck ( = 0.030) and tumor diameter ≤20 mm ( < 0.001), respectively. Factors related to metastatic lymph nodes in the lateral neck were extrathyroidal extension ( = 0.007) and no biochemical cure ( = 0.028).

Conclusions: Basal calcitonin cannot predict the need for prophylactic lateral lymph node dissection in patients with MTC. Further prospective, randomized studies are warranted.
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http://dx.doi.org/10.1159/000499018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6587193PMC
June 2019

Trends in Diagnostics, Surgical Treatment, and Prognostic Factors for Outcomes in Medullary Thyroid Carcinoma in Norway: A Nationwide Population-Based Study.

Eur Thyroid J 2019 Jan 8;8(1):31-40. Epub 2018 Nov 8.

Institute of Clinical Medicine, University of Oslo, Oslo, Norway.

Background: Medullary thyroid carcinoma (MTC) is rare. Nationwide population-based studies are important to evaluate its clinical course.

Objectives: To describe all patients with MTC in Norway during 1994-2016 and compare time-related trends in diagnostics and surgical treatment, including prognostic factors for biochemical cure and disease-specific survival (DSS).

Methods: This retrospective population-based cohort study includes data for 228 out of 237 patients (96%) with MTC; 201 patients were surgically treated. Patients were identified in the 4 regional centers treating MTC and by the Cancer Registry of Norway. Data were collected from patients' files. Trends were compared over 2 study periods.

Results: MTC accounted for 4.2% of thyroid carcinomas. During the study periods, the incidence increased from 0.18 to 0.25: 100,000 per year, preoperative diagnostics improved with increased use of calcitonin, ultrasound, and fine-needle cytology ( = 0.010, < 0,001, and = 0.001), patients were diagnosed at an earlier tumor stage ( = 0.004), and more patients were cured ( = 0.002). Via multivariate analysis of patients with metastatic lymph nodes, independent prognostic factors for cure were: a low ratio of metastatic and total number of dissected lymph nodes ( = 0.021) and no extrathyroidal extension ( = 0.030). Independent prognostic factors for DSS were: no distant metastasis, a younger age, and a low ratio of metastatic and dissected lymph nodes ( = 0.005, = 0.020, = 0.022).

Conclusions: Preoperative diagnostics have improved over time with increased therapeutic control. A low ratio of metastatic and dissected lymph nodes predicts better outcomes in patients with metastatic lymph nodes.
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http://dx.doi.org/10.1159/000493977DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6381913PMC
January 2019

International neuromonitoring study group guidelines 2018: Part II: Optimal recurrent laryngeal nerve management for invasive thyroid cancer-incorporation of surgical, laryngeal, and neural electrophysiologic data.

Laryngoscope 2018 10 6;128 Suppl 3:S18-S27. Epub 2018 Oct 6.

Department of Otolaryngology, Harvard Medical School, Boston, Massachusetts, U.S.A.

The purpose of this publication was to inform surgeons as to the modern state-of-the-art evidence-based guidelines for management of the recurrent laryngeal nerve invaded by malignancy through blending the domains of 1) surgical intraoperative information, 2) preoperative glottic function, and 3) intraoperative real-time electrophysiologic information. These guidelines generated by the International Neural Monitoring Study Group (INMSG) are envisioned to assist the clinical decision-making process involved in recurrent laryngeal nerve management during thyroid surgery by incorporating the important information domains of not only gross surgical findings but also intraoperative recurrent laryngeal nerve functional status and preoperative laryngoscopy findings. These guidelines are presented mainly through algorithmic workflow diagrams for convenience and the ease of application. These guidelines are published in conjunction with the INMSG Guidelines Part I: Staging Bilateral Thyroid Surgery With Monitoring Loss of Signal. Level of Evidence: 5 Laryngoscope, 128:S18-S27, 2018.
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http://dx.doi.org/10.1002/lary.27360DOI Listing
October 2018

International neural monitoring study group guideline 2018 part I: Staging bilateral thyroid surgery with monitoring loss of signal.

Laryngoscope 2018 10 5;128 Suppl 3:S1-S17. Epub 2018 Oct 5.

Mount Sinai Hospital, Department of Otolaryngology, Toronto, Ontario, Canada.

This publication offers modern, state-of-the-art International Neural Monitoring Study Group (INMSG) guidelines based on a detailed review of the recent monitoring literature. The guidelines outline evidence-based definitions of adverse electrophysiologic events, especially loss of signal, and their incorporation in surgical strategy. These recommendations are designed to reduce technique variations, enhance the quality of neural monitoring, and assist surgeons in the clinical decision-making process involved in surgical management of recurrent laryngeal nerve. The guidelines are published in conjunction with the INMSG Guidelines Part II, Optimal Recurrent Laryngeal Nerve Management for Invasive Thyroid Cancer-Incorporation of Surgical, Laryngeal, and Neural Electrophysiologic Data. Laryngoscope, 128:S1-S17, 2018.
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http://dx.doi.org/10.1002/lary.27359DOI Listing
October 2018

Injury mechanisms and electromyographic changes after injury of the recurrent laryngeal nerve: Experiments in a porcine model.

Head Neck 2018 02 30;40(2):274-282. Epub 2017 Sep 30.

Department of Anesthesia and Intensive Care, Haukeland University Hospital, Bergen, Norway.

Background: Recurrent laryngeal nerve (RLN) injury during surgery may reveal differences in electromyographic (EMG) changes after sustained compression or traction.

