Superiority of continuous over intermittent intraoperative nerve monitoring in preventing vocal cord palsy.

BACKGROUND: Continuous intraoperative nerve stimulation (IONM) with uninterrupted monitoring is likely better than intermittent IONM in preventing vocal cord palsy after thyroid surgery. METHODS: This was a comparative study of intermittent versus continuous IONM in patients with benign and malignant thyroid disease treated at a tertiary centre over 10 years. Early postoperative and permanent vocal cord palsy rates were estimated. Multivariable logistic regression analysis was used to quantify the contributions of clinical and histopathological variables to early postoperative and permanent vocal cord palsy. RESULTS: A total of 6029 patients were included, of whom 3139 underwent continuous and 2890 intermittent IONM. Based on nerves at risk (5208 versus 5024 nerves), continuous IONM had a 1·7-fold lower early postoperative vocal cord palsy rate than intermittent monitoring (1·5 versus 2·5 per cent). This translated into a 30-fold lower permanent vocal cord palsy rate (0·02 versus 0·6 per cent). In multivariable logistic regression analysis, continuous IONM independently reduced early postoperative vocal cord palsy 1·8-fold (odds ratio (OR) 0·56) and permanent vocal cord palsy 29·4-fold (OR 0·034) compared with intermittent IONM. One permanent vocal cord palsy per 75·0 early vocal cord palsies was observed with continuous IONM, compared with one per 4·2 after intermittent IONM. Early postoperative vocal cord palsies were 17·9-fold less likely to become permanent with continuous than intermittent IONM. CONCLUSION: Continuous IONM is superior to intermittent IONM in preventing vocal cord palsy.

Prediction of biochemical cure in patients with medullary thyroid cancer.

BACKGROUND: The impact of number of node metastases versus metastatic lymph node ratio versus AJCC node category on biochemical cure in medullary thyroid cancer (MTC) is not well defined. METHODS: Multivariable logistic regression analysis was used to determine clinical and histopathological variables that contribute to biochemical cure in node-positive MTC. RESULTS: Some 584 of 1026 patients with MTC underwent systematic lymph node dissections for node-positive disease; 27·4 per cent (54 of 197) were biochemically cured after the initial operation and 13·5 per cent (42 of 310 patients) after repeat surgery. Cured patients had significantly less extrathyroid extension (11-14 versus 33·2-55·6 per cent), fewer lymph node metastases (median 2-4 versus 12-16), a lower metastatic lymph node ratio (median 0·05-0·08 versus 0·23-0·28), and were less likely to have AJCC pN1b disease (56-76 versus 89·9-91·6 per cent) and distant metastases (0 versus 28·4-37·1 per cent) than patients who were not cured. Biochemical cure curves advanced steadily up to 7-12 node metastases and a metastatic lymph node ratio of 0·33, eventually levelling off after 16-17 node metastases and metastatic lymph node ratios of 0·45-0·65. In logistic regression analysis, number of lymph node metastases (odds ratio (OR) 17·24 for more than 20 metastases, OR 5·28 for 11-20 metastases, OR 2·22 for 6-10 metastases), preoperative basal serum calcitonin (OR 6·24 for over 1000 pg/ml), reoperation (OR 5·34) and extrathyroid extension (OR 2·42) independently predicted failure to reach biochemical cure. CONCLUSION: Number of lymph node metastases, unlike metastatic lymph node ratio or AJCC node category, determines likelihood of biochemical cure after initial and repeat surgery for node-positive MTC.