Methods: In 20 pigs with the NIM-FLEX EMG-endotracheal tube, EMG was recorded at baseline, during sustained RLN compression, or traction until 70% amplitude decrease and during 30 minutes of recovery.

Results: Seventy percent amplitude decrease from baseline was reached after 110 ± 98 seconds (compression group) and 2034 ± 2108 seconds (traction group). Traction induced a pronounced latency increase, peaking at 122 ± 8% in contrast to compression with 106 ± 5% (P < .001). The EMG amplitude recovery to ≥50% of baseline failed in 7 nerves after compression and 8 nerves after traction.

Conclusion: Compression caused a fast decrease of EMG amplitude with minor effects on latency. In contrast, RLN traction showed early and significant latency increase preceding a delayed amplitude decrease. Recovery rate of the EMG signals were similar in both groups.
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http://dx.doi.org/10.1002/hed.24940DOI Listing
February 2018

A Nationwide Study of Multiple Endocrine Neoplasia Type 2A in Norway: Predictive and Prognostic Factors for the Clinical Course of Medullary Thyroid Carcinoma.

Thyroid 2016 09 11;26(9):1225-38. Epub 2016 Aug 11.

2 Institute of Clinical Medicine, University of Oslo , Oslo, Norway .

Background: Multiple endocrine neoplasia type 2A (MEN 2A) is an autosomal dominant syndrome caused by activating germline mutations in the RET (REarranged during Transfection) proto-oncogene. MEN 2A has a strong (>95%) and age-dependent (5-25 years) clinical penetrance of medullary thyroid carcinoma (MTC). Several major studies have analyzed the predictive and prognostic factors for MEN 2A to find indicators that predict the optimal timing of prophylactic thyroidectomy. The aims of this study were to describe all known RET positive MEN 2A patients diagnosed in Norway and to evaluate the clinical course of MTC, as well as its predictive and prognostic factors.

Methods: This nationwide retrospective cohort study included data for 65 (14 index and 51 screening patients) out of a total of 67 MEN 2A patients with the RET gene mutation who were diagnosed in Norway since 1974. Data were collected by reviewing patient files. The variables analyzed were genotype, phenotype, preoperative basal calcitonin, age at thyroid surgery, central lymph node dissection and nodal status at primary surgery, number of surgical procedures, and biochemical cure. Of the 65 patients, 60 had undergone thyroid surgery. The median follow-up period was 9.9 years. The patients were divided into pre-RET-and RET-era, which included patients who had thyroid surgery before January 1, 1994, and after, respectively.

Results: In index and screening patients, MTC was found, respectively, in 100% and 45% of cases, central lymph node dissection at primary surgery was done for 64% and 52% of patients, and the median total number of surgical procedures was two (range 1-6) and one (range 1-4). At primary surgery, all patients (n = 13) with lymph node metastases had preoperative basal calcitonin levels ≥68 pg/mL, and all patients (n = 17) without central lymph node dissection and preoperative basal calcitonin <40 pg/mL were biochemically cured. Multivariate analysis showed that preoperative basal calcitonin was a significant predictive factor for MTC superior to age at thyroid surgery when analyzing the entire period (p = 0.009) and the RET-era separately (p = 0.021). Prognostic factors for biochemical cure were preoperative basal calcitonin, central lymph node dissection, and nodal status at primary surgery (p = 0.037, p = 0.002, and p = 0.005) when analyzing the entire period, but only nodal status at primary surgery when the RET-era was considered separately (p = 0.006).

Conclusions: Preoperative basal calcitonin alone can serve as an indicator for optimal timing and the extent of thyroid surgery for MEN 2A patients that could be considered safe. The results are consistent with previously reported data.
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http://dx.doi.org/10.1089/thy.2015.0673DOI Listing
September 2016

EMG changes during continuous intraoperative neuromonitoring with sustained recurrent laryngeal nerve traction in a porcine model.

Langenbecks Arch Surg 2017 Jun 16;402(4):675-681. Epub 2016 Apr 16.

Department of Clinical Medicine, University of Bergen, Bergen, Norway.

Purpose: Traction is the most common cause of injury to the recurrent laryngeal nerve (RLN) in endocrine neck surgery. The purpose of this study was to evaluate specific alterations to the electromyogram (EMG) and verify safe alarm limits in a porcine model of sustained traction of the RLN using continuous intraoperative neuromonitoring (C-IONM).

Methods: Sixteen Norwegian Landrace pigs were anesthetized and intubated with a tracheal tube with a stick-on laryngeal electrode. EMG was recorded at baseline (BL) and during sustained traction applied to each RLN until 70 % amplitude decrease from BL, and during 30-min recovery.

Results: In 29 nerves at risk (NAR), BL amplitude and latency values were 1098 ± 418 (586-2255) μV (mean ± SD (range)) (right vagus) and 845 ± 289 (522-1634) μV (left vagus), and 4.7 ± 0.5 (4.1-5.9) ms and 7.9 ± 0.8 (6.7-9.6) ms, respectively. At 50 % amplitude decrease, latency increased by 14.0 ± 5.7 % (right side) and 14.5 ± 9.1 % (left side) compared with BL. Corresponding values for 70 % amplitude depression were 17.9 ± 6.1 % and 17.3 ± 12.8 %. Traction time to 50 and 70 % amplitude decrease ranged from 3 to 133 min and 3.9-141 min, respectively. In 16 NAR (55 %), time from 50 to 70 % reduction in amplitude was ≤5 min, but in six NAR (21 %) ≤1 min. In only 11 (38 %) of 29 nerves, the amplitude recovered to more than 50 % of BL.