ANTECEDENTES: El impacto del número de metástasis ganglionares versus la relación de ganglios linfáticos metastásicos (metastatic lymph node ratio, MLNR) versus el estadio ganglionar según el American Joint Committee on Cancer (AJCC) sobre la curación bioquímica en el cáncer medular de tiroides (medullary thyroid cancer, MTC) no está bien definido. MÉTODOS: Se utilizaron análisis de regresión logística multivariable y análisis estratificados de Kaplan-Meier para determinar las variables clínicas e histopatológicas que contribuyen a la curación bioquímica en el MTC con ganglios positivos. RESULTADOS: En total, 584 de 1.026 pacientes con MTC se sometieron a disecciones sistemáticas de los ganglios linfáticos en caso de enfermedad con ganglios positivos, el 27,4% (54 de 197 pacientes) de los cuales se curaron bioquímicamente después de la cirugía inicial y el 13,5% (42 de 310 pacientes) después de la reintervención quirúrgica. Los pacientes curados tuvieron una extensión extratiroidea significativamente menor (11,1-14% versus 33,2-55,6%), menos metástasis en los ganglios linfáticos (2-4 versus 12-16 metástasis), una MLNR más baja (0,05-0,08 versus 0,23-0,28), una menor frecuencia de estadio ganglionar AJCC pN1b (55,6-76 versus 89,9-91,6%) y no tenían metástasis a distancia (0% versus 28,4-37,1%), Las curvas de tiempo hasta la curación bioquímica avanzaron de manera constante hasta las metástasis de 7 a 12 ganglios y una MLNR de 0,33, y finalmente se nivelaron después de las metástasis de 16 a 17 ganglios y una MLNR de 0,45 a 0,65. En la regresión logística, el número de metástasis en los ganglios linfáticos (razón de oportunidades, odds ratio, OR 17,2 para > 20 metástasis, OR 5,3 para 11-20 metástasis y OR 2,2 para 6-10 metástasis), la calcitonina sérica basal preoperatoria (OR 6,2 para> 1000 pg/mL), la reoperación (OR 5,4) y la extensión extratiroidea (OR 2,4) predijeron de forma independiente el fracaso para alcanzar la curación bioquímica, CONCLUSIÓN: El número de metástasis en los ganglios linfáticos, a diferencia de la MLNR y del estadio ganglionar AJCC, determina la probabilidad de curación bioquímica después de la cirugía inicial y la reintervención para el MTC con ganglios positivos.

Time to calcitonin normalization after surgery for node-negative and node-positive medullary thyroid cancer.

BACKGROUND: It remains unclear when postoperative serum calcitonin levels should be measured in patients with medullary thyroid cancer (MTC) and, specifically, whether this decision should be based on the preoperative calcitonin level or nodal status. METHODS: A cohort of patients with previously untreated MTC was studied. Kaplan-Meier analyses, stratified by preoperative calcitonin level, nodal status and number of nodal metastases, were performed to determine time to calcitonin normalization after initial surgery, with statistical analysis by means of the log rank test. RESULTS: Some 213 patients with node-negative and 182 with node-positive MTC were included in the study. Postoperative calcitonin levels normalized in a mean of 3·5 versus 3·7 days respectively among patients with preoperative calcitonin levels of 10-100 pg/ml (P = 0·815); 4·8 versus 5·3 days in those with preoperative calcitonin levels of 100·1-500 pg/ml (P = 0·026); 5·3 versus 9·9 days in patients with preoperative calcitonin levels of 500·1-1000 pg/ml (P = 0·004); and 6·6 versus 57·7 days among those with preoperative calcitonin levels exceeding 1000 pg/ml (P < 0·001). Calcitonin levels normalized in a mean of 4·7 days when nodal metastasis was not present, 5·2 days in those with one to five nodal metastases, 7·0 days in patients with six to ten nodal metastases, and 57·1 days among patients with more than ten nodal metastases. Postoperative calcitonin normalization curves paralleled each other in patients with node-negative MTC, but diverged in those with node-positive disease and with more nodal metastases. CONCLUSION: Calcitonin levels typically normalize within 1 week; and within a fortnight in those with node-positive MTC and preoperative calcitonin levels of 500·1-1000 pg/ml. With node-positive MTC and preoperative calcitonin levels exceeding 1000 pg/ml, and with more than ten nodal metastases, calcitonin normalization takes longer.

Long-term outcome of prophylactic thyroidectomy in children carrying RET germline mutations.