Conclusions: Latency increase may be the first warning of RLN stretch injury. Given the short interval between 50 and 70 % amplitude reduction of the EMG, amplitude reduction by 50 % can be taken as an appropriate alert limit.
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http://dx.doi.org/10.1007/s00423-016-1419-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5437198PMC
June 2017

Impact of EMG Changes in Continuous Vagal Nerve Monitoring in High-Risk Endocrine Neck Surgery.

World J Surg 2016 Mar;40(3):672-80

Department of Surgery, Haukeland University Hospital, Jonas Lies vei 65, 5021, Bergen, Norway.

Background: Continuous vagal intraoperative neuromonitoring (CIONM) of the recurrent laryngeal nerve (RLN) may reduce the risk of RLN lesions during high-risk endocrine neck surgery such as operation for large goiter potentially requiring transsternal surgery, advanced thyroid cancer, and recurrence.

Methods: Fifty-five consecutive patients (41 female, median age 61 years, 87 nerves at risk) underwent high-risk endocrine neck surgery. CIONM was performed using the commercially available NIM-Response 3.0 nerve monitoring system with automatic periodic stimulation (APS) and matching endotracheal tube electrodes (Medtronic Inc.). All CIONM events (decreased amplitude/increased latency) were recorded.

Results: APS malfunction occurred on three sides (3%). A total of 138 CIONM events were registered on 61 sides. Of 138, 47 (34%) events were assessed as imminent (13 events) or potentially imminent (34 events) lesions, whereas 91 (66%) were classified as artifacts. Loss of signal was observed in seven patients. Actions to restore the CIONM baseline were undertaken in 58/138 (42%) events with a median 60 s required per action. Four RLN palsies (3 transient, 1 permanent) occurred: one in case of CIONM malfunction, two sudden without any significant previous CIONM event, and one without any CIONM event. The APS vagus electrode led to temporary damage to the vagus nerve in two patients.

Conclusions: CIONM may prevent RLN palsies by timely recognition of imminent nerve lesions. In high-risk endocrine neck surgery, CIONM may, however, be limited in its utility by system malfunction, direct harm to the vagus nerve, and particularly, inability to indicate RLN lesions ahead in time.
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http://dx.doi.org/10.1007/s00268-015-3368-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4746223PMC
March 2016

Prospective study of vocal fold function after loss of the neuromonitoring signal in thyroid surgery: The International Neural Monitoring Study Group's POLT study.

Laryngoscope 2016 05 15;126(5):1260-6. Epub 2015 Dec 15.

Department of General, Visceral, and Vascular Surgery, University Hospital of Martin Luther University, Halle (Saale), Germany.

Objectives/hypothesis: Intraoperative neuromonitoring identifies recurrent laryngeal nerve (RLN) injury and gives prognostic information regarding postoperative glottic function. Loss of the neuromonitoring signal (LOS) signifies segmental type 1 or global type 2 RLN injury. This study aimed at identifying risk factors for RLN injury and determining vocal fold (VF) function initially and 6 months after definitive LOS.

Study Design: Prospective study encompassing 21 hospitals from 13 countries.

Methods: Included in this study were patients with persistent intraoperative LOS.

Results: At first postoperative laryngoscopy, early VF palsy was present in 94 of all 115 patients with LOS (81.7%): in 53 of 56 patients (94.6%) with type 1 injury and 41 of 59 patients (69.5%) with type 2 injury. In LOS type 1, women outnumbered men >5-fold. Traction produced LOS type 1 in 38 of 56 patients (67.9%) and LOS type 2 in 54 of 59 patients (91.5%). Course of the RLN posterior and/or anterior to the inferior thyroid artery, extralaryngeal branching, or tuberculum of Zuckerkandl did not increase VF palsy rates. Permanent VF palsy rates were also lower (P = .661) after LOS type 2 than after LOS type 1: 6.8% (four of 59 patients) versus 10.7% (six of 56 patients). Intraoperative administration of steroids did not diminish postoperative VF palsy rates.

Conclusions: LOS type 1 entails more severe nerve damage than LOS type 2, affecting women disproportionately. Both LOS types, being primarily associated with traction injury, are unaffected by variant neck anatomy in expert hands and unresponsive to steroids.

Level Of Evidence: 2b Laryngoscope, 126:1260-1266, 2016.
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http://dx.doi.org/10.1002/lary.25807DOI Listing
May 2016

F18-FDG-PET for recurrent differentiated thyroid cancer: a systematic meta-analysis.

Acta Radiol 2016 Oct 9;57(10):1193-200. Epub 2015 Jul 9.

Nuclear Medicine/PET-Center, Department of Radiology, Haukeland University Hospital, Bergen, Norway Department of Clinical Medicine, University of Bergen, Bergen/Norway

Background: Positron emission tomography (PET) with fluor-18-deoxy-glucose (FDG) is widely used for diagnosing recurrent or metastatic disease in patients with differentiated thyroid cancer (DTC).

Purpose: To assess the diagnostic accuracy of FDG-PET for DTC in patients after ablative therapy.

Material And Methods: A systematic search was conducted in Medline/PubMed, EMBASE, Cochrane Library, Web of Science, and Open Grey looking for all English-language original articles on the performance of FDG-PET in series of at least 20 patients with DTC having undergone ablative therapy including total thyroidectomy. Diagnostic performance measures were pooled using Reitsma's bivariate model.

Results: Thirty-four publications between 1996 and 2014 met the inclusion criteria. Pooled sensitivity and specificity were 79.4% (95% confidence interval [CI], 73.9-84.1) and 79.4% (95% CI, 71.2-85.4), respectively, with an area under the curve of 0.858.

Conclusion: F18-FDG-PET is a useful method for detecting recurrent DTC in patients having undergone ablative therapy.
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http://dx.doi.org/10.1177/0284185115594645DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5015757PMC
October 2016

Post-PET ultrasound improves specificity of 18F-FDG-PET for recurrent differentiated thyroid cancer while maintaining sensitivity.

Acta Radiol 2015 Nov 13;56(11):1350-60. Epub 2015 Mar 13.

Section for Endocrine Surgery, Haukeland University Hospital, Bergen/Norway Department of Clinical Science, University of Bergen, Bergen/Norway.

Background: Positron emission tomography (PET) using fluor-18-deoxyglucose (18F-FDG) with or without computed tomography (CT) is generally accepted as the most sensitive imaging modality for diagnosing recurrent differentiated thyroid cancer (DTC) in patients with negative whole body scintigraphy with iodine-131 (I-131).

Purpose: To assess the potential incremental value of ultrasound (US) over 18F-FDG-PET-CT.

Material And Methods: Fifty-one consecutive patients with suspected recurrent DTC were prospectively evaluated using the following multimodal imaging protocol: (i) US before PET (pre-US) with or without fine needle biopsy (FNB) of suspicious lesions; (ii) single photon emission computed tomography (≥3 GBq I-131) with co-registered CT (SPECT-CT); (iii) 18F-FDG-PET with co-registered contrast-enhanced CT of the neck; (iv) US in correlation with the other imaging modalities (post-US). Postoperative histology, FNB, and long-term follow-up (median, 2.8 years) were taken as composite gold standard.

Results: Fifty-eight malignant lesions were identified in 34 patients. Forty lesions were located in the neck or upper mediastinum. On receiver operating characteristics (ROC) analysis, 18F-FDG-PET had a limited lesion-based specificity of 59% at a set sensitivity of 90%. Pre-US had poor sensitivity and specificity of 52% and 53%, respectively, increasing to 85% and 94% on post-US, with knowledge of the PET/CT findings (P < 0.05 vs. PET and pre-US). Multimodal imaging changed therapy in 15 out of 51 patients (30%).

Conclusion: In patients with suspected recurrent DTC, supplemental targeted US in addition to 18F-FDG-PET-CT increases specificity while maintainin sensitivity, as non-malignant FDG uptake in cervical lesions can be confirmed.
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http://dx.doi.org/10.1177/0284185115574298DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4768638PMC
November 2015

Latencies longer than 3.5 ms after vagus nerve stimulation does not exclude a nonrecurrent inferior laryngeal nerve.

BMC Surg 2014 Aug 28;14:61. Epub 2014 Aug 28.

Department of Surgery, Haukeland University Hospital, Bergen, Norway.

Background: It has recently been reported that a signal latency shorter than 3.5 ms after electrical stimulation of the vagus nerve signify a nonrecurrent course of the inferior laryngeal nerve. We present a patient with an ascending nonrecurrent inferior laryngeal nerve. In this patient, the stimulation latency was longer than 3.5 ms.

Case Presentation: A 74-years old female underwent redo surgery due to a right-sided recurrent nodular goitre. The signal latency on electrical stimulation of the vagus nerve at the level of the carotid artery bifurcation was 3.75 ms. Further dissection revealed a nonrecurrent but ascending course of the inferior laryngeal nerve. Caused by the recurrent goitre, the nerve was elongated to about 10 cm resulting in this long latency.

Conclusion: This case demonstrates that the formerly proposed "3.5 ms rule" for identifying a nonrecurrent course of the inferior laryngeal nerve has exceptions. A longer latency does not necessarily exclude a nonrecurrent laryngeal nerve.
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http://dx.doi.org/10.1186/1471-2482-14-61DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4149872PMC
August 2014

High cardiac background activity limits 99mTc-MIBI radioguided surgery in aortopulmonary window parathyroid adenomas.

BMC Surg 2014 Apr 23;14:22. Epub 2014 Apr 23.

Department of Radiology, Centre for Nuclear Medicine/PET, Haukeland University Hospital, Jonas Liesvei 65, Bergen 5021, Norway.

Background: Radioguided surgery using 99m-Technetium-methoxyisobutylisonitrile (99mTc-MIBI) has been recommended for the surgical treatment of mediastinal parathyroid adenomas. However, high myocardial 99mTc-MIBI uptake may limit the feasibility of radioguided surgery in aortopulmonary window parathyroid adenoma.

Case Presentation: Two female patients aged 72 (#1) and 79 years (#2) with primary hyperparathyroidism caused by parathyroid adenomas in the aortopulmonary window were operated by transsternal radioguided surgery. After intravenous injection of 370 MBq 99mTc-MIBI at start of surgery, the maximum radioactive intensity (as counts per second) was measured over several body regions using a gamma probe before and after removal of the parathyroid adenoma. Relative radioactivity was calculated in relation to the measured ex vivo radioactivity of the adenoma, which was set to 1.0. Both patients were cured by uneventful removal of aortopulmonary window parathyroid adenomas of 4400 (#1) and 985 mg (#2). Biochemical cure was documented by intraoperative measurement of parathyroid hormone as well as follow-up examination. Ex vivo radioactivity over the parathyroid adenomas was 196 (#1) and 855 counts per second (#2). Before parathyroidectomy, relative radioactivity over the aortopulmonary window versus the heart was found at 1.3 versus 2.6 (#1) and 1.8 versus 4.8 (#2). After removal of the adenomas, radioactivity within the aortopulmonary window was only slightly reduced.