BACKGROUND: A comprehensive assessment has not been undertaken of long-term outcomes in children carrying germline RET mutations and undergoing prophylactic thyroidectomy with the aim of preventing medullary thyroid cancer (MTC). METHODS: A retrospective outcome study (1994-2017) of prophylactic thyroidectomy in children, with and without central node dissection, was performed at a tertiary surgical centre. RESULTS: Some 167 children underwent prophylactic thyroidectomy, 109 without and 58 with concomitant central node dissection. In the highest-risk mutational category, MTC was found in five of six children (83 per cent) aged 3 years or less. In the high-risk category, MTC was present in six of 20 children (30 per cent) aged 3 years or less, 16 of 36 (44 per cent) aged 4-6 years, and 11 of 16 (69 per cent) aged 7-12 years (P = 0·081). In the moderate-risk category, MTC was seen in one of nine children (11 per cent) aged 3 years or less, one of 26 (4 per cent) aged 4-6 years, three of 26 (12 per cent) aged 7-12 years, and seven of 16 (44 per cent) aged 13-18 years (P = 0·006). Postoperative hypoparathyroidism was more frequent in older children (32 per cent in the oldest age group versus 3 per cent in the youngest; P = 0·002), whether or not central node dissection was carried out. Three children developed recurrent laryngeal nerve palsy; all had undergone central node dissection (P = 0·040). All complications resolved within 6 months. Postoperative normalization of calcitonin serum levels was achieved in 114 (99·1 per cent) of 115 children with raised preoperative values. No residual structural disease or recurrence was observed. CONCLUSION: Early prophylactic thyroidectomy is a viable surgical concept in experienced hands, sparing older children the postoperative morbidity associated with delayed neck surgery.

Twenty-year experience of paediatric thyroid surgery using intraoperative nerve monitoring.

BACKGROUND: There are few data on intermittent and continuous intraoperative nerve monitoring (IONM) during thyroidectomy in children. METHODS: All children aged 18 years or younger who had standard thyroid operations using intermittent or continuous IONM between January 1998 and December 2016 were included in the study. The impact of age and type of IONM on basal amplitude, latency and complications after thyroidectomy were assessed. RESULTS: A total of 504 children were included in the study. With continuous IONM, median basal amplitude and latency increased significantly with age, more on the left side (from 199 to 870 µV, and from 3·88 to 5·75 ms) than on the right (from 340 to 778 µV, and from 2·63 to 3·50 ms). Compared with intermittent IONM with needle electrode, continuous IONM with tube electrode resulted in an increase in median basal amplitude in children aged 13-18 years on both sides (from 675 to 778 µV on the right and from 450 to 870 µV on the left), and a decrease in median latency in all children older than 3 years: in children aged 4-6 years, from 4·20 to 3·00 ms on the right and from 6·10 to 4·63 ms on the left; in children aged 7-12 years, from 4·60 to 3·50 ms and from 6·00 to 5·25 ms respectively; and in children aged 13-18 years, from 4·60 to 3·50 ms and from 6·40 to 5·75 ms. Overall, wound infection, but not bleeding/haematoma or vocal fold palsy, affected younger children more: 3 per cent of children aged 3 years or less; 2 per cent of children aged 4-6 years; and 0 per cent of children aged over 6 years (P = 0·031). With continuous IONM, no wound infection, bleeding/haematoma or permanent vocal fold palsy was noted in any age group. CONCLUSION: Continuous IONM measures nerve electrophysiology more accurately than intermittent IONM during thyroidectomy in children.

Postoperative vocal fold palsy in patients undergoing thyroid surgery with continuous or intermittent nerve monitoring.