Conclusion: High myocardial uptake of 99mTc-MIBI limits the feasibility of radioguided surgery in aortopulmonary parathyroid adenoma.
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http://dx.doi.org/10.1186/1471-2482-14-22DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4003509PMC
April 2014

Impact of extent of resection for thyroid cancer invading the aerodigestive tract on surgical morbidity, local recurrence, and cancer-specific survival.

Surgery 2010 Dec;148(6):1257-66

Department of General, Visceral and Vascular Surgery, University Hospital Halle, Germany.

Background: The appropriate resection for thyroid cancer invading the aerodigestive tract remains controversial.

Methods: A total of 174 patients underwent resections for aerodigestive tract invasion from differentiated thyroid cancer (103 patients), medullary thyroid cancer (40 patients), and undifferentiated thyroid cancers/unusual thyroid neoplasms (31 patients). In all, 82 patients submitted to transmural resections (window resection, sleeve resection, or cervical evisceration), 65 patients underwent nontransmural resections (shaving or extramucosal esophageal resections), and 27 patients had grossly incomplete resections. The measures of outcome included surgical morbidity, locoregional recurrence, and disease-specific survival.

Results: Surgical morbidity was 38% after transmural and 25% after nontransmural resection (P = .02). On histopathologic examination, surgical margins were microscopically involved in 9% of patients after transmural and 23% of patients after nontransmural resection (P = .014). At a mean follow-up of 35.3 months, locoregional recurrence developed in 10 (46%) of 22 patients with microscopically incomplete and 18 (15%) of 121 patients with microscopically complete resection (P = .001). After grossly complete resection, the mean disease-specific survival was 101.2, 69.8, and 25.5 months for differentiated thyroid cancer, medullary thyroid cancer, and undifferentiated thyroid cancer/unusual neoplasms, respectively (P < .001). This outcome was independent of the type of resection.

Conclusion: The type of cancer and resection are key determinants of outcome among thyroid cancer patients with aerodigestive tract invasion.
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http://dx.doi.org/10.1016/j.surg.2010.09.011DOI Listing
December 2010

Premonitory symptoms preceding metastatic medullary thyroid cancer in MEN 2B: An exploratory analysis.

Surgery 2008 Dec;144(6):1044-50; discussion 1050-3

Department of General, Visceral and Vascular Surgery, Martin-Luther-University, Halle-Wittenberg, Germany.

Background: More than 90% of M918T carriers with multiple endocrine neoplasia type 2B (MEN 2B) harbor de novo mutations in the REarranged during Transfection (RET) protooncogene. DNA-based screening for RET germline mutations is rarely useful for early diagnosis, which thus is contingent on the clinical ascertainment of MEN 2B-specific symptoms as soon as they emerge. Little information exists about the presence of these symptoms in infancy.

Methods: Detailed information was gathered regarding the development of MEN 2B-associated symptoms from the parents of 25 M918T RET carriers and 50 age- and sex-matched controls with the use of a disease-specific questionnaire.

Results: Until the end of the study, at a median age of 16.2 (range, 0.5-34.9 years), all 25 M918T RET carriers had developed medullary thyroid cancer. By that time, 96%, 91%, 71%, 75%, and 28% of carriers displayed oral manifestations, ocular abnormalities, intestinal symptoms, musculoskeletal malformations, and pheochromocytoma, respectively. During the first year of life, fewer than 20% of carriers were found to express the typical MEN 2B phenotype, whereas 86% and 61% of these children, but none of the controls, were noted for their inability to cry tears and for constipation.

Conclusion: Because the classic MEN 2B phenotype is rare during the first year of life, more emphasis should be placed on the more subtle features of the syndrome. Additional studies are needed to validate the usefulness of the symptoms "inability to cry" and "constipation" for earlier diagnosis of MEN 2B.
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http://dx.doi.org/10.1016/j.surg.2008.08.028DOI Listing
December 2008

Limitations of intraoperative adrenal remnant volume measurement in patients undergoing subtotal adrenalectomy.

World J Surg 2008 May;32(5):863-72

Department of General, Visceral, and Vascular Surgery, Martin-Luther-University of Halle-Wittenberg, Ernst-Grube-Strasse 40, 06097 Halle/Saale, Germany.

Background: Recent studies have shown that a minimum of approximately one-third of one normal adrenal gland is required for sufficient adrenocortical stress capacity. Correlation between intraoperative measurement, determination of remnant size by computed tomography (CT), and adrenocortical stress capacity has not been examined so far.

Methods: Twenty-two patients with familial pheochromocytoma (n=13), sporadic pheochromocytoma (n=3), and adrenocortical tumors (n=6) who underwent unilateral or bilateral subtotal adrenalectomy (STAE, 28 adrenal remnants) were prospectively studied. Patients were examined in a multi-slice CT to determine residual adrenal tissue and by ACTH test 4 days and 3 months postoperatively.

Results: There was a slight significant correlation between intraoperative and CT calculated volumes (r=0.77; p<0.001). However, volumes assessed by CT were almost doubled compared with intraoperative determination (p<0.001). Although recovery of adrenal function could be observed, no significant changes of remnant volumes could be detected within 3 months. In patients with familial pheochromocytoma, there was a significant correlation between residual adrenal volume and stimulated cortisol levels (P<0.001). A distinct minimum of adrenal volume for intact adrenocortical stress capacity could not be exactly determined; however, in one patient with only 10% residual adrenal tissue intact stress capacity was found.

Conclusions: Residual adrenal tissue of approximately 10-15% offers intact stress capacity. However, an exact determination of the size of an adrenal remnant after STAE has limitations. CT gives larger volumes compared with intraoperative determination. For calculation of a volume-function correlation of residual adrenal tissue, in clinical practice, the determination of relative adrenal residual volume is acceptable.
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http://dx.doi.org/10.1007/s00268-007-9402-yDOI Listing
May 2008

Long-term results and functional outcome after cervical evisceration in patients with thyroid cancer.

Surgery 2006 Dec;140(6):953-9

Department of General, Visceral, and Vascular Surgery, Halle/Saale, Germany.

Background: Surgical strategy in patients with thyroid cancer (TC) infiltrating the aerodigestive system is controversial. This study was undertaken to examine the long-term results of cervical evisceration (CE).

Patients And Methods: Since 1995, 14 consecutive patients with advanced TC underwent total laryngectomy (LE, n = 6) or esophagolaryngectomy (ELR, n = 8). Patients with unusual thyroid neoplasms or metastases to the thyroid (n = 3) were excluded. For esophageal reconstruction, free jejunal grafts (n = 6) and gastric tubes (n = 2) were used.

Results: Procedure-related morbidity and mortality were 42% and 14%, respectively. ELR was associated with a significant higher frequency of complications and reoperations compared with LE. Twelve-month and 30-month survival rates were 73% and 55%, respectively; 85% of the patients were satisfied with the surgical results. There were no long-term problems concerning food intake in the ELR patients. Two ELR patients were able to learn a substitutive voice.

Conclusions: Cervical evisceration in patients with TC is associated with significant perioperative morbidity and mortality requiring careful patient selection. Regarding long-term survival, local tumor control, and patient's satisfaction, however, CE should be taken into account in suitable patients with advanced TC.
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http://dx.doi.org/10.1016/j.surg.2006.09.001DOI Listing
December 2006

Selective arterial chemoembolization for hepatic metastases from medullary thyroid carcinoma.

Surgery 2005 Dec;138(6):986-93; discussion 993

Department of General, Visceral and Vascular Surgery, Martin-Luther University of Halle-Wittenberg, Germany.

Background: Hepatic metastases from medullary thyroid carcinoma (MTC) may impair quality of life by hypercalcitonemia-associated diarrhea and pain. In this prospective study, the effect of selective arterial chemoembolization (SACE) was evaluated.

Methods: Eleven patients with hepatic metastases from MTC received 1 to 9 courses of SACE using epirubicine. Symptomatic, biochemical, and morphologic responses on SACE were recorded.

Results: Symptomatic response was observed in all symptomatic patients. However, biochemical and radiologic response occurred only in 6 patients. Liver function was not affected by SACE. One patient with unexpected concurrent pheochromocytoma metastases died after the first course. Development of side effects in the course was observed in 8 patients but were only World Health Organization grade 1. Patients' satisfaction with SACE was excellent. Long-term follow-up found 7 patients alive (1-72 months). Three patients died with tumor 6, 12, and 24 months after SACE, respectively.

Conclusion: SACE provided good symptom palliation for the majority of patients with hepatic metastases from MTC. However, transient remission or stabilization of hepatic metastases resulted in only 60%. Further studies using a randomized protocol are required.
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http://dx.doi.org/10.1016/j.surg.2005.09.020DOI Listing
December 2005

Multiple endocrine neoplasia 2B syndrome due to codon 918 mutation: clinical manifestation and course in early and late onset disease.

World J Surg 2004 Dec 4;28(12):1305-11. Epub 2004 Nov 4.

Department of General, Visceral and Vascular Surgery, Martin-Luther-University Halle-Wittenberg, Ernst-Grube-Strasse 40, D-0609 Halle/Saale, Germany.

More than 50% of patients with typical MEN-2B have a de novo M918T germline mutation of the RET protooncogene. However, even in typical MEN-2B, extrathyroidal manifestations of MEN-2B can be found to be differently expressed. We analyzed the clinical manifestation and course in 21 patients harboring a de novo RET M918T mutation. Mean age at MEN-2B diagnosis was 14.2 years (range: 1-31 years). All patients had medullary thyroid carcinoma (MTC). At the time of syndrome diagnosis, oral manifestations (bumpy lips, ganglioneuroma), ocular manifestations (corneal fibers, conjunctivitis sicca), intestinal dysfunctions, musculoskeletal manifestations, and pheochromocytoma were found in 86%, 90%, 74%, 79%, and 19% of the patients, respectively. At the time of follow-up examination, the symptoms were found at higher frequency. Severe intestinal manifestation was predominantly found in patients with prepubertal onset (< or = 12 years) of MTC (n = 4/10) compared with patients with late onset (> 12 years) of MTC (n = 0/11) (40% versus 0%; p = 0.019). Although biochemical cure was found only in four patients with early onset of MTC, the long-term prognosis for patients with early onset of MTC was poorer than for patients presenting with late onset of MTC (p = 0.005). During mean follow-up of 55.8 months (range: 3-161 months), seven patients (33%) died from MTC. In conclusion, whereas most typical MEN-2B symptoms were found to be age-related, severe intestinal manifestation was found to be predominantly expressed in patients with early onset of MTC. Furthermore, in patients with early onset of MTC who could not be biochemically cured, the long-term prognosis was found to be worse than that of non-cured patients with late onset of MTC, suggesting an additional pathological process in the younger subgroup reinforcing the very high transforming in vitro activity of the M918T RET mutation.
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http://dx.doi.org/10.1007/s00268-004-7637-4DOI Listing
December 2004

Repeat adrenocortical-sparing adrenalectomy for recurrent hereditary pheochromocytoma.