BACKGROUND: Continuous monitoring of electromyographic (EMG) amplitudes of the vocal muscles detects impending injury of the recurrent laryngeal nerve (RLN) during thyroid operations earlier than intermittent EMG monitoring. This may alert the surgeon to stop a manoeuvre causing stretching or pressure on the RLN, with better recovery of nerve function. METHODS: Patients with intact preoperative RLN function who underwent thyroid surgery for benign disease between January 2011 and September 2014 under continuous intraoperative nerve monitoring (CIONM) or intermittent intraoperative nerve monitoring (IIONM) were included in this observational study conducted at a tertiary surgical centre. For CIONM, combined EMG events indicative of imminent nerve injury were defined as an EMG amplitude decrease of 50 per cent or more and a latency increase of 10 per cent relative to baseline values. The rates of early and permanent palsy for the two groups of patients were compared. RESULTS: There were 1526 patients, 788 of whom (1314 nerves at risk) underwent thyroid surgery using CIONM and 738 (965 nerves at risk) had IIONM. With the use of CIONM, 63 (82 per cent) of 77 combined events were reversible during the operation. No permanent vocal fold palsy occurred with CIONM, whereas four unilateral permanent vocal fold palsies (0·4 per cent) were diagnosed after IIONM (P = 0·019). CONCLUSION: Operation with CIONM resulted in fewer permanent vocal fold palsies compared with IIONM after thyroid surgery in patients with benign disease.

[Hemithyroidectomy or total thyroidectomy for low-risk papillary thyroid cancer? : Surgical criteria for primary and secondary choice of treatment in an interdisciplinary treatment concept]. / Hemithyreoidektomie oder totale Thyreoidektomie beim papillären Niedrigrisikokarzinom der Schilddrüse? : Chirurgische Kriterien der primären und sekundären Therapiewahl im interdisziplinären Behandlungskonzept.

The increase in small intrathyroid papillary thyroid cancer (PTC) observed worldwide over the past two decades, with no increase in cancer-specific mortality, has challenged the previous concept of total thyroidectomy as a one-size-fits-all panacea. After exclusion of papillary microcarcinomas, a systematic review of 20 clinical studies published since 2002, which compared hemithyroidectomy (HT) to total thyroidectomy (TT), found comparable long-term oncological outcomes for low-risk papillary thyroid cancer (LRPTC) 1-4 cm in diameter, whereas postoperative complication rates were markedly lower for HT. To refine individual treatment plans, HT should be combined with ipsilateral central lymph node dissection and intraoperative frozen section analysis for staging. Based on recent evidence from studies and in consideration of individual risk factors, patients with LRPTC can be offered the concept of HT as an alternative to the standard TT. A prerequisite for the treatment selection and decision is a comprehensive patient clarification of the possible advantages and disadvantages of both approaches.

Loss of the nerve monitoring signal during bilateral thyroid surgery.

BACKGROUND: This study aimed to assess current use of recurrent laryngeal nerve monitoring (RLNM) for bilateral thyroid surgery in Germany. It explored the willingness of surgeons to change strategy after loss of signal (LOS) on the first side of resection. METHODS: Surgical departments in Germany equipped with nerve monitors were asked to complete a structured questionnaire, specifying the number of thyroidectomies done in 2010, and the frequencies of RLNM, vagal stimulation, and electromyographic (EMG) recording before and after thyroidectomy. They were also asked about the surgical plan for bilateral goitre after LOS on the first side of resection. RESULTS: Based on manufacturers' sales data, 1119 (89·1 per cent) of 1256 surgical departments in Germany were equipped with nerve monitors in 2010. A total of 595 departments (53·2 per cent), accounting for approximately 75 per cent of all thyroidectomies in Germany during that year, returned a completed questionnaire. RLNM was used in 91·7-93·5 per cent of thyroidectomies, with the addition of routine vagal stimulation in 49·3 per cent before, and 73·8 per cent after resection. EMG responses to vagal stimulation were recorded in 54·8 per cent before, and 72·5 per cent after resection. Some 93·5 per cent of surgeons changed the resection plan for the other side in bilateral thyroid surgery after LOS had occurred on the first side. CONCLUSION: RLNM is now the standard of care during thyroidectomy in Germany. After LOS on the first side of resection in bilateral goitre, more than 90 per cent of respondents declared their willingness to change the resection plan for the contralateral side to avoid the risk of bilateral recurrent laryngeal nerve palsy.

Primary surgery for differentiated thyroid cancer in the new millennium.