Surg Today 2004 ;34(3):251-5

Department of General, Visceral, and Vascular Surgery, Martin Luther University Halle/Wittenberg, Ernst-Grube-Strasse 40, 06097 Halle/Saale, Germany.

Purpose: Many endocrine surgeons advocate subtotal adrenalectomy for patients with bilateral hereditary pheochromocytoma despite the risk of recurrence. However, as the effectiveness of this procedure for locally recurrent pheochromocytoma is not well known, we investigated two patients who underwent this operation.

Methods: We performed repeat subtotal adrenalectomy for recurrent hereditary pheochromocytoma in two patients who had undergone primary subtotal adrenalectomy.

Results: Patient 1 was a 23-year-old woman with multiple endocrine neoplasia type 2A, in whom about 25% of the right adrenal gland was left in situ. Patient 2 was a 22-year-old man with von-Hippel-Lindau syndrome, in whom about 25% of both normal adrenal glands was left in situ. No steroid replacement was required postoperatively, and adrenocorticotropic hormone stimulation revealed sufficient adrenocortical function in both patients. No sign of recurrent pheochromocytoma has been found in 96 months and 11 months of follow-up, respectively.

Conclusion: Recurrent hereditary benign pheochromocytoma after subtotal adrenalectomy may be treated successfully by repeated subtotal adrenalectomy. However, the risk of recurrence and malignancy must be weighed carefully against the risk of lifelong steroid replacement and potential Addisonian crisis. Thus, repeated subtotal adrenalectomy should be considered for selective patients who want to avoid steroid replacement.
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http://dx.doi.org/10.1007/s00595-003-2690-4DOI Listing
June 2004

Critical size of residual adrenal tissue and recovery from impaired early postoperative adrenocortical function after subtotal bilateral adrenalectomy.

Surgery 2003 Dec;134(6):1020-7; discussion 1027-8

Department of General, Visceral, and Vascular Surgery, Martin-Luther-University Halle-Wittenberg, Ernst-Grube-Strasse 40, 06097 Halle/Saale, Germany.

Background: Subtotal bilateral adrenalectomy may preserve adrenocortical function. Little is known about the early postoperative function of the adrenal remnant.

Method: In 10 patients with bilateral adrenal tumors (pheochromocytomas, adrenocortical nodular hyperplasia, and adrenal metastases), plasma adrenocorticotropic hormone (ACTH), serum cortisol, and maximal cortisol liberation were examined with an ACTH test after subtotal bilateral adrenalectomy, which left 15% to 30% of adrenal tissue in situ.

Results: In the early postoperative period, all patients had normal basal serum cortisol levels (mean, 415+/-208 nmol/L; normal morning range, 138-690 nmol/L) but pathologically increased plasma ACTH levels (mean, 55+/-42 pmol/mL; normal, <10.1 pmol/L). In 6 patients, a pathologic ACTH test result was observed. During follow-up (mean, 11.3+/-7.6 months), all patients were found to have a normal ACTH test result. None of the patients required steroid supplementation. However, in patients with both familial pheochromocytoma and impaired adrenocortical function during the early postoperative period, the maximal increase of serum cortisol after ACTH stimulation was significantly reduced (mean, 301+/-86.8 nmol/L) compared with control subjects (mean, 490+/-132.6 nmol/L; P=.019).

Conclusion: After subtotal bilateral adrenalectomy left 15% to 30% of adrenal tissue in situ, functional recovery could be observed in all patients. However, subclinical impairment of the adrenocortical function with questionable clinical significance has to be considered in some of the patients. Especially during the early postoperative period, careful observation of the patients without exogenous steroid administration is required.
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http://dx.doi.org/10.1016/j.surg.2003.08.005DOI Listing
December 2003

Functional results after endoscopic subtotal cortical-sparing adrenalectomy.

Surg Today 2003 ;33(5):342-8

Department of General, Visceral, and Vascular Surgery, Martin-Luther-University Halle/Wittenberg, Ernst-Grube-Strasse 40, 06097 Halle/Saale, Germany.

Purpose: We examined the required amount of residual adrenal tissue and whether an intact adrenal vein are necessary to achieve sufficient function after endoscopic subtotal adrenalectomy.

Method: Endoscopic subtotal adrenalectomy was performed in 14 patients. Two patients underwent unilateral subtotal and contralateral total adrenalectomy and another two patients underwent unilateral subtotal adrenalectomy after contralateral total adrenalectomy several years earlier. We analyzed the postoperative serum levels of cortisol and adrenocorticotropic hormone (ACTH). Patients with bilateral tumors underwent an ACTH test.

Results: We had to cut the main adrenal vein in ten patients, and less than one third of the adrenal gland was left in situ in four patients. Subtotal adrenalectomy was performed unilaterally in two patients with bilateral tumors. One third of the adrenal gland was preserved in these patients, and also in the two patients with unilateral subtotal adrenalectomy after previous contralateral total adrenalectomy. The postoperative ACTH test confirmed satisfactory adrenocortical function. During the follow-up period of about 24 months no recurrent tumors have been found.