Differentiated thyroid cancers (DTC) are malignancies of follicular cell derivation. Histopathologically and oncologically, DTC fall into two broad tumor categories: papillary (PTC) and follicular thyroid cancer (FTC). These major tumor categories, based on clinical manifestation and biological behavior, are further subdivided into low-risk [papillary microcarcinoma (mPTC); minimally invasive follicular cancer (MIFTC)] and high-risk DTC [PTC>1 cm or metastatic; MIFTC with histopathological angioinvasion; widely invasive FTC (WIFTC)]. Recently, a surgical approach has been adopted that differentiates between low-risk and high-risk DTC. The rationale behind this new concept is to better balance oncologic risk (high vs low) with the surgical morbidity attendant to the procedure (recurrent laryngeal nerve palsy and hypoparathyroidism). This surgical risk is larger with routine total thyroidectomy (TT) and central node dissection (CND) than with less than TT or TT without CND.Whereas TT with CND remains the treatment of choice for high-risk DTC with metastases, the extent of thyroid resection and lymph node dissection can be reduced in low-risk PTC and FTC without demonstrable loss of oncological benefit. In the new millennium, the surgical approach to DTC, especially low-risk PTC and FTC, has undergone considerable change, resulting in less extensive procedures. This risk-adapted strategy relies not only on the skillful histopathologic detection of multifocality in PTC and vascular invasion in MIFTC, but likewise necessitates diligent follow-up to spot and adequately treat local recurrences and distant metastases as they become clinically apparent.

European endocrine surgery in the 150-year history of Langenbeck's Archives of Surgery.

INTRODUCTION: Founded in 1861 as a German language scientific forum of exchange for European surgeons, Langenbeck's Archives of Surgery quickly advanced to become the premier journal of thyroid surgery before World War I, serving as a point of crystallization for the emerging discipline of endocrine surgery. During the interwar period and, in particular, in the first decades after World War II, Langenbeck's Archives of Surgery lost its dominant position as an international and European medium of publication of top quality articles in the area of endocrine surgery. Nevertheless, the journal remained the chief publication organ of German language articles in the field of endocrine surgery. After a series of key events, Langenbeck's Archives of Surgery managed to reclaim its former position as the leading European journal of endocrine surgery: (1) the formation of endocrine surgery in the early 1980s as a subdiscipline of general and visceral surgery; (2) the change of the language of publication from German to English in 1998; and (3) the journal's appointment in 2004 as the official organ of publication of the European Society of Endocrine Surgeons. CONCLUSION: All in all, the 150-year publication record of Langenbeck's Archives of Surgery closely reflects the history of European Endocrine Surgery. Following the path of seminal articles from Billroth, Kocher, and many other surgical luminaries published in the journal more than 100 years ago, Langenbeck's Archives of Surgery today stands out as the principal European journal in the field of endocrine surgery.

[Extent of resection in intrathyroidal medullary thyroid cancer]. / Resektionsausmaß beim intrathyreoidalen medullären Schilddrüsenkarzinom.

Improvements in preoperative diagnostic modalities in conjunction with highly sensitive calcitonin assays, ultrasound and functional imaging modalities and differentiated genetic testing for detection of hereditary forms, have enabled detection and resection of medullary thyroid carcinoma at an increasingly earlier stage. These developments open up possibilities to deescalate primary surgery adapted to these stages and avoid surgical overtreatment in locally limited tumor growth: thus, promoting a shift from routinely recommended total thyroidectomy with bilateral central lymph node dissection in favor of limited unilateral thyroid resection. Prerequisites for limited thyroid resection include clinical evidence that the tumor is sporadic, unifocal and confined to the thyroid. Corresponding calcitonin levels should also indicate that a biochemical cure will be achieved after unilateral resection. A decisive structural prerequisite for such a limited concept is the low threshold availability of intraoperative frozen section analysis that reliably detects and evaluates a medullary thyroid carcinoma and can assess a breach of the thyroid capsule and desmoplasia with certainty.

Constitutive RET tyrosine kinase activation in hereditary medullary thyroid cancer: clinical opportunities.

The ground-breaking discovery of genotype-phenotype relationships in hereditary medullary thyroid cancer has greatly facilitated early prophylactic thyroidectomy. Its timing depends not solely on a positive gene test but, more importantly, on the type of the REarranged during Transfection (RET) mutation and its underlying mode of RET receptor tyrosine kinase activation. In the past decade, the therapeutic corridor opened by molecular information has been defined down to a remarkable level of detail. Based on mutational risk profiles, preemptive thyroidectomy is recommended at 6 months of age for carriers of highest-risk mutations, before the age of 5 years for carriers of high-risk mutations, and before the age of 5 or 10 years for carriers of least-high-risk mutations. Additional lymph node dissection may not be needed in the absence of increased preoperative basal calcitonin levels. Better comprehension of RET function should enable the design of targeted therapies for RET carriers beyond surgical cure in whom the DNA-based 'window of opportunity' has been missed.

Prediction of lateral lymph node metastases in medullary thyroid cancer.

BACKGROUND: In medullary thyroid cancer (MTC), there is a concordance between central and lateral neck involvement, but this relationship has not been assessed quantitatively. METHODS: After compartment-oriented lymphadenectomy for untreated MTC, the numbers of central lymph node metastases with ipsilateral (195 patients) and contralateral (185 of 195 patients) lateral lymph node metastases were analysed retrospectively. RESULTS: With one to three positive central lymph nodes, involvement of the ipsilateral lateral neck increased from 10.1 per cent (with no central node involvement) to 77 per cent, and from a mean of 0.6 to 3.7 nodal metastases (P < 0.001). With four or more central nodes, the rate was 98 per cent, with 10.7 nodal metastases (P = 0.001). A weaker increase was observed in the contralateral lateral neck: with one to nine positive central nodes, contralateral lateral neck involvement increased from 4.9 to 38 per cent, and from a mean of 0.6 to 2.3 nodal metastases (P = 0.011). With ten or more positive central nodes, the rate rose to 77 per cent, with 6.2 nodal metastases (P = 0.009). With one exception, contralateral lateral nodal metastases coexisted with metastases in the central and ipsilateral lateral neck. CONCLUSION: These data may lay the groundwork for more informed decision-making regarding dissection of the lateral neck compartments.

[Hereditary thyroid cancer]. / Hereditäre Schilddrüsenkarzinome.

Hereditary thyroid carcinomas are present in about 5% of differentiated (DTC) and 25% of medullary thyroid carcinomas (MTC). They are part of a multiorgan tumour syndrome (e. g. FAP Gardner's syndrome with DTC and MEN 2 syndrome with MTC) or confined to the thyroid gland. Hereditary thyroid carcinomas typically show multifocal growth and occur in young patients. Due to germ cell mutations as the underlying cause of disease, partial thyroidectomies that may be justified in early sporadic carcinomas are not indicated in this type of tumours. In the case of hereditary DTC, the genetic basis of the disease has been demonstrated only in syndromatic tumour variants. In most nonsyndromatic cases, specific genetic alterations have not yet been identified. In both types of hereditary DTC, prophylactic thyroidectomy is not warranted due to the favourable prognosis of tumours that do not differ from sporadic ones. Point mutations of the RET proto-oncogene have been known for 15 years to be the genetic basis of hereditary MTC. Recently several new mutations were discovered; however, final conclusions regarding their clinical significance are not possible at present. Basically it has been shown that the clinical aggressivity of tumour development follows a genotype-phenotype correlation (risk groups 1-3). However, in mutations of all risk classes there exists a wide spectrum of different stages of hereditary C-cell disease in individual risk groups. Regarding time and extent of prophylactic thyroidectomy (without or with lymph node dissection) a combined molecular-biochemical concept including the use of pentagastrin-stimulated calcitonin values is therefore recommended.

Breach of the thyroid capsule and lymph node capsule in node-positive papillary and medullary thyroid cancer: Different biology.