Conclusion: Subtotal cortical-sparing adrenalectomy can be successfully performed laparoscopically. The venous drainage of the main adrenal vein does not seem to be crucial for sufficient adrenocortical function. We estimate that leaving about one third of the entire adrenal gland as remnant adrenal tissue will result in sufficient function.
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http://dx.doi.org/10.1007/s005950300078DOI Listing
October 2003

First experiences in intraoperative neurostimulation of the recurrent laryngeal nerve during thyroid surgery of children and adolescents.

J Pediatr Surg 2002 Oct;37(10):1414-8

Department of General, Visceral, and Vascular Surgery, Martin-Luther-University Halle-Wittenberg, Halle/Saale, Germany.

Background: Intraoperative neurostimulation of the recurrent laryngeal nerve may reduce nerve palsy during thyroid surgery and is well established in adults. No data regarding the value of neuromonitoring during thyroid surgery in children have been available.

Methods: In a retrospective study, the authors analyzed all children who underwent surgery in our department since 1995. Neurostimulation was performed as electromyography of the vocal muscle using an electrical stimulation electrode for identification of the recurrent nerve.

Results: The authors performed thyroid resections in 97 children (mean, 11.1 years), 75 because of thyroid carcinoma. The recurrent nerve was identified in each patient. The neuromonitoring was used in 53 patients. Postoperatively, one temporary nerve palsy was identified in this group (1.89%). In the group of 44 nonstimulated patients, 2 temporary (4.55%) and one permanent nerve dysfunctions (2.27%) occurred. In all stimulated patients, the results of intraoperative neurostimulation were identical with the postoperative function of the vocal cords.

Conclusions: The intraoperative neurostimulation of the recurrent laryngeal nerve is a safe and reliable procedure in children and adolescents. It may reduce nerve damage during thyroid surgery. The neuromonitoring of the recurrent nerve is of high prediction for the postoperative function of the vocal cords.
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http://dx.doi.org/10.1053/jpsu.2002.35403DOI Listing
October 2002

Papillary thyroid carcinoma in patients with RET proto-oncogene germline mutation.

Thyroid 2002 Jul;12(7):557-61

Department of General, Visceral and Vascular Surgery, Martin-Luther-University Halle-Wittenberg, Halle, Germany.

The occurrence of papillary thyroid carcinoma in patients with RET germline mutations has been described in only eight cases since 1993. We report three women with a RET germline mutation in exon 13 and 14, affecting codon 790, 791, and 804, respectively, who underwent prophylactic thyroidectomy at the age of 29, 39, and 24 years, respectively. Histologic examination revealed C-cell hyperplasia and a small medullary thyroid carcinoma in the first patient and no pathologic changes of the C-cells in either of the other patients. However, all patients had papillary thyroid carcinoma (PTC). Concerning the frequency of PTC in patients with RET germline mutations who underwent surgery at our center (n = 104), it was found in 9.1% of all patients with RET mutation in codon 790, 791, and 804 (n = 33) but in none of the 104 patients with RET germline mutations not affecting codon 790, 791, or 804 (p = 0.0015). Our data and the data from the literature suggest a possible pathogenesis of PTC caused by exon 13 and 14 RET mutations that affect the intracellular domain of the encoded protein. Further investigation is necessary to confirm a potential pathogenetic role of exon 13 and 14 RET mutations with regard to the development of PTC.
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http://dx.doi.org/10.1089/105072502320288393DOI Listing
July 2002

Identification of the non-recurrent inferior laryngeal nerve using intraoperative neurostimulation.

Langenbecks Arch Surg 2002 Jan 27;386(7):482-7. Epub 2001 Oct 27.

Klinik für Allgemeinchirurgie, Martin-Luther-Universität Halle-Wittenberg, Ernst-Grube-Strasse 40, 06097 Halle/Saale, Germany.

Introduction: The non-recurrent inferior laryngeal nerve occurs at a frequency of about 0.5% and usually on the right side. The identification of a non-recurrent laryngeal nerve may be difficult. We describe a new method for its identification using intraoperative neurostimulation.

Methods: We examined nine patients with a non-recurrent inferior laryngeal nerve and five patients with a normal inferior laryngeal nerve anatomy who were operated on trans-sternally. Neurostimulation of the vagal nerve producing electromyographic signal in the intrinsic laryngeal musculature was performed at different points proximally and distally.

Results: : Electromyographic signals were found proximally but not distally of the separation of the inferior laryngeal nerve from the vagus in 14 patients. In nine patients with a non-recurrent inferior laryngeal nerve, we performed neurostimulation of the vagus opposite the lower and the upper thyroid poles. In all patients we found no electromyographic signals at the distal stimulation point. In contrast, proximal neurostimulation of the vagus opposite the upper thyroid pole produced positive electromyographic signals.

Conclusion: Neurostimulation of the vagal nerve distally of the separation of the inferior laryngeal nerve did not produce electromyographic signals in the intrinsic laryngeal musculature, perhaps due to the different modalities in the vagal fascicles. Negative electromyographic signals following neurostimulation of the distal vagal nerve opposite the lower thyroid pole should lead to proximal neurostimulation of the vagus opposite the upper thyroid pole. Positive electromyographic signals proximally and negative electromyographic signals distally predict the occurrence of a non-recurrent inferior laryngeal nerve which allows its diagnosis before surgical dissection of the thyroid gland and may prevent nerve palsy.
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http://dx.doi.org/10.1007/s00423-001-0253-yDOI Listing
January 2002
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