AIMS: The higher incidence of extranodal growth (breach of a lymph node capsule) in the presence of extrathyroidal extension (breach of the thyroid capsule) in papillary thyroid cancer prompted conclusions that the biology of thyroid cancer is conferred to the lymph nodes, causing invasion of perinodal tissues. This study aimed at quantifying the independent contributions of clinical-pathological factors to extranodal growth in thyroid cancer. METHODS: Multivariate analyses of 1250 patients operated on for node-positive papillary (PTC; 702 patients) or node-positive medullary thyroid cancer (MTC; 548 patients), 138 and 130 of whom harbored extranodal growth. RESULTS: After correction for multiple testing, extranodal growth correlated with number of lymph node metastases (means of 17.0 vs. 10.1 nodes for PTC, 20.6 vs. 13.4 nodes for MTC; each P < 0.001) and male gender (49 vs. 35% for PTC, P = 0.005; 62 vs. 46% for MTC; P = 0.002); and in MTC also with extrathyroidal extension (46 vs. 30%; P = 0.002). On multivariate analysis, independent determinants of extranodal growth were number of lymph node metastases (odds ratios of 2.1, 3.7 and 3.7 for PTC (P ≤ 0.01) and 2.7, 3.3, and 4.0 for MTC (P ≤ 0.004) looking at 6-10, 11-20 and >20 involved nodes against a 1-5 node baseline) and male gender (odds ratio 1.6 for PTC, 1.7 for MTC; each P = 0.02), but not extrathyroidal extension. CONCLUSIONS: In PTC and MTC, extranodal growth develops independently from extrathyroidal extension. This finding argues against mere transference of primary tumor characteristics to lymph nodes, pointing more to accrual of invasive properties by nodal tumor deposits.

[Surgical strategy during intended total thyroidectomy after loss of EMG signal on the first side of resection]. / Operative Strategie bei geplanter totaler Thyreoidektomie und Verlust des Neuromonitoring-Signals auf der erstoperierten Seite.

BACKGROUND: Unambiguous identification of the recurrent laryngeal nerve with detection of nerve dysfunction giving rise to postoperative vocal cord palsy (VCP) is the principal objective of intraoperative neuromonitoring (IONM) in thyroid surgery. Because intraoperative loss of the electromyographic (EMG) signal (LOS) does not result in VCP in one third of patients, controversy surrounds the issue of whether a change in strategy is needed in planned total thyroidectomy after LOS on the first side of resection. PATIENTS AND METHODS: This was a retrospective institutional study of 1,049 consecutive patients (2,086 nerves at risk) with intended bilateral thyroid surgery who were operated on between April 2010 and July 2012 with the use of IONM. The rates of temporary and permanent VCP were analyzed on the basis of the IONM results of the first side of resection and the extent of contralateral resection for completion: resection without LOS (group 1); resection with LOS and contralateral thyroidectomy (group 2); resection with LOS and contralateral subtotal resection (group 3); resection with LOS without any contralateral resection (group 4). RESULTS: LOS on the first side of resection was noted in 27 patients (2.6 %). All VCPs were unilateral. The rates of temporary and permanent VCP were 2.5 and 0.4 %, respectively, overall; specifically: group 1: 0.5 and 0 %; group 2: 64 and 9.1 %; group 3: 100 and 50 %; group 4: 83 and 8.3 %, respectively. CONCLUSION: Because an abnormal intraoperative electromyogram carries an 80 % risk for early postoperative VCP, the initial plan of bilateral surgery needs to be critically reviewed after LOS has occurred on the first side of resection, taking into account the underlying thyroid disease of the patient and surgeon expertise. Since more than 80 % of affected nerves will fully recover after the operation, staged completion thyroidectomy is recommended.

[Vocal cord paralysis after thyroid surgery : Current medicolegal aspects of intraoperative neuromonitoring]. / Stimmlippenparesen nach Schilddrüsenoperationen : Aktuelle medikolegale Aspekte des intraoperativen Neuromonitorings.

Intraoperative neuromonitoring (IONM) has been commercially available for approximately 15 years and is highly predictive in thyroid gland surgery concerning either postoperative vocal fold mobility in the case of an intact signal for muscle action electromyogram (EMG, > 99 % right negative) or vocal fold dysfunction in the case of loss of signal (> 70 % right positive). The use of IONM improves the intraoperative identification of recurrent laryngeal nerve function and due to the high predictive value with respect to the expected vocal cord function the result of IONM has to be integrated into the surgical concept of thyroidectomy. Unilateral loss of function of the recurrent laryngeal nerve cannot be completely avoided despite correct application of IONM; however, bilateral vocal fold palsy can be safely avoided when contralateral surgery is cancelled after a loss of signal occurs during resection of the first side in planned bilateral surgery (alternative strategy). Patients have to be informed preoperatively about the limitations of IONM and potential strategy changes during planned bilateral surgery. Surgeons should apply IONM according to the published current recommendations and by selecting a risk-oriented intraoperative strategy in the case of loss of signal from the recurrent laryngeal nerve.

Genotype-phenotype correlations in hereditary medullary thyroid carcinoma: oncological features and biochemical properties.

In hereditary medullary thyroid carcinoma (MTC), few genotype-phenotype correlations have been established. RET genotypes (exons 10, 11, 13, and 14) of 63 patients with hereditary MTC (from November 1994 to October 1999) were correlated with age at diagnosis, sex, the TNM system, and basal calcitonin levels. Mutations in exons 10, 11, 13, and 14 were demonstrated in 22% (14 of 63), 54% (34 of 63), 21% (13 of 63), and 3% (2 of 63). The median ages at diagnosis differed significantly (38, 27, 52, and 62 yr; P = 0.003). When grouped by cysteine codons (exons 10 and 11 vs. exons 13 and 14), this difference became even more evident (30 vs. 56 yr; P = 0.001). Apart from age at diagnosis, no other significant associations were noted. Based hereon, three MTC risk groups were devised according to genotype: a high risk group (codons 634 and 618) with the youngest ages of 3 and 7 yr at diagnosis; an intermediate risk group (codons 790, 620, and 611) with ages of 12, 34, and 42 yr; and a low risk group (codons 768 and 804) with ages of 47 and 60 yr, respectively. Age at diagnosis was unrelated to specific nucleotide and amino acid exchange within each codon. The current data demonstrate that there is a significant genotype-phenotype correlation, allowing for a more individualized approach to the timing and extent of prophylactic surgery.

The impact of HLA on long-term outcome after thymectomy for myasthenia gravis.

In a retrospective series of 86 patients with myasthenia gravis, the only factors predictive of improvement in muscular strength after transsternal thymectomy were preoperative severity of myasthenia (90% versus 54%, p = 0.0014) and HLA-B8 (79% versus 50%, p = 0.0060) in bivariable and multivariable analyses. Both factors were not interrelated (p = 0.824). The statistical effect of HLA-B8 was independent from preoperative severity of disease. Typing for HLA-B8 may thus be a valuable adjunct in predicting the benefit of thymectomy in myasthenia. The observation that an MHC class I allele is associated with clinical improvement after thymectomy suggests that the clinical course of myasthenia may be influenced by class I restricted T-cells.

Human autoantibodies to spermatogenic antigens and Sertoli cells.

Immunofluorescence staining using human autoantibodies is a simple and reliable method for investigation of meiotic and post-meiotic cells. Patients suffering from autoimmune diseases often produce circulating autoantibodies to antigens of germ cells and Sertoli cells. Four hundred human autoimmune sera were screened by indirect immunofluorescence on mouse seminiferous tubule cells. Autoantibodies of several specificities were found: one group reacted with organelles of meiotic prophase spermatocytes or spermatozoa. Included in this group were autoantibodies to synaptonemal complexes, sex vesicle, acrosome, and sperm tail. A second group of autoantibodies was found to stain different spermatogenic cell types uniformly, such as round spermatids or Sertoli cells.